2025 ESC／EACTS指南：瓣膜性心脏病的管理

Author/Task Force Member affiliations are listed in author information.

ESC Clinical Practice Guidelines(CPG) Committee: listed in the Appendix.

# ESC subspecialty communities having participated in the development of this document:

Associations: Association for Acute Cardiovascular Care (ACVC), European Association of Cardiovascular Imaging (EACVI), European Association of Preventive Cardiology (EAPC),European Association of Percutaneous Cardiovascular interventions (EAPCI), European Heart Rhythm Association (EHRA), and Heart Failure Association (HFA)

Working Groups: Cardiovascular Pharmacotherapy

Patient Forum

Disclaimer.The European Society of Cardiology(ESC)/European Association for Cardio-Thoracic Surgery(EACTS) Guidelines represent the views of the ESC and the EACTS and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC and the EACTS are not responsible in the event of any contra-diction, discrepancy and ambiguity between the ESC/EACTS Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC/EACTS Guidelines fully into account when exercising their clinical judgement, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC/EACTS Guidelines do not override, in any way whatsoever, the individual re-sponsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver. Nor do the ESC/EACTS Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices prior to making any clinical decision and to check whether a more a recent version of this document exists. The ESC and the EACTS warn readers that the technical language may be misinterpreted and decline any responsibility in this respect.

Permissions. The content of these ESC/EACTS Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC/EACTS Guidelines may be translated or reproduced in any form without written permission from the ESC and the EACTS. Permissions can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC(journals.permissions@oup.com).

This article has been co-published with permission in the European Heart Journal and European Journal of Cardio-Thoracic Surgery. All rights reserved.© The European Society of Cardiology and the European Association for Cardio-Thoracic Surgery 2025.

The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Ether citation can be used when citing this article.

ESC Guidelines

Document Reviewers: Alec Vahanian,(ESC Review Co-ordinator)(France), Carlos-A. Mestres,(EACTS Review Co-ordinator)(South Africa), Leila Abid(Tunisia), Suleman Aktaa(United Kingdom), Eoch F. Akowuah(United Kingdom),Elena Arbelo(Spain), Folkert W. Asselbergs(Netherlands), Emanuele Barbato(Italy), Giuseppe Boriani(Italy), Margarita Brida(Croatia), Sergio Bucheri(Sweden), Robert A. Byrne(Republic of Ireland), Ovidiu Chioncel(Romania), Lenard Conradi(Germany), Michele De Bonis(Italy), Victoria Delgado(Spain), Anna Franzone(Italy),Kristina Hermann Haugaa(Norway), Bettina Heidecker(Germany), Borja Ibanez(Spain), Bernard lung(France),Stefan James(Sweden), Lars Kober(Denmark), Konstantinos C. Koskinas(Switzerland), Ulf Landmesser(Germany),Gregory Y.H. Lip(United Kingdom), John William McEvoy(Ireland), Gil Meltzer(Israel), David Messika-Zeitoun(Canada), Borislava Mihaylova(United Kingdom), Richard Mindham(United Kingdom), Inge Moelgaard(Denmark),Jens Cosedis Nielsen(Denmark), Gareth Owens(United Kingdom), Agnes A. Pasquet(Belgium), Thomas Pilgrim(Switzerland), Eva Prescott(Denmark), Eduard Quintana(Spain), Volker Rudolph(Germany), Rafael Sadaba(Spain),Anna Sannino(Germany), Felix C.Tanner (Switzerland), Marina Urena (France), Ionca Vaartjes (Netherlands),Christiaan Vrints(Belgium), Alexander Wahba(Norway), Thomas Walther(Germany), Adam Witkowski(Poland),and Katja Zeppenfeld(Netherlands)

SD All experts involved in the development of these guidelines have submitted declarations of interest,which are reported in a supplementary document to the guidelines. See the European Heart Journal online or https://www.escardio.org/Guidelines for supplementary documents as well as evidence tables.

Keywords

Guidelines● European Society of Cardiology(ESC)● European Association for Cardio-Thoracic Surgery(EACTS)●Valvular heart disease● Aortic stenosis● Aortic regurgitation● Mitral stenosis● Mitral regurgitation● Tricuspid regurgitation● Tricuspid stenosis● Multivalvular disease● TAVI● SAVR● Heart surgery● Transcatheter edge-to-edge repair● Transcatheter valve replacement

Table of contents

1. Preamble 6

2. Introduction 8

2.1.What is new 9

3.The Heart Team and Heart Valve Centre 15

3.1. The Heart Valve Network 15

3.1.1. Composition of the Heart Team 16

3.1.2. Procedural volume and clinical outcomes

4. Imaging of patients with valvular heart disease 18

4.1. Initial valve assessment 18

4.2. Associated diseases and conditions 19

4.3. Evaluation of valvular heart disease 19

4.4. Assessment of extravalvular cardiac consequences from

valvular heart disease 19

4.5. Evaluation of eligibility, planning, and guiding of interventions

5.Clinical evaluation of patients with valvular heart disease 19

5.1. Clinical examination 19

5.2. Assessment of comorbidities and risk stratification

5.3. Biomarkers 20

5.4. Exercise testing 21

5.5. Invasive investigations 21

5.5.1. Coronary angiography 21

5.5.2. Cardiac catheterization 21

5.6. Patient-centred care and shared decision-making 21

6. Management of conditions associated with valvular heart disease

6.1. Diagnosis and management of coronary artery disease

6.2. Atrial fibrillation 23

6.3. Cancer and radiation therapy 23

6.4. Prophylaxis of rheumatic fever 24

6.5. Cardiogenic shock and acute heart failure 24

6.6. Palliative care 24

7. Aortic regurgitation 24

7.1. Prevalence and aetiology 24

7.2. Evaluation 24

7.3. Medical therapy 26

7.4. Indications for intervention 26

7.5. Follow-up 26

7.6. Special patient populations 28

8.Aortic stenosis 28

8.1. Prevalence and aetiology.28

8.2. Evaluation 28

8.2.1. Echocardiography and cardiac computed tomography

8.2.2. Additional diagnostic and prognostic parameters 29

8.2.3. Procedural planning 29

8.3. Medical therapy 29

8.4. Indication for intervention 31

8.4.1. Symptomatic severe aortic stenosis $\boxed{31}$

8.4.2. Asymptomatic severe aortic stenosis 31

8.4.3. Moderate aortic stenosis 31

8.5. Treatment options 33

8.5.1. The mode of intervention in candidates for a bioprosti

8.5.1.1. Age and life expectancy 34

8.5.1.2. Anatomical features 34

8.5.1.3. Lifetime management 34

8.6. Follow-up 37

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9. Mitral regurgitation $\ldots$ 37

9.1. Primary mitral regurgitation $\ldots$ 37

9.1.Prevalence and aetiology 37

9.1.2. Evaluation $\ldots$ 37

9.1.2.1. Echocardiography and right heart catheterization $\ldots$ 37

9.1.2.2. Biomarkers 37

9.1.2. Cardiac magnetic resonance and computed

tomography.38

9.1.2. Genetic evaluation 40

9.1.3. Medical therapy 40

9.1.4. Indications for intervention $\ldots$ 40

9.1.5. Follow-up 41

9.2. Secondary mitral regurgitation 41

9.2.1. Prevalence and aetiology $\ldots$ 41

9.2.2. Evaluation $\ldots$ 41

9.2.3. Definition of atrial secondary mitral regurgitation 41

9.2.4. Management of ventricular secondary mitral

regurgitation 42

9.2.4.1. Medical and device therapy 42

9.2.4. Indications for intervention $\ldots$ 43

9.2.4.3. Follow-up 44

9.2.5. Management of atrial secondary mitral regurgitation 45

9.2.5.1. Medical therapy and rhythm management.45

9.2.5.2. Indications for intervention 45

9.2.5. Follow-up $\ldots$ 45

10. Mitral stenosis $\ldots$ 45

10.1. Prevalence and aetiology $\ldots$ 45

10.2. Rheumatic mitral stenosis 45

10.2.1. Evaluation 45

10.2.2. Medical therapy 46

10.2.3. Indications for intervention 46

10.2. Follow-up 46

10.3. Degenerative mitsten asiation with mitral annular calcification

10.3.1. Evaluation 47

10.3. Indications for intervention $\boxed{47}$

11. Tricuspid regurgitation $\boxed{48}$

11.1. Prevalence and aetiology $\ldots$ 48

11.2. Evaluation $\ldots$ 49

11.3. Medical therapy 49

11.4. Indications for intervention $\boxed{49}$

11.4.1. Surgery 49

11.4.1.1. Patients without indication for left-sided valve

surgery\longdots51

11.4.1.2. Patients with indication for left-sided valve surgery.

11.4. Transcatheter techniques $\ldots$ 52

12. Tricuspid stenosis $\ldots$ 53

12.1. Prevalence and aetiology $\ldots$ 53

12.2. Evaluation 53

12.3. Medical therapy 54

12.4. Indications for intervention $\ldots$ 54

13. Multiple and mixed valvular heart disease 54

13.1. Prevalence and undertreatment 54

13.2. Evaluation and diagnostic pitfalls

13.3. Indications for intervention $\ldots$ 54

13.3.1. Multiple valvular heart disease 54

13.3.2. Mixed aortic valve disease 56

13.3.3. Mixed mitral valve disease $\ldots$ 56

13.4. Follow-up $\ldots$ 56

14.Management of patients with prosthetic valves or valve repair

14.1. Choice of prosthetic valve 56

14.2. Follow-up of patients with prosthetic valves $\ldots$ 57

14.3. Antithrombotic therapy in patients with treated valvular

heart disease $\underline{57}$

14.3.1. Mechanical heart valves 57

14.3.1.1. Post-operative anticoagulation and therapeutic

targets 57

14.3.1.2. Prevention and management of bleeding.59

14.3.1. Management of anticoagulation therapy before and

after non-cardiac invasive procedures 59

14.3.2. Biological heart valves 61

14.3.2.1. Patients with a surgical biological heart valve and no indication for oral anticoagulation 61

14.3.2. Patients with a transcatheter heart valve and no

indication for oral anticoagulation 61

14.3.2.3. Patients with a surgical biological heart valve and an

indication for oral anticoagulation 62

14.3.2.4. Patients with a transcatheter biological heart valve and an indication for oral anticoagulation 62

14.4. Management of prosthetic valve dysfunction and 63

14.4.1. Structural valve deterioration $\boxed{63}$

14.4.2. Non-structural valve dysfunction 64

14.4.2. Prosthesis-patient mismatch 64

14.4.2. Paravalvular leak and haemolysis $\ldots$ 64

14.4.4. Endocarditis 64

14.4.4. Valve thrombosis 64

14.4.4.1. Hypo-attenuated leaflet thickening

14.4.4.2. Clinically significant valve thrombosis 64

15. Management during non-cardiac surgery 66

15.1. Pre-operative evaluation 66

15.2. Specific valve lesions 66

15.2.1. Aortic stenosis $\ldots$ 66

15.2.2. Mitral stenosis $\boxed{67}$

15.2.3. Aortic and mitral regurgitation 67

15.3. Peri-operative monitoring $\boxed{67}$

16. Management of valvular heart disease during pregnancy $\boxed{68}$

16.1. Management before pregnancy 68

16.2. Management during pregnancy $\longdots$ 69

16.2.1. Patients with native valve disease 69

16.2.2. Patients with prosthetic valves 69

17.Sex-specific considerations in patients with valvular heart disease

17.1. Aortic valve disease $\boxed{69}$

17.2. Mitral valve disease $\boxed{70}$

17.3. Tricuspid valve disease $\boxed{70}$

18.Key messages $\ldots$ 70

19.Gaps in evidence $\boxed{71}$

20.What to do 'What not to do 'messages from the Guidelines 73

21. Evidence tables $\ldots$ 76

22.Data availability statement.

23. Author information $\underline{76}$

24. Appendix

25. References 77

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ESC Guidelines

Tables of Recommendations

Recommendation Table 1-Recommendations for the management of chronic coronary syndrome in patients with valvular heart disease(see also Supplementary data online, Evidence Table 1) 22 Recommendation Table 2- Recommendations for the management of atrial fibrillation in patients with native valvular heart disease(see also Supplementary data online, Evidence Tables 2 and 3)23 Recommendation Table 3- Recommendations on indications for intervention in severe aortic regurgitation(see also Supplementary data online, Evidence Tables 4-8)28 recommendation Table 4-Recommendations on indications for intervention in symptomatic and asymptomatic severe aortic stenosis,and recommended mode of intervention(see also Supplementary data online, Evidence Tables 9-13)36 Recommendation Table 5-Recommendations on indications for concomitant aortic valve replacement at the time of coronary artery bypass grafting or ascending aorta surgery 37 Recommendation Table 6- Recommendations on indications for intervention in severe primary mitral regurgitation(see also Supplementary data online, Evidence Tables 14-16)40

Recommendation Table 9-Recommendations on indications for intervention in tricuspid regurgitation(see also Supplementary Table 10-Recommendations on indications for

Recommendation Table 10-Recommendations on indications for intervention in tricuspid stenosis

Recommendation Table 11-Recommendations on indications for surgery of concomitant left-sided valvular heart disease.Recommendation Table 12-Recommendations on indications for intervention in patients with mixed moderate aortic stenosis and moderate aortic regurgitation(see also Supplementary data online,

moderate aortic regurgitation(see also Supplementary data online,Evidence Table 24) 56

Recommendation Table 13-Recommendations for prosthetic valve selection $\ldots$ 57

Recommendation Table 14-Recommendations for the management of antithrombotic therapy in patients with a mechanical heart valve 59

Recommendation Table 15-Recommendations for the management of antithrombotic therapy in patients with a mechanical heart valve undergoing elective non-cardiac surgery or invasive procedures

Recommendation Table 16- Recommendations for the management of antithrombotic therapy in patients with a biological heart valve or valve repair 62

Recommendation Table 17- Recommendations for the management of prosthetic valve dysfunction(see also Supplementary data online, Evidence Table 25)66

List of tables

Table 1 Classes of recommendations 7

Table 2 Levels of evidence $\boxed{7}$

Table 3 New recommendations $\boxed{9}$

Table 4 Revised recommendations $\longdots$

Table 5 Requirements for a Heart Valve Centre 17

Table 6 Complex procedures ideally performed in the most experienced Heart Valve Centres 17

Table 7 Clinical and echocardiographic criteria predicting outcome improvement in patients with severe ventricular secondary mitral regurgitation undergoing mitral transcatheter edge-to-edge repair....44

Table 8 Contraindications for percutaneous mitral commissortry in rheumatic mitral stenosis $\ldots$ 48

Table 9 Echocardiographic pitfalls, robust measures, and complementary multimodality imaging parameters in multiple or mixed valvular heart disease

Table 10 International normalized ratio targets and therapeutic

Table 11 Peri-operative management of antithrombotic treatment in patients with a mechanical heart valve undergoing non-cardiac surgery based on type of procedure and underlying risk 60

Table 12 Criteria for the diagnosis of moderate or severe aortic and mitral haemodynamic valve deterioration 63

Table 13'What to do' and'what not to do' $\ldots$ 73

List of figures

Figure 1 The Heart Valve Network 16

Figure 2 Integrative imaging assessment of patients with valvular heart disease $\ldots$ 18

Figure 3 Central illustration. Patient-centred evaluation for treatment of valvular heart disease $\longdots$

Figure 4 Imaging assessment of patients with aortic regurgitation 25

Figure 5 Management of patients with aortic regurgitation 27

Figure 6 Integrative imaging assessment of patients with aortic stenosis

Figure 7 Management of patients with severe aortic stenosis $\boxed{3}$

Figure 8 Aortic valve treatment options $\boxed{3}$ 3

Figure 9 Factors to be considered when selecting the mode of intervention for aortic stenosis $\ldots$ 35

Figure 10 Echocardiographic assessment of patients with mitral regurgitation

Figure 11 Management of patients with severe primary mitral

Figure 12 Most frequently used criteria for the diagnosis of atrial secondary mitral regurgitation 42

Figure 13 Treatment of severe secondary mitral regurgitation

without concomitant coronary artery disease $\boxed{43}$

Figure 14 Management of clinically severe rheumatic mitral stenosis

(mitral valve area≤1.5 cm2)47

Figure 15 Echocardiographic and invasive assessment of tricuspid

regurgitation 50

Figure 16 Stepwise evaluation of patients with tricuspid regurgitation 51

Figure 17 Management of patients with tricuspid regurgitation 52

Figure 18 Antithrombotic therapy following mechanical heart valve implantation

Figure 19 Antithrombotic therapy following biological heart valve

implantation or surgical valve repair 61

Figure 20 Management of left-sided obstructive and non-obstructive

mechanical heart valve thrombosis $\ldots$ 65

Figure 21 Management of non-cardiac surgery in patients with

severe aortic stenosis $\boxed{67}$

Figure 22 The Pregnancy Heart Team model of care 68

ESC Guidelines

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Abbreviations and acronyms

|2D|Two-dimensional|DSE|Dobutamine stress echocardiography| |---|---|---|---| |3D|Three-dimensional|DVI|Suropler velocity index| |4D|Four-dimensional|EARLS|European Association for Cardio-Thoracic Surgery| |ACE-I|Angiotensin-converting enzyme-inhibitor|EARLY TAVR|Evulation of TAVR Compared to Surveillance| |ACTIVATION|PercutAneous Coronary in Tervention prol to transcatheter aortic VAlve implantaTION trial|For Patients with Asymptomatic Severe Aortic Stenosis trial|Stenosis trial| |AF|Atrial fibrillation|ECG|Electrocardiogram| |AO|Aorta|EDV|End-diastolic velocity| |AP|Anteroposterior|ENVISAGE-TAVI AF|Edoxaban vs. Standard of Care and Their Effects on Clinical Outcomes in Patients| |AR|Aortic regurgitation||Having Undergone Transcatheter Aortic Valve| |ARB|Angiotensin receptor blocker||Implantation-Atrial Fibrillation| |AS|Aortic stenosis|EOA|Effective orifice area| |ASA|Acetylsilacylic acid|EROA|Effective orifice area| |ATLANTIS|Anti-Thrombotic Strategy to Lower All|ESC|European Society of Cardiology| ||Cardiovascular and Neurologic Ischemic and Hemorrhagic Events after Trans-Aortic Valve|EuroSCORE|European System for Cardiac Operative Risk Evaluation| |AU|Agatston units|EVLoVe|Early Valve Replacement guided by Biomarkers of LV Decompton in Asymptomatic Patients with Severe Aortic Stenosis| |AVA|Aortic valve area|FAC|of LV Decompton in Asymptomatic FFR| |AVA|Aortic valve area|FFR|Fractional flow reserve| |AVATAR|Aortic valve Replacement Versus|FWS|Free wall strain| |AVATAR|Conservative Treatment in Asymptomatic Severe Aortic Stenosis|GALILEO|Global multicenter, open-label, randomized, event-driven, active-controlled study comparing a rivAroxaban-based| |AVCS|Aortic valve calcium score||vent-driven, active-controlled study| |AVr|Aortic valve repair||comparing a rivAroxaban-based| |BASILICA|Bioprosthetic or native Aortic Scallop||antithrombotic strategy to an| ||Intentional Laceration to prevent ratogenic||antipatLatelet-based strategy after transcatheter| ||Coronary Artery obstruction||aortic vaLe rReplacement (TAVR) to Optimize| |BAV|Bicuspid aortic valve||clinical outcomes trial| |BHV|Biological heart valve|GLS|Guideline-directed medical therapy| |BNP|Brain natriuretic peptide|GLS|Global longitudinal strain| |BP|Blood pressure|h|Hour| |BSA|Body surface area|HALT|Hypo-attenuated leaflet thickening| |CABG|Coronary artery bypass grafting|HF|Heart failure| |CAD|Coronary artery disease|HFpEF|Heart failure with preserved ejection fraction| |CCT|Cardiac computed tomography|HF|Heart failure with reduced ejection fraction| |CCTA|Coronary computed tomography|HR|Hazard ratio| |CHA2DS2-VASSc|angiography|HTx|Heart transplantation| ||Cretngive heart failure or left ventricular|INR|International normalized ratio| ||dysfunction,hypertension,age≥75(doubled),|IU|International unit| ||diabetes,stroke(doubled), vascular disease,|KCCQ|Kansas City Cardiomyopathy Questionnaire| ||age 65-74, sex category(female)|LA|Left atrium/left atrial| |CI|Confidence interval|LAAO|Left atrial appendage occlusion| |CIED|Cardiac implantable electronic device|LAAOS|Left Atrial Appendage Occlusion Study| |CKD|Chronic kidney disease|LAMPOON|Laceration of the Anterior Mitral leaflet to| |CMR|Cardiac magnetic resonance||Prevent Outflow ObstructionN| |COAPT|Cardiovascular Outcomes assessment of the|LAVI|Left atrial volume index| ||MitraClip Percutaneous Therapy for Heart Failure|LMWH|Low-molecular-weight heparin| ||Patients with Functional Mitral Regurgitation|LV|Left ventricle/left ventricular| ||Cardiac resynchronization therapy|LVAE|Left ventricular assist device| |CT|Computed tomography|LFVE|Left ventricular ejection fraction| |CW|Continuous wave|LVESDI|Left ventricular end-systolic diameter| |CYP|Cytochrome P|LVESDi|Left ventricular end-systolic diameter indexed to BSA| |DAPT|Dual antiplatelet therapy|LVESVi|Left ventricular end-systolic volume indexed to| |DEDICATE|Randomized, Multicenter, Event-Driven Trial of TAVI versus SAVR in Patients with|LVESVi|BSA| ||Symptomatic Severe Aortic-Valve Stenosis|LVOT|Left ventricular outflow tract| |DOAC|Direct oral anticoagulant|MA|Lutral annulus|

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ESC Guidelines

MAC MATTERHORN

MAC MATTERHORN

MHV MITRA-FR

MR

MRI

MS

M-TEER

MV

MVA

MVHD

N

NCS

NOTION

NT-proBNP

NYHA

OAC

PAWP

PCI

PET

PH

PHT

PISA

P mean

PMC

PMR

POPular TAVI

PPM

PROM

PVL

PVL

RA

RCT

RECOVERY

RESHAPE-HF2

RF

RHC

RHD

RV

RVEF

RV

SAM

SAPT

SAV

SAVR

SGLT2i

SMR

Mitral annular calcification

Multicenter, Multicenter, Controlled Study to Assess Mitral Valve Reconstruction for Advanced Insufficiency of Functional or Ischemic Origin trial

Ischemic Origin trial

Mechanical heart valve

Percutaneous Repair with the MitraClip

Device for Severe Functional/Secondary Mitral

Regurgitation trial

Mean pulmonary artery pressure

Mitral regurgitation

Magnetic resonance imaging

Mitral stenosis

Mitral transcatheter edge-to-edge repair

Mitral valve

Mitral valve area

Multiple valvular heart disease

No

Non-cardiac surgery

Nordic Aortic Valve Intervention trial

N-terminal pro-B-type natriuretic protein

New York Heart Association

Oral anticoagulation

Pulmonary artery wedge pressure

Percutaneous coronary intervention

Positron emission tomography

Pulmonary hypertension

Pressure half-time

Proximal isovelocity surface area

Mean pressure gradient

Percutaneous mitral commissotomy

Primary mitral regurgitation

Antiplatelet Therapy for Patients Undergoing

Transcatheter Aortic Valve Implantation

Prosthesis-patient mismatch

Patient-reported outcome measure

Paravalvular leak

Pulmonary vascular resistance

Right atrium/right atrial

Randomized controlled trial

Randomized Comparison of Early Surgery versus Conventional Treatment in Very Severe Aortic Stenosis

Randomized Investigation of the MitraClip

Device in Heart Failure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation

Regurgitant fraction

Right heart catheterization

Rheumatic heart disease

Right ventricle/right ventricular

Right ventricular ejection fraction

Regurgitant volume

Systolic anterior movement

Single antiplatelet therapy

Surgical aortic valve

Surgical aortic valve replacement

Sodium-glucose co-transporter 2 inhibitor

Secondary mit regurgitation

SPAP

STS

STS-PROM

Systolic pulmonary artery pressure

Society of Thoracic Surgeons

Society of Thoracic Surgeons predicted risk of

mortality

SVD

Structural valve deterioration

Stroke volume index

TAPSE

Tricuspid annular plane systolic excursion

TAV

Transcatheter aortic valve

TAV

Transcatheter aortic valve implantation

TDI

Tissue Doppler imaging

TEER

Transcatheter edge-to-edge repair

THV

Transcatheter heart valve

TMVI

Transcatheter mitral valve implantation

Transoesophageal echocardiography

TR

TRILUMINATE

Clinical Trial to Evaluate Cardiovascular

Outcomes in Patients Treated With the

Tricuspid Valve Repair System trial

TRISCEND

Edwards EVOQUE Transcatheter Tricuspid

Valve Replacement: Pivotal Clinical

Investigation of Safety and Clinical Efficacy

using a Novel Device

TS

TTE

Transhoracic echocardiography

TTR

Time in therapeutic range

.TR

Tricuspid valve

Unfractionated heparin

VCA

Vena contracta area

VHD

Vvalular heart disease

VKA

Vitamin K antagonist

V_{max}

Vmaxak transvalvular velocity

VSARR

VSARR Valve-sparing aortic root replacement

VTE

Venous thromboembolism

VTI

VTI Velocity time integral

WHO

World Health Organisation

WU

WU Wood unit

Y

Y

1. Preamble

Guidelines evaluate and summarize available evidence with the aim of as-sisting health professionals in proposing the best diagnostic or therapeutic approach for an individual patient with a given condition. ESC/EACTS Guidelines are intended for use by health professionals but do not override their individual responsibility to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with the patient or the patient's caregiver where appropriate and/or necessary.It is also the health professional's responsibility to verify the rules and reg-ulations applicable in each country to drugs and devices at the time of pre-scription and to respect the ethical rules of their profession.

ESC Guidelines represent the official position of the ESC on a given topic. Guideline topics are selected for updating after annual expert re-view of new evidence conducted by the ESC Clinical Practice Guidelines (CPG) Committee. ESC Policies and Procedures for formu-lating and issuing ESC Guidelines can be found on the ESC website(https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Guidelines-development/Writing-ESC-Guidelines).

This guideline updates and replaces the previous version from 2021. This Task Force was selected by the ESC and the EACTS to include professionals

ESC Guidelines

7

|Classes of recommendations|Wording to use|Wording to use|| |---|---|---|---| |Classes of recommendations|Class I|Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective.|Is recommended or indicated| |Classes of recommendations|Class II|Conflicting evidence and/or a divergence of opinion about the usefulness/ efficacy of the given treatment or procedure.|| |Class II|Class Ia|Weight of evidence/opinion is in favour of usefulness/efficacy.|Should be considered| |Class II|Class IIb|Usefulness/efficacy is less well established by evidence/opinion.|May be considered| |Class II|Class III|Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful.|Is not recommended| |Class II|Table 2 Levels of evidence|Level of evidence A|ESCEACTS 2025| |Class II|Level of evidence B|Data derived from a single randomized clinical trial or large non-randomized studies.|| |Level of evidence C|Consensus of opinion of the experts and/or small studies, retrospective studies, registries.|||

8

ESC Guidelines

enhance comprehension of recommendations after publication, and to reinforce transparency in the guidelines development process. The ta-bles are published in their own section of the guidelines and reference specific recommendation tables.

After an iterative process of deliberations, a first Task Force vote on all recommendations is conducted prior to the initiation of rounds of review. A second Task Force vote on all recommendations is con-ducted after the final round of review and revision. For each vote.the Task Force follows ESC voting procedures and all recommenda-tions require at least 75% agreement among voting members to be ap-proved. Voting restrictions may be applied based on declarations of interests.

The writing and reviewing panels provide declaration-of-interest forms for all relationships that might be perceived as real or potential sources of conflicts of interest. Their declarations of interest are re-viewed according to the ESC declaration-of-interest rules, which can be found on the ESC website(http://www.ecsardio.org/doi) and are compiled in a report published in a supplementary document with the guidelines. Funding for the development of these ESC/EACTS Guidelines was derived entirely from the ESC and the EACTS with no involvement of the healthcare industry.

The ESC CPG Committee supervises and co-ordinates the prepar-ation of new guidelines and approves their publication. In addition to review by the ESC CPG Committee, these ESC/EACTS Guidelines underwent multiple rounds of double-blind peer review on a dedicated online review platform.The review was conducted by topic experts, in cluding members from ESC National Cardiac Societies, EACTS Network of National Cardiac Surgery Societies and from relevant ESC Subspecialty Communities.The Guideline Task Force considered all review comments and was required to respond to all those classified as major. After appropriate revisions, the Task Force, the ESC CPG Committee members and the EACTS Council members approved the final document for publication in the European Heart Journal and in the European Journal of Cardio-Thoracic Surgery.

Unless otherwise stated, the guideline content refers to sex, under-stood as the biological condition of being male or female, defined by genes, hormones, and sexual organs. Off-label use of medication may be presented in this guideline if a sufficient level of evidence shows that it can be considered medically appropriate for a given condition.However, decisions on off-label use must be made by the responsible health professional giving special consideration to ethical rules concern-ing healthcare, the specific situation of the patient, patient consent, and country-specific health regulations.

2. Introduction

New evidence has accumulated since the publication of the 2021 European Society of Cardiology(ESC)/European Association for Cardio-Thoracic Surgery(EACTS) Guidelines for the management of valvular heart disease, leading to the need for new recommendations(Table 3 New recommendations) and revision of existing recommendations(Table 4 Revised recommendations) concerning the following topics:

● The importance of shared and patient-centred decision-making by multidisciplinary expert Heart Teams working within a regional net-work has been reinforced. Patients with complex conditions or re-quiring complex procedures should be referred to high-volume

centres, where corresponding expertise is concentrated to ensure high-quality treatment.

● Advanced imaging modalities-such as three-dimensional(3D) echo-cardiography, cardiac computed tomography(CCT), and cardiac magnetic resonance(CMR) imaging-have gained importance and become a central aspect in the screening and evaluation of patients with valvular heart disease(VHD).

● Emphasis is put on the importance of correctly assessing the cause(s)and mechanism(s) of all valve diseases. In particular, the distinction between atrial and ventricular secondary mitral regurgitation(SMR)has clear implications in terms of prognosis and management.

● New evidence has been published regarding the benefits of intervention for the treatment of severe aortic stenosis(AS) irre-spective of symptoms, left ventricular ejection fraction(LVEF), and flow reserve.

● The criteria used for decision-making concerning the optimal modal-ity of AS treatment[transcatheter aortic valve(AV) implantation(TAVI) or surgical AV replacement(SAVR)] based on a Heart Team approach have been refined, including the combination of key aspects such as age, procedural risk, and anatomical suitability, incorporating estimated life expectancy and lifetime management considerations.

● Further randomized evidence confirming the mid-term safety and ef-ficacy of TAVI in low-risk patients has been published.

● The indications for TAVI in patients with bicuspid AV(BAV) stenosis or severe aortic regurgitation(AR) at high surgical risk, based on ana-tomical suitability and a comprehensive Heart Team evaluation, are discussed.

● Several advancements have been made regarding the treatment of patients with primary mitral regurgitation(PMR): refinement of the criteria for intervention in asymptomatic patients, demonstration of the value of minimally invasive mitral valve(MV) surgery to reduce the length of hospital stay and accelerate recovery; and large-scale data confirming the role of transcatheter edge-to-edge repair(TEER) in high-risk patients.

● Longer-term follow-up data and two new randomized controlled trials(RCTs) concerning the management of patients with ventricular SMR have been published.

● The evidence for the treatment of tricuspid valve(TV) disease is growing-including new randomized data supporting concomitant TV repair during left-sided valve surgery, and transcatheter options(repair and replacement) that reduce tricuspid regurgitation(TR),promote reverse right ventricular(RV) remodelling, and improve quality of life compared with medical treatment.

● Efforts have been made to provide improved guidance regarding the diagnostic steps and management of patients with multiple and mixed VHD.

● Definitions of structural valve deterioration(SVD) have been up-dated and unified.

● The recommendations concerning the use of direct oral anticoagu-lants(DOACs) in patients with VHD have been updated, and the im-portance of education and(self-)monitoring is emphasized.

● Sex-specific considerations in patients with VHD have been ex-tended and regrouped into a new dedicated section(see Section 17).

Because of demographic changes, patients with VHD frequently present with concomitant cardiovascular diseases, increasing the com-plexity of treatment strategies. These Guidelines focus on acquired

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9

VHD and do not deal in detail with overlapping cardiovascular diseases such as infective endocarditis,5 chronic coronary syndrome,6 and atrial fibrillation(AF),7 as well as all scenarios of aortic or congenital dis-ease,8,9 because these topics are covered in separate Guidelines.

The 2025 ESC/EACTS Guidelines for the management of valvular heart disease aim to be concise, focused on relevant issues for clinicians and patients, and to provide clear and simple practical recommendations,assisting healthcare providers in their daily clinical decision-making. A compilation of the evidence considered for new recommendations, or those with an updated class of recommendation or level of evidence,can be consulted online(see Supplementary data online, Evidence Tables). The Task Force for these Guidelines acknowledges that

multiple factors influence and ultimately determine the most appro-priate treatment of individual patients within a given community.These factors include the availability of equipment and technology,and the expertise and volumes, in complex procedures, such as valve repair or transcatheter interventions. Moreover, given the lack of evi-dence on some topics related to VHD, several recommendations are the result of expert consensus opinion. Therefore, deviations from these Guidelines may be appropriate in certain clinical circumstances,and decision-making should always be based on a collaborative, multi-disciplinary Heart Team approach centred on individual characteris-tics,needs,and prognosis,as well as the preferences of the informed patient.

2.1. What is new

Table 3 New recommendations

|Recommendations|Classa|Levelb| |---|---|---| |Diagnosis of coronary artery disease-Section 6.1||| |Omission of invasive coronary angiography should be considered in TAVI candidates, if procedural planning CT angiography is of sufficient quality to rule out significant CAD.|lla|B| |PCI should be considered in patients with a primary indication to undergo TAVI and≥90% coronary artery stenosis in segments with a reference diameter≥2.5 mm.|lla|B| |Indications for intervention in severe aortic regurgitation-Section 7.4||| |TAVI may be considered for the treatment of severe AR in symptomatic patients ineligible for surgery according to the Heart Team, if the anatomy is suitable.|llb|B| |Indications for intervention in symptomatic and asymptomatic severe aortic stenosis, and recommended mode of intervention-Section 8.5||| |Intervention should be considered in asymptomatic patients(confirmed by a normal exercise test, if feasible) with severe, high-gradient AS and LVEF≥50%, as an alternative to close active surveillance, if the procedural risk is low.|lla|A| |TAVI may be considered for the treatment of severe BAV stenosis in patients at increased surgical risk, if the anatomy is suitable.|llb|B| |Indications for intervention in severe primary mitral regurgitation-Section 9.1||| |Surgical MV repair is recommended in low-risk asymptomatic patients with severe PMR without LV dysfunction(LVESD<40 mm, LVESDi||| |<20 mm/m2, and LVEF>60%) when a durable result is likely, if at least three of the following criteria are fulfilled:||| |· AF||| |● SPAP at rest>50 mmHg||| |● LA dilatation(LAVI≥ 60 mL/m2 or LA diameter≥55 mm)||| |● Concomitant secondary TR≥ moderate.||| |Minimally invasive MV surgery may be considered at experienced centres to reduce the length of stay and accelerate recovery.|llb|B| |Indications for intervention in secondary mitral regurgitation-Section 9.2||| |MV surgery,surgical AF ablation, if indicated, and LAAO should be considered in symptomatic patients with severe atrial SMR under optimal medical therapy.|lla|B| |TEER may be considered in symptomatic patients with severe atrial SMR not eligible for surgery after optimization of medical therapy including rhythm control, when appropriate.|llb|B| |MV surgery may be considered in patients with moderate SMR undergoing CABG.|llb|B| |Indications for mitral valve surgery and transcatheter intervention in clinically severe rheumatic and degenerative mitral stenosis- Section 10.3||| |TMVI may be considered in symptomatic patients with extensive MAC and severe MV dysfunction at experienced Heart Valve Centres with expertise in complex MV surgery and transcatheter interventions.|||

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ESC Guidelines

Indications for intervention in tricuspid regurgitation-Section 11.4

Careful evaluation of TR aetiology, stage of the disease(i.e. degree of TR severity,RV and LV dysfunction,and PH), patient operative risk,and likelihood of recovery by a multidisciplinary Heart Team is recommended in patients with severe TR prior to intervention.

Surgery of concomitant severe mitral regurgitation-Section 13.3

MV surgery is recommended in patients with severe MR undergoing surgery for another valve.

Indications for intervention in patients with mixed moderate aortic stenosis and moderate aortic regurgitation-Section 13.3

Intervention is recommended in symptomatic patients with mixed moderate AV stenosis and moderate regurgitation, and a mean$$\text{ gradient}\geq 40\,\text{mmHg or}\,V_{\text{max}}\geq 4.0\,\text{m/s.}$$

Intervention is recommended in asymptomatic patients with mixed moderate AV stenosis and moderate regurgitation, with V max≥4.0 m/s and LVEF<50% not attributable to other cardiac disease.

Prosthetic valve selection-Section 14.1

An MHV should be considered in patients with an estimated long life expectancy, if there are no contraindications for long-term OAC.

Management of antithrombotic therapy in patients with a mechanical heart valve-Section 14.3

It is recommended that INR targets are based on the type and position of MHV, patient's risk factors, and comorbidities.

Patient education is recommended to improve the quality of OAC.

Management of antithrombotic therapy in patients with mechanical heart valves undergoing selective non-cardiac surgery or invasive procedures-Section 14.3

Continuing VKA treatment is recommended in patients with an MHV for minor or minimally invasive interventions associated with no or minimal bleeding

Interruption(3-4 days before surgery), and resumption of VKA without bridging, may be considered to reduce bleeding in patients with new-generation aortic MHV and no other thromboembolic risk factors undergoing major non-cardiac surgery or invasive procedures.

Management of antithrombotic therapy in patients with a biological heart valve or valve repair-Section 14.3

Surgical biological heart valve without indication for oral anticoagulation

Lifelong low-dose ASA(75-100 mg/day) may be considered 3 months after surgical implantation of an aortic or mitral BHV in patients without clear indication for OAC.

Transcatheter aortic valve implantation without indication for oral anticoagulation

DAPT is not recommended to prevent thrombosis after TAVI, unless there is a clear indication.

Surgical repair without indication for oral anticoagulation

Low-dose ASA(75-100 mg/day) may be considered after surgical MV or TV repair in preference to OAC in patients without clear indication for OAC and at high bleeding risk.

Surgical biological heart valve with indication for oral anticoagulation

OAC continuation is recommended in patients with a clear indication for OAC undergoing surgical BHV implantation.

DOAC continuation may be considered after surgical BHV implantation in patients with an indication for DOAC.

Surgical repair with indication for oral anticoagulation and/or antiplatelet therapy

Continuation of OAC or antiplatelet therapy should be considered after surgical valve repair in patients with a clear indication for an antithrombotic therapy.

Management of mechanical heart valve failure-Section 14.4

Reoperation is recommended in symptomatic patients with significant valve dysfunction not attributable to valve thrombosis.

Management of valve thrombosis-Section 14.4

TOE and/or 4D-CT are recommended in patients with suspected valve thrombosis to confirm the diagnosis.

4D,four-dimensional;AF,atrial fibrillation;AR,aortic regurgitation;AS,aortic stenosis;ASA,acetylsallicylic acid;AV,aortic valve;BAV,bicuspid aortic valve;BHV,biological heart valve;CABG,caryary artery bypass grafting; CAD, coronary artery disease; CT, computed tomography; DAPT, dual antplatelet therapy; DOAC, direct oral anticoagulant; INR, international normalized ratio;LA, left atrium/left atrial;LAAO, left atrial appendage occlusion;LV,L left atrial volume index,LV, left ventricle/left ventricular;LVEF, left ventricular ejection fraction;LVESD,left ventricular end-systolic diameter;LVESD, left ventricular end-systolic diameter indexed to body surface area;MAC,Miral annular calcification;MHV,mechanical heart valve;MR,mitral regurgitation;MV,mital valve;OAC,oral anticoagulation;PCI,percutaneous coronary intervention;PH,pulmonary hypertension;PMR,primary mitral regurgitation;RV,right ventricle/right ventricular;SMR, secondary mitral regurgitation;SPAP,systolic pulmonary artery pressure;TAVl, transcatheter aortic valve implantation;TEER,transcatheter edge-to-edge repair;TMVI,transcatheter mitral valve implantation; TOE, transoesophageal echocardiography;TR,tricuspid regurgitation;TV,tricuspid valve;KVA, vitamin K antagonist; V'max peak transvalvular velocity.

bLevel of evidence.

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11

Table 4 Revised recommendations

|Recommendations in 2021 version Classa Levelb|Recommendations in 2025 version|Classa|Levelb||||| |---|---|---|---|---|---|---|---| |Management of coronary artery disease in patients with valvular heart disease-Section 6.1|||||||| |CCTA should be considered as an alternative to coronary angiography before valve surgery in patients with severe VHD and low probability of CAD.|lla|C|CCTA is recommended before valve intervention in patients with moderate or lower(≤50%) pre-test likelihood of obstructive CAD.|1|B||| |Coronary angiography is recommended before valve surgery in patients with severe VHD and any of the following: ● History of cardiovascular disease ● Suspected myocardial ischaemia ● LV systolic dysfunction ● In men> 40 years of age and post-menopausal women ● One or more cardiovascular risk factors.|lIa|C|Invasive coronary angiography is recommended before valve intervention in patients with high and very high (>50%) pre-test likelihood of obstructive CAD.|1|C||| |Coronary angiography is recommended in the evaluation of severe SMR.|I|C|Invasive coronary angiography is recommended in the evaluation of CAD in patients with severe ventricular SMR.|1|C||| |PCI should be considered in patients with a primary indication to undergo TAVI and coronary artery diameter instenosis>70% in proximal segments.|lla|C|PCI may be considered in patients with a primary indication to undergo transcatheter valve interventions and coronary artery stenosis≥70% in proximal segments of main vessels.|116|B||| |PCI should be considered in patients with a primary indication to undergo transcatheter MV intervention and coronary artery diameter stenosis>70% in proximal segments.|lla|C|The use of DOACs is not recommended in patients with A and FMRatic MS with an MVA≤2.0 cm2.|116|B||| |Management of atrial fibrillation in patients with native valvular heart disease-Section 6.2|||||||| |LAAO should be considered to reduce the thromboembolic risk in patients with AF and a CHA2DS2-VASc score≥2 undergoing valve surgery.|lla|Surgical closure of the LA appendage is recommended as an adjunct to OAC in patients with AF undergoing valve surgery to prevent cardioembolic stroke and systemic thromboembolism.|1||B||| |Concomitant AF ablation should be considered in patients undergoing valve surgery, balancing the benefits of freedom from atrial arrhythmias and the risk factors for recurrence(LA dilatation, years in AF, age, renal dysfunction, and other cardiovascular risk factors).||Concomitant surgical ablation is recommended in rhythm control strategy to prevent symptoms and recurrence of AF, according to an experienced team of biophrysiologists and arrhythmia surgeons.|1||A||| |Ila|Ila|A|Concomitant surgical ablation should be considered in response of AF, according to an experienced team of patients undergoing non-MV surgery with AF suitable for a 116|11a||B|| |The use of DOACs is not recommended in patients with AF and moderate-to-severe MS.|III|C|The use of DOACs is not recommended in patients with AF and rheumatic MS with an MVA≤2.0 cm2.|111|B||| |Indications for surgery in severe aortic regurgitation-Section 7.4|||||||| |AV repair may be considered in selected patients at experienced centres when durable results are expected.|IIb|C|AV repair should be considered in selected patients with severe AR at experienced centres, when durable results are expected.|11a||B|| |Surgery may be considered in asymptomatic patients with LVESD>20 mm/m2 BSA(especially in patients with small body size) or resting LVEF≤55%, if surgery is at low risk.|IIb|C|AV surgery may be considered in asymptomatic patients with severe AR and LVESDi>22 mm/m2 or LVESVi>45 mL/m2[especially in patients with small body size(BSA<1.68 m2)], or resting LVEF≤55%, if surgical risk is low.|11b||B|| |Indications for intervention in symptomatic severe aortic stenosis-Section 8.4.1|||||||| |Intervention is recommended in symptomatic patients with severe low-flow(SVi≤35 mL/m2), low-gradient (<40 mmHg) AS with reduced LVEF(<50%), and evidence of flow (contractile) reserve.|I|B|||I|||

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ESC Guidelines

Intervention should be considered in symptomatic patients with low-flow, low-gradient(<40 mmHg) AS with normal LVEF after careful confirmation that the AS is severe.

<EndOfPara>Intervention should be considered in symptomatic patients with low-flow(SV≤35 mL/m2), low-gradient(<40 mmHg) AS with normal LVEF(≥50%) after careful confirmation that AS is severe.

lla

Ⅲa

Indications for intervention in asymptomatic severe aortic stenosis-Section 8.5

Intervention should be considered in asymptomatic patients with severe AS and LV dysfunction(LVEF<55%) without another cause.

Intervention should be considered in asymptomatic patients with LVEF>55% and a normal exercise test if the procedural risk is low and one of the following parameters is present:

● Very severe AS(mean gradient≥60 mmHg or V max>5 m/s).

● Severe valve calcification(ideally assessed by CCT)and V max progression≥0.3 m/s/year.

● Markedly elevated BNP levels(more than three times age- and sex-corrected normal range) confirmed by repeated measurements and without other explanation.

Intervention should be considered in asymptomatic patients with severe AS and LVEF≥50%, if the procedural risk is low and one of the following parameters is present:

• Very severe AS(mean gradient≥60 mmHg or V_{\max}>5.0 m/s).

• Severe valve calcification(ideally assessed by CCT)and V max progression≥0.3 m/s/year.

● Markedly elevated BNP/NT-proBNP levels(more than three times age- and sex-corrected normal range, confirmed on repeated measurement without other explanation).

• LVEF<55% without another cause.

Mode of intervention in symptomatic severe aortic stenosis-Section 8.5

The choice between surgical and transcatheter intervention must be based upon careful evaluation of clinical, anatomical, and procedural factors by the Heart Team, weighing the risks and benefits of each approach for an individual patient. The Heart Team

It is recommended that the mode of intervention is based on Heart Team assessment of individual clinical,anatomical, and procedural characteristics,

incorporating lifetime management considerations and estimated life expectancy.

TAVI is recommended in older patients(≥75 years), or in those who are high risk(STS-PROM/EUTOSCORE II>8%) or unsuitable for surgery.

TAVI is recommended in patients≥70 years of age with tricuspid AV stenosis, if the anatomy is suitable.

SAVR is recommended in younger patients who are low risk for surgery(<75 years and STS-PROM/EuroSCORE II<4\%), or in patients who are operable and unsuitable for transfemoral TAVI.

SAVR is recommended in patients<70 years of age, if the surgical risk is low.

SAVR or TAVI are recommended for remaining patients according to individual clinical, anatomical, and procedural characteristics.

SAVR or TAVI are recommended for all remaining candidates for an aortic BHV according to Heart Team ess ${}^{1-4}$

Non-transfemoral TAVI may be considered in patients who are inoperable and unsuitable for transfemoral TAVI.

Non-transfemoral TAVI should be considered in patients who are unsuitable for surgery and

I

C

Indications for intervention in severe primary mitral regurgitation-Section 9.1.4

Surgery should be considered in asymptomatic patients with preserved LV function(LVESD<40 mm and LVEF>60%) and AF secondary to MR or PH(SAPP at rest>50 mmHg).

MV surgery should be considered in asymptomatic patients with severe PMR without LV dysfunction<40 mm,LVESDi<20 mm/m2,and LVEF>60%) in the presence of PH(SAP at rest>50 mmHg), or AF secondary to MR.

Ⅲa B

Surgical MV repair should be considered in low-risk asymptomatic patients with LVEF>60%, LVESD<40 mm, and significant LA dilatation(volume index≥60 mL/m2 or diameter≥55 mm) when performed in a Heart Valve Centre and a durable repair is likely.

Surgical MV repair should be considered in low-risk asymptomatic patients with severe PMR without LV dysfunction(LVESD<40 mm,LVESDi<20 mm/m2,and LVEF>60%) in the presence of significant LA dilatation(LAVI≥60 mL/m2 or LA diameter≥55 mm),when performed in a Heart Valve Centre and a durable repair is likely.

Continued

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13

|TEER may be considered in symptomatic patients who fulfil the echocardiographic criteria of eligibility,are judged in orable at high surgical risk by the Heart Team, and for whom the procedure is not considered futile.|GB|TEER should be considered in symptomatic patients with severe PMR who are anatomically suitable and at high surgical risk by the Heart Team, and|IIa|B|| |---|---|---|---|---|---| |Severe ventricular secondary mitral regurgitation and concomitant coronary artery disease-Section 9.2|||||| |In symptomatic patients who are judged not appropriate for surgery by the Heart Team on the basis of their individual characteristics, PCI(and/or TAVI) possibly followed by TEER (in case of persisting severe SMR) should be considered.|lla|C|PCI followed by TEER after re-evaluation of MR may be considered in symptomatic patients with chronic severe ventricular SMR and non-complex CAD.||| |Indications for intervention in severe ventricular secondary mitral regurgitation without concomitant coronary artery disease- Section 9.2|||||| |TEER should be considered in selected symptomatic patients not eligible for surgery and fulfilling criteria suggesting an increased chance of responding to the treatment.|lla|B|TEER is recommended to reduce HF hospitalizations and improve quality of life in haemodynamically stable, symptomatic patients with impaired LVEF(<50%) and persistent severe ventricular SMR, despite optimized GDMT and CRT(if indicated),fulfilling specific clinical and echocardiographic criteria.||| |In high-risk symptomatic patients not eligible for surgery and not fulfilling the criteria suggesting an increased chance of responding to TEER, the Heart Team may consider in selected cases a TEER procedure or other transcatheter valve therapy if applicable, after careful evaluation for ventricular assist device or heart transplant.|C|TEER may be considered for symptom improvement in selected symptomatic patients with severe ventricular SMR not fulfilling the specific clinical and echocardiographic criteria,after careful evaluation of LVAD or HTx.|IIb|B|| |Valve surgery may be considered in symptomatic patients judged appropriate for surgery by the Heart Team.|IIb|C|MV surgery may be considered in symptomatic patients with severe ventricular SMR without advanced HF who are not suitable for TEER.|IIb|C| |Indications for intervention in tricuspid regurgitation in patients with left-sided valvular heart disease requiring surgery-Section 11.4|||||| |Surgery is recommended in patients with severe primary TR undergoing left-sided valve surgery.|I|C|Concomitant TV surgery is recommended in patients with severe primary or secondary TR.|I|B| |Surgery is recommended in patients with moderate primary TR undergoing left-sided valve surgery.|I|B|Concomitant TV repair should be considered in patients with moderate primary or secondary TR, to avoid progression of TR and RV remodelling.|IIa|B| |Surgery should be considered in patients with mild or moderate secondary TR with a dilated annulus (≥40 mm or >21 mm/m² by 2D echocardiography) undergoing left-sided valve surgery.|lla|B|Concomitant TV repair may be considered in selected patients with mild secondary TR and tricuspid annulus dilatation(≥40 mm or>21 mm/m²) to avoid progression of TR and RV remodelling.|IIb|B| |Indications for intervention in patients with severe tricuspid regurgitation without left-sided valvular heart disease requiring surgery- Section 11.4|||||| |Transcatheter treatment of symptomatic secondary severe TR may be considered in inoperable patients at a Heart Valve Centre with expertise in the treatment of TV disease.|Ilb|C|Transcatheter TV treatment should be considered to improve quality of life and RV remodelling in high-risk patients, with symptomatic severe TR despite optimal medical therapy, in the absence of severe RV dysfunction or pre-capillary PH.|lla|A| |Prosthetic valve selection-Section 14.1|||||| |A mechanical prosthesis may be considered in patients already on long-term anticoagulation due to the high risk for thromboembolism.|llb|C|An MHV may be considered in patients with a clear indication for long-term OAC.|llb|C| |Management of antithrombotic therapy in patients with a mechanical heart valve-Section 14.3|||||| |OAC using a VKA is recommended lifelong for all patients with an MHV prosthesis.|||Lifelong OAC with a VKA is recommended for all patients with MHVs to prevent thromboembolic complications.|1|A|

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ESC Guidelines

|For patients with a VKA, INR self-management is recommended provided appropriate training and quality control are performed.|I|B|INR self-monitoring and self-management are recommended over standard monitoring in selected, trained patients to improve efficacy.|I|A| |---|---|---|---|---|---| |In patients with MHVs, it is recommended to(re)initiate the VKA on the first post-operative day.|I|C|Following cardiac surgery with MHV implantation, it is recommended to start UFH or LMWH bridging and VKA within 24 h, or as soon as considered safe.|I|B| |In patients who have undergone valve surgery with an indication for post-operative therapeutic bridging, it is recommended to start either UFH or LMWH 12-24 h after surgery.|I|C||I|B| |The addition of low-dose ASA(75-100 mg/day) to VKA may be considered in selected patients with MHVs in case of concomitant atherosclerotic disease and low risk of bleeding.|IIb|C|The addition of low-dose ASA(75-100 mg/day) to VKA should be considered in selected patients with MHVs in case of concomitant symptomatic atherosclerotic disease, considering the individual bleeding risk profile.|lla|B| |The addition of low-dose ASA(75-100 mg/day) to VKA should be considered after thromboembolism despite an adequate INR.|IIa|C|Either an increase in INR target or the addition of low-dose ASA(75-100 mg/day) should be considered in patients with MHVs who develop a major thromboembolic complication despite documented adequate INR.|lla|C| |DOACs are not recommended in patients with an MHV prosthesis.|III|B|DOACs and/or DAPT are not recommended to prevent thrombosis in patients with an MHV.|III|A| |Management of antithrombotic therapy in patients with mechanical heart valves undergoing selective non-cardiac surgery or invasive procedures-Section 14.3|||||| |It is recommended that VKAs are timely discontinued prior to elective surgery to aim for an INR<1.5.|I|C|It is recommended to discontinue VKA at least 4 days before major elective non-cardiac surgery, aiming for an INR<1.5, and to resume VKA treatment within 24 h after surgery, or as soon as considered safe.||B| |In patients with MHVs, it is recommended to(re)initiate the VKA on the first post-operative day.|I|C|INR<1.5, and to resume VKA treatment within 24 h after surgery, or as soon as considered safe.||| |Therapeutic doses of either UFH or subcutaneous LMWH are recommended for bridging.|I|B|VKA interruption and resumption with bridging should be considered in patients with an MHV and thromboembolic risk factors undergoing major non-cardiac surgery.||| |Bridging of OAC, when interruption is needed, is recommended in patients with any of the following indications: ● MHV ● AF with significant MS ● AF with CHA2DS2-VASc score≥3 for women or 2 for men ● Acute thrombotic event within the previous 4 weeks ● High acute thromboembolic risk.|I|C|lla|B|| |Management of antithrombotic therapy in patients with a biological heart valve or valve repair-Section|||||| |Lifelong SAPT is recommended after TAVI in patients with no baseline indication for OAC.|I|Low-dose ASA(75-100 mg/day) is recommended for 12 months after TAVI in patients without indication for OAC.|I|A|| |OAC is recommended lifelong for TAVI patients who have other indications for OAC.|I|A|lla|C|| |OAC is recommended lifelong for TAVI patients who have other indications for OAC.|I|B|I|B|| |OAC with VKA should be considered during the first 3 months after mitral and tricuspid repair.|IIa|C|OAC, with either VKAs or DOACs, should be considered during the first 3 months after surgical MV or TV repair.|IIa|B| |Routine use of OAC is not recommended after TAVI in patients without baseline indication.|III|B|Routine use of OAC is not recommended after TAVI in patients without baseline indication.|III|A|

Management of haemolysis and paravulavular leak-Section

Decision on transcatheter or surgical closure of clinically significant PVLs should be considered based on patient risk status, leak morphology, and local expertise.

lla

It is recommended that the decision between transcatheter or surgical closure of clinically significant PVLs is based on Heart Team evaluation, including patient risk, leak morphology, and local expertise.

Continued

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15

|Transcatheter closure should be considered for suitable PVLs with clinically significant regurgitation and/or haemolysis in patients at high or prohibitive surgical risk.|IIa|B|Transcatheter closure should be considered for suitable PVLs with clinically significant regurgitation and/or haemolysis.|IIa|B| |---|---|---|---|---|---| |Management of biological heart valve failure-Section 14.4|||||| |Reoperation is recommended in symptomatic patients with a significant increase in transprosthetic gradient (after exclusion of valve thrombosis) or severe regurgitation.|1|C|Reintervention is recommended in symptomatic patients with significant valve dysfunction not attributable to valve thrombosis.|I|C| |Transcatheter, transfemoral valve-in-valve implantation in the aortic position should be considered by the Heart Team depending on anatomical considerations, features of the prosthesis, and in patients who are at high operative risk or inoperable.|IIa|B|Transcatheter transfemoral valve-in-valve implantation in the aortic position should be considered in patients with significant valve dysfunction who are at intermediate or high surgical risk, and have suitable anatomical and prosthesis features, as assessed by the Heart Team.|IIa|B| |Transcatheter valve-in-valve implantation in the mitral and tricuspid position may be considered in selected patients at high risk for surgical reintervention.|IIb|B|Transcatheter transvenous mitral or tricuspid valve-in-valve implantation should be considered in patients with significant valve dysfunction at intermediate or high surgical risk, if the anatomy is suitable.|IIa|B| |Management of mechanical heart valve thrombosis-Section 14.4|||||| |Urgent or emergency valve replacement is recommended for obstructive thrombosis in critically ill patients without serious comorbidity.|I|B|Heart Team evaluation is recommended in patients with acute HF(NYHA class III or IV) due to obstructive MHV thrombosis to determine appropriate management(repeat valve replacement or low-dose slow infusion fibrinolysis).||| |Ila B|Ila B|Ila B|Ila B|Ila B|I| |Imp 1a B|Imp 1a B|Imp 1a B|Imp 1a B|Imp 1a B|| |Management of biological heart valve thrombosis- Section 14.4||||||

2D,two-dimensional;AF,atrial fibrillation;AR,aortic regurgitation;AS,aortic stenosis;ASA,acetylsalicylic acid;AV,aortic valve;BHV,biological heart valve;BNP,brain natriuretic peptide;BSA,body surface area;CAD,coronary artery disease;CCT,cardiac computed tomography;CCTA,coronary computed tomography angiography;CHA2DS2-VASc,congestive heart failure or left ventricular dysfunction, hypertension,age≥75(doubled),diabetes,stroke(doubled),vascular disease,age 65-74,sex category(female);CRT,cardiac resynchronization therapy,DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulant; EuroSCORE, European System for Cardiac Operative Risk Evaluation; GDMT, guideline-directed medical therapy; h-hour;HF,heart failure;HTx,heart transplantation;INR,international normalized ratio;LA,left atrium/leftA;LANO, left atrial appendage occlusion; LAVI, left atrial volume index;LMWH, low-molecular-weight heparin; LV, left ventricle/left ventricular;LVAD, left ventricular assist device;LVEF, left ventricular end-systolic diameter;LVESDI, left ventricular end-systolic diameter indexed to BSA;LVESVI, left ventricular end-systolic volume indexed to BSA;MHV,mechanical heart valve;min,minute;MR,mitral regurgitation; MS, mitral stenosis; MV, mitral valve; MVA, mitral valve area; NT-proBNP,N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; OAC,oral anticoagulation; PCI, percutaneous coronary intervention; PH, pulmonary hypertension; PLM, primary mitral regurgitation; PVL, paravalvular leak; RV, right ventricle/right ventricular;SAPT, single antiplatelet therapy; SAVR, surgical aortic valve replacement; SMR, secondary mitral regurgitation; SPAP, systolic pulmonary artery pressure; STS-PROM, Society of Thoracic Surgeons predicted risk of mortality; SV, stroke volume index; TAVI, transcatheter aortic valve implantation; TEER, transcatheter edge-to-edge repair; TR, tricuspid regurgitation;TV,tricuspid valve;UFH,unfractionated heparin;VHD, valvular heart disease; VKA, vitamin K antagonist; V_{max} peak transvavalur velocity.

bLevel of evidence.

3.The Heart Team and Heart Valve Centre

3.1. The Heart Valve Network

Despite increasing attention within the medical community, VHD con-tinues to be underdiagnosed and undertreated in the general popula-tion, and public awareness remains low.10-13.89 Side screening using auscultation and imaging when appropriate, the co-ordinated imple-mentation of Heart Teams, Heart Valve Centres, and Heart Valve Networks at a local level represents an essential step to timely diagnose and treat patients with VHD.

An integrated regional Heart Valve Network, incorporating out-patient Heart Valve Clinics(for initial diagnosis and ongoing surveil-lance) and specialist Heart Valve Centres(for advanced imaging and surgical or transcatheter intervention), allows optimal patient care through timely access to specialist assessment, accurate diagnosis, im-proved decision-making and matching of patients to healthcare provi-ders with appropriate expertise, experience, and resources(Figure 1).In addition, dedicated Heart Valve Clinics ensure consistent application of clinical guidelines, efficient use of resources, and overall high-quality patient care, which in turn may improve outcomes.14,15 Medical goals include careful clinical and echocardiographic evaluation, monitoring at appropriate time intervals(so-called‘watchful waiting’), application

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 Figure 1 The Heart Valve Network. HF, heart failure; VHD, valvular heart disease.

of guideline-directed medical therapy(GDMT), timely referral, and post-procedural follow-up. ${}^{15,16}$ Broader aims include patient education,the training of physicians and nurse specialists, swift and efficient access to specialist care, and recruitment into clinical trials.

Heart Valve Centres should ensure that their facilities match institu-tional and local statutory requirements(Table 5), report procedural vo-lumes and outcomes, and monitor treatment quality. They hold responsibility for the training and education of surgeons, interventional and imaging cardiologists, dedicated nurses, and allied professionals. ${}^{17,18}$ Expertise in the surgical management of coronary artery disease(CAD), vascular diseases, and complications must be available. New techniques should be taught by trained mentors using simulator mod-els, when feasible, to minimize learning-curve effects. More broadly,Heart Valve Centres co-ordinate the management of patients with VHD across the entire Heart Valve Network, supporting services at community level, encouraging early referral, and promoting education and communication with other medical departments, referring cardi-ogists, primary care physicians, and rehabilitation clinics.

3.1.1. Composition of the Heart Team

The Heart Team is now an established feature of VHD programmes that has been formally endorsed by previous ESC/EACTS Guidelines ${}^{19,20}$ and corresponding organizations worldwide. ${}^{17}$

The value of the Heart Team approach has become increasingly apparent as options for the treatment of VHD have extended to in-clude high-risk and inoperable patients(most of whom now undergo transcatheter interventions), and low-risk and asymptomatic pa-tients(who derive prognostic benefit from increasingly safe proce-dures). Despite significant accumulation of data concerning the management of VHD over the last two decades, many patients in daily practice have clinical characteristics that do not match those of participants included in clinical trials. The Heart Team approach is therefore particularly helpful when there is uncertainty or a lack of strong evidence.

The Heart Team meeting facilitates balanced presentation of all appropriate options for medical, interventional, and surgical treatment, using tools and techniques for shared decision-making.

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The patient's preference plays a central role in this process, although the Heart Team recommendation should be based upon key objective medical considerations (particularly the relative risks and benefits of any procedure).

Meetings should take place on a regular basis with standardized minimum datasets(to ensure that all relevant information is avail-able) and appropriate administrative support (often provided by specialist nurses with expertise in the care of patients with VHD).In-person meetings of the full Heart Team may not be feasible for every patient, and local standardized protocols may be implemen-ted to facilitate swift decision-making for specific cohorts (e.g. eld-erly TAVI candidates or young patients with BAV disease). Equally,the need for Heart Team evaluation should not paralyse clinical decision-making, and ad hoc discussions remain appropriate in ur-gent situations.

Core members of the Heart Team include the cardiologist treating the patient(who is best placed to present their case and act as their ad-vocate), specialists in advanced cardiovascular imaging and peri-procedural guiding,21,22 surgeons, and interventional cardiologists with training and expertise in surgical and transcatheter valve proce-dures. Specialized nursing personnel play an essential role to improve patient information and education, as well as co-ordinate work-up and management steps in high-volume centres (Figure 1; Table 5).Cardiologists with expertise in heart failure (HF) and electrophysiology,as well as geriatricians, cardiovascular anaesthetists, and intensivins in-volved in peri-procedural care, should also be available to facilitate the discussion of particularly complex clinical scenarios when needed (ex-tended Heart Team) (Figure 1; Table 5).

Table 5 Requirements for a Heart Valve Centre

Requirements

Centre performing heart valve procedures with on-site interventional cardiology and cardiac surgery departments providing 24-h/7-day services.

Heart Team core members: Cardiologist with imaging expertise,interventional cardiologist, cardiac surgeon.

Additional specialists, if required (Extended Heart Team):

Specialized nursing personnel, HF specialist, electrophysiologist cardiovascular anaesthetist, geriatrician, and other specialists(e.g.intensive care, vascular surgery, infectious diseases, neurology,radiology).

The Heart Team must meet on a regular basis and work according to locally defined standard operating procedures and clinical governance arrangements.

A hybrid cardiac catheterization laboratory is desirable.

High volume for hospital and individual operators.

Multimodality imaging (including advanced echocardiography, CCT,MR,and nuclear techniques) and expertise in peri-procedural imaging guidance of surgical and transcatheter procedures.

Heart Valve Clinic for outpatient assessment and follow-up.

Data review: continuous monitoring, evaluation, and reporting of procedural volumes and quality indicators, including clinical outcomes, as well as PROMS complemented by local/external audits.

Education programmes targeting primary care and referring physicians,operators, and diagnostic and interventional imaging specialists.

CCT,cardiac computed tomography;CMR,cardic magnetic resonance;HF,heart failure;PROM, patient-reported outcome measure.

3.1.2. Procedural volume and clinical outcomes

The correlation between high institutional(and individual operator)volume and best procedural outcomes is intuitive, yet complex.Nevertheless, there is evidence of such a relationship for many cardio-vascular procedures including SAVR,23,24 surgical MV repair,25,26 mitral and tricuspid TEER,27-30 and TAVI(particularly in centres with an as-sociated high-volume SAVR programme).31-33 Studies have shown that an annualized operator volume of approximately 25 surgical mitral valve procedures,26 50 TAVIs(~100 per centre),33 a cumulative ex-perience of~50 M-TEER procedures per operator/centre,27 and a site volume of more than 20 T-TEERs/year30 are associated with im-proved technical and clinical outcomes. Higher institutional surgical volume is associated with lower complication rates,34-36 improved management,37 and better infrastructural support.38,39

National procedural activity varies widely between high-, middle-, and low-income countries, and it is therefore difficult to provide recommendations concerning the precise number of institutional or oper-ator procedures that is required for high-quality care, excellent facilities,and processes.Instead, a network approach that highlights the importance of centres performing a high volume of procedures(e.g. based upon quar-tiles in individual countries or regions) seems more suitable, with complex procedures concentrated in the centres with the highest volumes(Table 6).

Table 6 Complex procedures ideally performed in the most experienced Heart Valve Centres

|Transcatheter interventions|Surgical interventions| |---|---| |● Transfemoral TAVI in patients|● High-risk procedures (especially in patients with LV and/or RV| |- Low coronary ostia|- Low coronary ostia| |- Difficult femoral anatomy|- Redo procedures| |- Bicuspid valve|- Minimally invasive and robotic| |- Severe calcification protruding|valve surgery| |-Pure AV regurgitation|● Complex MV repair| |-Severe LV and/or RV impairment|- Barlow disease| |- Pure AV regurgitation|- Anterior or bileaflet prolapse| |- Multiple valve disease|- High risk of SAM| |- Complex coronary artery disease|- Severe MAC| |- Severe extracardiac disease|● AV repair| |(e.g. renal failure, PH)|● Ross procedure| |- Non-transfemoral TAVI|● Valve surgery combined with| |● Valve-in-valve (including|complex surgery of the aorta| |TAV-in-TAV)|● Endocarditis surgery| |- All leaflet modification procedures (BASILICA,LAMPOON etc.)|| |- PVL closure procedures|| |- Complex M-TEER ${}^{a}$|| |- Redo M-TEER procedures|| |- Complex or mitral valve-in-ring or|| |- Valve-in-valve, valve-in-MAC|| |·TMVI|| |- All tricuspid procedures||

AV, aortic valve: BASILICA, Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent lterogenic Coronary Artery obstruction; LAMPOON, Laceration of the Anterior Mitral leaflet to Prevent Outflow Obstruction:N; LV, left ventricular/left ventricle; LVOT, left ventricular outflow tract; MAC, mitral annular calcification; M-TEER, mitral transceter edge-to-edge repair; MV,mitral valve; PH, pulmonary hypertension; PVL: paravavular leak; RV,right ventricular/right ventricle; SAM, systolic anterior movement; TAV, transcatheter aortic valve; TAVI, transcatheter aortic valve implantation; TMVL, transcatheter mitral valve implantation.

<BeginOfPara>See Supplementary Table S2.

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Internal quality assessment(see dedicated document concerning TAVI from the ESC ${ }^{11}$ ), systematic recording, and public availability of the volume and outcome data of the performed procedures are essential.Participation in national or international registries should be encouraged. These consid-erations are of particular importance regarding asymptomatic low-risk pa-tients(where low mortality and procedural safety are paramount), those with multiple comorbidities(where the need for multidisciplinary collabor-ation is essential), and new techniques with a steep learning curve(where better results may be obtained at experienced centres).

There is a pressing need to ensure higher dispersion and adoption of interventions for VHD, especially(but not exclusively) in middle- and lower-income countries where rheumatic heart disease(RHD) remains the principal cause of VHD.42,43 Key strategies include awareness pro-grammes, increased public and medical education, simplified and im-proved diagnostic tools, and measures to reduce costs and facilitate access to evidence-based treatment options. ${}^{44}$

4.Imaging of patients with valvular heart disease

Multimodality imaging is now the standard approach in VHD management to determine the pathophysiology, assess severity,

<EndOfPara>plan interventions, and identify complications (Figure 2). The use of imaging for the assessment of each specific valve lesion is de-scribed in the corresponding sections. The role of imaging is trans-versal from diagnosis to follow-up and should encompass an integrative assessment.

4.1. Initial valve assessment

Comprehensive transthoracic echocardiography(TTE) is the first-line examination to confirm valve dysfunction, and determine the aetiology,mechanism, and severity of VHD, as well as cardiac chamber anatomy and damage.45,46 It should be performed by properly trained ima-gers.47-49 Quantitative imaging analysis(as opposed to visual) should be the goal in all patients with relevant VHD, complemented by quali-tative and semi-quantitative evaluation. The severity of VHD should be assessed using an integrative approach of all criteria checked for con-sistency. When TTE is of poor quality or inconclusive, transoesophageal echocardiography(TOE) and/or additional diagnostic imaging modal-ities should be applied(e.g. calcium scoring and anatomy of the valve using CCT). In specific clinical scenarios[e.g. thrombosis, pros-thetic valve dysfunction, endocarditis,mitral stenosis(MS),assessment of MV or TV anatomy]. TOE has a central diagnostic role.50,51

 Figure 2 Integrative imaging assessment of patients with valvular heart disease. 3D, three-dimensional; CAD, coronary artery disease; CCT, cardiac computed tomography; CMR: cardiac magnetic resonance; TOE; transoesophageal echocardiography; TTE, transthoracic echocardiography; VHD, valvular heart disease.

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Moreover, in patients with regurgitant lesions, particularly AR,CMR has gained key value in clinical practice.

4.2. Associated diseases and conditions

lmaging plays a crucial role in identifying associated diseases and condi-tions.The presence of concomitant left ventricular(LV) systolic or dia-stolic dysfunction, RV systolic dysfunction, red flags indicating cardiomyopathies(e.g. amyloidosis, hypertrophic cardiomyopathy),and aortopathy should prompt further examinations to ensure optimal risk stratification and VHD management. In addition to TTE, advanced imaging modalities, like CCT, may be required to assess the aorta,single-photon emission computed tomography(CT) for detection of ischaemia/necrosis, positron emission tomography(PET) for inflamma-tion, nuclear scintigraphy for cardiac amyloidosis, or CMR for tissue characterization.

4.3. Evaluation of valvular heart disease dynamics and variability

Serial imaging studies to detect changes over time, or variability due to haemodynamic conditions or initiation/up-tritation of medical ther-apy,are of utmost importance to guide decisions.The dynamic pat-tern of VHD may convey additional prognostic information.Exercise echocardiography helps to identify the cause of dyspnoea,unvel symptoms in apparently asymptomatic patients, identifies dy-namic changes of VHD severity, and can contribute to refinement of the indication for an intervention, especially for AS and mitral re-gurgitation(MR).52

4.4. Assessment of extravulavular cardiac consequences from valvular heart disease

Several studies investigating different valve lesions have established the relevance of extravularic cardiac damage in terms of progno-sis,53-55 recovery after intervention,56 and quality of life.57 The pres-ence of LV hypertrophy, left atrium(LA) dilatation, LV or RV dysfunction and/or remodelling, myocardial fibrosis, and pulmonary hypertension(PH) provide important prognostic information, and may influence the timing and type of treatment. Although not neces-sarily chronological in their order of appearance, the understanding of cardiac damage, particularly damage involving the LV, is essential to guide appropriate medical therapy before and after any interven-tion. Transthoracic echocardiography(TTE) including global longitu-dinal strain(GLS) and CMR can be particularly useful in that regard.58-60

4.5. Evaluation of eligibility, planning, and guiding of interventions

Transoesophageal echocardiography(TOE)(preferentially 3D) is the preferred tool for the assessment of suitability for aortic, mitral, and TV repair.45,49,61-63 Risk stratification for an intervention should inte-grate all the points mentioned above.

Transoesophageal echocardiography(TOE), including standard 3D views, is also the modality of choice to guide atrioventricular trans-catheter interventions and should be performed by specially trained interventional echocardiographers. 61,64 Cardiac computed tomog-raphy(CCT) is frequently used to evaluate the relationship of the

valve with adjacent structures[e.g. coronary arteries and left ventricu-lar outflow tract(LVOT)], the extension of calcification[e.g. in mi-tral annular calcification(MAC)], and for sizing of the prosthesis.CT angiography is frequently employed to evaluate the anatomy of surgical, arterial, or venous access routes and detect cardiac or extracardic complications(e.g. bleeding or embolic events).Coronary CT angiography(CCTA) is increasingly utilized to assess the presence of CAD.

5.Clinical evaluation of patients with valvular heart disease

5.1. Clinical examination

Patients with VHD can be either asymptomatic or present with a wide spectrum of symptoms, including acute or chronic HF. An initial meticu-lous history and a comprehensive physical examination of the patient with auscultation, documentation of clinical signs of HF such as dys-pnoea, impaired physical capacity and fatigue, peripheral oedema, and pleural effusion, as well as a systematic frailty assessment, are crucial.In addition, comorbidities and coexisting cardiac conditions should be documented(Figure 3). Particular attention should be given to recent changes in symptoms or physical findings indicating a potential worsen-ing of the valve lesion or ventricular function.

5.2. Assessment of comorbidities and risk stratification

Risk stratification of patients with VHD has been mainly developed based on surgical populations. The European System for Cardiac Operative Risk Evaluation II(EuroSCORE II)66,67(https://www.euroscore.org) and the Society of Thoracic Surgeons predicted risk of mortality(STS-PROM) score68(http://riskcalc.sts.org/stwestrskcalc/calculate) are the most commonly used scoring systems to estimate surgical risk. Both risk scores have been calibrated to pre-dict post-operative outcomes.69-71 The STS-PROM score is dynamic to account for changes in patient risk profiles, the type of procedure(aor-tic,mitral,and tricuspid),and outcomes over time.The outdated(logis-tic) EuroSCORE I model systematically overestimated surgical mortality.70,72

In patients considered for TAVI, surgical risk scores have lower ac-curacy and tend to overestimate the risk of events.73-75 Discrepancies between observed and predicted peri-procedural mortality after TAVI using surgical risk scores point towards a need for TAVI-specific scores. Models predicting short- and medium-term sur-vival specifically designed for TAVI are rarely used in daily clinical prac-tice due to limitations of their predictive performance.76-79 Specific scores have also been developed for patients undergoing mitral TEER(M-TEER),80-82 but the high heterogeneity of the population with MR limits their external validity and therefore routine clinical use so far.83 Recently, a dedicated clinical score has been calibrated and validated to stratify the risk associated with first-time and repeat isolated TV surgery (TRI-SCORE; https://www.tri-score.com/), and its use should be encouraged for patients with TV disease,84,85 as an al-ternative to the more complex Society of Thoracic Surgeons (STS)score for isolated TV surgery (https://isolatedtvsurgalc.research.sts.org/).

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 Figure 3 Central illustration. Patient-centred evaluation for treatment of valvular heart disease.

