2025 ESC指南：心血管疾病和妊娠的管理
Keywords
Guidelines● Pregnancy● Cardiovascular● Heart failure● Arrhythmias● Genetic counselling● Risk stratification● Pregnancy heart team● Cardiomyopathies● Drugs in pregnancy● Aortic disease● Adult congenital heart disease● Peripartum cardiomyopathy● Hypertensive disorders of pregnancy● Adverse pregnancy outcomes
Table of contents
1. Preamble 7
2.Introduction 8
2.1. Why we need new Guidelines on cardiovascular disease and
pregnancy 8
2. Why these Guidelines are important $\boxed{8}$
2.3. What is new 8
2.4. What has changed 11
3. General considerations $\boxed{1}$ 1
3.1. Epidemiology 12
3.2. Physiology of pregnancy
4. The Pregnancy Heart Team 14
4.1. Concept and requirements
4.2. Pre-pregnancy counselling and family planning 14
4.2.1.Risk assessment 14
4.2.1.1. Maternal risk assessment. 14
4.2.2. Genetic counselling 14
4.2.1. Pre-natal and pre-implantation diagnosis 14
4.2.3. Reproductive technology 14
4.2.4. Contraception 21
4.2.5. Termination of pregnancy including psychological
support 21
4.3. Diagnostic methods in pregnancy 23
4.3.1. Electrocardiogram, including mobile rhythm devices 23
4.3. Echocardiography 23
4.3. Cardiopulmonary exercise testing $\boxed{2}$
4.3. Biomarkers.23
4.3.5. lonizing radiation exposure 23
4.3.5.1. Chest radiography 23
4.3.5.2. Computed tomography and nuclear medicine
imaging 23
4.3.5.3. Cardiac catheterization 24
4.3.6. Cardiovascular magnetic resonance 24
4.4. Foetal assessment.24
4.4.1.Risk of foetal/obstetric complications 24
4.4. Screening for congenital heart disease in the foetus
4.4.3. Assessing foetal well-being 24
4.4. Faoal tessment of heritable primary arrhythmias 25
4.5. Timing and mode of delivery 25
4.5.1. Timing of delivery 25
4.5.2. Induction of labour 25
4.5. Vaginal or caesarean delivery 25
4.5.4. Haemodynamic monitoring during delivery 25
4.5. Anaesthesia/analgesia 25
4.5