Other cardiac conditions and comorbidities-such as CAD, con-comitant multiple valve and aortic disease, and RV dysfunction, as well as chronic kidney disease(CKD)-are not always appropriately captured in risk models, even if they are known to impact outcomes. ${}^{86}$ Similarly, specific unfavourable characteristics like porcelain aorta, mo-bile aortic atheroma, and previous mediastinal radiation therapy in-crease the surgical risk, and therefore may favour transcatheter treatment options.Fraity,including nutritional state, represents another important determinant of outcomes after valve interventions, ${}^{87-89\text{a}}$ which can be evaluated using appropriate tools as summarized in a re-cent consensus statement. ${}^{90}$ Several methods have been proposed,from the simple Fried Frailty Index to more complex scores ${}^{91}$ such as the Hospital Frailty Risk Score, which has been validated in a large cohort of TAVI and M-TEER patients. ${}^{92}$

The use of PROMs that engage patients in the co-evaluation of their health and wellbeing is encouraged. Several scoring systems have been proposed and validated for reproducibility and association with clinical outcomes, like the Quality of Recovery 15-item PROM or the Kansas City Cardiomyopathy Questionnaire(KCCQ).93-95

5.3. Biomarkers

Biomarker levels indicating either cardiac wall stress[e.g. brain natri-uretic peptide(BNP)] or myocardial damage(e.g. troponin), in asymp-tomatic and symptomatic patients, may help to monitor VHD progress and determine the most appropriate timing of intervention.In patients with VHD, the natriuretic peptide ratio of measured BNP or N-terminal pro-B-type natriuretic protein

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(NT-proBNP) to upper limit of normal for age, sex, and assay]has been shown to be a powerful, independent, and incremental predictor of mortality. ${}^{96-98}$ In patients undergoing AV replacement,the accumulation of several elevated biomarkers of cardiovascular stress was associated with higher all-cause and cardiovascular mortal-ity, and a higher rate of repeat hospitalization. ${}^{99,100}$

5.4. Exercise testing

Because of the slow progression of valve lesions, patients may gradually limit their activity levels over several years and deny having actual symp-toms that can be unmasked by exercise testing.12 This is particularly im-portant in cases of AS, because once symptoms occur there is a sharp increase in the risk of sudden cardiac death, unless a valve intervention is performed.101-104 Exercise testing may provide additional informa-tion about the haemodynamic severity of VHD and help determine the risk and optimal timing of intervention by objectively evaluating functional capacity.101,103 Cardiopulmonary exercise testing has a prognostic role and can assist decision-making in patients with VHD of intermediate severity, particularly those with asymptomatic AR.101,105,106

Exercise echocardiography is used for the assessment of LV global and segmental function, pulmonary artery pressure, and aortic and mi-tral pressure gradients. 101,107 It also documents exercise-induced in-crease of MR and TR severity, especially in patients with secondary disease.108,109 Prognostic impact has been shown mainly for AS and MR.110,111 Misconceptions regarding its risk and tolerability contribute to the overall underuse of exercise testing in patients with VHD.12 des-pite data confirming its safety in most asymptomatic patients.112,113

5.5. Invasive investigations

5.5.1. Coronary angiography

Coronary artery assessment is recommended to evaluate the need for revascularization when valve surgery or an intervention is planned. The information regarding the existence of concomitant CAD should be available at the time of Heart Team discussion. CCTA is recommended as an alternative to coronary angiography to rule out CAD in patients who are at low or moderate risk of obstructive CAD.

Coronary blood flow and fractional flow reserve(FFR) are altered in the setting of concomitant VHD, and functional haemodynamic assess-ment of CAD in these patients is not well established.114-118

5.5.2. Cardiac catheterization

Right heart catheterization(RHC) should be performed in patients with equivocal echocardiographic findings, particularly those with MV dis-ease, as well as in all candidates for the treatment of severe TR. In ex-ceptional cases with unclear AS severity, it can be combined with measurements of the transaortic gradients allowing estimation of the aortic valve area(AVA). Right heart catheterization contributes to as-sess the repercussions of any left-sided VHD or LV impairment on the pulmonary circulation and right side of the heart. It provides infor-mation regarding volume state, cardiac output, and vascular resistance,differentiating between pre- and post-capillary PH, and should be ideally performed in evolemia.

Measurements of the pulmonary capillary wedge pressure v-wave can inform about MR severity, but are neither sensitive nor specific,and may also be increased if the compliance of the LA is reduced or in case of diastolic LV dysfunction, as in patients with MS or chronic HF.119

Similarly, the height of the right atrium(RA) v-wave, and the pres-sure curve mimicking the RV pattern('ventricularization' of the RA pressure), are signs of relevant TR, which are frequently accompan-led by increased RV diastolic pressure in case of associated RV dysfunction. In patients with severe TR, pulmonary vascular resist-ance(PVR) should be calculated to unmask pulmonary vascular dis-ease, which may not be captured by echocardiography due to RV systolic dysfunction or underestimation of pulmonary pressures be-cause of TR.

5.6. Patient-centred care and shared decision-making

Given that treatment of VHD typically involves several modalities and specialties, and may result in a complex and sometimes time-consuming decision-making process, patient education and informa-tion, using online material and face-to-face conversations, are essen-tial at each step. A clearly defined point of contact for all questions relating to the disease or type of treatments should be communicated to the patient and their relatives.120 The symptomatic and prognostic benefits, as well as the advantages and disadvantages of any treatment option, should be presented in an open and evidence-based manner.This includes mortality and risks of reintervention and complications(also over the long term), as well as recovery time and the need for cardiac, and if necessary psychological, rehabilitation until return to physical activity and work. Other issues to be discussed before the procedure include the need for oral anticoagulation(OAC) and its monitoring, as well as the noise generated by mechanical heart valves(MHVs). Information regarding centre experience and volume for a specific procedure should be provided. Misconceptions(e.g. subject-ive overestimation of the risk of surgery) should be addressed and po-tential interactions with individual lifestyle factors-including social activities, family and professional life, and hobbies-should be dis-cussed in detail.

The Heart Team recommendation regarding the treatment and its modality must be based on evidence and anatomical considerations,balancing the risks and benefits of available treatment options.16 The patient and patient's relatives need to be well informed about the ra-tionale leading to the Heart Team recommendation, and given ample time to share personal preferences.121 At the end of the process, a shared decision is made between the treating team and the informed patient and relatives(Figure 3).

6. Management of conditions associated with valvular heart disease

6.1. Diagnosis and management of coronary artery disease

The presence of CAD plays an important role in decision-making regarding the timing and modality of treatment, and should be assessed before Heart Team discussion. In patients with a low or moderate pre-test likelihood of obstructive CAD(≤50%),CCTA is recommended to rule out relevant CAD with high sensi-tivity. ${}^{122-124}$

Several studies have investigated the value of CCT angiography for CAD screening in elderly TAVI candidates. While sensitivity for the de-tection of obstructive CAD is high(95%-97%), specificity(68%-73%) is

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modest, mainly explained by the high prevalence of coronary artery cal-cification and AF in patients with severe AS, which limit imaging reso-lution and interpretability.125,126 If CCT angiography obtained during standard pre-TAVI evaluation is of sufficient quality to exclude relevant CAD, omission of invasive coronary angiography should be consid-ered.125-129

The value of invasive functional haemodynamic assessment of CAD in patients with severe AS may be limited, because AS impacts coronary haemodynamics. Therefore, caution is warranted in the interpretation of functional measurements in the presence of severe AS until more data are available.115,116

Recommendations for the management of chronic CAD associated with VHD are provided below(Recommendation Table 1), as well as in dedicated guideline documents. The indications for coronary artery bypass grafting(CABG) in patients undergoing surgery for the treat-ment of VHD are mainly based on observational data, which do not provide detailed information on the degree of stenosis and the com-plexity of CAD.130 It has been demonstrated that subendocardial blood flow in the myocardium improves early after SAVR, most likely due to improved cardiac output and reduction of LV wall stress.131 The pres-ence of CAD is associated with peri-operative and late adverse events in patients with AS undergoing SAVR132 that likely outweigh the in-creased risk of peri-procedural adverse events of combined SAVR and CABG compared with isolated SAVR. Indeed, in a large observa-tional study, patients with CAD demonstrated better long-term sur-vival after combined SAVR and CABG compared with SAVR alone,despite longer cross-clamp times.133 In patients with a primary indica-tion for valve surgery, CABG is recommended in patients with coron-ary artery stenosis of≥70% and should be considered in those with stenosis of≥50%-70%, given the opportunity of concomitant full revascularization.

The impact of CAD in patients undergoing TAVI remains under inves-tigation.The randomized Nordic Aortic Valve Intervention(NOTION)-3 trial compared a strategy of routine percutaneous coronary interven-tion(PCI) versus conservative management in 455 patients with severe symptomatic AS undergoing TAVI, who also had stable CAD and at least one stenosis of≥90% based on visual angiographic assessment or FFR of≤0.80 in a segment with≥2.5 mm reference diameter.134 Percutaneous coronary intervention was associated with lower risk of a composite endpoint event including all-cause death, myocardial in-farction or urgent revascularization at a median follow-up of 2 years.Exploratory analyses suggest that the increased risk in the conserva-tive treatment arm was driven by differences in the risk of myocardial infarction and urgent revascularization in patients with a diameter stenosis of≥90%, rather than those with positive FFR and stenosis of<90%.The risk of bleeding was higher in the PCI than in the conservative treatment group. Another multicentre RCT, the PercutAneous Coronary inTervention pur to transcatheter aortic VAlve implantaION(ACTIVATION) trial, was discontinued due to slow recruitment.135 In this underpowered and thus inconclusive trial, a routine PCI strategy of $\geq 70\%$ stenoses in main epicardial vessels (or $\geq 50\%$ ) protected left main or vein graft) did not meet non-inferiority compared with conserva-tive CAD treatment with respect to the composite of all-cause death and rehospitalization; moreover, PCI was associated with higher bleeding rates. Observational data show that TAVI can be performed safely in pa-tients with untreated CAD with low short- and long-term rates of acute coronary syndrome and unplanned coronary revascularization.135-139 In two recent meta-analyses of mostly observational data, PCI was not associated with a mortality benefit in patients with chronic CAD undergoing TAVI.140,141

Optimal timing of PCI in patients undergoing TAVI remains yet to be determined. In NOTION-3, PCI was performed before TAVI in the majority of the patients(concomitantly or shortly after in only 26% of the patients). Decision-making concerning the timing of PCI should take into account the type of valve used for TAVI and the complexity of the coronary lesions.142,143 Valves with a high frame-particularly in the context of a narrow aortic root, commis-sural misalignment, or valve-in-valve procedures-can pose chal-lenges for coronary access following TAVI.144,145 The presence of significant CAD should therefore be considered for optimal transcatheter valve selection and reinforces the importance of opti-mized implantation technique and commissural alignment.143,146 Several RCTs comparing the value and timing of PCI with medical therapy are ongoing(NCT04634240, NCT04310046, and NCT05078619).

Based on the available data, PCI should be considered in patients with a primary indication to undergo TAVI and high-grade(≥90%) coronary artery stenosis in large vessels of≥2.5 mm. In patients with stenosis of≥70%, PCI may be considered based on symptom status.142,143 In pa-tients with ischaemic ventricular SMR, surgical revascularization of CAD has been associated with MR reduction147 and favourable clinical outcomes in observational studies.148,149 According to very limited data, improvement of SMR may occur in a minority of patients(about one-third) after PCI, which may therefore be considered prior to MV intervention.150

For patients with VHD presenting with acute coronary syndrome,treatment decisions should be made according to the most recent ESC Guidelines.151 In patients presenting with non-ST-segment eleva-tion acute coronary syndrome, it may be particularly challenging to determine the leading cause of elevated troponim levels, which are also frequently observed in decompensated VHD. Therefore, the treatment strategy should be determined by the Heart Team, taking into account symptoms, as well as coronary, valve, and access anatomy.136,138,139

Recommendation Table 1-Recommendations for the management of chronic coronary syndrome in patients with valvular heart disease(see also Supplementary data online, Evidence Table 1)

|Recommendations|Classa|Levelb| |---|---|---| |Diagnosis of coronary artery disease||| |CCTA is recommended before valve intervention in patients with moderate or lower(≤50%) pre-test likelihood of obstructive CAD.122-124||| |Invasive coronary angiography is recommended before valve intervention in patients with high and very high(>50%) pre-test likelihood of obstructive CAD.||C| |Invasive coronary angiography is recommended in the evaluation of CAD in patients with severe ventricular SMR.|I|C| |Omission of invasive coronary angiography should be considered in TAVI candidates, if procedural planning CT angiography is of sufficient quality to rule out significant CAD.125-129|lla|B|

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|Indications for myocardial revascularization|| |---|---| |CABG is recommended in patients with a primary indication for valve surgery and coronary artery stenosis≥70%.°|I| |CABG should be considered in patients with a primary indication for valve surgery and coronary artery stenosis≥50%-70%.|lla| |PCI should be considered in patients with a primary indication to undergo TAVI and≥90% coronary artery stenosis in segments with a reference diameter≥2.5 mm.|lla| |PCI may be considered in patients with a primary indication to undergo transcatheter valve interventions and coronary artery stenosis≥70% in proximal segments of main vessels.135-137|IIb|

CABG, coronary artery bypass grafting; CAD, coronary artery disease; CCTA, coronary computed tomography angiography; CT, computed tomography; PCI, percutaneous coronary intervention; SMR, secondary mitral regurgitation; TAVl, transcatheter aortic valve implantation.

${}^{a}$ Class of recommendation.

bLevel of evidence.

$^{*}$ Stenosis $\geq 50\%$ can be considered for left main stenosis.

6.2. Atrial fibrillation

The interplay between AF and VHD is complex, and has an essential role in the prognosis and evolution of VHD during the patient's lifetime.Valuvular heart disease is independently associated with AF and almost one-third of patients with AF have a history of VHD.152 Conversely,AF is the main trigger of the development of atrial secondary MR and TR. In a recent cohort study,8% of individuals with AF developed mod-erate or severe TR within 3 years of follow-up compared with only 2% in those in sinus rhythm.153 While disturbed annular dynamics have been postulated,150,154 the exact pathophysiology leading to secondary atrioventricular VHD in some, but not all patients with AF remains largely unclear.

Detailed recommendations on the anticoagulation management of patients with VHD and AF are provided below(Recommendation Table 2) and in Section 14, as well as in specific Guidelines.7 Patients with a combination of VHD and AF have a high incidence of thrombo-embolic or bleeding complications.155 DOACs have replaced vitamin K antagonists(VKAs) in most clinical scenarios and are recommended for patients with VHD presenting with AF, except for patients with a MHV or mitral stenosis with a valve area≤2.0 cm2. The use of apabanin,156 dibagtran,157 edoxaban,157 and rivaroxaban159 is supported by sub-group analyses of large RCTs. Recommendations regarding the antith-rombotic treatment of patients with MHVs and biological heart valves(BHVs) are described in Section 14 of these Guidelines.

<BeginOfPara>In the Left Atrial Appendage Occlusion Study(LAAOS) III trial, sur-gical left atrial appendage occlusion(LAAO) in patients with AF and a CHA2DS2-VASc[congestive heart failure or left ventricular dysfunc-tion,hypertension,age≥75(doubled),diabetes,stroke(doubled),vasc dular disease,age 65-74, sex category(female)] score of≥2 points undergoing cardiac surgery was associated with a 33% reduction of the risk of stroke or systemic embolic in a mean follow-up of 3.8 years.160 These findings were confirmed by a large meta-analysis in-cluding four RCTs.161 A subanalysis of LAOSA III showed that the bene-fit of LAAO remains consistent irrespective of the use of VKAs or DOACs, as well as in the absence of OAC(although representing

<EndOfPara>only 10% of the included population).162 In an RCT including patients with severe AS and AF undergoing TAVI, concomitant transcatheter LAAO was non-inferior to medical therapy with respect to a composite primary endpoint including all-cause mortality,stroke,and major bleed-ing at 2 years.Of note,rates of major or life-threatening bleeding were similar in the two groups and arterial or venous thromboembolisms more frequent in the TAVI/LAAO arm, leaving uncertainty regarding the usefulness of combining both procedures.163

Recommendation Table 2-Recommendations for the management of atrial fibrillation in patients with native valvular heart disease(see also Supplementary data online,Evidence Tables 2 and 3)

|Recommendations|Classa|Levelb| |---|---|---| |Anticoagulation||| |DOACs are recommended for stroke prevention in preference to VKAs in patients with AF and AS,AR, or MR who are eligible for OAC.156-159,164|I|A| |The use of DOACs is not recommended in patients with AF and rheumatic MS with an MVA≤2.0cm2.165|Ⅲ|B| |Surgical interventions||| |Concomitant surgical ablation is recommended in patients undergoing MV surgery with AF suitable for a rhythm control strategy to prevent symptoms and recurrence of AF,according to an experienced team of electrophysiologists and arrhythmia surgeons.166-173|I|A| |Surgical closure of the LA appendage is recommended as an adjunct to OAC in patients with AF undergoing valve surgery to prevent cardioembolic stroke and systemic thromboembolism.160-1621|I|B| |Concomitant surgical ablation should be considered in patients undergoing non-MV surgery with AF suitable for a rhythm control strategy to prevent arrhythmia surgeons.167,169,174,175|lla|B|

AF,atrial fibrillation;AR, aortic regurgitation;AS, aortic stenosis; DOAC, direct oral anticoagulant; LA, left atriumleft atrial; MR,mitral regurgitation;MS,mitral stenosis;MV,mitral valve;MVA,mitral valve area;OAC,oral anticoagulation;VKA,vitamin K antagonist.

${}^{b}$ Level of evidence.

6.3. Cancer and radiation therapy

Valvular heart disease is commonly associated with cancer and repre-sents a well-known long-term side effect of intensive radiation ther-apy^{176} for treatment of Hodgkin or non-Hodgkin lymphoma, breast cancer, and other therapeutic malignancies.177 Clinically significant VHD most commonly appears decades after radiotherapy. The incidence of radiation-induced VHD is increasing owing to longer survival of pa-tients with cancer. Risk factors are summarized in Supplementary data online, Table S1. Patients at risk should be screened for VHD using TTE 10 years after radiation exposure and followed up every 5 years thereafter.178

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Radiotherapy may lead to aortic and/or valvular calcification, CAD of proximal segments, restrictive cardiomyopathy, pericardial adhesions and calcifications with constriction, restrictive lung disease, chest wall scarring, and impaired wound healing, especially in patients who under-went radiation by means of older techniques(>20 years ago). The above factors complicate any surgical approach and increase the operative risk,which is underestimated by traditional risk scores.179-181 TAVI is pro-posed as an alternative for patients presenting with radiation-induced AS in the 2022 ESC Guidelines on cardio-oncology 182 based on favourable,but limited, observational data,183,184 because this category of patients has been excluded from RCTs.183,184 Furthermore, M-TEER in patients presenting with radiation-induced MV disease with MR is often limited by thickened leaflets with restricted movement and subsequent risk of iatrogenic stenosis.

In patients with active or stable cancer and severe AS, both TAVI and SAVR can be considered based on life expectancy, age, prognosis, and disability following cancer treatment, with a trend towards more TAVI utilization.185 TAVI procedural complication rates appear similar com-pared with those of control subjects without cancer.186 To avoid futile-ity,treatment decisions discussed by the Heart Team should involve the treating oncologists.5,182

6.4. Prophylaxis of rheumatic fever

Rheumatic heart disease remains the most common cause of death from VHD worldwide.187 Prevention should preferentially target the first occurrence of acute rheumatic fever. Correct diagnosis and early antibiotic treatment of group A Streptococcus throat or skin infection is key for primary prevention. Large-scale screening combined with prophylaxis in children or adolescents with latent RHD appears to be an effective strategy to reduce the risk of disease progression and RHD prevalence.188-190 In patients with established RHD, secondary long-term prophylaxis with benzathine benzyl penicillin 1.2 million international units(IU) every 3-4 weeks over 10 years is recom-mended to prevent recurrent episodes, especially in children and ado-lescents. Long-term prophylaxis into adulthood should be considered in high-risk patients according to the severity of VHD and exposure to group A Streptococcus.191,192

6.5. Cardiogenic shock and acute heart failure

Acute presentation or decompensation of VHD can result in cardio-genic shock due to rapid haemodynamic deterioration and altered car-diac function. Alternatively, pre-existing VHD can be a bystander of an acute cardiovascular condition further exacerbating circulatory impair-ment until the occurrence of cardiogenic shock. In this setting, assess-ment of the severity of VHD, as well as its contribution to acute HF,may be difficult. Evidence concerning acute VHD management in this context is scarce and only exists for the MV and AV.193,194

Hospital admission for acute compensated AS is a frequent prob-lem seen in up to 25% of AS hospitalizations. However, only a mi-nority of these patients(1.6%-3.2%) present with cardiogenic shock. ${}^{197,198}$ While intensive care treatment remains the cornerstone of haemodynamic stabilization and support, an intervention should be considered early, because it represents the only way to reverse pro-gressive organ dysfunction due to low cardiac output. Balloon aortic valuloplasty has been used in this context in the past, but has been largely replaced by TAVI in recent years, due to the high risk of severe AR and mortality in the acute setting. ${}^{199-201}$ Several large observational studies have established the feasibility of TAVI in patients with

cardiogenic shock with similar device success, even if LVEF is low, al-though 30-day mortality remains higher(13%-19%) compared with routine TAVI.194,197,198 Surgery represents the preferred treatment in patients with acute AR, while TAVI has only been described in indi-vidual cases or patients with a failed surgical valve(valve-in-valve). Fast pacing over a temporary pacemaker lead shortens the diastole and may temporarily improve hemodynamics until the intervention.

Except for papillary muscle rupture, acute PMR rarely leads to car-diogenic shock and may be best treated by surgical valve repair or re-placement. In contrast, increasing evidence supports the use of M-TEER in patients with acute ventricular SMR, particularly following acute myocardial infarction, due to lower mortality compared with sur-gery or medical treatment in propensity-matched analyses.194,202,203 This strategy might also be helpful to facilitate weaning from mechanical circulatory support.

6.6. Palliative care

In some patients with advanced VHD not qualifying for surgical or transcatheter therapies, medical HF treatment remains the only, and sometimes best, available option. These patients usually present late,have extensive cardiac damage, develop terminal HF during the natural evolution of VHD, and are ineligible for mechanical circulatory support or heart transplantation(HTx). Early implementation of expert multi-disciplinary pallative and end-of-life care, with the support of HF spe-cialists, 204-206 reduces the number of hospitalizations and improves quality of life and symptom burden, in particular dyspnoea, pain, and anxiety.207 Continuous co-ordination between all involved subspecial-ties, and transparent communication with the patient and their rela-tives, are key to ensure high quality of care.

7. Aortic regurgitation

7.1. Prevalence and aetiology

Chronic AR is mainly due to intrinsic abnormalities of the AV cusps and or secondary to progressive dilatation of the aortic root and/or ascend-ing aorta. In high-income countries, degenerative changes are the lead-ing cause of AR, while RHD is more frequent in middle- and low-income countries.12 Acute presentations are usually related to in-fective endocarditis or extension of aortic dissection into the aortic root. Chronic pure severe AR is more frequent in men and is associated with BAV and concomitant dilatation of the aorta in more than one-half of cases.208

7.2. Evaluation

During stepwise AR evaluation, the following aspects should be ad-dressed: the severity of AR, its mechanism, and aetiology; the haemo-dynamic impact on LV function and pulmonary pressure; and evaluation of the ascending aorta. While echocardiography is the first-line modality, CMR and CT are more accurate for the measurement of specific parameters(Figure 4). The results of the evaluation need to take into consideration the haemodynamic condition of the patient,particularly the blood pressure(BP), since high pressures can lead to overestimation of the regurgitant volume(RVol).

Assessment of AR severity with TTE follows an integrative approach considering qualitative, semi-quantitative, and quantitative parameters,but remains challenging. ${}^{45}$ Consequences of AR on LV size and function must be carefully assessed. Cut-offs for intervention are mostly based on two-dimensional(2D) echocardiographic measurements.However, 3D echocardiography and CMR allow more accurate

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evaluation of LV volumes and LVEF than 2D echocardiography, and are useful in borderline cases(Figure 4).45,209 Strain imaging can be helpful in identifying subclinical LV dysfunction ${}^{209-211}$ and can therefore influence the optimal timing of intervention. Reduced longitudinal strain and con-tractile reserve at stress echocardiography, ${}^{212}$ elevated biomarkers(BNP),213,214 and the presence of myocardial fibrosis detected by CMR need to be integrated in the decision-making process, even if not entirely validated yet. ${}^{209}$

Given its close relationship with AV function, accurate measure-ments of the aortic diameter are required at all levels: the annulus,sinuses of Valsalva, sinotubular junction, and ascending aorta. ${}^{8,215,216}$ The largest diameter is used to indicate the specific aortic pheno-type: root phenotype, ascending phenotypes, and extended or mixed forms(see Supplementary data online, Figure S1). ${}^{8}$ The mech-anism of AR and aortic diameters determine suitability for AV spar-ing or repair.

 Figure 4 Imaging assessment of patients with aortic regurgitation. AR, aortic regurgitation; CCT, cardiac computed tomography; CMR, cardiac mag-netic resonance; EDV, end-diastolic velocity; EROA, effective regurgitant orifice area; LV, left ventricle/left ventricular; LVEF, left ventricular ejection fraction;LVESDi,left ventricular end-systolic diameter indexed to body surface area;LVESVi,left ventricle end-systolic volume indexed to body sur-face area;LVOT,left ventricular outflow tract;PHT, pressure half-time; RF,regurgitant fraction; RVol;regurgitant volume.aSee Recommendation Table 3 for specific cut-offs.

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The morphology of the AV represents a critical aspect in the diagno-sis and treatment of AR. Pure AR in the context of BAV uncommon manifests with normal aortic diameters, being more often associated with a dilated ascending aorta and/or root. It is important to define the valve phenotype to determine the repair probability and long-term result of AV repair or AV-sparing procedures. The degree of symmetry is an important predictor of BAV reparability with better long-term re-sults in more symmetric phenotypes. ${}^{219-221}$

7.3. Medical therapy

Medical therapy, especially angiotensin-converting enzyme-inhibitors(ACE-Is) or dihydropyridine calcium channel blockers, may provide symptomatic improvement in individuals with chronic severe AR for whom surgery is not feasible or contraindicated. The value of ACE-Is or dihydropyridines in delaying surgery in the presence of moderate or severe AR in asymptomatic patients has not been established, and their use is not recommended for this indication. The use of beta-blockers increases the length of the diastole and therefore the RVol,and should be used with caution if indicated for another reason.However, beta-blockers can be used along with ACE-Is or angiotensin receptor blockers(ARBs) after surgery, if indicated(systolic HF or heart rate control).

7.4. Indications for intervention

Acute severe AR usually requires immediate surgery depending on the aetiology, such as infective endocarditis or spontaneous, traumatic,or iatronic aortic dissection.5,8 Surgery for the treatment of chronic severe AR is indicated depending on symptoms and/or the effects of the RVol on LV size and function(see Recommendation Table 3 and Figure 5).The presence of associated aortic dilatation dictates surgery,irrespective of AR severity. When the patient is symptomatic and AR severe, surgery is recommended unless the anticipated surgical risk is prohibitive.224-228 Concomitant surgical treatment of severe AR is also recommended, irrespective of symptoms, in patients requiring CABG, ascending aorta surgery, or any other cardiac surgical procedures.229,230

For the asymptomatic patient with severe AR, indications for surgery are based on the degree of functional impairment of the LV(LVEF≤50%, left ventricular end-systolic diameter(LVESD) $>50~mm$ , or left ventricular end-systolic diameter indexed to body sur-face area(BSA)(LVESDi) $>25~mm/ m^{2}$ , especially in those with small BSA(BSA<1.68 m2) and elderly patients with low ventricular compli-ance].226,228,231-234 If surgery is deemed low risk, there is observational evidence from echocardiographic studies that early intervention might be beneficial for long-term prognosis when LVEF is≤55%, LVESDi is>22 mm/m2, and/or left ventricular end-systolic volume indexed to BSA(LVESVi) is>45 mL/m2.235-239 A volumetric cut-off value of LVESVI≥43 mL/m2 using CMR was recently proposed to guide the management of asymptomatic patients ${}^{240,241}$ and appears to have bet-ter predictive value than LV diameter. ${}^{242}$ Surgery may also be discussed in selected low-risk asymptomatic patients with significant LV dilatation(left ventricular end-diastolic diameter>65 mm) and progressive in-crease of LV diameters and/or decrease of LVEF during follow-up.Exercise testing should be performed, when feasible, in patients with severe AR who do not report symptoms and do not meet criteria for surgery. ${}^{212}$

AV replacement is still the standard surgical approach in most AR cases(see Section 14.1 regarding prosthesis type considerations).However, owing to a better understanding of the pathophysiology of

the aortic root(see Supplementary data online, Figure S1) paralleled with favourable long-term results, valve-sparing aortic root replace-ment(VSARR) and AV repair are increasingly performed in centres with appropriate expertise(Figure 5). 243-255 In patients with root en-largement and good tissue quality(i.e. pliable AV cusps with normal mo-tion), a valve-sparing procedure has been demonstrated to be superior to the use of a composite valve graft(Bentall procedure) in terms of long-term mortality and overall morbidity(thromboembolism and endocarditis, with similar need for reoperation),250-253,255-257 and should be therefore favoured by experienced centres, in particular in patients with an estimated long life expectancy.258 Valve preserva-tion or valve repair should also be considered for patients with BAV based on age, anatomical presentation, and centre experience(Figure 5). 220,245,246,259

When performed by experienced surgeons in well-selected young individuals, pulmonary autograft implantation(Ross operation) may also be a good alternative to prosthetic valve replacement. ${}^{260-263}$

TAVI may be considered at experienced centres for selected patients with AR who are ineligible for surgery. The use of non-dedicated trans-catheter values for this indication is off-label and associated with an in-creased risk of valve malpostioning and residual AR, with consecutively higher rates of second valve implantation(about 10%) or surgical con-version, as compared with TAVI in AS.264-268 Dedicated devices appear to minimize the risk of valve migration and residual AR in selected pa-tients, but are associated with a high new permanent pacemaker im-plantation rate(24%).267-269

Aortic dilatation is closely linked to AR. Dedicated ESC Guidelines give guidance regarding the evaluation and management of aortic root and ascending aortic dilatation.8 The aortic phenotype(see Supplementary data online, Figure S1), degree and rate of progression of aortic dilatation, and the underlying aetiology all affect timing of sur-gery, with the main indication being maximum aortic diameter. ${}^{270-272}$ Dilation of the aortic root, which typically occurs in Marfan syndrome and other patients with connective tissue disease, has a worse progno-sis compared with isolated dilatation of the ascending aorta and re-quires closer surveillance.270-272 Surgery is recommended in all patients with a maximal aortic root or ascending aeurysm diameter of≥55 mm. In the presence of additional risk factors, a threshold of 50 mm may be considered for selected low-risk patients treated at ex-periences centres.8 If the patient has an established indication for AV surgery(due to AR or AS), concomitant surgery of the aortic root or the ascending aorta should be considered at a diameter of≥45 mm. This threshold has been more clearly demonstrated in pa-tients with BAV and should also be based on the patient's height or specific intraoperative findings, such as the shape and thickness of the aortic wall.

7.5. Follow-up

A multimodality imaging approach 45,274 and biomarkers like BNP213,214 might help identify patients at increased risk of LV damage early and guide the appropriate timing of intervention. Yearly follow-up is re-commended in asymptomatic patients with severe AR. Closer follow-up(3-6 months) is recommended for those approaching thresholds for surgery, or showing a progressive dilatation of the LV or decrease of LVEF. Cardiac magnetic resonance can be especially useful in such a setting. Patients with moderate AR should be followed on a yearly ba-sis, with echocardiography performed every 2 years.

When a dilated ascending aorta is initially diagnosed by TTE, a multi-sis, with echocardiography triggered CCT/CMR scan is recommended

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 Figure 5 Management of patients with aortic regurgitation. AR, aortic regurgitation; AV, aortic valve; LVEF, left ventricular ejection fraction; LVESD,left ventricular end-systolic diameter; LVESDi, left ventricular end-systolic diameter indexed to body surface area; LVESVi, left ventricular end-systolic volume indexed to body surface area; SAVR, surgical aortic valve replacement; TAVI,transcatheter aortic valve replacement; VSARR, valve-sparing aor-tic root replacement. ${}^{a}$ Indications for surgery on the root/ascending aorta are described in the 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases. ${}^{b}$ Concomitant replacement of the aortic root or ascending aorta should be considered if the maximal diameter is $\geq 45~mm$ and the predicted surgical risk is low.

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to confirm maximal diameter, rule out isolated single sinus dilatation,and provide a baseline reference. When the baseline aortic diameter is>45 mm, a second TTE examination is recommended at 6 months to confirm the stability of the finding, followed by serial examinations on a yearly basis thereafter. ${}^{275}$ Any increase of>3 mm should be vali-dated by CT angiography/CMR and compared with baseline data. ${}^{275}$ After repair of the ascending aorta, patients with Marfan syndrome and other connective tissue diseases remain at risk for dissection of un-treated portions of the aorta, and require lifelong regular multidisciplin-ary follow-up at an expert centre. ${}^{8}$

7.6. Special patient populations

Patients with concomitant VHD and those with AS combined with AR are discussed in Section 13.3.3. In patients with moderate AR and indica-tion for CABG or MV surgery, the decision to treat the AV should be discussed by the Heart Team based on the aetiology of AR and other clinical factors, like the estimated life expectancy and the operative risk,as data show that progression of moderate AR may be very slow.276

The presence of aortic dilation and AR in asymptomatic patients poses the problem of limiting the level of physical activity, but consist-ent data are lacking. Current recommendations for participation in competitive sport are restrictive, especially regarding isometric exer-cise in patients with connective tissue disease, ${}^{277}$ while a more liberal approach is likely to be appropriate in other patients.

Given the familial risk of thoracic aortic aneurysms, screening with appropriate imaging studies and testing for genetic abnormalities in first-degree relatives is indicated in patients with connective tissue dis-ease. ${}^{278}$ Since aortic dilation is present in $\sim 10\%$ of first-degree relatives of patients with a BAV, it is also considered appropriate to encourage echocardiographic screening in this specific population.

Recommendation Table 3-Recommendations on in-dications for intervention in severe aortic regurgitation(see also Supplementary data online, Evidence Tables 4-8)

|Recommendations|Classa|Levelb| |---|---|---| |Severe aortic regurgitation||| |AV surgery is recommended in symptomatic patients with severe AR regardless of LV function.224-228|I|B| |AV surgery is recommended in asymptomatic patients with severe AR and LVESD>50 mm or LVESD>25 mm/m2[especially in patients with small body size(BSA<1.68 m2)] or resting LVEF≤50%226,228,231,233,234|I|B| |AV surgery is recommended in symptomatic and asymptomatic patients with severe AR undergoing CABG or surgery of the ascending aorta.|I|C| |AV repair should be considered in selected patients with severe AR at experienced centres, when durable results are expected.220,245,246,259|lla|B| |AV surgery may be considered in asymptomatic patients with severe AR and LVESD>22 mm/226,228,231-234 or LVESV<45 mL/m2 [especially in patients with small body size(BSA<1.68 m2)] or resting LVEF≤50%226,228,231,233,234|IIb|B| |risk is low.|||

|TAVI may be considered for the treatment of severe AR in symptomatic patients ineligible for surgery according to the Heart Team, if the anatomy is suitable. 264,265,268,269| |---| |Concomitant surgery of the ascending aorta| |Valve-sparing aortic root replacement is recommended in young patients with aortic root dilatation at experienced centres, when durable results are expected. 247,250-253,255| |When AV surgery is indicated and the predicted surgical risk is low, replacement of the aortic root or ascending aorta should be considered if the maximal diameter is≥45 mm.d|

AR,aortic regurgitation;AV,aortic valve;BSA,body surface area;CABG,coronary artery bypass grafting; CMR, cardiac magnetic resonance; LV, left ventricle/left ventricular; LVEF,left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter or indexed to BSA; LVESVi, left ventricular end-systolic volume indexed to BSA; TAVI, transcatheter aortic valve implantation.

${}^{a}$ Class of recommendation.

bLevel of evidence.

${}^{a}$ Using echocardiography or CMR.

${}^{a}$ Considering age, BSA, the aetiology of the valvular disease, the presence of a bicuspid AV,and the intraoperative shape and thickness of the ascending aorta.

8. Aortic stenosis

8.1. Prevalence and aetiology

Even if AS is the most common primary valve lesion referred for inter-vention in Europe and North America,12 underdiagnosis and under-treatment remain relevant concerns. ${}^{10}$ Degenerative pathogenesis with cusps calcification is most common in developed countries and prevalence is rising rapidly because of the ageing population.BAVs, or more rarely unicuspid AVs, are prone to earlier degeneration,constitute the dominant valve morphology in younger patients requir-ing AV replacement, and are frequently associated with dilatation of the aortic root or ascending aorta.280,281 In low- and middle-income coun-tries, rheumatic aetiology remains frequent and AS usually presents combined with rheumatic MV disease.

8.2. Evaluation

8.2.1. Echocardiography and cardiac computed tomography

Aortic stenosis is a disease slowly evolving from mild to severe valve obstruction as a consequence of increasing valve fibrosis and calcifi-cation, although progression accelerates as haemodynamic severity increases. ${}^{283}$

Echocardiography is key to confirm the diagnosis and allows compre-hensive assessment of the anatomy and severity of stenosis. Evaluation of the haemodynamic consequences on cardiac function and geometry,and the detection of aortic pathology or concomitant valve disease,provide important prognostic information that may influence manage ment.284 Staging of extravularg damage has been proposed. ${}^{53}$ but it may be difficult to attribute other cardiac abnormalities to AS itself,because comorbidities are frequent in patients with AS and the observed damage may not occur in the expected chronological se-quence. However, the detection of concomitant cardiac conditions[e.g. HF with preserved EF(HFpEF), amyloidosis, or hypertrophic

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cardiomyopathy] may help to optimize medical treatment before and after valve intervention.285,286

Current European recommendations for the echocardiographic grading of AS rely on measurement of the mean pressure gradient(most robust parameter), peak transvalvular velocity(Vmax), and effect-ive AVA. Although AVA is theoretically the ideal parameter for asses-sing severity, there are numerous technical limitations associated with its calculation.284,287

Aortic stenosis may be further categorized according to flow state based on stroke volume index(Svi) when there is discordance between echocardiographic parameters(Figure 6). A threshold of 35 mL/m2 is conventionally accepted to discern low from normal flow, although sex-specific thresholds have been proposed. ${}^{292}$

#

● High-gradient AS[mean gradient≥40 mmHg, V_{max}≥4.0 m/s, AVA≤1 cm2(or≤0.6 cm2/m2)] is considered severe irrespective of LV function and flow conditions.

Discordant criteria:

● Low-flow, low-gradient AS with reduced LVEF(mean gradient<40 mmHg,AVA≤1cm2,SVi≤35mL/m2,LVEF<50%).

● Low-flow, low-gradient AS with preserved LVEF(mean gradient<40 mmHg,AVA≤1cm2,SVi≤35mL/m2,LVEF≥50%).

● Normal-flow, low-gradient AS with preserved EF(mean gradient<40 mmHg,AVA≤1cm2,SVi≥35mL/m2,LVEF≥50%).

● Discordant high-gradient AS(mean gradient≥40mmHg,AVA>1cm2).

Patients with discordant normal-flow, low-gradient AS usually have moderate stenosis. ${}^{293-295}$ Discordant high-gradient AS is considered severe if not caused by a reversible high-flow status. ${}^{296-298}$

In patients with low-flow, low-gradient AS with reduced LVEF, dobu-tamine stress echocardiography (DSE) can help to discriminate be-tween pseudo-severe and true severe AS in the presence of flow reserve(increase stroke volume of≥20%).289,299

Cardiac computed tomography calcium AV scoring is readily avail-able and provides important adjunctive information in patients with low-flow, low-gradient AS because it correlates with haemodynamic severity, progression, and clinical outcomes.300,301 Values of>2000 Agatston units(AU) in men and>1200 AU in women indicate severe AS with high sensitivity and specificity(~85%).302,303 While higher thresholds(men>3000 AU, women>1600 AU) are very specific, se-vere AS becomes unlikely in patients with calcium AV scoring of<1600 AU in men and<800 AU in women.284,302,303 Cautious inter-pretation is required in patients who can develop severe AS without pronounced AV calcification such as in BAV, concomitant amyloidosis,and predominantly fibrotic stenosis associated with post-rheumatic,radiation-induced and inflammatory disease.304-308

In low-flow, low gradient AS with reduced LVEF, CCT AV calcium scoring and DSE provide complementary information. If findings are equivocal, an integrated assessment considering all available clinical,morphological, and haemodynamic factors is required.

8.2.2. Additional diagnostic and prognostic parameters

The ratio of the LVOT to the AV Doppler jet velocity time integral(VTI, dimensionless index or velocity ratio) does not require

calculation of LVOT area and may assist evaluation when other para-meters are equivocal(<0.25 suggests that severe AS is highly likely). 309 Assessment of GLS can be useful for risk stratification 310 and evalu-ation of extravularic cardiac damage.311,312 It provides additional infor-mation regarding LV function and a threshold of-15% may contribute to identifying patients with severe asymptomatic AS at increased risk of clinical deterioration or premature mortality.

Estimated valvuloarterial impedance has been shown to be prognostic of adverse clinical outcomes before and after valve replacement.

Transsoesophageal echocardiography(TOE) allows morphological evaluation of the valve, planimity of AVA and assessment of potential sub-valvular obstruction(unless there is acoustic shadowing caused by calcifi-cation), and evaluation of concomitant valve disease, and can be of value for per-procedural imaging in challenging clinical or anatomical scenarios.316

Natriuretic peptides can be used to arbitrate the sources of symp-toms in patients with multiple potential causes and help to identify those with high-risk asymptomatic AS who may benefit from early intervention. ${}^{97,317}$

Exercise testing can unmask symptoms and haemodynamic intolerance(fall in BP>20 mm Hg) and is recommended for risk stratification in asymptomatic patients with severe AS. 102,318 Exercise echocardiography may provide additional prognostic information by assessing the increase in mean pressure gradient and change in LV function. 319 Cardiopulmonary exercise testing, eventually complemented by echocardiography, can help to uncover cardiac dysfunction in asymptomatic patients, discrimin-ate cardiac from pulmonary limitation or deconditioning in patients with non-specific symptoms, and inform risk stratification.105,106,320,321

Cardiac magnetic resonance is used to identify altered global LV geometry due to remelling, as well as to quantify myocardial scarring and diffuse fibrosis, which are associated with the occurrence of ad-verse events.322-324

Transthyretin cardiac amyloidosis may coexist with AS in elderly pa-tients and the two conditions may causally interrelate.325 When transthry-etin cardiac amyloidosis is suspected, the presence of monoclonal protein in serum and urine should be excluded using immunofixation and quanti-tative determination of free light chains, and diagnosis ascertained by means of diphosphonate scintigraphy.326 Despite the limited long-term prognosis associated with cardiac transthyretin amyloidosis, patients with concomitant severe AS usually benefit from valve intervention.327

LV catheterization is not recommended unless there are symptoms and signs of severe AS, and non-invasive investigations are inconclusive.

8.2.3. Procedural planning

Cardiac computed tomography is key to determining suitability for TAVI and planning the procedure. It is the preferred imaging tool to as-sess AV anatomy including annulus size, dimensions of the aortic root and ascending aorta, the extent and distribution of valve and LVOT cal-cification as the distance of coronary ostia from the annular plane, optimal fluoroscopic projections for transcatheter valve deployment, and the feasibility of vascular access.49,328,329

Transecophageal echocardiography(TOE), which is more operator-dependent and does not allow assessment of coronary and peripheral vascular anatomy, or CMR may be considered when CCT is difficult to in-terpret or relatively contradicated(e.g.in patients with renal failure).330,331

8.3. Medical therapy

No medical therapies have been shown to influence the natural history of AS to date. Neither statins, which demonstrated favourable effects in pre-clinical studies,332-334 nor substances

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 Figure 6 Integrative imaging assessment of patients with aortic stenosis. AS, aortic stenosis; AU, Agatston units; AV, aortic valve; AVA, aortic valve area; AVA; aortic valve area indexed for body surface area; AVCS, aortic valve calcium score; CCT, cardiac computed tomography; CT, computed tomography; DSE, dobutamine stress echocardiography; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; MRI, magnetic resonance imaging; mean PG, mean pressure gradient; SVi, stroke volume indexed for BSA; TOE, transoesophageal echocardiography; TTE, transthor-acic echocardiography; $V_{\max}$ , peak transvalvular velocity. ${}^{\wedge}$ In particular, verify LVOT diameter and multiwindow Doppler interrogation. ${}^{\text{bHigh flow may}}$ be reversible(anaemia, hyperthyroidism, or arteriovenous fistulae). Upper limit of normal flow using pulsed Doppler: cardiac index 4.3 L/min/m2, SVi 58 mL/m2 288 cAvailable evidence refers to patients with preserved LVEF. Check for bradycardia or uncontrolled hypertension, which may lead to pro-longed ejection time and reduced flow rate. Depending on symptoms, integrated assessment complemented by CCT AV calcium scoring may be pur-sued. dFlow reserve:≥20% increase in stroke volume in response to low-dose dobutamine or if change in stroke volume of 10%-20%, calculate projected AVA. ${}^{289,290}$ e1f one test is not conclusive, complement diagnostics with other test. ${}^{b}$ Based on clinical judgement(typical symptoms without other explanation), morphological valve changes, LV hypertrophy(in absence of coexistent hypertension; and consistent findings using different modes of assessment[TTE and TOE, invasive assessment, AV planimetry by CT or MRI(cut-off 1.2 cm2)]291.

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targeting calcification pathways after disease progression. ${}^{335,336}$ Coexistent hypertension should be treated to avoid additional after-load, preferably using renin-angiotensin system blockers, although careful titration is required to avoid symptomatic hypotension. ${}^{337}$

In patients with symptomatic severe AS and HF, initiation of medical therapy or temporary improvement in symptoms should not delay intervention. Medication frequently requires re-adjustment following valve intervention and preventive therapies should be implemented according to current Guidelines.38 In patients with persisting HF and/or reduced LVEF, medical therapy should be introduced before and up-titrated after valve intervention according to the current HF Guidelines.339,340

8.4. Indication for intervention

8.4.1. Symptomatic severe aortic stenosis

Symptomatic severe AS has an unfavourable prognosis if left untreated,and early intervention is strongly recommended in all patients with an estimated life expectancy exceeding 1 year10(Figure 7).

Intervention is recommended in all eligible symptomatic patients with high-gradient severe AS. However, management of patients with low-gradient AS is more challenging:

● Low-flow, low-gradient AS with reduced LVEF: reduced LV func-tion usually improves after intervention if it is predominantly caused by excessive afterload.341-343 However, improvement is unlikely if the primary cause is fibrosis due to myocardial infarction or cardiomyopathy. Intervention is recommended when severe AS is confirmed by CCT(calcium scoring) or stress echocardiog-raphy,341 while patients with pseudo-severe AS should receive GDMT.339,344 Although the absence of flow reserve is associated with increased surgical and long-term mortality, both modes of intervention improved LVEF and clinical outcomes in observational studies.341,342,345-347

● Low-flow, low-gradient AS with preserved LVEF: outcomes are im-proved with intervention(either TAVI or SAVR) compared with medical treatment alone in patients with low-flow, low-gradient AS and preserved LVEF.348,349 Intervention should therefore be consid-ered in patients with symptoms after careful confirmation that AS is severe.

● Normal-flow, low-gradient AS with preserved LVEF: prognosis of these patients is similar to that of moderate AS. Unless multimodality diagnostic evaluation clearly suggests severe AS, regular clinical and echocardiographic surveillance is recommended.293,294,350

8.4.2. Asymptomatic severe aortic stenosis

Up to 40% of patients with severe AS do not report symptoms at the time of diagnosis.351,352 In roughly one-third of these, exercise testing can uncover symptoms or reduced exercise capacity attributable to AS,102,103,318 and such patients should be treated as symptomatic.However, exercise testing is not always feasible because of frailty or im-paired mobility.353 Intervention is recommended in asymptomatic pa-tients with severe AS and an LVEF of<50% without another cause.14,102,318,319,354-360 For patients with severe high-gradient AS and no adverse prognostic features, close active clinical surveillance,so-called‘watchful waiting’, has previously been the default manage-ment strategy. However, four RCTs comparing early AV intervention with clinical surveillance suggest that early intervention should be considered as an alternative in patients at low procedural risk.360-363

This approach is reinforced if additional adverse prognostic features(very high V 14,353,364 elevated natriuretic peptides,97,317,365,366 se-vere valve calcification,303,364 rapid V max progression,353,364 or LVEF of<55%14,354,356-359) are present. Restricted local resources(that may impede close surveillance) or long waiting lists(that preclude prompt treatment when symptoms develop) are further arguments fa-vouring an early intervention.

The Evaluation of TAVR Compared to Surveillance for Patients with Asymptomatic Severe Aortic Stenosis(EARLY TAVR) trial ${}^{360}$ rando-mized 901 patients to early TAVI or clinical surveillance and demonstrated a reduction of 50% in the primary composite endpoint of all-cause mor-tality stroke, or unplanned hospitalization for cardiovascular causes asso-ciated with pre-emptive intervention. ${}^{360}$ The result was driven by 26.2%of the patients in the clinical surveillance group who converted to TAVI within 6 months of randomization due to the development of symptoms or adverse prognostic factors. There was no significant difference in strokes and all-cause mortality over 5-year follow-up.

In the Early Valve Replacement Guided by Biomarkers of LV Decomensation in Asymptomatic Patients with Severe AS(EVoLVeD) RCT, which included 224 asymptomatic patients with severe AS and myocardial fibrosis(late gadolinium enhancement on CMR), early valve intervention(with SAVR or TAVI) failed to reduce the incidence of all-cause death or unplanned AS-related hospitalization compared with clinical surveillance.361 However, the study was under-powered and the median time to intervention was prolonged to 5 months in the experimental arm.

Two previous smaller trials compared early SAVR with clinical surveillance. In the Randomized Comparison of Early Surgery vs Conventional Treatment in Very Severe Aortic Stenosis(RECOVERY) trial(145 patients), there was a reduction in all-cause mortality following early SAVR over a mean follow-up of 6.2 years.362 In the Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Seven Aortic Stenosis(AVATAR) trial(157 patients), a reduction in the composite primary endpoint was noted after a mean follow-up of 2.5 years with a significant reduction in HF hospitalizations and mortality at long-term follow-up. 363,367 Limitations of these surgical studies included their small sample sizes,enrolment of selected young populations at low surgical risk(mean ages 64 and 67 years, respectively), and inclusion of patients with most-ly very severe AS.

A meta-analysis of the four RCTs showed that early intervention is associated with a significant reduction in unplanned cardiovascular or HF hospitalization and stroke, but not all-cause or cardiovascular mor-tality. Limitations of this analysis include the heterogeneity of the pooled trials and lack of granularity with respect to specific events ow-ing to the study-level analysis. ${}^{368}$

Additional RCTs(NCT04204915 and NCT03972644) will further inform and refine the management of patients with severe asymptom-atic AS.

8.4.3. Moderate aortic stenosis

Surgical intervention for moderate AS should only be performed in pa-tients undergoing CABG,369 surgery of the ascending aorta or other valve disease(see Section 13). There is evidence of an association be-tween moderate AS and adverse outcomes in patients with and with-out HF with reduced EF(HFrEF),370-372 but it is unknown whether this is causal or related to comorbidities. In an early terminated trial ran-domizing 178 patients with moderate AS and HFREF to TAVI or clinical surveillance, no differences with respect to hard clinical endpoints were

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 Figure 7 Management of patients with severe aortic stenosis. AS, aortic stenosis; AVCS, aortic valve calcium score; BNP, brain natriuretic peptide; BP,blood pressure; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; SAVR, surgical aortic valve replace-ment; TAVI, transcatheter aortic valve implantation; V_{max}， peak transvalval velocity。^{a Integrative imaging} assessment of AS(Figure 6).^{b}Confirmed by a normal exercise test，if feasible.‘AVCS>2000 in men，>1200 in women.‘More than three times age- and sex-corrected normal range.‘Educate patient and reassess at least every 6 months(or promptly if symptoms occur).‘Heart Team assessment based upon individual patient factors(Figure 9; Recommendation Table 4). Dashed arrow only applies to asymptomatic patients.

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 Figure 8 Aortic valve treatment options. OAC, oral anticoagulation; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation.

found, while patients undergoing TAVI had improved quality of life(change in KCCQ of 12.8±21.9 points vs 3.2±22.8 points;P=0.018). ${}^{373}$ Ongoing trials are expected to provide new insights(NCT04889872 and NCT05149755).

8.5. Treatment options

The mode of AV intervention depends on the estimated life expect-ancy, expected prosthesis durability, patient preference, and specific trade-offs associated with different treatment options(Figure 8).Most patients with AS undergoing valve intervention in Europe and North America receive a BHV(by either SAVR or TAVI).374 BHVs do not require long-term anticoagulation but have limited durability that varies between devices and is inversely associated with age.375 MHVs are durable but require long-term anticoagulation, with asso-ciated thromboembolic and bleeding risks.260,376 in general, an MHV should be preferred in patients aged<60 years and a BHV in patients aged>65 years in aortic position(see Section 14.1).

The Ross procedure(replacement of the AV with the patient's pul-monary autograft combined with homograft pulmonary valve replacement) is associated with excellent long-term survival when per-formed in selected patients at centres with high expertise.260,263,3773 Although a valuable surgical option in young patients with prolonged life expectancy in whom anticoagulation is undesirable or contraindicated,it is associated with procedural complexity and the need for reinterven-tion in~15% of patients within 15 years(Figure 8).263,377

Balloon aortic valuoplasty may be rarely considered as a bridge to TAVI or SAVR in carefully selected patients with decompensated AS,and in those with severe AS who require urgent high-risk non-cardiac surgery(NCS)(see Section 15.2.1). The procedure carries significant risks of acute complications.379

A substantial increase in the number of patients undergoing AV inter-vention has been observed over the past decade as a consequence of the introduction of TAVI, improved diagnostic techniques, and evolving indi-cations for intervention. ${}^{374,380-383}$ Nevertheless, there is still wide vari-ation in worldwide access to TAVI as a result of high device costs in comparison with surgical prostheses and variation in healthcare re-sources and reimbursement systems between countries.384-386 In add-ition, registries suggest that late referral and undertreatment remain frequent. ${}^{12,387}$

8.5.1. The mode of intervention in candidates for a bioprosthesis

The two modes of BHV replacement,TAVI and SAVR, have been com-pared in RCTs across the spectrum of surgical risk in predominantly elderly patients with tricuspid AS.

In patients unsuitable for surgery, TAVI was superior to medical therapy with a number-needed-to-treat of five to prevent one death at 1-year follow-up. ${}^{388}$ Subsequently, RCTs showed non-inferiority of TAVI compared with SAVR in patients at high, ${}^{389-391}$ intermedi-392,393 and low surgical risk,1,394,395 with comparable longer-term outcomes demonstrated during follow-up periods ranging from 4 to 10 years.2,4,396-398 Of note, the majority of patients included in RCTs were male, while patients with low-flow low-gradient AS or ad-verse anatomical characteristics(including BAVs or complex CAD)were excluded per protocol.

Meta-analyses of RCTs show a risk reduction in all-cause death and disabling stroke with TAVI in low-risk patients at 1 year, but no differ-ences to SAVR at longer-term follow-up or in patients at intermediate or high surgical risk.399,400 The early benefit of TAVI in low-risk patients has since been corroborated in the investigator-initiated Randomized,Multicenter, Event-Driven Trial of TAVI vs SAVR in Patients with Symptotic Severe Aortic-Valve Stenosis(DEDICATE), which met its non-inferiority target with a composite of death and stroke rate at 1 year of 5.4% in the TAVI group vs 10.0% in the SAVR group[hazard ratio(HR),0.53;95% confidence interval(CI),0.35-0.79] and all-cause death rates of 2.6% and 6.2%(HR 0.43; 95% CI, 0.24-0.73),respectively.395

Rates of vascular complications and paravulav leak(PVL) are con-sistently higher after TAVI despite refined transcatheter heart valve(THV) designs, whereas severe bleeding, acute kidney injury, and new-onset AF are more frequent after SAVR. ${}^{2,4,399,401}$ Even though PVL has been associated with adverse clinical outcomes, ${}^{402,403}$ it does not seem to impact the comparison of clinical outcomes between TAVI and SAVR in RCTs. ${}^{2,4,395}$

New pacemaker implantations are more frequent after TAVI, par-ticularly when using self-evanding valves.3,394,404 Conflicting data exist regarding the long-term impact of new pacemaker implantation or new-onset left bundle branch block following AV intervention.405-407 Patients undergoing TAVI have quicker recoveries, shorter hospital

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stays, and more rapid improvements in quality of life compared with those who undergo SAVR.1,2,408,409

Available data do not suggest systematic differences in durability be-tween the two treatment modalities. Randomized controlled trials and observational studies have reported comparable rates of BHV failure re-lated to SVD with transcatheter and surgical valves up to 10 years.2,398,410 However, potential selection and survival bias, the use of variable defini-tions of SVD, limited follow-up durations, differential attrition rates, ${}^{2,4,396,400}$ competing risk of death, and the use of multiple valve types in the surgical arms of RCTs may limit direct comparison. ${}^{411}$

Although conclusive evidence is still lacking, concomitant non-complex CAD can be addressed either by CABG or PCL, while complex CAD favours CABG(see Section 6.1).In the only RCT com-paring these two strategies, the transchateter valve and vessels(TCW) trial, randomization of patients with severe AS and concomi-tant CAD to FFR-guided PCI plus TAVI resulted in fewer deaths and major bleeding events compared with combined SAVR plus CABG at 12 months.412 However, inferences from trial results are limited due to early termination, modest sample sizes, event rates deviating from those observed in registries and other RCTs, and a low prevalence of complex CAD.

8.5.1.1. Age and life expectancy

The relationship between estimated life expectancy and prosthetic heart valve durability determines the likelihood of a future reintervention.Although life expectancy may be a theoretically better guide than age alone for treatment decisions, it is difficult to estimate for an individual pa-tient owing to large geographical(https://ghdx.healthdata.org/record/imte-data/gbd-2019-life-tables-1950-2019) and interindividual variabil-ity. ${}^{413}$ In combination with cardiac and extracardiac comorbidities, as well as anatomical factors, age contributes to risk estimation and repre-sents a pragmatic surrogate for life expectancy.In addition,age thresholds characterize the populations enrolled in RCTs better than life expectancy.It is notable that younger patients with AS seem to have lower life expect-ancy than the general population despite valve replacement, whereas life expectancy almost normalizes after treatment in older cohorts. ${}^{414,415}$ While several trials compared TAVI with SAVR in study populations aged 70-85 years across the surgical risk spectrum, the representation of patients aged<70 years in RCTs is low and therefore evidence limited. ${}^{1394,395,416}$

8.5.1.2. Anatomical features

The advantages of TAVI demonstrated in RCTs are largely confined to patients treated via the transfemoral approach.401 While SAVR remains the preferred treatment option when illofemoral artery disease pre-cludes transfemoral TAVI,TAVI via a non-transfemoral access(transax-illary, transcarotid, transcavart, transnominate, or transapical)constitutes an alternative supported by observational data in patients unsuitable for surgery. ${}^{417-423}$

Other anatomical factors that favour SAVR or led to exclusion of pa-tients from RCTs comparing TAVI with SAVR are(Figure 9):

● Aortic annular dimensions that lie outside sizing recommendations for currently available transcatheter devices.

● Excessive or bulky calcifications of the annulus or LVOT, which in-crease the risk of PVL and annular rupture.424,425

● Increased risk of coronary obstruction with TAVI(cusp height greater than coronary height in combination with shallow sinuses of Valsalva,or high calcium burden of corresponding cusp). 329

In contrast, anatomical findings such as porcelain aorta, severe chest deformation, or intact grafts post-CABG favour TAVI. Right anterior thoracotomy or upper hemisternotomy are minimally invasive access alternatives to rotational energy for performing SAVR, which are being used with increasing frequency.426,427

In BAV patients, severe AS usually occurs earlier compared with tri-cuspid AV and is frequently associated with aortopathy. 219,281,428 Prevalence of BAV anatomy sharply increases in younger AS pa-tients.429 BAV anatomy adds complexity to TAVI because of asymmet-ric AV calcification and elliptical annular shape, as well as the lack of standardization of valve sizing.

Patients with BAV have been excluded from almost all landmark RCTs comparing TAVI with SAVR to date.429,430 In the NOTION 2 trial, the composite of all-cause death, stroke, or valve- or HF-related rehospitalization was numerically more frequent(seven vs two events)at 1 year in the underpowered subgroup of 100 patients with BAV(HR,3.8;95% CI,0.8-18.5;P=0.07).416 Whereas some observational studies report favourable outcomes with TAVI in selected BAV patients,430-432 others suggest higher stroke, annular rupture, and PVL rates as com-pared with TAVI in tricuspid AS.433 Heavy cusp calcification, particularly in conjunction with a calcified raphe, is associated with increased risk of aortic root injury, PVL, and mortality after TAVI.434 Data on TAVI in two-sinus BAV(Sievers type 0) are scarce.219,435

For the above-mentioned reasons, SAVR remains the primary mode of treatment for stenotic BAV, particularly if patients are young or have coexistent aortopathy or unfavourable valve morphology. TAVI may be considered in patients at increased surgical risk, if anatomy is suitable.

Patients with small annuli in relation to their body stature are at in-creased risk of prosthesis-patient mismatch(PPM) after valve replace-ment. Annular enlargement allows for implantation of larger BHVs with SAVR. Given its technical complexity it should be performed in experienced centres, and the benefit must be balanced against a possibly higher risk of operative mortality.436 Prostheses with supra-annular design reduce PPM risk with TAVI, although randomized long-term data evaluating the impact on clinical outcomes or valve durability are pending.394,437,438

8.5.1. Lifetime management

Decision-making concerning the mode of intervention and type of prosthesis needs to integrate expected valve durability, and the poten-tial risks of future reinterventions(Figure 9). Surgical THV explantation followed by SAVR is a rare(<1% of all TAVI procedures) but technically challenging procedure.439-441 Although its incidence among patients undergoing TAVI is stable, absolute numbers are increasing due to the total increase in TAVI procedures performed and the peri-operative risk remains high(early mortality rates as high as 12%-17%).440-445 The majority of surgical THV explantations are performed in patients at high surgical risk with urgent or emergent,n-SVD-related indication for reintervention(frequently endocardi-tis) within 2 years after TAVI.440,442-444

Implanting a transcatheter aortic valve inside a surgical(TAV-in-SAV)or prior transcatheter valve(TAV-in-TAV) is associated with lower peri-procedural risk compared with redo SAVR.446-451 However,valve-in-valve implantation(particularly TAV-in-SAV) increases the risk of severe PPM,448 which has been linked to adverse outcomes in observational studies.452-455 In addition, valve-in-valve implantation im-mobulates the leaflets of the failed prosthesis in an open position, creat-ing a covered tube(or neuro-skirt) that may cause direct coronary obstruction in patients with shallow sinuses of Valsalva or indirect

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 Figure 9 Factors to be considered when selecting the mode of intervention for aortic stenosis. CAD, coronary artery disease; LV, left ventricular;LVOT, left ventricular outflow tract; SAVR, surgical aortic valve replacement; TAVI,transcatheter aortic valve implantation; THV,transcatheter heart valve; VHD, valvular heart disease. ${}^{11}$ LV thrombus and infective endocarditis are relative contraindations to TAVI and are therefore not listed.bParticularly relevant for patients in whom the anticipated life expectancy is thought to exceed valve durability.

<BeginOfPara>coronary flow obstruction as a result of sinus sequestration if the as-cending aorta is narrow and the neo-skirt reaches the sinotubular junction.456,457

The risk of coronary obstruction varies considerably depending on the index valve type, and is particularly increased if a stentles SAV or stented SAV with externally mounted leaflets is in place. ${}^{457}$ The risk of sinus sequestration at the time of TAV-in-TAV implantation is par-ticularly increased in supra-annular valves with a high neo-skirt. ${}^{458,459}$ Even if coronary flow is preserved, coronary access may be difficult or impossible in a relevant proportion of patients after valve-in-valve implantation, especially after TAV-in-TAV. ${}^{460-462}$

<BeginOfPara>In patients who require a reintervention due to dysfunction of a sur-gical or transcatheter bioprostheism, but are at increased risk of severe PPM or coronary obstruction, redo SAVR may be preferable despite the increased surgical risk. Fracture of surgical valves and leaflet modi-fication techniques have been proposed for patients at high surgical risk

<EndOfPara>and, if contemplated, should be performed in carefully selected patients at experienced centres (Table 6).463,464

The need for a meticulous CT-based anatomical analysis is para-mount in patients with an estimated life expectancy exceeding the assumed valve durability to anticipate future risks at the time of the index valve intervention. Based on individual assessment, the following measures should be considered with respect to lifetime management:

• Use of surgical and transcatheter valves with proven long-term dur-ability to reduce the likelihood of reintervention. 2,4,375,410,411,465-467

● SAVR with aortic root enlargement or implantation of a supra-annular transcatheter valve in patients with a small annulus at risk of severe PPM based on the predicted effective orifice area(EOA).436,438,468,469

● No implantation of stentless prostheses or prostheses with external-ly mounted leaflets in patients at risk of coronary obstruction during future TAV-in-SAV implantation. ${}^{457}$

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● Anticipation of the feasibility and risks of a possible future TAV-in-TAV procedure considering related technical aspects at the index TAVI(device choice, neo-skirt height, commissural alignment, and implant-ation depth).456,470

Considering life-time management aspects and the scarcity of rando-mized data in patients younger than 70 years, SAVR remains the pre-ferred treatment in patients<70 years of age if surgical risk is low.TAVI is recommended as the primary treatment modality in elderly pa-tients≥70 years of age with a tricuspid AV, if anatomy is suitable and

transfemoral access is feasible, to reduce the risk of early adverse out-comes and accelerate recovery.

For all other candidates for a bioprosthesis, the most appropriate mode of intervention should be carefully selected by the Heart Team, taking into account procedural risk based on anatomical charac-teristics and comorbidities, expected outcomes, lifetime management considerations, and patient preference(Figure 9; Recommendation Table 4). Recommendations for concomitant valve replacement at the time of CABG or ascending aortic surgery are listed in Recommendation Table 5.

Recommendation Table 4-Recommendations on indications for intervention in symptomatic and asymptomatic severe aortic stenosis, and recommended mode of intervention(see also Supplementary data online, Evidence Tables 9-13)

|Recommendations||Classa|Levelb| |---|---|---|---| |Symptomatic patients with severe aortic stenosis|||| |Intervention is recommended in symptomatic patients with severe, high-gradient AS[mean gradient≥40 mmHg, Vmax≥4.0 m/s, AVA≤1.0 cm2(or≤0.6 cm2/m2 BSA)].||I|B| |Intervention is recommended in symptomatic patients with low-flow(SVi≤35 mL/m2), low-gradient(<40 mmHg) AS with reduced LVEF (<50%) after careful confirmation that AS is severe.||I|B| |Intervention should be considered in symptomatic patients with low-flow(SVi≤35 mL/m2), low-gradient(<40 mmHg) AS with normal LVEF(≥50%) after careful confirmation that AS is severe.c 293,348,349,476-481||IIa|B| |Asymptomatic patients with severe aortic stenosis|||| |Intervention is recommended in asymptomatic patients with severe AS and LVEF<50% without another cause.|14,354,359|I|B| |Intervention should be considered in asymptomatic patients with low-flower(SVi≤35 mL/m2), if feasible, high-gradient AS and LVEF≥50% as an alternative to close active surveillance, if the procedural risk is low.|IIa|A|| |Intervention should be considered in asymptomatic patients with severe AS and LVEF≥50% if the procedural risk is low and one of the following parameters is present:|||| |● Very severe AS(mean gradient≥60 mmHg or Vmax>5.0 m/s).|14,362,363,482-484||| |● Severe valve calcification(ideally assessed by CCT) and Vmax progression≥0.3 m/s/year.|303,353,364|IIa|B| |● Markedly elevated BN/PNT-proBNP levels(more than three times age- and sex-corrected normal range, confirmed on repeated measurement without other explanation). 97,365|||| |● LVEF<55% without another cause.|14,354,356-359||| |Intervention should be considered in asymptomatic patients with severe AS and a sustained fall in BP(>20 mmHg) during exercise testing.|IIa|C|| |Mode of intervention|||| |It is recommended that AV interventions are performed in Heart Valve Centres that report their local expertise and outcome data, have on-site interventional cardiology and cardiac surgical programmes, and a structured collaborative Heart Team.|1|C|| |It is recommended that the mode of intervention is based on Heart Team assessment of individual clinical, anatomical, and procedural characteristics, incorporating lifetime management considerations and estimated life expectancy.|1|C|| |TAVI is recommended in patients≥70 years of age with tricuspid AV stenosis, if the anatomy is suitable.|1-4,389-397,465,485,486|I|A| |SAVR is recommended in patients<70 years of age, if the surgical risk is low.|1-413,429,487|I|B| |SAVR or TAVI are recommended for all remaining candidates for an aortic BHV according to Heart Team assessment. 2,4,396,397,429,488-490|1|B|| |Non-transfemtional TAVI should be considered in patients who are unsuitable for surgery and transfemoral access.|117-423,491-498|IIa|B| |TAVI may be considered for the treatment of severe BAV Senosis in patients at increased surgical risk, if the anatomy is suitable.|llb|B|| |Balloon aortic valotomy may be considered as a bridge to SAVR or TAVI in haemodynamically unstable patients, and(if feasible) in those with severe AS who require urgent high-risk NCS.|llb|C||

AS, aortic stenosis;AV, aortic valve; AVA, aortic valve area; BAV, bicuspid aortic valve; BH, biological heart valve; BNP, brain natruiretic peptide; BP, blood pressure; BSA, body surface area;CCT,cardic computed tomography;EuroSCORE,European System for Cardiac Operative Risk Evaluation; LVEF, left ventricular ejection fraction; NCS, non-cardiac surgery; NT-proBNP,N-terminal pro-B-type natriuretic peptide; SAVR, surgical aortic valve replacement; STS-PROM, Society of Thoracic Surgeons predicted risk of mortality; SVi, stroke volume index; TAVI,transcatheteric sortic valve implantation; V_{max}, peak transvalvular velocity.

${}^{2}$ Class of recommendation.

Level of evidence.

"Explanations(such as measurement errors, uncontrolled blood pressure, and conditions lowering the stroke volume) other than severe AS for a small AVA but low gradient despite preserved VAE were frequent and must be carefully excluded.

dSuitability regarding transfemoral access, annulus dimensions, device landing zone calcification pattern, and coronary obstruction risk(Figure 9).

Surgical risk based on STS-PROM(http://riskcalsc.sts/otswebriskcalc/#/calculate) and EuroSCORE II(http://www.euroscore.org/calc.html)<4% and Heart Team assessment.

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Recommendation Table 5-Recommendations on in-dications for concomitant aortic valve replacement at the time of coronary artery bypass grafting or ascending aorta surgery

|Recommendations|Classa|Levelb| |---|---|---| |SAVR is recommended in symptomatic and asymptomatic patients with severe AS undergoing CABG or surgical intervention on the ascending aorta.||C| |SAVR should be considered in symptomatic and asymptomatic patients with moderate ASC from undergoing CABG or surgical intervention on the ascending aorta.|lla|C|

AS, aortic stenosis; AVA, aortic valve area; CABG, coronary artery bypass grafting; SAVR, surgical aortic valve replacement.

aClass of recommendation.

bLevel of evidence.

${}^{c}$ Defined as an AVA of 1.0-1.5 cm ${}^{2}$ (or mean aortic gradient of 25-40 mmHg) in normal-flow conditions. Clinical assessment is essential to determine whether SAVR is appropriate for an individual patient.

8.6. Follow-up

The rate of progression of AS varies widely and asymptomatic patients,their family, and medical caregivers need careful education, with particu-lar emphasis on the importance of regular follow-up(ideally at a Heart Valve Centre)14 and prompt reporting of symptoms. Asymptomatic pa-tients with severe AS should be followed up at least every 6 months to allow detection of early symptoms(using exercise testing if complaints are inconclusive) and any change in echocardiographic parameters(par-ticularly LVEF). Serial measurements of natriuretic peptides can provide additional useful information regarding the timing of treatment.

Younger patients with mild AS and no significant leaflet calcification may be followed up every 2-3 years. With increasing stenosis severity,progression accelerates and follow-up intervals should be gradually re-duced.283,503 Several studies suggest that the prognosis of moderate de-generative AS is worse than previously considered,504,505 particularly if there is significant valve calcification, and these patients should be re-evaluated at least annually.

Cardiac rehabilitation is frequently performed after AV intervention,especially after surgery and in elderly patients, and is associated with im-proved activities of daily living and 6-minute walking distance.506 After valve intervention, an early echocardiographic examination within the first weeks after valve replacement is recommended to document base-line prosthetic valve function. Cardiological evaluations and echocardio-graphic examinations are recommended annually in patients with a bioprosthesis, and whenever changes in clinical symptoms or signs sug-gestive of valve dysfunction are noted.

9. Mitral regurgitation

Chronic MR is one of the most common acquired valve patholo-gies, 12,187 while acute MR is observed in the context of infective endo-carditis, chordal rupture, or as a complication of myocardial infarction(papillary muscle rupture). MR either relates to anatomical changes of the MV apparatus(primary), or to LV or LA dilatation and dysfunction(secondary).193 Since natural history, prognosis, and management differ according to aetiologies, populations should be clearly distinguished in clinical practice and research.12,507

9.1. Primary mitral regurgitation 9.1.1. Prevalence and aetiology

Primary mitral regurgitation relates to an anatomical lesion of one or more of the three main components(not including the annulus) of the MV apparatus(valve leaflets, chordae tendineae, and papillary muscles).PMR is observed in 55% of patients with MR who require treatment.While degenerative disease related to fibroelastic deficiency or myxoma-tous alterations(in its most severe form, Barlow's disease) are the most common aetologies in higher-income countries, RHD is most frequently found in the rest of the world. MV endocarditis is a separate entity of PMR caused by acute or chronic infectious conditions and is discussed in the corresponding Guidelines.5 In a small subgroup of patients, PMR is asso-ciated with a higher incidence of ventricular arrhythmias, and sudden car-diac death has been reported in individual cases, especially in patients with Barlow's disease.508 The arrhythmogenic burden is independent from MR severity and has been associated with mitral annular disjunction. Atrial dis-placement of the posterior MV leaflet hinge point is assumed to cause ex-cessive mobility of the valvular apparatus and increases tension on the papillary muscles and the posterobasal myocardium, causing local fibrosis,which may lead to ventricular arrhythmias and sudden cardiac death.509

9.1.2. Evaluation

9.1.2.1. Echocardiography and right heart catheterization

Echocardiography is the diagnostic method of choice for the quantifica-tion of MR, determination of its aetiology, and identification of cardiac consequences(Figure 10). TTE is used for initial evaluation that includes:(i) assessment of valve morphology(presence and location of prolapse or flail, calcifications, and/or mitral annular disjunction);(ii) integrative severity grading; and(iii) quantification of LV and LA dimensions and function, as well as assessment of concomitant RV dysfunction.46 Quantitative parameters such as the effective regurgitant orifice area(EROA) have prognostic implications.510,511 Volumetric methods pro-vide additional information on MR severity[RVol and regurgitant frac-tion(RF)].512 Accurate colour flow settings must be used to avoid overestimation of MR severity.

Transoesophageal echocardiography(TOE) represents the method of choice to assess valve anatomy, leaflet quality,motion, and coaptation, as well as to confirm MR severity. ${}^{513}$ Three-dimensional TOE provides an excellent morphological and functional view of the different valve seg-ments, and should be used systematically when planning and performing surgical or transcatheter repair. ${}^{514}$

Exercise echocardiography evaluates dynamic changes in regurgitant jet and pulmonary pressures during peak exercise, and might be helpful in pa-tients with discordant symptoms and regurgitation severity at rest.515,516

In asymptomatic patients with severe PMR, increased LV or LA di-mensions, as well as elevated pulmonary pressures(>50 mmHg at rest),moderate or more secondary TR, and AF are important markers of worse prognosis, and should be considered for intervention timing(Figure 11; Section 9.1.4).517,518

Right heart catheterization remains important in patients with PMR for confirmation of pulmonary artery pressures in case of discrepancy between echocardiographic MR severity and clinical symptoms, as well as in the presence of concomitant lung disease.519

9.1.2.2. Biomarkers

Cardiac biomarkers are recognized indicators of disease severity with prognostic implications, but may also be non-specific. NT-probNP levels are directly related to the New York Heart Association(NYHA) functional class in PMR.520

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 Figure 10 Echocardiographic assessment of patients with mitral regurgitation.EROA,effective regurgitant orifice area; LAVI,left atrial volume index;LVEF,left ventricular ejection fraction; LVESD,left ventricular end-systolic diameter; LVOT,left ventricular outflow tract; MR,mitral regurgitation; PMR,primary mitral regurgitation; RF, regurgitant fraction; RVol, regurgitant volume; SMR, secondary mitral regurgitation; SPAP, systolic pulmonary artery pressure; TR, tricuspid regurgitation; VTI, velocity time integral. ${}^{a}$ See Table 7 for criteria predicting outcome improvement.

In a multicentre registry including more than 1300 patients with PMR,increased BNP level was an independent predictor of long-term mor-tality under medical treatment. However, pre-operative BNP activation did not impact long-term mortality after surgical treatment. ${}^{96}$

9.1.2.3. Cardiac magnetic resonance and computed tomography Cardiac magnetic resonance imaging is an alternative to precisely quan-tify RVol and RF in cases of inconclusive or discordant measurements,and the gold standard to determine cardiac dimensions and chamber volumes. ${}^{521,522}$ The combination of planimetered volumetric methods

and phase contrast measurement of the MV inflow are used for this purpose. ${}^{523}$ In patients with Barlow's disease and mitral annular disjunc-tion,CMR-detected myocardial fibrosis ${}^{524}$ has been associated with ventricular arrhythmias and sudden cardiac death. ${}^{525}$

Cardiac computed tomography provides high-resolution anatomical details of the entire MV apparatus523,526 and increasingly plays a role in MV intervention planning, particularly in the assessment of arterial access for extracorporeal circulation and the presence of MV calcification in min-imally invasive surgery,527 as well as the feasibility of transcatheter MV im-plantation(TMVI) based on annulus size and risk of LVOT obstruction.528

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 Figure 11 Management of patients with severe primary mitral regurgitation. AF,atrial fibrillation; LA, left atrial; LAVI, left atrial volume index; LV, left ventricle/left ventricular; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; LVESDi, left ventricular end-systolic diam-eter indexed to BSA; MV,Mitral valve; SPAP,systolic pulmonary artery pressure; TEER, transcatheter edge-to-edge repair; TMVI, transcatheter mitral valve implantation; TR, tricuspid regurgitation. ${}^{a}$ See Supplementary data online, Table S2.

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Due its high sensitivity for detection of calcifications, CCT is instru-mental for procedural planning(surgical and transcatheter) in patients with MAC.529

9.1.2.4. Genetic evaluation

There is increasing evidence that specific mitral pathologies may be as-sociated with genetic conditions. A meta-analysis of six genome-wide association studies identified 14 potential genetic loci associated with primary MR. By comprising epigenetic, transcriptional, and proteomic data,the following genes could be identified as potential genetic sources of the pathology: LMCD1, SPTBN1, LTBP2, TGFβ2, NMB, and ALPK3.530 However, genetic testing is not recommended in routine practice.

9.1.3. Medical therapy

Medical therapy has a limited role in patients with PMR. Afterload re-duction with sodium nitroprusside has been used as a bridge to an intervention in patients with acute severe PMR without signs of hypo-tension. Inotropic agents and diurets are usually indicated to reduce filling pressures and control pulmonary congestion, while the implant-ation of an intra-aortal balloon pump helps to further reduce afterload in exceptional cases of acute PMR.

In chronic PMR without signs of LV dysfunction or criteria for an intervention, there is no evidence supporting prophylactic afterload re-duction. Patients with PMR and impaired LV function should receive GDMT according to HF Guidelines. ${}^{340}$

9.1.4. Indications for intervention

Urgent surgery or transcatheter treatment is indicated in patients with acute severe PMR because it is poorly haemodynamically tolerated. in pa-tients with papillary muscle rupture and endocarditis, surgical valve replace-ment is generally required, while acute degenerative chordra rupture can be treated with surgical MV repair or TEER in high-risk patients.

Indications for surgery in patients with chronic asymptomatic and symptomatic PMR are summarized in Recommendation Table 6 and Figure 11. In cases of severe PMR, restoring the anatomy by surgical MV repair, including annuloplasty, is the treatment of choice in operable patients when an optimal and durable result is expected. According to contemporary data, the procedure can be performed with a low mortality risk(1.2%) in appropriately selected patients. ${}^{531}$ Compared with replacement, MV repair has been associated with lower peri-operative mortality along with significantly better long-term survival and functional outcomes. ${}^{532,533}$ Repair of more com-plex pathologies such as valves with annular or leaflet calcifications,as well as in cases of RHD, is challenging and should be attempted in experienced Heart Valve Centres.534-536 When MV repair is not feasible, valve replacement with preservation of the subvalvular ap-paratus should be performed. ${}^{537}$

High-risk and elderly patients with chronic PMR, though uncommon,may benefit from a less-invasive M-TEER procedure. 538 Peri-interventional and mid-term results with regard to residual MR and mean transmitral gradient are closely related to patient outcomes.538 The use of latest-generation devices along with a growing team experi-ence have improved results, and allow for the successful treatment of more complex anatomical conditions(Supplementary data online,Table S2).539,540 The decision regarding the mode of intervention or conservative treatment should be made by the Heart Team, considering clinical and anatomical characteristics, as well as procedural risks and

patient preference. The longer-term efficacy of TEER compared with surgery is still under investigation in high-(NCT03271762) and intermediate-risk PMR patients(NCT04198870), as well as in all-risk-category patients>60 years of age(NCT05051033).541 TMVI is very effective in abolishing MR in selected high-risk patients, particular-ly those with complex MV anatomy for TEER(Supplementary data online, Table S2).542,543 The major drawbacks of current TMVI systems include limited availability, high screening failure rate, as well as the risk of LVOT obstruction and valve thrombosis. Limited data exist for PMR pa-tients and regarding mid-term prosthesis durability.

In patients with asymptomatic PMR with signs of LV dysfunction(i.e.LVEF≤60%,LVESD≥40mm,or LVESDi≥20mm/m2) the bene-fit of early surgery is well established.544-546 Furthermore, there is in-creasing evidence that the presence of LA dilatation[LA volume index(LAVI)≥60 mL/m2 or LA diameter≥55 mm],AF,systolic pulmonary artery pressure(SAPP) at rest of>50 mmHg, and concomitant mod-erate or severe secondary TR are associated with worse long-term prognosis irrespective of LV function after corrective surgery, and should therefore prompt referral in low-risk patients, particularly if a high probability of MV repair is expected.517,518,547 A recent study showed that women have a higher risk of long-term mortality after MV repair than men, even at lower degrees of ventricular dilatation and dysfunction, suggesting the potential usefulness of sex-specific in-dexed thresholds.548 Ventricular arrhythmias in patients with MV pro-lapse have been linked to impaired prognosis and possibly sudden cardiac death, especially in the presence of mitral annular disjunc-tion.549-551 Ring annuloplasty stabilizes the posterior annulus, reduces traction on the subvalvular apparatus,552 and may lower the risk of ar-rhythmias.553 Minimally invasive surgery via right mini-thoracotomy is used with increasing frequency in experienced centres.554-556 A re-cent RCT demonstrated similar safety and efficacy compared with conventional sternotomy. Mini-thoracotomy was associated with shorter hospital stay and improved physical activity within the first 6 weeks after surgery, a difference that disappeared at 12 weeks.557 The use of minimally invasive MV surgery may therefore be consid-ered to reduce hospital stay and accelerate recovery in experienced centres. However, in a national registry, these benefits were less clear.558

Recommendation Table 6- Recommendations on indications for intervention in severe primary mitral regurgitation(see also Supplementary data online,Evidence Tables 14-16)

|Recommendations|Classa|Levelb| |---|---|---| |MV repair is the recommended surgical technique to treat patients with severe PMR when the result is expected to be durable.26,532,533,559,560|$\begin{array}{c}\\ \\ \\ \end{array}$|B| |MV surgery is recommended in symptomatic patients with severe PMR considered operable by the Heart Team.26,532,533,561|$\begin{array}{c}\\ \\ \\ \end{array}$|B| |MV surgery is recommended in symptomatic patients with severe PMR considered operable by the Heart Team.26,532,533,561|$\begin{array}{c}\\ \\ \\ \end{array}$|B|

Continued

<FIGTEXT=></FIGTEXT>

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|Surgical MV repair is recommended in low-risk asymptomatic patients with severe PMR without LV dysfunction(LVESD<40 mm,LVESDi<20 mm/m2, and LVEF>60%) when a durable result is likely, if at least three of the following criteria are fulfilled: ${}^{517,547,562-564}$|1|B| |---|---|---| |●AF SPAP at rest>50 mmHg ● LA dilatation(LAVI≥60 mL/m2 or LA diameter≥55 mm)||| |● Concomitant secondary TR≥ moderate.||| |MV surgery should be considered in asymptomatic patients with severe PMR without LV dysfunction (LVESD<40 mm,LVESDi<20 mm/m2, and LVEF >60%) in the presence of PH(SAPP at rest >50 mmHg), or AF secondary to MR. 517,518,562,565|lla|B| |Surgical MV repair should be considered in low-risk asymptomatic patients with severe PMR without LV dysfunction(LVESD<40 mm,LVESDi<20 mm/m2, and LVEF>60%) in the presence of MR. 517,518,562,565|lla|B| |diameter≥55 mm), when performed in a Heart Valve Centre and a durable repair is likely. ${}^{-517,565}$|lla|B| |TEER should be considered in symptomatic patients with severe PMR who are anatomically suitable and at high surgical risk according to the Heart Team. 538,540,566|lla|B| |Minimally invasive MV surgery may be considered at experienced centres to reduce the length of stay and accelerate recovery. ${}^{557,567}$|llb|B|

AF, atrial fibrillation; LA, left atrium/left atrial; LAVI, left atrial volume index; LV, left ventricle/left; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; LVESD, left ventricular end-systolic diameter indexed to body surface area; MR, mitral regurgitation; MV, mitral valve; PH, pulmonary hypertension;PMR, primary mitral regurgitation; SPAP, systolic pulmonary artery pressure; TEER,transcatheter edge-to-edge repair; TR, tricuspid regurgitation.

Class of recommendation.

bLevel of evidence.

9.1.5. Follow-up

Asymptomatic patients with severe MR not fulfilling the criteria for an intervention, and with documented preserved exercise capacity, should undergo clinical and echocardiographic follow-up twice per year(watch-ful waiting strategy), ideally in the setting of a Heart Valve Clinic.F68 Follow-up may also include serial measurements of BNP levels, electro-cardiogram(ECG) and/or Holter monitoring, and(in selected cases) ex-ercise echocardiography and CMR to confirm MR severity, and cardiac chamber function and dimensions.46 Asymptomatic patients with mod-erate MR and preserved LV function can be followed on a yearly basis with echocardiographic assessment every 1 or 2 years.

The frequency of follow-up after an intervention depends on the type of procedure performed. Very good long-term durability of MV repair in PMR due to valve prolapse with a low recurrence rate has been reported at experienced centres with freedom from moderate or severe MR of 87.5% at 20 years.533,559 Serial clinical and echocardiographic follow-up in patients without pre-operative LV dysfunction or rhythm abnormal-ities every 2-3 years thereafter is sufficient. Patients with atrial or ven-tricular arrhythmias possibly related to MV disease should be further evaluated using continuous ECG monitoring. Patients with recurrent

MR after surgical ring annuloplasty frequently undergo repeat surgery(usually MV replacement), while transcatheter alternatives are reserved for selected high-risk patients because of the risk of increased gradients(M-TEER), PVL, and LVOT obstruction(mitral valve-in-ring proce-dures).569,570 In patients undergoing MV replacement, closer follow-up on a yearly basis is required due to the risk of prosthetic valve dysfunction or SVD(see Section 14.4). Following TEER, reported rates of residual MR and increased transmitral gradients are higher than after surgical repair,suggesting that yearly follow-up is appropriate.571 Although rare, the need for surgical treatment after failed TEER is associated with increased peri-operative mortality and low valve repair rates,541,572 while trans-catheter solutions to detach TEER implants and replace the valve have been described in few cases.573,574

9.2. Secondary mitral regurgitation

9.2.1.Prevalence and aetiology

Secondary mitral regurgitation is present when the MV structure appears grossly normal but the MV is nonetheless incompetent, due to alterations in LV and LA geometry, dyssynchrony, and imbalances between MV clos-ing and tethering forces.575 The prevalence of severe SMR in patients with chronic HF is~10% and higher in patients with reduced vs preserved LVEF(25% vs 4%).576 Secondary mitral regurgitation can be classified as atrial or ventricular with different pathophysiological and morphological character-istics, as well as contrasting prognostic and therapeutic implications.Ventricular SMR is more common and associated with worse long-term prognosis.513,578-580 Dilated or ischaemic cardiomyopathy are the most frequent causes of severe ventricular SMR. Acute HF exacerbation may occur in patients with chronic HF due to a renewed ischaemic event, ar-rhythmia,infection, or volume overload. Atrial SMR is due to pure mitral annular dilation and is observed in patients with long-standing AF and/or HFEFp.581 Factors predisposing to atrial SMR include age≥65 years, fe-male sex, LA dilatation, and diastolic dysfunction.582 From a morphological point of view, ventricular SMR is characterized by leaflet tethering and re-stricted motion combines with annular dilation, while annulus enlarge-ment and flattening leading to planar coaptation are predominantly observed in atrial SMR. The prevalence of atrial SMR has been underesti-mated in the past and was occasionally misclassified as PMR due to pseudo-prolapse with leaflet tethering in advanced stages.

9.2.2. Evaluation

Echocardiographic criteria to define significant SMR according to aeti-ology are reported in Figure 10. Importantly, SMR assessment should be performed after optimization of medical therapy and in a evoluemic and normotensive state. When quantifying EROA and RVol in SMR,lower thresholds may apply to define severe regurgitation because of the potential elliptical regurgitant orifice and/or the low-flow state.An EROA of≥30 mm2 and/or an RVol of≥45 mL has been identified as having a significant impact on outcomes,45 with prognosis improved after treatment.583,584 Cardiac magnetic resonance is used to confirm SMR severity and assess cardiac chamber function and dimensions.The extent of myocardial fibrosis, as assessed with CMR, has been as-sociated with poor prognosis.585 Owing to the dynamic nature of SMR,exercise echocardiography may help to identify patients with severe SMR when values at rest are inconclusive.

9.2.3. Definition of atrial secondary mitral regurgitation

Characteristics distinguishing between atrial and ventricular SMR are displayed in Figure 12.

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 Figure 12 Most frequently used criteria for the diagnosis of atrial secondary mitral regurgitation.AO,arts;AP,anteroposterior;HFpEF,heart failure with preserved ejection fraction;LA, left atrium/left atrial;LAVI,left atrial volume index;LV,left ventricle/left ventricular;LVEF,left ventricular ejection fraction;MA,mitral annulus;MR,mitral regurgitation;MV,mitral valve;SMR,secondary mitral regurgitation.LV end-diastolic dimension of<56 mm in females and<63 mm in males; indexed LV end-diastolic volume<71 mL/m2(in women) or<79 mL/m2(in men). b Additional echocardiographic criteria for atrial SMR may no longer be fulfilled in advanced stages.

Atrial SMR is most frequently defined by the presence of the follow-ing key criteria:513,578-580,586-590

● preserved LVEF(≥50%) without regional wall motion abnormalities or leaflet tethering; AND

● no or mildly dilated LV cavity[LV end-diastolic dimension of<56 mm in women and<63 mm in men; indexed LV end-diastolic volume of<71 mL/m2(in women) or<79 mL/m2(in men)]; AND

● mitral annulus(MA) dilatation[anteroposterior(AP) diameter of>35 mm];AND

● enlarged LA(LAVI>34 mL/m2).

Echocardiography frequently reveals normal leaflet motion with pla-nar coaptation, and normal leaflet morphology with a central MR jet in atrial SMR. However, at advanced stages, an overlap between atrial and ventricular SMR criteria can be observed in the case of late LV damage due to continuous volume overload.591,592 Clinical criteria(i.e. history of AF and/or diagnosis of HFEF) are also useful and should be taken into consideration.

9.2.4. Management of ventricular secondary mitral regurgitation

9.2.4. Medical and device therapy

In patients with ventricular SMR, GDMT for the treatment of HF is re-commended prior to any MV intervention. ${}^{339,340}$ The combination of ACE-Is/ARBs or angiotensin receptor/neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors(SGLT2is) at the maximum tolerated doses is recommended according to the HF Guidelines. ${}^{340}$ Initiation and up-titration of neurohormonal drugs need to be tailored according to the patient profile, mainly based on BP, heart rate, potassium levels,and renal function. ${}^{593}$ Notably, GDMT up-titration must be rapid(with-in 6 weeks) and take place in the context of close follow-up visits, es-pecially in the case of a recent hospitalization for acute HF. ${}^{594}$ About 40% of patients with ventricular SMR experience improvement of SMR severity after 1-3 months of optimized GDMT. ${}^{595,596}$ Cardiac re-synchronization therapy(CRT) should also be considered as part of HF management before an MV intervention according to HF guideline cri-teria(LVEF≤35% and wide QRS). ${}^{597,598}$ Although no dedicated RCTs

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exist,SMR reduction by at least one grade has been described in 40%-60% of patients and is associated with reverse LV remodelling and im-proved clinical outcomes. ${}^{597,599,600}$

9.2.4.2. Indications for intervention

The management of patients with ventricular SMR should be discussed by a multidisciplinary Heart Team including HF specialists. The indica-tion for intervention is based on the persistence of symptoms(i.e.NYHA class II-V) despite adequate GDMT and CRT, if indicated

(Figure 13). GDMT is the only option for very frail patients or those with limited life expectancy.

In the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation(COAPT) trial, M-TEER was shown to be safe and reduced recurrent HF hospitalization and all-cause mortality at 2 and 5 years of follow-up, compared with optimized GDMT in patients with ventricular SMR without relevant CAD.583,584 In a second study(Percutaneous Repair with the MitraClip Device for

 Figure 13 Treatment of severe secondary mitral regurgitation without concomitant coronary artery disease. CAD, coronary artery disease; CRT,cardiac resynchronization therapy; GDMT,guideline-directed medical therapy; HF,heart failure; HTx,heart transplantation; LVAD,left ventricular assist device; MV,mitral valve;SMR,secondary mitral regurgitation;TEER,transcatheter edge-to-edge repair.aSee Table 7.bSee Supplementary data online,Table S2.

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Severe Functional/Secondary Mitral Regurgitation, MITRA-FR), no dif-ferences were demonstrated for the combined primary endpoint of all-cause mortality or HF hospitalization at 1 and 2 years. 601,602 These di-verging results might be explained by effect sizes of the trials, differences in trial design, patient selection and follow-up, echocardiographic assess-ment of SMR severity, use of GDMT, and technical factors.603-605 A third RCT, the Randomized Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation(RESHAPE-HF-2) trial showed a 36%reduction in the rates of HF hospitalization or cardiovascular death at 2 years in the intervention arm driven by reduction of first or recur-rent HF hospitalization. When considered in isolation, cardiovascular mortality was not significantly reduced during the observation period.In addition, there was a significant improvement in quality of life as measured by the KCQ overall score(mean difference between study groups,10.9 points;95% CI,6.8-15.0;P<0.001).606 A recent study-level meta-analysis of these three trials showed a significant reduction of HF rehospitalization at 24 months(HR, 0.63, 95% CI, 0.50-0.80) and the composite of death and all-cause hospitalizations(HR,0.72,95% CI,0.51-0.999). ${}^{607}$ However, there was no statistically significant difference in death from any cause or cardiovascular death at 24 months.Transcatheter edge-to-edge repair is therefore recommended to re-duce HF hospitalizations, and improve quality of life, in symptomatic pa-tients with persisting severe SMR despite optimized GDMT fulfilling specific clinical and echocardiographic criteria(Table 7). Although less challenging than in PMR, anatomical suitability for TEER needs to be as-sessed upfront(Supplementary data online, Table S2). There is also in-creasing observational evidence supporting the use of TEER for the improvement of symptoms, functional capacity, and quality of life in pa-tients with ventricular SMR not fulfilling the clinical and echocardio-graphic criteria for outcome improvement. 608-612 This particularly applies to patients not tolerating GDMT in whom TEER may help up-titation, as well as those with recent myocardial infarction and persist-ent severe ventricular SMR. ${}^{203,613}$

Transcatheter implantation of an indirect annuloplasty device into the coronary sinus has been proposed as an alternative that preserves valve integrity. Despite rather modest SMR reduction(22.4% decrease in mitral RVol) and no significant effect on quality of life in a small sham-controlled RCT, symptomatic improvement and reverse remodelling were observed in registries at 1 year. ${}^{614,615}$ Heart transplantation or left ventricular assist device(LVAD) implantation should be considered in selected patients with severe ventricular SMR and advanced HF.

In patients with ventricular SMR without relevant CAD, indications for isolated MV surgery are restrictive owing to procedural risks and the absence of proven mortality benefits. The Multicenter,Randomized, Controlled Study to Assess Mitral Valve Reconstruction for Advanced Insufficiency of Functional or Ischemic Origin(MATTERHORN) trial, which included a mixed population mainly com-posed of patients with ventricular SMR(84%), demonstrated that TEER is non-inferior to surgical repair or replacement with regard to a com-posite endpoint of death, HF hospitalization, MV reinvention, im-plantation of an assist device, or stroke within 1 year after the procedure, and showed a better safety profile.617 In patients with se-vere ischaemic ventricular SMR and concomitant CAD requiring coron-ary revascularization, MV surgery at the time of CABG is recommended, unless the patient is at high surgical risk and/or the cor-onary anatomy is suitable for PCI. Although isolated undersized mitral annuloplasty is the most commonly performed MV repair procedure,

recurrent MR rates were high with this technique in an RCT618 and re-verse LV remodelling is limited, especially in patients with an increased tenting area(>1.35 cm2/m2 BSA), 619 in whom MV replacement is usu-ally required.620 The addition of subvalvular modification in patients with LV dilatation and pronounced MV leaflet tenting may improve re-sults for MV repair,621 but durability and impact on HF symptoms with this technique require further investigation.

The treatment of moderate ischaemic SMR in patients undergoing CABG remains controversial. Meta-analyses, including four RCTs com-paring CABG with concomitant MV surgery vs CABG alone, have shown lower rates of recurrent MR but no benefit in terms of mortality and clinical outcomes.622-624 Therefore, clinical decision-making should weigh peri-operative risks of more complex surgery against the long-term risk of MR progression.

9.2.4.3. Follow-up

Patients with ventricular SMR need to be followed up carefully after intervention by an HF specialist, because they remain at increased risk of events despite intervention. The 5-year cumulative incidence of all-cause death or HF hospitalization was 73.6% in the device arm of the COAPT study.584 Clinical, laboratory, and echocardiographic evaluation every 3 or 6 months, according to the HF stage, is recom-mended. Durability of the procedural result, as well as congestion status and the need for further GDDM optimization facilitated by SMR reduc-tion,613 need to be assessed. Patients and families should be trained in monitoring vital signs, body weight, and HF symptoms to avoid late hos-pital admissions and facilitate management of possible decompensation.Also, patients must be educated on the importance of not discontinuing medical therapies after intervention since the two treatments(devices and drugs) are complementary.

Patients with ventricular SMR, who are asymptomatic and/or have moderate or dynamic MR, should undergo clinical and echocardio-graphic follow-up at least twice per year.

Table 7 Clinical and echocardiographic criteria pre-dicting outcome improvement in patients with severe ventricular secondary mitral regurgitation undergoing mitral transcatheter edge-to-edge repair

|Anatomy deemed suitable for M-TEER| |---| |NYHA class≥II| |LVEF 20%-50%| |LVESD≤70 mm| |At least one HF hospitalization within the previous year or increased| |natriuretic peptide levels(BNP≥300 pg/mL or NT-proBNP≥1000 pg/mL)| |SPAP≤70 mmHg| |No severe RV dysfunction| |No Stage D or advanced HF| |No CAD requiring revascularization| |No severe AV and/or TV disease| |No hypertrophic, restrictive, or infiltrative cardiomyopathies| |AV,aortic valve; BNP, brain natriuretic peptide; CAD, coronary artery disease; HF, heart| |failure; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic| |diameter; M-TEER, mitral transchateter edge-to-edge repair; NT-proBNP, N-terminal| |pro-B-type natriuretic protein; NYHA, New York Heart Association; RV, right ventricle/| |right ventricular; SPAP, systolic pulmonary artery pressure; TV, tricuspid valve.|

AV,aortic valve; BNP, brain natriuretic peptide; CAD, coronary artery disease; HF, heart failure; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; M-TEER, mitral transchatheter edge-to-edge repair; NT-proBNP, N-terminal pro-B-type natriuretic protein; NYHA, New York Heart Association; RV, right ventricle/right ventricular; SPAP, systolic pulmonary artery pressure; TV, tricuspid valve.

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9.2.5. Management of atrial secondary mitral regurgitation

9.2.5.1. Medical therapy and rhythm management

In patients with atrial SMR, underlying causes need to be recognized and treated. Associated HFpEF and AF should be managed according to the relevant Guidelines. ${ }^{7,340}$ The use of SGLT2is should be encouraged in patients with HFpEF due to their proven efficacy in reducing cardiovas-cular death and HF hospitalization. ${ }^{625}$ Limited data show that rhythm control may contribute to reduce arial SMR severity and reverse LA dilatation. ${ }^{626}$

9.2.5.2. Indications for intervention

Registry data demonstrate that patients with atrial SMR are typically elderly with associated AF. Mitral valve surgery has been recently asso-ciated with lower rates of HF hospitalizations and mortality compared with GDMT in a matched population, despite a higher risk profile in the surgical arm at baseline.627 Data from several observational studies also suggest that surgical annuloplasty is effective and durable in patients with atrial SMR, because it counteracts the main mechanism of MR progres-sion.628-630 Its combination with surgical AF ablation(Maze procedure)and concomitant LAAO may have further advantages,630,631 while the fre-quently associated relevant TR can also be addressed during the same pro-cedure.627 Transcatheter edge-to-edge repair may also be considered because observational studies have demonstrated high safety and proced-ural success,588-590,632,633 as well as compared with surgery in a small sub-group(n=34) of the MATTERHORN RCT.634 However, the risk of increased gradient due to planar leaflet coaptation, large regurgitant jet,and limited MV area(MVA) needs to be taken into consideration.592,635 Further studies are warranted to investigate the treatment modalities of patients with atrial SMR.

9.2.5.3. Follow-up

Patients with atrial SMR undergoing surgical or transcatheter intervenent tion should be followed up on a yearly basis, including clinical and echo-cardiographic evaluation. In cases of HFpEF, as an underlying cause of atrial SMR, consultation with an HF specialist is necessary.

Asymptomatic patients with severe atrial SMR not fulfilling the cri-teria for an intervention should undergo clinical and echocardiographic follow-up at least once per year.

Recommendation Table 7-Recommendations on in-dications for intervention in secondary mitral regurgitation(see also Supplementary data online,Evidence Tables 17-20)

|Recommendations|Classa|Levelb| |---|---|---| |Severe atrial secondary mitral regurgitation||| |MV surgery, surgical AF ablation, if indicated, and LAAO should be considered in symptomatic patients with severe atrial SMR under optimal medical therapy.627-630,636,637|lla|B| |TEER may be considered in symptomatic patients with severe atrial SMR not eligible for surgery after optimization of medical therapy including rhythm control, when appropriate.588,590,638,639|lb|B|

|Ventricular secondary mitral regurgitation and concomitant coronary artery disease||| |---|---|---| |MV surgery is recommended in patients with severe ventricular SMR undergoing CABG.640|I|B| |MV surgery may be considered in patients with moderate SMR undergoing CABG.622-624,641,642|llb|B| |PCI followed by TEER after re-evaluation of MR may be considered in symptomatic patients with chronic severe ventricular SMR and non-complex CAD.150|llb|C| |Severe ventricular secondary mitral regurgitation without concomitant coronary artery disease||| |TEER is recommended to reduce HF hospitalizations and improve quality of life in haemodynamically stable, symptomatic patients with impaired LVEF(<50%) and persistent severe ventricular SMR, despite optimized GDMT and CRT(if indicated),fulfilling specific clinical and echocardiographic criteria.c58,584,606,608,643|I|A| |TEER may be considered for symptom improvement in selected symptomatic patients with severe ventricular SMR not fulfilling the specific clinical and echocardiographic criteria,c after careful evaluation of LVAD or HTx.203,608-610|llb|B| |MV surgery may be considered in symptomatic patients with severe ventricular SMR without advanced HF who are not suitable for TEER.617|llb|C|

AF,atrial fibrillation; CABG, coronary artery bypass crafting; CAD, coronary artery disease;CRT, cardiac resynchronization therapy; GDMT, guideline-directed medical therapy; HF,heart failure; HTx, heart transplantation; LAAO, left atrial appendage occlusion; LVAD,left ventricular assist device; LVEF, left ventricular ejection faction; MR, mitral regurgitation; MV, mitral valve; PCI, percutaneous coronary intervention; SMR,secondary mitral regurgitation; TEER, transcatheter edge-to-edge repair.

${}^{3}$ Class of recommendation.

Ⓑ Level of evidence.

<EndOfPara>See Table 7.

10. Mitral stenosis

10.1. Prevalence and aetiology

The aetiology of MS is most frequently rheumatic or degenerative,while rare forms can be drug-induced, inflammatory, or carcinoid-related. Rheumatic fever is the most common cause of MS and death due to VHD worldwide. Its prevalence has decreased in high- and middle-income countries, but remains a major health-care problem in low-income countries, where it predominantly affects young patients.12,187,644 Degenerative MS related to MAC is a distinct age-dependent pathology requiring different treatment strategies.645-647 Both aetiologies are more frequent in females.648

10.2. Rheumatic mitral stenosis

10.2.1. Evaluation

Echocardiography is the preferred method for screening in endemic re-gions and the assessment of the severity, extent of anatomical lesions,and haemodynamic consequences of MS. Involvement of other valves,particularly secondary TR, should be identified. Mitral valve area using

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2D planimetry is the most commonly used measurement to assess stenosis severity, but 3D TTE and TOE have additional diagnostic value. ${}^{649}$ An MVA of≤1.5 cm2 in conjunction with clinical factors(symptoms, high risk of thromboembolism, or haemodynamic decom-pensation) is indicative of clinically severe MS. Mean transvalvular gradi-ent and pulmonary pressures reflect its consequences and have prognostic value. ${}^{649,650}$ Leaflet thickening and fibrosis, along with com-missural fusion and shortening of the subvalvular apparatus, are the most important pathomechanisms of stenosis associated with RHD.The presence and extent of leaflet and subvalvular calcifications influ-ence treatment decisions. Scoring systems have been developed to as-sess the suitability of patients for percutaneous mitral commissorutomy(PMC)(see Supplementary data online, Table S3).651-653

Exercise testing is indicated in asymptomatic patients or patients with symptoms that are equivocal or discordant with the severity of stenosis. Exercise echocardiography provides additional information on exercise capacity and related changes in mitral gradient and pulmon-ary artery pressure, and is preferred over DSE, especially when there are contraindications to dobutamine. ${}^{654}$ Transoesophageal echocardi-ography should be systematically performed in PMC candidates to ex-clude LA thrombus or after an embolic episode, and may play an essential role for procedural guidance. ${}^{52,655}$

10.2.2. Medical therapy

Diurets, beta-blockers, digoxin, non-dihydropyridine calcium channel blockers, and inabradine can improve symptoms by controlling volume overload and heart rate. Anticoagulation with a VKA with a target inter-national normalized ratio(INR) between 2 and 3 is indicated in patients with AF, and DOACs should be avoided in patients with an MVA of≤2.0 cm2 according to current evidence. 165,656,657 Interventions to re-store sinus rhythm(cardioversion or catheter pulmonary vein isolation)are unlikely to be successful in patients with untreated severe MS. If AF is of recent onset and the LA moderately enlarged, cardioversion can be attempted soon after successful intervention or in patients with mod-erate MS combined with anamoroid treatment. 658,659 In patients in sinus rhythm, OAC is indicated after systemic embolism or if a throm-bus is present in the LA, and should also be considered when TOE shows dense spontaneous echocardiographic contrast or an enlarged LA(M-mode diameter>50 mm or LA volume>60 mL/m2).660 Prophylaxis of infective endocardits is indicated as appropriate.5

10.2.3. Indications for intervention

The type(PMC or surgery) and timing of treatment should be decided based on clinical characteristics, the anatomy of the valve and subvalv-ular apparatus, and local expertise. 661-663 The management of clinically severe rheumatic MS is summarized in Figure 14 and Recommendation Table 8.

In general, indication for intervention should be limited to patients with clinically severe rheumatic MS(MVA<1.5 cm2) in whom PMC is expected to have a significant impact on clinical outcome. In higher-income countries, where the incidence of rheumatic fever and the num-ber of PMCs performed is low, this treatment should be restricted to expert operators in specialized centres to improve safety and proced-ural success rate. ${}^{661,664}$ Efforts should be made to increase the availabil-ity of PMC in lower-income countries, where access to treatment is limited for economic reasons. ${}^{665,666}$ Percutaneous mitral commissorotomy may be also considered in symptomatic patients with an MVA of>1.5 cm2, if symptoms cannot be explained by another cause and if the anatomy is favourable(see Table 8). Percutaneous mitral

commissoromy should be considered as a first-line treatment for pa-tients with anatomically suitable rheumatic MS and mild-to-moderate calcification without severe subvalvular impairment. Selected patients with unfavourable anatomical and clinical characteristics can still benefit from PMC, particularly if they are at increased surgical risk. When symptomatic restenosis occurs after surgical commissorotomy or PMC,reintervention in most cases requires surgical valve replacement,but redo PMC can be proposed in selected candidates with favourable characteristics, if the predominant mechanism is commissaral refusion.Long-term follow-up has shown favourable results following PMC des-pite a growing number of elderly patients with suboptimal clinical and anatomical characteristics.663-665

For patients in whom PMC is contraindicated(Table 8), surgical MV repair or, more frequently, replacement are good alternatives.Although repair is much more challenging than for PMR, it can be at-tempted at experienced centres. 663

For patients with multiple VHD including MS, a comprehensive evaluation by the Heart Team and an individualized approach is neces-sary. Surgery is preferable to PMC in patients with severe MS and se-vere AV disease, unless the surgical risk is high. In selected cases with severe MS and moderate AV disease, PMC can be performed to post-pone surgical treatment of both valves.

In high-risk cases with concomitant severe TR, PMC may be consid-ered in selected patients with sinus rhythm, moderate atrial enlarge-ment, and secondary TR due to post-capillary PH. In non-high-risk cases, surgery on both valves is preferred.651,652,662,667 Treatment of patients with low-gradient severe MS(MVA<1.5 cm2, mean gradient<10 mmHg) is challenging, because these patients are often older and have unfavourable anatomy. 668,669

10.2.4. Follow-up

Asymptomatic patients with clinically severe MS who have not under-gone intervention should be followed up yearly by TTE, and at longer in-tervals(2-3 years) in cases of moderate stenosis. After PMC, the post-procedural MVA and mean mitral gradient are important para-meters that influence long-term clinical outcomes. Follow-up of patients after successful PMC is necessary because asymptomatic restenosis may occur. Progressive rheumatic involvement of other valves should be peri-odically assessed, irrespective of the therapy modality.Finally, education and the engagement of the family is key in patients with rheumatic MS,since it usually affects young individuals and women of childbearing age.

10.3. Degenerative mitral stenosis with mitral annular calcification

Patients presenting with MAC are elderly and have significant comorbid-ities, including disease of other valves. Mitral annular calcification is also an indicator of cardiovascular disease severity and is associated with an in-creased risk of AF, stroke, and death.670,671 The incidence of MAC varies substantially, depending on the age of the studied population and the im-aging modality used. It can be a consequence of many different patho-logical processes and, depending on the underlying disease, can be accompanied by stenosis, regurgitation, or both. However, most patients with MAC do not have significant valvular dysfunction.647,672

Generally, MS occurs due to calcific extension into the MV leaflets or subvalvular apparatus, and in some patients it is associated with com-bined MR.673 Treatment options(including transcatheter and surgical approaches) are high-risk procedures and evidence from RCTs is lacking.

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 Figure 14 Management of clinically severe rheumatic mitral stenosis(mitral valve area≤1.5 cm2). AF, atrial fibrillation; LA, left atrium; MS, mitral stenosis; MV,mitral valve;MVA,mitral valve area;NCS,non-cardiac surgery;NYHA,New York Heart Association;PH, pulmonary hypertension;PMC, percutaneous mitral commissotomy; SPAP, systolic pulmonary artery pressure; TR, tricuspid regurgitation. High thromboembolic risk: history of systemic embolism, dense spontaneous contrast in the LA, new-onset AF. High-risk of haemodynamic decompensation: SPAP>50 mmHg at rest,need for major NCS, desire for pregnancy or pregnant.bSee Table 8.‘Favourable=absence of unfavourable characteristics for PMC defined by un-favourable anatomical characteristics[echocardiographic score>8,Cormier score 3(calcification of MV of any extent as assessed by fluoroscopy),severe TR] or unfavourable clinical characteristics(old age, history of commissotomy, NYHA class IV, permanent AF, severe PH)(for the definition of scores see Supplementary data online, Table S3). dIf operative risk is low.

10.3.1. Evaluation

Echocardiography is used for initial evaluation, but is frequently limited by acoustic shadowing due to severe calcification. Evaluation of MVA by planimetry is less reliable than in rheumatic MS, and TOE should therefore be used liberally. Degenerative MS can coexist with varying degrees of MR. Mean transmitral gradient has been shown to be asso-ciated with increased mortality irrespective of MR severity. ${}^{674}$ Electrocardiogram-gated CCT is necessary to assess the degree and lo-cations of calcifications, especially if an intervention is planned. ${}^{647,674-676}$

Calcifications are usually more prominent at the posterior aspect of the annulus.

10.3.2. Indications for intervention

Intervention is recommended in symptomatic patients who are not re-sponsive to medical therapy, weighing the potential benefits of the pro-cedure against its associated risks. In elderly patients with degenerative MS and MAC, surgery is technically challenging and high risk. However,

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surgical MV repair or replacement with extensive decalcification and patch reconstruction of the annulus can be performed in selected patients at experienced centres(e.g. young patients post-chest radiation), where mortality rates of<5% have been reported. 677-679

Degenerative MS is not amenable to PMC because commissural fu-sion is absent. In symptomatic high-risk patients with suitable anat-omy, transcatheter implantation of a TAVI prosthesis in the mitral position is feasible but associated with frequent complications, includ-ing LVOT obstruction, valve embolization, stroke, and haemolysis due to PVL. Open surgical valve replacement via the LA with a TAVI device is an alternative that allows complete anterior leaflet removal,680 however, mortality remains high. The use of dedicated TMVI devices is therefore encouraged because it appears to be safer.542,681 Heart Team evaluation should guide the choice of treatment avoiding futility,because mortality remains high, even after successful treatment(10%-30% within 1 year).

Recommendation Table 8- Recommendations indications for percutaneous mitral commissorutomy,rmital valve surgery, and transcatheter intervention in clinically severe rheumatic and degenerative mitral stenosis(see also Supplementary data online,Evidence Table 21)

|Recommendations|Classa|Levelb| |---|---|---| |PMC is recommended in symptomatic patients in the absence of unfavourable characteristics for PMC. c 651-653,662,665|1|B| |PMC is recommended in any symptomatic patients with a contraindication or at high risk for surgery.|1|C| |MV surgery is recommended in symptomatic patients who are not suitable for PMC.|1|C| |PMC should be considered as initial treatment in symptomatic patients with suboptimal anatomy but no unfavourable clinical characteristics for PMC. c|1|C| |PMC should be considered in asymptomatic patients without unfavourable clinical and anatomical characteristics for PMC, and:||| |● High thromboembolic risk (history of systemic embolism, dense spontaneous contrast in the LA, new-onset or paroxylamal AF), and/or|1Ia|C| |● High risk of haemodynamic decompensation (SPAP>50 mmHg at rest, need for major NCS, pregnant or desire for pregnancy).||| |TMVI may be considered in symptomatic patients with extensive MAC and severe MV dysfunction at experienced Heart Valve Centres with expertise in complex MV surgery and transcatheter interventions.|1Ib|C|

AF,atrial fibrillation; LA, left atrium/left atrial; MAC,mitral annular calcification; MV,mitral valve;NCS,non-cardiac surgery;NYHA,New York Heart Association;PH,pulmonary hypertension; PMC, percutaneous mitral commissortry; SPAP, systolic pulmonary artery pressure; TMVI, transcatheter mitral valve implantation; TR, tricuspid regurgitation.Class of recommendation.

bLevel of evidence.

aLvel of evidence. ${}^{c}$ Unfavourable characteristics for PMC can be defined by the presence of several of the following characteristics: clinical characteristics(old age, history of commissoratory,NYHA class IV, permanent AF, severe PH); anatomical characteristics[echocardiographic score>8,Cormier group 3 (calculation of MV of any extent as assessed by fluoroscopy),severe TR] (for the definition of scores see Supplementary data online, Table S3).

Table 8 Contraindications for percutaneous mitral commissorotomy in rheumatic mitral stenosis

|Contraindications| |---| |MVA>1.5 cm2 a| |LA thrombusb| |More than mild MR| |Severe or bi-commissural calcification| |Absence of commissural fusion| |Severe concomitant AV disease, or severe combined tricuspid stenosis and| |regurgitation requiring surgery| |Concomitant CAD requiring bypass surgery|

AV, aortic valve; CAD, coronary artery disease; LA, left atrium/left atrial; MR, mitral regurgitation; MVA, mitral valve area; OAC, oral anticoagulation; PMC, percutaneous mitral commissorotomy; TOE, transoesophageal echocardiography.

aPMC may be considered in patients with MVA of>1.5 cm2 with symptoms that cannot be explained by another cause and if the anatomy is favourable.

bWhen the thrombus is located in the LA appendage, PMC may be considered in patients with contraindications to surgery or those without urgent need for intervention, in whom OAC can be safely given for 1-3 months, provided repeat TOE confirms resolution of thrombus.

11. Tricuspid regurgitation

11.1. Prevalence and aetiology

TR is a common echocardiographic finding in the general population,with higher prevalence in women and older patients. Trivial or mild TR is mostly a benign condition. Significant TR(≥ moderate) has a re-ported age- and sex-adjusted prevalence of 0.55%(4% in people aged≥75 years).682 Severe TR is associated with increased risk of death and HF, independent of comorbidities, ventricular function, and pul-monary pressures.683-686

Only 8%-10% of patients with TR present with clear anatomical ab-normalities of the TV apparatus(primary TR), which can be due to infect-ive endocarditis,RHD,carcinoid syndrome, congenital abnormalities(e.g.Ebstein's anomaly), chest radiation, or myxomatous disease, as well as trauma or atrogenic valve damage(e.g.after endomyocardial biopsy).Cardiac implantable electronic device(CIED)-related TR represents a separate entity requiring a specific diagnostic approach and manage-ment. ${}^{687}$ In patients with a CIED, diagnostic efforts should be made to clarify if the lead is the cause of TR(CIED-related TR) or incidental(CIED-associated TR).

In patients with secondary TR,TV leaflets are structurally normal and regurgitation is caused by annular dilatation and/or leaflet tethering due to RA dilatation, and/or RV dilation and dysfunction. Based on the main morphological and haemodynamic characteristics, two phenotypes of secondary TR have been proposed:689(i) atrial secondary TR,mainly due to AF and characterized by the absence of significant leaflet tether-ing, but with marked RA and annular dilatation along with preserved RV size/function, pulmonary pressure, and LV function; and(ii) ventricular secondary TR, due to annular dilatation and leaflet tethering as a con-sequence of left-sided ventricular or valvular disease(post-capillary PH), pre-capillary PH, or primary RV cardiomyopathy/ischaemia(also after left-sided valve surgery). At an advanced disease stage, these two phenotypes may no longer be distinguishable, and therefore early characterization is key to determine outcome. 691,692 Evidence of an im-pact on patient management is currently lacking; therefore, current recommendations for intervention consider mainly primary vs second-ary TR.

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11.2. Evaluation

Echocardiography is recommended to assess patients with TR45 and should include evaluation of severity and aetiology(including character-ization of left-sided heart disease and, if applicable, CIED lead location and interaction with the valve apparatus), the impact of TR on the right-sided chambers(RV and RA size and function), and assessment of cen-tral venous(inferior vena cava) and pulmonary pressures. Transthoracic echocardiography provides sufficient diagnostic information in most patients. Transoesophageal echocardiography is necessary for when visualization of the TV apparatus. In candidates for an intervention, ad-vanced techniques, such as strain analysis and 3D echocardiography,should also be applied when available.

Assessment of TR severity should be ideally performed in evolupe-mic status, with optimized pulmonary and systemic pressures, and based on an integrative approach considering multiple qualitative and quantitative parameters(Figure 15). 45,693 A grading scheme extending beyond severe, including'massive' and'torrentor' grades, has been pro-posed to refine TR reduction assessment after transcatheter interven-tions and has been used in several studies. ${}^{694,695}$ Although this five-grade scale may be associated with a proportional increase in symptoms and event risk, ${}^{694,695}$ an intervention should be considered without delay, as soon as TR is severe, with the aim of reducing TR to moderate or less. ${}^{696,697}$

Echocardiographic assessment of the RV is challenging due to its complex geometry, imaging constraints, and the high dependency on loading conditions. When accurate measurements of RV size and func-tion, as well as RV volume, are necessary for decision-making, CMR should be used because of its high accuracy and reproducibility. 698,699 In Figure 15, upper limits of normal for different RV size parameters are provided to guide definition of RV dilatation and remodelling. In the setting of severe TR, RV function is often overestimated and there-fore the most conservative/cautious thresholds are suggested for the currently used echocardiographic parameters to identify RV dysfunc-tion at the earliest stage possible. Cut-off values for severe RV dysfunc-tion are also provided to indicate high-risk or possibly futile interventions. Although robust validation is lacking, all these reference values are chosen based on large multicentre reports of normative data and outcomes. 60,697,700-704

Echocardiography often underestimates pulmonary pressures in cases of severe TR.705 Right heart catheterization is therefore recom-mended in all candidates for an intervention to assess the haemo-dynamic consequences of TR on the RA and venous circulation(e.g.ventricularization of the RA pressure curves), measure end-diastolic RV pressure, and document volume overload. The assessment of pul-monary pressures and vascular resistance are key to exclude masked severe pre-capillary PH.706

RV-pulmonary artery coupling refers to the ability of the RV systolic performance to match a given pulmonary afterload maintaining ad-equate cardiac output, and can be measured invorally or approxi-mated using echocardiography[i.e. tricuspid annular plane systolic excursion(TAPSE)/SPAP].707,708 RV-pulmonary artery uncoupling(low TAPSE/SPAP) occurs when sustained increases in afterload can-not be matched by RV contractile reserve and has been associated with poor prognosis in different HF conditions, including severe TR.Although not yet prospectively validated, this index may improve risk stratification.

Electrocardiogram-gated CCT with dedicated protocols ensuring sufficient contrast enhancement of the right heart cavities provides de-tailed characterization of the RA, RV, and vena cava anatomy, the loca-tion of the right coronary artery, and is crucial to assess suitability and device sizing for several transcatheter interventions. 689,697

Before any intervention is considered, careful evaluation of TR aeti-ology, disease stage(TR severity,RV and LV dysfunction, and PH),pa-tient operative risk, and likelihood of recovery by a dedicated collaborative Heart Team is recommended(Figure 16). Dedicated clin-ical risk scores for TR patients have been described recently. The TRI-SCORE ${}^{709}$ and the TS isolated TV risk calculator ${}^{710}$ take into con-sideration clinical and echocardiographic signs of RV dysfunction, and secondary organ(particularly hepatic and renal) impairment. They both allow improved estimates of peri-procedural risk in patients with severe TR undergoing surgery and possibly help to avoid futile in-terventions.84,711 The importance of risk stratification was demon-strated in a recent registry analysis(n=2413) comparing any interventions with conservative management. Early TV intervention(transcatheter valve repair or surgery) was associated with improved mid-term survival in patients with a low or intermediate TRI-SCORE(up to 5 points), while patients with a high TRI-SCORE(≥6) did not de-rive any benefit compared with conservative management.Moreover, isolated TV surgery(repair or replacement) improved sur-vival at 10 years in patients with a low TRI-SCORE(≤3). The same benefit was observed in patients with an intermediate TRI-SCORE(4-5) after successful TV repair only. ${}^{689,697,709}$ Patients with moderate or severe TR should be regularly followed up clinically and by echocar-diography at least every 6 months.

11.3. Medical therapy

Patients with relevant TR should be first treated according to the as-sumed aetiology, including optimal HF treatment, pulmonary vasodila-tors for PH, and rhythm control for AF.339,693

In the case of HF symptoms, diuretics should be initiated in a step-wise approach,339 beginning with loop diuretics eventually combined with aldosterone antagonists, thiazide diuretics, and/or SGLT2is.71 However, according to current knowledge, medical therapy has very limited effect on the evolution of TR severity and none of these mea-sures should delay evaluation of an intervention at an expert centre.

11.4. Indications for intervention

11.4.1. Surgery

Patients are often referred too late for surgery when significant RV and other organ failure have occurred. Isolated TV surgery has therefore been considered to be generally high risk, with in-hospital mortality rates of 8%-10% in several reports, ${}^{714,715}$ but contemporary cohorts have demonstrated improved outcomes when patients are referred earlier and more effective techniques are used. ${}^{716}$ Valve repair using an annuloplasty ring is preferred over replacement, whenever technic-ally feasible, especially in low-risk patients with suitable anatomy. ${}^{709}$ However, TV replacement may be necessary in cases of advanced dis-ease with marked annular dilatation and leaflet tethering. ${}^{688,717}$ For CIED-related TR, preparation of any entrapped tricuspid leaflet and possibly lead extraction with implantation of an epicardial system has been associated with improved TV function. ${}^{688,717}$

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 Figure 15 Echocardiographic and invasive assessment of tricuspid regurgitation. 3D, three-dimensional; CIED, cardiac implantable electronic device;CW,continuous-wave;EROA,effective regurgitant orifice area;FAC,fractional area change;FWS,free wall strain;GLS,global longitudinal strain;mPAP,mean pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; PH, pulmonary hypertension; PISA, proximal isovelocity surface area; PVR,pulmonary vascular resistance; RF, regurgitant fraction; RV, right ventricle/ventricular; RVEF, right ventricle ejection fraction; RVol, regurgitant volume;TAPSE, tricuspid annular plane systolic excursion;TDI,tissue Doppler imaging;TR,tricuspid regurgitation;VCA, vena contracta area; WU, wood unit.S'RV apical focused view.

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 Figure 16 Stepwise evaluation of patients with tricuspid regurgitation.RV, right ventricle/right ventricular."See Supplementary data online, Table S4.

11.4.1.1. Patients without indication for left-sided valve surgery

In patients with severe TR but without the need for left-sided valve sur-gery, surgical intervention is recommended in operable symptomatic patients with primary TR(Figure 17; Recommendation Table 9).178 Furthermore, it should be considered in symptomatic patients with sec-ondary TR, or in asymptomatic patients with primary or secondary TR and signs of RV dilatation or RV function deterioration. ${}^{719}$ However,patients with severe LV/RV dysfunction or PH do not qualify due to high operative risk.84,686,720

11.4.1.2. Patients with indication for left-sided valve surgery

Severe primary or secondary TR is unlikely to improve after isolated surgical treatment of left-sided valve disease, and reoperation for TR treatment is associated with high peri-operative mortality. ${}^{721}$ Therefore, TV surgery is recommended at the time of the index procedure.

Mild TR with associated significant annular dilatation or moderate TR, if left uncorrected at the time of left-sided valve surgery, will pro-gress in approximately one-quarter of patients and is associated with worse outcome. ${}^{690,722}$ In patients with moderate TR, TV repair annu-loplasty during MV surgery should be considered, because large retro-spective studies ${}^{723,724}$ and two recent RCTs have shown beneficial effects on TR progression and RV remodelling over time." ${}^{725,726}$ However,no effects on mortality,HF events, or reoperation were ob-served in the repair group. ${}^{725,727}$ Concomitant TV repair has also been associated with a higher risk of conduction disturbances requir-ing pacemaker implantation(up to 14%), ${}^{725,728}$ with potential negative impacts on longer-term outcomes. ${}^{729,730}$ In patients with mild TR and annular dilatation(≥40 mm or>21 mm/m2) undergoing left-sided valve surgery, previous observational studies have demonstrated a benefit of concomitant TV repair in terms of TR progression ${}^{723,724}$ and RV function, ${}^{731}$ and a trend towards improved long-term survival.However, a subanalysis of a recent RCT did not identify any difference in the progression of TR or other outcomes in this category of patients

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during a 2-year follow-up period. ${}^{725}$ In turn, the need of pacemaker im-plantation after surgery led to a subsequent increase in HF hospita-lizations,endocarditis,and mortality. ${}^{729}$ Annuloplasty may therefore be considered after careful evaluation of the risk factors for progres-sive annular dilatation and TR(AF, RA size, pulmonary pressures,etc.), balancing against the risk of possible pacemaker implantation(Supplementary data online, Table S5). ${}^{732}$

11.4.2. Transcatheter techniques

Several transcatheter approaches for the treatment of TR have been developed,including TEER,direct annuloplasty,and orthotopic and het-erotopic TV replacement.Data from large multicentre registries,single-arm clinical trials, and two recent RCTs in patients with severe TR at intermediate and high risk for surgery have shown the safety of trans-catheter repair, as well as the ability to reduce TR to moderate or less in

 Figure 17 Management of patients with tricuspid regurgitation. LV, left ventricle/left ventricular;RV, right ventricle/right ventricular;TA, tricuspid annulus;TR,tricuspid regurgitation;TV,tricuspid valve.3The Heart Team with expertise in the treatment of TV disease evaluates anatomical eligibility for transcatheter therapy including jet location, coaptation gap, leaflet tethering, and potential interference with pacing lead. ${}^{b}$ Repair whenever possible,particularly in cases of moderate TR or mild TR with significant TA dilatation.

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more than 80% of cases when anatomical suitability was con-firmed.713,733-735 The Clinical Trial to Evaluate Cardiovascular Outcomes in Patients Treated With the Tricuspid Valve Repair System(TRILUMINATE) Pival trial showed also a lower incidence of the composite endpoint of death from any cause or TV surgery,HF hospitalization, and improvement in quality of life as measured with the KCCQ score after tricuspid TEER compared with medical treatment that was exclusively driven by improved quality of life[11.7 points(95% CI, 6.8-16.6); P<0.001].713 At 2 years, a lower inci-dence of HF hospitalizations has been observed in the intervention group, despite a high rate of crossovers(59%).736

Another investigator-initiated RCT(the FriTri) demonstrated the benefit of tricuspid TEER in combination with GDMT over medical therapy alone, for a composite score driven by improved PROMs. ${}^{737}$ Another recent RCT(the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy using a Novel Device(TRISCEND) II trial),compar-ing transcatheter TV replacement with optimized medical therapy in patients with symptomatic severe TR, showed similar results with a win ratio favouring TV replacement mainly explained by symptom and quality-of-life improvement. In these studies, reverse RV remodel-ing(15%) and post-procedural pacemaker implantation in about one-quarter of the pacemaker-naive patients after 12 months of follow-up. ${}^{738}$ Based on these data, transcatheter treatment should be consid-ered to improve quality of life and RV remodeling in high-risk patients with symptomatic severe TR, despite optimal medical therapy, but without severe RV dysfunction or pre-capillary PH.

Transvenous CIED lead repositioning or extraction can be consid-ered in selected patients to improve TR or avoid lead jailing before any tricuspid interventions, although the efficacy of this procedure is uncertain and the risk of damaging the TV not negligible.68,717,739

Recurrent TR after previous tricuspid annuloplasty usually requires car-diac reoperation for surgical TV replacement. Transcatheter valve-in-ring implantation is an off-label procedure to treat residual TR in high-risk pa-tients.Challenges are the non-circular shape and the open form of the sur-gical annuloplasty ring.470 However, transcatheter tricuspid valve-in-valve procedures have been performed with satisfactory results. ${}^{741}$

Transcatheter TV procedures should be performed at an ex-perienced Heart Valve Centre with expertise in the treatment of TV disease(Table 6). Careful evaluation of clinical and anatomical suitability is key for appropriate patient and device selection to achieve optimal TR reduction and symptomatic response to the therapy.

Recommendation Table 9-Recommendations on in-dications for intervention in tricuspid regurgitation(see also Supplementary data online, Evidence Tables 22 and 23)

|Recommendations|Classa|Levelb| |---|---|---| |Careful evaluation of TR aetiology, stage of the disease(i.e. degree of TR severity,RV and LV dysfunction, and PH), patient operative risk, and likelihood of recovery by a multidisciplinary Heart Team is recommended in patients with severe TR prior to intervention.691,742|1|C|

Continued

Patients with tricuspid requiring and left-sided valvular heart disease requiring surgery

Concomitant TV surgery is recommended in patients with severe primary or secondary 1275,731,743,744 Concomitant TV repair should be considered in patients with moderate primary or secondary TR, to avoid progression of TR and RV IIa remodelling.723,724,726,731 Concomitant TV repair may be considered remodelling.723,724,726,731 in selected patients with mild secondary TR and tricuspid annulus dilatation(≥40 mm or>21 mm/m2), to avoid progression of TR and RV remodelling.723-726,731,743

Patients with severe tricuspid regurgitation without left-sided valvular heart disease requiring surgery

TV surgeryc is recommended in symptomatic patients with severe primary TR without severe RV dysfunction or severe PH.TV surgeryc should be considered in asymptomatic patients with severe primary TR who have RV dilatation/RV function deterioration, but without severe LVRV dysfunction or severe PH.TV surgeryc should be considered in patients with severe secondary TR who are symptomatic or have RV dilatation/RV function deterioration, but without severe LVRV dysfunction or symptomatic or have RV dilatation/RV function deterioration, but without severe LVRV dysfunction or or PH.685,720,745-747

Transcatheter TV treatment should be considered to improve quality of life and RV remodelling in high-risk patients with symptomatic severe TR despite optimal medical therapy in the absence of severe RV dysfunction or pre-capillary PH.

LV, left ventricle left ventricular; PH, pulmonary hypertension; RV, right ventricle/right ventricle; TR, tricuspid regurgitation;TV,tricuspid valve.

Class of recommendation.

bLevel of evidence.

cValve repair whenever possible.

12. Tricuspid stenosis

12.1. Prevalence and aetiology

Tricuspid stenosis(TS) is a relatively rare disease that is most commonly associated with congenital conditions or enzymatic disorders, such as Whipple's or Fabry's disease. It can also be acquired as an isolated mani-festation of RHD or occur in combination with aortic and/or MV involve-ment. Moreover, TS can be the consequence of carcinoid disease due to serotonin-mediated proliferation, causing apposition of fibroblasts and extracellular matrix on the valve leaflets and the subvalvular apparatus.Rare causes include modifications(e.g. fenfluramine or methysergide) or in-flow obstruction due to CIED-associated thrombus formation or endo-carditis with large vegetations.

12.2. Evaluation

Valve valuation and diagnosis of TS is based on echocardiography, and consists of the anatomical assessment of the leaflet tissue and the sub-valvular apparatus. Leaflet thickening with or without calcifications and

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commissar fusions are pathognomonic findings of rheumatic involve-ment. A mean diastolic transvalvular gradient of>5 mmHg at a normal heart rate indicates severe TS. 649

12.3. Medical therapy

Medical therapy is a bridge to surgical or transcatheter intervention.Intensive sodium restriction and concomitant diuretic therapy can lead to symptom improvement and diminish hepatic congestion.

12.4. Indications for intervention

Although valve repair is preferred in younger patients, ${}^{752}$ valve replace-ment is frequently required(see Recommendation Table 10). Biological heart valves have demonstrated adequate mid- and long-term results,and are preferred over MHVs because of high thrombogenicity in the low-pressure system. ${}^{753}$ In the case of BHV degeneration, transchater valve-in-valve procedures are good alternatives to re-replacement. ${}^{754}$ Transcatheter TV implantation is an emerging field, although limited ex-perience is available for the treatment of TS. ${}^{749,755}$ In patients with car-cinoid disease, a stable oncological situation is a prerequisite for any valve intervention to maximize survival and valve durability. ${}^{756}$

Although data are very limited, TV balloon vuloplasty can be an option in selected patients with TS(and no relevant TR), as well as in those with concomitant mitral and tricuspid rheumatic pathology.757 However, in contrast to rheumatic MS, tricuspid rheumatic disease more frequently presents as combined stenosis and regurgitation,which limits the applicability of balloon vuloplasty.

Recommendation Table 10- Recommendations on indications for intervention in tricuspid stenosis

|Recommendations|Classa|Level| |---|---|---| |Surgeryc is recommended in symptomatic patients with severe TS.d|1|C| |Surgeryc is recommended in patients with severe TS undergoing left-sided valve intervention。|1|C|

MV, mitral valve; PMC, percutaneous mitral commissoratory; TS, tricuspid stenosis; TV,tricuspid valve.

aClass of recommendation.

bLevel of evidence.

aUsually TV replacement.

dPcrutaneous balloon valuloplasty can be attempted as a first approach if TS is isolated. ePcrutaneous balloon valuloplasty can be attempted if PMC can be performed on the MV.

13. Multiple and mixed valvular heart disease

13.1. Prevalence and undertreatment

Patients frequently present with disease of more than one native heart valve[multiple VHD(MVHD)], or coexisting stenosis and regurgitation of the same valve(mixed VHD).758 While the main cause of MVHD or mixed VHD has shifted to degeneration in high-income countries, the leading aetiology in low- and middle-income countries remains RHD.758,759 Regurgitation of atrioventricular valves secondary to cardio-myopathy or long-standing primary valve disease, and late effects of radi-ation therapy, are further causes of MVHD.758,760 Challenges in diagnostic evaluation coupled with limited data to guide clinical decisions contribute to late referral and undertreatment of patients with MVHD.758

13.2. Evaluation and diagnostic pitfalls

In view of the complex haemodynamic interplay of multiple and mixed valve lesions,assessment by a Heart Team at a Heart Valve Centre and use of an integrative multimodality approach is key to gain diagnostic certainty, detect cardiac damage, and evaluate therapeutic op-tions.761,762 In the light of paucity of data on diagnostic and prognostic parameters in patients with MVHD, assessment largely focuses on pathophysiological considerations and evidence derived from isolated valve lesions.

Echocardiography is the main tool to diagnose MVHD, assess mech-anism, severity, and associated cardiac damage, and monitor disease progression.761 Haemodynamic interdependence between multiple valve defects alters the leading and flow conditions, thereby limiting the diagnostic validity of measures established to grade single valve de-fects(Table 9). In the presence of MVHD, low-flow states are frequent.The continuity equation becomes erroneous if transvalvular flows are unequal, and pressure half-time(PHT)-derived methods are inaccurate if the ventricular compliance or filling is altered.761 In this context,TOE can provide important detailed anatomical and mechanistic flow-independent information. 46,761

If symptoms or echocardiographic findings are equivocal, multimod-ality diagnostics should be considered on an individual basis to assess the cumulative repercussions of MVHD.

Measures obtained during cardiopulmonary exercise testing reflect the effect of MVHD on functional capacity.52,105,654,761,779 Levels of natriuretic peptides such as NT-proBNP correlate with functional and echocardiographic parameters, and provide incremental prognos-tic value in patients with mixed aortic disease and MVHD.98,780 AV cal-cium scoring confirms the diagnosis of true severe AS under low-flow conditions, as described in Section 8.2.777 Cardiac magnetic resonance imaging enables the independent assessment of valvular regurgitation using volumetric methods or direct flow quantification.45,46,522,762,781 Importantly, invasive cardiac output-derived measures based on thermodilution or the Fick equation using estimated oxygen uptake are inaccurate in low-flow conditions or severe TR, commonly pre-sent in MVHD.782

13.3. Indications for intervention

Given the heterogeneity of clinical scenarios and the lack of evidence on optimal treatment pathways, it is recommended that patients with MVHD are evaluated for intervention by a collaborative Heart Team at a Heart Valve Centre with experience in multimodality imaging and treatment of complex VHD.16,764

Patients presenting with a lesion fulfilling criteria for an intervention based on recommendations for single VHD should be treated accord-ingly.In the remaining patients, assessment of symptoms and functional status, as well as cardiac damage(which may be masked by the conse-quences of concomitant lesions and occur before symptoms manifest),is required. The risk-benefit ratio of intervention needs to take into account diagnostic(uncertability, the mechanisms and severity of MVHD, and patient-specific factors, as well as procedural options and risks to determine the mode, timing, and sequence of valve treatment.

13.3.1. Multiple valvular heart disease

Multiple VHD with primary(as opposed to secondary) valvular disease usually requires surgical treatment of all relevant valvular lesions.Sultaneous treatment of concomitant severe valve defects is recom-mended and treatment of concomitant moderate AS, or moderate TR,should be considered(Recommendation Table 11).

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Table 9 Echocardiographic pitfalls, robust measures, and complementary multimodality imaging parameters in mul-tiple or mixed valvular heart disease

|||Valve lesion to be assessed|||| |---|---|---|---|---|---| |Concomitant valve lesion|AS AR||MS|MR|| |Concomitant valve lesion|AS AR|PHT unreliable LV volume increase less pronounced (hypertrophy, disproportionate diastolic LV pressure overload763)|PHT unreliable (LV compliance ↓ 764) Low gradient due to low flow possible (low-flow state669)|Regurgitant volume↑ MR colour-flow jet area↑ (increased afterload and transmitral systolic pressure gradient46)|| |AR|Simplified Bernoulli equation overestimates gradient if LVOT velocity ↑ 765|-|PHT unreliable (gradient 1, altered LV compliance766) MVA by continuity equation using aortic forward flow unreliable|Doppler volumetric method using net aortic forward flow invalid Mitral-to-aortic VTI ratio unreliable (increased transaortic flow46)|| |AR|Simplified Bernoulli equation overestimates gradient if LVOT velocity ↑ 765|Low-flow low-gradient possible (low-flow state761)|-|Mital-to-aortic VTI ratio unreliable (increased mitral VTI due to stenosis 767) Calcifications may shadow jet area|| |MR|Low-flow low-gradient (MR-induced low-flow state768) AS confused with MR jet|PHT unreliable (altered LV compliance763) Doppler volumetric method using net mitral forward flow invalid (increased flow46)|PHT unreliable (altered LA and LV compliance769,770) Continuity equation (low flow761)|-|| |MR|TR|-|Low gradient possible (TR induced low-flow state"71)|Low gradient possible (low-flow state668) PHT may be less reliable (impaired LV filling due to ventricular|Regurgitant volume↓ in SMR possible (decreased preload774)| |Robust echocardiography measurements||AVA(continuity equation), DVI761 In mixed AR and AS: Vmax and mean gradient reflect combined burden765|EROA(PISA), vena contracta46,761|Planimetry and 3D MVA(TOE)529,775 In mixed MR & MS: mean gradient reflects combined burden674,776|EROA(PISA), vena contracta46,761| |Alternative imaging modalities|CT: AV calcium scoring|CMR: regurgitant volume and fraction 45,46|-||CMR: regurgitant volume and fraction 45,46|

Measures reported refer to assessment of the valve lesions listed in the columns. Adapted from ${}^{761}$

3D,three-dimensional;AR,aortic regurgitation;AS,aortic stenosis;AV,aortic valve;AVA,aortic valve area;CMR,cardic magnetic resonance;CT,computed tomography;DVI,Doppler velocity index;EROA,effective regurgitant orifice area;LA,left atrium/left atrial;LV,left ventricle/left ventricular;LVOT,left, ventricular outflow tract;MR,mitral regurgitation;MS,mitral stenosis;MVA,mital valve area;PHT,pressure half-time;PISA,proximal isovelocity surface area;SMR,secondary mitral regurgitation;TOE,transoesophageal echocardiography;TR,tricuspidregurgitation;VHD,valvular heart disease;Vmax,peak transvalvular velocity;VTI,velocity time integral;↑,increase;↓,decrease;-,none.

Transcatheter treatment options are established for severe AS(TAVI), rheumatic MS(PMC), and primary MR and TR(TEER or trans-catheter replacement) in patients with MVHD at high surgical risk, if anatomy is suitable.401,783 In the context of a transcatheter strategy,a staged approach-typically beginning with the downstream lesion

(aortic, followed by mitral and tricuspid)-is generally preferred to avoid potential haemodynamic deterioration. ${}^{784,785}$

MVHD with severe secondary regurgitation of both atrioventricular valves is usually the consequence of either HFrEF with ventricular SMR and secondary TR, or atrial dilatation leading to both atrial MR and TR

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(often TR> MR). While surgery aims to address all relevant valve lesions in a single procedure, a stepwise transcatheter strategy offers the possi-bility of reassessing the upstream valve(s) under altered loading condi-tions, usually 3 months after the initial intervention. In very selected cases simultaneous transcatheter valve treatment may be consid-ered.788,789 However, evidence is limited and primarily derived from modestly sized observational studies.786-789

13.3.2. Mixed aortic valve disease

The severity of mixed AV disease is often underestimated and patients with balanced moderate AR and AS show adverse event rates compar-able to patients with severe isolated AS.790,791

Transvalvular gradients measured by Doppler reflect the overall haemodynamic burden of both regurgitation and stenosis, and are strong-ly associated with adverse outcomes.765,791-793 Therefore, the presence of high transvalvular gradients justifies valve intervention in patients with moderate mixed AV disease, even if regurgitation is graded as mod-erate and the calculated or planimetric AVA is>1 cm2(Recommendation Table 12). Patients presenting with mixed AV disease, but with gradients below thresholds for intervention, should undergo careful multimodality diagnostics including assessment of cardiac damage to inform individual treatment strategies. Global longitudinal strain and natriuretic peptides have shown incremental prognostic value beyond symptom status and single lesion severity in patients with preserved LVEF.762,794-796

13.3.3. Mixed mitral valve disease

Mixed MV disease is usually present in patients with rheumatic valve dis-ease or MAC. If MVA is≤1.5 cm2, recommendations for isolated MS apply. However, patients with an MVA of>1.5 cm2 and moderate MR may be evaluated for valve replacement based on symptoms, ana-tomical characteristics,transmitral gradient, and signs of cardiac damage such as LA dilatation, AF, or PH.529,674,776,797

Recommendation Table 11- Recommendations on indications for surgery of concomitant left-sided valu-lar heart disease

|Recommendations|Classb|Level| |---|---|---| |Concomitant aortic stenosis||| |SAVR is recommended in patients with severe AS undergoing surgery for another valve.|I|C| |SAVR should be considered in patients with|lla|C| |moderate Asd undergoing surgery for another valve.||| |Concomitant aortic regurgitation||| |AV surgery is recommended in patients with severe AR undergoing surgery for another valve.|I|C| |MV surgery is recommended in patients with severe MR undergoing surgery for another valve.|||

AR, aortic regurgitation; AS, aortic stenosis; AV, aortic valve; AVA, aortic valve are; MR, mitral regurgitation; MV, mitral valve; SAVR, surgical aortic valve replacement; TV, tricuspid valve;Recommendations for surgery of concomitant TV disease are listed in Section 11 and Section 12.bClass of recommendation.

Level of evidence.

${}^{d}$ Defined as an AVA of 1.0-1.5 cm ${}^{2}$ (or mean aortic gradient of 25-40 mmHg) in normal-flow conditions. Clinical assessment is essential to determine whether SAVR is appropriate for an individual patient.

Recommendation Table 12- Recommendations on indications for intervention in patients with mixed mod-erate aortic stenosis and moderate aortic regurgitation(see also Supplementary data online, Evidence Table 24)

|Recommendations|Classa|Levelb| |---|---|---| |Intervention is recommended in symptomatic patients with mixed moderate AV stenosis and moderate regurgitation||| |||| |Intervention is recommended in symptomatic patients with mixed moderate AV stenosis and moderate regurgitation||| |||| |Av, aortic valve; AV, aortic valve; LVEF, left ventricular ejection fraction; V max, peak|||

AV,aortic valve;AVA,aortic valve area;LVEF,left ventricular ejection fraction;V max,peak transvalvular velocity.

aClass of recommendation.

bLevel of evidence.

cVA>1cm2.

13.4. Follow-up

Due to the cumulative haemodynamic impact of MVHD or mixed VHD, progression of its severity and the development of cardiac dam-age may be faster than in single VHD.761 Therefore, follow-up intervals should be adjusted according to individual patient characteristics.

14. Management of patients with prosthetic valves or valve repair

14.1. Choice of prosthetic valve

When choosing between an MHV and a BHV prosthesis for an individual patient, age, life expectancy, lifestyle, bleeding and thromboembolic risks,possibility of pregnancy, and patient preference should be considered Life expectancy is estimated according to age, sex, comorbidities, ethnicity,and geographical area.798 An MHV is preferred in younger patients with longer life expectancy and in those with a pre-existing indication for long-term OAC(Recommendation Table 13). Generally, a BHV is implanted in patients with shorter life expectancy, increased bleeding risk due to fraility or comorbidities, in women contemplating pregnancy, and in patients in whom stable INRs with adequate times in therapeutic range are unlikely.799 Importantly, the performance of different BHV prostheses can vary consid-erably.800 The impact of the aetiology of the native valve disease, if any, on the choice between an MHV and a BHV remains unexplored.

Several large observational studies, smaller RCTs, and meta-analyses have compared long-term mortality with BHV and MHV prostheses in patients aged 50-70 years.376,801-805 Some of the studies showed lower mortality with MHV in AV patients<60 years and MV patients<65 years old,801,804 while others failed to show any differ-ences.376,802,803 Most of these studies were limited by their observa-tional nature and missing information on the type of prostheses implanted. RCTs with sufficient statistical power comparing biological and mechanical prostheses are warranted.

Replacement of the AV using an autograft(Ross procedure) is an alternative to an MHV in young patients that should be performed at experienced entries by operators with dedicated expertise(see also Section 8). 806 General recommendations are summarized in Recommendation Table 13.

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Recommendation Table 13- Recommendations for prosthetic valve selection

|Recommendations|Classa|Levelb| |---|---|---| |Mechanical heart valve||| |An MHV is recommended according to the desire of the informed patient and if there is no contraindication to long-term anticoagulation.||C| |An MHV should be considered in patients with an estimated long life expectancy, if there are no contraindications for long-term OAC. 801,807-811|lla|B| |An MHV should be considered in patients aged<60 years for prostheses in the aortic position and aged<65 years for prostheses in the mitral position. ${}^{801,807-811}$|lla|C| |An MHV should be considered in patients with a pre-existing MHV in another position.|lla|C| |An MHV may be considered in patients with a clear indication for long-term OAC.|lb|C| |Biological heart valve||| |A BHV is recommended according to the desire of the informed patient.||| |A BHV is recommended when an adequate quality of anticoagulation with VKA is unlikely, in patients at high bleeding risk, or with estimated short life expectancy.c|l|C| |A BHV should be considered in patients aged>65 years for prostheses in the aortic position or aged>70 years for prostheses in the mitral position.|lla|C| |A BHV should be considered in women contemplating pregnancy.|||

BHV,biological heart valve;MHV,mechanical heart valve;OAC,oral anticoagulation;VKA,vitamin K antagonist.

aClass of recommendation.

°Level of evidence.

Life expectancy should be estimated according to age, sex, comorbidities, ethnicity, and geographical area.

14.2. Follow-up of patients with prosthetic valves

All patients with prosthetic valves require lifelong clinical and echocar-diographic follow-up to detect deterioration of prosthetic function,associated cardiac damage, or progressive disease of another valve.Serial TTE measurements of transprosthetic gradients, calculation of the effective valve area, and evaluation of leaflet motion and morph-ology should be performed in patients receiving a BHV within 3 months after valve implantation, again at 1 year, and annually there-after, or sooner if new cardiovascular symptoms occur.812 TOE is re-commended in all cases of suspected prosthetic valve dysfunction or endocarditis. In the latter case, CCT and PET-CT are also recom-mended, if the diagnosis is unclear, and to identify primary or second-ary infection foci.

Cinefluoroscopy for MHVs and CCT provide useful additional infor-mation, if valve thrombus or pannus is suspected. ${}^{812}$ Imaging should be repeated in the case of thrombolytic and antithrombotic treatment of MVH thrombosis, even if gradients are normalized. ${}^{813}$

14.3. Antithrombotic therapy in patients with treated valvular heart disease

14.3.1. Mechanical heart valve

14.3.1.1. Post-operative anticoagulation and therapeutic targets Mechanical heart valves require lifelong treatment with a VKA guided by the INR. Bridging with either therapeutic unfractionated heparin(UFH) or low-molecular-weight heparin(LMWH) and VKA should be initiated within 24 h after MHV implantation, or as soon as considered safe. Heparin can be stopped when the INR is documented for 2 consecutive days within the therapeutic range(Figure 18). 814 Two meta-analyses and a prospective study have sug-gested slightly lower bleeding rates using UFH bridging compared with LMWH after MHV replacement or cardiac surgery. 814-816 However, RCTs comparing the timing and dosage of each bridging strategy are lacking.

For all patients with an MHV, lifelong VKA is recommended to avoid major thrombotic complications, since cardioembolic or valve thrombosis rates without anticoagulation are substantial(12% per year and 22% per year for first-generation aortic and mitral MHVs,respectively).187 The INR target and range should be chosen consid-ering the type, position, and number of valves, the patient's thrombot-ic risk, and comorbidities(see Table 10 and Recommendation Table 14). In patients with an MHV developing a major thrombo embolic complication despite adequate INR and time in therapeutic range(TTR, usually defined as>60%),°20 either increased VKA inten-sity(e.g. INR target and range increased by 0.5 units) or the addition of low-dose acetylsilicylic acid(ASA)(75-100 mg/day) should be con-sidered.818 Direct oral anticoagulants or dual antiplatelet therapy(DAPT) are contraindicated to prevent thromboembolism in patients with an MHV.821-824

Given the complexity of lifelong VKA therapy due to high intra-and interpatient variability, the need for monitoring, drug and food interactions,825,826 the narrow therapeutic window, influence of co-morbidities, and non-modifiable characteristics(e.g. ageing,genetics,and ethnicity), RCTs have shown that patient's education, as well as disease and treatment awareness, significantly improves antico-gulation quality and adherence.827-830 International normalized ra-tio self-monitoring and/or self-management increase efficacy, but not safety, as compared with a standard approach; INR self-monitoring can be used by motivated patients after adequate training.827-830

The indication for VKA and DAPT combination in MHV patients presenting with acute coronary syndrome is described in the corre-sponding ESC Guidelines.151,831 In patients with an MHV and an in-dication for single antiplatelet therapy(SAPT) due to symptomatic major atherosclerotic diseases and low bleeding risk, low-dose ASA in combination with a VKA should be considered, because this strategy has been shown to significantly lower the incidence of major adverse cardiovascular events.818 However, the combin-ation of antiplatelet agents(single or dual) and VKA increases the risk of bleeding,825 and therefore their use should be carefully weighted. In a large meta-analysis that included MHV patients, the combination of VKA with either ASA or clopidogrel increased clin-ically relevant bleeding compared with VKA alone(clopidogrel odds ratio, 3.55; 95% CI, 2.78-4.54; ASA odds ratio, 1.50; 95% CI, 1.29-1.74), which may be aggravated because of potential pharmacoki-netic drug interactions on the cytochrome P(CYP)450s 2C19 and 3A4.825

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 Figure 18 Antithrombotic therapy following mechanical heart valve implantation. AF, atrial fibrillation; ASA, acetylsalicylic acid; INR, international normal-ized ratio; LMWH, low-molecular-weight heparin; LV, left ventricle/left ventricular;LVEF, left ventricular ejection fraction;MHV, mechanical heart valve;MS,mitral stenosis;N,no;NCS,non-cardiac surgery;TTR,time in therapeutic range;UFH: unfractionated heparin;VKA,vitamin K antagonist;Y,yes.3Skin;minor eye surgery including cataract; dental cleaning, treatment of caries, and dental extractions; pacemaker or device implantation; and diagnostic cardiac catheter-ization.3MHV in mitral or tricuspid position,older MHV generations in any position, inherited or acquired hypercoagulable state, LV dysfunction(LVEF<35%),AF with significant MS,recent(<12 months) major thrombotic event(i.e. cardioembolic stroke, deep vein thrombosis, pulmonary embolism).Cbridging needs to be started as soon as INR reaches a sub-therapeutic value and on the first postoperative day or as soon as considered safe.

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Recommendation Table 14- Recommendations for the management of antithrombotic therapy in patients with a mechanical heart valve

|Recommendation|Recommendation|Recommendation|Recommendation| |---|---|---|---| |Re|Recommendations|Classa|Levelb| |Following cardiac surgery with MHV implantation,it is recommended to start UFH or LMWH bridging and VKA within 24 h, or as soon as considered safe. 815,816,832-834|I|I|B| |Lifelong OAC with a VKA is recommended for all patients with MHVs to prevent thromboembolic complications. 821-823,835-838|I|A|| |INR self-monitoring and self-management are recommended over standard monitoring in selected, trained patients to improve efficacy. 827,828|I|I|A| |It is recommended that INR targets are based on the type and position of the MHV, patient risk factors, and comorbidities.c 818,819,835-838|I|I|A| |It is recommended that INR targets are based on the type and position of the MHV, patient risk factors, and comorbidities.c 818,819,835-838|Patient education is recommended to improve the quality of OAC. 827-830|I|A| |The addition of low-dose ASA(75-100 mg/day) to VKA should be considered in selected patients with MHVs in case of concomitant symptomatic atherosclerotic disease considering the individual bleeding risk profile. 818|lla|B|| |Either an increase in INR target or the addition of low-dose ASA(75-100 mg/day) should be considered in patients with MHVs who develop a major thromboembolic complication despite documented adequate INR. 818|lla|C|| |DOACs and/or DAPT are not recommended to prevent thrombosis in patients with an MHV. 821-824|III|A||

ASA, acetylsicalylic acid; DAPT, dual atplatelet therapy; DOAC, direct oral anticoagulant; h,hour; INR, international normalized ratio; LMWH, low-molecular-weight heparin; MHV,mechanical heart valve; OAC,oral anticoagulation; UFH, unfractionated heparin; VKA, vitamin K antagonist.

aClass of recommendation.

bLevel of evidence.

$c\infty$ Table 10 for details.

Table 10 International normalized ratio targets and therapeutic ranges for patients with a mechanical heart valve

|MHV type and position|Additional pro-thrombotic factorsa|INR target and(range)| |---|---|---| |First-line treatment with VKA only||| |Ball-in cage, tilting disc valve|No|3(2.5-3.5)| |in any position, all MHV in|Yes|3.5(3-4)b| |mitral/tricuspid position||| |Bileaflet, current-generation|No|2.5(2-3c)| |single-tilting aortic MHV|Yes|3(2.5-3.5)|

AF,atrial fibrillation; ASA, acetylsalicylic acid; INR, international normalized ratio; LV, left ventricle/left-lvent; LVEF, left ventricular ejection fraction; MHV, mechanical heart valve;MS, mitral stenosis; VKA, vitamin K antagonist.

$^{a}$ Inherited or acquired hypercoagulable state, LV dysfunction(LVEF<35%), AF with significant MS, recent(<12 months) major thrombotic event(i.e. cardioembolic stroke, deep vein thrombosis, pulmonary embolism).

bIn patients at very high thrombotic risk, low-dose ASA may be added instead.818 In patients at high bleeding risk, INR target could be maintained at a lower interval:2(1.5-2.5).819

14.3.1.2. Prevention and management of bleeding

Since patients with MHVs receive lifelong VKA, strategies to prevent bleeding need to be implemented. Proton pump inhibitors reduce the risk of upper gastrointestinal bleeding by approximately 40% in pa-tients taking VKAS 825,839,840 and should therefore be prescribed to pa-tients with MHVs, particularly in those with additional bleeding risk factors (e.g. elderly, antiplatelet agent co-administration, chronic use of non-steroidal anti-inflammatory drugs, high INR, or alcohol abuse).Randomized controlled trials and a meta-analysis did not demonstrate a benefit of oral vitamin K1 supplementation in addition to temporary VKA cessation in non-bleeding patients with a supratherapeutic INR(4.5-10.0), with a trend toward reduced safety, which may be relevant for MHV patients. 841,842 For non-bleeding patients with an INR of

>10.0,oral vitamin K1(2.0-3.0 mg) should be administered, avoiding overcorrection.841,843

In cases of uncontrolled life-threatening or other major bleeding,VKA use must be interrupted and reversal with non-activated four-factor prothrombin complex concentrates is preferred over fresh frozen plasma, because of higher safety and effectiveness.845-848 A reduced starting dose(12.5 rather than 25 IU/kg) in patients with more thrombo-genic MHVs may be considered.849 In addition, vitamin K1 should be ad-ministered to reverse the effect of VKA. Intravenous route corrects INR~4h faster than oral administration,850 with no differences at 24 h and an unknown clinical impact. VKA should be restarted as soon as major bleeding is controlled.

14.3.1.3. Management of anticoagulation therapy before and after non-cardiac invasive procedures

In patients with an MHV,VKA treatment should not be interrupted for:minor or minimally invasive procedures on the skin or eyes(including cataract with topical anaesthesia); dental cleaning,treatment of caries,and dental extractions, pacemaker implantation; cardiac catheterization;and endoscopic procedures(Recommendation Table 15; Table 11).851-851 Topical antibirnilyotic or haemostatic agents may improve local haemostasis.853

In patients with an MHV and high thromboembolic risk(Recommendation Table 16; Table 11) undergoing non-cardiac, elective major invasive procedures with high risk of bleeding (see Supplementary data online, Table S6), VKA treatment must be inter-rupted at least 4 days before the procedure, bridging with LMWH should be started as soon as the INR reaches a subtherapeutic value,and the INR should be <1.5 on the day of surgery.816,857,858 Measuring anti-Xa activity at peak and trough may be appropriate to manage LMWH dosing in selected patients, such as those with severe obesity or underweight.859 In cases of urgent, major invasive proce-dures, four-factor thrombotic complex concentrate should be admi-nistrated to timely correct the INR for the intervention, if needed. For the management of antithrombotic drugs in patients undergoing major cardiac surgery, please refer to recent EACTS Guidelines.860

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Recommendation Table 15- Recommendations for the management of antithrombotic therapy in patients with a mechanical heart valve undergoing elective non-cardiac surgery or invasive procedures

|Recommendations|Classa|Levelb| |---|---|---| |Continuing VKA treatment is recommended in patients with an MHV for minor or minimally invasive interventions ${}^{c}$ associated with no or minimal bleeding $_{51}-856$|I|A| |It is recommended to discontinue VKA at least 4 days before major non-cardiac elective surgery, aiming for an INR<1.5, and to resume VKA treatment within 24 h after surgery, or as soon as considered safe. ${}^{816,857,858}$|I|B| |VKA interruption and resumption with bridging ${}^{d}$ should be considered in patients with an MHV and thromboembolic risk factors ${}^{e}$|lla|B| |undergoing major NCS. ${}^{816,857,858}$||| |Interruption(3-4 days before surgery) and resumption of VKA without bridging may be considered to reduce bleeding in patients with new-generation aortic MHVs and no other thromboembolic risk factors ${}^{e}$ undergoing major NCS or invasive procedures.|llb|B|

AF,atrial fibrillation; h, hour; INR, international normalized ratio; LV,left ventricular; LVEF,left ventricular ejection fraction; MHV,mechanical heart valve; MS,mitral stenosis; NCS,non-cardiac surgery; VKA, vitamin K antagonist.

aClass of recommendation.

bLevel of evidence.

{Skin; minor eye surgery including cataract; dental cleaning, treatment of caries, and dental extractions; pacemaker or device implantation; diagnostic cardiac catheterization; gastroscopic,colonoscopic, bronchoscopic, or genitourinary diagnostic or therapeutic procedures considered at low bleeding risk.

Bridging needs to be started as soon as INR reaches a subtherapeutic value and on the first post-operative day or as soon as considered safe.

M4HV in mitral or tricuspid position, older MHV generations in any position, inherited or acquired hypercoagulable state, LV dysfunction(LVEF<35%), AF with significant MS, recent(<12 months) major thrombotic event(i.e. cardiopolebolic stroke, deep vein thrombosis, pulmonary embolism).

Table 11 Peri-operative management of antithrombotic treatment in patients with a mechanical heart valve undergo-ing non-cardiac surgery based on type of procedure and underlying risk

||Minimally invasive procedures|Major NCS or invasive procedures| |---|---|---| |Pre-procedure|Post-procedure|Post-procedure|

|Low thromboembolic risk|||||| |---|---|---|---|---|---| |New-generation aortic MHV and no additional risk factorsb|OAC|No interruption of VKA|Continue VKA|Interrupt VKA at least 3-4 days prior to procedure with target INR<1.5 on the day of surgery|Resume VKA as soon as feasible, within 24 h| |New-generation aortic MHV and no additional risk factorsb|Bridging|||No bridging may be considered|No bridging may be considered, unless unable to administer OAC| |New-generation aortic MHV and no additional risk factorsb|Supporting measures||Topical antifibrinolytic or haemostatic agents may be considered to improve local haemostasis||Mechanical and pharmacological VTE prophylaxis, if indicated| |Moderate-to-high thromboembolic risk|||||| |MHV in mitral or tricuspid position or other thromboembolic risk factorsb|OAC|No interruption of VKA|Continue VKA|Interrupt VKA at least 4 days prior to procedure with target INR<1.5 the day of the procedure|Resume VKA within 24 h| |MHV in mitral or tricuspid position or other thromboembolic risk factorsb|Bridging|||Bridging with LMWH or UFH if CKD stage IV or V, starting at INR below the therapeutic range|Bridging with UFH or LMWH post-operatively within 24 h| |MHV in mitral or tricuspid position or other thromboembolic risk factorsb|Supporting measures||Topical antifibrinolytic or haemostatic agents may be considered to improve local haemostasis||Appropriate mechanical and pharmacological VTE prophylaxis|

<FIGTEXT=></FIGTEXT>

AF,atrial fibrillation; CKD, chronic kidney disease; h,hour; INR,international normalized ratio; LMWH, low-molecular-weight heparin; LV, left ventricle/left ventricular; LVEF,left ventricular ejection fraction;MHV, mechanical heart valve;MS,mitral stenosis;NCS,non-cardiac surgery;OAC,oral anticoagulation;UFH,unfractionated heparin;VKA,vitamin K antagonist;VTE,venous thromboembolism.

See Supplementary Table S6.

Inherited or acquired hypercoagable state, LV dysfunction(LVEF<35%), AF with significant MS, recent(<12 months) major thrombotic event(i.e. cardioembolic stroke, deep vein thrombosis, pulmonary embolism).

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For patients with an MHV and low cardioembolic risk (e.g. a new-generation MHV in the aortic position without additional risk factors)undergoing elective major NCS or invasive procedures, VKA interrupt-tion (3-4 days before surgery) 816,857,858,861-864 and resumption 861-863 within 24h may be performed without bridging to reduce post-surgical bleeding without increasing the risk of thrombosis (see Figure 18).

14.3.2. Biological heart valves

The management of antithrombotic treatment after BHV implantation or valve repair is summarized in Recommendation Table 16 and Figure 19.

14.3.2.1. Patients with a surgical biological heart valve and no indication for oral anticoagulation

The optimal antithrombotic strategy early after surgical implantation of aortic BHV remains controversial due to the lack of high-quality evi-dence. Multiple observational studies support the short-term use of VKAs to reduce the risk of thromboembolism, ${}^{865,866}$ while data on DOACs are missing. A small RCT and a meta-analysis found that VKA treatment for 3 months significantly increased major bleeding compared with low-dose ASA, without reducing mortality or

<EndOfPara>brroomboembolic events, but statistical power was low.867,868 Therefore, both strategies (OAC or ASA) are reasonable within 3 months of surgical aortic BHV implantation. In the absence of rando-mized evidence, patients undergoing mitral or tricuspid BHV implant-ation should receive OAC for at least 3 months due to the increased risk of AF and thromboembolisms.

14.3.2. Patients with a transcatheter heart valve and no indication for oral anticoagulation

Based on evidence from RCTs, lifelong low-dose ASA is the recom-mended antithrombotic treatment after TAVI in patients without OAC indication.In the Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation(POPular TAVI) trial (cohort A),the incidence of bleeding and the composite of bleeding or thromboembolic events were both reduced with ASA compared with DAPT at 1 year.869 One RCT [Global multicenter, open-label, ran-domized, event-driven, active-controlled study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortic valve rEplacement(TAVR) to Optimize clinical outcomes, GALILEO], which investigated a systematic

 Figure 19 Antithrombotic therapy following biological heart valve implantation or surgical valve repair. ASA, acetylsalicylic acid; MV, mitral valve;MVR, mitral valve replacement; OAC, oral anticoagulation; SAVR, surgical aortic valve replacement; TAV, transcatheter aortic valve implantation;TV, tricuspid valve; TVR, tricuspid valve replacement.

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antithrombotic strategy of rivaroxaban(10 mg/day) in combination with low-dose ASA compared with DAPT with clopidogrel for the first 3 months, was halted prematurely due to an increased risk of death or thromboembolic complications, and an increased risk of bleeding in the rivaroxaban/ASA group.870 The systematic use of DOACs after TAVI in patients without indication for OAC is therefore not recom-mended. Data on antithrombotic management after implantation of transcatheter mitral BHs or tricuspid BHs are vricuspid KBH's are kunitist treatment for≥3 months is commonly prescribed, while DOACs may represent an alternative allowing for earlier discharge and a lower risk of short-term bleeding complications(median follow-up, 4.7 months).871

For patients without baseline OAC undergoing mitral or tricuspid transcatheter valve implantation, OAC(either with DOAC or VKA)is initiated and usually pursued for at least 6 months or indefinitely(in particular after valve implantation in the tricuspid position), while patients undergoing TEER usually receive single long-term antiplatelet therapy with ASA.

14.3.2.3. Patients with a surgical biological heart valve and an indication for oral anticoagulation

Lifelong OAC is recommended for patients with surgical BHVs with other indications for OAC. The evidence supports the use of DOACs in preference to VKAs in patients with AF, even during the early post-operative period.872-877 A previously existing therapy with a DOAC may be continued after BHV implantation and should be re-started, as soon as considered surgically, safe usually, usually within 2-3 days of surgery.860

14.3.2.4. Patients with a transcatheter biological heart valve and an indication for oral anticoagulation

In the POPULAR TAVI trial(cohort B), the incidence of bleeding over a per-iod of 1 month or 1 year was lower with OAC than with OAC plus clo-pidogrel.878 Oral anticoagulation alone was non-inferior to OAC plus clopidogrel with respect to ischaemic events, but the non-inferiority mar-gin was large. In Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having undergone Transcaterhe Aortic Valve Implantation-Atrial Fibrillation(ENVISAGE-TAVI-AF),879 edoxaban was non-inferior to VKA regarding the composite primary endpoint(death from any cause, myocardial infarction, ischaemic stroke, systemic thromboembolic event, valve thrombosis, or major bleeding), but the in-cidence of major bleeding was higher with edoxaban than with VKA.The Anti-Thrombotic Strategy to Lower All Cardiovascular and Neurologic isemic and Hemorrhemic Events after Trans-Aortic Valve Implantation for Aortic Stenosis(ATLANTIS) trial880 showed that apixaban was not superior to VKA after TAVI when there was a pre-existing indication for OAC, and there was a signal of higher non-cardiovascular mortality with apixaban. Therefore, no definitive recommendation can be made concerning the use of VKAs vs DOACs in patients who have undergone TAVI with a pre-existing indication for OAC.

Antithrombotic therapy after transcatheter MV or TV implantation remains empirical because data are limited. A high proportion of pa-tients are already under OAC because of AF(almost 50% of the popu-lation with MR and 80%-90% of the candidates for TR treatment).Common practice is to continue the pre-existing anticoagulation regi-men. Vitamin K antagonists and DOACs have been used in this setting with or without combination with ASA. ${}^{871}$ However, the high bleeding risk of this usually elderly population needs to be taken into consideration.

Recommendation Table 16- Recommendations for the management of antithrombotic therapy in patients with a biological heart valve or valve repair

|Recommendations|Classa|Levelb| |---|---|---| |Surgical biological heart valve without indication for oral anticoagulation||| |Low-dose ASA(75-100 mg/day) or OAC using a VKA should be considered for the first 3 months after surgical implantation of an aortic BHV in patients without clear indication for OAC.865,866|IIa|B| |A VKA should be considered for the first 3 months after surgical implantation of a mitral or tricuspid OHV in patients without clear indication for OAC.867,868|IIa|B| |Lifelong low-dose ASA(75-100 mg/day) may be considered 3 months after surgical implantation of an aortic or mitral BHV in patients without clear indication for OAC.|IIb|C| |Transcatheter aortic valve implantation without indication for oral anticoagulation||| |Low-dose ASA(75-100 mg/day) is recommended for 12 months after TAVI in patients without 869,880-883|I|A| |Long-term(after the first 12 months) low-dose ASA (75-100 mg/day) should be considered after TAVI in patients without clear indication for OAC.|IIa|C| |DAPT is not recommended to prevent thrombosis after TAVI, unless there is a clear indication.881|III|B| |Routine use of OAC is not recommended after TAVI in patients without baseline indication.869,880|III|A| |Surgical repair without indication for oral anticoagulation||| |OAC, with either VKAs or DOACs, should be considered during the first 3 months after surgical MV or TV repair.884-888|IIa|B| |Low-dose ASA(75-100 mg/day) should be considered for the first 3 months after surgical AV repair in patients without indication for OAC.|IIa|C| |Low-dose ASA(75-100 mg/day) may be considered after surgical MV or TV repair in preference to OAC in patients without clear indication for OAC and at high bleeding risk.884-888|IIb|B| |Surgical biological heart valve with indication for oral anticoagulation||| |OAC continuation is recommended in patients with a clear indication for OAC undergoing surgical BHV implantation.877,889,890|I|B| |DOACs should be considered over VKAs after patients with A BHV in patients with A BHV in|IIa|B| |3 months following surgical implantation of a BHV in patients with AF.872-874,876,891|IIa|B| |DOAC continuation may be considered after surgical BHV implantation in patients with an indication for DOAC.877,889,890|IIb|B|

Continued

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Transcatheter biological heart valve with indication for oral anticoagulation OAC is recommended for TAVI patients who have other indications for OAC.879,892-894 Surgical repair with indication for oral anticoagulation and/or antiplatelet therapy continuation of OAC or antiplatelet therapy should be considered after surgical valve repair in patients with a clear indication for an antithrombotic therapy.890

AF,atrial fibrillation; ASA, acetylsalicylic acid; AV, aortic valve; BHV, biological heart valve;DAPT,dual antiplatelet therapy; DOAC,direct oral anticoagulant; MV,mitral valve; OAC,oral anticoagulation; TAVI, transcatheter aortic valve implantation; TV,tricuspid valve; VKA,vitamin K antagonist.

aClass of recommendation.

${}^{a}$ Level of evidence.

14.4. Management of prosthetic valve dysfunction and complications

Prosthetic valve dysfunction can occur due to intrinsic permanent changes to the prosthetic valve(defined as SVD) or non-structural valve dysfunction resulting from any abnormality not intrinsic to the pros-thetic valve itself. Valve thrombosis and endocarditis are considered separate entities due to their specific presentation and management,but may both result in SVD.

14.4.1. Structural valve deterioration

Structural valve deterioration has been defined by several consensus documents812,895.896 and includes wear and tear, leaflet disruption,

leaflet fibrosis or calcification, and stent or strut fracture or deform-ation. BHV(transchater or surgical) SVD is more frequent than MHV SVD.The incidence of SVD may be underestimated by the simple analysis of patients with valve-related deaths or those undergoing rein-tervention. To ensure timely diagnosis, serial measurement should be performed and compared with the TTE performed at discharge, or within 1-3 months after valve implantation.

The criteria for haemodynamic deterioration associated with aortic and mitral SVD can be found in Table 12.895,896 The diagno-sis of moderate or severe haemodynamic deterioration should prompt referral to an experienced Heart Valve Centre for evalu-ation and treatment, and to exclude all causes of non-structural valve dysfunction, particularly PVL or PPM, as well as thrombosis and endocarditis. This step requires the use of advanced imaging techniques(TOE,CCT, and/or PET-CT) to document SVD-related morphological changes and elucidate its mechanism.Structural valve deterioration associated with corresponding clinic al criteria(e.g. new onset or worsening of symptoms, LV or RV dilation/dysfunction, or PH) indicates BHV failure with potential need for reintervention. Decisions about the treatment modality(redo surgery or transcatheter valve-in-valve implantation) should be made within the interdisciplinary Heart Team, depending on re-operation risk and anatomical considerations,445,897 including the risk of coronary obstruction,144,442,446,461 as well as prosthesis type and size.898-900 When considering a valve-in-valve procedure for a degenerated aortic BHV, the possibility of creating a PPM in small valves should be anticipated and may impact intervention or valve selection.448

Given the larger sizes of BHVs in mitral or tricuspid positions, trans-femoral/transseptal valve-in-valve implantation represents an attractive alternative to redo open surgery. ${}^{570,900-903}$ In the case of mitral valve-in-valve implantation.

Table 12 Criteria for the diagnosis of moderate or severe aortic and mitral haemodynamic valve deterioration

||Moderate|Severe| |---|---|---| |Aortic BHV SVD or non-structural valve dysfunction(except PVL or PPM),a thrombosis, or endocarditis|Increase in mean transvalvular gradient≥10 mmHg resulting in mean gradient≥20 mmHg AND Decrease in EOA≥0.3 cm2 or≥25%, and/or decrease in DVI≥0.1 or≥20%, compared with echocardiographic assessment performed 1-3 months post-procedure OR|Increase in mean transvalvular gradient≥20 mmHg resulting in mean gradient≥30 mmHg| ||OR|| ||New occurrence or increase of≥1 grade of intraprosthetic AR resulting in≥ moderate AR|OR| |Mitral BHV SVD or non-structural valve dysfunction(except PVL or PPM),b thrombosis, or endocarditis|Increase in DVI≥0.4 or≥20%, resulting in DVI≥2.2, or decrease in EOA≥0.5 cm2 or≥25%, resulting in EOA <1.5 cm2, usually associated with increase of transmitral gradient≥5 mmHg|Increase in DVI≥0.8 or≥40%, resulting in DVI≥2.7, or decrease in EOA≥1.0 cm2 or≥50%, resulting in EOA <1 cm2, usually associated with increase of transmitral gradient≥10 mmHg| ||OR|OR| ||New occurrence or increase of≥1 grade of intraprosthetic AR resulting in≥ moderate AR|New occurrence or increase of≥2 grades of intraprosthetic gradient≥10 mmHg|

Adapted from 895.896

AR, aortic regurgitation; AV, aortic valve; BHV, biological heart valve; DVI, Doppler velocity index; EOA, effective orifice area; MR, mitral regurgitation; PPM, prosthesis-patient mismatch;PVL,paravalvular leak;SVD,structural valve deterioration.

${}^{a}$ Obstruction by pannus; dilatation of the aortic root after stentless BHV; or AV-sparing operations.

${}^{b}$ Leaflet entrapment by pannus, chordae, or suture.

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infrequent, should be carefully ruled out, especially in patients with small and hypertrophic ventricles. 904

14.4.2. Non-structural valve dysfunction

14.4.2.1. Prosthesis-patient mismatch

Prosthesis-patient mismatch should be prevented whenever pos-sible after either transcatheter or surgical valve-replacement pro-cedures(see Section 8.5.1.2). When occurring in the aortic position, severe PPM is associated with decreased quality of life, in-creased rate of rehospitalization and reintervention, and possible reduction in long-term survival, although findings are not consistent throughout all studies.454,905-909 Moderate PPM is more common,but seems to have a limited impact on outcomes. The projected indexed EOA may be predicted prior to valve implantation to avoid severe PPM, although this concept has been challenged.910 Less is known about the prevalence and consequences of PPM in the mitral and tricuspid positions, and established definitions are lacking.

Prosthesis-patient mismatch is an infrequent indication for rein-tervention. However, reoperation should be considered in symp-tomatic patients with severe PPM, particularly if the patient is low risk.394,437,438

14.4.4.2. Paravularv leak and haemolysis

The diagnosis of PVL requires systematic TOE, because TTE may be inconclusive. Haemolytic anaemia can often be detected in patients with prosthetic valves and is best assessed by measuring lactate de-hydrogenase and haptobulin serum levels, but rarely leads to symp-toms. Intervention is needed if a PVL causes haemolysis requiring blood transfusions or symptoms, or if secondary to valve endocarditis.Transcatheter PVL closure is a valid alternative to surgery in the case of significant regurgitation or haemolysis, if feasible depending on the size and location of the leak, but requires specific expertise and plan-ning. Care must be taken not to interfere with mechanical leaflet mo-tion in MHV patients. Reported results for transcatheter PVL closure are inconsistent, with several patients returning with recurrent PVL and/or haemolysis. ${}^{911}$ When surgery or transcatheter intervention are contraindicated, medical therapy aims to counteract the effect of haemolysis(iron supplementation and erythropoietin) or reduce it(beta-blockers. ${}^{912}$

14.4.3. Endocarditis

Antibiotic prophylaxis is recommended in all patients with a pros-thetic valve(including transcatheter valve prostheses) and after valve repair using prosthetic material or with previous episode(s) of infect-ive endocarditis, and should also be considered after transcatheter MV or TV repair.5 It is recommended in such patients when under-going dental extractions, oral surgery, or other procedures requiring manipulation of the gingival or peri-apical region of the teeth.Particular attention to dental and cutaneous hygiene, and strict aseptic measures during any invasive procedure, are also advised in this population. Additional details on endocarditis prophylaxis are mentioned in the 2023 ESC Guidelines for the management of endocarditis.5

14.4.4. Valve thrombosis

Valve thrombosis occurs mainly in MHVs, ${}^{913,914}$ but can also be ob-served in BHVs.915,916 The spectrum of BHV thrombosis ranges from incidental CCT findings, such as hypo-attenuated leaflet thick-ening(HALT) with or without reduced leaflet motion but normal gradients, to clinically apparent presentations with elevated gradients, symptoms of valve obstruction, or thromboembolic events.917-919

14.4.4.1. Hypo-attenuated leaflet thickening

Hypo-attenuated leaflet thickening is detected by CCT in 10%-30% of aortic BHVs depending on antithrombotic management, the definition of HALT, the timepoint of assessment, and the type of valve.917,919-921 The significance and clinical implications of these findings with respect to thromboembolic risk and valve durability remain uncertain.Accordingly, routine use of CCT to detect HALT is not indi-cated.918-920 In patients with relevant increases in gradients, in whom HALT and restricted leaflet motion is confirmed by CCT,elective use of DOACs or VKAs should be considered to resolve leaf-let thrombosis.918,921,922

14.4.4.2. Clinically significant valve thrombosis

Obstructive valve thrombosis should be suspected in any patient with any type of prosthetic valve who presents with new-onset dyspnoae or HF symptoms, an embolic event, or an unexpected in-crease in transvargular gradients. If TTE findings are uncertain, the diagnosis should be confirmed by TOE and/or CCT to distinguish between thrombus, pannus,and degeneration.923-925 Cinefluorcopy can detect impaired MHV leaflet motion and re-duced opening angles.

Adequate anticoagulation must be promptly restored in all patients with MHV thrombosis and subtherapeutic INR. Although surgery re-mains the first-line option in critically ill patients, emergency valve re-placement is associated with increased risk, whereas bleeding and systemic embolism are increased with fibrinolysis.926-928 Slow, low-dose infusion appears to lower complication rates, while preserving thrombolytic success rates. It is recommended that the deci-sion between surgery and fibrinolysis is taken within the Heart Team, and individualized by weighing clinical factors and local expert-ise(Figure 20).

Management of non-obstructive thrombosis or obstructive thrombosis of an MHV without pronounced HF symptoms de-pends mainly on the occurrence of a thromboembolic event and the size of the thrombus. Surgery should be considered for a large(>10mm) non-obstructive prosthetic valve thrombus that is complicated by embolism or persists despite optimal OAC.913,932,933

Anticoagulation using a VKA is the first-line treatment for clinically relevant BHV thrombosis, unless urgent reintervention or fibrinoly-sis is required due to progressive acute HF or haemodynamic instability. 934-938 Because clinically relevant BHV thrombosis is asso-ciated with recurrence and may contribute to prosthetic degener-ation, indefinite anticoagulation may be considered after a confirmed episode, but this strategy must be balanced against the risk of bleeding. ${}^{936,939}$

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 Figure 20 Management of left-sided obstructive and non-obstructive mechanical heart valve thrombosis.ASA,acetylsalicylic acid;CCT,cardiac com-puted tomography;INR, international normalized ratio;MHV,mechanical heart valve; NYHA,New York Heart Association;OAC,oral anticoagulation;TOE,transoesophageal echocardiography; TTE,transthoracic echocardiography;VKA,vitamin K antagonist.

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Recommendation Table 17- Recommendations for the management of prosthetic valve dysfunction(see also Supplementary data online, Evidence Table 25)

|Recommendations|Classa|Levelb| |---|---|---| |Haemolysis and paravalvular leak||| |It is recommended that the decision between transchater or surgical closure of clinically significant PVLs is based on Heart Team evaluation, including patient risk, leak morphology, and local expertise.|1|C| |Reoperation is recommended if a PVL is related to endocarditis, or causes haemolysis requiring repeated blood transfusion or leading to HF symptoms.|1|C| |Transcatheter closure should be considered for suitable PVLs with clinically significant regurgitation and/or haemolysis.|11|B| |Mechanical heart valve failure||| |Reoperation is recommended in symptomatic patients with significant valve dysfunction not attributable to valve thrombosis.|1|C| |Biological heart valve failure||| |Reintervention is recommended in symptomatic patients with significant valve dysfunction not attributable to valve thrombosis.|1|C| |Transcatheter, transfemoral valve-in-valve implantation in the aortic position should be considered in patients with significant valve dysfunction who are at intermediate or high surgical risk, and have suitable anatomical and prosthesis features, as assessed by the Heart Team. 447,448,450,451,941|11a|B| |Transcatheter transavenous nitric-tricuspid valve-in-valve implantation should be considered in patients with significant valve dysfunction at intermediate or high surgical risk, if the anatomy is suitable. ${}^{569,570,681,942-944}$|11a|B| |Reoperation should be considered in asymptomatic patients with significant prosthetic dysfunction, if surgical risk is low.|11a|C| |Valve thrombosis||| |TOE and/or 4D-CT are recommended in patients with suspected valve thrombosis to confirm the diagnosis.|914,918,923,925,945-948|C| |Mechanical heart valve thrombosis||| |Heart Team evaluation is recommended in patients with acute HF(NYHA class III or IV) due to obstructive MHV thrombosis to determine appropriate management(repeat valve replacement or low-dose slow infusion fibrinolysis).|11a|B| |Surgery should be considered for large(>10 mm) prosthetic thrombus complicated by embolism.|913,932,933|C| |Biological heart valve thrombosis||| |OAC using VKA is recommended in BHV thrombosis before considering reintervention. ${}^{867,934-937,955,956}$||| |OAC should be considered in patients with leaflet thickening and reduced leaflet motion leading to elevated gradients at least until resolution. ${}^{918,920-922}$|11a|B|

4D,four-dimensional;BHV,biological heart valve;CT,computed tomography;HF,heart failure;MHV,mechanical heart valve;NYHA,New York Heart Association;OAC,oral anticoagulation; PVL,paravulvular leak;TOE,transoesophageal echocardiography;VKA,vitamin K antagonist.

aClass of recommendation.

bLevel of evidence.

15. Management during non-cardiac surgery

In patients with significant VHD who undergo NCS, the risk of peri-operative cardiovascular complications is increased and related to both the timing of the procedure(i.e. urgent vs non-urgent) and type of surgery(low, intermediate, or high risk), as well as patient-specific factors(type and severity of VHD, LV function, etc.).194,957-959 Detailed recommendations related to NCS are available in the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.960

15.1. Pre-operative evaluation

Echocardiography should be performed in all patients with VHD requiring NCS. Patient- and surgery-specific factors, along with risk calculators, can be used to guide the treatment strategy. Determination of functional cap-acity is a pivotal step for pre-operative risk assessment, measured either by

the ability to perform activities in daily life or by exercise testing. Screening for frailty using validated tools is advisable. Decisions on pre- and peri-operative management, surveillance, and continuation of chronic cardio-vascular medical treatment should be taken after multidisciplinary discus-sion involving cardiologists, surgeons, and cardiac anaesthesiologists, as well as the team who will be in charge of the NCS. Patients receiving OAC treatment should be managed as described in Section 14.

15.2. Specific valve lesions

15.2.1. Aortic stenosis

In patients with severe symptomatic AS, the treatment depends on the urgency and risk of NCS. If life-saving time-sensitive NCS is needed, it should be performed under careful haemodynamic monitoring avoiding rapid changes of volume status, with prompt treatment of arrhythmia re-gardless of AS severity. In cases of urgent high-risk NCS, TAVI or balloon aortic valuloplasty should be considered in patients with critical AS prior to surgery, considering the risk of developing severe acute AR after

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balloon aortic valuloplasty.194,961 Urgent low- and intermediate-risk NCS can be performed relatively safely in patients with severe AS.962 Patients in whom NCS can be deferred(i.e. non-urgent NCS)should undergo pre-operative Heart Team evaluation to determine whether SAVR or TAVI is preferable. TAVI may be preferred to SAVR if faster recovery plays a role, particularly in elderly patients in whom complex or high-risk NCS is planned.963 The treatment of asymptomatic patients with severe AS should be individualized(Figure 21). ${}^{964}$

Heart rate and fluid balance should be controlled to prevent pulmonary oedema during NCS and arterial vasodilators should be avoided Non-cardiac surgery is safe in patients with an MVA of $>1.5 cm^{2}$ , and in asymptomatic patients with MVA $\leq 1.5 cm^{2}$ and SPAP of $<50 mmHg$ .

Symptomatic patients or those with SPAP of>50 mmHg should undergo PMC or other appropriate valve intervention before high-risk NCS, if pos-sible.°965.966 Asymptomatic patients with MVA≤1.5 cm² can undergo low-to-moderate-risk NCS under careful monitoring, especially if PMC is unsuitable. Multidisciplinary management is advised for patients with sig-nificant MS who are ineligible for valve intervention.

15.2.3. Aortic and mitral regurgitation

Non-cardiac surgery can usually be performed safely in asymptomatic pa-tients with severe MR or AR and preserved LV function. If NCS is urgent,patients should undergo surgery under strict haemodynamic monitoring,regardless of symptom status. In cases of elective(non-urgent) NCS in patients with severe ventricular SMR, medical therapy should be opti-mized. If symptoms persist and NCS is intermediate or high risk, TEER should be considered after Heart Team discussion based on clinical

 Figure 21 Management of non-cardiac surgery in patients with severe aortic stenosis. AS, aortic stenosis; AV,aortic valve; LV, left ventricular; NCS,non-cardiac surgery; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation.

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and anatomical selection criteria. ${ }^{194,584}$ Valve treatment should be per-formed for patients with AR meeting the criteria for valve intervention before any elective intermediate- or high-risk NCS. 96,967

15.3. Peri-operative monitoring

Heart rate control(particularly in MS) and careful fluid management(particularly in AS and MR with reduced LVEF) are needed throughout the procedure. The involvement of specialized cardiovascular anaesthe-siologists should be considered in complex situations because TOE monitoring may be considered. Pulmonary catheterization is not routinely used.

16. Management of valvular heart disease during pregnancy

Specific ESC Guidelines on this topic are available(the 2025 ESC Guidelines on cardiovascular disease during pregnancy) and should be con-sulted for further details. ${ }^{968}$ Pregnancies in patients with VHD should be considered high risk and managed under the close supervision of a

<EndOfPara>cardiologist and a multidisciplinary Pregnancy Heart Team. The import-ance of midwives and other specialized nursing personnel is increasingly recognized for high-quality direct patient interactions. Shared decision-making is especially important when addressing the cardiovascular risk of pregnancy and the benefit-risk ratios of therapeutic options and modes of delivery (Figure 22).

16.1. Management before pregnancy

Ideally, women should undergo a thorough physical examination by their general practitioner for VHD screening prior to pregnancy. A spe-cialized evaluation including TTE should be performed by a cardiologist in the case of clinical suspicion. ${}^{968,969}$

If VHD is diagnosed, pre-pregnancy counselling is imperative.Unplanned pregnancies in patients with VHD should be discouraged.Contraception methods should be recommended after discussion with the patient in the presence of a significant maternal and/or foetal risk. In patients contemplating pregnancy, the maternal risk should be assessed using the modified WHO classification and other scores such as the CARPREG or DEVI risk score (see Supplementary data online,Table S7).970

Pre-conception assessment

● Clinical screening: history,physical examination,ECG

● If clinical suspicion of VHD:TTE,exercise capacity assessment

● In case of definite VHD: risk assessment(mWHO, CARPREG II, DEVI)

●Correction of severe MS,AS,aortic dilatation with high risk of aortic dissection

Management during pregnancy

• Serial monitoring(symptoms,biomarkers,TTE)

● Drug therapy(anticoagulation)

Delivery/post-partum

● Vaginal delivery usually preferred

•Regional anaesthesia

● Monitoring during delivery and early post-delivery

● Extended in-hospital surveillance/treatment

● In case of definite VHD: risk assessment(mWHO, CARPREG II, DEVI)

shared decision-making with the patient

other specialists

Midwives and other nursing personnel

 ESC EACTS

Figure 22 The Pregnancy Heart Team model of care. AS, aortic stenosis; ECG, electrocardiogram; MS, nitral stenosis; TTE, transthoracic echocar-diography; VHD, valvular heart disease.

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Before recommending pregnancy, the following conditions need to be corrected:

● MS with MVA<1.5 cm2, even when asymptomatic.971

● Severe AS with symptoms, or abnormal exercise test, or LV systolic dysfunction. ${}^{972}$

● Heritable aortic disorders and high risk of aortic dissection: prophylactic aortic repair is recommended prior to pregnancy in women with Marfan syndrome and an aortic diameter of>45 mm, and may be con-sidered in women with an aortic diameter between 40 and 45 mm when risk factors for dissection exist.973 Aneurysmal dilation in women with BAV should be corrected when the aortic diameter is≥50 mm.974 Close follow-up in dedicated units and beta-blocker therapy during pregnancy and post-partum are recommended unless contraindicated,although strong evidence is only available for Marfan syndrome.

Valvular regurgitant lesions are generally well tolerated during preg-nancy. Prophylactic intervention is therefore not recommended in the absence of class I or la indications.

The first therapeutic option for MS in a woman considering preg-nancy should be PMC. When implantation of a prosthetic valve is ne-cessary, BHVs are recommended, although early SVD remains a serious concern. 975 Mechanical heart valves must be avoided due to the high risk of maternal and foetal complications linked to the potential teratogenic effects of VKAs, as well as the increased risk of bleeding. ${}^{976}$ The Ross procedure may be considered for the treatment of AV dis-ease at centres with expertise.

16.2. Management during pregnancy 16.2.1. Patients with native valve disease

Pregnancy can worsen the clinical course of left-sided stenotic valvular lesions because increased cardiac output causes an increment of trans-valvular gradient of~50%, mainly between the first and second time-drivers. Regurgitant lesions are less likely to cause complications, except in high-risk cases(LV systolic dysfunction, PH, and cardiac events before pregnancy).977

Mild MS is generally well tolerated. 978 Heart failure occurs in one-third of pregnant women with an MVA of<1.5 cm2 and in one-half of those with an MVA of<1.0 cm2, most often during the second tri-mester. 971 Percutaneous mitral commissorotomy should be consid-ered if symptoms or SPAP of>50 mmHg persist despite optimal medical therapy(diurets and beta-1-selective beta-blockers), prefer-ably after the 20th week of pregnancy.

Regarding AS, pregnancy is generally well tolerated if prior exercise tolerance was normal, even in severe AS, while HF has been reported to occur in up to 25% of symptomatic patients.972 In symptomatic patients despite medical therapy(i.e. diuretics), TAVI seems to be the preferred option in very selected patients, although evidence is lacking. Percutaneous balloon valvoplasty may be an alternative op-tion. Procedures should be performed in an experienced valve centre.972,979,980

Surgery under cardiopulmonary bypass is associated with a high rate of foetal loss and should be restricted to conditions that threaten the mother's life if transchateter intervention is not possible or has failed.

Vaginal delivery is the first choice for the majority of patients.Caesarean section is preferred if there is an obstetric indication,and in the case of severe MS or AS, ascending aortic diameter of>45 mm, severe PH, or if delivery starts while the patient is being treated with OAC.

16.2.2. Patients with prosthetic valves

Pregnant patients with MHVs should be followed in a centre with cor-responding expertise. In a cohort of 212 women with MHVs, valve thrombosis occurred in 10(4.7%) pregnancies and haemorrhagic events occurred in 49(23.1%). 976 Therapeutic OAC during pregnancy is essential to avoid thrombosis. The higher efficacy of VKAs compared with LMWH to prevent thrombosis must be balanced against increased foetal risks.°

In patients requiring≤5 mg/day of warfarin, OAC with warfarin throughout pregnancy, changing to UFH before delivery, is advocated,in order to reduce the risk of thrombosis. In patients requiring higher doses, switching to dose-adjusted LMWH at least twice per day with strict anti-Xa monitoring during the first trimester is recommended to avoid the teratogenic effect of VKAs(for corresponding flowcharts see the 2025 ESC Guidelines for the management of cardiovascular dis-eases during pregnancy98).

Lifetime management of women with a BHV considering pregnancy is central and transcatheter valve-in-valve implantation may be consid-ered as a bridge to MHV implantation.

17. Sex-specific considerations in patients with valvular heart disease

Although men and women are equally likely to experience VHD, sex-specific prevalence exists according to valve type and disease patho-physiology.644,648,983 Women more frequently suffer from MV disease such as prolapse, RHD or TR, while men more often present with AS or AR, especially associated with BAV.984 Men also suffer from endocardi-tis of any valve more frequently.985

Female sex is associated with higher mortality in the presence of vari-ous VHDs,986 including early post-treatment,987 and is included as a risk factor in surgical risk prediction tools such as the STS and EuroSCORE calculators. However, risk scores are often derived from populations including a majority of men.988 In addition, risk pre-diction scores are susceptible to referral bias that results in a well-established higher risk of undertreatment or delayed treatment of VHD in women.983,984,986

17.1. Aortic valve disease

Female patients with severe AS present more often with shortness of breath, whereas males more frequently have angina, presumably due to the higher incidence of CAD.989 The pathophysiology of AS seems to differ according to sex, with women having less calcium and more fibro-sis.990 Concentric ventricular hypertrophy and remodelling are also more frequently observed in women than in men, resulting in higher LVEF but smaller LV cavity and stroke volume.991 Consequently, para-doxical low-flow, low-gradient constellations are frequent and may both contribute to the underdiagnosis of severe AS in women and delay an intervention.992 The use of sex-specific thresholds to define flow limitation(<40 mL/m2 for men and<32 mL/m2 for women) has there-fore been suggested,292 and the use of CCT to quantify the calcium score should be performed in women with discordant echocardio-graphic parameters.777

Women are less likely to be referred to a cardiologist and undergo investigations. Surgical aortic valve replacement is per-formed less frequently in women, especially if echocardiographic parameters are discordant.993 In patients presenting with severe

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AS and Class I indications for SAVR, a significantly higher proportion of men than women are referred for evaluation by a cardiac surgeon.994,995

Male patients derive a clearer benefit from SAVR compared with wo-men, who have higher in-hospital and long-term mortality and morbid-ity,987,996 possibly explained by more severe concentric hypertrophy and a smaller aortic annulus predisposing to PPM.997 Conversely, in a randomized trial(RHEIA) that compared TAVI with SAVR in 443 wo-men with a mean age of 73 years, TAVI was superior in reducing the primary endpoint composed of death, stroke, or rehospitalization at 1 year, predominantly driven by a reduction in rehospitalization for valve- or procedure-related symptoms or worsening HF.998 Several ob-servational studies suggest that elderly women have lower mortality after TAVI,999 even if the rates of major vascular complications and bleeding tend to be higher.997

Indexed cut-offs to indicate treatment of AR are validated, but only partially account for sex differences. Newer studies using echocardio-graphic volumes ${}^{1000}$ and $CMR^{1001}$ suggest that women may experience higher event rates at lower cut-offs compared with men, but this re-quires further investigation.

17.2. Mitral valve disease

Patients with RHD are often young women and have a high prevalence of major cardiovascular complications with far-reaching impacts on re-productive health and access to care.282 Although women experience favourable outcomes compared with men when treated by percutan-eous balloon valuloplasty, access to these procedures is still limited in low-income countries. 662

Fibroelastic disease with MV prolapse is also more frequent in wo-men, and may be accompanied by morphological abnormalities of the MA associated with fibrosis of the papillary muscles or the infer-obasal LV that may act as the substrate for sudden cardiac death,even in the absence of severe MR.1002 Recent evidence has sup-ported considering lower women-specific cut-offs for intervention with regard to LVESD(36 mm; indexed LVESD, 1.8 cm/m2), while the LVEF cut-off was similar to men(58%), albeit with higher mortality.548

Ventricular SMR associated with low LVEF is more frequent in men with HF, ${}^{1003}$ while atrial SMR due to chronic AF and/or HFEF affects more women(58% vs 42% male). ${}^{579}$

Female sex is a risk factor for the development of MAC and was re-ported to account for 68% of the patients included in a large-scale transcatheter MV replacement in MAC registry.1004 Furthermore, wo-men present with a faster disease progression.1005

17.3. Tricuspid valve disease

Tricuspid regurgitation is more prevalent in women,208 and female sex is associated with accelerated disease progression.1006-1008 Hypotheses to explain these observations include the overall higher prevalence of HFpEF and AF in women.1009 Women are usually diagnosed at an older age and the cause of TR is most frequently a consequence of left valular disease or annular dilatation attributable to RA dilatation.1010 No differences have been detected to date in terms of adverse events after surgery 1011 or transcatheter TV interventions. 1012,1013

18. Key messages

Heart Team and Heart Valve Centre

● An integrated regional Heart Valve Network incorporating out-patient Heart Valve Clinics and specialist Heart Valve Centres allows optimal patient care.

● Heart Valve Centres should fulfil institutional and local statutory re-quirements, and strive for high procedural volume and excellent clin-ical outcomes.

● Heart Team recommendations should be based upon these guideline recommendations, relevant updated evidence, key medical consid-erations, and patient preferences.

● Core members of the Heart Team include the primary clinical cardi-ologists, cardiologists with specialty expertise in VHD, specialists in advanced cardiovascular imaging and peri-procedural imaging guid-ance, and surgeons and interventional cardiologists with training and expertise in valve interventions.

● A network approach that distinguishes between higher- and lower-volume centres is appropriate, with more complex proce-dures focused in the most experienced(i.e. upper quartile)centres. Information on the network organization should be com-municated to patients, as well as referring cardiologists and general practitioners.

Aortic regurgitation

● Assessment of AR severity with TTE remains challenging and current cut-offs for intervention are mostly based on 2D measurements, al-though 3D echocardiography and CMR allow more accurate evalu-ation of LV volumes and LVEF.

● Mechanisms of AR may be closely related to the aortic diameters that should be measured accurately at all levels of the aortic root(annulus,sinuses, and sinotubular junction).

● Indication for operation is based on symptoms, LV volumes, LVEF,and aortic diameters. Although valve replacement remains the stand-ard treatment, AV repair(or AV sparing when associated with root aneurysm) is being increasingly used to avoid prosthesis-related com-plications, especially in experienced centres.

● Current transcatheter options for AR are limited and applicable only in patients who are ineligible for surgery.

Aortic stenosis

● Diagnosis of severe AS requires integrative evaluation of pressure gradients(the most robust measurements), AVA, flow conditions,the extent of valve calcification, and LV function.

● Selection of the most appropriate mode of intervention should take into account clinical characteristics(age and estimated life expect-ancy,concomitant conditions),access and valve anatomy(particularly the feasibility of temporal TAVI and calcification patterns), and surgical risk, as well as repeat procedure options and risks(lifetime management).

Mitral regurgitation

● The echocardiographic diagnostic workup of patients with MR in-cludes multiparametric assessment of MR severity, evaluation of

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MV anatomy(often of with 3D TOE), identification of the mechanism(PMR, ventricular SMR, or atrial SMR), and evaluation of cardiac damage.

● Surgical MV repair is the preferred method of treatment in severe PMR.Transcatheter edge-to-edge repair is recommended in patients who are inoperable or high risk according to the Heart Team.

● Surgical MV repair is the procedure of choice for asymptomatic pa-tients with primary MR and signs of cardiac damage, including mod-erate or more TR.

● In patients with ventricular SMR, GDMT(including CRT if indicated)is the initial and essential treatment step. In symptomatic patients without CAD needing revascularization, M-TEER is recommended.In patients with concomitant complex CAD and those not suitable for TEER, mitral surgery may be considered.

● In patients with atrial SMR, MV surgery, AF ablation if indicated, and LAAO should be considered after optimization of medical therapy.Transcatheter edge-to-edge repair may be considered in patients at high surgical risk.

Mitral stenosis

● Most patients with severe rheumatic MS and favourable valve an-omy should undergo PMC, which is the standard of care. Surgery is recommended for symptomatic patients with contraindications or unfavourable anatomical and clinical characteristics for PMC.

● Decision-making in patients with unfavourable anatomy should take into account local PMC experience.

● In selected patients with clinically severe degenerative MS and MAC,transcatheter intervention or surgery may improve symptoms.

Tricuspid regurgitation

● Concomitant TV repair is the preferred method for patients with left-sided valve pathology and associated moderate or severe TR.

● The use of risk scores for the assessment of RV and secondary organ dysfunction should be strongly encouraged in patients with isolated severe TV disease.

● In isolated severe TR without severe RV dysfunction, surgery should be performed at an early stage in patients at low operative risk.

● In isolated severe TR patients at increased surgical risk, tricuspid TEER or transcatheter replacement should be considered to im-prove quality of life and RV remodelling, in the absence of severe RV dysfunction or pre-capillary PH.

Tricuspid stenosis

● TS is a very rare manifestation of acquired VHD in high-income countries.

● TS is mainly associated with rheumatic valve disease, carcinoid syn-drome, or enzymatic disorders such as Fabry's or Whipple's disease.

● Treatment of symptomatic TS mainly involves surgical TV replacement.

Multiple and mixed valvular heart disease

● Transvalvular gradients and velocities reflect the combined burden of regurgitation and stenosis in mixed aortic and mitral disease.

● Treatment decisions should be based on the assessment of symptom and functional status, cardiac damage, anatomical suitability, and the

risk-benefit ratio of intervention and lifetime management considerations.

● Patients with mixed moderate AS and AR have similar detrimental outcomes compared with those with severe isolated AS.

● In transcatheter procedures, which allow a sequential approach,downstream lesions should be treated first to prevent potential haemodynamic deterioration and allow improvement of upstream lesions due to changing loading conditions and reverse remodelling.

Antithrombotic treatment in patients with a mechanical heart valve

● International normalized ratio therapeutic range should be balanced to the type and anatomical site of MHV, as well to the thrombotic risk profile of the individual patient.

● Patient training, self-monitoring, and education can increase INR sta-bility and TTR.

● Minor or minimally invasive NCS procedures do not require VKA interruption in patients with an MHV.

● In patients with an MHV undergoing elective major NCS, bridging may be omitted if the thromboembolic risk is low.

Non-cardiac surgery

● The risk of peri-operative cardiovascular complications related to surgery and to patients-specific factors should be evaluated and com-municated to the patient and surgical team.

● In patients with symptomatic severe AS requiring urgent high-risk NCS,BAV or TAVI should be considered prior to surgery.In patients planned for elective NCS,AV intervention is recommended prior to NCS.

Pregnancy

● In women with VHD, decisions regarding management before and dur-ing pregnancy should be taken after discussion by the multidisciplinary Pregnancy Heart Team. Unplanned pregnancies should be discouraged.

● The following conditions should be corrected prior to considering pregnancy:

- clinically severe MS(MVA<1.5 cm2), even when asymptomatic- severe symptomatic AS, or asymptomatic patients with impaired LV function or a pathological exercise test

- heritable aortic disorders and high risk of aortic dissection.

● Vaginal delivery is the first choice for the majority of patients.Indications for Caesarean section include pre-term labour in patients on OAC, severe MS or AS, aggressive aortic pathology, acute intract-able HF, and severe PH.

● Women with MHVs should be managed in expert centres.

19. Gaps in evidence

General aspects

● Patient-reported outcome measures are infrequently reported in VHD studies. Patient-reported outcome measure-oriented studies are required to improve quality of life and patient satisfaction.

● Methods to address underdiagnosis and undertreatment of VHD need to be identified and implemented.

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Heart Team and Heart Valve Centre

● Structured research is required to investigate the relationship be-tween procedural volume and clinical outcomes, in order to define minimum annual thresholds for individual operators and institutions undertaking surgical and transcatheter valve interventions.

● There is a pressing need to ensure higher dispersion and adoption of interventions for VHD, especially in middle- and low-income countries.

Conditions associated with valvular heart disease

● CAD:

- The prognostic value of functional assessment of stable, moderate coronary stenosis in VHD patients remains to be determined.

- The optimal strategy(invasive vs non-invasive) for CAD assess-ment in specific VHD populations remains to be elucidated.

- The optimal timing of PCI in patients with CAD undergoing TAVI is yet to be determined.

- The benefit of complete coronary revascularization with CABG in patients with combined VHD and CAD requires further research.

● AF:

- It is unclear which patients with chronic persistent AF and con-comitant VHD are deemed to be suitable for rhythm control therapy.

- The protective effect against stroke of OAC with VKA or DOACs in patients after surgical or transcatheter LAAO remains to be determined.

● Cardiogenic shock and acute HF:

- The optimal treatment strategy in VHD patients presenting with cardiogenic shock and acute HF is unknown.

Aortic regurgitation

● Impact of early LV remodelling on prognosis in asymptomatic AR pa-tients is unknown.

● Prognostic value of CMR-derived indices in asymptomatic patients needs to be determined.

● More data are required on long-term results of surgical AV repair for AR.

● More evidence is required on transcatheter treatment options for AR, in particular using dedicated devices.

Aortic stenosis

● Better understanding of the pathophysiology of AS is needed to pro-pose innovative medical therapy.

● Further research is required on:

- Refined prognostic markers to guide timing of intervention in asymptomatic patients.

- The role of revascularization in patients with severe AS and asymp-tomatic concomitant CAD.

- Further data on the long-term durability of transchateter valves in comparison with surgical BHVs in younger patients.

- The role of TAVI in patients with BAV AS and patients<70 years of age.

Results of intervention(valve or coronary) after TAVI or SAVR.

- Determining the optimal lifetime management strategy for AS patients.

Mitral regurgitation

● The association between primary MR and ventricular arrhythmias re-quires more investigation, including the impact of intervention on ventricular arrhythmias.

● More data are required on the role of TEER in patients with advanced HF.

● Long-term results of TEER need to be further assessed, including the clinical relevance of transmitral gradients after treatment of both pri-mary and secondary MR.

Results of ongoing trials comparing MV surgery with TEER in non-high risk primary MR patients are awaited.

● Data on the mid- and long-term clinical impacts of transcatheter MV replacement are required.

● More data on the clinical impacts of surgical and transcatheter treat-ment of atrial SMR are required.

Mitral stenosis

● The potential role of TMVI using dedicated devices in high-risk patients is to be determined, particularly those with severe MAC.

Tricuspid regurgitation

● The long-term risks and benefits of concomitant TV surgery in pa-tients with less than moderate TR and annular dilatation undergoing left-sided valve surgery need to be determined.

● Further investigations are required on the outcomes of TV interven-tion in asymptomatic patients with severe TR and RV dysfunction or significant dilation.

● The importance of addressing concomitant AF in patients with TR needs to be investigated.

More data are required on the indications, timing, and long-term out-comes of TV repair and replacement for TV disease.

● Better understanding is required of the respective role of surgery vs transcatheter TV therapy for TR treatment.

Tricuspid stenosis

● The role of transcatheter TV replacement remains unexplored in pa-tients with TS. The most efficient way to achieve ventricular pacing in patients after TV replacement needs to be investigated.

Multiple and mixed valvular heart disease

● Further evaluation of the impact on outcomes and indication for intervention, as well as timing and modalities of intervention, is required.

Prosthetic valves

● Further development of current prosthetic valve devices is required to address their main complications(e.g. improved tissue processing to reduce degeneration of bioprostheses or new mechanical valve designs to reduce risk of thrombosis).

● Antithrombotic drugs in MHV patients:

- Whether UFH or LMV HWH should be preferred as bridging therapy after MHV implantation, as well as their timing and dosage, remains to be established.

- For patients with MHV undergoing major NCS, the optimal post-operative management and bridging of VKA needs further investigation.

- The role of pharmacogenomics for VKORC1, CYP2C9, and CYP4F2 in patients with highly variable INR, and low TTR or major vascular complications despite good adherence, should be further investigated.

- More data on the risks and benefits of slow thrombolysis for valve thrombosis are required.

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Pregnancy

● More data are required on optimal management of anticoagulation in pregnant women with MHVs. Prospective studies comparing differ-ent antithrombotic regimens are lacking.

Non-cardiac surgery

● Clinical utility of scales for peri-operative risk evaluation needs to be determined.

Sex-specific considerations

● The development of sex-adjusted surgical risk prediction tools is required.

● Additional data are needed to validate sex-specific cut-offs indicating interventions.

● Further research is needed to investigate sex-related differences in the prognosis and treatment of specific valve diseases, especially TR.

20.‘What to do’ and‘What not to do’ messages from the Guidelines

Class I and Class III recommendations from throughout the guideline document are summarized in Table 13.

Table 13‘What to do’ and‘what not to do’

|Recommendations|Class|Level| |---|---|---| |Recommendations for the management of coronary artery disease in patients with valvular heart disease||| |CCTA is recommended before valve intervention in patients with moderate or lower(≤50%) pre-test likelihood of obstructive CAD.|I|B| |Invasive coronary angiography is recommended before valve intervention in patients with high and very high(>50%) pre-test likelihood of obstructive CAD.|I|C| |Invasive coronary angiography is recommended in the evaluation of CAD in patients with severe ventricular SMR. CABG is recommended in patients with a primary indication for valve surgery and coronary artery diameter stenosis≥70%.|I|C| |Recommendations for the management of atrial fibrillation in patients with native valvular heart disease||| |DOACs are recommended for stroke prevention in preference to VKas in patients with AF and AS, AR, or MR who are eligible for OAC.|I|A| |Concomitant surgical ablation is recommended in patients undergoing MV surgery with AF suitable for a rhythm control strategy to prevent symptoms and recurrence of AF, according to an experienced team of electrophysiologists and arrhythmia surgeons.|I|A| |Surgical closure of the LA appendage is recommended as an adjunct to OAC in patients with AF undergoing valve surgery to prevent cardiobembolic stroke and systemic thromboembolism.|I|B| |The use of DOACs is not recommended in patients with AF and rheumatic MS with an MVA≤2.0 cm2.|III|B| |Recommendations on indications for surgery in severe aortic regurgitation||| |AV surgery is recommended in symptomatic patients with severe AR and LVESD>50 mm or LVESDi>25 mm/m2 [especially in patients with small body size(BSA<1.68 m2)] or resting LVEF≤50%.|I|B| |Valve-sparing aortic root replacement is recommended in young patients with aortic root dilation at experienced centres when durable results are expected.|I|B| |AV surgery is recommended in symptomatic and asymptomatic patients with severe AR undergoing CABG or surgery of the ascending aorta.|I|C| |Recommendations for intervention and mode of intervention in severe aortic stenosis||| |Symptomatic patients with severe aortic stenosis||| |Intervention is recommended in symptomatic patients with severe, high-gradient AS [mean gradient≥40 mmHg,Vmax≥4.0 m/s, and AVA≤1.0 cm2 (or ≤0.6 cm2/m2 BSA) ].|I|B| |Intervention is recommended in symptomatic patients with low-flow(SVi≤35 mL/m2), low-gradient(<40 mmHg) AS with reduced LVEF (<50%) after careful confirmation that AS is severe.|I|B| |Asymptomatic patients with severe aortic stenosis||| |Intervention is recommended in asymptomatic patients with severe AS and LVEF<50% without another cause.|I|B| |Mode of intervention in patients with symptomatic severe aortic stenosis||| |It is recommended that AV interventions are performed in Heart Valve Centres that report their local expertise and outcome data, have on-site interventional cardiology and cardiac surgical programmes, and a structured collaborative Heart Team.|I|C| |It is recommended that the mode of intervention is based on Heart Team assessment of individual clinical, anatomical, and procedural characteristics, incorporating lifetime management considerations and estimated life expectancy.|I|C|

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|TAVI is recommended in patients ≥70 years of age with tricuspid AV stenosis, if the anatomy is suitable.|I|A| |---|---|---| |TAVI is recommended in patients ≥70 years of age with tricuspid AV stenosis, if the anatomy is suitable.|I|B| |SAVR is recommended in patients <70 years of age, if the surgical risk is low.|I|B| |SAVR or TAVI are recommended for all remaining candidates for an aortic BHV according to Heart Team assessment.|I|B| |Concomitant aortic valve surgery at the time of coronary artery bypass grafting or ascending aorta surgery||| |SAVR is recommended in symptomatic and asymptomatic patients with severe AS undergoing CABG or surgical intervention on the ascending aorta.|I|C| |Recommendations for intervention in severe mitral regurgitation||| |Primary mitral regurgitation||| |MV repair is the recommended surgical technique to treat patients with severe PMR when the result is expected to be durable.|I|B| |MV surgery is recommended in symptomatic patients with severe PMR considered operable by the Heart Team.|I|B| |MV surgery is recommended in asymptomatic patients with severe PMR with LV dysfunction(LVESD≥20 mm/m² or LVEF ≤60%).|I|B| |Surgical MV repair is recommended in low-risk asymptomatic patients with severe PMR without LV dysfunction(LVESD<40 mm,LVESDi <20 mm/m², and LVEF >60%) when a durable result is likely, if at least three of the following criteria are fulfilled:|I|B| |●AF||| |● SPAP at rest>50 mmHg||I| |● LA dilatation(LAVI≥60 mL/m2 or LA diameter≥55 mm)||| |● concomitant TR≥ moderate.||| |Ventricular secondary mitral regurgitation and concomitant coronary artery disease||| |MV surgery is recommended in patients with severe ventricular SMR undergoing CABG.|I|B| |Ventricular secondary mitral regurgitation without concomitant coronary artery disease||| |TEER is recommended to reduce HF hospitalizations and improve quality of life in haemodynamically stable, symptomatic patients with impaired LVEF(<50%) and persistent severe ventricular SMR, despite optimized GDMT and CRT(if indicated), fulfilling specific clinical and echocardiographic criteria.|I|A| |Recommendations for mitral stenosis||| |Indications for mitral valve surgery and transcatheter intervention in clinically severe rheumatic and degenerative mitral stenosis||| |PMC is recommended in symptomatic patients in the absence of unfavourable characteristics for PMC.|I|B| |PMC is recommended in any symptomatic patients with a contraindication or a high risk for surgery.|I|C| |MV surgery is recommended in symptomatic patients who are not suitable for PMC.|I|C| |Recommendations for tricuspid regurgitation||| |Indications for intervention in tricuspid regurgitation||| |Careful evaluation of TR aetiology, stage of the disease (i.e. degree of TR severity,RV and LV dysfunction,and PH),patient operative risk,and likelihood of recovery by a multidisciplinary Heart Team is recommended in patients with severe TR prior to intervention.|I|C| |Patients with left-sided valvular heart disease requiring tricuspid valve surgery||| |Concomitant TV surgery is recommended in patients with severe primary or secondary TR.|I|B| |Patients with severe tricuspid regurgitation (without left-sided valvular heart disease requiring surgery)||| |TV surgery is recommended in symptomatic patients with severe primary TR without severe RV dysfunction or severe PH.|I|C| |Recommendations on tricuspid stenosis||| |Surgery is recommended in symptomatic patients with severe TS.|I|C| |Surgery is recommended in patients with severe TS undergoing left-sided valve intervention.|I|C| |Recommendations for surgery of concomitant left-sided valvular heart disease||| |Concomitant aortic stenosis||| |SAVR is recommended in patients with severe AS undergoing surgery for another valve.|I|C| |Concomitant aortic regurgitation||| |AV surgery is recommended in patients with severe AR undergoing surgery for another valve.|I|C| |Concomitant mitral regurgitation||| |MV surgery is recommended in patients with severe MR undergoing surgery for another valve.|I|C| ||||

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|Recommendations on indications for intervention in patients with mixed moderate aortic stenosis and moderate aortic regurgitation||| |---|---|---| |Intervention is recommended in symptomatic patients with mixed moderate AV stenosis and moderate regurgitation, and a mean||| |gradient≥40 mmHg or Vmax≥4.0 m/s.||| |Intervention is recommended in asymptomatic patients with mixed moderate AV stenosis and moderate regurgitation with Vmax≥4.0 m/s, and LVEF<50% not attributable to other cardiac disease.||| |Recommendations for prosthetic valve selection||| |Mechanical heart valves||| |An MHV is recommended according to the desire of the informed patient and if there is no contraindication to long-term anticoagulation.||| |Biological heart valves||| |A BHV is recommended according to the desire of the informed patient.||| |A BHV is recommended when an adequate quality of anticoagulation with VKA is unlikely, in patients at high bleeding risk, or with estimated short life expectancy.||| |Recommendations for the management of antithrombotic therapy in patients with a mechanical heart valve replacement||| |Lifelong OAC with a VKA is recommended for all patients with MHVs to prevent thromboembolic complications.||| |INR self-monitoring and self-management are recommended over standard monitoring in selected, trained patients to improve efficacy.||| |It is recommended that INR targets are based on the type and position of the MHV, and the patient's risk factors and comorbidities.||| |Patient education is recommended to improve the quality of OAC.||| |Following cardiac surgery with MHV implantation, it is recommended to start UFH or LMWH bridging and VKA within 24 h, or as soon as considered safe.||| |DOACs and/or DAPT are not recommended to prevent thrombosis in patients with an MHV.||| |Recommendations for the management of antithrombotic therapy in patients with mechanical heart valves undergoing elective non-cardiac surgery or invasive procedures||| |Continuing VKA treatment is recommended in patients with an MHV for minor or minimally invasive interventions associated with no or minimal bleeding.|I|A| |It is recommended to discontinue VKA at least 4 days before major elective NCS, aiming for an INR<1.5, and to resume VKA treatment within 24 h after surgery, or as soon as considered safe.|I|B| |Recommendations for the management of antithrombotic therapy in patients with a biological heart valve or valve repair||| |Transcatheter aortic valve implantation without indication for oral anticoagulation||| |Low-dose ASA(75-100 mg/day) is recommended for 12 months after TAVI in patients without indication for OAC.|I|A| |DAPT is not recommended to prevent thrombosis after TAVI, unless there is a clear indication.|III|A| |Routine use of OAC is not recommended after TAVI in patients without baseline indication.||| |Surgical biological heart valve with indication for oral anticoagulation||| |OAC continuation is recommended in patients with a clear indication for OAC undergoing surgical BHV implantation.|I|B| |Transcatheter biological heart valve with indication for oral anticoagulation||| |OAC is recommended for TAVI patients who have other indications for OAC.||| |Recommendations on management of prosthetic valve dysfunction||| |Haemolysis and paravalvular leak||| |It is recommended that the decision between transcatheter or surgical closure of clinically significant PVLs is based on Heart Team evaluation, including patient risk, leak morphology, and local expertise.|I|C| |Reoperation is recommended if a PVL is related to endocarditis, or causes haemolysis requiring repeated blood transfusion or leading to HF symptoms.|I|C| |Mechanical heart valve failure||| |Reoperation is recommended in symptomatic patients with significant valve dysfunction not attributable to valve thrombosis.|I|C| |Biological heart valve failure||| |Reintervention is recommended in symptomatic patients with significant valve dysfunction not attributable to valve thrombosis.|I|C| |Valve thrombosis||| |TOE and/or 4D-CT are recommended in patients with suspected valve thrombosis to confirm the diagnosis.||C|

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Mechanical heart valve thrombosis

Heart Team evaluation is recommended in patients with acute HF(NYHA class III or IV) due to obstructive MHV thrombosis to determine appropriate maintenance(repeat valve replacement or low-dose slow infusion fibrinolysis).

Biological heart valve thrombosis

OAC using VKA is recommended in BHV thrombosis before considering reintervention.

4D,four-dimensional;AF,atrial fibrillation;AR,aortic regurgitation;AS,aortic stenosis;ASA,acetylsaliclic acid;AV,aortic valve;AVA,aortic valve area;BHV,biological heart valve;BSA,body surface area;CABG,coronary artery bypass grafting;CAD,coronary artery disease;CCTA,coronary CT angiography;CRT,cardic resynchronization therapy;CT,computed tomography;DAPT,dual antiplatelet therapy;DOAC,direct oral anticoagulation;GDMT,guideline-directed medical therapy;h,hor;HF, heart failure;INR,international normalized ratio;LA,left atrium/left ALY, left atrial volume index; LMWH, low-molecular-weight heparin; LV,left ventricular left ventricular;LV, left ventricular ejection fraction; LVVESD, left ventricular end-systolic diameter;LVESD, left ventricular end-systolic diameter indexed to BSA; MHV, mechanical heart valve; MR,mitral regurgitation; MS,renical stenosis;MV,mrital valve;MVA,mitral valve area;NCS,non-cardiac surgery;NYHA,New York Heart Association;OAC,oral anticoagulation;PH,pulmonary hypertension;PMC,percutaneous mitral commissurotomy;PMR,primary mitral regurgitation;PV,parulaventricular leak;RV,right ventricular/right ventricular;SAVR,surgical or aortic valve replacement;SMR,secondary mitral regurgitation; SPAP,systolic pulmonary artery pressure; SV, stroke volume index; TAVl, transcatheter aortic valve implantation; TEER, transcatheter edge-to-edge repair; TOE,transoesophageal echocardiography; TR, tricuspid regurgitation;TS,tricuspid stenosis;TV,tricuspid valve;UFH,unfractionated heparin;VKA, vitamin K antagonist;Vmao peak transvularial velocity.AClass of recommendation.bLevel of evidence.

bLevel of evidence.

21. Evidence tables

Evidence tables are available at European Heart Journal online.

22. Data availability statement

No new data were generated or analysed in support of this research.

23. Author information

Jonas Lanz, Department of Cardiology, Bern University Hospital, Bern, Switzerland; Mateo Marin-Cuartas, University Department of Cardiac Surgery, Leipzig Heart Center, Leipzig, Germany; Ana Abreu,Faculdade de Medicina da Universidade de Lisboa(FMUL), ISAMB, IMPSP, CCUL, CAML, Lisboa, Portugal;Servico Cardiologia, Unidade de Reabilitacao Cardiovascular, ULS Santa Maria/FMUL, Lisboa, Portugal; Marianna Adamo, Institute of Cardiology, ASST Spedali Civili, Brescia, Italy; Department of medical and surgical specialties, radiological sciences, and public health, University of Brescia, Italy; Nina Ajmone Marsan,Department of Cardiology, Leiden University Medical Center,Leiden, Netherlands; Fabio Barili, Department of Biomedical and Clinical Sciences, Universita Degli Studi Di Milano, Milan, Italy;University Cardiac Surgery Unit, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Milan, Italy; Department of Epidemiology, Harvard T.H. Chan School of Public Health Boston, MA, United States of America; Nikolaos Bonaros, Department of Cardiac Surgery,Medical University of Innsbruck, Innsbruck, Austria; University Hospital Innsbruck, Innsbruck, Austria; Bernard Cosyns,Cardiology department, Universitat Ziekenhuis Brussell, Brussels,Belgium; Ruggero De Paulis, Department of cardiac surgery,European Hospital, Rome, Italy; Unicamillus University, Rome,Italy; Habib Gamra, Cardiology University of Monastir, Monastir,Tunisia; Marjan Jahangir,Cardiac Surgery,St George's Hospital,London, United Kingdom; Anders Jeppsson, Cardiothoracic sur-gery, Sahlgrenka University Hospital, Gothenburg, Sweden;Molecular and clinical medicine, Institute of medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Robert J.M. Klautz, Department of Cardiothoracic Surgery,Leiden University Medical Center, Leiden, Netherlands;Department of Cardiothoracic Surgery, Amsterdam University

Medical Center, Amsterdam, Netherlands; Benoit Mores(Belgium), ESC Patient Forum, Sophia Antipolis, France; Esther Pérez-David, Cardiology Department, Hospital Universitario La Paz, IdiPaz(Hospital la Paz Research Institute), Facultad de Medicina Universidad Europea de Madrid, Madrid, Spain; Janine Poss, Department of internal medicine/cardiology, Heart Centre Leipzig at University of Leipzig, Leipzig, Germany; Bernard Poss, Department of Invasive& Thoracic Institute, Cleveland Clinic London, London, United Kingdom; Department of Cardiology, St Thomas' Hospital, London, United Kingdom;Bianca Rocca, Department of Medicine and Surgery, LUM University Casammasa (Ba), Italy; Xavier Rossello, Cardiology Department, Hospital University Son Espases, Palma de Mallorca,Spain; Health Research Institute of the Balearic Islands(IdISBa),Universitat de les Illles Balears(UIB), Palma de Mallorca,Spain; Mikio Suzuki,(Serbia), ESC Patient Forum, Sophia Antipolis,France; Holger Thiele, Department of Internal Medicine/Cardiology, Heart Centre Leipzig at Leipzig University, Leipzig,Germany; Leipzig Heart Science, Leipzig, Germany; Christophe Michel Tribouilloy, Cardiology department, Amiens University Hospital, Amiens, France; and Wojtek Wojakowski, Division of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland.

24. Appendix

ESC/EACTS Scientific Document Group

Includes Document Reviewers, ESC National Cardiac Societies and EACTS Network of National Cardiac Surgery Societies

Document Reviewers: Alec Vahanian(ESC Review Co-ordinator)(France), Carlos-A. Mestres(EACTS Review Co-ordinator)(South Africa), Leila Abid(Tunisia), Suleman Aktaa(United Kingdom), Elena Arbelo(Spain), Folkert W. Asselbergs(Netherlands), Emanuele Barbato(Italy), Giuseppe Boriani(Italy),Margarita Brida(Croatia), Sergio Bucheri(Sweden), Robert Byrne(Republic of Ireland), Ovidui Chioncel(Romania), Lenard Conradi(Germany), Michele De Bonis(Italy), Victoria Delgado(Spain), Enoch F. Akowuah(United Kingdom), Anna Franzone(Italy), Kristina Hermann Hauga(Norway), Bettina Heidecker(Germany), Borja lbanez(Spain), Bernard lung(France), Stefan James(Sweden), Lars Kober(Denmark), Konstantinos C. Koskinas(Switzerland), Ulf

ESC Guidelines

77

Landmesser(Germany), Gregory Y.H. Lip(United Kingdom), John William McEvoy(Ireland), Gil Meltzer(Israel), David Messika-Zeitoun(Canada), Borislava Mihaylova(United Kingdom), Richard Mindham(United Kingdom), Inge Moelgaard(Denmark), Jens Cosedis Nielsen(Denmark), Gareth Owens(United Kingdom), Agnes A. Pasquet(Belgium), Thomas Pilgrim(Switzerland). Eva Prescott(Denmark), Eduard Quintana(Spain), Volker Rudolph(Germany), Rafael Sadaba(Spain), Anna Sannino(Germany), Felix C.Tanner (Switzerland), Marina Urena(France), Ionca Vaartjes(Netherlands), Christiana Vrints(Belgium), Alexander Wahba(Norway), Thomas Walter(Germany),Adam Witkowski(Poland), and Katja Zeppenfeld(Netherlands)

Contributor either withdrew or was engaged in only a part of the re-view process: Davide Capodanno

ESC National Cardiac Societies actively involved in the review process of the 2025 ESC/EACTS Guidelines for the management for valuar heart disease:

Albania: Albanian Society of Cardiology, Natin Nshu: Alaska: Algeria/Albanian Society of Cardiology, Brahim Kichou; Armenia: Armenian Cardiologists Association, Aram L. Chilingaryan; Austria: Austrian Society of Cardiology, Philipp Emanuel Bartko; Azerbaijan: Azerbaijan of Cardiology, Fud Samadado, Belgium: Belgium Society of Cardiology, Caroline M. Van de Heyning; Bosnia and Herzegovina: Association of Cardiologists of Bosnia and Herzegovina, Zumreta Kuslugjic; Bulgaria: Bulgarian Society of Cardiology, Elena Kinova: Croatia: Croatian Cardiac, Society, Josko Bulum; Cyprus: Cyprus Society of Cardiology, Christes Oftyciou; Czechia: Czech Society of Cardiology, Hana Linkova; Denmark:Danish Society of Cardiology, Emil Fosbol; Egypt: Egyptian Society of Cardiology, Hesham Baha, Estonia: Estonia; Estonia: Estonia: Jianville; Yorkmukleina: Jiaagup Trusultu; Finland: Finnish Cardac Journal, Jarkko Piuhola; France: French Society of Cardiology, Erwan Donal;Georgia: German Society of Cardiology, Shalva Petrashivli;Germany: German Cardiac Society, Tanka Katharina Rudolph;Greece: Hellenic Society of Cardiology, Maria Drakopoulos; Hungary: Hungarian Society of Cardiology, Attila Kertész; Iceland:Icelandic Society of Cardiology, Haliji: Guangdson: Ireland: Irish Cardiac Society, Ben Cole: Israel; Israel Heart Society, Shemy Carasso: Italy: Italian Federation of Cardiology, Alessandro Navazio;Kazakhstan: Association of Cardiologists of Kazakhstan, Madina Sugalimova; Kosovo Republic of: Kosovo Society of Cardiology,Gani Bajraktari; Kyrgyzstan: Kyrgyz system of Cardiology, Alina Kerminokulova; Libya: Libya Cardiac, Eliam Ohm Ingehldfig;Lithuania: Lithuanian Society of Cardiology, Sigta Glavekaitec;Luxembourg: Luxembourg Society of Cardiology, Frederic Lebrun;Malta: Maltese Cardiac Society, Daniela Cassar Demarco; Moldova(Republic of): Moldavian Society of Cardiology, Dorin Mihail Lisii;Netherlands; Netherlands Society of Cardiology, Sebastian Streukens; North Macedonia: National Society of Cardiology of North Macedonia: Emilja Avonso: Norway; Norwegian Society of Cardiology, Havard Dalen; Poland: Polish Cardiac Society, Tomasz Kukulski; Portugal: Portuguese Society of Cardiology, Cristina Gavina; Romania: Romanian Society of Cardiology, Bogdan A. Popescu: San Marino; San Marino Society of Cardiology,Roberto Bini; Serbia: Cardiology Society of Serbia, Igor Ivanov;Slovakia: Slovak Society of Cardiology, Martin Hudec; Slovenia;Slovenian Society of Cardiology, Mataz Bunc; Spain: Spanish Society of Cardiology, Thomas Javier Bermejo; Sweden: Swedish Society of Cardiology, Carl John Cronstedt Meurling; Switzerland; Swiss Society of Cardiology, Raban Jeger; Tunisia: Tunisia Society of Cardiology and Cardio-vascular Surgery, Leila Abid; Türkiye:

Turkish Society of Cardiology, Muzaffer M. Degertekin; Ukraine:Ukrainian Association of Cardiology, Elena G. Nesukay; United Kingdom of Great Britain and Northern Ireland: British Cardiovascular Society, Madalina Garbi; Uzbekistan: Association of Cardiologists of Uzbekistan, Guzal Mullabayeva.

EACTS Network of National Cardiac Surgery Societies ac-tively involved in the review process of the 2025 ESC/EACTS Guidelines for the management for valvular heart disease:

Austria: Austrian Society of Cardiac and Thoracic Vascular Surgery, Martin Grabenwoeger; Belgium: Belgian Association for Cardio-Thoracic Surgery, Frederic Vanden Eynden; Czechia: The Czech Society for Cardiovascular Surgery, Jan Vojacek; France: The French Society for Thoracic and Cardiovascular Surgery; André Rcentinelli; Germany: German Society for Thoracic and Cardiovascular Surgery, Volkmar Falk; Greece: Hellenic Society of Thoracic and Cardiovascular Surgeons, Panagiotis Dedelias; Italy: Italian Society for Cardiac Surgery, Alessandro Parolari; Netherlands: Netherlands Association for Cardio-thoracic surgery, Jerry Braun;North Macedonia: North Macedonian Society of Cardiac Surgery, Aleksandar Nikolic; Norway: Norwegian Association for Cardiothoracic Surgery, Vegard S. Ellensen; Portugal: Sociedade in Portugalues de Cirurgic Cardiaca Toracicica e Vascular, Miguel Sousa-Uva;Serbia Serbian Society for Cardiovascular Surgery, Slobodan Micovic;Spain: Sociedad Espanola de Cirugia Cardiovascular y Endovascular,Juan J. Legara; Switzerland: Swiss Society for Thoracic and Cardiovascular Surgery, Benrico Ferrari; United Kingdom: The Society for Cardiothoracic Surgery in Great Britain and Ireland, Narain Morojani Cardiovascular Surgery, Benrico Technical, Christice CprCg Committee:

ESC Clinical Practice Guidelines(CPG) Committee:Ulf Landmesser(Chairperson)(Germany), Stefan James(Co-Chairperson) Sweden), Marifania Adamo(Italy), Suleman Aktaa(United Kingdom), Folbert W. Asselbergs(Netherlands), Colin Baentig(United Kingdom), Michael A. Borger(Germany), Giuseppe Boriani(laly), Margarita Brida(Croatia), Robert A. Byrne(Ireland),Estelle Gandbakhch(France), Bettina Heidecker(Germany), Anja Henmethen(Germany), Borja Ibanez(Spain), Peter Juni(United Kingdom), Gregory Y.H. Lip(United Kingdom), John William McEvoy(Ireland), Borislara Mihaylova(United Kingdom), Inge Moelgaard(Denmark), Lis Neubeck(United Kingdom), Eva Prescott(Denmark),Bianca Rocca(lty), Xavier Rossello(Spain), Anna Sannino(Germany), Felix C. Tanner(Switzerland), Wojtek Wojakowski(Poland), and Katja Zeppenfeld(Netherlands)

ACTS Council: Volkmar Falk(President)(Germany), Patrick Myers(Secretary General)(Switzerland), Joseph Bavaria(United States of America), Korkut Bostanci(Turkiye), Filip Casselman(Belgium), Mario Gaudino(United States of America), Jurgen Hoerer(Germany), Nabil Hussein(United Kingdom), Virginia Litle(United States of America), Franca Melfi(Italy), Rafael Sadaba(Spain), Florian Schoenhoff(Switzerland), Matthias Siepe(Switzerland), and Tanya Warburton(United Kingdom)

25. References

1. Mack MJ, Leon MB, Thourani VH,Makkar R, Kodali SK, Russo M,et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med 2019:380:1005-705.https://doi.org/10.1056/NEJMoa1814052

2. Mack MJ,Leon MB,Thourani VH,Paborot P,Hahn RT,Genereux P,et al.Transcatheter aortic-valve replacement in low-risk patients at five years. N Engl J Med 2023;389:1949-960.https://doi.org/10.1056/NEJMoa2307447

3. Reardon MJ, Van Mlegehm N, Popma JJ, Kleiman NS, Sondergaard L, Mumtaz M, et al.Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med 2017;376:1321-31.https://doi.org/10.1056/NEJMoa1700456

78

$$\text{ ESC Guidelines}$$

4. Forrest JK, Deeb GM, Yakubov SJ, Gada H, Mumtaz MA, Ramlawi B, et al.4-Year out-comes of patients at aortic stenosis in the Evolutol risk from Jl. Coll Marniol C 2023;82:2163-65.https://doi.org/10.1016/j.jacc.2023.09.813

5. Delgido F, Aymor Nans M., de Waish S. Borona Nans, Birds M., Burri H. et al. 2023 ESC Guidelines for the management of endocarditis. Eur J Heart J 2023;44:3948-402.https://doi.org/10.1093/ourheart/ehjeh19

6. Virts C,Androberti, K. Kobinsik, Roselli,X. Adamio M, Inseal J, 2023 ESC Guidelines for the management of chronic coronary syndromes: developed by the task force for the management of chronic coronary syndromes of the European Society of Cardiology(ESC) Endered by the European Association for Cardio-Thoracic Surgery(EACTS). Eur Heart J 2024:45:3413-17777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777777

7. Van Gelder IC,Riernstra M,Bunting KV,Cado-arroyo R,Caso C,Vrijns H,et al.2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery(EACTS). Eur Jt 2014;2024;45:3314-414.https://doi.org/10.1093/eurilheart/ehae1766

8. Mazzoli L, Teixo-Tura G,Lanzzi S,Boc Vuson,Becne A, Brodmann M,et al.,2024 ESC Guidelines for the management of peripheral arterial and aortic diseases. Eur Heart J 2024;45:3341-414.https://doi.org/10.1093/eur�in/heae176

9.Baumgartner H, De Backer J, Babu-Narayan V, Budts W, Chessa, W Chella, Dinger G-P,et al.2020 ESC Guidelines for the management of adult congenital heart disease of the Task Force for the management of adult congenital heart disease of the European Society of Cardiology(ESC). Endons by Association for European Paudric and Congential Chemistry(AECP) International Society for Adult Congenital Heart Disease(SACHD). Eur Heart J 2020:42:563-645. https://doi.org/10.1093/epsilon/hehua534

10. Genetrema,Fh,Sharp,Rambu,Cydren AJ,Ronaldlef TeMopul,OKanisidopis,KP,et al.The mortality burden of untreated aortic stenosis. J Am Coll Cardiol 2023;82:2101-9.https://doi.org/10.1016/j.jacc.2023.09.796

11.d.Arfeyi C.J.Joffery,S.Loudon MA,Kennedy A,Person-Stuttard J,Birks J.et al.Large-scale community echocardiographic screening reveals a major burden of undag-nosed valvular heart disease in older people: the OxValVE Population Cohr Study.Eur Heart J 2016;37:3515-22:15. https://doi.org/10.1093/ourear/whh229

12. lung, Delgado V, Rosenhek R, Price S, Prendast B, Wendler O, et al.Preurobital presentation and management of valvular heart disease: the Eurovol assessment research programme val heart disease II survey. Circulation 2019;140:1156-69.https://doi.org/10.1161/CIRCULATIONAHA.119,041080

13.Gaedeal D,Bl.Dolartolomco,R van der Pfe,E,Alisserav,L.Mollmann H,Aortic valve stenosis. What do people know: A heart valve disease awareness survey of over 8,800 people aged 60 or over. Neurolentment 2016;12:883-9. https://doi.org/10.4244/6eijn06.02

14. Lancelotti P,Magne,D.Julgherul R,Cavelma L,Donal E,Dannan VMA,et al.Outcomes of patients with asymptomatic atotic stenosis followed up in heart valve clinics JAMA Cardiol 2018;603-86.https://doi.org/10.1001/jamascor.2018.3152

15. Lancelotti P, Rosenhek R, Pibrot P, Lung Bo, Ttose R, Cumorn Tos, P et al. ESC Working Group on Valvular Heart Disease Position Paper-heart valve clinics organization,structure, and experiences. Eur Heart J 2013;34:1597-606. https://doi.org/10.1093/ecur.ourel heart/ehs443

16.Chambers JB, Prendengat B, Lung, Resenek R, Zamorozon, PJ. Perardal A, et al.Standards defining a'Heart Valve Centre': ESC Working Group on Valveular Heart Disease and European Association for Cardiothoracic Surgery Overview. Eur Heart J(2017;38:2177-83; https://doi.org/10.1093/eurrieh/ehj370

17. Nishimura RA,O'GA Part, Bavaria Br, Jindneig RD, Carroll JD, Kavinsky CJ, et al. 2019 AATS/ACC/ASE/SCI/STS Expert Consensus Systems of Care document a proposal to optimize care for patients with valvent heart disease a joint report of the American Association for Thoracic Surgery, American College of Cardiology, American Society of Chocardiography, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2019;73:2609-35. https://doi.org/10.1016/j.jacc.2018.10.007

18.Dreyfau W, Dinede Wfer, Sche 2018 to the future of cardinality card and cardiac surgery?Eur Heart J 2020;41:3693-701. https://doi.org/10.1093/eurheart/ehha707

19. Vahanian, Beyersford,Fraz P,Milfojevic,Malbdus,Sausbauers J,et al.2021 ESC/EACTS Guidelines for the management of valuar heart disease. Eur JH 2022:1456-631.https://doi.org/10.1093/eurheart/ehab395

20. Leonard S, Capadano D,Sousa-Uva M-Vins, Rnt Cexs, R S, Guaracino R, F et al.Composition, structure, and function of heart teams a joint position paper of the ACVC, EPACI, EACTS, and EACTA focused on the management of patients with complex coronary artery disease requiring myocardial revascularization. Eur Heart J Acute Cardiovasc Care 2021;10:83-93.https://doi.org/10.1093/ehjacc/zaua013

21. Agricola Ancon, Fnbroch E, Donel D, Weck D, Melfafer, Fra et al. The structural heart disease interventional rager ration, skills and training a position paper of the European Association of Cardiovascular Imaging. Eur Heart J 2016/j.jacc.2018.10.007

22.Hahn RT, Mahmood F, Kodal S. Lang, R. Monaghan, M. Gillam L, Ltd. et al. Core compe-tencies in echocardiography for imaging structural heart disease interventions: ex-pert consensus statement. JACC Cardiovascular Imaging 2019;12:2560-70.https://doi.org/10.1016/j.ccmj.2019.1008

23. Birkmerey JD, Stukue TA, Tsowers AE, Goodney PP, Wennberg DE, Lucas FL. Surgeon volume and operative mortality in the United States. N Engl J Med 2003;349:2117-27.https://doi.org/10.1056/NEJlms035205

24. Khera R,Pandley A,Koshty T,Ayers C,Nallamothu BK,Das SR,et al.Role of hospital volumes in identifying low-performing and high-performing aortic and mitral valve sur-gical centers in the United States. JAMA Cardiol 2017;2:1322-31. https://doi.org/10.1001/jamaccardo.2017;4003

25. Gammie JS,O'Brien SM, Giffith BP,Ferguson TB,Peterson ED.Influence of hospital procedural volume on care process and mortality for patients undergoing elective sur-gery for mitral regurgitation. Circulation 2007;115:881-7. https://doi.org/10.1161/CIRCULATIONAHA.106.634436

26. Chilowei,Joyto N,Narywamal AC,Itagaki S,Egorova NN,Boateng P,et al.Relation of mitral valve surgery volume to repair rate, durability, and survival. J Am Coll Cardiol 2017;69:2397-406.https://doi.org/10.1016/j.jacc.2017.02.026

27.Chahwalla R,Yemavulpal S,Zserplip M,Kodali S,Hahn RT,Saxon JT,et al.Operator experience and outcomes of transcatheter mitral valve repair in the United States.J Am Cell Cardiol J,2019:79:2955-45. https://doi.org/10.1016/j.jacc.2019.09.014

28. Bonrow RO,G'A Pato, Transdah BD, Badhwar V, Bavaria JE, Lemiah S, et al.2019 AATS/ACC/SCI/STS Eongrist Consensuss of Care document: operator and institutional recommendations and requirements for transcatheter variable inter-vention: a joint report of the American Association for Thoracic Surgery, the American College of Cardiology, the Society for Cardiovascular Angiography and interventions, and The Society of Thoracic Surgeons. J Am Coll Cardiol 2020;76-96.117.https://doi.org/10.1016/j.jacc.2019.12.002

29. Grayman PAB, Mack MP, Mánandhar P, Kosinski AS, Sannino A, Smith RL 2nd, et al.Comparison of transcatheter edge-to-edge mitral valve repair for primary mitral regur-gitation outcomes to hospital volumes of surgical mitral valve repair. Circ Cardiovasc Interv 2024:17:0381.https://doi.org/10.1161/circinterventions.123.013581

30. Wild MG, Stolz L,Rosh S,Rudolph F, Goebel B, Koll B, et al. Transcatheter valve re-pair for tricuspid regurgitation: 1-year results from a large European real-world regis-try J.An Coll Cardiol 2015;220-31.https://doi.org/10.1016/j.jacc.2024.10.068

31.Carroll JD, Vemulapilul S, Dai D, Matsouka R, Blackstone E, Edwards F, et al.Proc rocedural experience for transcatheter aortic valve replacement and relation to out-comes: the STS/ACC TVT registry.J Am Coll Cardiol 2017;70:29-41.https://doi.org/10.1016/j.jacc.2017.04.056

32 Mao J. R. Redberg RF, Carroll JD, Marinab, D. Marinab, D. Kinchinger J., Thourani V, et al.Association between surgical aortic valve replacement volume and transcath-eter aortic valve replacement outcomes.JAMA Cardiol 2018;3:1070-8.https://doi.org/10.1001/j.camardica.2018.3562

33.Vemulapalli S,Carrinoll JD,Marl L,Zai D,Dosinski AS,et al.Procedural volume and outcomes for transcatheter aortic-valve replacement. N Engl J Med 2019:380:1001.https://doi.org/10.1056/NEJMsa1901109

45-504,Edwards FH,Ferrarais,KA,VurlanskyPA,PlobellkKW,He X,O'Brien SM,et al.Failure to rescue rates after coronary artery bypass grafting: an analysis from the Society of Thoracic Surgeons adult Cardiac surgery database. Ann Thorac Surg 2016;102:458-64.https://doi.org/10.1016/j.athoracsur.2016.04.051

35.Wallen T, Habhertheer A.Bavaria J, Hughes GC, Badhwar V, Jacobs JP, et al. Elective aortic root replacement in North America: analysis of STS adult cardiac surgery data-base. Ann Thorac Surg 2019;107:1307-12.https://doi.org/10.1016/j.athorascur.2018.12.039

36. Geirsson A, Ahlson, France-Cereceda A, Fuglsang S, Gunn J, Hansson EC, et al.Hospital volumes and latter year of operation correlates with better outcomes in acute Type A aortic dissection. Eur J Cardiothorac Surg 2018;53:276-81. https://doi.org/10.1093/ejc.esx/223

37. Gonzalez AA, Dirich JB, Birkmeyer JD, Ghaferi AA. Understanding the volume-outcome effect in cardiovascular surgery: the role of failure to rescue.JAMA Surg 2014;119-239.https://doi.org/10.1001/jamasurg.2013.3649

38. Wakeam E,Asu-Adei JD, Alyshy SW, Cooper Z, Weissman JS. The association of intensivs with failure-to-rescue rates in outlier hospitals: results of a national survey of intensive care unit organizational characteristics. J Crit Care 2014;29:930-5. https://doi.org/10.1016/j.jcrc.2014.06.010

9. Ward ST, Dimick JB,Zhang W,Campbell DA, Ghaferi AA. Association between hos-ptial staffing models and failure to rescue. Ann Surg 2019;270:91-4.https://doi.org/10.1097/sla000000000002744

40.Timnis A, Townsend N, Gwee CP, Torbica A, Lettino M, Petersen SE,et al. European Society of Cardiology: cardiovascular disease 2019. Eur Heart J 2020;41:12-85.https://doi.org/10.1093/eurheart/ehz859

41.Ai N,Atakas S,Yoursl T,Beska B,Batra G,Blackman DJ,et al.European Society of Cardiology quality indicators for the care and outcomes of adults undergoing trans-catheter aortic valve implantation. Eur Heart J Qual Care Clin Outcomes 2024;10:723-36.https://doi.org/10.1093/ehjqco/cqae006ae

42. Messka-Zetoun D, Baumacher H, Burwash IG, Vahanian A, Bax J, Pibarot P, et al.Unmet needs in valhar in heart disease. Eur Heart J 2023;44:1862-73. https://doi.org/10.1093/eurishet/1201

ESC Guidelines

79

43. van Djik WB, Schuit E, van der Graaf R, Groenver R, GHerrow DRLH, Lauriissen S, Casadei B, et al.Applicability of European Society of Cardiology guidelines according to gross national income.Eur Heart J 2022;44:598-607.https://doi.org/10.1093/eur�/hetac606

44.Sengupta P.Ku,Pln J.Lee,SPf,OhSm S.A.The future of valcardin heart disease as-sessment and therapy. Lancet 2024;403:1590-602. https://doi.org/10.1016/s0140-6736(23)02754-x

45.Lancolotti P,Pbarot P,Chambers J. La Canma P, Peg P, Mduhe Rur, et al.Multi-modality imaging assessment of native valvular regurgitation: an EACVI and ESC council of valvular heart disease position paper. Eur Heart J Cardiovasc Imaging 2022:23:e171-322.https://doi.org/10.1093/ehjci/jeab253.

46.Zoghbi WA, Adams D,Bonrow RO,Enrique-Sarano M,Foster E,Grayburn PA,et al.Recommendations for noninvasive evaluation of native valvular regurgitation: a report from the American Society of Echocardiography developed in collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr 2017;303-71.https://doi.org/10.1016/j.choe.20171.007

47. Popescu BA, Andrade MJ, Badano LP, Fox KF, Kflashampfa, Lncellotti P, et al.European Association of Echocardiography for recommendations for training, compe-tence, and quality improvement in echocardiography. Eur J: Echocardiography 2009;109-893.https://doi.org/10.1093/ejochecardjop/1511

48. Chambers JB, Garbi M, Nieman K, Myerson S, Pierard A, Habib G, et al.Appreatus criteria for the use of cardiovascular imaging in heart valve disease in adults: a European Association of Cardiovascular Imaging report of literature review and current practice. Eur Heart J Cardiovasc Imaging: Eur Heart J 10.1093/ehjew309

49. Agricola E,Ancona F,Bartel T,Brotet,E Dweck M,Faletra,F et.al. Multimodality im-aging for patient selection, procedural guidance, and follow-up of transcatheter inter-ventions for structural heart disease: a consensus document of the EACVI Task Force on Interventional Cardiovascular Imaging: part 1: access routes, transcatheter aortic valve implantation, and transcatheter mitral valve interventions. Eur Heart J

50.Zoghbi WA, Jone PN, Chamsi-Pasha, MA Chen T, Collins KA, Desai MY, et al.Guidelines for the evaluation of prosthetic valve function with cardiovascular imaging a report from the American Society of Echocardiography developed in collaboration with the Society for Cardiovascular Magnetic Resonance and the Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr 2024;37:2-63.https://doi.org/10.1016/j.echo.2023.10.004

51. Fraletus F, Agricola E, Chaskamfá Fa, H Rin P, Pemi A, Monmani Ran et al.,N Three-dimensional transoesophageal echocardiography: how to use and when to use-a clinical consensus statement from the European Association of Cardiovascular Imaging of the European Society of Cardology. Eur. Heart J Cardiovasc Imaging 2023:24e-119:97.https://doi.org/10.1093/ehjci/eady094

52. Picano P,Eibarot P,Lancottini P,Munon JL,BornRO.The emerging role of exercise testing and stress echocardiography in valular heart disease. J Am Coll Cardiol 2009;52551-60.https://doi.org/10.1016/j.jacc.2009.07.046

53. Generoo P, Pabirot P, Redorfi B, Mac M, Plas M, Kirkar R, Jaberla F, Staging clas-sification of a stortenic stosenosis based on the extent of cardiac damage. Eur Heart J 2017;38:3351-8.https://doi.org/10.1093/eurheart/ehx381

54. Solil L, Doldi P, Orman B, Marant M, Pusas T, Wild GPA, et al. Staging class patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge repair.JACC Cardiovasc Interv 2023;16:140-51.https://doi.org/10.1016/j.jc.2022.10.023

55. Dietz MF, Prihadi EA, van der Bilj A, Pmonears Nan, Delgado V, Bax, JJj. Prognostic implications of staging right heart failure of staging right heart failure of Stanghan sub-2020.12.1666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666

56. Genevre,P. Pibarot,P. Redforres,B.Bax,Zhao Y.J. et al. Carducard damage-ostic impact of cardiac damage after aortic valve replacement. Am Coll Cardiol 2022;80:783-800.https://doi.org/10.1016/j.jacc.2022.05.006

57. Generae,P. Cohen D,Chen D,Borplar,Fredos B,Bax,Zhao Y.The Jocard cardiac damage of quality after a fortic valve replacement in the PARTNER trials. J Am Coll Cardiol 2023;81:743-52.https://doi.org/10.1016/j.jacc.2022.11.059

58.Kwak S, Evertewert, R.Betra T, Yang H, Swang D, KoT, et al. Mark of myocardial damage predict mortality in patients with aortic stenosis. J Am Coll Cardiol 2021;7854-58.https://doi.org/10.1016/j.jacc.2021.05.047

M9. Magres,Socos B, Popescu BA,Carstenens HG,Dahl,Desai Y,Mf et al.Distribution and prognostic significance of left ventricular global longitudinal strain in asymptomatic significant aortic stenosis: an individual participant data meta-analysis. JAC Cordoscop 2019;12:84-9.https://doi.org/10.1016/j.jcpm.2018.11.005

60. Prihadi EA, van der Bilp J, Dietz M, Abou R, Volena EM, Marsan NA, et al. Prognostic implications of right ventricular free wall longitudinal strain in patients with significant functional tricuplimus degurgitation. Circ Cardiovasc Imaging 2019;12:e008666. https://doi.org/10.1161/CIRCIMAGING.118.008666

6. Little Sh, R. Sigulin V. Harbin Q, Casaen H. Rahn H., Yang. Jc, K. J. Zhao, J. E. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B. B

62. Hahn RT, Saric M,Faletra F,Farg,GRill,Lordoris LD,Horton K,et al.Recommended stan-dards for the performance of transesophageal echocardiographic screening for struc-tural heart intervention: from the American Society of Echocardiography.J Am Soc Echocardiology 2022:35-1:76.https://doi.org/10.1016/j.echo.2021.07.006

63. Nicara O,Skubas N,Ad In,Finley A,Hahn RT,Mahmood F,et al.Guidelines for the use of transseophageal echocardiography to assist with surgical decision-making in the operating room: a surgery-based approach: from the American Society of Echocardiography in collaboration with the Society of Cardiovascular Anesthesiologists and the Society of Thoracic Surgeons. J Am Soc Echocardiogr 2020;3392-734 https://doi.org/10.1016/j.ieeh.2020.03.002

64. Popescu BA, Stefanidis A, Fox KF, Cosynbs B, Delgado V, Di Salvo GD, et al. Training competence, and quality improvement in echocardiography: the European Association of Cardiovascular Imaging Recommendations: update 2020. Eur Heart J Cardiovasc Imaging: 2020:21:1305-19. https://doi.org/10.1093/ehci/jea.266

65. lung B, Delgado V, Laure P, Murray S, Sirmes PA, Rosenhek R, et al. Educational needs and application of guidelines in the management of patients with mitral regurgitation. A European mixed-methods study. Eur Heart J 2018;39:1295-303. https://doi.org/10.1093/erjaceh's2009;

6. Nashe Fashun, Roques F, Sharples LD, Nilsson J, Smith C, Goldstone AR, et al.EuroSCORE RII, original JF Jor Cardorathor Surg 2012;41:734-44; discussion 744-735. https://doi.org/10.1093/ejcbs:202433

7. Ad N, Holms SD, Patel J, Pritchard G, Shuman DJ, Halpin L. Comparison of EuroSCRE, original EuroSCORE, and the Society of Thoracic Surgeons Risk Score in Cardiac Surgery Patients. Ann Thorac Surg 2016;102:573-9. https://doi.org/10.1016/j.atorsurgar.2016.101.105

68.OBrien SM,Shahan DM,Flardo G,Ferraris VA,Hanao CK,Hacki RK,Chib et al.The Society of Thoracic Surgeons Bicardiac surgery risk models: part 2-isolated valve surgery.Ann Thorac Surg 2009:88:523-42.https://doi.org/10.1016/j.athoracsur.2009.05.056

69. Duchowski P, Hryniewelde T, Kuismierczyk M, Szymanski P. Performance of the EuroSCORE II and the Society of Thoracic Surgeons score in patients undergoing aor-tic valve replacement for aortic stenosis. J Thorac Dis 2019;11:2076-81.https://doi.org/10.21037/jtd.2019.04.48

70. Provenchev S, Chevalie A, Ghodbane W, Bouleti C, Montravers P, Longrois D, et al.is the EuroSCORE II reliable to estimate operative mortality among octogenarians?PLOs One 2017;12:01870056.https://doi.org/10.1371/journal.pone.0187056

71. Taleb Betti B, Trusbab E, Tusbab E, Astagnostie P, Squara P, Nguyen LS. Performance of EuroSCORE II and Society of Thoracic Surgeons risk scores in elderly patients under-going aortic valve replacement surgery. Arch Cardiovasc Dis 2021;114:474-81.https://doi.org/10.1016/j.acv.2020.12.004

72. Roques F,Michel P, Goldstone AR, Nashe SAMF. The logistic EuroSCORE. Eur Heart J 2003;24:882-3.https://doi.org/10.1016/S0195-668X(02)00799-6

7.Az-Alzis,Ki Shu,E.DiAlmo S,Joubarak M,Gluis A et al. Assessment of TVT and STS score risk performances in patients undergoing transcatheter aortic valve re-placement. JSCAI 2023:2100600.https://doi.org/10.1016/j.jcai.2023.100600

74. Compagnone M. Moretti C, Marcelli C, Taglieri N, Ghetti G, Corsini A, et al. Surgical risk scores applied to transcatheter aortic valve implantation: friends or foes?Short-term and long-term outcomes from a single-center registry. J Invasive Cardiol 2019;31:E282-88.

75. Tarantin G,Lefweire T, Terkelsen CJ, Frerker C, Ohmlman P, Mojmoli M, et al. One-year outcomes of a European transcatheter aortic valve implantation cohort according to surgical risk. Circ Cardiovasc Interv 2019;12:00e6724. https://doi.org/10.1161/CIRCINTVENTIONS.118.006724

67.Amold SV,Reynolds MR,Lei Y,Magnuson EA,Kirtane AJ,Kodali SK,et al.Predictors of poor outcomes after transcatheter aortic valve replacement: results from the PARTNER(Ptacement of Aortic Transcatheter Valve) trial. Circulation 2014;129:26829-90.https://doi.org/10.1016/j.circulationa.113.007477

77.Edwards FH,CHen DJ,O'Brien SM,Peters ED,Mack MJ,Shahian DM,et al.Development and validation of a risk prediction model for in-hospital mortality after transcatheter aortic valve replacement. JAMA Cardiol 2016;1:46-52.https://doi.org/10.1001/jamacardol.2015.0326

78L lung,Bu Lauoncin,C.Himbert D,Elchaninoff H,Chevreul K,Donzeau-Gouge P,et al.Predictive factors of early mortality after transcatheter aortic valve implantation: indi-vidual risk assessment using a simple score. Heart 2014;100:1016-23.https://doi.org/10.1136/hearj2013-303314

79. Arnold SV, Afilo J, Spertus JA, Tang Y, Baron SJ, Jones PG, et al. Prediction of poor outcome after transchateteric aortic valve replacement. J Am Coll Cardiol 2016:68186-77. https://doi.org/10.1016/j.jacc.2016.706.762

80. Raposeirs-Roubin A, Simica M, Freixa X, Arzamendi D, Benito-Gonzalez T,Montefusco,A et al. A study to assess mortality after percutaneous mitral valve repair.J Am Coll Cardiol 2023:79. https://doi.org/10.1016/j.jacc.2021.2021.11.041

11. Shah N,Madhavan MV,Grow WA,Brener SJ,Ahmad Y,Lindenfeld J,et al. Prediction of death or HF hospitalization in patients with severe FMR: the COAPT risk score. JACC Cardiovascular Interv 2022:15:1893-905.https://doi.org/10.1016/j.jcin.2022.08.005

82. Hausleiter, J. Machmann, Stolz L, Bedogni F, Rubbio AP, Estévez-Loureiro R, et al.Artificial intelligence-derived risk score for mortality in secondary mitral regurgitation

80

ESC Guidelines

treated by transcatterate edge-to-edge report: the EuroSMR risk score. Eur Heart J 2004;45:922-36.https://doi.org/10.1093/eurinerth/ehab2871

83.ADamo M,Rubbio AP,Zaccone G,Pighi M,Massmas,M.,Tasonomi D,et al.Prediction of mortality and heart failure hospitalins in patients undergoing M-TEER; external validation of the COPT risk score.Eurolntervention 2023;18:1408-17.https://doi.org/10.4244/EJl-D-22-00992

84.Dreyfus J,Audreese B,Obtott Y,Cineos A,Laine Bryadie B,Yourch M,et al.CRIORE: a new risk score for in-hospital mortality prediction after isolated tricus-tid peric-sug surgery. Eur Heart J 2022:43:654-62. https://doi.org/10.1093/eurheartj/ehab679

85. Dreyfu J5, Bohbot Y,Cisne A, Lavie-Badie Y, Flagiello B, Barei B, et al. Predictive va-lue of the TRI-SCORE for in-hospital mortality after redio isolated tricupale sur-vage.erH 2023;109:951-8.https://doi.org/10.1136/heartjnl-2022-322167

86. Lantelme P,Aubry M,Peng JC,Riche B,Souteyner G,Jaaraf P,et al. Comorbidities may offset expected improved survival after transcatheter aortic valve replacement. Eur Heart J Open 2022;2:0aeoc2029.https://doi.org/10.1093/ehjopen/oeac029

87. Plankova P,Aflalo J,Prevalence and prognostic implications of frailty in transcatheter aortic valve replacement. Cardiol C.2003:2875-785.https://doi.org/10.1016/j.cci.2019/09:011

88.Kim DH,Aflalo,Shi SM,Popja JJ,Khabbarz Ka,Rlahm J,R alet. Evaluation of changes in functional status in the year after aortic valve replacement. JAMA Intern Med 2019;17938-91.https://doi.org/10.1001/jamainterned.2018.6378

89. Scotti, CoAine, Granada JF, Drignig E, Madhavan MV,Zhou Z,et al. Impact of mal-nution in patients with heart failure and secondary mitral regurgitation: the COAPT Trial.J Am Coll Cardiol 2023;82:128-38.https://doi.org/10.1016/j.2023.04.047

89a. Pagnes M, Adamo Stolz, L. Pancalid, E: Kresoja KP, von Stein J, al. Malnuttnor and outcomes in patients with triquisid regurgitation undergoing transcatheter triculus valve repair. Eur Heart Fail 2025. https://doi.org/10.1002/ehjF362. Epub ahead of print PMID: 39980251.

90.Sundermann SH,BCischoff-Ferrari HA,Debhi HM.Szekely A,Voller H,et al.Preinterventional frailty assessment in patients scheduled for cardiac surgery or trans-catheter aortic valve implantation: a consensus statement of the European Association for Cardioharor/THEIC Surgery(EACTS) and the European Association of Preventive Cardiology(EAPC) of the European Society of Cardiology(ESC). Eur J Cardiothoroc Surg,2023:46:3811,https://doi.org/10.1093/acs.eckst/8181.

91.Richter Gu, D. Stuqi L, Walker D, Lambrinou E, Lions C, Abreu A, et al.Frailty in cardiology:definition,assessment and clinical implications for general cardiology. A consen-sus document of the Council for Cardiology Practice(CCP), Association for Acute Cardio� Vascular Case(ACVC), Association of Cardiovascular Nursing and Aulfled Professions(ACNAP), European Association of Preventive Cardiology(EAPC),European Heart Rhythm Association(EHRA), Council on Valuar Heart Diseases(VHD), Council on Hypertension(CHT), Council of Cardiol(Cncodio/Cnc)C,Working Group(WG) Aorta and Peripheral Vascular Diseases, WG e-Cd CardiolG Wtmosi, the European Society of Cardiology, European Primary Care Cardiology Society(EPCES). Eur J Prev Cardiol 2022;29:216-27.https://doi.org/10.1091/cj.1993-10783179.103951746176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176176

92.Kundi H, Popma JJ, Roemskyi MR, Strom JB, Pao DS, Velimert LR, et al. Frailty and related outcomes in patients undergoing transcatheter valve therapies in a nationwide cohort Eur JHT 2019;4231-2023.91:https://doi.org/10.1093/erjeh@187

93. Brusco NK, Atkinson V, Woods J, Myles P, Hods P, Hodge J, C et al. Implementing PROMS for elective surgery patients: feasibility, response rate, degree of recovery and patient acceptability.J Patient Rep Out Occes 2022;73:https://doi.org/10.1186/s41687-022-00483-6

94.Arnold SV,SperusJA,Lei Y,Allen KB,Chatriwalla AK,Leon MB,et al. Use of the Kansas City Cardiomyopathy Questionnaire for monitoring health status in patients with aortic stenosis.Circ Heart Fail 2013;6:61-7.https://doi.org/10.1161/cirparfalli.112970053

95.Amold SV,Spernus JA,Gosch-Kuny,Shol DM,Olts IPG,et al.Ovaluation of Kansas Kansas City Modophyronity Questionnaire in patients with tricuspid regurgitation.JAMA Cardiol 2025;10:117-25 https://doi.org/10.1001/jamacard.2024.4266

96. Clavel MA, Tribouliny C, Vansversely Jl, P. Surar R, Sui RM, Symanski C, et al.Association of B-type natureticite peptide with survival in patients with degenerative mitral regurgitation.J Am Coll Cardiol 2016;68:1297-307.https://doi.org/10.1016/j.jcc.2016.06.047

97. Clavel MA,Malouf J,Michela H, Suri R, Jarmie AS, Mahoney DW, et al. B-type natriate uretic peptide de ederly patients with venlular disease: on J Coll Coll 2014;63:2016-25.https://doi.org/10.1016/j.jacc.2014.02.581

98. Zhang B,Xu H,Zhang H,Liu Q,Ye Y,Hao J,Hao J. Prognostic value of N-terminal pro-B type-natric peptide in elderly patients with valular heart disease. J Am Coll Cardiol 2020;75:1659-72.https://doi.org/10.1016/j.jacc.2020.02.031

99.Lindman BR,Breyley JG,Schilling JD, Vatterton A2, Zajarias A, Maniar HS, et al.Prognostic utility of novel biomarkers of cardiovascular stress in patients with aortic stenosis undergoing valve replacement. Heart 2015;101:1382-8.https://doi.org/10.116/Alha.119.10357-2015-307742

100 Lindman BR,Clavah MA,Abu-Alhayaya§ R, Cote N., Gadenias F, Novak, E et al.Multimarker approach to identify patients with higher mortality and reshospital rate after surgical aortic valve replacement for aortic stenosis. JACC Cardiovasc Interv 2018;11:2172-81.https://doi.org/10.1016/j.jcin.2018.07.039

101. Henri P, Perdard L, Lancard Lotti P, Mongeon F-P, Pibarot P, Basmadjian AJ. Exercise testing and stress imaging in valvular heart disease. Can J Cardiol 2014;30:1012-26.https://doi.org/10.1016/j.cca.2014.03.013

102. Das,P.Rimington H,Chambers J.Exercise testing to stratify risk in aortic stenosis.Eur Heart J 2005;26:1309-13.https://doi.org/10.1093/eurheart/ehi/250

103. Redfors B, Pibarot P, Gillam LD, Burkhoff D, Bax JJ, Lindman BR, et al. Stress testing in asymptomatic toric stenosis. Circulation 2017;135:1956-76. https://doi.org/10.1161/CIRCULATIONAHA.116.25457

10. Lund O,Nielsen T,Emmersen K,Flo C,Rasmussen B,Jensen FT,et al.Mortality and worsening is prognostic profile during waiting time for valve replacement in aortic stenosis. Stenosis or Cardiovasc Surg 1996;44:289-95.https://doi.org/10.1055/s-2007-1012039

105. Guazzi,Amera,R.Halle M,Piepoli MF,Myers J,Lavie CJ.2016 focused update: clinical recommendations for pulmonary exercise testing data assessment in specific pa-tient populations. Eur Heart J 2018;39:1144-61.https://doi.org/10.1093/eurheartj/ehw180

106. Hoedemers S, Puglle Resur, Stassen J, Vanoppenen A, Claessens J, Gojevic T, et al.mAPICO slope and oxygen uptake add prognostic value in aortic stenosis.Circulation 2024;149:1172-82. https://doi.org/10.1161/CIRCULATIONAHA.123.06730

10.Lancelotti P,Chen R.,Luronge R.,Go YY,Sugimoto T,Marchetta S,Oury C,et al.Stress echo-cardiography in patients with native valvular heart disease. Heart 2018;104:807-13.https://doi.org/10.116/13earjini-2017-311682

10.Gentry JL,Phelan,Das,Delai MY,Griffin BP.The role of stress echocardiography in valvarial heart disease: a current appraisal. Cardiology 2017;137:137-50. https://doi.org/10.1159/000460274

109.Lancellotti P, Magne J, Donald echocardiography in regurgitant valve disease. Circ Cardiovasc Imaging 2013;6:840-9.https://doi.org/10.1161/CIRCIMAGING.113.000474

110.Lancollotti P.,Magre J.,Donald E,O'Connor K,Dulghuler R,Rosca M,et al. Determinants and prognostic significance of exercise pulmonary hypertension in asymptomatic se-vere tortic stenosis. Circulation 2012;126:851-9. https://doi.org/10.1016/CIRCIVACIMING.AII.1188427

111. Coisne A,Ahegazzf,S.Gall E,Mouton S,Richardson M,Dubois D,et al.Prognostic va-lues of exercise echocardiography and cardiopulmonary exercise testing in patients with primary mitral regurgitation. Eur Heart J Cardiovasc Imaging 2022;23:1552-61.https://doi.org/10.1093/ehcijejaab231

12.Saeed S,Rajani R,Sefert R,Parkin D,Chambers JB. Exercise testing in patients with asymptomatic moderate or severe aortic stenosis. Heart 2018;104:1836-42.https://doi.org/10.1016/11392018-312939

11.Saeed S,Chambers JB. Exercise testing in aortic stenosis; safety,tolerability,clinical benefits and prognostic value. J Clin Med 2022;11:4983.https://doi.org/10.3390/jcm11149783

114. Sarners Ri, Percinah Z, Givereong C, Piccoli A, Ferrero V, Lunardi M, et al. Physiologic evaluation of coronary lesions using instantaneous wave-free ratio(iFR) in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.Uerolmentenol 2018:13:1512-9.https://doi.org/10.4244/EJl-D-17-00542

115.Pesarini G, Scarsini R, Zivelonghi C, Piccoli A, Gambaro A, Gottlin L, et al. Functional assessment of coronary artery disease in patients undergoing transcatheter aortic valve implantation: influence of pressure overload on the evaluation of lesions severity.Circ Cardovasis Interv 2016;9e004088. https://doi.org/10.1161/circinterventions.116.116

116.Ahmad Y,Gotberg M,Cok C,Howard JP,Malik I,Mikhail G,et al. Coronary hemo-dynamics in patients with severe aortic stenosis and coronary artery disease undergo-ing transcatheter aortic postline replacement: implications for clinical indices of coronary stenosis severity.JACC Cardiovasc Interv 2018;11:2019-31.https://doi.org/10.1016/j.jon.2018/07.019

117. Ardehali A, Segal J, Cheitin MD. Coronary blood flow reserve in acute aortic regurgi-tation. J Am Coll Cardiol 1995;25:1387-92. https://doi.org/10.1016/0735-1097(95)00018-Y

118. Akasaka T,Yoshida K,Hozumi T,Takagi T,Kaji S,Kawamoto T,et al. Restricted cor-onary flow reserve in patients with mitral regurgitation improves after mitral recon-structive surgery.J Am Coll Cardiol 1998:32:1923-30.https://doi.org/10.1016/S0735-1097(98)0049-20

119. DA to M, Dimopoulos K, Coghlan JG, Kovacs G, Rosenkranz S, Naeije R. Right heart catheterization for the diagnosis of pulmonary hypertension: controversies and prac-tical issues. Heart Fail Clin 2018;14:467-77.https://doi.org/10.1016/j.hfc.2018.03.011

120. Lindman BR, Arnold SV, Bagur R, Clarke L, Coyewright M, Evans F, et al. Priorities for patient-centered research in valvular heart disease: a report from the National Heart,Lung, and Blood Institute Working Group.J Am Heart Assoc 2020;9:e015975. https://10.1016/11.1914:119.015795

121.Dharmarajan K, Foster C, Loyewright M, Green P, Vavalle JP, Faheem O, et al. The medically managed patient with severe symptomatic aortic stenosis in the TAVR era: patient characteristics, reasons for medical management, and quality of shared de-cision making at heart valve treatment centers. PLoS One 2017;12:0e175926. https://doi.org/10.1371/journal.pone.0175926

ESC Guidelines

81

122. Ren X,Liu K,Zhang H,Meng Y,Li H,Li Sun,X et al. Coronary evaluation before heart valurgurary using by coronary computed tomography angiography versus invasive coronary angiography.J Am Heart Assoc 2021;10:e019531.https://doi.org/10.1161/ja.120.10931

123. Opoljski MP, Staruch AD,Jakubczyk M,Min James K, Gransar H, Staruch M, et al CT angiography for the detection of coronary artery stenoses in patients referred for car-diac valve surgery. J ACCcdosung 2016;19:509-7.https://doi.org/10.1016/j.jcpm.2015.09.028

124. Meijboom Willem B, Mollet No.R, Van Miehem Carlos AG,Kulin J, Weustink Annick P,Cuglisee F, et al. Pre-operative computed tomography coronary angiography to de-tect significant coronary artery disease in patients referred for cardiac valve surgery.J Am Card Cell 2006;48:1658-65.https://doi.org/10.1016/j.jc.2006.06:054

125. Gatti,Mallone Gorg,Pone Vlin,BFer Vano,Fraseri A,Depaoli A,et al.Diagnostic accuracy of coronary computed tomography angiography for the evaluation of obstructive coron-ary artery disease in patients referred for transcatheter aortic valve implantation: a system-termatic review and meta-analysis. Eur Radiol 2022:315-8920. https://doi.org/10.1007/s00330-022-08603-y

126. Diller GP, Germing M, Borroni Gzolaol. Se-Torres-Alba F, Radue RM, Vombrock J,et al. Utility of coronary computed tomography angiography in patients undergoing transcatheter or aortic valve implantation: a meta-analysis and meta-regression based on published data from 7458 patients. J Clin Med 2024;13:631.https://doi.org/10.3390/cm1302631

127.Kondelonof NP,Layouna H,Silpas N,Kipao J,Kanar B,Culcoa V,Stand B,et al.Effectiveness of pre-TAVR CTA as a screening tool for significant CAD before TAVR. JACC Cardiovasc_2023;16:1990-2000.https://doi.org/10.1016/j.jcin.2023.05.030

128. Malebranide D,Hoffer MPM.,Huber AT,Cicaoic,Sano G,Bernhard B,et al.Diagnostic performance of quantitative coronary artery disease assessment using computed tomography in patients with aortic stenosis undergoing transcatheter aortic valve implantation. BMC Cardiovasc Disord 2022:22:178. https://doi.org/10.1186/s12872-022-02623-8

129. Cheflo A. Ginoust G, Pagoplanou, P. Panoulas IV. Montorano M. Labat et al. R. Unittane screening of coronary artery disease with computed tomographic coronary angiog-raphy in place of invasive coronary angiography in patients undergoing transcetathere aortic valve replacement. Circ Cardivocres 2012:58-2022.10001118.1161/circinventions.114.002025

130. Patel KP, Michail M, Treibel TA, Rathod K, Jones DA, Ozorko M,et al. Coronary re-circulation patients in undergoing aortic valve replacement for severe aortic stenosis.JACC Cardiovasc Interv 2021;14:2083-96.https://doi.org/10.1016/j.jcin.2021.07.058

131.Miyagawa,Sasai,Futik,HaudaYam,Tuakawa,Tlakawa,Hetho K,Tehor al Coronary circulatory dysfunction in stectonic as myocardial contrast echocardiography study.Ann Thorac Surg 2009;87:715-9.https://doi.org/10.1016/j.jacc.2018.1108.078

13. Beach MJ,Mijelvatic,T.Sensong L.,Rjawarich,W.,Kerarich,W.,Griffin,B.,et al.Coronary artery disease and outcomes of aortic valve fragment for severe aortic stenosis.J.Am Coll Cardiol 2013:61:837-48.https://doi.org/10.1016/j.jacc.2012.10.049

13.Thalji N,Surm Ri,Plad yDRC,Greson ZLaronear J,Aro,Stuigul et al.The prognostic impact of concomitant coronary artery bypass grafting during aortic valve imaging for revascularization in the transcatheter a year; Thorco Cordovus Surg 2015;149:451-60.https://doi.org/10.1016/j.jtcvs.2014.08.073

134. Lenborg,J. Jabbari,R.Sabbah,M Vienik Ni,KTemi,Mreeman,Fan P,et al.PCI in patients undergoing transcatter aortic valve implantation. EnRfJ Med 2024191299-2005.https://doi.org/10.1056/NEJMoa2401513

13. Patterson T, Clayton T, Dodd M, Kawhay Z, Morice MC, Wilson K, et al ACTIVATION(Percutaneous Coronary In-Terivation prior to transcatheter aortic VAVE Implantation: a randomized clinical trial. JACC Cardiovasc Interv 2021;14:1965-74.https://doi.org/10.1016/j.jcin.2021.06.041

136. Okuno T, Demirel C,Tomii, D Heg, D Haer N, Siontis G.M., et al. Long-term risk of unplanned percutaneous coronary intervention after transcatheter aortic valve preparation.Inemultention 2021:187-793:803.https://doi.org/10.1016/j.cpsid.202144/

137. Persits, Layoun H, Kondoleon NP, Spilias N, Badwan D, Ospiko, J. et al. Impact of un-treated chronic obstructive coronary artery disease on outcomes after transcatteret aortic valve replacement. Eur. Heent 2014;451890-900. https://doi.org/10.1093/ernehe/aehe/hoae

138. Ogami T, Kiner D, Toma C, Sanon S, Smith AJC, Serna-Galogades P, et al. Acute cor-onary syndrome after transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forerary and transcetathar a valve forer

139 Mentias A, Desi A, Maryd, SoH, Morritz PA, Rossen JA, Pandich S, et al. Indidence and outcomes of acute coronary syndrome after transcatheter aortic valve replacement.JACC Cordovac Inc. 2020:1938-50. Smith, D. D. Henera, P. Rossman, J. et al. Indidence and

140. Yassen M, Moustofa A, Venkataraman B, Schodowski E, Royrfman R, Ethawy E Clinical outcomes of transcatheter aortic valve replacement with and without percu-taneous coronary intervention- an updated meta-analysis and systematic review. Corprol Blardiol 2023;48:101980.https://doi.org/10.1016/j.cpcardiol.2023.101980

141. Altib AM,Gham Fman,Ham Fmann,Fhated,Pfel,Jong,S.Hoqz,Gelvaia et al.Clinical outcomes of revascularization with percutaneous coronary intervention to transchater

aortic valve replacement: a comprehensive meta-analysis. Curr Probl Cardiol 2022;47:101339.https://doi.org/10.1016/j.cpcardiol.2022.101339

142.Tomil D,Pilgrim T,Borgor Ma,De Backer O,Lanz J,Reineke D,et al.Aortic stenosis and coronary artery disease: decision-making between surgical and transcatheter man-agement. Circulation 2024;150:2046-69.https://doi.org/10.1161/circulationha.124.070502

143.Tarantini G, Tang G, Nai Fovino L, Blackman D, Van Mieghem NM, Kim WK, et al.Management of coronary artery disease in patients undergoing transcatheter aortic valve implantation. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Intertices in collaboration with the ESC Working Group on Cardiovascular Surgery. EuroIntervention 2023;19:37-52. https://doi.org/10.4244/ej-d-22-00998

14. Barbanti M, Costa G, Picci A, Criscione E, Reddavid C, Valvo R, et al. Coronary cannu-lation after transcatheter aortic valve replacement: the RE-ACCESS study. JACC Cordovics Intercres 2020:13:2542-55. https://doi.org/10.1016/j.jcin.2020.07.006

145. Costa G, Sammarino S, Tazzierori O, Motta S, Fittittra V, Dietro E, et al. Coronary cannulation following TAVR using self-expanding devices with commissural alignment:the RE-ACCESS 2 study.JACC Cardiovascular Interv 2024;17:727-37. https://doi.org/10.1016/j.jcin2021.12.015

146. Tang GHL,Amatos Santos,§i Backer OD, Awedimento M, Redondo A, Barbanti M, et al.Rationale, definitions, techniques, and outcomes of commissural alignment in TAVR.JACC Cardiovasc Interv 2021;15:1497-518.https://doi.org/10.1016/j.jcin.2022.06.001

14. Tang CHL,Amatos N2,BCurang N,Razzouk A,Pai RG.Factors affecting regression of mitral regurgitation following isolated coronary artery bypass surgery. Eur J Cardiothor Surg 2005;28:73-7.https://doi.org/10.1016/j.ejctics.2005.10.010

148.Castberry ABW,Williams JB,Daneshmand MA,Honeycutt E,Shaw LK,Samad Z,et al.Surgical revascularization is associated with maximal survival in patients with ischemic mitral regurgitation: 20-2019.Circulation: 2014;129:2547-56.https://doi.org/10.1611/CIRCULATIONAHA.113.005223

14. Samad Z,Shaw L,KPhelan M,Ersbol M,Risum N,AI-Khalidi HR,et al.Management and outcomes in patients with moderate or severe functional mitral regurgitation and se-vere left ventricular dysfunction.Eur Heart J 2015;36:2733-41.https://doi.org/10.1093/eurven/h343

Y. Youseafar R, Bajnaj, K. Krishnaswamy A, Goel SS, Agarwal S, Aksoy O, et al. Outcomes of patients with ischemic microgaturation undergoing percutaneous coronary inter-vention.Am J Cardiol 2014;114:1011-7.https://doi.org/10.1016/j.amjcard.2014.07.012151.

151. Byrne A.Rossio X,Coughanjian J,Barbato E,Cerry C,Chiefo A,et al.2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J 2023;44:3270-826.https://doi.org/10.1093/ourheartj/ehad191

12. Thomas KL, Jackson LR 2nd, Shrader P, Ansell R, Fonarow GC, Gersh B, et al.Prevalence, characteristics, and outcomes of valvular heart disease in patients with at-rial fibrations: insights from the ORBIT-AF(outcomes registry for better informed treatment for atrial fibrillation). J Am Heart Assoc 2017;6:e006475. https://doi.org/10.1161/ja.1176.006475

15.Naser J.A, Pislaru C,Rosalin M,Chabin A,Oujo N,Hnkoi N,Morko VT,et al.Unfavorable tricuspid annulus dynamics: a novel concept to explain development of tricuspid regur-ingation in atrial fibrillation.J Am Soc Echocardiogr 2022;35:664-6. https://Unfavorable tricuspid annulus dynamics: a novel concept to explain development of tricuspid regur-

15. Naser J, Pisarlu C, Roslan A, Ciobanu A, OJuni H, Nkomo VT, et al. Unfavorable tricuspid annulus dynamics: a novel concept to explain development of tricuspid regur-gitation in atrial fibrillation.J Am Soc Echocardiogr 2022:35:664-6. https://Unfavorable

15. Vinreenareu D,Wang A,Maulder H,Lopes RD,Jansky P,Lewis BS,et al. Outcomes in anticogulated patients with atrial fibrillation and mitral or aortic valve disease.2018:104:1292-9. https://doi.org/10.1136/heartjnl-2017-312272

15.Avecum A, Lopes R, Schulte PJ, Lanas F, Gersh BJ, Hanna M, et al. Apixaban in com-parison with warfarin in patients with atrial fibrillation and valvular heart disease: find-ings from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation in ARSTOTLE) trial. Circulation 2015;132:624-32. https://doi.org/10.1161/CIRCULATIONAHA.114.014807

15.97. Ezkowitz MD, Nagar-Nagardi T,Roack H,Brueckmann M, Litherland C,Jacobs M,et al.Comparison of dibagtrian and warfarin in patients at atrial fibrillation and valvular heart disease in the RE-LY trial(randomized evaluation of long-term anticoagulant ther-apy). Circulation 2016;134:589-98.https://doi.org/10.1161/CIRCULATIONAHA.115.020950

158 De Caterina R, Renda G,Carnicelli AP, Nordio F, Trevisan M, Mercuri MF, et al.Valvular heart disease patients on edoxaban or warfarin in the ENGAGE AF-TIMI 48 trial. J Am Coll Cardiol 2017;69:1372-82.https://doi.org/10.1016/j.jacc.2016.12.031

15. Breitthard G, Baumgartner H, Berkowitz SD, Hellkamp AS, Piccini JP, Stevens SR, et al.Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-varvalular fibrillation but underlying native mitral and aortic valve disease par-ticipating in the ROCKET PF trial. Eur Heart J 2014;35:3377-85. https://doi.org/10.1093/earheilux305

160. Whitlock RP, Belley-Cote EP,Paparella D, Healey JS, Brady K, Sharma,et al. Left at-rial appendage occlusion during cardiac surgery to prevent stroke.N Engl J Med 2021;384:2081-91.https://doi.org/10.1056/NEJMoa2101897

82

$$\text{ ESC Guidelines}$$

161. Martin Gutierrez E., Castanoi Mao, Gualis J, Martinez-Comendorad JM, Maiorano P,Castillo L, et al. Beneficial effect of left atrial appendage closure during cardiac surgery:meta-analysis of 280 585 patients. Eur J Cardiothoraco Surg 2020;57:252-62. https://doi.org/10.1097/tejezz289

16.Connelly J9,Lealey J1,Belley J3,Berley C-Eotpe A,Basubramanian K.,Pesultina A,Braday R,Eot al.Orcal anticoagulation use and left atrial appendage occlusion in LAAOS III. Circulation 2023;148:1384-3001:https://doi.org/10.1161/CIRCULATIONAHA-12.060315

13. Kapadia SR, Krishnaswamy A, Whisenant B, Petluri S, Liver y, Aragon J, et al.Concomitant left atrial appendage occlusion and transcatheter aortic valve replace-ment among patients with atrial fibrillation. Circulation 2024;149:743-743.https://doi.org/10.1161/circulationa.123.067312

16. Dawgwas GK,Dietrich E,Cuker A,Barnes GD,Leonard CE,Lewis JD.Effectiveness and safety of direct oral anticoagulants versus varfwinar in patients with valvular atrial fibril-lation: a population-based cohort study. Ann Intern Med 2021;174:910-9. https://doi.org/10.7326m216-6194

16. Connolly SJ,Karthikeyan N, Antsekhe M, Haileamak A, Elakov A, El Grammyaw A,et al. Rivoxaban in rheumatic heart disease-associated atrial fibrillation. N Engl J Med 2023;3879-988-https://doi.org/10.1056/NnPao.20920501

16. Rankin JS, Grau-Spepulyeda MV,AD,Namiano RJ,Rilgin AM,Annan J.M.,et al.Associations between surgical ablation and operative mortality after mitral valve pro-cedures.Am Thorco Surg,2018;1790-60,https://doi.org/10.1016/j.athoracursar.2017.12.035

16. Bhavwar V, Rankin JS, Ad N, Grau-Sepulveda M, Damino RJ, Gillin AM, et al.Surgical ablation of atrial fibrillation in the United States: trends and propensity matched outcomes. Ann Thoroc Surg 2017;104:493-500. https://doi.org/10.1016/j.athoracur.2017.05.016

168. Gillin AM, Gelins AC, Parides MK,De Rose JrJr, Noosky WJ, 若�osine P,et al.Surgical ablation of atrial fibrillation during mitral valve-varying nerve. NJ Engl J Med 2015;372:1999-409.https://doi.org/10.1016/NEv140055820

19.Huffman MD, Karmal KKN, Berendsen MA, Andrei Ac, Kruse J, McCarthy PM, et al.Concomitant atrial fibrillation surgery for people undergoing cardiac surgery.Crochovae Synet 2016;2016:CD101814.https://doi.org/10.1016/j.14651858.CD011814.pub2

170.WangH,Han,JWang,Zin Y.Zin,Zu Jin,Y.Zin,Jet al.A prospective randomized trial of the cut-and-sew Maze procedure in patients undergoing surferatic viral mematicity during a Jelfor. Cardiovascular Surg 2018;155:608-17.https://doi.org/10.1016/j.tcvs.2017.07.084

171. Lawrance CP,Henn MC,Miller JP,Sinn L.A. Schussler RB, ManéHs,et al.A minimally invasive Cox maze IV procedure is as effective as steronomy as�sterity while decreasing major morbidity and hospital study. Thorj. Cardiovasc Surg: 2014:14855-9; discussion 962-952.https://doi.org/10.1016/j.jtcvs.2013.

172.Cheng DC,Ad N,Martin J,Berglin EE,Chang BC,Doukas,Gas et al.Surgical ablation of atrial fibrillation in cardiac surgery, a meta-analysis and systematic review. Innovations(Philo) 2010;5:84-96.https://doi.org/10.1097/LmI0b031e3181d91999

173. McClure GR,Belley-Cotter,Jefer,Shi R.,Unhigam N.,A. Korrein, F. G., Alshar, C. Alab, a lation of atrial fibrillation: a systematic review and meta-analysis of randomized con-trolled trials. Europce 2018;20:1442-50.https://doi.org/10.1093/eurospace/eux336

174.Yoo J.Sim,Ki)B,Ro SK,Yung J.Shong J.Shong C.J,et al of concomitant surgesal atrial fibrillation ablation in patients undergoing aortic valve replacement. Circ J 2014;78:1364-71.https://doi.org/10.1253/circj.13-1533

157. Malisine SC, Lee R, Kruse J, Lavin B, Wang EC. Bonrow R, et al. Astral fibration ablation in patients undergoing aortic valve replacement. J Heart Valve Dis 2012:21:305-7.

176. Galir DM,黎GLi B, Bhattacharyya S, Radation-induced vascular heart disease. Heart 2016;102:269-76.https://doi.org/10.1136/heartjini-2015-30876

177. Lee C.Hahin R. Valutin Heart disease associated with radiation therapy a contemary por review. Struct Heart 2023:7:10014.https://doi.org/10.1016/j.shj.2022.100104

178.Lancellotti P.,Knomo VT, Badano LP, Bergler-Klein, Boga Jert, Wang L, et al. Expert consensus for multi-modality imaging of cardiovascular complications of radiotherapy in adults: report as a from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J Am Soc Echocardiology 2013;26:1013-32.https://doi.org/10.1016/jacho.2013.07.005

179. Wu W, Masri A, Popovic ZB, Smedira NG, Lytle BW, Marwick TH, et al. Long-term survival of patients with radiation heart disease undergoing cardiac surgery: a short study.Circulation 2013;127:1476-85.https://doi.org/10.1161/CIRCULATIONAHA.113.001435

180.Donnelan E,Ali A,Johnston DR, Pettersson GB, Rodriguez Popson, L'Quilis, N'wharper 2021 and long-term outcomes of patients with mediastinal radiation-associated severe aortic stenosis and subsequent surgical aortic valve replacement: a matched cohort study.J Am Heart Assoc 2017;Ct0359305;https://doi.org/10.1016/j.116A.1100539

181.Donnellan A, Alashi, Johnston DR, Gillinov AM, Pettersson GB, Svensson LG, et al. Outcomes of patients with mediastinal radiation-associated mitral valve disease under-going cardiac surgery. Circulation 2023:1949:1288-90. https://doi.org/10.1016/j.circulation.

18. Lyon LR, Volérng-Fernandez T,Couch LS, Astegnajo R, Anzar MC,Bergler-Klein J,et al.2022 ESC Guidelines on cardio-oncoly developed in collaboration with the

European Hematology Association(EHA), the European Society for Therapeutic Radiology and Oncology(ESTRO) and the International Cardio-Oncology Society(IC-OS). Eur Heart J 2022;43:4229-361.https://doi.org/10.1093/eurheart/ehac244

18. Yazdych,Fi Huiy,N A,Noriah A,Percy E,Harloff M, Malarczyk A,et al. Transcatheter compared with surgical aortic valve replacement in patients with previous chest-directed radiation therapy. JACC Cardioonol 2021:3:397-407. https://doi.org/10.1016/j.jaccao:2021.07.005

18. Zafar MR, Mustafa SF, Miller TW, Alkhawlani T, Sharma UC. Outcomes after trans-catheter aortic valve replacement in cancer survivors with prior chest radiation ther-ap a systematic review and meta-analysis. Cardioconology 2020;6:8. https://doi.org/10.1186/s40959-020-00062-y

18. Utah W., Thalambere N., Zahid S, Muhammadzai Hamza Zahid U, Sandhyavenu H,Kumar A.et al. Trends and outcomes of TAVI and SAVR in cancer and noncancer pa-tients.JACC Adv 2023:2:100167.https://doi.org/10.1016/j.jaccad.2022.100167

16. Lind A.Toetzke M, Mahadiab A, Janosi RA, El Gabry M, Ruhparwar A, et al. Impact of cancer in patients undergoing transcatheter aortic valve replacement: a single-center study.JACC Cardioonol 2020;7:353-43.https://doi.org/10.1016/j.jaccao.2020.11.008

187.Yager S, Johnson CO, Aboyans V, Adebayo OM, Abedoyin RA, Afardeih M, et al.Global, regional, and national burden of calcific aortic valve and degenerative mitral valve diseases: 1990-2017. Circulation 2020;141:1670-80. https://doi.org/10.1161/CIRCULATIONAHA.119.403391

18.Rwebemberma, Marangou J,Mwita JC,Mocumbi AO,Mota C,Okello E,et al.2023 World Heart Federation guidelines for the echocardiographic diagnosis of rheumatic heart disease. Not Rev Cardiol 2023;21:250-63. https://doi.org/10.1038/s41569-023-00940-9

19.Karpi K,Prune W,�Bastisol M, Shahorna R, Shrestna NR, Sherpa K,et al. Effectiveness of systematic echocardiographic screening for rheumatic heart disease in Nepalese schoolchildren: a cluster randomized clinical trial. JAMA Cardiol 2021;6:420-26.

19. Beaton Aokon,ElRokel,Ewbernejabera,J.Grobler A,Engelman D,Alepere J,et al.Secondary antibiotic prophylas for latent rheumatic heart disease. N Engl J Med 2022;386:230-40.https://doi.org/10.1016/j.shi.2022.1007204

191.Kumar RK, Antunes MJ, Beaton A, Mirabel M, Nkomo VT, Okello E, et al.Contemporary diagnosis and management of rheumatic heart disease: implications for closing the gap: a scientific statement from the American Heart Association.Circulation 2020;142:e337-57. https://doi.org/10.1161/cir.000000000000921

19. World Health Organization. WHO Guideline on the Prevention and Diagnosis of Rheumatic Fever and Rheumatic Heart Disease. https://www.who.int/publications/i/n7978920140077(2028 March 2025, date last accessed).

13.Choncelio and Adamo M.,Nikoua M.,Kaoua M.,Parisis J.,Mebazaa A,Yilmaz MB,et al.Acute heart failure and valular heart disease: a scientific statement of the Heart Failure Association, the Association for Acute Cardiovascular Care and the European Association of Percustaneous Cardiovascular Introductions of the European Society of Cardiology. Eur J Heart Farf,2013;2025:1025-48.https://doi.org/10.1002/ehjf.2018f.

194. Luseknir L, Kereh L, Kehlarir A, Karam N, Kapadia S, Makkar R, et al.(December 11,2024) Management of acute decompensated valvular heart disease. Eur J Heart Fail,https://doi.org/10.1002/efjh.3549

15.Kolte D,Khera S,Vemulapal i S,Dai D,HeoS,SGawmeig AM,et al. Outcomes follow-ing urgent-emergent transatheter aortic valve replacement: insights from the STS/ACC TVT registry,JACC Cardovic Resintv 2018;11:1175-85.https://doi.org/10.1016/j.jcin.2018.03.002

196. Elbadwai A, Elgendy IY, Menatias A, Saad M, Mohamed AH, Choudhry MW, et al.Outcomes of urgent versus nongutens catheter aortic valve replacement. CatheteroCardiosiv Interv 2019;96:189-95.https://doi.org/10.1002/cd.28563

19. Masha,L.Vemulamal,Salandh P,Balan P,Shah P,Kosinski AS,et al.Demographics,procedural characteristics, and clinical outcomes when cardiogenic shock precedes TAVR in the United States. JACC Cardiovasc Interv 2020;13:1314-25.https://doi.org/10.1016/j.cn.2020.02.033

18. Goel K, Shah P, Jones BM, Kornold E, Bhardwaj A, Kar B, et al. Outcomes of trans-catheteric aortic valve replacement in patients with cardiogenic shock. Eur Heart J 2023:44181-951.https://doi.org/10.1093/eurhearti/ehad387

1993. Buchwald B,Aheier,Teng R,Stochen B,Unterberg C.Efficacy of balloon valvulo-plasty in patients with critical aortic stenosis and cardiogenic shock-the role of shock duration. Clin Cardiol 2001:24:14:8. https://doi.org/10.1002/clc.4960240308

200.Moreno PR,Jang IK,Newell JB,Block PC,Palacios IF.The role of percutaneous aortic balloon valulopysity in patients with cardiogenic shock and critical aortic stenosis. J Am Coll Cardiol 1994;23:1071-5. https://doi.org/10.1016/0735-1074/90952-4

201. Lahl ST,Sharif S, Uhali S, Shahh SA, Shah MA, Shafi OM, et al. TAVR vs balloon aortic valotomy for severe aortic stenosis and cardiogenic shock: an insight from the nation-alample data sample detection in cardiovascular cavity. Cardiovasc Resang Med 2023;55:1-7. https://doi.org/10.1016/j.carrev.2023.05.006

2022. Tang GHL.Estverle-Louroerio R,Yu Y,Prillinger JB,Zaid S,Psotka MA.Survival following edge-to-edge transcatheter mitral valve repair in patients with cardiogenic shock: a na-tionwide analysis. J Am Heart Assoc 2021;10:e019882. https://doi.org/10.1161/jaha.120.

ESC Guidelines

83

203. Haberman D,Estevel-Lourere Rino,Benito-Gonzalez T,Denti P,Arzendomi D,Adamo M,et al. Conservative, surgical, and perturbancy of treatment for mitral regurgitation shortly after acute myocardial infarction. Eur Heart J 2021;43:641-50. https://doi.org/10.1091/earheur/jabh96

204. Hill L,Prager Geller T,Baruah R,Beattie JM,Boyeen J,Deutzout N,et al.Integration of a palliative approach into heart failure care: a European Society of Cardiology Heart Failure Association position paper. Eur J Heart Of Health 2020;22:2373-39. https://doi.org/10.1002/ajehf.1994.

205. Kyriakou M,Middleton N,Kisti S,Philippou K,Lambrouin E. Supportive care interven-tions to promote health-related quality of life in patients living with heart failure: a sys-tematic review and meta-analysis. Heart Lung Circ 2020;29:1633-47.https://doi.org/10.1016/j.hlc.2020.04.019

206. Fendler TJ,Swetz KM, Allen LA. Team-based pallative and end-of-life care for heart failure. Heart Fall Clin 2015;11:479-98.https://doi.org/10.1016/j.jfc.2015.03.010

207. Brannstrom, P. Boman K. Effects of person-centred and integrated chronic heart fail-ure and all hypative home. PAREF: a randomized controlled study. Eur J Heart Fail 2014;16:1142-51.https://doi.org/10.1002/efh1.151

208.SinghJP,EvsJC,Leyu D,Larson MG,Freed LA,Fulder DL,et al.Prevalence and clinical determinants of mittric, tricuspid, and aortic regurgitation(the Framingham Heart Study).Am J Cardiol 1999;83:897-902. https://doi.org/10.1016/s0002-9149(98)01064-9

209. Lee JKT,Franzone A,Lanz J,Siontis GCM,Stortecyng S,Chrani C,et al.Early detection of subclinical myocardial damage in chronic or aortic regurgitation and strategies for timely treatment of asymptomatic patients. Circulation 2018;137:184-96.https://doi.org/10.1161/circulationahha.117.029858

210.Aashi A.Khulian T,Mentias A.Gillino AVam,Rell EE.Sencey LG,Let al.Long-term outcomes after aortic valve surgery in patients with asymptomatic chronic aortic regurgitation and preserved LVEF: impact of baseline and follow-up global longitudinal strain.J. Jaccard Convescider: Imaging 2013;12:13-2011.https://doi.org/10.1016/j.jcsg.2018.12.021

211.de Campos D,Teixeira,R.,Saleiro C,Botelho,AGongale L.Gongal Global longitudinal strain in chronic asymptomatic aortic regurgitation: systematic review. Echo Res Proct 2020:739-48.https://doi.org/10.1530/erp-20-0024

212. Lee SY,Park J,Nek,Chang CA,Lev ASa,Chin JH,et al.Preditive value of exercise stress echocardiography in asymptomatic patients with severe aortic regurgitation and preserved left ventricular systolic function without LV dilatation. Int J Cardiovasc Imaging 2019;35141-714;https://doi.org/10.1007/s105549-019565-1

21. Pizarro R, Bazzoo O, Oobert PF, Falcon MI, Aran M, Arias KM, Arauis KM, J. et al. Prospective validation of the prognostic usefulness of B-type natriuretic peptide in asymptomatic patients with chronic severe aortic regurgitation.J Am Cardiol 2010.1016/j.1016/j.1011.07.016(1995)https://doi.org/10.1016/j.1016/j.1011.017.016(1995)https://doi.org/10.1016/j.1016/j.1011.017.016(1995)https://doi.org/10.1016/j.1016/j.1011.017.016(1995)https://doi.org/10.1016/j.1016/j.1011.017.016(1995)https://doi.org/10.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.1016/j.

124.Kokova R,Linkova H, Hublockao Z,Médikle T, Tan M, Voajek,et al.Multiparametric strategy to predict early disease decomposition as anymptotic severe aortic regurgitation. Circ Cardiovasc Imaging 2022;15:e014901.https://doi.org/10.1011/circimaging.122.014901

215. Goldstein SA,Evangista et A.Abans S,Ara,Ai Asch,Fam LPo et al.,Multinodality imaging of diseases of the thoracic aorta in adults: from the American Society of Echocardiography and the European Association of Cardiovascular Imaging endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance.J.Am Soc Echocardiog 2015;28:119-82.https://elvard/1016/j.echo.2014.11.015

216. Zerny M., Grabenwoger M, Berger T, Aboyans V, Dela Corte, Chen E, EP et al.EACTS/STS Guidelines for diagnosing and treating and acute chronic syndromes of the aortic organ. Eur J Cardiothoros Surg 2024:65:32ead 426.https://doi.org/10.1093/ejcets/3024

17. Is polian de Wavoux J,Bouperau G,Chofinet Cningaveraynet, D Van Duyk M, Robert A.et al. Functional anatomy of aortic regurgitation: accuracy, prediction of surgical re-pairability, and outcome implications of transphasesophageal echocardiography. Circulation 2007;116:264-9.https://doi.org/10.1161/circulation.AN18,Chen B,2018a

218. Lanas C,De Zin A,Diora F,Al Attar N, Aar C, Joudan T,et al. A las losal clas-sification to standardize surgical management of aromatic insufficiency towards valve re-pair.J Eur. Cardiolosar 2008:33:872-86. Section 878-880. https://doi.org/10.1016/j.ejts.2007.12.033

219. Michelena H, Della Corte A, Evangelista A, Maleszewski JJ, Edwards WD, Roman MJ,et al. International consensus statement on nomenclature and classification of the con-benticus bicipustal sortic valve and its atopropity, for clinical, surgical, interventional and research purposes. Eur J. Cardiothor Surg: 20216:448-468. https://doi.org/10.1093/erjects/az308

220.Ehrlich T, de Kerchove L, Vojacek J,Boodhwan M, El-Hamamsy I, De Paulis R, et al.State-of-the plant abpicic atal repair were in 2020. Prog Cardiovasc: Dis 2020:635-475.https://doi.org/10.1016/j.ppcad.2020.04.010

22. Elvangelista Masip A, Galian-Gay L, Guala A, Lopez-Sainz A, Teixido-Tura G, Ruiz Mufoz A, et al. Untravelic buckic atic valve engras by multimodality imaging clin-ical implications. J Clin Med 2022;11:456.https://doi.org/10.113902/11020456

222. Elder DHJ,Wei ZSwekowskiBR,Libiano,R.Nadir A,Pauriah M,et al.The impact of renin-angiotins-asterolideone system blockade on heart failure outcomes and

mortality in patients identified to have aortic regurgitation: a large population cohort study.J Am Coll Cardiol 2011:58:2084-91.https://doi.org/10.1016/j.jacc.2011.07.043

223. Seferovic PM, Ponikowski IP, Anker SD,Bauversachs J, Chioncel O, Cleland JGF,et al.Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2019;21:1169-86.https://doi.org/10.1002/ejhf.1531

224. Chaliki HP,Mohty D,Avinos JF,Scott CG,Saffch HV,Tajik,AJ,et al.Outcomes after aortic valve replacement in patients with severe aortic regurgitation and markedly re-duced left ventricular function. Circulation 2002;106:2687-93.https://doi.org/10.1161/01.circ.000038498.59283.88

225. Kaneko J, Eijor J, Jeforor K, Neely RC, McGurk S, Ivovic V, Stevenson LW, et al. Aortic re-gurgitation with markedly reduced left ventricular function is not a contraindication for aortic valve replacement. Ann Thorac Surg 2016;102:41-7. https://doi.org/10.1016/j.gharorac.2015.12.068

226.Tornos P,Sambola A,Permany-Miralda G,Evangelaista A,Gomez Z,Soler-Soler J.Long-term outcome of surgically treated aortic regurgitation: influence of guideline ad-hence toward early surgery.J Am Coll Cardiol 2006;47:1012-7.https://doi.org/10.1016/j.jacc.2005.10.009

227. Lodas E,Enriquez-Sarano M,Tajik AJ,Mullany CJ,Bailey KR,Seward JB. Optimizing timing of surgical correction in patients with severe aortic regurgitation: role of symp-toms.J Am Coll Cardiol 2005-1997;30:746-52.https://doi.org/10.1016/s0735-1097(97)00205-2

D28ujin DARS,Enriquez-Sarano M,Maffh BV,Hailey KR,Seward JB,Tajik.A.Mortality and morbidity of aortic regurgitation in clinical practice. A long-term follow-up study.Circulation 1999;99:1851-7.https://doi.org/10.1161/1.69ir.99.14.1851

29. Dierling AG, Bhambman V,Laikhter P, Picard MH, Wasfy MM, Tolis G,et al. Aortic valve replacement associated with survival in severe regurgitation and low ejection fraction.Heor 2018;104:835-40. https://doi.org/10.1136/heartjnl-2017-312024

T. Chouribou 31, C. Enriquez, C. Sarano M, Schaff HV, Orszulak TA, Fett SL, Bailey KR, et al.Excess mortality due to coronary artery disease after valve surgery. Secular trends in valvular regurgitation and effect of internal mammary artery bypass. Circulation 1998;98:1108-115.

21.Forman for R.Third BG,Barnard MS.Prognostic significance of preoperative left ventricurc-lar fraction selection and valve lesion in patients with aortic valve replacement. Am J Cardiol 1980;45:1120-5. https://doi.org/10.1016/0002-9149(80)90468-3

23.Bonrow Ro, Lakibova, P. Aron BJ, Epstein SE. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventril-

23.Budhiy KS,Carky McPMonts,Gkumpati GS,Helou J,Hoercher KJ,Rajeswaran J,et al.Improved outcomes after aortic valve surgery for chronic aortic regurgitation with se-vere left ventricular dysfunction.J Am Coll Cardiol 2007;49:1465-71.https://doi.org/10.1016/j.jacc.2007.01.026

23. Sambola T,Aornos T.,Fernira-Zonzalez I,Evangelista A.Prognostic value of preopera-tive indexed end-systolic left ventricle diameter in the outcome after surgery in pa-tients with chronic aortic regurgitation. Am Heart J 2008;155:1114-20. https://doi.org/10.1016/j.ah2007.12.025

25. Yang LT, Michena Helia, Smallr CG, Enriquez-Sarano M, Pislaru SV, Schaff HV, et al.Outcomes in chronic hemodynamics significantly sufficient aortic regurgitation and limitations of current guidelines. J Am Coll Cardiol 2019;73:1741-52.https://doi.org/10.1016/j.jacc.2019.01.024

26. Menias A,Feng,K Alashi A,Rodriguez LL,Gillinov AM,Johnston DR,et al.Long-term outcomes in patients with aortic regurgitation and preserved left ventricular ejection fraction.J Am Coll Cardiol 2016;68:2144-53.https://doi.org/10.1016/j.jacc.2018.045

27. Shao Metern, C. Gerber BL, Vanneyraet N, Douleur A, Noirhomme P, Pasquet A,et al. Do guideline-based indications result in an outcome penalty for patients with se-vere aortic regurgitation? JACC Cardiovasc Imaging 2019;12:2126-38.https://doi.org/10.1016/j.cst.2018.11.022

28. Yang LT, Anand V, Zambio T, Pellicka PA, Scott CG, Thapa P, et al. Association of echocardiographic left ventricular end-systolic volume and volume-derived ejection fraction with outcome in asymptomatic chronic aortic regurgitation. JAMA Cardiol 2021;61:189-98.https://doi.org/10.1001/jamacardio.2020.5268

29. Yang LT, Lee CC, Su CH, Amano M, Nabeshima Y, Kitano T, et al. Analysis of left ven-tricular indexes and mortality among Asian adults with hemodynamically significant chronic aortic regurgitation. JAMA Translow J Open 2023;6:234632. https://doi.org/10.1001/jamanteworkopen.2023.4632

20. Hashimoto G, Enriquezano M, Stanberry Li, Oh F, Wang, Acosta K, et al.Association of left ventricular remodeling assessment by cardiac magnetic resonance with outcomes in patients with chronic aortic regurgitation. JAMA Cardiol 924-33.https://doi.org/10.1001/jamacardio.2022.2108

241.Malafhi M,Crudo V,Kaolaawanhich Y,Nguyen DT,Telmesani,A Saeed M,et al.Influence of cardiac remodeling on clinical outcomes in patients with aortic regurgitation. J Am Coll Cardiol 2023;81:1885

24. Vermes E, lacuzio L, Levy F, Bohbot Y, Renard C, Gerber B, et al. Role of cardiovascular magnetic resonance in native valvular regurgitation: a comprehensive review of

84

$$\text{ ESC} G\text{ Guidelines}$$

protocols,grading of severity, and prediction of valve surgery. Front Cardiovasc Med 2022;9:881141.https://doi.org/10.3389/fcm2.2022.881141.

243.Flynn CD,Tian DH,Wilson-Smith A,David T,Matalanis G,Misfeld M,et al.Systematic review and meta-analysis of surgical outcomes in Marfan patients undergoing aortic root surgery by composite-gval valve for graft or simeptair replacement. Ann Cardiohorac Surg 2017;6:570-81.https://doi.org/10.21037/acs.2017.11.06

244.Chavette V,Kulin J,de Kerchove L,El Kourky G,Saffers H.JLansac,E et al.Outcomes of valve-sparing surgery in heritable or disorders: results from the AVIATOR registry.Eur J Cardiothorac Surg 2022;62:ezac366.https://doi.org/10.1093/ejcsec/3266

245. Wilson-Smith AR, Wilson-Smith CJ, Strode Smith J, Ng D, Muston BT, Eranki A, et al.The outcomes of three decades of the David and Yacoubic procedures in bicuspid aortic valve patients-a systematic review and meta-analysis. Ann Cardiothorac Surg 2023;1286-94.https://doi.org/10.21037/acs-2023-avs2-19

246. Zuo Y,Tan R,Qn C. Outcomes of valve-sulfuric aortic root replacement in patients with bicuspid aortic valve and tricuspid aortic valve: a systematic review and pulsic atic arctic valve: a systematic review and meta-analysis of hydroxial asortic and nematic analysis.

247. Mastrobuoni S, Govers PJ, Veen KM, Jahanyar J, van Saane S, Segreto A, et al.Valve-sparing aortic root replacement with the replantation(Dvath) technique: a systematic review and meta-analysis on survival and clinical outcome. Ann Cardiothorac Surg 2023;12:149-58.https://doi.org/10.2103/acs-2023-avcs-3012-083

248.Acheri D,Fries R.;Rodoryeva S,Schmidt K.;Langer,F.Schaffres J.H.Aortic valve repair leads to a low incidence of valve-related complications. Eur J Cardiothorac Surg 2010:37:127-3.https://doi.org/10.1016/j.eijts.2009.06.021

29. de Meester C, Pasquet A, Gerber BL, Vanacryastec D, Norhomme P, El Khoury G,et al. Valve repair improves the outcome of surgery for chronic severe aortic regurgi-tation: a propensity score analysis. J Thorac Cardiovasc Surg 2014;148:1913-20. https://doi.org/10.1016/j.jctv.2014.020.014.020.

250.Klotz,S Stock,S.,Sievers HH,Diwoyk,Metersen,Sliorle,Uet al. Survival and re-operation pattern after 20 years of experience with aortic valve-saring root replace-ment in patients with tricuspid and bicuspidal valves. J Thorac Cardiovasc Surg 2018;155:1403-11.e1401.https://doi.org/10.1016/j.jtcvs.2017.12.039

251. Ebatary Tam,M.TY Dedelman J.Roach,Ru WMA,Petersen MD,et al.Valve-sparing root replacement versus valve compaticity using aortic root dilation: a meta-analysis. Ann Thoroc Surg 2020;110:296-306. https://doi.org/10.1016/j.�c.

252. Leentovys S, Schamberger L, Davierwala PM, Von Asperk T, Etz C, Lehmann S, et al.Early and late results after David vs Bellant procedure a propensity matched analysis.Ann Thoroc Surg 2019;110:120-6.https://doi.org/10.1016/j@thorasurs.2019.10.020

253. Mastrobuoni S, Kechvero L, Navarra W, Etremazue C, Vanneastyao R, Dubilar, J, et al. Long-term experience with valve-squaring implantation technique for the treatment of aortic aneurysm and aortic regurgitation.J Thorac Cardiovasc Surg 2019;158-123.https://doi.org/10.1016/j.tjcsv.2018.10.155

25. Lanans C,Dei Z,Salario L, Selagine L, Geopre S, Kheh N, Bernebi A, et al. Long-term results of external aortic ring annuloplasty or aortic valve repair. Eur J Cardiothorac Surg 2016;95:30-60.https://doi.org/10.1093/ejctvs/0ezw/027w

255. Lee,Cho YH,Sung,Ki Wms,Park KH,Jeon DS,Lesnel alncos of root reimplantation and Bentall procedure: propensity score matching analysis. Ann Thorco Surg.2018;106:539-47.https://doi.org/10.1016/j.athrescu.2018.02.057

25.Norton EL,Patel,Pal,Peline,D.Wiel JW,Binonog,JL Neshower BG,et al.Bentall ver-sus valve-sparating or aortic root replacement for root pathology with moderate-to-severe aortic insufficiency: a propensity-matched analysis. Eur J Cardioarol Surg.20234:3623-21

257.Arabkhani B,Klaut RJM,de Heer F,De Kerchove L,El Kourky G,Salacans,E et al.A multicentre, propensity score matched analysis comparing a valve-sparing approach to valve replacement in aortic root aneurysm: insight from the AVIATOR database.Eur J Cardiacovs: Sociov 2013:63:032:363:432.

258.Levin D,Patel P,Zhao Y,Chung M,Singh S,Childress P,et al.Valve-sparing aortic root replacement versus composite valve graft with bioprostiosis in patients under age 50./Thoracic Convodc Surg 2023;1982-1992.002-1002.1@chjvs2023.07.030.16

259. Schneider U,Hofmann,C.Schope,J Niewald AK,Giebels,C Karivalio,L al.Long-term results of differentiated anatomic reconstruction of bucial dortical vices. JAMDi 2020;5:1366-73.https://doi.org/10.1001/jamacardio.2020.3749

260.Zamine A,Roche R.VHamamyl,Mouzian Uyan,Maragawa B,Bhattl DL,et al.Ross procedure vs mechanical aortic valve replacement in adults: a systematic review and meta-analysis.JAMA Cardiol 2018;3:978-87.https://doi.org/10.1001/jamacardio.2018.2946

21. Takrenberg JJM, Klieverrik LMA, Schoof PH, van Syuln RJ, van Herwenle LA,Zondervan PE,et al.The Ross procedure: a systematic review and meta-analysis.Circulation 2009;1199:22-8,https://doi.org/10.1016/CRCUATIONHA.107.72634

262. Yokoyama Y,Kuno T, Youno T, Fujida N, Fujisaki T, Takagi H, Taagl S, et al. Ross procedure versus mechanical versus bioprostiotic aortic valve replacement: a network

meta-analysis. J Am Heart Assoc 2023;12:e8066. https://doi.org/10.1161/jaha.122.027715

263. El-Hamamsy I, Toyoda N, Itagaki S, Stelzer P, Varghese R, Williams EE, et al.Propensity-matched comparison of the Ross procedure and prosthetic aortic valve re-placement in adults.J Am Coll Cardiol 2022;79:805-15.https://doi.org/10.1016/j.jacc.2021.11.057

264. Sawya FJ, Deutsch Ma, Selfert M, Yoon SH, Codner P, Wickramarachchi U, et al.Safety and efficacy of transcatheter aortic valve replacement in the treatment of pure aortic regurgitation in native valves and failing surgical bioprostheses: results from an international registry study. JACC Cardiovasc Interv 2017;10:1048-56. https://doi.org/10.1016/j.jcin.2017.03.004

25. Yoon SH, Schmidt T, Biefer S, Schofer N, Fiorina C, Munoz-Garcia AJ, et al.Transcatheter aortic valve replacement in pure native aortic valve regurgitation.J Am Coll Cardiol 2017;70:2752-63.https://doi.org/10.1016/j.jacc.2017.10.006

26.Poletti E,De Recker O,Scotti A,Costa G,Bruno F,Fiorina C,et al.Transcatheter aor-tic valve replacement for pure native aortic valve regurgitation: the PANTHEON inter-national j.CACC Jaccardic Interv 2023;16:1974-85.https://doi.org/10.1016/j.jcin.

267,Garcia,Ye J,Webb,JReond M,Kleiman N,Goel S,et al.Transcatheter treatment of native aortic valve regurgitation: the North American experience with a novel de-vice. JACC Cardiovasc Interv 2023;16:1953-60. https://doi.org/10.1016/j.jcin.2023.05.

268. Adam M, Tamr A, Weinemann H, Unbeahan A, Klein C, Arnold M, et al.Transcatheter aortic valve replacement for isolated aortic regurgitation using a new self-expanding TAVR system. JACC Cardiovasc Interv 2023;16:1965-73. https://doi.org/10.1016/j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.ianf.1016/j.j.

26. Yuhel TP, Thorani Vuh, Khoura RR, Hamid N, Khalique OK, Daniels D, et al.Transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic reglaturation(ALIGN-AR): a prospective, multicentre, single-arm study. Lancet 2024;403:1451-9.https://doi.org/10.1016/s0140-6736(23)02806-4

270. Borger MA,Preston M,Ivanov J,Fedak PW,Davierwala P,Armstrong S,et al.Should the ascending aorta were replaced more frequently in patients with bicuspid aortic valve disease.J Thorac Cardiovasc Surg 2004;128:677-83.https://doi.org/10.1016/j.jtcvs.2004.07.09

271.Cody A, Rizzo JA, Hammer GL, Mandapati D, Darr U, Kopf GS, et al. What is the appropriate size criterion for resection of thoracic aortic aneurysms? J Thorac Cardovacs Surg 2009;117:3146-791; discussion 489-491. https://doi.org/10.1016/s0022-5233(97)70360-X

272.Davies RR,Goldstein LJ,Coady MA,Ittle SL,Rizzo JA,Kopf GS,et al.Yearly rupture or dissection rates for thoracic aortic aneurysms: simple prediction based on size.Ann Thorac Surg 2002;73:17-27; discussion 27-18.https://doi.org/10.1016/s0003-4975(01)03236-2

273.Farina LA,Y L,rizo JA,Charilaou P,Saeyeldin A,Velasquez CA,et al.Height height alone,rather than body surface area, suffices for risk estimation in ascending aortic aneurysm.J Thorac Convex Cardovus Surg 2018;155:1938-50.https://doi.org/10.1016/j.tjcvs.2017.10.140

274. Popovic ZB. Desai MY,Griffin BP. Decision making with imaging in asymptomatic aor-tic regurgitation: JACC Cardiovasc Imaging 2018;11:1499-513.https://doi.org/10.1016/j.jcng.2018.05.027

25. Elavengel A, Patis G, Jmedon A, Grujield R, Pei M, Cuelhan H, et al. Multimodality imaging in thoracic disagingases: a clinical consensus statement from the European Assocction of Cardiovascular Imaging and the European Society of Cardiology work-ing group on and parts per peripheral vascular diseases. Eur Heart J Cardiovasc Imaging 2023:24:e65-85.https://doi.org/10.1093/ehjide024

276. Weisenberg D, O omlichenko A, Shapira Y, Vaturi M, Monakier D, Bental T, et al.Mid-term echocardiographic progression of patients with moderate aortic regurgita-tion: implications for aortic valve. J Heart Valve Dis 2013;22:192-4.

275. Butwis P. Pleiles Ge, Rous-Hesselink JW, Sanz de la Garza M, D'Ascenzi F,Giannakoulas G,et al.Recommendations for participation in competitive sport in ado-lescent and adult withletes with Congenital Heart Disease(CHD): position statement of the Sports Cardiology& Exercise Section of the European Association of Preventive Cardiology(EAPC), the European Society of Cardiology(ESC) Working Group on Adult Congental Heart Disease and the Sports Cardiology, Physical Activity and Prevention Working Group of the Association for European Paediatric and Congentinal Heart Disease(ECP). Eur Heart J 2020;41:4191-9.https://doi.org/10.1093/erheuria/habE041

278. Robertson EN, van der Linde E, Shrah AG, Valley MP, Wilson M, Bannon PG, et al.Familial non-syndormal thoracic aineurysms and dissections-incidence and family screening outcomes. Int J Cardiol 2016;220:43-51.https://doi.org/10.1016/j.icard.2016.06.086

279. Bray JH.Freer R.Pcher A.Kharbanda R. Family screening for bicuspid aortic valve and aortic dilation: a meta-analysis. Eur. Heart J2023;44:3152-64.https://doi.org/10.1093/eurheart/ehad320

280. Roberts WC, KO. P.Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation 2005;111:920-5. https://doi.org/10.1161/001.Cirillo.0005526158.48408.C5

ESC Guidelines

85

281. Verma,Su S12. SC Aortic dilatation in patients with bicuspid aortic vale. N Engl J Med 2014;37019:1920.https://doi.org/10.1056/NEJMR1072059

28.Zuhke L,Engel M, Krathkeyigen, Grangarajan S, Mackie P, Cupido B, et al.Characteristics, complications, gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry(the REMYed study). Eur Heart J 2015:36:1115-22a.https://doi.org/10.1093/eurinj/ehu449

283.Wilner N.Prosporters L.Guaz,Lu N. Hamui DY.A Boccar,K. Poulin A.et al. Aortic stenosis: progression a systematic and meta-analysis.JACC Cardiovasc Imaging 2023;16:314-28.https://doi.org/10.1016/j.jmc.2022.10.009

28.Dweck MR,Lanogath R,Bing R,Treibel TA,M.Cann GP,Newdy DE,et al.Multi-modality imaging in a stenotic stenosis: an EACVI clinical consensus document. Eur Heart J Cardiovesc Imaging 2003:24140:33.403.https://doi.org/10.1093/icjus[15:03]

28. Jaiswal V,Agrawal V,Kulbe Y,Hanif M,Huang H,Meamed M,et al.Cardiac amyloid-osis and a stenosis: state-of-the-art-reheur. Eur J Open 2023:3:ead0106.https://doi.org/10.1093/phenjeh/1105

28. Desei MY, Alashi A, Popovic ZB, Wierup P, Griffin Bramp, Thamarilarsan, M et al.Outcomes in patients with obstructive hypertrophic cardiomyopathy and concomi-tant staticenosis undergoing surgical anymity or aortic valve replacement.J Am Heart Assoc 2021;10:e018435.https://doi.org/10.1161/AHA.120.018435

287.Baumvarrner H, Jung Befro, Jemjois R, James B, Edarsen T, Goldstein S, et al.Recommendations on the echocardiographic assessment of aortic valve stenosis: a fo-cused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J Am Soc Echocardiogr. J 2015;372-92.https://doi.org/10.1016/j.echo.2017.02.009

288.Rusinaru D,Bohbot Y,Debliari F,Delpierre Q,Altes A,Serbout S,et al.Normative ref-erence values of cardiac output by pulsed-wave Doppler echocardiography in adults.Am JCD/2021:140:128-33.https://doi.org/10.1016/j.amjcard.2020.10.046

289. Annab MS,Touboul E,Dahou A,Bawur AB,Gongle-Bierler,KinJem,Eusmaro-Sano et al.Dobutamine stress echocardiography for management of low-flow, low-gradient aor-tic stenosis.J Am Coll Cardiol 2018:7175-485.https://doi.org/10.1016/j.jacc.2017.11.052

290.Clavel MA,Wurshag L,Mundigler G,Dumsenil JG,Baumgartner H,Bergler-Klein J,et al. Valdation of conventional and simplified methods to calculate projected valve area at normal flow rate in patients with low flow, low gradient aortic stenosis at normal flow rate in patients with low flow, low gradient aortic stenosis at multicenter TOPAS(True or Pseudo Severe Aortic Stenosis) study. J Am Soc Echocardiorgen 2010:28:380.6-https://doi.org/10.1016/j.echo.2010.02.002

291. Ash J, Sandhu GS, Arriola-Montenegro J, Agakisynieh D, Cavello M, Pbarot P, et al.Performance of computed tomographic angiography-based aortic valve area for as-sessment of aortic stenosis. J Am Heart Socc2023:12:e029973.2:e029973.1611/ja.1239237.

292.Guzzetti E, Poulin A, Annabi MS, Zhang B, Kalavrouziotos D, Couture C, et al.Transvular flow, sex, and survival after valve replacement surgery in patients with severe aortic stenosis.J Am Coll Cardiol 2020;75:1897-909.https://doi.org/10.1016/j.jacc.2020.07.065

293.Mehrora Pans,Jian Fyang,AW Tanw,AY Tan,Celharia S,Picard MH,et al.Differential left ventricular remodelling and longitudinal function distinguishes low flow from normal-flow preserved ejection fraction low-gradient severe aortic stenosis. Eur Heart|2013;34:1906-14.https://doi.org/10.1093/eurieh/ett094

294. Tribouli R, Ruscarinu D, Marechauxus S, Castel AL, Debry N, Maizel J, et al Low-gradient, low-flow severe aortic stenosis with preserved left ventricular ejection fraction: characteristics, outcome, and implications for surgery.J Am Coll Cardiol 2015;65:56-66. https://doi.org/10.1016/j.1016/j.2014.09.080

29. Wander 13. Miners Houl, Gertsedt R, Bonomi B, Krudi P, et al. Outcome of patients with low-gradient"severe" aortic and preserved ejection fraction. Circulation 2011:123:887-95.https://doi.org/10.10161/CIRCULATIONAHA:110.983510

296. Bohbot Y, Kubala M, Rusinaru D, Marechaux N., Vasenschoveled JL, Triboulay L C. Survival and management of patients with discordant high-acteristic nosis: property-matched study.JAC Cardiovasc Imaging 2021;14:1672-4.https://doi.org/10.1016/j.jcm.2021.02.010

297. Uger P.,owers P. Le Neze L., Betecassine Laxue-Exang, Coullo X, Cavelang Ll. Prevalence and outcomes of patients with discordant high-gradient aortic stenosis. J Am Coll Cardiol 2024:83:119-19.https://doi.org/10.1016/j.jacc.2024.01.025

28. Wo, Oh, Oh, Khemilena H, Elge AC, Connolly H.Pellika Pa, et al. High-gradient aortic stenosis with valve area>1.0 cm2:“the forgotten” condiderant hemodynamic phenotype. JACC Cardocvision Imaging 2025:18:166-76. https://doi.org/10.1016/j.jccm.2024.07.025

299. Ribeiro HB, Berlakis S, Gilard M, Cavalcante JL, Makkar R, Herrmann HC, et al.Transcatheter aortic valve replacement in patients with low-flow, low-gradient aortic stenosis: the TOPAS-TAVI registry. J Am Coll Cardiol 2018;7:1972-308. https://doi.org/10.1016/j.jacc.2018.01.054

300.Clavel MA,Pibarot P,Messiz-Yardn,Couplard,MoualJ,FjagnarAL,A5 et al.Impact of aortic valive calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study.J Am Coll Cardiol 2014;642:1202-13.https://doi.org/10.1016/j.jacc.2014.05.066

301. Tastet L,Enriquez-Sarano M,Capoulade R,MaloufJ,AraozPA,Shen M,et al.Impact of aortic valve calcification and sex on hemodynamic progression and clinical outcomes in AS.J Am Coll Cardiol 2017;69:2096-8.https://doi.org/10.1016/j.jacc.2017.02.037

302.Cralave M, Messka-Zetouni D, Pibarot P, Aggarwal SR, Malouf J, Araozo PA, et al. The complex nature of discordant severe calcified aortic valve disease grading: new insights from combined Doppler echocardiographic and computed tomographic study.J Am Cal Cardiol 2013:2239-38.https://doi.org/10.1016/j.jacc.2013.08.1621

303. Pawade T,Clavel Tr, APlouiloy C,Dreyfus J, Mathieu T, Tastet L, et al. Computed tomography tomography atortic valve calcium scoring in patients with aortic stenosis. Circ Cardiovasc 2018;11:e001746. https://doi.org/10.1161/CIRCIMAGING.117.007146

304. Shen M,Oh J,KuGzzetti E,Singh GK,Pawade T,Tastet L,et al.Computed tomography aortic valve calcium scoring in patients with bicuspid atortic valve stenosis. Struct Heart 2022;6:100027.https://doi.org/10.1016/j.shj.2022.100027

5035. Shen T, Tastet L, Capouad, E,Bédard E,Arsenault M,et al.Effect of age and aortic valve anatomy on calcification and haemodynamic severity of aortic stenosis.Hort 2017;103:32-9.https://doi.org/10.1136/heartjinl-2016-309665

30. Wanchaattawong W, Kanjanavitan R, Srisuwan T, Wongcharoen W, Phrommintkul A.Diagnostic role of aortic valve calcium scoring in various etiologies of aortic stenosis Sci Rep 2023;13:8019.https://doi.org/10.1038/s41598-023-34118-7

307 Ye.Z,Clavel MA,FoleTA,Fayor,PIBotar,PEnriquez-Sarano M,Michelena Hl.Computed tomography calcium scolorism inging in aortic stenosis; bicuspid versus tricuspid morphology.Jeast 2014;110:594-602. https://doi.org/10.1136/heartjln-2023-323281

30.Mazycarsak A,Tomii D,Angelotti D,Baekke PS,Nakase M,Samim D,et al.Fibrotic vs calcific atortic stenosis characteristics and outcomes in patients undergoing transc-eter aortic valve replacement. JACC Cardiovasc incert.2024;17:2969-71.https://doi.org/10.1016/j.jc.2024.09.041

309. Rusinaru D, Malaquin D, Marechaux S, Debry N, Triboullou C. Relation of dimension-less index to long-term outcome in aortic stenosis with preserved LVEF. JACC Cardiovasc Imaging 2015;876-75.https://doi.org/10.1016/j.jcm.2015.01.023

3018. Thellier N, Altes, R. Aresit M, Menet A, Layec J, Outteryck, F et al. Additive prognostic value of left ventricular dispersion and deformation in patients with severe aortic stenosis. JACC Cardiovasc Imaging 2023;17:235-45. https://doi.org/10.1016/j.jcmg.2023.09.010

31.Volena EMa, EMranahul MR, Prihadi EA, Ng ACT, van der Bijl P, Sin YK, et al.Incremental value of left ventricular global longitudinal strain in a newly proposed sta-ging classification based on cardiac damage in patients with severe aortic stenosis.Eur Heart J Cardiovascular Imaging 2020;21:1248-58.https://doi.org/10.1093/enjciae220

31. Ternacle J, Bodde G, Gullich A, Audureau R, Eappeneau S, Lim P, et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac myocardialis. J,ACC Cardiovasc Imaging 2016;9:126-38. https://doi.org/10.1016/j.cmc.2015.05.014

31. Harada K, Saito T, Tanakla J, Shibayama K, Berdejo J, Shiota T. Valvuloarterial imped-ance, but not a stortic stenosis severity, predicts syncope in patients with aortic stenosis.Circ Cardocvision Imaging 2013;6:1024-31. https://doi.org/10.1161/circimaging.113.000584

314. Hachachi Z, Dumesnl JG, Pibarot P. Usefulness of the valvuloarterial impedance to predict adverse outcome in asymptomatic aortic stenosis. J Am Coll Cardiol 2009;54:1003-11.https://doi.org/10.1016/j.jacc.2009.04.079

315. Pibrotar P, Salau E, Yuhou A, Avenatti E, Guzzetti E, Annabi MS, et al.Echocardiographic results of transcatheter versus surgical aortic valve replacement in low-risk patients: the PARTNER 3 trial. Circulation 2020;141:1527-37. https://doi.org/10.1161/circulationa.119.044574

31. Zamorollano J, BadLano, IP. Bruce C, Chan KL, Goncalves A, Hahn RT, et al. EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valular heart disease. Eur Heart J 2011;32:2189-214.https://doi.org/10.1093/eurvalo/hr259

317. Bergler-Klein J, Klaar U, Heger M, Rosenhek R, Mundigler G, Gabriel H, et al.Natriacetic phenesis. Circulation-2004;109:2302-8. https://doi.org/10.1161/01.161CIR.1000012855903018

318. Rafique AM,Biner,Say,Lir,Forrester JS,Tolstrup K,Siegel RJ. Meta-analysis of prognos-tic value of stress testing in patients with asymptomatic severe aortic stenosis. Am J Cardiol 2009;104:972-7. https://doi.org/10.1016/j.amjcard.2009.05.044

319. Lancellotti P, Lebofi F, Sonn M, Tombeux C, Chauvel C, Pierard LA. Prognostic im-portance of quantitative exercise Doppler echocardiography in asymptomatic valvular storicenosis. Circulation 2005;112:1377-82. https://doi.org/10.1161/circulationha.104253274

320. Le VD.Jensen K.Ven-Gk,Jahansen L.Prognostic usefulness of cardiopulmonary exer-cise testing for managing patients with severe aortic stenosis. Am J Cardiol 2017;120:844-9.https://doi.org/10.1016/j.camcard.2017.05.047

301. Hoodemakers, V. Verwerf J, Reddy YNV, Delvaux R, Stroobants S, Jogani S, et al.Cardiac dysfunction rather than aortic valve stenosis severity drives exercise intoler-ance and adverse hemodynamics. Eur Heart J Cardiovasc Imaging 2023;25:302-12.https://doi.org/10.1016/j.jacc.2014.05.066

86

ESC Guidelines

32. Bing, R. Cavalcal J, Everett RJ, Carlina New, MAY DEw, Dweck MR. Imaging and im-pact of myocardial fibrosis in aortic stenosis. JACC Cardiovasc Imaging 2019;2:198-23.https://doi.org/10.1016/j.jcmg.2018.11.026

32. Evertral, ReBJ et al.,Fulul,Mé R,ligi,Nang S.,Ming A et al.,Extralucary myocardial volume in patients with a stenosis. J Am Coll Cardiol 2020;75:304-16. https://doi.org/10.1016/j.jacc.2019.11.032

32.Thornton GD,Vassiliou VS,MSA A,Azminin A,Gina D.Nattani A,of Myocardial scar and remodelling predict long-term mortality in severe aortic stenosis beyond 10 years. Eur Heart J 2024:45:2019-22.https://doi.org/10.1093/eurheart/ehae067

35.Nische C, Scully PR, Patel KP, Kammerlander AA, Koschukmik, D. Dona C, et al.Prevalence and outcomes of concomitant aortic stenosis and amyloidosis.J,Am Coll Cardiol 2021:17:28-39. https://doi.org/10.1016/j.jacc.2020.11.006

326. Maurer MS, Bokhari D, Yamada S, Drachman BM, Fontana M, et al. Expert consensus recommendations for the suspicion and diagnosis of transtyrinet cardiac amyloidosis. Circ Heart Fall 2019:12e06075. https://doi.org/10.1016/cr1.1ccrtraturef11.19,006075.

327. Cannata F, Chiarito M, Pinto G, Villaschi A, Sanz-Sanchez J, Fazzari F, et al.Transchateri aortic valve replacement in aortic stenosis and cardiac amyloidosis. a systematic review and meta-analysis. ESC Heart Fail 2022:9-3188-97. https://doi.org/10.1002/elfh:18376

328. Blanke P, Weir-McCall JR, Achenbach S, Delgado, Hauslest J, Jialhari H, et al.Computed tomography imaging in the context of Transcatheter Aortic Valve Implantation(TAVJ)Transcatheter Aortic Voleg Replacement(TAVR). JACC Cardiovascular Imaging 2019;12:1-24.https://doi.org/10.1016/j.jcm.2018.12.003

329. Khan JM,Kamioka N,Lisko JC, Perdoncin,E.Zhang C,Mainani,A. Coronary obstruc-tion from VRAT in active nortic stenosis; development and validation of multivariate prediction model.JACC Cardiovasc Interv 2023;16:415-25. https://doi.org/10.1016/j.jcin.2022.11.018

320. Reindil M,Lechner I,Holknechtoi R,Fopren,Boherholzeren F.;of Cardac mag-netic resonance imaging versus computed tomography to guide transcatheter aortic valve replacement: a randomized, open-label, noninferiority: Circulation 2023;148:1220-30.https://doi.org/10.1161/CIRCULATIONAHA.123.066498

331. Gleting S. Elabz:Greener G, Ghanim D, Kusniess R, Fabin A, Sudarsky D, et al. Similar procedural success of transcutaneous aortic valve replacement with prosthesis valve sizing by either three-dimensional transesophageal echocardiography modeling or computed tomography.J Am Soc Echocardiogr 2020:33:1149-51.https://doi.org/10.1016/j.echo.2020.05.026

32. Rosbebo AB, Pedersen TR, Boman K, Brudi P, Chibas RB, Egustek R, et al. Intensive lipid lowering with transastimatin and acetatein is enotic stenosis. NEng| Med 2008:359-1346-51.https://doi.org/10.1056/NEJMoa0804602

333. Cowell SJ, Newby DE, Prescott RJ, Bloomfield P, Reid, North ridge DB, et al. A ran-domized trial of intensive lipid-lowering therapy in calcic stenosis. N Engl J Med. 2005:3522-3389-97.https://doi.org/10.1056/NEmJoa04384

334.Chan KL,Teo K,Dumesnilg JG,Ni,Tam J.E. Impact of lipid lowering with rosvatatin on progression of aortic stenosis: results of the aortic stenosis progression observation:measuring effects of rosvatatin(ASTRONOMER) trial. Circulation 101:2010:36-14. https://doi.org/10.1161/CIRCULATIONAHA.109.900027

35. PawaDE,TA toris,M.King R,Bing White,A.Corsf L,Evans E,et al. Effect of endosumab or alendonic acid on the progression of aortic stenosis: a double-blind randomized controlled trial. Circulation 2011;434:2418-27. https://doi.org/10.1161/CIRCULATIONAHA.12105370

336. Diederischenk AP, Lindhol JS,Møller,Ovrehus KA,Auscher S,Lambretschen J,et al.Vitamin K2 and D in patients with aortic valve calculation: a randomized double-blinded clinical trial. Circulation 2023;145:1387-97.https://doi.org/10.1016/j.CRCIVATIONAHA-121.057008

337.McEvoyJW,McCarthy CR,Pun,Robrun S,Carnay Danscar,CDecel al.2024 ESC Guidelines for the management of elevated blood pressure and hypertension.Eur.Heart 2024:453-912-4018. https://doi.org/10.1093/ourearhe(1)heah 178.

338. Vissener FLJ,Machul Smersy YM,Carballo D,Koskinas KC,Back M,et al.2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur J Heart 2021;42:3227-377.https://doi.org/10.1039(eurhe)ehab48

33.McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M,et al.2021 Esc. Guidelines for the diagnosis and treatment of acute and chronic heart failure: de the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology(ESC) with the Heart Failure Association(HFA) of the ESC. Eur J 12023-19/77, http://doi.org/10.1093/earheil/ehab368

340. McDonagh TA,Metra M,Adamo M,Gardner RS,Baumbach A,Bohm M,et al.2023 Focused update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic failure 1039, E-mail: 10934(eurho)ehab 368

34. Monin JL, Quére JP, Monchi M, Petright, Béhuaen S, Cauhr et al. Low-gradient aortic stenosis: operative risk stratification and predictors for long-term outcome: a

multicenter study using dobutamine stress hemodynamics. Circulation 2003;108:319-24.https://doi.org/10.1161/101.CIR.0000079171.43055.46

34. Triboullary C, Levy F, Rusinaru D, Gueret P, Petit-Eisenmann H, Baleynaud S, et al.Outcome after vortic stroke for low-flow/low-gradient aortic stenosis without contractile reserve on dobutamine stress echocardiography. J Am Coll Cardiol 2009;53:1865-73. https://doi.org/10.1016/j.jacc.2009.02.026

344. Quenpe JP, Monin JL,Leyva F,Pitahleya S,Chuan T.,Cavels C,et al.Influence of pre-operative left ventricular contractile reserve on postoperative ejection fraction in low-gradient cortosis. Circulation 2006;113:1738-44. https://doi.org/10.1161/circulationa.105.56824

344.Fougeres,E.Triboulioy C,Monchi M,Petit-Eisenmann H,Baleynaud S,Pasquet A,et al.Outcomes of pseudo-severe stenosis under conservative treatment. Eur Heart J 2013;22:3426-33.https://doi.org/10.1093/eurheart/ehs176

345. Levy F, Laurent M, Monin JL, Mallet JM, Pasquet A, Le Tourneau T, et al. Aortic valve replacement for low-flow-gradient aortic stenosis under conservative treatment. Eur Heart 2012;23:3426-33.https://doi.org/10.1093/eurheartj/ehs176

346. Mas F. Lerales S, Barbosa Ribeiro H, Gilard M, Cavalcante JL, Makkar R, et al.Outcomes from transchatterst aortic valve replacement in patients with low-flow, low-gradient aortic stenosis and left ventricular ejection fraction less than 30%: a substudy from the TOPAS-TAVI regaryry. JAMA Cardiol 2019;4:64-70.https://doi.org/10.1001/jamacardio.2018.4320

347.Sato K,Sankaramangalam K, Kandregula K, Bullen JA, Kapadia SR, Krishnaswamy A et al. Contemporary outcomes in low-gradient aortic stenosis patients who under-wontobutamine stress echocardiography. J Am Heart Assoc 2019;8e:011168.https://doi.org/10.11617/AHA.116101168

38. Uyema H, Kuno T, Harrington M, Takagi H, Krishnamoorthy P, Sharma SK, et al.Impact of surgical and transcatiether aortic valve replacement in low-gradient aortic tascinetic ncc. Jacc 2021;14:1481-92.https://doi.org/10.1016/j.jcin.2021.04.038

349.Clavel MA,Dumsiln GJ,Capoulade R,Mathieu P, Sencheal M, Pibarot P. Outcome of patients with aortic stenosis, small valve area, and low-flow, low-gradient despite pre-served left ventricular ejection fraction. J Am Coll Cardiol 2012;60:1259-67.https://doi.org/10.1016/j.jacc.2011.12.054

350. Chadha G, Bohb B, Robus Y, Rangu D, Marechaux S, Tribouilley C. Outcome of normal-flow low-gradient severe aortic stenosis with preserved left ventricular ejection frac-tion: a propensity-matched study.J Am Heart Assoc 2019;8:e012301.https://doi.org/10.1161/j.echo.2020.05.026

351. Pellika Pa, Sarano ME, Nishimura RA, Malouf JF, Bailey KR, Scott CG,et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation 2005;111:3290-5. https://doi.org/10.1161/circulationa.104.495903

35. Heuvelman Hi, van Geldorp M,Wappetein AP,Geljeinse ML,Galema TW,Bogers AJ,et al. Clinical course of patients diagnosed with severe aortic stenosis in the Rotterdam: arcs: insights from the AVARJN N. Nethr J 2012:20:487-93. https://doi.org/10.1007/s1471-012039-038

353.Otto CM,Burish LG,Agget ME,Munt B,Fujioka M,Healy NL,et al.Prospective study of asymptomatic valular aortic stenosis. Clinical, echocardiographic, and exer-cise predictors of outcome. Circulation 1997;95:2262-70.https://doi.org/10.1161/cir.95.2292

35. Bohot B. Vo, de Meester de Ravenstein C, Chadha G, Rusinaru D, Belkhir K, Trouillet C,et al. Relationship between left ventricular ejection fraction and mortality in asymp-tomatic and minimally symptomatic patients with severe aortic stenosis. JACC Cardiacovara: Imaging 2019:12:39-48.https://doi.org/10.1016/j.jcm.2018.07.029

35. Capouale R, Le Ven F, Clavel MA, Dumesnil JG, Dahou A, Thebault C, et al.Echocardiographic predictors of outcomes in adults with aortic stenosis. Heart 2016;102:934-42.https://doi.org/10.1136/heartjnl-2015-308742

356. Dahl J,Edle F,Mehlich,Mechrano H,Scott C, Sursi RM,Schaff HV,et al.Effect of left ven-tricular ejection fraction on postoperative outcome in patients with severe aortic sten-ositions undergoing aortic vary replacement. Circ Cardiovasc Imaging 2015;8e002917.https://doi.org/10.1161/CIRCIMAGING.114.002917

357. Pattang J, Morimoto T, Sriomi H, Ando K, Kanamori N, Murata K, et al. Prognostic impact of left ventricular ejection fraction in patients with severe aortic stenosis. JACC Cardiovasc Interv 2018;11:145-57.https://doi.org/10.1016/j.jcin.2017.08.036

35. To Mira, Sinda, Mirr Ouna, Viroan, Mortini, P. Pisarmu SV, Greason KL, et al. Reduced left ventricular ejection fraction in patients with aortic stenosis. J Am Coll Cardiol 2018;71:1311-21.https://doi.org/10.1016/j.jacc.2018.01.045

35. DeAvedo R, Dute M, Triboulayl C, Maréchaux S, Pouleur AC, Bohbot Y, et al.Quantifying the survival loss linked to late therapeutic indication in high-gradient se-vere aortic stenosis. JACC Adv 2024;3:100830. https://doi.org/10.1016/j.jacadv.2024.

36. Généreux P, Schwartz A, Oldemeyer JB, Pibrot P, Cohen DJ, Blanke P, et al.Transcatter aortic-valve replacement for asymptomatic severe aortic stenosis. N Engl J Med 2024;392:217-217.https://doi.org/10.1056/NEJMao2405880

16. Loganat K,Craig J.Neir,Rev Jr,Bing R,Taspasmian V,Molek P,et al.Early interven-tion in patients with asymptomatic severe aortic stenosis and myocardial fibrosis: the

ESC Guidelines

87

EVOLVED randomized clinical trial. JAMA 2024;333:213-21.https://doi.org/10.1001/jama.2024.22730

36. Kang DH,Park SJ,Lee S, Lee S, Kim DH, Kim HK,et al. Early surgery or conservative care for asymptomatic aortic stenosis. EN Engl J Med 2020:32:11:9. https://doi.org/10.1056/NEJMoa1912846

36. Banovic M, Putnik S, Penicka M, Doros G, Deja Ma, Kockova R, et al. Oortic valve re-placement versus conservative treatment in asymptomatic severe aortic stenosis by AVATAR Trial. Circulation 2022;145:648-58.https://doi.org/10.1161/CIRCULATIONAHA-121.057639

36. Rosenhek R, Binder T, Porenta G, Lang L, Christo G, Schemper M, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med 2000;343:611-7.https://doi.org/10.1056/NEJ/M2000088313430903

36. Nakatsuama K, Tanitchagi T, Morimoto T, Shiomi H, Ando K, Karamori N, et al-B: pipe taniureptide peptide in patients with asymptomatic severe aortic stenosis. Heart 2019;105:384-70.https://doi.org/10.1166/hearqin-2018-313746.

366. Parikh V,Kim,Cie,Siegel RJ,ArsjanRani,J.Rader F.Natriuretic peptides for risk stratifica-tion of patients with valvular atortic stenosis. Circ Heart Fail 2015;8:373-80.https://doi.org/10.1161/CIRHEARTFAILURE 114.01649

367. Banovic M, Putn S, Da Costa BP, Renka Fickin M, Da Mya, Korneal M, et al. Aortic valve replacement versus conservative treatment in asymptomatic severe aortic stenosis;long-term follow-up of the AVATAR trial. Eur Heart J 2024;45:4525-35; https://doi.org/10.1093/eurheart/ehae585

368. Genéreux P, Banovic M, Kang DH, Giustino G, Prendergast BD, Lindman BR, et al.Aortic valve replacement vs clinical surveillance in asymptomatic severe aortic stenosis: a systematic review and meta-analysis. J Am Coll Cardiol 2024;85:912-22. https://doi.org/10.1016/j.jacc.2024.11.006

369. Smith WTI,Ferguson TBJ,Ryan T,Landolfock CP,Estoned. Should coronary artery bypass graft surgery patients with mild or moderate aortic stenosis undergo concomi-tant aortic valve replacement? A decision analysis approach to the surgical dilemma.J Am Coll Cardiol 2004;44:1241-7.https://doi.org/10.1016/j.jacc.2024.06.031

370.Jean G, Van Mieghem N,MGeegen T, van Gils L, Bernard J, Gielesein NL, et al.Moderate a scronic stenosis in patients with heart failure and reduced ejection fraction.J Am Coll Cardiol 2021;77:2798-803.https://doi.org/10.1016/j.jacc.2021.04.014

37.Jiaquemym.XM,Shiro,Bngar,Sngay Ford,Payland,Stut K.,Yutts,et al.Moderate ar-tic valve stenosis is associated with increased mortality rate and lifetime loss: system-atic review and meta-analysis of reconstructed time-to-event data of 40980 patients.J Am Heart Assoc 2024;33872 https://doi.org/10.1161/https://doi.org/10.1161/https://doi.org/10.1161/https://doi.org/10.1161/j.jc.2023.01.04.009

37.Amanul Man,RP Si,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,Shu,

373. Van Mieghem NM,Elariah S, Spitzer E, Pabirot P, Nazif, TM, Bax JJ, et al.Transcatheter aortic valve replacement in patients with systolic heart failure and mod-erate aortic stenosis: TAVR UNLOAD.J Am Coll Cardiol 2024;85:878-90. https://doi.org/10.1016/j.jacc.202140.070

374.Graversen PL, ButH J, Ostergaadi L, Jorgen AD, Warming PE, Struege JE, et al.Changes in aortic valve replacement procedures in Denmark from 2008 to 2020.Heart 2023;109:557-63.https://doi.org/10.1163/hearji�-2022-321594

37. Johnston DR, Soltesz EG, Vakani R, Rajeswaran J, Roselliee, Esabik JF 3rd,et al.Long-term durability of bioprotetic and varyal implications: J.126.59m implants. Am Thorac Surg,2015:129:139-47.https://doi.org/10.1016/j.athorcsur.2014.10.070

36. Goldstone AB, Chiu P., Baipecchi M, Lingla B, Patrick WL, Eschille MB, et al.Mechanical or biologic prostheses for aortic valve and mitral valve replacement. N Engl J Med 2017;377:1847-375.https://doi.org/10.1056/NEmJ01637192

377. Mazine A, David TE, Stoklosa K, Chung, Jafrenier-Roula M, Ouzunian M. Improved outcomes following the Ross procedure compared with bioprostetic aortic valve replacement.J Am Coll Cardiol 2022;79:993-1005.https://doi.org/10.1016/j.jacc.2021.12.026

378. Notenboom PM, Melaig, Vena Ku, DePhys R. Copulae G, De Seraa P, et al.Long-term clinical and echocardiographic outcomes following the Ross procedure: a post hoc analysis of a randomized clinical trial. JAMA Cardiology 2023;9:6-14. https://doi.org/10.1016/jamacardio.202430.4090

379. Alkouhi M, Zack CJ, Sarraf M, Bashir R, Nishimura RA, Lieel MF, et al. Morbidity and mortality associated with balloon aortic voluplasty: a perspective. Circ Cardiovasc Interv 2017;10:e004841.https://doi.org/10.1161/CIRCINVENTIONS.116.004481

380.Sharma T,Kranshina AML,Rahoudi Pol,Rolomysi,M.Daupernan H.Lational trends in TAVAS and VRAV for patients with severe isolated a stortosis stenosis. J Am Coll Cardiol 2022:2054-205.6 https://doi.org/10.1016/j.jacc.2022.08.787

381.Gaede L, Blumenstein Jekel C, Grothusen C,Tyerli V, Sotemann D, et al.Transcheter-based aortic valve replacement vs. isolated surgical aortic valve replacement in present 2000.Clin Res Cardiol 2022;111:924-33.https://doi.org/101007/s00392-022-000601-

382.Nguyen V,Willner N,Eltchanoffin H,Wurshw IG,Michel M,Durand E,et al.Trends in atic valve replacement for a stenosis: a French daywise study. Eur Heart J 2022:43:66-79.https://doi.org/10.1093/eur�in/heah7eb

383. Mori M,Gupta A,Wang Y,Vahl T,Nazif T,Kirtane AJ,et al.Trends in transcatheter and surgical aortic valve replacement among older adults in the United States.J Am Coll Cardiol 2021;78:2161-72.https://doi.org/10.1016/j.jacc.2021.09.855

38. Plurgim T, Windecker S. Expansion of transcatheter aortic valve implantation: new in-dlications and socio-economic considerations. Eur Heart J 2018;39:2643-45. https://doi.org/10.1093/eourhart/ehy228

35. Durko AP, Anrabuger RL, Van Mieghem NM, Miljoevg NM, Mylojevic, D, Nkomo VT,et al. Annual number of candidates for transcatheter aortic valve implantation per country: current estimates and future projections. Eur Heart J 2018;39:2635-42.https://doi.org/10.1093/erhurti/ethy228

36. Barbato E,Noc,M.Baumbach A,Dudek D,Bunc M,Skalidis E,et al. Mapping interven-tional cardiology in Europe: the European Association of Percutaneous Cardiovascular Interventions(EAPCl) Atas project. Eur Heart J 2020;41:2579-88. https://doi.org/10.1093/erhara/eh475

387. Benar G,Esysagh, R,Michelaen HI,Ye Z,Inojosa JM,Ribichini FL,et al. Severe aortic stenosis; secular trends of incidence and outcomes. Eur Heart J 2024;45:1877-86.https://doi.org/10.1093/eurtheri/ehad887

38. Leon MB,Smith CR,Mack M,Miller DC,Moses JW,Svenson LG,et al.Transcheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.N Engl J Med 2010;363:1597-607.https://doi.org/10.1056/NEMOJ408232

19.Gleason TG, Reardon MJ, Popma JJ, Deeb GM, Yakubov SJ, Lee JS, et al. 5-Year out-comes of self-expanding transcatheter versus surgical aortic valve replacement in high-risk patients.J Am Coll Cardiol 2018,72:2687-96.https://doi.org/10.1016/j.jacc.2018.08.

30.Mack MJ,Leon MB,Smith QR,Miller,Med D,Moses JW,Tuzcu EM,et al.5-Year outcomes of transchatterate aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis(PARTNER 1): a randomised controlled trial.Lancet 2015;385:2477-84.https://doi.org/10.1016/S0140-6736(15)60308-7

391.SM CR Leon MB,Mack MJ,Miller DC,Moses JW,Svenson LG,et al.Transcatheter versus surgical aortic valve replacement in high-risk 1978-99; http://doi.org/10.1016/NSM4o1103510

32. Leon MB,Smith CR,Mack MJ,Makkar RR,Svensson LG,Kodani SK,Let al.Transcatheter or surgical aortic valve replacement in intermediate-risk patients. N Engl J Med 2016;374:16969-20.https://doi.org/10.1056/NEJMoA11351031

39.Tff WoD, Hildick-Smith Kopel, Kovac J.,Mullen MJ, Wendler O, Mansouri A,et al.Effect of transcatheter aortic valve replacement vs surgical aortic valve replacement on all-cause mortality in patients with aortic stenosis: a randomized clinical trial./AMA 2022:327:1875-87.https://doi.org/10.1001/jama.2022.5776

34. Popma JJ,Deeb GM,Yakubov SJ,Mumtaz M,Gada H,O'Hair D,et al.Transcatheter and aortic valve replacement with a self-expanding valve in low-risk patients. N Engl J Med 2019;380:1706-15.https://doi.org/10.1056/NEJMoa1816885

95 Blankenberg S,Seifert M, Vonthein R, Baumgartner H, Bleiziffer S, Borger MA,et al.Transcatheter or surgical treatment of aortic-valve stenosis. N Engl J Med 2024;390:1572-83.https://doi.org/10.1056/NEJMoa2400685

396. Makar Rhur-Thourant VH, Mack MJ,Kodali SK, Kapadia, S Webb JG,et al. Five-year out-comes of transcatheter or surgical aortic-valve replacement. N Engl J Med 2020;382:799-809.https://doi.org/10.1056/NEJMoa1910555

397. Van Mieghem N, Deeb GM, Sondergaard L, Grube E, Windecker S, Gada H, et al.Self-expanding transcatheter vs surgical atic valve replacement in intermediate-risk patients. 5-year outcomes of the SURAVTI randomized clinical trial. JAMA Cardiol 2022:71008-8.https://doi.org/10.1001/jamacardio.2022.2695

398. Thregod HG, Jernberg TH, Ihlemann N, Steinbruchel DA, Nissen H, Kjeldsen BJ,et al. Transchatteter or surgical aortic valve implantation: 10-year outcomes of the International Trial. HenR and J 2024;45:1116-24. https://doi.org/10.1093/eurheart/jehae043

39.Hmad Y.,Howard JP, Arnold AD, Madhavan MV, Cook CM, Alu M, et al.Transcheterase versus surgical aortic valve replacement in lower-risk and higher-risk pa-tients: a meta-analysis of randomized trials. Eur Heart J 2023;44:836-52. https://doi.org/10.1093/erhout/ehac1642

40. Baril F, Brobjiy, Frobji, N. Moride D, Myers PO, Uva MS, Almeida RMS, et al. Risk of bias in randomized clinical trials comparing transcatheter and surgical aortic valve replace-ment: a systematic review and meta-analysis. JAMA Net Open 2023;6:e2249321.https://doi.org/10.1001/jamanetworkopen.2024.49231

401. Siont Gms. Choutherk P, Cahill TJ, Modine T, Prendergast B, Praz F, et al.Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treat-ment of symptomatic severe aortic stenosis: an updated meta-analysis. Eur Heart J 2019:40:3143-53.https://doi.org/10.1093/eurheart/ehz275

402. Pibarot P, Hahn RT, Weissman NJ, Arsenouit M, Beaudoin J, Bernier M, et al.Association of paravulavital regurgitation with 1-year outcomes after transcatheter aortic valve replacement with the SAPIEN 3 valve. JAMA Cardiol 2017;2:1208-16.https://doi.org/10.1001/jamacacardio.2017.3425

403.Kodal,Sj,Porotop,D.Gouglas PS,Williams M,Xu K,Thourani V,et al.Paravalvular re-gurgitation after transceter aortic valve replacement with the Edwards sapien valve in the PARTNTER trial characterizing patients and impact on outcomes. Eur Heart J 2015;36:449-56.https://doi.org/10.1093/eurheart/ehu384

88

$$\text{ ESC Guidelines}$$

404. Lerman TT,Levi A,Kornowski R.F.Meta-analysis of short- and long-term clinical out-comes of the self-expanding Evol. Riro valve versus the balloon-expandable Sapien 3 view for transcatheter aortic valve implantation. Int J Cardiol 2023;371:100-8.https://doi.org/10.1016/j.icard.2022.09.035

405.Faroux L,Chen S.,Muntan L,Cheski R,Guereiro A,Philippon F,Sondergard L,et al.Clinical impact of conduction disturbances in transchatateric aortic valve replacement recipients: a systematic review and meta-analysis. Eur J Heart 2020;471:2771-81.https://doi.org/10.1093/eurjehz/ehz241

406.Greason KL,Lahr BD,Stulk JM,Cha YM,Rea RF,Schaff HV,et al.Long-term mortality effect of early pacemaker implantation after surgical aortic valve replacement. Am Thorac Surg 2017;104:1259-64.https://doi.org/10.1016/j.athorascur.2017.01.083

407. Rick A. Salei GHner, Las Noutions: Following permanent pacemaker implantation after transcatheter aortic valve replacement: SWEDEHEART observational study.JACCardioviscnt 2021;14:2173-81.https://doi.org/10.1016/j.jcin.2021.07.043

408 Baron Sj, Wang G., House JA. Maguson EA. Reynolds MR, Makar R, et al.Cost-effectiveness of transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at intermediate risk. Circulation 2019;139:877-88. https://doi.org/10.1161/CIRCULATIONAHA.1180.035236

409.Tam DY,Azizi,Fremes SE,Chikwe J,Gaudino M,Weijysundera HC.The cost-effectiveness of transcatheter aortic valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical risk patients with severe staticheteris at sorticatorty valve replacement in low surgical rate

410.Pibrot P.Terrade J.Wabin SAL,Dahun A.Sahang D.Achro et al. Sputurtal deteriorate of transchatterate versus surgical aortic valve proobestheses in the PARTNER-2 trial.J Am Coll Cardiol 2020;76:1830-43.https://doi.org/10.1016/j.jacc.2020.08.049

411. Fatima B, Mohananye D, Khan W, Hopulavar J, Tumura R, Banerjee K, et al.Durability data for bioprosthetic surgical aortic valve: systematic review. JAMA Cardiol 2019;47:81.https://doi.org/10.1001/jamacardiol.2018.4045

1203. Keldi H, Hermanides RS, Dambrink J, Singh SN, King Ten B, Kim Guank, J et al.TransCatheter aortic valve implantation and fractional flow reserve-guided percutan-eous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and com-plex or multivesselary disease(TCEW): an international, multicentre, prospect-ive, open-label, non-inferiority, randomised controlled trial. Lancet 2025:4045-2932.605-2021.org/doi/10.1016/j/s20140-6736(2024)0210-7

413. Martinsson A,Nielsen SJ,Milojevic M,Redfors B,Omerovic E,Tennes T,et al.Life expectancy after surgical aortic valve replacement. SWEEDHEART study.J Am Coll Cardiol 2019;74:26-33.https://doi.org/10.1016/j.jacc.2019.04.053

414. Glaser N. Person, J1Moyceck N, Voloroffi, M. Franco-Cereceda A, Sartipy U. Loss in life expectancy after surgical aortic valve replacement: SWEHEHEART study.J Am Coll Cardiol 2019;74:26-33.https://doi.org/10.1016/j.jacc.2019.04.053

415 Attinger-Toler A, Ferrari E, Tuerel D, Temjin C, M. Muller E, Netschp F, et al.Oar-related outcomes after transcatheter aortic valve replacement from the SwissTAVI registry. JACC Cardiovasc Interv 2012;14:950-62.https://doi.org/10.1016/j.jc.2021.04:02:05.

416. Jorgensen TH, Thyroged HGH, Savontus M, Wilenley B, Lie O, Tang, M et al.Transcatheter aortic valve implantation in low-risk triscupic acid or stenosis. The NOTION-2 trial. Eur Heart J 2024:45:3804-14. https://doi.org/10.1093/eourhart/ehae331

417. Danble TG, Kangel,Tcabe,C.Mebin Outcomes following subcian and axialary artery access for transcatheter aortic valve replacement: Society of the Thoracic Surgeons.American College of Cardiology TVT registry report.J. Cardacciv Oscintvus 2019:1263-9.2001://doi.org/10.1016/j.jc.2019.01.219

148. Gleason,TG, Schindert JP, Hagberg, RC Deeb GM, Adams DH, Conte JV, et al.Subclavian/axialary access for self-expanding transcatheter aortic valve replacement renders equivalent outcomes as transferanal. Amorn Thorc Surg. 20185:1077-43.https://doi.org/10.1016/j.hactorasur.2017.07.017

149. Kirkey,E.Korgold,Hedosn RW,Jones BM,Cayky,R.Chemia M.,et al.Transcular versus subclavian/axillary access for transcatheter aortic valve replacement with SPIAN 2. Ann Thorac Surg 2020;110:1892-7.195://doi.org/10.1016/j.jcas.2021.04.051

420. Deberry N,Trimeh,Grandet T,Vincentr,F.HysiI,Delayer C.et al./Transvallary com-pared with transcardot access for TAVR: a propensity-matched comparison from a French multicentre registry,Enultention 2020;16:842-9. https://doi.org/10.1091/j.ejid-20-00117

421. Beurther S, Karam N, Resesguier N, Houel R, Modine T, Folot et al., Femorous versus nonfemallyal frequency trans atccharior o valve replacement. J Am Coll Cardiol 2019;74:2728-39.https://doi.org/10.1016/j.jacc.2019.05.042

422. Greenbaum AB, Babalarvic 3. Chen, Myr, Sine AM, Rogers T, ONrell WW, et al.Transcaval access and closure for transcatheter aortic valve replacement: a prospect-ive investigation. J Am Coll Cardiol 2017;69:511-21. https://doi.org/10.1016/j.jc.2021.2010

423. Lederman RJ, Babalaralos VC,Lisko JR, Rogers T, Mahoney P, Foerst Jr, et. Transcavalle versus transaxial TAVR in contemporary practice: a propensity-weighted analysis.JACC Cardiovasc Interv 2022;15:965-75.https://doi.org/10.1016/j.jcin.2022.03.014

424. Okuno T,Asami M,Heg,D.LanzJ,Rase F,Hagemeyer D,et al.Impact of left ventricular outflow tract calcification on procedural outcomes after transcatheter aortic valve re-placement. Jaccardivoynt Interv 2020;13:1789-99. https://doi.org/10.1016/j.jcin.2020.04.015

425. Barbanti M, Yang THor, Rode Cabau J, Tamburino C, Wood DA, Jialawiah H, et al.Anatomical and procedural features associated with aortic root rupture during balloon-expandable transchaterate aortic valve replacement. Circulation 2013;128244-53.https://doi.org/10.1016/circulationa.113.002947

426. Kirmani BH,Jones SG,Muir A,Malisary SC,Chung DA,Williams RJ,et al.Limited ver-sus full stemotometry for aortic valve replacement. Cochrane Database Syst Rev 2023;12:CD011793.https://doi.org/10.1002/14651858.CD011793.pub3

427. Papareella D, Maldinév, McGali, Santarpino G, Moscarelli M, Guida P, Fattouch, K et al. Full sternotomy and minimal access approaches for surgical aortic valve replacement: a multicentre propensity-matched study. Eur J Cardiothorac Surg 2020;57:709-16.https://doi.org/10.1016/j.jcin.2021.07.043

485.Finert Z.,Tench Jen, Jidenal T, Shen M, Redfors B, Delhaye C, et al. Transcatheter aortic valve replacement in bicuspid aortic valve stenosis. Circulation 2021;143:1043-61.https://doi.org/10.1161/CIRCULATIONAHA.120.048048

429. Alperai, A Voisine P, Kalvoroyi D. Dumont, D Eagenais F, Perron J, et al. Aortic valve replacement in low-risk patients with severe aortic stenosis outside randomized trials.J Am Coll Cardiol 2021;7:556-63.

430.Makkar RR,Yoon SH,Leon MB,Chakravarty T,Rinaldi M,Shah PB,et al.Association between transchaterate aortic valve replacement for bicuspid vus tricuspid aortic stenosis and mortality or stroke.JAMA 2019;321:2193-202.https://doi.org/10.1001/jama.2019.7108

431. Halma SA,Edwards FH.Dai D,Li Z,Mack MJ,Holmes DR,et al. Outcomes of trans-catheter aortic valve replacement in patients with bicuspidal ovaric disease: a re-port from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy. Circulation 2020;141:1071-9. https://doi.org/10.1161/CIRCULATIONA.119.119.040333

432. Forrest JK, Kaple RK, Ramlawi B, Gleason TG, Merukai CU, Yakubov SJ, et al.Transcatheteric aortic valve replacement in bicuspid versus tricuspid aortic valves from the STS/ACC TVT registry. JACC Cardiovasc Interv 2020;13:1749-59. https://doi.org/10.1016/j.cn/2000.032.032

433. Montalco,C.Stiich,Crimic,A Lricachia A,Khokhar AA,Giannini F,et al. Outcomes after transcatheter aortic valve replacement in bicuspid versus tricuspid anatomy: a systematic review and meta-analysis. JACC Cardiovasc Interv 2021;14:2144-55.https://doi.org/10.1016/j.jc.2021.07.052

434. Yoon SH,Bleiziffer S.De Baker O,Delgado V,Arai T,Ziegmueller J,et al.Outcomes in transcatheter aortic valve replacement for bicuspid versus tricupid aortic valve$$\text{ stenosis. J Am Coll Cardiol 2017:69:2579-89. https://doi.org/10.1016/j.jacc.2017.03.017.03}$$

435.Jliahui H,Chen M,Webb J, Himbert D,Ruiz CE,Rodes-Cabau J,et al.A bicuspid aor-tic valve imaging classification for the TAVR era. JACC Cardiovasc Imaging 2016;9:1145-58.https://doi.org/10.1016/j.jcmg.2015.12.022

436.54.MSQ Blarogos,Zhirogak V,Calcancali LRP,Escorel Neto AC,Rayol SC,Weymann A,et al.Impact of aortic annulus enlargement on the outcomes of aortic valve replacement: a meta-analysis.Semin Thorac Cardiovasc Surg 2021:33:316-25.https://doi.org/10.1053/j.semextos.2020.06.046

437. Head SJ, Reardon MJ, Deebor GM, Van Mieghem NM, Popma JJ, Gleason TG, et al.Computed tomography-based indexed aortic annulus size to predict prosthesis-patment mismatch. Circ Cardiovasc Interv 2019;12:e007396. https://doi.org/10.1016/116/circinterventions.118.007396

438.Herrmann HC,Mehran R,Baldman DJ,Bailey S,Mollmann H,Bdual-Wahab M,et al.Self-expanding or balloon-expandable TAVR in patients with a small aortic annulus. N Engl J Med 2024;390:1959-71.https://doi.org/10.1056/NE|Moa2312573

439 Yokoyama K,Yun,Taz,Kaneko,T Takagi,Hang L,Fang H,Stang L, Surgical exptallation of transcatheter aortic bioprostosis: a systematic review and meta-analysis. JCVJOS Open 2011:8-2077.https://doi.org/10.1016/j.jxon.2021.09.023

440.Marn-Curtaas M,Tang GH,Liefer P,Fukuhara S,Lange R, Harrington KB,et al.Transchatteter valve heat exoplanet with infective endocarditis-associated prosthesis failure and outcomes. The EXPLANT-TAVR international registry. Eur Heart J 2024;45:2519-32.https://doi.org/10.1093/eurhearti/ehae292

411. Hirji SA, Percy, McGurk S, Malarczyk A, Harloff MT, Yazdchi F, et al. Incidence,characteristics, predictors, and outcomes of surgical explanation after transceteric aortic valve replacement.J Am Coll Cardiol 2020;76:1848-59. https://doi.org/10.1016/j.jacc.2020.08.048

447.Jawzit,K.Gulack BC,Frau-Sepvedla MV,Matsouaka RA,Mack MJ,Holmes DR Jr,et al. Reoperation after transcatheter aortic valve replacement: an analysis of the Society of Thoracic Surrogates database. JACC Cardiovasc Interv 2020;13:1515-25.https://doi.org/10.1016/j.jc2020.04.029

443. Hawkins RB, Deeb GM, Sukular D, Patel HJ, Gualano SK, Chutetc SJ, et al. Redo surgical aortic valve replacement after prior transcatheter versus surgical aortic valve replace-tion. JACC Cardiovasc Interv 2023;16:942-53. https://doi.org/10.1016/j.jc.2023.03.015

444. Bapat VN,Zaid,S.Fukuhara S,Saha S,Vtitanova K,Kiefer P,et al.Surgical explanation after TAVR failure: mid-term outcomes from the EXPLANT-TAVR international

ESC Guidelines

89

registry. JACC Cardiovasc Interv 2021;14:1978-91.https://doi.org/10.1016/j.jcin.2021.07.015

44. Bowdish ME, Habib RH, Kaneko T., Thourani VH, Badhwar V. Cardiac surgery after transcatheter aortic valve replacement trends and outcomes. Ann Thorac Surg. 2024;118:155-62.https://doi.org/10.1016/j.jathorasurps.2024.03.024

44. Landes U, Webb JG, De Backer O, Sondergaard L, Abdel W.-Abhar M, Crusius L, et al.Repeat Transcatheter aortic valve replacement for transcatheter prosthesis funcys-tion.J Am Coll Cardiol 2020;75:1882-93.https://doi.org/10.1016/j.jacc.2020.02.051

447.Tam DY,Haarma,C Rocha RV,Quzounian M,Wijeyundera HC,Austin PC,et al.Transchater VV versus red surgical AVR for the management of failed biological prosthesis: early and late outcomes in a propensity-matched cohort. JACC Cardiovasc in 10/2020:1765-74.https://doi.org/10.1016/j.jcin.2019.10.3030

48. MaSMBV,Pan den EyneJ,Simonato M,Calcivalanti LRP,Douamlis IP,Weixler,V et al.Valve-valve transchatterate aortic valve replacement versus redo surgical aortic valve replacement an updated meta-analysis.JACC Cardiovasc Interv 2021;141:211-2020;doi.org/10.1016/j.jcin.2020.10.020

49.Fercy ED,Harloff MT,Hirji,S.McGurk S,Yazdchi F,Newell P,et al.Nationally repre-sentative repeat transcatheter aortic valve replacement outcomes: report from the centers for Medicare and Medicaid services. JACC Cardiovasc Interv 2021;14:1716-27.https://doi.org/10.1016/j.jcin.2021.06.011

450. Makkar RR, Kapadia S, Chakravarty T, Cubedue RJ, Kaneko T, Mahoney P, et al. Outcomes of repeat transcatheter aortic valve replacement with balloon-expandable valves: a registry study. Lancet 2023:452:19-40. https://doi.org/10.1016/j.jc.2020.0215

451. Deharo P, Bisson A, Herbert J, Lacour T, Etienne CS, Porto A, et al. Transcatheter valve-valve aortic valve replacement as an alternative to surgical re-replacement.J Am Coll Cardiol 2020;76:489-99.https://doi.org/10.1016/j.jacc.2020.06.010

452. Smordm M,Glaser N,Froca-Cereceda S, A�uptity U.F. Effect of prosthesis-patient mis-match on long-term clinical outcomes after bioprosthetic aortic valve replacement.J Am Coll Cardiol 2023;81:964-75.https://doi.org/10.1016/j.jacc.2022.12.023

453. Head Sj. Mohles M, Anprubin, R. Blapart, P. Mack, Tsenberg, J. et al. The impact of prosthesis-patient mismatch on long-term survival after aortic valve replace-ment a systematic review and meta-analysis of 34 observational studies comprising 27 188 patients with 13314 patient years-Eur Heart 2012;23:158-15. https://doi.org/10.1016/j.jc.2021.2018

45. Herrmann HC, Daneshvar SA,Fonarow GC, Stebbins A, Vemulapali S, Desai ND,et al. Prosthesis-patient mismatch in patients undergoing transcatheter aortic valve re-placement; from the STS/ACC TVT registry.J Am Coll Cardiol 2018;72:2701-11.https://doi.org/10.1016/j.jacc.2018.09.001

455. Wernacle J, Pobar P, Herrmann HC, Kodali S, Jiepsik, J. Blanke P, et al.Prosthesis-patient mismatch after aortic valve replacement in the PARTNER 2 trial and registry.J Lancic Cardiovasc Interven 2021:1466-77.https://doi.org/10.1016/j.jcin.2021.03.069

456.Akodad M, Sellers S, Landes U, Meier D, Tang Gilbert Hal, Gada H, et al.Balloon-deparable valve for treatment of Evolute failure. JACC Cardiovascular Interv 2021;13:586-77.https://doi.org/10.1016/j.jcin.2021.12.021

457. Ribeiro HB, Rodes-Cabau J, Blanke P, Leipici J, Kwan Park J, Bapat V, et al. Incidence,predictors, and clinical outcomes of coronary obstruction following transcatheter aor-tic valve replacement for degenerative biosprostical surgical valves. insights from the VIVID registry. Eur Heart J 2018;39:687-95. https://doi.org/10.1016/j.jc.2020.0921

458. Ochiai T, Oakley S, Sekhon N, Komatsu I, Flint N, Kaemkes D, et al. Risk of coronary obstruction due to sinus sequestration in retochancater attilic valve replacement.JACC Cardiovasc Interv 2013;2016-37.27 https://doi.org/10.1016/j.jin.2023.09.022

459.Akodad S.,Mellers S.,Gulsin G.Tzas,Gina L.,Landets Ghawel G.et,Leaflet and neoskirt height in transchatter heat valves. JACC Cardiovasc Interv 2021;2398-30017.

460. Tang GH, Spencer J., Rogers T., Grubb KJ, Gleason P, Gada H, et al. Feasibility of cor-orary access followed zero-TAVR for Evolutine failure: computed tomography simu-lation study. Circ Cardiovasc Interv 2023;16:e013238. https://doi.org/10.1061/1161/CIRCINTERVENTIONS.123.013238

461. De Backer O, Landes U.Fu A, Yoon SH, Mathanna OSen, Sedaght et al. A Coronary access after TAVR-in-TAVR as evaluated by multidetector computed tom-ography.JACC Cardiovasc Interv 2020:13:2528-38.https://doi.org/10.1016/j.jcin.2020.06.016

462.Fukui M, Okada A, Zhao KR, Burns MR,Koke H,Wang C,et al. Feasibility of redo-transcatheter aortic valve replacement in Sapien valves based on in vivo tomography assessment. Circ Cardiovasc Interv 2023:16:013497. https://doi.org/10.1161/CIRCINTERVENTIONS.123.013497

463. Chatriwakali A, Kalen KB, Pejod P, Irnean T, Vorhou A, Whvensenant BK, et al.Outcomes of bioprosture valve fracture in patients undergoing valve-in-valter V.RACT

464. Khan JM.Balabaricova SC, Greenbaum AB, Spies C, Daniels DePta, J. et al: Preventing coronary obstruction during transcatheter aortic valve replacement results from the multicenter International BASILICA registry. JACC Cardiovasc Interv 2021;14:941-8.https://doi.org/10.1016/j.jcin.2021.0233

465. Jorgensen TH, Thyregd HGH, Ihlemann N, Nissen H, Petrusson P, Kjeldsen BJ, et al.Eight-year outcomes for patients with aortic valve stenosis at low surgical risk rando-mized to transcatheter vs. surgical aortic valve replacement. Eur Heart J 2021;42:2912-9,https://doi.org/10.1016/j.cursus/10.0093/eurhart/ehab375

66. O'Hair D, Yakubov SJ, Gubb KJ, Oh JK, Ito S, Deeb GM, et al. Structural valve deteri-oration after self-expanding transcatheter or surgical aortic valve implantation in pa-tients at intermediate or high risk. JAMA Cardiol 2023;8:111-9. https://doi.org/10.1001/jamacardi.2022.4627

46. Rodriguez-Gabella T, Vosine P, Puri R, Pibrot P, Rodés-Cabau J,Aortic bioprosthetic valve durability: incidence, mechanisms, predictors, and management of surgical and transcatheter valve degeneration.J Am Coll Cardiol 2017;70:1013-28.https://doi.org/10.1016/j.jacc.2017.07.715

468. Pibarot P, Magne J, Leipice J, Cote N, Blanke P, Thourani VH, et al. Imaging for predict-ing and assessing prosthesis-patient mismatch after aortic valve replacement. JACC Cardiovascular imaged 2019;12:49-62.https://doi.org/10.1016/j.jcm.2018.10.020

469.Freitas-Frez Aforaz Bono, Trirado-Come G, Dagenais F, Ruel M, Al-Atassi, Tum Dontem,E et al. Aortic stenosis and small aortic annulus. Circulation 2019;139:2685-702. https://doi.org/10.1161/IRCULATIONAHA.118.038408

470. Tang GHL,Zaid S,Fuchs A,Yamabe T,Yazdichi F,Gupta E,et al. Alignment of trans-catheter aortic-valve neo-commissures(ALIGN TAVR): impact on final valve orienta-tion and coronary artery overlap.JACC Cardiovascular Interv 2020;13:1030-42.https://doi.org/10.1016/j.jcin.2020.02.005

471.Kapada SR,Len MB,Makkar RR,Tuzcu EM,Svenson LG,Kodali S,et al.5-Year out-comes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis(PARTNER 1): a randomised controlled trial. Loncer 2015;385-2495-91.https://doi.org/10.1016/S0140-6736(15)60290-2

472. Makkar RR, Fontana GP, Jialhawi H, Kapadia S, Pichard AD, Douglas PS, et al.Transcheteratic aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med 2012;366:1969-704.https://doi.org/10.1056/NEJMao1202277

473. Turina J,Hes,Ose,Prupell,F.,KrayenbueH HP.Sontaneous course of aortic valve dis-ease.Eur Heart J 19978-7:417-83.https://doi.org/10.1093/oxfordjournals.eurheartj.

474. Pellikka P, Nishura R,Aailey KR, Tajik AJ. The natural history of adults with asymptomatic, hemodynamics rically significant stenosis. J Am Coll Cardiol 1990;15:102.107.https://doi.org/10.1016/0735-1097(90)90234-g

475. Manger N, Stachel G, W., Potitek F, Haussig S, Schlotter F, Hollriegel R, et al. Predictors of mortality and symptomatic outcome of patients with low-flow severe aortic stenosis of undergoing transcatheter aortic valve replacement. J Am Heart Assoc 2018;7:e007977 https://doi.org/10.1161/AHA.117.007977

476. Elle MF, Padang R, Al-Hijji M, Pisaru SV, Greason KL, Maltaais S,et al. Hemodynamic response in low-flow low-gradient aortic stenosis with preserved ejection fraction after TAVR.J Am Coll Cardiol 2019;73:1731-2.https://doi.org/10.1016/j.jacc.2019.01.034

477. Rusinaru D, Bohbot Y, Ringle A, Marechaux S, Diouf M, Tribouilloy C. Impact of low stroke volume on mortality in patients with severe aortic stenosis and preserved left ventricular ejection fraction. Eur Heart J 2018;39:1992-9. https://doi.org/10.1093/erurich122

478.Zheng Q, Djohan A,H.Alin E,Ding ZP,Ling LH,Shi L,et al.Effects of aortic valve re-placement on severe aortic stenosis and preserved systolic function: systematic review and network meta-analysis. Sci Rep 2017;7:5092.https://doi.org/10.1038/s41598-017-05021-901

459.Sakura E, Clavel M, Hahr RT,Jaber WA, Asch FM, Rodriguez L, et al. Outcome of flow-gradient patterns of aortic stenosis after aortic valve replacement: an analysis of the PARTONER 214.1016/CIRCINTERnterventions. Inc. 118,007892

480.Annis ABC, C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C. C.

481.Mosebi W,Amer MR,Ding Y,Megaly M,Mather JF,McMahon S,et al.Benefit of trans-catheter aortic valve replacement in patients with paradoxical low-flow low-gradient versus high-gradient aortic stenosis and preserved left ventricular function. Circ Cardiovasc: Interv 2012;14:001004. https://doi.org/10.1161/circintentions.120.010042

482. Bobhtov K, Yowakski, C. Rusinaru D, Ringle A, Marechaux S, Tribouilloy C. Impact of mean transortic pressure gradient on long-term outcome in patients with severe aor-tic stenosis and preserved left ventricular ejection fraction. J Am Heart Assoc 2017;6:e05850.https://doi.org/10.1161/AHA.117.005850

483.Costa GN,Chofosar LFL,Oiveirobs B,Gongalves L,Teixeira R.Early surgical interven-tion versus conservative management of asymptomatic severe aortic stenosis: a sys-tematic review and meta-analysis. Heart 2023;109:314-21.https://doi.org/10.1136/2022-341211

484. Bohbot Y, Rusinar D, Pierre Q, Marechaux S, Triboullio C. Risk stratification of severe aortic stenosis with preserved left ventricular ejection fraction using peak aortic

90

$$\text{ ESC Guidelines}$$

jet velocity: an outcome study. Circ Cardiovasc Imaging 2017;10:e006760.https://doi.org/10.1161/CIRCIMAGING.117.006760

485. Adams DH, Popma JJ, Reardon MJ. Transcatheter aortic-valve replacement with a self-expanding prothesis. N Engl J Med 2014:37197-86:8 https://doi.org/10.1056/NEjMC1408396

486.Thyroged H,Steinbrichel U, Hamlen N, Nissen H, Kjeldsen BJ, Petrusson P,et al. Transcatheter versus surgical aortic valve replacement in patients with severe aortic valve stenosis: 1-year results from the all-comers NOTion randomized clinical trial.J Am Coll Cardiol 2015;65:2184-94.https://doi.org/10.1016/j.jac.2015.03.014

487. Thourani V,Huri S, Ramur G, Zheng L, Sheng S, O'Brien SM, Aaliwad G, et al.Contemporary real-world outcomes of surgical aortic valve replacement in 141,905 low-risk, intermediate-risk, and high-risk. authors. Thorc Surg 2015;59:55-61.https://doi.org/10.1016/j.athorasur.2014.06.050

488. Thourani VH, Kodal S, Makkar RR, Herrmann HC, Williams M, Babaliaros V, et al.Transchate aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Lancet 2016:387:2218-25.https://doi.org/10.1016/s140-6736(16)30073-3

49. Loyover Mright, Gubb J. Arnoldi S. Batchelor W, Dbohible A, Home A Jr. et al.Outcomes of balloon-expanding canatable transchaterate aortic valve replacement in younger outcomes. 49. Liocarth M, Kogai M, Cardiol 2025;12:137-35. https://doi.org/10.1001/jamocard.2024.4237

490.Ullah W,Di-Meglio M, Sana MK, Muhammadzai HZU, Kochar K, Zahid S, et al.Outcomes after transcatheter aortic valve implantation in patients excluded from clin-ical 1.Jaccv Adv 2023;2:100271.https://doi.org/10.1016/j.jac.2023.100271

491.Reen W,Barth S, Griese DP, Winkler S, Babin-Ebell J, Kerber S, et al. Transfemoral versus transpatical transcatheter aortic valve implantation: a single-centre experiences.Eur J Cardiothor Surg 2019:55:744.https://doi.org/10.1016/j.ekcs/ethyz63

492. Allen KB,Chhatriwalla K,Cohen D,Saxon J,Hawa Z,Kennedy KF,et al.Transcarotc versus transical and aortic access for transcarcotic aortic valve replacement.Ann Thorac Surg 2019;109:715-22.https://doi.org/10.1016/j.athorcsurac.2019.02.007

493. Overthouk P, Follut P, Rein P, Fouquet C, Protom M, Bonnet G, et al.Transcarotric approach for transcatheter aortic valve replacement with the Sapien 38inproscthesis. JACC Cardiovasc Interv 2019;12:413-9.https://doi.org/10.1016/j.jcbin.2018.11.014

494. Kumar N,Kher,Ronafou Green,G.Bhatt DL.Comparison of outcomes of transpirad versus transpiradical approach for transchatterate aortic valve implantation. Am J Cardiol 2018;122:1520-6.https://doi.org/10.1016/j.amjord.2018.07.025

495. van Wely M, van Nieuwkerk AC, Rooijekers M, van der Wulp K, Gehlmann H,Rovekro M et al. Transculatory versus transfolar extension as default access in TAVA: a propensity matching analysis. Int J Cardiol 2024;394:131353.https://doi.org/10.1016/j.jicard.2023.131353

496. Allen KB. Watson, D. Vora AN. Mahoney P., Chatriwalla AK. Schwartz Jg, et al.Transcarotric versus transaxial access for transcatheter aortic valve replacement with a self-expanding valve: a propensity-matched analysis. JTCVS 2023:21:45-55.https://doi.org/10.1016/j.xc.2023.07.019

497.Salhiu A,Ferlay C,Kirsch M,Shah PB,Skali H,Fournier S,et al. Outcomes of safety of transcavato transchater aortic valve replacement: a systematic review and meta-analysis. Can J Cardiol 2024;40:2054-62.https://doi.org/10.1016/j.cjca.2024.05.016

49. Abraham B.S.,Soush M.,Regam M.,MARM S.,Sweeney J.,et al.Meta-analysis on cartrastorid versus transforsal and other alternate accesses for transcatheter aortic valve implantation.Am J Cardiol 2023;19:1925-206.https://doi.org/10.1016/j.jacc.

49. Williams MR,Jialhawi H,Makkar R,O'Neill WW,Wuyger T,Ramisalie SC,et al.The PARTNER 3 bicuspid registry for transcatheter aortic valve replacement in low-surgical-risk patients. JACC Cardiovascular 1e:2002:15-532-32.https://doi.org/10.1016/j.jcin.2022.2017

500.Wakman R,Craig PE,Torguson R,Asch FM,Weissman G,RuizD,et al.Transcheteratic aortic valve replacement in low-risk patients with systematic severe bicuspid at volez stenosis. JACC Cardiovasc Interv 2020;13:1019-27.https://doi.org/10.1016/j.jcian.2020.02.008

01. Elbadawi A, Sa A, Mendejly I, Barsoum K, Omer MA, Soliman A, et al. Temporal trends and outcomes of transcatter whereas surgical aortic valve replacement for bi-cupid aortic valve stenosis, JACC Convodarc Intvav 2019;12:1811-22. https://doi.org/10.1016/j.jcin.2019.06.037

502. Tchétché D. Ziellov F, De Biase C. De Backer O, Hovasse T, Leroux L, et al.Transcatheter aortic valve implantation with the Evolut platform for bicuspid aortic valve stenosis: the international, multicentre, prospective BIVOLUTX registry.Euletnentment 2023:19:502-11.https://doi.org/10.4244/ej-23-00021

503. Yang L-T, Boler A, Medina-Ionojosa Jose R, Scott Christopher G, Maurer Matthew J,Eleid Mackram F, et al. Aortic stenosis progression, cardiac damage, and survival.JACC Cardioscosim Imaging 2021:14:113-26. https://doi.org/10.1016/j.ceng2021.01.017

504.Strange G,Stewart,C. Selmierager,P.Drior D,Scalia GM,Marwickl,T. Poor et al. long-term survival in patients with moderate aortic stenosis. J Am Coll Cardiol 2019:74:1851-63.https://doi.org/10.1016/j.jacc.2019.18:004.08

50.Samad Z,Rora AN,Dunning A,Schulte PJ,Shaw LK,Al-Enezi F,et al.Aortic valve sur-gery and survival in patients with moderate or severe aortic stenosis and left ventricu-lar dysfunction. Eur. Heart J 2016;37:2276-86. https://doi.org/10.1093/eurheartj/ehv701

05. Oz A. Tosumas L, Lmporopoulos K, Xanthos T, Karpettas N, Papadopoulos D. Cardiac rehabilitation after TAVI-7a systematic review and meta-analysis. Curr Probl Cardiol 2023:48:10151.https://doi.org/10.1016/j.cpcardiol.2022.101531

507. Monteagudo Ruiz JM,Galerisi M, Buonano A, Badano L, Aruta P, Swaans MJ,et al.Overview of mitral regurgitation in Europe: results from the European Registry of mi-ral regurgitation(EuClMic) Eur. Heart J Cardiovasc Imaging 2018;19:503-7.https://doi.org/10.1093/ehjci/jey1011

508.Naliah,C|Mahajan,R|Elliott AD,Haqqani H,Lau DH,Vohra JK,et al.Mitral valve pro-lapse and sudden cardiac death: a systematic review and meta-analysis. Heart 2019:105:144-51.https://doi.org/10.1136/heartjnl-2017-312932

509. Van der Bij P, Stassen J., Haugaa KH, Essayagh B, Basso C,Thiene G,et al.Tmiral annular disjunction in the context of mitral valve prolapse: identifying the at-risk patient. JACC Cardiovascular Imaging 2024:17:1229-45.https://doi.org/10.1016/j.ccm.2024.03.006

10. Antineo C, Benfari G,Michelaen H, Maalouf JF, Nkomo VT, Thapa P, et al. Clinical out-come of degenerative mitral regurgitation. Circulation 2018;138:1317-26. https://doi.org/10.1161/CIRCULATIONAHA.117.033173

11. Enriquez-Sarano M, Avierinos JF, Messia-Zeitoun D, Detaint D, Capps M, Nkomo V,et al.Quantitative determinants of the outcome of asymptomatic mitral regurgitation.N Engl J Med 2005.325:875-83.https://doi.org/10.1056/NEjMoA041451

512. O'Gara PT, Grayburn PA,Badhwar V,Afonso LC, Carroll JD,Elmaria S,et al.2017 Expert Consensus Decision Pathway on the management of mitral regurgitation:a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways.J Am Coll Cardiol 2017;70:2421-49.https://doi.org/10.1016/j.jacc.

315. Zddizadz V, Dzadzko M, Medina-Inojosa JR, Benfari G, Michelena HI, Crestanello JA,et al. Causes and mechanisms of isolated mitral regurgitation in the community: clinical context and outcome. Eur J 2019;40:2194-202. https://doi.org/10.1093/erhej/314

514.Samad Z,Shaw LK, Phelan M,Glower DD,Erbsoll M,Toptine HJ,et al.Long-term out-comes of mitral regurgitation by type and severity. Am Heart J 2018;203:39-48.https://doi.org/10.1016/j.ajh.2018.05.001

515. Bakrestrom R, Barke A, Christensen NL, Pecini R, Irmukhamedov A, Andersen M,et al.Hemodynamic characteristics in significant symptomatic and asymptomatic pri-mary mitral valve regurgitation at rest and during exercise. Circ Cardiovasc Imaging 2018:11c07171.https://doi.org/10.1161/CIRCIMAGING.117.007171

519.Usumnoka H, Hida T, Susawa H, Izumi K, Harada Y, Kinoshita M, et al.Ercise-stchocardiography and effort in intolerance in asymptomatic/minimally symptomatic patients with degenerative mitral regurgitation combined invasive-noninvasive hemodynamic monitoring. Circ Cardiovasc Imaging 2018;11:e007282.https://doi.org/10.1016/CIRCIMAGING.117.007282

517. Butcher SC,Essayagh B, Steyberg EW, Benfari G, Contrionia C,Grigioni F,et al.Factors influencing post-surgical survival in degenerative mitral regurgitation. Eur Heart J 2023;44.6781-81.https://doi.org/10.1093/eurheartj/ehad004

518. Grigioni C,Flavel CA, Vanoverschelde JL, Tribouilloy C, Pizarro R, Huebner M, et al.The MIDA mortality risk core: development and external validation of a prognostic model for early and late death in degenerative mitral regurgitation. Eur Heart J 2018;39:1281-91.https://doi.org/10.1093/eurheartj/ehx465

519. Del Rio-Pertu F, Nugent K, Argueta-Sosa E. Right heart catheterization in clinical practice: a review of basic physiology and important issues relevant to interpretation.Am J Cardiovasc Dis 2023;13:122-37.

520.Mentas A Patel, Patel H. Gillinov AM, Rodriguez LL, Svensson LG,et al.Prognostic utility of brain natriate perptic in asymptomatic patients with significant mitral re-gurgitation and preserved left ventricular ejection fraction. Am J Cardiol 2016;117:258-63.https://doi.org/10.1016/j.amjcard.2015.10.040

521. Cawley PJ,Hamilton-Crig A, Owens DS, Krieger EV, Strugnel WE, Mitsumori L, et al.Prospective comparison of valve regurgitation quantitation by cardiac magnetic reson-ance imaging and transthoracic echocardiography. Circ Cardiovasc Imaging 2013;6:48-57.https://doi.org/10.1016/CIRCIMAGING.112.975623

52. Penica M. Vecera J. Mirca D, Krotc M, Kockova R, Van Camp G. Prognostic implica-tions of magnetic resonance-derived quantification in asymptomatic patients with or-ganic mitral regurgitation: comparison with Doppler echocardiography-derived integrative approach. Circulation 2018;137:1349-60. https://doi.org/10.1161/CIRCULAMHA.117.029332

523.Naoum C,Banke P,Cavalcante JL,Leipisc J. Cardiac computed tomography and mag-netic resonance imaging in the evaluation of tricuspid valve disease. Circ Cardiovasc Imaging 2017:1002:00531. https://doi.org/10.1161/CIRCIMAGING.116.00531

524. Kungtkan D, Nabi F, Kim R, Bonow RO, Khan MA, Xu, J et. Myocardial fibrosis in patients with primary mitral regurgitation with and without prolapse. J Am Coll Cardiol 2018;72:823-34.https://doi.org/10.1016/j.jacc.2018.06.048

ESC Guidelines

91

525. Garg P, Swift Aj, Zhong L, Carhall CJ, Ebers B, Twestenberg J, et al. Assessment of mitral valve regurgitation by cardiovascular magnetic resonance imaging. Nat Rev Cardiol 2020;17:298-312.https://doi.org/10.1038/s41569-019-0305-z

526. Feuchtner GM, Alliad H, Kiro, Car Sawar, M. Alerie A, Dicht W, et al. Cardiac CT angiography for the diagnosis of mitral valve prolapse: comparison with echocardi-raphy.Radiology 2010;254:374-83.https://doi.org/10.1148/radiol.2541090393

527.Gollmann-Tepozkyu C,Kiagelio Y,Fhofer H,Dof-Holej Hirsch,Jirozeku CPEU,et al.A qualitative improvement for program minimally invasive mitral surgery: technical adro vancements ameliorate outcome and operative times. Interdiscipario Cardiovasc Surg.2023;36:11003.https://doi.org/10.1093/icsv/ivad030.

528.Tarzia P, Ciampi P, Lanza O, Canali E, Canestrelli S, Calo L. Multi-modality imaging for pre-procedural planning of transcatterath mit valve interventions. Eur Heart J Suppl 2023;25:C205-11.https://doi.org/10.1093/erheartipsup/s0201

529. Elle MF,Foley TA,Said SM,Pislar Vu,Rhil S.CS were mitral annular calcification:multimodality imaging for therapeutic strategies and interventions. JACC Cardiovasc Imaging 2016;9:1318-37.https://doi.org/10.1016/j.jcmg.2016.09.001

530.Roselli C,Yu M,Nauffal V,Georges A,Yang Q,Love K,et al.Genome-wide association study reveals novel genetic to a new polygenic risk score for mitral valve propse. Eur Heart J 2022:43:1688-80.https://doi.org/10.1093/eurheartj/hec049

531. Badhwar V,Chikwe J,Gillinov AM,Vemulapaliou,S'O_7cAMP,Mahefey JH,et al.Risk of surgical viral valve repair for primary mitral regurgitation. J Am Coll Cardiol 2023:81:636-48.https://doi.org/10.1016/j.jacc.2021.11/07

532. Lazazin S, Vanoverschelle T, Brobouliy C, Grigoni F, Suri RM, Avinenos JF, et al.Twenty-year outcome after mitral repair versus replacement for severe degenerative mitral regurgitation: analysis of a large, prospective, multicenter, international regurgication.2017:135:40-21.https://doi.org/10.1161/circLUTIONNAHA-116.023340

533. David TE, David CM,Tsang W, Lafreniere-Roula M, Manlihot C. Long-term results of mitral valve repair for regurgitation due to leaflet proapse. J Am Coll Cardiol 2019:74104-53.https://doi.org/10.1016/j.jacc.2019.06.052

534.Deja MA, MaPlawniik M, Widenko K, Szynski R, Kanftos K, Kapelak B, et al.Comparison of repair vs replacement in calcific and rheumatic mitral disease. Ann Thorac Surg 2023;116:954-61.https://doi.org/10.1016/j.athorasur.2023.04.048

535. Bresca A.Wa, Watt TM, Hawley K, Scrosylen BM, Uroleman K, Kimieo K, Algierov H. et al.Rheumatic valmit valve repair or replacement in the valve-in-vale era. J Thorac Cardiovasc Surg 2022;163:591-602.e2.1001.org/doi.org/10.1016/j.jctvcs.2020.04.118

536. Chen SW,Chen Cr,Cheh W,Chu V,Achou Cheng,Shu Y,Chonga J.Mheng,Chu T,Shel.

536. Yun KL,Sincetr CF,Miller DC,Fpleter TA,Kochamcaa,GShansari,S al. Randomized trial comparing partial versus complete chiral-polarizing mitral valve refinement:ef-fects on left ventricular volume and function J.Thorod Cardioscus Surg 2002:1237-704.14 https://doi.org/10.1001/j.mcte2021.121048

538. Makkar R, Chikwe J, Chakravarty T, Chen T, Q.O' G. Parte Art, Gilmovin M, et al.Transcatheter mitral valve repair for degenerative mitral regurgitation. JAMA 2023;329:1778-88.https://doi.org/10.1001/jama.2023.7089

539. von Bardelebsen RS,Mahoney P,Morse MAe,PJ,Menti,D.Paisma F,et al.1-Year outcomes with fourth-generation mitral valve transcatheter edge-to-edge repair from the EXPANG D49 study.JACC Cardiovasc Intervas 2023;16:2600-10.https://doi.org/10.1016/j.jc.2023.09.029

540.Zahr F,Smith RL, Gillam LD, Chadderon S, Makar R, von Bardeleles RS, et al.One-year outcomes from the CLASP IDI randomized trial for degenerative nitrative mitrogurgitation. JACC Cardiovasc Incowv 20215:3803-16. https://doi.org/10.1016/j.jcin.2023.10.0020

541.Kaneko T,Hirji,S Zaid,Lange R,Kempfer J,Conradi L,et al.Mitral valve surgery after transchetate edge-to-edge repair; mid-term outcomes from the CUTTING-EDGE international registry.JACC Cardiovasc Interv 2021;2014:2010-21.https://doi.org/10.1016/j.jc.2021.07.029

542. Wild MG, Kreide F, Hell MM, Praz F, Mach M, Adam M, St. Transapical mitral valve implantation for treatment of symptomatic mitral valve disease: a real-world multilucture tree experience. Eur J Heart Fall 2024:299-907. https://doi.org/10.1016/j.jc.2020.2441

543. Ludwig S, Perrin N., Coisne A,Ben Ali W, Weimann J, Duncan A, et al. Clinical out-comes of transcatheter mitral valve replacement: two-year results of the CHO-161 MZR University. Eurontervention 2023;19:25-25. https://doi.org/10.1042446/EJ-D-22-01037

544. Suri RM, Vanverselchede JL, Grigioni F, Schaff HV, Triboulirey C, Avinosier J-F,et al.Association between early surgical intervention vs watching waiting and outcomes for mitral regurgitation due to fail fall vector leaf lakes[JAMA 2013;310:609-16.https://doi.org/10.1001/jama.2013.8643

545. Tribouliloy C, Grioni F, Avinosier J, Barbariier A, Rusinaru D, Syramzkini C, et al.Survival implication if left ventricular end-systolic diameter in mitral regurgitation due to fall leaf levels a long-term follow-up multicenter study.J Am Coll Cardiol 2009;541:1961-68.https://doi.org/10.1016/j.jacc.2009.06.047

546. Tribouliy B, Rusinu D, Grignioni F, Avinosier B, Vanroschellever J, Benfowerscheldey, Benfari G,et al.Indexing left ventricular end-systolic dimension to body size association with mortality

in patients with degenerative mitral regurgitation. Eur J Heart Fail 2024;26:2563-9.https://doi.org/10.1002/ejcf.3393

547. Essayagh B, Antoine C, Benfari G, Messika-Zeintoun D, Michelena H, Le Tourneau T,et al. Progostic implications of left atrial enlargement in degenerative mitral regurgi-tation.J Am Coll Cardiol 2019;74:858-70.https://doi.org/10.1016/j.jacc.2019.06.032

548. Ababie R, CuepreC, Verlakamudi S, Gillinov AM, Svensson LG, Cho L. Sex-specific prognosis of left ventricular size and function following repair of degenerative mitral regurgit-olography. J Am Coll Cardiol 2024;83:303-12. https://doi.org/10.1016/j.jacc.2023.10.033

549. Deigard LA,Skjvik,ET,Lie OH,Ribe M,Stokke MK,Hegbom F,et al.The mitral annulus annulus disjunction arrhythmic syndrome.J Am Coll Cardiol 2018;72:1600-9.https://doi.org/10.1016/j.jacc.2018.07.070

550. Essayagh B,Sabbag A,Antineo C,Benfari G,Batista R,Yang LT,et al.The mitral annular disjunction of mitral valve preprolapse: presentation and outcome.JACC Cardiovasc Imaging 2021:14.2073-87.https://doi.org/10.1016/j.jcmg.2021.04.029

51. Asseyagh B,Sabbag A,Boine C,Benfari G,Yang LT,Maalouf J,et al. Presentation and outcome of arrhythmic mitral valve prolapse. Am J Coll Cardiol 2020;76:637-49.https://doi.org/10.1016/j.jcms.2020.06.029

552. Weimner JM,Boang P,Andis D,Miller MA,Adams DH.Impact of mitral valve repair on the Pickelaheign set. Eur Heart J 2019;40:2267.https://doi.org/10.1093/eurheartj/ethy458

553. Pandis D, David N, Ei-Eshmawi A, Miller MA, Boateng P, Costa AC,et al. Noncomplex ventricular arrhythmia associated with greater freedom from recurrent etctopy at 1 year after mitral repair surgery. JTCVS Open 2024;19:94-113. https://doi.org/10.1016/j.xjcm.2024.04.005

554. Bonaros N, Hofero D, Oepezeker C, Gollmann-Tepekoyu C, Hofeld J, Dumfarth J,et al. Predictors of safety and success in minimally invasive surgery for degenerative mit-tral disease. Eur J Cardiothorc Surg 2022;61:637-44.https://doi.org/10.1093/ejcts/az348

55. Berretta P, Kempert J, Van Praet F, Salvador L, Lamelas J, Nguyen TC, et al.Risk-related clinical outcomes after minimally invasive mitral valve surgery: insights from the Mai-Mitral International Registry. Eur J Cardiothoroc Surg 2023;63:ezad090.https://doi.org/10.1093/ejcbs/2023.04.048

565. Phannella B, Mefleukin, M. Verkevin A, Garbade J, Holzhey DM, Davierwala P, et al.Loop Coord~neorously versus left resection techniques for minimally invasive mitral valve repair: long-term results. Eur J Cardiothoroc Surg 2021;59:180-6. https://doi.org/10.1093/ecj.org et al.1093/ecjrs/2020.114

57.Akowian Fu,Laer RH,Hancock and KH,Karthakopoiac E, Vale L,Fernandez-Garcia C,et al. Mintorotomyc vs conventional sternotomy for mitral valve repair: a rando-mized clinical trial. JAMA 2023;329:1957-66.https://doi.org/10.1001/jama.2023.7800

55. Olshooorn JR, Hutsen S, Voroutman S, Maessen JG, Sardari Nia P. Effect of minimally invasive mitral valve surgery compared to sternotomy on short- and long-term-out comes: a retrospective multicentre interventional cohort study based on Netherlands Heart Registry. Eur J Cardiothorac Surg 2022;61:1099-106. https://doi.org/10.1093/eks7.507

55. Lang M, Vitanova K, Voss B, Feirer N, Rheude T, Krane M, et al. Beyond the 10-year horizon: mitral valve repair solely with chordal replacement and annuloplasty. Ann Thorco Surg 2023;115-96.103.https://doi.org/10.1016/j.athorasursac.2022.05.036

560. New Pell,Pereir,J.Hirji,Harloff M,McGurk S,Malarczyk A,et al. Outcomes of mitral valve repair among high- and low-volume surgeons within a high-volume institution.An Thorac Surg.2023115-412-19.https://doi.org/10.1016/j.athorasursac.2022.05.057

56.Renoshek R, Rader F, Klaan U, Gabriel R, Krejc M, Kalbeck D, et al. Outcome of watch-ful waiting in asymptotically severe mitral regurgitation. Circulation 2006;113:2238-44.https://doi.org/10.1161/CIRCULATIONAHA.105.599175

562. Grigioni F,Benfari G,Vanoverschelde JL,Triboulio C, Avierinos JF, Bursi F, et al.Long-term implications of atrial fibrillation in patients with degenerative mitral regurgitation. J am. Coll Cardiol 2019;73:264-74.https://doi.org/10.1016/j.jacc.2018.10.067

33. Ratwatse,S Strange,P. Fieldord D,Stewart S,Celermajer DS, Prevalence of pulmonary hypertension in mitral vitraling and its influence on outcomes. Open Heart 2023;10.0026268.https://doi.org/10.1136/openhrt-2023-002268

56. Assayhag B, Antoine C, Benfari G, Maalouf J, Michelena H, Crestanello JA, et al.Functional triscupid regurgitation of degenerative mitral valve disease: a crucial deter-minant of survival. Eur H Heart J 2020;41:1918-29. https://doi.org/10.1093/eurheart/jhaea192

56.Sessayah B, Benfari G, Antoine C, Cingiori F, Le Tourneau T, Roussel JC, et al. The MIDA-Q mortality risk score: a quantitative prognostic tool for the mitral valve pro-lapse spectrum. Circulation 2023;147:798-811. https://doi.org/10.1161/CIRCULA TIONAHA.122.0626120

56. Benfari G, Soraja P, Pedazzini G, Taramasso M, Gavazzoni M, Biasco L, et al.Association of transchateter edge-to-edge repair with improved survival in older pa-tients with severe, symptomatic degenerative mitral regurgitation. Eur Heart J 2022;43:1626-325. https://doi.org/10.1093/eurheart/jehab910

567.Spezale G, Nasso,G.,Esposito G, Conte M, Greco E, Fattouch, et al. Results of mitral valve repair for Barlow diase(bileaflet prolapse) via right minhorotacomy versus conventional median stromy: a randomized trial. J Thorac Cardiovasc Surg 2011;142:77-83.https://doi.org/10.1016/j.tcvs.2010.08.033

$$\text{ ESC Guidelines}$$

568. Zilberszag, R. Heinze G. Binder T, Laufer G. Gabriel R, Rosenhek H. Long-term out-come of active surveillance in severe but asymmetry of primary mitral regurgitation.JACC Cardiovasc Imaging 2018;11:1213-21.https://doi.org/10.1016/j.jcm.2018.05.014

569. Suparacya,Y.Azidae F,Axisine SL,Percy,Erenka Purin,Ahris J.et al.Reoperative mi-tral surgery versus transcathetral valve replacement: a systematic review.J Am Heart Assoc 2021;10:e019854.https://doi.org/10.1161/AHA.120.019854

57. Simonato M, Whissenar B, Riberbe H, WBg II, Kjomowski R, Guerrner M, oel T. Transcatheter mitral valve replacement after surgical repair or replacement: comprehers hensive midterm evaluation of valve-in-valve and valve-in-ring implantation from the VIVID registry. Circulation 2021:143:104-16. https://doi.org/10.1161/CIRCULATIONAHA.120.049088

571.Sugura A.Kasurys,PKEeril,Iadis C,Goto T,Colturz C,Tet al.Rocentural mitre-gurgitation after Mitra Clip: predictive factors, morphology, and clinical implication. Circ Cardiovasc. Interv 2022;15:e01895.https://doi.org/10.1161/CIRCININTERVENTIONS.121.010895

52. Zaid S,Avmedino V,Mitanova K,Akansel K,Akhada S,Bhadra OD,Ascione G,Lj:joc.2011/1016/111990 of mitral regurgitation etiology on mitral surgery after transchetter edge-to-edge repair,from the CUTTING-EDG regionYJ. ICCardovres Interv 2023;16:1176-88. https://doi.org/10.1016/j.jcin.2023.02.029

573. Bartkowak,J.Reineke D,Tomii D,Brugger N,Plitor,Terbeck S,et al.Electrosolrgic leration and stabilization of MitraClip followed by valve implantation for a nitrogen mitral stenosis.JACC Cardiovasc Interv 2021:15:10-12.https://doi.org/10.1016/j.jcin.2021.01.01

574. Liska JC, Greenbaum AB, Guyton RA, Kamika N.,Gleason BJ, et al.Ptectrolus Transcatheter mitral valve implantation. JACC Cardiovasc Interv 2023:123:361-70.https://doi.org/10.1016/j.jcian.2020.06.047

575. Huang AL,Dal-Bianco JP,Levine RA,Hung JW. Secondary mitral regurgitation: cardiac remodeling, diagnosis, and management. Struct. Heart Acte 2021:100719.https://doi.org/10.1016/j.jsh.2022.100129

576. Bartko P.Heit G.,PaNO,Heitzinger,M.Pansigra,Stuem Plausr,M.;Burden,tureinuse,and outcome of secondary mitral regurgitation across the spectrum of heart failure: observational cohort study. BMJ 2021;373:1431.https://doi.org/10.1016/j.chm/brn1421

577. Defern, Bernd PB, Verbrugne FL, Verhaert D, Rega D, Thomas JD, et al. Atrial functional mitral regurgitation: JACC review topic of the week. J Am Coll Cardiol 2019;73:2465-76.https://doi.org/10.1016/j.jsc.2019.02.0617

578. Mori M,ZogCK C,Amable A,Fereydooni S,Agarwal R,Weineringer L,et al.Impact of secondary mitral regurgitation on survival in atrial and ventricular dysfunction. PlaS 2010:1727:0385.https://doi.org/10.1016/j.jsc.20210.026

579. Moonen A, NgMKC, Playford D, Strange G, Scala GM, Celclammers J. Datal function al mitral regurgitation; prevalence, characteristics and outcomes from the National Echo Database of Australia. Open Heart 2023;10:e002180. https://doi.org/10.116/open-henpr-2022-002180

580 Okamoto C, Okada A, Nishimara K, Moruchi K, Mano Akiu, M. Talakara H, et al.Prognostic comparison of atrial and ventricular functional mitrogurgitation. Open Heart 2021;8:e01574.https://doi.org/10.116/03penhrt-2021-001574

581.Farhan S,Sibiger J.,Halperin J.LZang D.,Klukpiati SR,Vogel B,et al. Pathophysiology,echocardiographic diagnosis, and treatment of atrial functional mitral regurgitation:JACC state-of-the-art review.J Am Col Cardiol 2022:83014-30. https://doi.org/10.1016/j.jacc.2022.09.046

58. Naser JA, Michela Hlin, L G, Scott CG, Lee E, Kennedy AM, et al. Riskence, fac-tors, and outcomes of atrial functional mitral regurgitation in patients with atrial fibril-lation or sinus rhythm. Eur J Heart Cardiovasc Imaging 2023;24:1450-7.https://doi.org/10.1093/ejci/jead199

583. Stone GW,Lnderfeld J,Abraham WT,Kar,S Lim DS,Mahmel J,et al.Transcheter mitral-valve repair in patients with heart failure. N Engl J Med 2018;379:2307-18.https://doi.org/10.1056/MnM1806460

58. Stone GW,Abraham WT,Lindenfeld J,Kar S,Grayburna PM,LS D.et al.Five-year follow-up after transcatterheep of secondary mitral regurgitation. N Engl J Med 2023:388:307-48.https://doi.org/10.1016/j.Mellis 2002312

58.Cavallek Jr.,Kusunose K,Obuchowski N.,Jellis,C.,Griffin Brpl,FFam,DL et al.Prognostic impact of ischemic mitral regurgitation severity and myocardial infarct quantification by cardiovascular magnetic resonance. JACC Cardosimaging 2020;13:1489-501.https://doi.org/10.1016/j.jcm.2019.11.008

586.Kim K,Kitai T,Kaj,Sak P,Moyoto T,Sasaki Y,Tak et al. Outcomes and predictors of cardiac events in medically treated patients with atrial functional mitral regurgitation.Int J/Cardiol 2020;316:195-202.https://doi.org/10.1016/j.1016/j.chm.2020.06.042

587.Mei O,Gad MM,Crane AD, Ramandan J.Purl, Z.�uay L.Het al. Severe atrial func-tional mitral regurgitation: clinical and echocardiographic characteristics, management and outcomes. JACC Cardiovasc Imaging 2021:14:797-808. https://doi.org/10.1016/j.jg.2021.02.008

588. Doldi P, Stolz L, Orban M, Karam N, Praz F, Kambler D, et al. Transcatheter mitral valve repair in patients with trial functional mitral regurgitation. JACC Cardiovasc Imaging: 2022:1543-151.https://doi.org/10.1016/j.jcm.2022.05.009

589. Masiero G. Montanoni C, Rubbio AP, Adamo M, Grasso C, Denti P, et al. Impact of transcatheter edge-to-edge mitral valve repair on atrial functional mitral regurgitation from the GLOT registry. Am J Cardiol 2024;211:2019-27.https://doi.org/10.1016/j.amerol.2023.11.007

Yoon.50 Yon Sh,Makar M,Kar S,Charkavarty T,Oakley L,Sekhon N,et al. Outcomes after transcheterate edge-to-edge mitral valve repair according to mitral regurgitation eti-ology and cardiac remodeling.JACC Cardiovasc Interv 2022;15:1711-22.https://doi.org/10.1016/j.jc.2022.07.004

591 Chen QF, Zhou X, Katsouras CS,Ni C,Zhu H,Liu C,et al. Atrial and ventricular func-tional mitrogurgitation:prevalence,characteristics,outcomes,deasprogres-sion. Eur Heart J Cardioscim Imaging 2024:26:545-56. https://doi.org/10.1093/ehjci/jaseo309

59.29. Stein von P, von Stein J, Hohmann C, Wienemann H, Guthoff H, Korber M, et al. Atrial functional mit regurgitation subtypes undergoing transcatheter edge-to-edge repair suboptimal outcomes in a extragalronic hamstring. JACC Cardiovasc Imaging 2025;18:16-29.https://doi.org/10.1016/j.jcm.2024.06.019

593. Rosano McGam,Moura,B Mettra M,Bohm M,Bauersachs J,Ben Gal T,et al. Patient pro-filing in heart failure for tailoring medical therapy. A consensus document of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2021;23:871.https://doi.org/10.1002/efjh.2206

59. Mazaza A, Davison B, Cicech O, Cohen-Solal A, Diaz R, Filippatos G, et al. Safety,tolerability and efficacy of up-tritration of guideline-directed medical therapies for acute heart failure(STRONG-HF): a multinational, open-label, randomised, trial. Lancet 2024;400:1938-52.https://doi.org/10.1016/s0140-6736(22)02076-1

95. Spinka G, Bartko PE, Heitzinger G, Prausmuller S, Winter MP, Arfsten H, et al.Guidelineed directed medical therapy and reduction of secondary mitral regurgitation.Eur Heart J Cardiovasig 2022:23:755-64. https://doi.org/10.1093/ehjci/jeac068

96. Pagnesi M, Adamo M, Sama R, Anker SD, Cleland JG, Dickstein K, et al. Clinical impact of changes in mitral regurgitation severity after medical therapy optimization in heart failure.Cin Res Cardiol 2022:111:912-23.https://doi.org/10.1007/s00392-022-01991-7

57.Dii Base, Auriochi M, Auriano P,Bai R,Kautzner J,Pieragnoli P,et al.Impact of car-diac resynchronization therapy on the severity of mitral regurgitation. Euroace 2011;138:29-38.https://doi.org/10.1093/europe/eur047

958. Giksoni M,Nielsen J,Krcbrong M,Bioar M,Wicowitz A,Abarbash IM,et al.20212021:42:3427:520.https://doi.org/10.1093/europe/eur047

599.Michalski B,Stankovic I,Pagourelias E, Ciarka A, Aarones M, Winter S, et al.Relationship of mechanical dysynchrony and LV remodeling in improvement of mi-tral regurgitation after CRT. JACC Cardiovasc Imaging 2022;15:2120-20. https://doi.org/10.1016/j.jcmg.20210.0810

60Ypenburg,C.Lancelotti,P.Tops LF,Bueker GB,Holman ER,Pierard LA,et al.Acute effects of initiation and withdrawal of cardiac resynchronization therapy on papillary muscle dysssynchry and mitral regurgitation.J Am Coll Cardiol 2007;50:2071-7.https://doi.org/10.1016/j.jacc.2007.08.019

601. Obadia J F, Messka-Zeitoun D, Leurent G, lung B, Bonnet G, Pirou N, et al.Purecutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med 2018:379:2397-306.https://doi.org/10.1056/NEJMoa1805374

62. Lung B, Armoyi X, Vahianan A, Boutite F, Mewton N, Trochu JN, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation: at 2 years of 2023.Hear J Heart Fail 2019;21:97.https://doi.org/10.1056/NEJMoa185374

63 Grayburn P, Sannino A, Kperger M. Proportionate and disproportionate functional mitral regurgitation: a new conceptual framework that reconciles the results of the MITRA-FR and COAP TART 2018;11.006

6064. Nemi Adam,M.,Metaan M.,Aflier O,Vahanian A.Treatment of functional mitral re-gurgitation in chronic heart failure: can we get a'proof of concept' from the MITRA-FR and COAPT trial?Eur J Heart Fair 2019;21:852-61.https://doi.org/10.1002/EJHF.1491

605.Piborol P, Delveden B, Vao JJ,C.,Mitrau-F, vs. COAPT: lessons from two trials with dia-metrically opposed results. Eur Heart J Cardiovasc Imaging 2019;20:620-24.https://doi.org/10.1093/ijc:eljioje37

606. Anker, D57, Friede T, von Bardieben RS, Butler J, Khan MS, Diek M, et al. Transcatheter valve repair in heart failure with moderate to severe mitral regurgitation. N Engl J Med 202431799-809 https://doi.org/10.1056/NEJMoa2314328

607.Anker MS,Porthun J,Bonner G,Schulze PC,Rassaf T,Landmesser U.Percutaneous transchattergate edge-to-edge repair for functional mitral regurgitation in heart failure:meta-analysis of 3 randomized controlled trials. J Am Coll Cardiol 2024:84:2364-68.https://doi.org/10.1016/j.jacc.2024.08.026

608. Koel B, Orban M. Weimann J, Kassar M, Karam N, Neuss M, et al. Outcomes stratified by adaptined inclusion criteria; after mitral edge-to-edge repair. J Am Coll Cardiol 2021;78:2408-21.https://doi.org/10.1016/j.jacc.2021.10.011

609 Scott A.Liabot A,Rubio ABP,Testa L,Adamo M,Denti P,et al. Derivation and valid-ation of a clinical risk score for COAPT-ineligible patients who underwent transcath-eter edge-to-edge repair. Am J Cardiol 2023;186:100-8. https://doi.org/10.1016/j.amc.2022.10.024

ESC Guidelines

93

610. Godino C, Munafo A, Scotti, Eastte-Evrezle-Loureiro R, Portleshernandez A, Arzamendi D,et al. MitraClip in secondary mitral regurgitation as a bridge to heart transplantation:1-year outcomes from the International MitraBridge Registry. J Heart Lung Transplant 2020:39:135-162.https://doi.org/10.1016/j.heunen.2020.09.005

611. Alawadi G,Lim DS,Mack MJ,Trento A,Kar a Gray,Carsyburn PA,et al.One-year outcomes after Mitral Clip for functional mitral regurgitation. Circulation 2019;139:37-47. https://doiorg/10.1161/CIRCULATIONAHAH 117:031733

612. Goel K, Lindenfeld J, Rakah N, Atakmuri S,Kahamoye,P et al. Transcatheter edge-to-edge to-edge in 4,000 patients with secondary mitral regurgitation: COAPT post-proposal study.J Am Coll Cardiol 2023:82:1281-97.https://doi.org/10.1016/j.jc.2023.07.015

613. Adamo TM. Sonod D, Stolz L, Stocker TJ, Panclano E, Kello B, et al. Impact of trans-catheter edge-to-edge mitral valve surgery in guideline-directed medical therapy utpi-tration.JACC Cardiovasc Interv 2023;186:995-905.https://doi.org/10.1016/j.jc.2023.01.362

41. Witte KK, Lipiec J, Siminiak T, Meredith T, Malkin CJ, Golds SL, et al.REREDU FMR4: trial a randomized sham-controlled study of percutaneous mitral anu-puloplasty in functional mitral regurgitation.JACC Heart Faly 2019:7495-55. https://doi.org/10.1016/j.jchf.2019.06.011

615. Anker Sd, Starling RC, Khan MS, Friede T, Filippatos G, Lindenfeld J, et al.Purecutaneous mitral valve anuloplastic in patients with secondary mitral regurgitation and severe left ventricular enlargement. JACC Heart Fol 2021;9:453-62. https://doi.org/10.1016/j.jchf.2021.03.002

616. Wu AH, Aaronson KD, Bolling SF, Pagani FD, Welch K, Koelling TM. Impact of mitral valve unalupody on mortality risk in patients with mitral regurgitation and left ven-tricular systolic dysfunction. Am Cell Colord 2005;481:7 https://doi.org/10.1016/j.jacc.2004.09.073

617. Baldus S, Doesten T, Pfister R, Gummert M, Kessler M, Boekstegers P, et al.Transcatheter repair versus mitral-valve surgery for secondary mitral regurgitation N.Eng NL Med 2024;391787-98.https://doi.org/10.1056/NEJMa02408739

618. Ackar MA, Parides MK, Perrault LP, Moskowitz AJ, Gelins AC, Voines P, et al.Mitral-valre repair versus replacement for severe ischemic mitral regurgitation. N Engl J Med 2014;370:23-32.https://doi.org/10.1056/NEJMOa1312808

619. von Summ M, Dude,Foht I, Resequieas-Grow,T. Pausche, Reiraich T.,Mukell R, U.Sastu, T. Weis et al.Openst clinical outcome by indexed mitral valve negation ventral mitral valve regurgitation.Open Heart 2021;8e001483.https://doi.org/10.1065/openhrt-2020-001483

620.Girdusas Pauk, J. Reuschigen Puer, Kempert, J. Kuntze T, Owais T, et al.Subannular repair for functional mitral regurgitation with reduced systolic ventricle function: rationale and design of REFORM-MR registry. J Cardiothor Surg 2022;17:343.https://doi.org/10.1016/j.1961202-022045-3.

621. Pausch,J.,Sequeira Gross,T.,Muller L.,on Stum M.,Klothl,B.Rechensompur,H.et al.Subannular repair for functional mitral regurgitation type llb in patients with ischemic versus dilated cardiomyopathy.Eurl Cardiothorc Surg 2021:12-30.https://doi.org/10.1093/ejctz/abez048

622.Kopar T,Gasparich,Hestamic Mar,Cidic B,Medica B, Meta-analysis of concomi-tant mitral valve repair and coronary artery bypass surges isolated coronary artery bypass surgery in patients with moderate ischaemic mitral regurgitation. Eur J Cardiolos 2016;2015-22-212.https://doi.org/10.1033/10933/2020

62. Altarabsher Se,Deo SV, Dunay SM, Erpin PJ, Obeid YMk, Navale S, et al.Meta-analysis of usefulness of concomitant mitol valve repair or replacement for moderate ischemic mitral regurgitation with coronary artery bypass grating. Am J Cardiol 2017;119:734-41.https://doi.org/10.1016/jjamard.2016.112.024

624. Michler Re,Smith P, Parides MK, Alwadi G, Thourani V, Moskowitz AJ,et al.Two years of outcomes of surgical treatment of moderate ischemic mitral regurgitation.N Engl J Med 2016;374:1932-41.https://doi.org/10.1056/NEJMoA1602003

625. Vadugradan M. Mostchery CF, Klagglett, Klüppard, PS de BoRA, Hernandez A, et al. and SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet 2022:4002-757-67. https://doi.org/10.1016/S014016-6723(02)1429-5.

626. Souat,Dufour L,Lang S,Addeta K, Ederhy S, Adavne-Scheuble, Chauvet-Droit M,et al. Restoring sinus rhythm reverses cardiac remodeling and reduces valvular regur-gitation in patients with atrial fibrillation. J Am Coll Cardel 2022;79:951-61.https://doi.org/10.1016/j.jacc.2021.12.029

627.Kagialyan,N Kaneko,TAmano S,Mato Y,Ohno Y,Obokata M,et al.Clinical outcomes of mitral valve surgery in arial functional mitral regurgitation in REVEAL-AFMGR registry.JAMA Netw Open 2024:7e2428032.https://doi.org/10.1001/janmorkewopten.2024-28032

628. Wagner CM, Brescia AA, Watt TM, Bergusti B, Lanczos LM, Cenza NN, et al.Surgical strategy and outcomes for arial functional mitral regurgitation: all functional mitral regurgitation is not the same| J Thorai Cardioscus 2024:1676:547-55.

92. Berogh Z.,Mizukami T.,Bartunek J. Collet C, Beles M, Albano M, et al. Mitral valve repair of a functional mitral regurgitation in heart failure with preserved ejection fraction.J Clin Med 2020;9:3432.https://doi.org/10.3390/jcm9113432

630. Ye. Li,YQ,Zhang,W.Zhao,Zhao Z,C.L.et al.Cheater ablation or surgical therapy in severe arial functional mitral regurgitation caused by long-standing persistent atrial

fibrillation-propensity score analysis. J Am Heart Assoc 2024;13:e035695. https://doi.org/10.1161/j.124.035695

631.Chen J,Wang Y,Lv M,Yang Z,Zhu S,Wei L,et al.Mitral valve repair and surgical ab-lation for arial functional mitral regurgitation. Ann Transl Med 2020;8:1420.https://doi.org/10.21602/3.2037/20-2958

632. Benito-Gonzalez T,Carrasco-Chinchilla F,Estévez-Louirero R, Pascualll,Arzamendi,D Garne-Torole Cola,C.et al. Clinical and echocardiographic outcomes of transcatheter mitral valve repair in atrial functional mitral regurgitation. Int J Cordiol 2021:345:29-35.https://doi.org/10.1016/j.icard.2021.09.056

63. Popolo Rubio,ATesta,L.Grossa C,Sinni,A Tusa,M.Agricola,E.et al.Transcatheter edge-to-edge mitral valve repair in atrial functional mitral regurgitation: insights from the multi-center MITRA-TUNE registry. Int J Cardiol 2022;349:39-45. https://doi.org/10.1016/j.icard.2021.10.027

634. Rudolph F, Geyer M, Balus S, De Luca VM, Doenten T, Pfister R, et al. Transcatheter repair versus surgery for afraid versus ventricular functional mitral regurgitation: a post hoc analysis of the MATRHORN trial. Circulation 2024;151:418-20. https://doi.org/10.1161/circulationaha.124.072648

35. Tanaka T.,Surgura A.Voghefuber J.,Ozturk C, Bohm L, Wilde N, et al. Outcomes of transcatheter edge-to-edge repair for atrial functional mitral regurgitation.Eurultretention 2024;20:250-60.https://doi.org/10.4244/ej-d-23-00819

63. Gemelli M,Gallo M,Addonizio M, Van deney Jr, Padegan N, Danesi TH, et al.Surgical ablation for atrial fibrillation during mitral valve surgery: a systematic review and meta-analysis of randomized controlled trials. Am J Cardiol 2023;209:104-13.https://doi.org/10.1016/j.jcard.2023.09.088

637. Suwalski P,Kowalewski J, Jasinski M, Staromlynski J,Zembala M,Widenka K,et al.Survival after surgical ablation for atrial fibrillation in mitral valve surgery: analysis from the Polish National Registry of Cardiac Surgery Procedures(KROK). J Thorac Cardiovasc Surg 20219;157:1007-18.e1004.https://doi.org/10.1016/j.tjcvs.2018.07.099

638. Hamada S, Ueyama H, Akikawa T, Kampkattsis PN, Misumida N, Takagi H, et al.Outcomes of transcatheter edge to-edge repair for atrial functional mitral regurgita-tion: a meta-analysis of observational studies. Catheter Cardiovasc Interv 2023;102:751-60.https://doi.org/10.1002/ccd.30806

39.Sohin N, Asch P., Asch P., Rui T, Pet derlebeen S, Lim DS, et al. Clinical out-comes with transcatheter edge-to-edge repair in a trivial functional MR from the EXPAND study.JACC Cardiovasc Interv 2022;15:1723-30.https://doi.org/10.1016/j.jan2022.07.023

640.Deja Ma,Grayburn PA,Sun B,Rao V,She L,Kreja M,et al.Influence of mitral regur-tigation repair on survival in the surgical treatment for ischemic heart failure trial.Circulation 2012;125:26:39-48.https://doi.org/10.1161/CIRCULATIONAHA.111.072256

41. Chan Klun Pajnsis PP. Fisher M, Wage R, Symmonds K, Roussin I, et al. Coronary ar-tary bypass surgery with or without mitral valve unplasty in moderate functional ischemic mitral regurgitation: final results of the Randomized Ischemic Mitral Evaluation(RME) trial. Circulation 2012;126:250-10. https://doi.org/10.1161/j.camha.114818

642. Virk Sai, Tian DH, Sriravindarajah A, Dunn D, Wolfenden HD, Suri RM, et al.Mitral valve surgery and coronary artery bypass grafting for moderate-to-severe ischemic mitral regurgitation: meta-analysis of clinical and echocardiographic out-comes J. Thorac Cardiovasc Surg 2017;154:127-36.https://doi.org/10.1016/j.tjcsv.

643.Adamo M,Fioreli,F.Mel,R.B'Dortona R,Lupi L,Giannini C,et al.COAPT-like profile predicts long-term outcomes in patients with secondary mitral regurgitation undergo-ing Mitra Clip implantation. JACC Cardiovasc Interv 2021;14:15-25. https://doi.org/10.1016/J.CIN.2020.059.2019

644 Coffey J, Roberts-Thomson R, Brown A, Carapetis J, Chen M, Enriquez-Sarano M,et al. Global epidemiology of valvular heart disease. Nat Rev Cardiol 2021;18:853-64.https://doi.org/10.1038841569-021-00570-2

45Gungie, S.Ba, Balde D, Diarra MB, Anzouan-Kacou JB, Anisubia B, et al.The VALVAFRACY: a study: a registry of rheumatic heart disease in Western and Central Africa,Ar Arch Cardovescu Dis 2016;109:321-9.https://doi.org/10.1016/j.acvd.2015.12.004

646 Timms A, Vardas P,Townsend N, Torbica A, Katus H, De Smedt D, et al. European Society of Cardiology; cardiovascular disease statistics 2021. Eur Heart J 2022;43:716-99.https://doi.org/10.1093/eurheartj/ehab892

647.Churchin TVY,Cuel E.Deferman S,Levine RA,Hung J,Bertrand PB. Mitral valve dysfunc-tion in patients with annular calcification: JACC review topic of the week. J Am Coll Cardiol 2022:80:739-51.https://doi.org/10.1016/j.jacc.2022.05.032

648. Andell P, U.L. Marxinson C, Stagmo M, Zoller B, et al. Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study. Heart 2017;103;1969-703.https://doi.org/10.1136/heartnjl-2016-310894

69. Baungtner H. Hung J. Bernejo J, Chambers JB, Evangelista A, Griffin BP, et al.Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for din-ical Journal. J CoM Socam Oscuemocardiogr 2009;22:1-23; quiz 101-102. https://doi.org/10.1016/j.echo.2008.11.029

94

$$\text{ ESC} G\text{ Guidelines}$$

650. Otto CM, Davis KB, Reid CL, Slater JN, Kronzon I, Kissko KB, et al. Relation between pulmonary artery pressure and mitral stenosis severity in patients undergoing balloon mitral commissoromy. Am J Cardiol 1993;71:874-8. https://doi.org/10.1016/0002-9149(93)90844-3

65. Bouleti C, Lung, Bauouen Chavah, B. Himbert, D. Brochet E, Messika-Zeitoun D. et al. Late results of percutaneous mitral commissuratory on 20 years: development and val-olation of a risk score predicting late functional results from a series of 912 patients.Circulation 2012;125:219-27. https://doi.org/10.1161/CIRCULATIONAHA.111.059505

65.Nunes MC,Tan,Elumara,S.Bado L,Rago R,Margy R,Cruz-Gonzalez L.et al.The echo score revisited: impact of incorporating commissturical morphology and leaflet discharge-ment to the prediction of outcome for patients undergoing percutaneous mitral vol-vulplasty. Circulation 2014;129:886-95. https://doi.org/10.1161/CIRCULATION AHA.113.001252

653. Wilkins GT, Weyman AE, Abscal V, Block, PCalas, PCalics IF. Percutaneous balloon dilatation of the mitral valve: an analysis of echocardiographic variables related to out-come and the mechanism of dilatation. Br Heart J 1978:60:299-308. https://doi.org/10.1136/hr604.299

65. Lancellotti P, Pellikka P, Budws W, Chaudhar F, NaAlon D, Dulghuler R, et al. The clin-ical use of stress echocardiography in non-schaemic heart disease: recommendations from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging 2016;17:1911-229.https://doi.org/10.1092/ijdeju1901

655. Brochet E,Detaint D., Fond T., Oazi-Mezalek A, Messka-Zeitoun D, Lung, B et al.Early hemodynamic changes versus peak values: what is more useful to predict occur-rence of dyspue during stress echocardiography in patients with asymptomatic mitral stenosis; J Am Soc Echocardiogr 2011;24:392-8.https://doi.org/10.1016/j.jecho.2011.01.006

656. Alrawal MNI, Al-Mapal J, Al-Namoulai, Al Ajami, AlAw Eseyag B, Novel oral ant-cagulants in patients with atrial fibrillation and moderate to severe mitosis as a systematic review. Cureus 2023;15:e3222.https://doi.org/10.7759/cureus.3322

657.Kim YJ,Shu Kim,HyMPou,J.Kymp,IR Zts,Km,Shi) et al. Outcomes of direct oral an-ticoagulants in patients with mitral stenosis. J Am Coll Cardiol 2019;73:1123-31.https://doi.org/10.1016/j.jacc.2018.12.047.2014.

658. Vivulanayan ,K Srivash,PyKong,JP R Kyn,Trsakun,Kim B,Anjappa PC, Pandan B,Bagi V,Kasturi,et al.Ranized placebo-controlled trial with amoradone for persistent atrial fibrillation in rheumatic stenosis; Al Chen, Najpara M, Pandan B, Bagi V, Kasturi,Indian Heart J 2016:68:71-7.https://doi.org/10.1016/j.ijh.2016.02.013

659. Sharma G, Anantha Krishnan R, Bohra V, Ramachrishnan S, Naikn S, Seth S, et al.Evaluation of early direct current cardioversion for maintenance of sinus rhythm in rheural fibrillation following successful balloon mitral valovlodynt. Indian Heart J 2016:68:49-7. https://doi.org/10.1016/j.ijh.2015.11.03

660 Keenan NG,Cuffe C,Cimadella E,Crochet B,Leage T, Lepelit D, Detant, U. et al. Usefulness of left atrial volume versus diameter to assess thromboorbic risk in mitral stenosis.Am J Gcardol 2010:106115-62.https://doi.org/10.1016/j.jiang.2010.06.024

66. Badheka AO, Shah N, Ghatak A, Patel N, Chothen A, Metahi K, et al. Balloon mitral voluplasty in the United States: a 13-year perspective. Am J Med 2014;127.1126:e112-1126.e1121.e1126;https://doi.org/10.1016/j.amjmed.2014.05.015

662.Tomai F,Gaspardone,A.Versaci F,Ghini AS,Amtalua L.DeLu et al.Twenty year follow-up after successful percutaneous balloon viraluloplasty in a large componary series of patients with mitral stenosis. Int J Cardiol 2014:17781-85.https://doi.org/10.1016/j.ijdard 2014.10.040

663. Bouleti C, Lung B, Himbert D, Messika-Zeitoun D, Brochet E, Garbarz,E et al.Relationship between valve calibration and long-term results of percutaneous mitral commersiromy or rheumatic mitral stenosis. Circ Circavous Intervan 2017;4:381-9.https://doi.org/10.1161/CIRCIRENTVENTIONS/11000858

664. Bouleti C, Lung B, Himbert D, Brochet E, Messigma-Zeitoun, Daitet D, et al.Reintentions after percutaneous mitral commersimotry during long-term follow-up, up to 20 years of the role of repeat percutaneous mitral commersimotry-Eur Heart J 2013;34:1923-30.https://doi.org/10.1093/eurieht097

665. Desnos C,Lung,BH,Bimbert,Duccrocq G,Urena M,Cormier B,E. Temporal trends on percutaneous mitral commisotromy: 30 years of experience.J Am Heart Assoc 2019;8:e012031.https://doi.org/10.1161/J/AHA.119.012031

666.Ambari AM,Setanto B,Santoso A,Dupwitra B,Radi B, AlkatiAA,et al. Survival ana-lysis of patients with rheumatic MS after PBPMV compared with MVS in a low-to-middle-income country. Neth Heart J 2019:27:55-64. https://doi.org/10.1007/s124719-01319-x

667. Song H,Kang DH, Kim JH, Park KM, Song JM, Choi KJ, et al. Percutaneous mitral val-vuloplasty versus surgical treatment in mitsten stenosis with severe tricuspid regurgita-tion. Circulation 2007;116/11674-264.50-https://doi.org/10.1161/CIRCULATIONAHA107.1678151

668 Soosanto AM,Roswita D,Atmosudigdo IS, Adiato S, Sahara C. Clinical and hemo-dynamic factors associated with low gradient severe rheumatosis. Int J Angiol 2022:32:43-7.https://doi.org/10.1055/s-0042-1751231

669.Sabbah A,Reddy Ynn,Bras-Cosrges S,Borrows-Bu,Ai,Marrna Jr,Burps-Larra,Misarva,Brans U,et al. Low-gradient severe mitral stenosis: hemodynamic profiles, clinical characteristics, and

outcomes.J Am Heart Soc 2019;8:e010736.https://doi.org/10.1161/j/AHA.118.

670.Okura H,Nakada Y,Nogi M, Ishihara S,Okamura A,Okayama S,et al. Prevalence of mitral annular calcification and its association with mitral valular disease.

671. Kato N, Padang R, Scott CG, Guerrero R, Pisaru SV, Pellekka PA. The natural history of severe calcitic mitral stenosis. J Am Coll Cardiol 2020;75:3048-57.https://doi.org/10.1016/j.jacc.2020.04.049

672. Chehab O, Roberts-Thomson R, Bivona A, Gill H, Patterson T, Pursnani A, et al.Management of patients with severe mitral annular calcification: JACC state-of-the-art review.J Am Coll Cardiol 2022;80:722-38.https://doi.org/10.1016/j.jacc.2022.06.009

673.673. Oukuno T,Brugger N,Aami M,Heg D,Siontis GCM,Winkel MG,et al.Clinical impact of mitral calcium volume in patients undergoing transcatheter aortic valve implant-ation.J Cardiovasc Comput Tomogr 2021;15:365-65. https://doi.org/10.1016/j.jcct.2020.10.003

674. Bertrand B, Churchill TW, Yucel E, Namasivasam M, Bernard S, Nagata Y, et al.Prognostic importance of the transmitral pressure gradient in mitral annular calcifica-tion with associated mitral valve dysfunction. Eur Heart J 2020;41:4321-8. https://doi.org/10.1093/eurheart/haeha819

675. Uremai H,Timber D,Broch et E,Carrasco JL,Lung B,Nataf P,et al.Transseptal trans-cetatheral valve replacement using balloon-expandable transcatheter heart valves:

676. Guerrero ME, Grayburn P,Smith RLI,Soraja P,Wang DD,Ahman Y,et al.Diagnosis,classification, and management strategies for mitral annular calcification.JACC Cardoview lntes:2013;26:1195-210.https://doi.org/10.1016/j.jcin.2023.06.044

[97] Uchimuro,Tuk,Fhimi,Tuak,A Takanashi S.Mitral valve surgery in patients with se-rence mitral annular calcification. Ann Thorac Surg 2016;101:889-95.https://doi.org/10.1016/jathorascu.2015.08.071

678.Fukui M,Cavalcante JL,Ahmed A,Bae R,Bapat N,Vossl M,et al.Clinical outcomes of mitral valve gas with mitral annular calcification. Am J Cardiol 2022;174:107-13.https://doi.org/10.1016/j.amj.2022.023.041

679.Kato N,Pellka PAi,Cotta SC,Cong,Lee AT,Jain V,Eleid MF,et al.Impact of mitral inter-vention on outcomes of patients with mitral valve dysfunction and annulus calcification.https://doi.org/10.1016/j.amj.2022.22.99:1807-16.https://doi.org/10.1002/ccd.30093

680.Brener MI,Hamandi M,Hong E,Pizano A,Harloff MT,Garner EF,et al.Early outcomes following transatrial transatrial transceiver application in patients with severe mi-tral annular calcification.Jiong E, Pizano A, Harloff MT, Garner EF,et al. Early outcomes following transatrial transatrial transceiver application in patients with severe mi-tral annular calcification.Jiong E, Pizano A, Harloff MT, Garner EF,et al. Early outcomes

G881.GuerreEM,Lie F.Mwang DD,Pursnani A,Kodali SK,George I,et al.5-Year pro-spective evaluation of mitral valve-vin-alve, valve-in-ring, and valve-in-MAC outcomes:MITRAL trial final results.JACC Cardiovasc Interv 2023;16:2211-27.https://doi.org/10.1016/j.jc.2023.06.041

682. Topisky Y,Maltais S,Medina Inojosa J,Oguz D,Michelena H,Maalouf J,et al.Burden of tricuspid regurgitation in patients diagnosed in the community setting, JACC Cardiovasc Imaging 2019;12:433-42.https://doi.org/10.1016/j.jcm.2018.06.014

683.Chorin E, Rozenbaum Z. Topilsky Y, Konigstein M, Ziv-Baran T, Richert E, et al.Tricuspid regurgitation and long-term clinical outcomes. Eur Heart J Cardiovasc Imaging:2020:21:157-65. https://doi.org/10.1093/ehcij/jez216

684. Topisky Y, Inoja P, Benfari G, Vaturi O, Maltais S, Michelena H, et al. Clinical pres-entation and outcome of tricuspid regurgitation in patients with systolic dysfunction.Eur Heart J 2018;39:3584-92.https://doi.org/10.1093/eurheart/ehy434

68. Kadin M, Renon M, Samouri YM,Gajulapalli RD, Meenakshisundam C, Nusatari L,et al. Outcomes of patients with severe tricuspid regurgitation and congestive heart failure. Heart 2019;105:1813-7. https://doi.org/10.1136/heartn-2019-315004

686.Dreyhus F.,Ghlem N,Garbarz E,Cimadevilla C,Nafat P,Vahanian A,et al.Timing of referral of patients with severe isolated tricuspid valve regurgitation to surgeons(from a French nationwide networkable database). Am J Cardiol 2018;122:323-6. https://doi.org/10.1016/j.amjard.2018.04.003

687.Hoke U, Auger, D. Thissjers, J. Wolterbeek R, van der Velde ET, Holman ER, et al.Significant lead-induced tricuspid regurgitation is associated with poor prognosis at long-term follow-up. Heart 2014;100:960-8.https://doi.org/10.1136/heartjni-2013-304673

68. Andreas B,Murris H,Fraz F,Badno L,Barreiro M,et al.Tricuspid valve dis-ease and cardiac implantable electronic devices. Eur Heart J 2024;45:346-65. https://dolorg.org/10193/10749/10193-x115-7

689 P. Frumur D, Kreidel F, Lurz P, Hahn RT, Delgado V, et al. Transcatheter treat-ment for tricuspid valve disease. Eurolntervention 2021;17:791-808. https://doi.org/10.4244(E)D-21-00695

69.Song H.Kim MJ,Chung CH,Choo SJ,Song MG,Song JM,et al. Factors associated with development of late significant tricuspid regurgitation after successful left-sided valve surgery. Heart 2009:95931-6. https://doi.org/10.1136/hrt.2008.152793

691.GalooX, Dietz MF, Fortiun F, Prihadi EA, Cosyns B, Delgado V, et al. Prognostic im-plications of atrial vs ventricular funcistic tricuspid regurgitation. Eur Heart J Cardiovasc Imaging 2023:24373-41.https://doi.org/10.1093/ehjci/jead016

ESC Guidelines

95

692. Schlotter F, Dietz MF, Stolz L, Kresoja JP, Besler C, Sannino A, et al. Atrial functional tricuspid regurgitation: novel definition and impact on prognosis. Circ Cardiovasc Interv 2022;15:e011958.https://doi.org/10.1161/CIRCINTERVENTIONS.122.011958

693. Adamo M,Chonico C, Pagneos M, BayesGeni A, Abdhamard M, Iankar SD, et al.Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association(HFA) and the European Association of Percutaneous Cardiovascular Intervanies(EAPCl) of the Esc. Eur J Heart Fail 2024;26:18-33.https://doi.org/10.1002/ejnf.3106

694.Fortun F,Miet PF,Mrifad EA,van der BijP,P.De Ferrari GM,Knujet,Jut et al. Prognostic implications of a novel algorithm to grade secondary tricuspid regurgitation. JACC Cardovics Invasive Chem 2021:14:1085-95. https://doi.org/1010.1016/j.jsc.2020.12.011

695. Peri Y, Sadeh B, Serech H, Hochstad A, Biner V, Swiram A, Guelti et al. Quantitative assess-ment of effective regurgitant orifice on risk stratification, cut-off for severe and torraltrusidic regurgitant grade. Eur. Heart J: Cardiosci: Imaging 2020:768-76.https://doi.org/10.1093/ehjcjez267

696. Dreyfus J, Galloo X, Taramasso M, Heitzinger G, Benfari G, Kresoja KP, et al. TRI-SCORE and benefit of intervention in patients with severe tricuspid regurgitation.Eur Heart| 2024;45:586-97.https://doi.org/10.1093/ehci/jehr0585

697. Hahn RT, Lawlor MK, Davidson CJ, Badhwar V, Sannino A, Spitzer et E, et tricuspid Valve Academic Research Consortium definitions for tricuspid regurgitation and trial endpoints. Eur Heart J 2024;45:458-97. https://doi.org/10.1093/eurieh/ahd653

698. Petersen SE, Khani JP, Many P, Lancelott P, Bucciarelli- Ducci C, European Association of Cardiovascular Imaging expert consensus paper: a comprehensive re-view of cardiovascular magnetic resonance normal values of cardiac chamber size and aortic root in adults and recommendations for grading severity. Eur Heart J Cardiovascular Imaging 2019;20:1321-311.https://doi.org/10.1093/ehjci:jez232

694. Kawel-Boehm N. Hetzel SJ, Ambale-Ventahkates, Captur G, Francois CJ,Jeroser-Herold M. et al. of Reference ranges("normal values") for cardiovascular magnetic resonance(CMR) in adults and children: 2020:22:311.2020:2020:11.

700. Lang RM, Badopen LD, Mor-Pavi A, Vflamal, J orrmant, AErnne L, et al.Recommendations for cardiac chamber quantification by echocardiography in adults:an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovascular Imaging 2015;16:233-70.https://doi.org/10.1093/ehjcj/veo141

701. Addeta K, Myloxy T, Ciro R, Daiman M, Cuteriffazos P, Kalwal R, Reil et al. Two-dimensional echocardiographic right ventricular size and systolic function mea-surements stratified by sex, age, and ethnicity of the World Alliance of Societies of Echocardiography study.J Am Soc Echocardiography 2021;34:1148-1157.e1.e.https://doi.org/10.1016/j.echo.2021.06.013

702.Addeta Kia, Myophori, T. Anutham, V. Croiro, R. Maimon, G. Tuteri Fazno, Pier et al.Normal values of three-dimensional right ventricular and function measurements:results of the World Alliance Societies of Echocardiography. J. Am. Soc Echocardiography 2013:36-866-86. et https://doi.org/10.1016/j.choo2023.04101

703. Dietz MF, Prihiad EA, van der Bij P, Goedemans L, Tertens BJA, Gurosley E, et al.Prognostic implications of right ventricular remodeling and function in patients with significant secondary tricuspid regurgitation. Circulation 2019:140:836-45. https://doi.org/10.1161/CIRCULATIONAHA.119.039360

040. Erken-Volines T, Grue J, Helium Olsen, S. Lettes JP, Nels B. Lavestken L, et al.Normalized echocardiographic values from guideline-cudited dedicated views for car-diac dimensions and left ventricular function. JACC Cardiovascular Imaging 2023:16:1501-15. https://doi.org/10.1016/j.jc:2021.220.020

705. Zurl P,Orman B,Mesler C,Braun D,Schlotter N,Facko T,et al.Clinical characteristics,diagnosis, and risk stratification of pulmonary hypertension in severe tricuspid regurgit, gptation and implications for transcatheter tricuspid repair. Eur Heart J 2020:41:2785-95.https://doi.org/10.1093/eurie/etaheh138

706. Stockier T, Hertell, HOran B, Braun D, Romuel KP M, Ruf, et al. Cardiopulmonary hemodynamic profile predicts mortality after transchirte tricuspid valve repair in chronic heart failure.JACC Cardiovascular Interv 2021;24:19-28;https://doi.org/10.1016/j.jc:2020.09.033

707. Brener ML,Mir L, Paushele J, Rodes-Cabau J, Fam N, Kodali SK, et al. Right ventricular-pulmonary arterial coupling and afterload reserve in patients undergoing transchateri upcidile repair.J Am Coll Cardiol 2022:79-48.61. http://doi.org/10.1016/j.jacc.2021.11.031

708. Stol. L Weckbach LT,Karan N,Kalbacher D,Praz,Flur,Z P.et al.Invasive right trucipar and tricupal to pulmonary artery coupling in patients undergoing transcatheer edge-to-edge tricuspid valve repair.JACC Cardiovasc Imaging 2023;16:564-6. https://doi.org/10.1016/j.jc.2021.2010

90. Freyud J.,Jreyas-CsoF,2.119. Salar,Aero-Caralca-Arzeri,Es-Eveper B. Botahot,Y.et al.Benefit of isolated surgical valve repair or replacement for functional tricuspid regurgi-gatation and long-term outcomes stratified by TRI. ZP-ORE; Cour 1997; Bao: 554.452-122.https://doi.org/10.1093/eur�/heafe758

70. Thourin VH,Bonell L,Wyler von Ballmoos McM,Heaffey J,Bowhend M,Kurlansky P.et al. Outcomes of isolated trucidic valve surgery: a Society of Thoracic Surgeons

analysis and risk model. Ann Thorac Surg 2024;118:873-81.https://doi.org/10.1016/j.atracorus:2024.04.014

711. Anguita-Gaméz M, Giraldo MA, Nombela-Franco L, Eixeres Esteve A, Cuerpo G,Lopez-Mendez an Ménéz et al. Validation of the TRI-SCORE in patients undergoing surgery for isolated triscid regurgitation. Heart 2023;109:1401-6. https://doi.org/10.1136/heartjnl-2022-322067

712.Nasfz Al,Grentar M, Windor SL,Jermyn R, Shavelle DM,Tang F,et al.Empagifllozin effects on pulmonary artery pressure in patients with heart failure: results from the EMBRASE-HF trial. Circulation 2021;143:1673-86. https://doi.org/10.1161/circulationa.12005530

713. Soraja P, Whisenant B, Hamid M, Naik H, Makkar R, Tadros P, et al. Transcatheter re-pair for patients with tricuspid regurgitation. N Engl J Med 2023;388:1833-42. https://doi.org/10.1056/NeJMO4300525

714. Dreyfus J, Flagiello M, Bazore B, Eggenspieler F, Viau F, Riant E, et al. Isolated tricuspid valve surgery: impact of a setiology and clinical presentation on outcomes. Eur J Heart 2020:4140-37. https://doi.org/10.1093/eurheartj/haega43

15 Scotti A, Sturla M, Granada JF, Kodali SK, Coisne A, Mangieri A, et al. Outcomes of iso-lated tricuspid valve replacement: a systematic review and meta-analysis of 5,316 pa-tients from 35 studies. Eurodention 2022;18:840-51.https://doi.org/10.4244/EJl-D-22-0042

16. Chen Q, Bowdish ME, Malas J, Roach A, Gill G, Rowe G, et al. Isolated tricuspid ions: the Society of Thoracic Surgeons adult cardiac surgery database analysis. Ann Thorac Surg.2023:115.1162-70.https://doi.org/10.1016/j@thorasurcs.2022.12.041

117. Hahn RT, Wilcoff BLK, Kodali S, Birgersdotter-Green UM, Ailawadi G, Addeta K, et al.Managing implanted cardiac electronic devices in patients with severe tricuspid regur-gitation: JACC state-of-the-art review.J Am Coll Cardiol 2024;2023-2024.https://doi.org/10.1016/j.jacc.2024.02.045

718. Taramasso M, Gavonzalez M, Pozzoli A, Dreyfus GD, Bolling SF, George I, et al.Tricupus regurgitation: predicting the need for intervention, procedural success,and recurrence of disease. JACC Cardiovasc Imaging 2019;12:605-21.https://doi.org/10.1016/j.cong.2018.11.034

119 Bnehm E, Medrimer, C. Kahn U, Liebchen J, Okamoto M, Hahnel V, et al. Natural course of tricuspid regurgitation and prognostic implications. Open Heart 2021:8:0001529,https://doi.org/10.1136/openhrt-2020-001529

70. Park SJ, Oh JK, Kim SQ, L. Lo SA, Kim HJ, Lee S, et al. Determinants of clinical outcomes of surgery for isolated severe tricuspid regurgitation. Heart 2021;107:403-10.https://doi.org/10.116/136earhi-jol-2020-317715

721. McCarthy PM, Bhudia SK, Rajeswaran J, Hoercher KJ, Lytle BW, Cosgrove DM,et al.Tricupid valve repair: durability and risk factors for failure. J Thorac Cardiovasc Surg

722.Kwak JJ,Kim YJ,Kim MK,Kim HK,Kup JS,Kim KH,et al.Development of tricuspid regurgitation late after left-sided valve surgery: a single-center experience with long-term echocardiographic examinations. Am Heart J 2008;155:732-7. https://doi.org/10.1016/j.ahj.2007.11.010

723.Dreyfus GD,Corbayl P,Chanhari T. Secondary tricuspid regurgitation or dila-tation: which should be the criteria for surgical repair? Ann Thorac Surg 2005;79:127-32.https://doi.org/10.1016/j.athorocras.2004.06.057

724.Dreyfus GD,Essayh B, Benfari G, Dulguorov F, Haley SR, Dormccer C, et al.Outcome of consistent guideline-based tricuspid management in patients undergoing degenerative mitral regurgitation correction.JTCVS Open 2021:7:125-38. https://doi.org/10.1016/j.xjmon.2021.07.010

755. Kimpeis J, Ch Wu M,Afl V, Overbey JR, Moskowitz AJ, Gillinov M, et al.Concomitant tricuspid repair in patients with degenerative mitral regurgitation. N Engl J Med 2022;38:3627-39.https://doi.org/10.1056/NEjMoA2115961

227.Pennati M, DeKerchov L, Lazam S, Pasquet A, Gerber B, Vanoverschelde JL, et al.Mid-term results of a randomized trial of tricuspid annuloplasty for less-than-severe functional tricuspid regurgitation at the time of mitral valve surgery. Eur J Cardoricov: Surg 2019:55.85:1-8.https://doi.org/10.1093/ejcte/3978

722.Ailwadi G, Voisine P, Raymond S, Gelijns AC, Moskowitz AJ,Falk V,et al. Pacemaker implantation associated with tricuspid repair in the setting of mitral valve surgery: in-sights from a Cardiothoracic Surgical Trials Network randomized trial. J Thorac Cardiovasc Surg 2022;16:47-16.e5.https://doi.org/10.1016/j.itcs.2022.11.031

728. Rarnagsson S,Taha,A.Nielsen SJ,Amable A,Geirsson A,Krane M,et al.Pacemaker implantation following tricuspid valve unanoplasty. JTCVS Open 2023;16:276-89.https://doi.org/10.1016/j.jxou.2023.08.017

729. Ibarne A, Albladw SA, Mohzowitz AJ, Ailawadi G, Badhwar V, Gillinov M, et al.Permanant pacemaker implantation and long-term outcomes of patients undergoing concomitant mitral and tricuspid valve surgery.J Am Coll Cardiol 2024:83:1656-68.https://doi.org/10.1016/j.jsc.2024.02.042

130. Kassab J, Harb SC, Desai YJ, Gillin Nov AM, Layoun H, El Dahahd J, et al. Incidence, risk factors, and outcomes associated with permanent pacemaker implantation following tricuspid valve surgery.J Am Heart Assoc 2024;13:e032760. https://doi.org/10.1161/j.123.032760

313. Kiewl, Kajlag, S. Anyamu A, Adams DH. Impact of concomitant tricuspid annulo-plasty on tricuspid regurgitation, right ventricular function, and pulmonary artery

96

$$\text{ ESC Guidelines}$$

hypertension after repair of mitral valve proprolus: A. J Coll Cardiol 2015;65:1931-8.https://doi.org/10.1016/j.jacc.2015.01.059

732. Chang JD,Manning WJ,Ebrile Z,Eimzenba PJ.Mtricus valve dysfunction following pacemaker or cardioverber-reflator implantation. J Am Coll Cardiol 2017:69:2331-41.https://doi.org/10.1016/j.jacc.2017.02.0258

733. von Bardelebs R, Lursz P, Soraja R,Puf, H: Tausheiro J, Tsges M, et al. Two-year-out comes for tricuspid repair with a transcatheter edge-to-edge valve repair from the transattratic TRILUMINATE trial. Circ Cardiovasc Interv 2023;16:e012888. https://doi.org/10.1016/CIRCINTERVENTIONS.122.012888

734. Lupor,Bes C.,Schmitz R.,Bekedrian R.,Nicken G.,Mollmann H. et al. Short-term outcomes of triscupic edge-to-edge repair in clinical practice.J Am Coll Cardiol 2023;82:281-91.https://doi.org/10.1016/j.jc.2023.03.008

735. Kodali SK, Hahn RT, Davidson CJ, Narang A, Greenbaum A, Gleason P, et al. 1-Year outcomes of transcatheter tricuplexic valve repair. J Am Coll Cardiol 2023:81:1766-76.https://doi.org/10.1016/j.jacc.2023.02.049

736. Kar,S Makkar,RR withSenant BK,Hamid,NNa,Kirk A,Hodt Pros,P.et al.(March 30,2025)Two-year outcomes of transchateter edge-to-edge repair for severe tricuspid regurg. 2025.1161/CIRCULATIONAHA.125.074536

737.Donal,Dreyf J.,Leusre G.,Coisne A,Rulenty,Panovet,G.,Anet et al.Transcheterage-edge to edge for severe isolated tricuspid regurgitation: The TrifrFornorized a clinical trial.JAMA 2025;333:124-32.https://doi.org/10.1014/joama.2024.21189

738 Hahn RT, Makar R, Thourani V,Huak, M. Sharma R, Haftele F, C. et al.Transchatertate transaveter反映 in severe tricuspid regurgitation. N Engl J Med 2024;392115-26.https://doi.org/10.1056/NEJMOa2401918

739. Park S6,Engtreni Y.,Varia N,Wavin O,Taralkoj,GMehta,A.The et al.Transvenous extra-tion of pacemaker and defibrator and leads the risk of triculose valve regurgitation.JACCC Clin Electrophysiol 2018;4:1421-8.https://doi.org/10.1016/j.jacep.2018.07.011

410 Abhoushn J,Cabalkal AK,Au,Li Deshim D,Testa L,Lab et al.,Transcatheter valve-in-ring implantation for the treatment of residual or recurrent tricuspid dysfunction after prior surgical repair. JCC Cardovici 57:2017-63-63. https://doi.org/10.1016/j.jcin-2016.10.036

741. Chen S, Dershowitz L, George I.Transchete valve implantation for degenerated tri-cuspid bioprostiophes and failed trucipid ring. Ann Cardorophus Surg 2021:10615-75.https://doi.org/10.1016/j.jcin-2021-tv11-

742.Rao VN,Giczewska A,Chiswell K,Felker GM,Wang A,Glower DD,et al.Long-term outcomes of phenocrins in severe trucidup regurgitation. Eur Heart J 2023:44:1910-23.https://doi.org/10.1093/eurheart/ehad/133

74. Van de Veire NR.Branel,Dajvel de Verstehtm_G DM in Rada,RJlaat,RJet al.Tricuspid annuloplasty prevents right ventricular dilatation and progression of tricuspid regurgi-tation in patients with tricuspid annular dilated undergoing mitveal valve repair.J Thorc and Spectroves: Surg 2011:441:31-995:https://doi.org/10.1016/j.cps.2010.0505

74. Brescia AA, Ward ST, Watt TMF, Rosenblom LM, Baker M, Khan S, et al. Outcomes of guideline-directed concomitant annuloplasty for functional tricuspid regurgitation.Am Thorcova Surg 2020;109:127-32;https://doi.org/10.1016/j.acpsurator.9079.034

745. Hammandi, Smith, RL Yan, WHY, Grayburn Pa, Vasudane A, George TJ, et al. Outcomes of Outcomes of isolated tricuspid valve surgery have improved in the modern development of Thoracans Surg 2019;Rur108-11:5.https://doi.org/10.1016/j.athoracsurac.2019.03.004

746. Russo,Di Muo,Maraito G,Lio,Beraretta,Paramo was,et al.Outcome of patients undergoing isolated tricuspid repair or replacement surgery. Eur J Cardioarachos Surg.2022:62:ezac230.https://doi.org/10.1016/j.acs.1003/ae:ecz230

747. Abdelar B, Kenawy A, Zacharias J. Minimally invasive tricuspid valve. JorThosar, D 2021;138:1982-92. https://doi.org/10.1023/jjs.20-1331

74. Taramo Massen,Benfari G,Van der Bij P,Alessandrini,HAttinger-Toller,A Biasco,L et al.Transceterway versus medical treatment of patients with symptomatic severe tricuspid regurgitation.J Am Coll Cardiol 2017,794:2998.https://doi.org/10.1016/j.jacc.2019.08.029

749. Kodal S, Hahn RT, Makr R, Makar M, Davidson CJ, Puthumanich J, et al. Transferential tricuspidal tricupole valence and one-year outcomes: the TRISCEND study. Eur JHT 2023;44:4862-73.https://doi.org/10.1093/eurheart/hehad667

750. Donal E,Stiges P,Manis V,Schelerou LG,Moll R.Amolman H.The Characterization of tricuspid valve anatomy and coapptation gap in subjects receiving tricuspid cat-eter edge-to-edge repair: observations from the bRIGHT TriClip study. J Am Soc Edchocology 2024:37:397-404.https://doi.org/10.1016/j.choo.2023.12.002

751. Wild MG, Low K, Rosch S, Gercek M, Higuchi S, Massberg S, et al. Multicenter experi-ence with the transchatriate leaflet repair system for symptomatic tricuspid regurgita-tion. JACC Cardiovasc Interv 2022;15:1352-63. https://doi.org/10.1016/j.jcin.2022.05.041

752.Saralle A,Balmin, P.Lorica on Ponton, D.Zles-Ronzolano R,Gimnez-Roire J,et al.Repair of rheumatic tricuspid valve disease: predictors of very long-term mortality and reoperation. Ann Thorac Surg 2010:90:503-8. https://doi.org/10.1016/j.achvoraus 2010.03105

753. Saran N, Renard JA, Said SM, Greason KL, Pochettino A, Stulak JM, et al. Long-term outcomes of patients undergoing trivadic surgery valve. Eur J Cardioaric Surg 2019;56:95-8.https://doi.org/10.1093/ejctz/0801

754. McElhinney DB,Cabalaka AK,Aboulhosn JA,Eicken A,Boudjemine Y,Schubert S,et al.Transchatertric tricuspid valve-in-valve implantation for the treatment of dysfunctional surgical bioprostatic valves: an international, multicenter registry study. Circulation 2016;131:1382-91.https://doi.org/10.1161/CIRCULATIONAHA.115.019533

75. Pereyara M,Fina JM,Chao CJ,Ayoub C,Arsanjani R,Percutaneous transcatheter pul-monary and tricupid valve preplacements in a patient with carcinoid heart disease. Eur Heart J) Cep Res 2023;73yad511.https://doi.org/10.1093/ehrcy/tyad511

75. Connolly HM,Schaff HV,Abel MD,Rubin J,Askew JW,Li Z,et al.Early and late out-comes of surgical treatment in carcinoid heart disease. J Am Coll Cardiol 2015;66:21989://https://doi.org/10.1016/j.jacc.2015.09.014

75. Yunokki N, Narukuo T, Itoh A, Ohashi J, Fujimoto K, Shirai N, et al. Percutaneous trans-catheter balloon valvoplasty for bioprosthetic tricuspid valve stenosis. Circulation 2006;114:558-9.https://doi.org/10.1161/CIRCULATIONAHA.106.618611

758. Triboullioy C, Bohotov B, Kubala M, Ruschitzka F, Pescupe B, Wendler O, et al.Characteristics, management, and outcomes of patients with multiple native valvular heart disease: a substudy of the EUROObservational Research Programme Valvular Heart Disease Survey. Eur Heart J 2022;43:2756-66. https://doi.org/10.1093/eurul@2029

759. Lung B,Baron G,Tornos P,Gohlke-Barwolf C,Butchart EG,Vahanian A. Valvular heart disease in the community a European experience. Curr Probi Cardiol 2007;32:609-61.https://doi.org/10.1016/j.cpc.2001.07.002

60.Cutter DJ, Schaapold M, Darby SC, Hauptmann M, van Nimwegen FA, Krol AD, et al.Risk of valular heart disease after treatment for Hodgkin lymphoma. J Natl Cancer Inst 2015;107:008.https://doi.org/10.1093/jnci/djv008

761. Unger P, Pibor Pribot, Tubrolovic C, Lancollotti P, Maisason F, lung B, et al. Multiple and mixed valular heart diseases.Circ Cardiovasc Imaging 2018:11:e007862. https://doi.org/10.1161/CIRCIMAGING.118.007862

72. Ameomar Mansar N, Delgado Sh, Shah DJ, Pellikka P, Bax JJ,Treibel T,et al. Valvular heart disease: shifting the focus to the myocardium. Eur Heart J 2023;44:28-40. https://doi.org/10.1093/erheac/choi540

763. de Marchy SF, Windecker S, Aeschbacher BC, Seiler C. Influence of left ventricular re-laxation on the pressure for aortic regurgitation. Heart 1999;82:607-13.https://doi.org/10.1161/hrt.82:507.607

764. Unger P.,Chibrouloytou C.Aortic stenosis with other concomitant valvular disease: aortic regurgitation, mitral regurgitation, mitral stenosis; or tricuspid regurgitation. Cardiol Clin 2020;38:33-46. https://doi.org/10.1016/j.ccl.2019.09.002

65. Uner P, Cavelstb A, M. Mixed Aortic valve disease: a diagnostic challenge, a prognostic threat. Structural Heart 2020;4:468-74. https://doi.org/10.1080/24748706.2020.

766 FlaskampfFA,Weyman AE,Gillam L,Liu CM,Abascal VM,Thomas JD.Aortic regur-ing shortens Doppler pressure half-time in mitral stenosis: clinical evidence, in vi-tro simulation and theoretic analysis. J Am Coll Cardiol 1990;16:396-404. https://doi.org/10.1016/j.735-109(109)50952-1

76.Tribouilloy C, Shen WF, Rey JL, Adam MC, Lesbre JP. Mitral to aortic velocity-time in-tegral ratio a non-geometric pulsed-Doppler regurgitant index in isolated pure mitral regurgitation. Eur Heart J 1994;15:1335-9. https://doi.org/10.1093/oxfordjournals.

76.Benfari G, Clavel M,A Natoi S, Maffeis C, Vassanelli C, Enriquez-Sarano M, et al.Concomitant mitral regurgitation and aortic stenosis: one step further to low-flow preserved ejection fraction aortic stenosis. Eur Heart J Cardiovasc Imaging 2018;19:569-73.https://doi.org/10.1016/j.jcin.17exj 1769

769.Mohan JC,Mukherjee S.Kumar A,Arora R,Patel AR,Pandian NG. Does chronic mitral regurgitation influence Doppler pressure half-time-derived calculation of the mitral valve area in patients with mitral stenosis? Am Heart J 2004;148:703-9. https://doi.org/10.1016/j.2013.12.04

770.Hauge Systen, Res-Eutters ME, Person R,Abebe S,Mekonnen D,Nega B,et al.The importance of concomitant mitral regurgitation for estimates of mitral valve area by pressure half time in patients with chronic rheumatic rheumatic heart disease. Int J Cardiol 2024;398:131600.https://doi.org/10.1016/j.icj.2023.131600

771.Dahou A,M.,Jagel M.,Capoulade R,Barko PE,Bergler-Klein J.,et al.Tricuspid regurgitation is associated with increased risk of mortality in patients with low-flow low-gradient or stenosis and reduced ejection fraction: results of the multicenter TOPAS study(True or Puesoe Vierak Stenosis). JACC Cardiovasc Interv 2015;88-986 https://doi.org/1016/j.jcin.2014.08.019

77. Shiran A, Sagje A. Tricuspid regurgitation in mitral valve disease: incidence, prognostic implications, mechanism, and management. J Am Coll Cardiol 2009;53:401-8. https://doi.org/10.1016/j.jacc.2008.09.048

733. Naeje R, Badagliac R. Theaore overloaded right heart and ventricular interdependence.Cordavescas Res 2017:1148:1475.https://doi.org/10.1093/cvr/cxv160

747. Furukawa A, Abe Y, Ito K, Ho Hosogi S, Yamamoto K, Ito H. Mechanisms of changes in functional mitral regurgitation by preload alterations. J Cardiol 2018;71:570-6.https://doi.org/10.1016/j.jc.2017.12.005

75. Wunderlich NC, Beigel R, Sigel R, J. Management of mitral stenosis using 2D and 3D 1016/j.jcm.2013.07.008

ESC Guidelines

97

776. Cho J, Lee SE, Jong H, Chang J. Demistants of clinical outcomes in patients with mixed mitral valve disease. Echocardiography 2020;37:1164-70. https://doi.org/10.111/echo.14673

777.Pawade T, Sheth T, Zheng Zutierrez D, Eweck M, Cravel C, Ravel X A.Why and how to measure aortic val calcification in patients with aortic stenosis. JACC Cardiovasc Imaging 2019;12:1835-48.https://doi.org/10.1016/j.jcm.2019.01.045

779. Bandera F, Generant,P.,Gelperino,G. Garmao A, Garla B, Alvarez O, et al. Mitral re-gurgitation in heart failure: insights from CPT combined with exercise echocardiog-rphy. Eur Heart J. Cardiovasc Imaging 2017;18:296-303.https://doi.org/10.1093/ehci/jew096

780. Bisssor N,Shanahan L,Wee YS,Stewart R,Lowe B,Kerr A,et al.The role of natri-uretic peptides in patients with chronic complex(mixed or multiple) heart valve di-ease. Gestard Heart Fail 2010;16:50-4.https://doi.org/10.1111/j.1751-7133.2009.00132.x

781.Myerson SG.CMR in evaluating valular heart disease: diagnosis, severity, and out-comes. JACC Cardiovascular Imaging 2021;14:2020-32. https://doi.org/10.1016/j.cmg.2020.09.029

782.Grafton G.CasinoTM,Cosirry TM,Pen Ashur C,D. Asharu K.Coelling TM: Resting oxygen consumption and heart failure: importance of measurement for determination of cardiota output with the use of the Fick principle. J Card J 2020;26:664-72. https://doi.org/10.1016/j.cardfallar.2019.02.004

783. Singh AD,Mian A, Devasenapathy N, Guyat G,Karthikeyan G. Percutaneous mitral commissoratory versus surgical commissoratory for rheumatic natal stenosis a systematic review and meta-analysis of randomised controlled trials. Heart 2020;106:104-101.https://doi.org/10.1136/heartjni-2019-319506

784. Winter MP, Bartjo, PE, Kricid A. Gatterier C. Dora,C. Nescche, et al. Adaptive devel-opment of concomitant secondary mitral and tricuspid regurgitation after transcath-eter aortic valve replacement. Eur Heart J Cardiovascular Imaging 2021:22045-53.https://doi.org/10.1093/ehjci/ea106

785. Khan F,Okuno T,Malebranche D,Lanz,JapZ,Frosttecky S,et al.Transcatheter aortic therapy replacement in patients with multivuralular heart disease. Jaccard Cardiovasc Intervar in 2020;13:1504-13.https://doi.org/10.1016/j.jc.2020.032.05

786.Adamo M,Pagnes M,Ghizzoni G,Estée-Lureo R,Raposeasir-Roubin S,Tomasoni D,et.Evolution of tricuspid regurgitation after transchate edge-to-edge mitral valve repair for secondary mitral regurgitation and its impact on mortality. Eur J Heart Fail 2022:24:2175-84.https://doi.org/10.1002/ijefh.2637.

787. Kawr R.,Bladosi C.,Speaker M, Trachendorf BM, Tyriev N, Mete C, et al. Predictors and prognostic relevance of tricusptid patterns in activated and myticleal mirror edge-to-edge mirror and mitralvide test. April Nervountent 2021;17:827-34.https://doi.org/10.4244/ej-d-201094

788.Mehr K,Maram T.,Naramamo T.,Oumarr T.,Schneider S.,Lurz P.,et al. Combined supland and mitral versus isolated mitral valve repair for severe MR and TR: an analysis from the TriValve and TRAMI registries. JACC Cardiovasc Tier 2003;153-54:https://doi.org/10.1016/j.jcin.2019.10.023

789. Besler, C.Bazek,S.Rommel KP,Nacack,T von Roader M, Lueckle et al. Combined triral and tricuspid versus isolated mitral valve transcatheter edge-to-edge repair in patients with symptomatic valve regurgitation at high surgical risk. JACC Cardiovasc Intervar 2018;11:1142-51.https://doi.org/10.1016/j.jc.2014.08.0140

79. Egbe AC, Luis SA, Padang R, Warnes CA. Outcomes in moderate mixed aortic valve disease: is it time for a paradigm shift? J Am Coll Cardiol 2016;67:2321-9. https://doi.org/10.1016/j.jacc.2016.03.509

791. Egbe AC, PotueraJc,T. Warnes CA. Mixed aortic valve disease: midterm outcome with predictors of adverse events. Eur Heart J 2016;37:2671-8.https://doi.org/10.1016/j.jacc.2013.059

792.Zilzersab, R. Gabriel, H. Schemper, Z. Mahler, Z. Cerny M, Maurer, G et al. Outcome of combined stenotic and regurgant or aortic valve disease. J Am Coll Cardiol 2013:168-1495.95.https://doi.org/10.1016/j.jacc.2012.11.070

793.zao ISa, Desai Myu, Kapadia SR, Krishnaswamy A, Rodriguez LL, Grimm RA, et al.Long-term outcomes in patients with mixed aortic valve disease and preserved left ventricular ejection fraction.J Am Heart Assoc 2020;9e014591.https://doi.org/10.1161/j.119.1491551

79.Sajo I,Yaza N,Conc Z,Desri M, Johnston D, Roselli E, et al. Left ventricular non-gitudinal strain in characterization and outcome assessment of mixed aortic valve dis-case phenotypes. JACC Cardioscovim Imaging 2021;14:1324-34.https://doi.org/10.1016/j.cmg.2021.01.020

795. Bernard J, Jean Bienjonetti-Boudreau D, Jacques F, Tastel L, Salunau E, et al.Prognostic utility of N-terminal pro B-type antiferroistic peptide ratio in mixed aortic valve disease. Open Heart 2023;10:e002631. https://doi.org/10.1136/openhrt-2023-002361

796. Onishi H,Nagahra T,Ulimo P,Ouchi T,Yukel Y,Hi Muhoto S,et al. Prognostic rele-vance of B-type antineuritic peptide in patients with moderate mixed aortic valve dis-ease. ESC Heart Fail 2022:9:2474-83.https://doi.org/10.1002/efh2.13946

797. Carperant AF, Pellerin M, Fuzeller JF, Randel YJ. Extensive calcification of the mitral valve anulus: pathology and surgical management. J Thorac Cardiovasc Surg 1996;111:1718-29; discussion 729-730. https://doi.org/10.1016/s0022-5223(96)7033-x

78. World Health Organization. Life Expectancy at Birth. https://www.who.int/data/gho-indicator-matared:registry/imr-details/3131(28 March 2025, date last accessed).

799. Johansson I, Berz A, Kovalova T, Balasubramanian K, Fukusaka B, Lynn MJ, et al.Outcomes of patients with a mechanical heart valve and poor anticoagulation control on warfarin. Thromb Homemost 2024;124:613-24. https://doi.org/10.1055/s-0043-1778278

80. Persson M,Glaser N,Nilsson J,Friberg O,Franco-Cereceda A,Sartipy U. Comparison of long-term performance of bioprosthetic aortic valves in Sweden from 2003 to 2018.JAMA New Open 2022;962.https://doi.org/10.1001/jamanetworkopen.2022.0962

81. Jiang Y,Wang S,Bian,Chen S,Shao Y. Mechanical versus bioprosthetic aortic valve replacement in middle-aged adults: a systematic review and meta-analysis. J Cardiovasc Dev Dis 2023;10:90.https://doi.org/10.3390/jcdd10020090

802.Kim MS,Kim HR,Lee SH,Lee S,Joo HC.Aortic valve replacement in patients aged 50 to years: analysis using Korean National Big Data J Card Surg 2022;37:3623-30.https://doi.org/10.1111/joc.16908

803. Vogf G, Santarsog G, Fujita B, Frerker C, Bauer T, Beckmann A, et al. Surgical aortic valve replacement in patients aged 50-69 years:insights from the German Aortic Valve Registry(GARY). Eur J Cardiothorogic Surg 2022;6:2ezac286. https://doi.org/10.1093/ects/azec 286)

804. Glaser N,Jackson V,Holzmann MJ,Franco-Cereceda A,Sartipy U.Aortic valve re-placement with mechanical vs. biological prostheses in patients aged 50-69 years.Eur J Heart 2016;37:658-https://doi.org/10.1093/eurheart/ehv580

806. KyoseT,AI, Suzumura EA,Laranjeira L,Buehler AM, Santo Jae,Berrwanger O,et al.Comparison of biological and mechanical prostheses for heart valve surgery: a system-atic review of randomized controlled trials. Arq Bras Cardiol 2019;11:292-201.https://doi.org/10.5933/abc.20180272

806. Bouhroul, G. Loneimem A, Porier N, Cartier R, Demers P, Perrault LP, et al. Impact of the learning curve on early outcomes following the Ross procedure. Can J Cardiol 2017;33:493-500.https://doi.org/10.1016/j.cca.2018.10.1016/j.cca.2016.11.014

Tazasis PD,TravonsigD. Vontros,D.,Vitrosok D,Vitrosok E,Mylonas KS,SáMP,Ikonomidis JS,et al.Mechanical versus bioprotic valve for aortic valve replacement: systematic review and meta-analysis of reconstructed individual participant data. Eur J Cardiothoros Surg 2022:6zec268.https://doi.org/10.1093/ejcets/ezac268

80.Leverine DB,Witberg G,Levi A,Landes U,Schwartz N,Shiran A,et al.Mechanical vs bioprostatic toric valve replacement in patients younger than 70 years of age: a haz-ard ratio meta-analysis. J Cardiol 2022;38:355-64. https://doi.org/10.1016/j.cja.2021.12.008

809. YuJ,QiaoE,Wang W.Mechanical or biologic prostheses for mitral valve replacement:a systematic review and meta-analysis. Clin Cardiol 2022;45:701-16.https://doi.org/10.1012/c.23854

80. Yanagawa B, Lee J, Luez Oujin, M Bagai A, Cheema A, Verma S, et al. Mitral valve pros-thesis choice in patients<70 years: a systematic review and meta-analysis of 20219 patients; J Card Surg 2020;35:818-25. https://doi.org/10.1111/jocs.14478

811. Ahmed A, Awad AK, Varghese KS, Sehgal VS, Hisham K, George J, et al. Bioprosthetic versus mechanical valves for mitral valve replacement in patients<70 years: an up-dated pairwise meta-analysis. Gen Thorac Cardiovasc Surg 2024:72:95-103. https://doi.org/10.1007/s11748-023-01956-1

812. Capodano D, Petronio AS, Prendergast B, Elchaninoff H, Vahanian A,Modine T, et al. Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions(EAPCl) endorsed by the European Society of Cardiology(ESC) and the European Association for Cardio-Thoracic Surgery(EACTS). Eur Heart J 2017;38:3382-90. https://doi.org/10.1093/eurphat1/ehx303

813. Meskin M, Dimas A, Votta E, Jaworek M, Fusini L, Muratori M, et al. A novel multipara-metric score for the detection and grading of prosthetic mitral valve obstruction in cases with different disc motion abnormalities. Ultrasound Med Biol 2019;45:1078-20.https://doi.org/10.1016/j.ultrasmedbio.2019.03.011

81. Passaglia PG, Le and Souma MR. Early postoperative bridging antic oagulation after mechanical heart valve replacement: a systematic review and meta-analysis.J.Thromb Homemost 2015;13:1557-67.https://doi.org/10.1111/jth.13047

81.56. Li BX, Liu, Li, Sun, Sun W, Li YM, et al. Comparison of different bridging antic-aogulation therapies used after mechanical heart valve replacement in Chinese patients-aproous therapy used after mechanical heart valve replacement in Chinese patients$$\text{-a prospective cohort study. J Cardiothorac Surg 2020; 15:40. https://doi.org/10.1186/$$130190-0208-14.806.

816. To Eu, Luo YL, Tao Z, Wan L A meta-analysis of bridging anticoagulation between low molecular weight harpine and heparin. Medicine(Baltimore) 2020;99:e18729. https://doi.org/10.1097/M.100000000000000018729

81. Baudet EM, Puel, V McBriode J, Grimmao J, Roques F, Clerc F, et al. Long-term results of valve replacement with the St. Jude Medical prosthesis. J Thorac Cardiovasc Surg 1995;109:85-70.https://doi.org/10.1016/s00222-5223(95)70309-8

98

$$\text{ ESC Guidelines}$$

818. Massel DR, Little SH. Antinode at antiagulation for patients with prosthetic heart valves. Cochrane Database Syst Rev 2013;2013:CD003464. https://doi.org/10.1002/14651858.CD003464.pub2

819. Torella,Morel and Chiodin,P.Franculi,M.Romano,G.De Santo,L.Loowering the Intensity of oral anticoGulant therapy in patients with bilelet mechanical acidic valve replacement: results from the“LOWERING-IT” Trial. Am J Heart 2010:166171-81.https://doi.org/10.1016/j.1016/2010.0055

820. Connolly S),Pogue J,Eikboom J,Faker G,Commerger F,PNozni G,et al.Eolifent of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the qual-ity of international normalized control achieved by centers and countries as mesa-sured by time in therapeutic range. Circulation 2008;118:2029-37.https://doi.org/10.1161/CIRCULATIONAHA.107.750000

821. Eikelboom JW,Connly SJ,Brueckmann M,Granger CB,Kappetein AP,Mack MJ,et al.Dabigranas versus warfarin in patients with mechanical heart valves.NEngJ/Med 2013;369:126-14.https://doi.org/10.1065/NEM)1300165

82. Puskas JD, Gerdisch M, Nichols D, Fermin L, Rhenman B, Kapoor D, et al.Anticoagulation and antiptlate strategies after X-Non M axical aortic valve replace-ment J.Am Coll Condil 2018;2017;2177-26.https://doi.org/10.1016/j.jac.2018.03.353

823. Schitt A, von Bardebeen RS, Erhich A, Erimmera M, Beept D, Dahm M, et al.Clopidogol and aspirin in the prevention of thrombombic complications after mechanical aortic valve replacement(CAPTA). Thromb Res 20019:131-35.https://doi.org/10.1016/s0049-3848(03)00143-9

824.Wang TY,Tvenson LG,Wen J,Veksten A,Gerdisch M,Rao VU,et al.Apaxibor and warfarin in patients on an On-X mechanical aortic valve. NEJM Evid 2023;2(EVIDa230067.https://doi.org/10.1056/EVDi230067

825.Wang T,Merazard O,Dbe OMB,Lecan M,Garcia N,Cuney L et al.Drug-drug inter-actions with warfarin: a systematic review and meta-analysis. Br Clin Pharmacol 2021;87:4051-100.https://doi.org/10.1111/bcp.14833

826.Tan CSS, Lee SWH-Warfarin and food, herbal or dietary supplement interactions: a systematic review. Br J Clin Pharmacol 2021;87:352-74. https://doi.org/10.1111/bcp.14833

827. Henehan Gj, Garcia-Alimw,PMc Spencer and W.A. Perma R.,Bank Bcelare,C. Thrombology

828 Khoua,C Brunton G,Richardson M,Stokes G,Blanchard L, Burchett H,et al.Oral anticoagulations: a systematic overview of reviews on efficacy and safety, genotyping,self-monitoring, and stakeholder experiences. Syst Rev 2021:1123. https://doi.org/10.1186/s13643-02-02098-w

829 Park YK,Lee MJ,Kim JH,Lee JS,Park RW,Kim GM,et al.Genetic and non-genetic fibr-$$\text{ torce effectsorobaves.2017.02:262098-w}$$

80 Praxedes MDS,Silva JPL,DARC AAD, Viana CC,Barbica HC,Huimares NS,et al.Assessment of the relationship between the level of patient knowledge on warfarin therapy and the quality of oral anticoagulation; a systematic review and meta-analysis.PLoS One 2023;18:e289836.https://doi.org/10.1017/journal.pone.0289836

831. Marx N,Federici M,Schott K,Muller-Wieland D,Ajan RA,Antunes M1,et al.2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J 2023;44:4043-140.https://doi.org/10.1016/1093/ourhead/ehad 1923

832. Meurin P, Tabet Y, Weber R, Henaud N, Ben Driss A. Low-molecular-weight heparin as a bridging anticoagulant early after mechanical heart valve replacement. Circulation 2006;113:564-9.https://doi.org/10.1161/circulationha.105.575571

83. Ferreira, I Dos, L Tornos, P. Nicolau, I Permayer-Nauralirgo, G. Soler-Soler J. Experience with enoparcin in patients with mechanical heart valves who must without acenoucr-marol. He 2003:89:527-30.https://doi.org/10.116/136/heart.89.527

834.Calerao D,David S, Cantos A, Cortiano, P2017, F. Ferreira J. Efficacy and safety of low molecular weight heparin in patients with mechanical heart valves that systematic review and meta-analysis. J Thromb Haemost 2014;12:650-9. https://doi.org/10.1111/thish.12544

853. Pengvo,P Valoare G,Cucchini U,Molinatti M,Del Bono R,Baudo F,et al.Low-intensity oral anticoagulant plus low-dose aspirin during the first six months versus standard-intensity oral anticoagulant therapy after mechanical heart valve replace-ment: a pilot study of low-intensity warfarin and aspirin in cardiac prostheses(LIWACAP). Clin Appl Thromper CG, Frontrothj, 2013:24-81. https://doi.org/10.100296702032544

836. Mesengieses S,Fondevia CG,Frontroth J,Santarelli MT,Lazari MA.Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical synthetic heart valves.J Thorac Cardiovasc Surg 1997;113:910-6.https://doi.org/10.1016/s00225232(97)70264-2

837.Puskas J.,Gerdisch M.,Nichols D,Quinn R,Anderson R,Chenman B,et al. Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X K valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial. J Thorac Cardiovasc Surg 2014;147:1202-10; discussion 1210-1201.https://doi.org/10.1016/j.tcs.2014.0.001

838. Hanigan S,Kong X,Hayman B,Kline-Rogers E,Kaatz S,Krol G,et al.Standard versus higher intensity anticoagulation for patients with mechanical aortic valve replacement and additional risk factors for thromboembolism.Am J Cardiol 2021;159:100-6.https://doi.org/10.1016/j.cammerg.2011.08.023

389. Ray WA, Chung CP, Murray KT, Smalley WE, Daugherty JR, Dupont WD, et al.Association of proton pump inhibitors with reduced risk of warfarin-related serious upper gastrointestinal bleeding. Gastroenterology 2016;151:105-12.e1110. https://doi.org/10.1053/g.astro.2016.08.054

840.Kurlander JE,Barnes GD,Fisher A,Gonzalez J,Helminski D,Saini SD,et al.Association of anticoagulation rights and upper gastrointestinal bleeding in patients using oral antic oagulants: a systematic review and meta-analysis. Am J Med 2022;135:1231-43.e1238.https://doi.org/10.1016/j.amymed.2022.05.031

41. Crowther MA,Ageno W,Garcia D,Wang L,Witt DM,Clark NP,et al.Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Inten Med 2009;150:293-300.https://doi.org/10.7326/0003-4819-150-5-200930-300035

842. Khatib R, Ludwikowski M, Witt DM, Ansell J, Clark NP, Holbrook A, et al. Vitamin K for reversal of excessive vitamin K antagonist anticoagulation: a systematic review and meta-analysis. Blood Adv 2019:3:789-96. https://doi.org/10.1182/bloodadvances.

849. Gunther KE,Conway,GLebach L,Crowther MA.Low-dose oral vitamin K is safe and effective for outpatient management of patients with an INR>10.Thromb Res 2004;113:95:https://doi.org/10.1016/j.thromres.2004.03.004

84. Schulman S,Kearon C,Subson committee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostic medicinal products in non-surgical patients. J Thromb Haemost 2005;3:692-4.https://doi.org/10.1111/1583-7836.2005.01204.x

845. Brekmans MPA, van Ginkel K, Damsa JG, Hutten BA, Middeldorp S, Coppens M.Benefits and harms of 4-factor prothrombin complex concentrate for reversal of vita min. K antagonist associated bleeding; a systematic review and meta-analysis. J Thromb

846.Chai-Adisakis Cophus,Cills,Ciegal DM, Movilla R, Heddle N, Lorio A,et al.Protrombin complex concentrates versus fresh frozen plasma for warfarin reversal.A systematic review and meta-analysis.Thromb Haoemst 2016;116:879-90.https://doi.org/10.1160/TH16-04-0266

847.Hood,C.,Goldtenen,TJ,Refaiai,M.Bajcic,P.Goldstein B,et al.INR and vita-16. Baxol,4027:2306-13.https://doi.org/10.1182/bloodadvances.2022009015

88a.Rarose,M.,Still,TJ Refaii,M.,Mangione A,Schneider,A Durn BL,et al.Efficacy and safety of a factor-probromicthene complex concentrate in patients on vitamin K antago-nists presenting major bleeding: a randomized, plasma-controlled, phase IIlb Study.Circulation 2013;128:1234-43.https://doi.org/10.1161/CIRCULATIONAHA.13.002283

849. Erdoes,G.Koster A,Ortmann E, Meesters Ml, Bolliger D, Baryshnikova E,et al.A European consensus statement on the use of four-factor prothrombin complex con-centrate for cardiac and non-cardiac surgical patients. Anesthesia 2021;76:381-92.https://doi.org/10.1111/ana.11018151

850. Eichinger S. Reversiving vitamin K antagonists: making the old new again. Hematology Am Soc Hemotani Educ Program 2016;2016:605-11.https://doi.org/10.1182/asheducation-2016.1.605

851. Birnie DH, Healey JS, Wells GA, Verma A, Tang AS, Krahn AD, et al. Pacemaker or defibrilator surgery without interruption of anticoagulation. N Engl J Med 2013;368:2084-93.https://doi.org/10.1016/506/NEJMoA1302946

852.Di Biase,L Burkard J,Hardzong A, Santangeli P, Sanchez JE, Horton R,et al.Periprocalatic stroke and bleeding complications in patients undergoing catheter ab-lation of atrial fibrillation with different anticoagulation management: results from the Role of Couradin in Preventing Thromboembolism in Atrial Fibrillation(AF) Patients Undergoing Catheter Ablation(COMPARE) randomized trial. Circulation 2014;129:2638-44.https://doi.org/10.1161/CIRCULATIONAHA.113.006426

83. Engelen ET, Schutgens RE, Mauser-Bunshoten EP, van Es RJJ, van Galen KPM.Antifribotinalytic therapy for preventing oral bleeding in people on anticoagulants under-going minor oral surgery or dental extractions. Cochrane Database Syst Rev 2018:7:CD102697032544

854. Ghanbari H, Phar WS, Al,Ameri H, Latchamsetty R, Jongnangnsin K, Crawford T,et al. Meta-analysis of safety and efficacy of uninterrupted warfarin compared to heparin-based bridging therapy during implantation of cardiac rhythm devices. Am J Cardiol 2012;110:1482-8. https://doi.org/10.1016/j.amjcard.2012.06.057

855. Makulouolwa AK,Tewi,S Rings M.Per-operative management of ophthalmic patients on anti-bromotrophic agents: a literature review. Eye(Lond) 2019:33:1044-59. https://doi.org/10.1038/s41433-019-0382-6

856.Nagata N,Yasuragah N,Hatsui N,Hushimi K,Watanabe K,Akiyama,J et al.Therapeutic endoscopy-related Gl bleeding and thromboembolic events in patients using warfarin or direct oral anticoagulants: results from a large nationwide database analysis. Gut 2018;67:1805-12.https://doi.org/10.1136/gutjnl-2017-313999

ESC Guidelines

99

857. Dohler R, Loder D, Schlesinger T, Nassen CA, Germer CT, Wieginger A, et al.Risk-adjusted perioperative bridging anticoagulation reduces bleeding complications without increasing thromboembolic events in general and visceral surgery. BMC Anesthesirol 2023; 23:56. https://doi.org/10.1186/12871-0203-2017=

858. Shah S, Nayfeh, Hasan B, Urtecho M, Firwana S, Saadi S, et al. Peroperative man-agement of vitamin K antagonists and direct oral anticoagulators: a systematic review and meta-analysis. Chest 2023;136:1245-57. https://doi.org/10.1016/j.chest2022.11.032

85. Gigante B, Tamargo,J Agewall S, Atar D, Ten Berg J, Campo G, et al. Update on an-thrombotic therapy and body mass a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and the European Society of Cardiology Working Group on Pharmacovirus and the European Society of Cardiology Working Group on 1093/ehcp/vpae064

86. Jepsson A, Roca B, Hansson EC, Gudbajart T, James S, Kask J, et al. 2024 EACTS Guidelines on perioperative medication in adult cardiac surgery. Eur J Cardiothorac Surg 2024;67:ezaes355. https://doi.org/10.1093/ijectesae355

86. Kovsson, Mels WS, Anderson DR, Lazo-Langerr A. Keronac, C. Bates SM, et al.Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism(PEROP2): double blind randomised controlled trial. BPM 2021:373n:1205.https://doi.org/10.1136/bmj.n1205

86. Kuo HC,Lu FL,Chen JT,Cheng YG,Tam KW,Tai YH.Thromboembolic and bleed-ing risk of periprocedary bridging anticoagulation: a systematic review and meta-analysis. Clin Cardiol 2020;43:441-9.https://doi.org/10.1002/ccl.23336

86. Segal D,Yudin J,Katz S,Doukets JD,Lim,W.Spyropoulos AC.Periprocedal hep-amin bridging in patients receiving vitamin K antagonists: systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation 2012;126:1630-9.https://doi.org/10.1161/CIRCULATIONAHA.112.105221

864. Yong JW,JYang LX,Hoene,ZH You,YJ,Wang Zhou,YJ,Wang Zhou,et al.500011999 of patients receiving oral anticoagulation: a systematic review and meta-analysis. Working oral anticoagulation: a systematic review and meta-analysis. BMC Cardiovasc Disordi 2017;17:295.https://doi.org/10.1186/s12872-017-0179-7

86. Brennan J.MlEds,THzao Y,O'Brien S.,Booth B.Moldoynis R.As,et al.Ean-10-ticoagulation of bioprosthetic aortic valenter of older patients: results from the Society of Thoracic Surgeons Adult Carducary Surgery National Database J.Ml Coroll Cardi 2020;6971-7.https://doi.org/10.1016/j.jacc.2012.05.029

866. Rafiq S,Steinbruchel DA, Lillear NB, Molter CH, Lund Jr, et al. Antithrombotic therapy after bioprotrophic catalive implantation varin versus aspirin, a rando-mized controlled trial. Thromb Res 2017;1504-10.104.https://doi.org/10.1016/j.throm.2016.11.021

86. Butraru A.,Shen Teujon,T. Buber T., Baruber B.,Tirban S. Smanides and Treat-ment of early bioprosthetic malfunction in the mitral valve position due to thrombus formation.Am J Cardiol 2013;112:1439-44.https://doi.org/10.1016/j.amjcard.2013.06.014

86. Russo A, Grigioni F, Avierinos F, Freeman WK, Suri R, Michena H, et al.Trombembolóclic complications after surgical correction of mitral regurgitation inci-dence, predictors, and clinical implications. J Am Coll Cardiol 2008;51:1203-11.https://doi.org/10.1016/j.jacc.2007.10.058

869. Dang GS,TDasen|GfW,Boresh G.,Wonderh's Gondard L,Glard M,Molmann H,et al.Con-triled trial of rivarovaban after transcatheter aortic-valve replacement. N Engl J Med 2020:382-120.9-https://doi.org/10.1056/NEJMoA1911425

870.Ahalilh M, Edwards R, Puri R, Kalra A, Zamara A, Das R, Aspirin versus dual antiplatelet therapy in patients undergoing trans-faceteric aortic valve implantation, updated meta-analysis. Cardovics Drus Ther 2022:36:2793-87. https://doi.org/10.1007/s10557-021-0714-6

87. El Beze N,Himbert D,Suc G,Brochet E,Ajzenberg N,Calliau A,et al. Comparison of direct oral anticoagulants via vitamin K antagonists after transcatheter mitral valve re-placement. J Am Coll Cardiol 2024;83:334-46. https://doi.org/10.1016/j.jacc.2023.10.031

872.Carcinic AP, De Caterina R, Halperin J, Renda R, Guff CT, Trev T,�an M, et al.Edoxaban for the prevention of thromboembolism in patients with atrial fibrillation and bioprosthetic valves. Circulation 2017;135:1273-5. https://doi.org/10.1161/CRCULATIONAHA-116,026714

873.Guaraes HP, Lopes RD, de Barros E Silva PGM, Liporaceil and I, SampaioRO, Tarsotropies et F, Livor Bohn, Zerousen B with atrial fibrillation with atrial fibrillation mitral valve. N Engl J Med 2020;383:2117-26. https://doi.org/10.1056-NJea02029603

874.Philipparr, Brunet-Bernar A. Clementy N, Bouranqignn T, Mraira A, Angouvant D et,et al. Oral anticoagulation, stroke and thromboemobism in patients with atrial fibril-lation and valve bioprostes. The Loire Valley Atrial Fibrillation Project. Thromb Haoemst 2016;15105-563.https://doi.org/10.1610/TH16-011-0007

875 Shim CY,Seo, Kim JY, Lee SH, De Caterina R, Lee S, et al. Efficacy and safety of edox-aban in patients early after surgical bioprostic valve implantation or valve repair: a randomized clinical trial. Thorc Cardovers Surg 2023:165:58-6745.https://doi.org/10.1016/j.jtcvs.2021.01.127

876. Siont KC, Yao X, Gen B, Noseworthy P. RA. Direct oral anticoagants in patients with atrial fibrillation and valiar growth heart disease other than significant tristonic senosis

and mechanical valves: a meta-analysis. Circulation 2017;135:714-6. https://doi.org/10.1161/CIRCULATIONAHA.116.026793

877. Suppah M, Kamal A, Saadoun R, Baradeya AMA, Abraham B, Alsdiaw S, et al. An evidence-based approach to anticoagulation therapy comparing direct oral anticoagu-lants and vitamin K antagonists in patients with atrial fibrillation and bioprosthetic valves: a systematic review, meta-analysis, and network meta-analysis. Am J Cardiol 2023:132-50. https://doi.org/10.1016/j.amjcard.2023.07.141

87.Nijenhuis VJ, Brower J, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, et al.Anticoagulation with without clopidogrel after transcatheter aortic-valve implant-ation N. Engl J Med 2020:362:1967-70. https://doi.org/10.1056/NEJMo19a15152

879. Van Mieghem NM, Undorben M, Hengstenberg C, Mollmann H, Mehran R,Lopez-Oero D, et al. Edesoxan versus vitamin K antagonist for atrial fibrillation after TAVR.N Engl J Med 2021;385:2150-60.https://doi.org/10.1056/NEJMaa2111016

880. Collet JP, Van Belle E,Thiele H, Berti S, Lhermusier T, Manigold T, et al. Apixaban vs standard of care after transcatcheterate aortic valve implantation. The AltANTIS trial. Eur Heart J 2223:473-987. https://doi.org/10.1093/eurhearti/ehac242

81. Brouwer J, Nijnuis VJ, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, et al.Aspirin with or without clopidogrel after transcatheter aortic-valve implantation. N Engl J Med 2020;383:1447-5.https://doi.org/10.1056/NEJMoa2017815

882. Maes F,Stable E,Usia GP,Tamburino C,Pucciarelli A,Masson JB,et al.Meta-analysis comparing single versus dual antiplatelet therapy following transcatheter aortic valve implantation. Am J Cardiol 2008;182:310-50.https://doi.org/10.1016/j.amjcard.2023.18.

83. Rodes-Cabau J,Masson JB,Welsh RC,Garcia Del Blanco B,Pelletier M,Webb JG,et al.Aspirin versus aspirin plus clopidogrel as antithrombotic treatment following trans-factethe aortic valve replacement with a balloon-expandable valve: the ARTE(Aspirin Versus Aspirin and Cloidogrel Following Transcatheter Aortic Valve Implantation) randomized clinical trial. JACC Cardiovasc Interv 2017;10:1357-65.https://doi.org/10.1016/j.jacc.2012.16:1350-

84.Meupin R,Telaj,Yli,CuI,Pierre B,Corone S,Cristofini P,et al.Thromboembolic events early after mitral valve repair: incidence and predictive factors. Int J Cardiol 2008;126-45-52.https://doi.org/10.1016/j.jacc.2007.03.115

885. van der Wall SJ, Oltholsov JR, Heuts S, Klautz RJ, Tomsic A Jansen EK, et al.Antrombotic therapy after mitral valve repair: VKA or asjinti? R^23 from Thrombolysis 2018;46:47-81.https://doi.org/10.1016/j.jacc.200207.045

86. Mazurk P, Arghami A, Marcielle S, King, King KS, et al. Apixaban for anticoagulation after robotic mitral valve repair. Ann Thorac Surg 2023;115:966-73.https://doi.org/10.1016/j.camard.2023.07.045

887.Paparella D,Di Mauro Man, Biotton Worms K, Bolotin G, Russo S, CTrunio S, et al.Antipatelet versus oral anticoagulant therapy as antithrombotic prophylaxis after mitral valve repair or thorialate perfusion to due to thrombus 1016/j.tcsv.2015.12.036

88.Trevis J,Aiowah E.Which antithrombotic strategy provides the best outcomes after mitral valve repair in patients who remain in sinus rhythm? Interact Cardiovasc Thorac Surg 2022;38:085. https://doi.org/10.1093/icvivas0840

889. Mosner N, Omar A, Kaoshman SL, Lin M, Youngson E,Kent W,et al. Direct oral antic oagulants for atrial fibrillation in early postoperative valve repair or bioprosthetic re-placement.J Thorco: Cardovisc Surg 2023;168:523-32.e3. https://doi.org/10.1016/j.tcsv.2023.03.004

89. Mentias A, Saad M, Michael M, Nakla S, Menon V, Harb S, et al. Direct oral anticoa-gulents versus warfarn in patients with atrial fibrillation and valve replacement or pair.J Am Heart Assoc 2022;11:e026666. https://doi.org/10.1161/j.ahe.122.026666

91. Philippart Brunen-Bretnard A,Clementy N,Bourgunignon T,Mirza A,Babuty D,et al.Prognostic value of CHA2DS2-VASCAS score in patients with non-valvular atrial fibrillation-tion' and valaral disease: the Loire Valley Atrial Fibrillation Project. Eur Heart J 2015;3622-30;https://doi.org/10.1093/eurheart/ehv16h

Jozchim E, Barbani M, Capretti G, Stefanini GG, Hapfelmeier A, Zadrozny M, et al.Oral anticoagulant type and outcomes after transcatheter aortic valve replacement.JACC Cardoviscnt Inter 2019;12:1566-76.https://doi.org/10.1016/j.jcin.2019.03.003

93. Dider R, Lhermier T, Averuft, E, Blettanoff in H, Bre Leton H, Cayla G, et al. TAVR patients requiring anticoagulation: direct oral anticoagulant or vitamin K antagonist?JACC Cardiovasc Inten 2021;14:1704-13.https://doi.org/10.1016/j.jcin.2021.05.025

94. Tanawutwat T, Stebins A, Marquis-Gvel R, Vemapulali S, Kosinski AS, Cheng A.Use of direct oral anticoagulant and outcomes in patients with atrial fibrillation after transchateter aortic valve replacement insights from the STS/ACC TVT registry.J Am Heart Assoc 2022:11:e023561. https://doi.org/10.1161/ja.123.02561

98. VARC 3 Writing Committee: Géénareux P, Piazza N, Alu MC, Nazif T, Hahn R T, et al.Vale academic research consortium 3: updated endpoint definitions for aortic valve clinical research. J Am Coll Cardiol 2021;77:2717-46. https://doi.org/10.1016/j.acc.2021.02.038

9. Biparot P, Herrmann H, Wu C, Hahn RT, Otto CM, Abbas AE, et al. Standardized definitions for bioprotstic valve dysfunction following aortic or mitral valve replace-ment; JACC state-of-the-art review. J Am Coll Cardiol 2022;80:545-61. https://doi.org/10.1016/j.jacc.2022.06.0021

97. Kaneko T, Bapat VN, Alakhtar AM, Zaid S, George I, Grubb KJ, et al. Transcatheter heart valve explanation for transcatheter aortic valve replacement failure: a Heart

100

$$\text{ ESC Guidelines}$$

Valve Collaboratory expert consensus document on operative techniques. J Thorac Cardiovasc Surg 2024;169:878-89.https://doi.org/10.1016/j.jtcvs.2024.04.025

898. Bleiziffer S, Rudolph TK. Patient prosthetic misafter than SVAR and TAVR. Front Cardiovasc Med 2022:761917.https://doi.org/10.3389f/m.2022.761917

89.Hirji SA,Percy and ZOGK,Malcarczyk,AHarloff MT,Yazdchi F,et al.Comparison of in-hospital outcomes and readmissions for valve-in-valve transchatterc aortic valve placement; vs.reoperative surgical aortic valve replacement: a contemporary assessment of real-world outcomes. Eur Heart J 2020:41:2747-55. https://doi.org/10.1093/eurinche/ah254

90.Tam DY,To TX,Wijyseyers HC,Dav,Dir F.Drich,NOJ FRes.Transcheterat valve-in-valve versus redo surgical aortic valve replacement for the treatment of de-generated bioprosthetic aortic valve a systematic review and meta-analysis. Coheteric Cardiovasc Interv 2018;92:1404-11.https://doi.org/10.1002/ccd27686

901. Blalectiger S, Simonato M, Webb JG, Rodes-Cabau J, Pibarot P, Kornowski R, et al.thymal-outcomes after transcatheter aortic valve implantation in failed biopro-thesic valves. Eur Heart J 2020;41:2731-42.https://doi.org/10.1093/earhiaa544

92.Guerrero M, Vemulapulai S, Xiang Q, Wang D, Elid M, Cakabak A, K al. T, Thirty-day of outcomes of transcatheter mitral valve replacement for degenerated mitbroph-ses(valve-in-fave), failed surgical rings(valve-in-ring), and native valve with severe mi-tral annular calcification(valve-in-mannular calcification) in the United States: data from the Society of Thoracic Surgeons/American College of Cardiology/Transcatheter Valve Therapy Registry. Circ Cardiovasc Interv 2020;13:e008425. https://doi.org/10.1161/CIRCINTERVENTIONS119,008425

903.Eleid MF,Whisenant BK,Cabalka AK,Williams MR,Nejari M,Attias D,et al.Eout early failed bioproxyed mitral valve, which are annullo study transchateter in validation of bioproxyed mitral valve, ring anulopasty, and severe mitral annular calcifica-tion.JACC Cardiovasc Interv 2017;10:1932-42.https://doi.org/10.1016/j.jcin.2017.08.014

904. Little SH B, Papat Blur, P Eguerror M, Rajagopal V, Siegel R. Imaging guidance for transcatheter mitral valve intervention on prosthetic valves, and annular calcifi-cations.JACC Cardovision Imaging:2021:142-40.https://doi.org/10.1016/j.jcin2018.2019.027

90. Falcon JM,DeSimone JP,Brennman JM,O'Brien S,Thibalta DP,Discipino AP; Let,et al.Inidence and consequence of prosthesis-patient mismatch after surgical respiration. Ann Thorac Surg 2018;106:14-12,https://doi.org/10.1016/j.athorsarsc.

906. Lamfl W, Regerous MC, Vercwalter M, Heniger P, Bogers K, Meurs B,Prosthesis-patient mismatch predicts structural valve degeneration in bioprostetic heart valve. Circulation 2010;1212123-9.https://doi.org/10.1161/CIRCULATIONAHA-1090.912727

97.Zorn GLI, Little SH, Tadros P, Deeb G.M., Gleas TGon, He Jiser,et al. Prosthesis-pa-tient mismatch in high-risk patients with severe sticent aortic stenosis: a randomized trial of a self-expanding prosthesis. J Thorac Cardiovasc Surg 2016;151:1014-23.eas 1023e-10113.https://doi.org/10.1016/jicts.2015.10.070

908.Thoruvani VH,Abbas AE, Ternale J, Hahn RT, Makkar R, Kodali SK, et al.Patient-prosthesis mismatch after surgical valve replacement: analysis of the PARTNITE trials. Ann Thorc Surg 2024;11:1164-71. https://doi.org/10.1016/j.achar.4024.01.023

909.Tomii D,Okuno T,Heg D,Nakase M,Lanz J,Praz F,et al.Long-term outcomes of mea-sured and predicted prosthesi-pantism mismatch following transcatheter aortic valve replacement. EuroIntervention 2023;19:746-56.https://doi.org/10.4244/eijd-23-00456

910.Vriesendorp MD, De Lin Vujwaginard RAF,Head SJ,Kappetin AP,Hickey GL,Rao V,et al.The falley of indexed effective orifice area charts to predict prosthesis-patient mismatch after prosthesis implantation. Eur J Cardovic Imaging 2020;21116-22.https://doi.org/10.1093/ehjcia/jeja/0044

91. Soraja P, Bae R, Lesser JA, Pedersen WA. Percutaneous repair of paravulpros v-thetic regurgitation: patient selection, techniques and outcomes. Heart 2015:1065-763.https://doi.org/10.1136/heartjnl-2014-306270

912. Ruzi C.Hah, ReLNA R, Beresb A, Roers JC, CutitDB, De Velirec, F. Fontara G, et al. Clinical prir-ciples and endpoint definitions for parvalvular leaks in surgical surphostics.Eur JHT 2018;39:1224-45.https://doi.org/10.1093/eurieft/ehx211

913 Laplace G, Laftere, Labulex JN, Poem JN, Maclod E, Devile E, C. et al. Clinical signifi-cance of early thrombosis after prosthetic mitral valve replacement: a postoperative monocentric study of 680 patients. J Am Coll Cardiol 2004;43:1283-90. https://doi.org/10.1016/j.jacc.2003.09.064

91. Sympersky P, BDue PJ, Reol de BMJAM, Prokop M. Comparison of multidetector-row computed tomography to echocardiography and fluoroscopy for evaluation of pa-tients with mechanical prosthetic valve obstruction. Am J Cardiol 2009;104:1128-34.https://doi.org/10.1016/j.amjac.2009.05.061

951. Egbe AC, Plarsu V. Pelrikka A. Potenuche J,TiSchff. HV- Maleszweij Lj et al.Bioprostetic valve thrombosis versus structural failure: clinical and echocardiographic predictors.J Am Coll Cardiol 2015;66:2285-94.https://doi.org/10.1016/j.jacc.2015.09.022

916. Rheude T,Pellegrini C,Stortecky S,Marwan M,Xhepa E,Ammon F,et al.Meta-analysis of bioprosthetic valve thrombosis after transcatheter aortic valve implantation. Am J Cardiol 2021;138:92-9.https://doi.org/10.1016/j.amjcard.2020.10.018

917. Banke P,Lepis J.Popara,J.Yakubov SJ,Deeb GM,Gada H,et al.Bioprosthetic aor-tic valve leaflet thickening in the Evolut Low Risk sub-study. J Am Coll Cardiol 2020;75:2430-42.https://doi.org/10.1016/j.jacc.2020.03.022

918. Charkarvary T,Sondergaard L,Friedman J,De Backer O,Berman D,Kofoed KF,et al.Subclinical leafburst thrombosis in surgical and transcatheter bioprosthetic aortic valves:an observational study. Lancet 2017;389:2383-92. https://doi.org/10.1016/S0140-6736(17)30757-2

919. Makkar RR, Blanke P, Leipsi J, Thourani V, Chakravarty T, Brown D, et al. Subclinical leaflet thrombosis in transcatheter and surgical bioprosthetic valves. PARTNER 3 car-diac computed tomography substudy. J Am Coll Cardiol 2020;75:3003-15. https://doi.org/10.1016/j.jacc.2020.04.043

90.De Backer O, Dangas GD, Jialhawi H, Leipsic JA, Terkelsen CJ, Makkar R, et al.Reduced leaflet motion after transcatheter aortic-valve replacement. N Engl J Med 2020:382:130-9.https://doi.org/10.1056/NEJMoa1911426

21. Montalescot G, Redheul A.Vincent F, Desch S, De Benedictis M, Etchanfinoff H,et al Apixaban and valve thrombosis after transchateater aortic valve replacement: the ALANT45-DT randomized clinical trial substudy. JACC Cardiovasc Interv 2022;15:1794-804.https://doi.org/10.1016/j.jcin.2022.07.014

922. Ruile P, Jander N, Blanke P, Schoechlin S, Reinohl J, Gick M, et al. Course of early sub-clinical leaflet fibrosis after transchate aortic valve implantation with or without oral antogaculation. Clin Res Cardiol 2017;106:85-95.https://doi.org/10.1007/s00392-016-10325-

93.Gundus Z.,Okan M. Kalq M., Gursoy om A, Staragioglu MA, Karakoyun S, et al.Sityleft-four-stionic cardiac computed tomography in mechanical prosthetic heart valve dysfunction: thrombotas or ambinsus. Circ Cardiovasc Imaging 2015;8:e003246. https://doi.org/10.1161/CRCIPMAGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMAGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMAGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/10.1161/CRCIPMENGING.2015;8:e003246.https://doi.org/1

924. Lancelotti P. Pibbar P. Caribamers J, Edvardsen T, Delgado V, Dulgheru R, et al.Recommendations for the imaging assessment of prosthetic heart values: a report from the European Association of Cardiovascular Imaging endorsed by the Chinese Society of Echocardiography, the Inter-American Society of Echocardiography, and the Brazilian Department of Cardiovascular Imaging, Eur Heart J Cardiovascular Imaging 2016;15:589-90.https://doi.org/10.1093/ehci/jew025

925.Tanis W, Fabens J, den Brink RBA, Syromersky P, Budde RP, Chamuleau SA Differentiation of thrombus from pannus as the cause of acquired mechanical pros-thetic heart valve obstruction by non-invasive imaging: a review of the literature. Eur Heart J Cardovicos Imaging 2014;15:119-29.https://doi.org/10.1093/ehci/jet127

926.Karhikey G,Senguttuvan NB,Joseph J, Devasenaathy N, Bahl VK, Aran B. Urgent surgery compared with fibryoltic therapy for the treatment of left-sided prosthetic heart valve thrombosis: a systematic review and meta-analysis of observational studies.Eur J 2013;34:1557-66. https://doi.org/10.1093/eurheart/ehs486

927.Castilho FM, De Sousa MR, Mendonca AL, Ribeiro AL, Caceres-Loriga FM,Thrombolytic therapy or surgery for valve prosthromis thrombosis: systematic review and meta-analysis. J Thrombolytic therapy for the Hoemost 2014;12:1218-28. https://doi.org/10.1111/jth.12577

928. Chopard R,Vidocai C, Beutti M, Ismail M, Ecarnot F, Favoulet B, et al. Surgery versus thrombolytic therapy for the management of left-sided prosthetic valve thrombosis without hemodynamic compromise: a systematic review and meta-analysis.J Am Heart Assoc 2024;13:e035143. https://doi.org/10.1161/ja.134.025133

929.Ozkan M,Gundz S,Guner A,Kalcik M,Gursoy MO,Uygur B,et al.Thrombolysis or surgery in patients with obstructive mechanical valve thrombosis: a multimenter with obstructive mechanical valve thrombosis: a multienter with obstructive mechanical valve thrombosis: a multienter with obstructive mechanical valve thrombosis: a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive mechanical valve of a multienter with obstructive

90Zan M,Gundzun S,Gurroy OM,Karakoyun S,Astarcioglu MA,Kalcik M,Elat al.Ultraslow thrombolytic therapy: a novel strategy in the management of PROSThetic Mechanical flow of the prudctors and the pr edindors of outcomE: the ultra-slow PROMETEE trial. Am Heart 2015;170:409-18.https://doi.org/10.1016/j.ahj.2015.04.

913. Sadeghipov P. Saed,Saneei L,Rafiee F, Yoosefi S, Parsaeet M, et al. Fast vs. ultraslow thrombolytic infusion in patients with obstructive mechanical prosthetic valve boresbata: a pilot randomized clinical trial. Eur Heart J Cardiovasc Pharmacophorso 2022:8:668-76. https://doi.org/10.1093/ehjcvp/pvab083

931a.Karthikeyan G,Rajashekar P,Devasenapathy N, Biswas S, Kidambi B, Singal A, et al.Urgent surgery vs fibromolytic therapy for left-sided prosthetic valve thrombosis: a randomized trial. Eur 1Hert ics of Nonobstrutive therapy for left-sided prosthetic valve thrombosis: a randomized trial. Eur 1Hert ics of Nonobstrutive therapy for left-sided prosthetic valve thrombosis: a

932. Bematur L, Laffar Dr, P. Devasenathy N, Biswas S, Kidambi B, Singal A, et al.Onturbative obstruction for left-sided prosthetic valve thrombosis: a randomized obstruction. Eur 1 and 1975. http://doi.org/10.1093/eurheartj/ehaf3913932. Abelurat L, Fravord, P. Devasenathy N, Biswas S, Kidambi B, Singal A, et al.Onturbative obstruction for left-sided prosthetic valve thrombosis: a randomized obstruction. Eur 1 and 1975. http://doi.org/10.1093/ourheartj/ehaf391

933. Mutberuk-Luridam N. Rodriguez-Lomalares JF, Ferreira L, Banferas J, Teixidó G,Gutierrez-Lurez et al. Non-obstructive prosthetic heart valve thrombosis(NOPVT): really a benign entity? J Int Cardiol 2015;197:16-22. https://doi.org/10.1016/j.ijcard.2015.06.021

References

community and effect of pregnancy on events. Am J Cardiol 2011;107:96–9. https://doi. org/10.1016/j.amjcard.2010.08.061

975. Wichert-Schmitt B, Grewal J, Malinowski AK, Pfaller B, Losenno KL, Kiess MC, et al. Outcomes of pregnancy in women with bioprosthetic heart valves with or without valve dysfunction. J Am Coll Cardiol 2022;80:2014–24. https://doi.org/10.1016/j.jacc.

2022.09.019

976. van Hagen IM, Roos-Hesselink JW, Ruys TPE, Merz WM, Goland S, Gabriel H, et al. Pregnancy in women with a mechanical heart valve: data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC). Circulation 2015; 132:132–42. https://doi.org/10.1161/CIRCULATIONAHA.115.015242

977. Pfaller B, Dave Javier A, Grewal J, Gabarin N, Colman J, Kiess M, et al. Risk associated with valvular regurgitation during pregnancy. J Am Coll Cardiol 2021;77:2656–64.

https://doi.org/10.1016/j.jacc.2021.03.327

978. Hameed A, Karaalp IS, Tummala PP, Wani OR, Canetti M, Akhter MW, et al. The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am Coll Cardiol 2001;37:893–9. https://doi.org/10.1016/s0735-1097(00)01198-0

979. Hoover E, Corlin T, Lohr J, Sabol B, Yamamura Y, Jacobs K, et al. TAVR beyond fetal viability: an alternative to preterm delivery in symptomatic severe aortic stenosis. JACC Case Rep 2023;27:102104. https://doi.org/10.1016/j.jaccas.2023.102104

980. Sajja A, Dassanayake M, Morales IA, Wenger NK, Smith C, Xie J, et al. Valve-in-valve transcatheter aortic valve replacement during second trimester of pregnancy. JACC Case Rep 2023;27:102074. https://doi.org/10.1016/j.jaccas.2023.102074

981. D’Souza R, Ostro J, Shah PS, Silversides CK, Malinowski A, Murphy KE, et al. Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis. Eur Heart J 2017;38:1509–16. https://doi.org/10.1093/eurheartj/ ehx032

982. Fuchs A, Urena M, Chong-Nguyen C, Kikoine J, Brochet E, Abtan J, et al. Valve-in-valve and valve-in-ring transcatheter mitral valve implantation in young women contemplating pregnancy. Circ Cardiovasc Interv 2020;13:e009579. https://doi.org/10.1161/ CIRCINTERVENTIONS.120.009579

983. Mascherbauer J, Kammerlander A, Nitsche C, Bax J, Delgado V, Evangelista A, et al. Sex-related differences in severe native valvular heart disease: the ESC-EORP Valvular Heart Disease II survey. Eur Heart J 2024;45:3818–33. https://doi.org/10. 1093/eurheartj/ehae523

984. Cote N, Clavel MA. Sex differences in the pathophysiology, diagnosis, and management of aortic stenosis. Cardiol Clin 2020;38:129–38. https://doi.org/10.1016/j.ccl.

2019.09.008

985. Habib G, Erba PA, Iung B, Donal E, Cosyns B, Laroche C, et al. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study. Eur Heart J 2019;40:3222–32. https://doi.org/10.1093/eurheartj/ehz620

986. Avierinos JF, Inamo J, Grigioni F, Gersh B, Shub C, Enriquez-Sarano M. Sex differences in morphology and outcomes of mitral valve prolapse. Ann Intern Med 2008;149: 787–95. https://doi.org/10.7326/0003-4819-149-11-200812020-00003

987. Brown JM, O’Brien SM, Wu C, Sikora JA, Griffith BP, Gammie JS. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database. J Thorac Cardiovasc Surg 2009;137:82–90. https://doi.org/10.1016/j.jtcvs.

2008.08.015

988. O’Brien SM, Feng L, He X, Xian Y, Jacobs JP, Badhwar V, et al. The Society of Thoracic Surgeons 2018 adult cardiac surgery risk models: part 2—statistical methods and results. Ann Thorac Surg 2018;105:1419–28. https://doi.org/10.1016/j.athoracsur.2018.

03.003

989. Shan Y, Pellikka PA. Aortic stenosis in women. Heart 2020;106:970–6. https://doi.org/

10.1136/heartjnl-2019-315407

990. Voisine M, Hervault M, Shen M, Boilard AJ, Filion B, Rosa M, et al. Age, sex, and valve phenotype differences in fibro-calcific remodeling of calcified aortic valve. J Am Heart Assoc 2020;9:e015610. https://doi.org/10.1161/JAHA.119.015610

991. Capoulade R, Clavel MA, Le Ven F, Dahou A, Thebault C, Tastet L, et al. Impact of left ventricular remodelling patterns on outcomes in patients with aortic stenosis. Eur Heart J Cardiovasc Imaging 2017;18:1378–87. https://doi.org/10.1093/ehjci/jew288

992. Simard L, Côté N, Dagenais F, Mathieu P, Couture C, Trahan S, et al. Sex-related discordance between aortic valve calcification and hemodynamic severity of aortic stenosis: is valvular fibrosis the explanation? Circ Res 2017;120:681–91. https://doi.org/10. 1161/CIRCRESAHA.116.309306

993. Bienjonetti-Boudreau D, Fleury MA, Voisine M, Paquin A, Chouinard I, Tailleur M, et al. Impact of sex on the management and outcome of aortic stenosis patients. Eur Heart J 2021;42:2683–91. https://doi.org/10.1093/eurheartj/ehab242

994. Tribouilloy C, Bohbot Y, Rusinaru D, Belkhir K, Diouf M, Altes A, et al. Excess mortality and undertreatment of women with severe aortic stenosis. J Am Heart Assoc 2021;10: e018816. https://doi.org/10.1161/JAHA.120.018816

995. Hartzell M, Malhotra R, Yared K, Rosenfield HR, Walker JD, Wood MJ. Effect of gender on treatment and outcomes in severe aortic stenosis. Am J Cardiol 2011;107:1681–6.

https://doi.org/10.1016/j.amjcard.2011.01.059

996. Lowenstern A, Sheridan P, Wang TY, Boero I, Vemulapalli S, Thourani VH, et al. Sex disparities in patients with symptomatic severe aortic stenosis. Am Heart J 2021;237: 116–26. https://doi.org/10.1016/j.ahj.2021.01.021

997. Onorati F, D’Errigo P, Barbanti M, Rosato S, Covello RD, Maraschini A, et al. Different impact of sex on baseline characteristics and major periprocedural outcomes of transcatheter and surgical aortic valve interventions: results of the multicenter Italian OBSERVANT registry. J Thorac Cardiovasc Surg 2014;147:1529–39. https://doi.org/

10.1016/j.jtcvs.2013.05.039

998. Tchetche D, Pibarot P, Bax JJ, Bonaros N, Windecker S, Dumonteil N, et al. Transcatheter vs. surgical aortic valve replacement in women: the RHEIA trial. Eur Heart J 2025:ehaf133. https://doi.org/10.1093/eurheartj/ehaf133

999. Saad M, Nairooz R, Pothineni NVK, Almomani A, Kovelamudi S, Sardar P, et al. Long-term outcomes with transcatheter aortic valve replacement in women compared with men: evidence from a meta-analysis. JACC Cardiovasc Interv 2018;11: 24–35. https://doi.org/10.1016/j.jcin.2017.08.015

1000. Akintoye E, Saijo Y, Braghieri L, Badwan O, Patel H, Dabbagh MM, et al. Impact of age and sex on left ventricular remodeling in patients with aortic regurgitation. J Am Coll Cardiol 2023;81:1474–87. https://doi.org/10.1016/j.jacc.2023.02.037

1001. Kammerlander AA, Donà C, Nitsche C, Koschutnik M, Zafar A, Eslami P, et al. Sex differences in left ventricular remodeling and outcomes in chronic aortic regurgitation. J Clin Med 2020;9:4100. https://doi.org/10.3390/jcm9124100

1002. Basso C, Iliceto S, Thiene G, Perazzolo Marra M. Mitral valve prolapse, ventricular arrhythmias, and sudden death. Circulation 2019;140:952–64. https://doi.org/10.1161/ CIRCULATIONAHA.118.034075

1003. Stolfo D, Uijl A, Vedin O, Stromberg A, Faxen UL, Rosano GMC, et al. Sex-based differences in heart failure across the ejection fraction spectrum: phenotyping, and prognostic and therapeutic implications. JACC Heart Fail 2019;7:505–15. https://doi. org/10.1016/j.jchf.2019.03.011

1004. El Sabbagh A, Al-Hijji M, Wang DD, Eleid M, Urena M, Himbert D, et al. Predictors of left ventricular outflow tract obstruction after transcatheter mitral valve replacement in severe mitral annular calcification: an analysis of the Transcatheter Mitral Valve Replacement in Mitral Annular Calcification Global Registry. Circ Cardiovasc Interv 2021;14:e010854. https://doi.org/10.1161/CIRCINTERVENTIONS.121.010854

1005. Willner N, Burwash IG, Beauchesne L, Chan V, Vulesevic B, Ascah K, et al. Natural history of mitral annular calcification and calcific mitral valve disease. J Am Soc Echocardiogr 2022;35:925–32. https://doi.org/10.1016/j.echo.2022.05.007

1006. Offen S, Playford D, Strange G, Stewart S, Celermajer DS. Adverse prognostic impact of even mild or moderate tricuspid regurgitation: insights from the National Echocardiography Database of Australia. J Am Soc Echocardiogr 2022;35:810–17. https://doi.org/10.1016/j.echo.2022.04.003

1007. Mutlak D, Khalil J, Lessick J, Kehat I, Agmon Y, Aronson D. Risk factors for the development of functional tricuspid regurgitation and their population-attributable fractions. JACC Cardiovasc Imaging 2020;13:1643–51. https://doi.org/10.1016/j.jcmg.

2020.01.015

1008. Prihadi EA, van der Bijl P, Gursoy E, Abou R, Mara Vollema E, Hahn RT, et al. Development of significant tricuspid regurgitation over time and prognostic implications: new insights into natural history. Eur Heart J 2018;39:3574–81. https://doi.org/

10.1093/eurheartj/ehy352

1009. Beale AL, Nanayakkara S, Segan L, Mariani JA, Maeder MT, van Empel V, et al. Sex differences in heart failure with preserved ejection fraction pathophysiology: a detailed invasive hemodynamic and echocardiographic analysis. JACC Heart Fail 2019;7: 239–49. https://doi.org/10.1016/j.jchf.2019.01.004

1010. Dietz MF, Prihadi EA, van der Bijl P, Fortuni F, Marques AI, Ajmone Marsan N, et al. Sex-specific differences in etiology and prognosis in patients with significant tricuspid regurgitation. Am J Cardiol 2021;147:109–15. https://doi.org/10.1016/j.amjcard.2021.

02.016

1011. Pfannmueller B, Eifert S, Seeburger J, Misfeld M, Borger M, Mende M, et al. Gender-dependent differences in patients undergoing tricuspid valve surgery. Thorac Cardiovasc Surg 2013;61:37–41. https://doi.org/10.1055/s-0032-1324406

1012. Fortmeier V, Lachmann M, Körber MI, Unterhuber M, Schober AR, Stolz L, et al. Sex-related differences in clinical characteristics and outcome prediction among patients undergoing transcatheter tricuspid valve intervention. JACC Cardiovasc Interv 2023;16:909–23. https://doi.org/10.1016/j.jcin.2023.01.378

1013. Scotti A, Coisne A, Taramasso M, Granada JF, Ludwig S, Rodes-Cabau J, et al. Sex-related characteristics and short-term outcomes of patients undergoing transcatheter tricuspid valve intervention for tricuspid regurgitation. Eur Heart J 2023; 44:822–32. https://doi.org/10.1093/eurheartj/ehac735

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ESC Guidelines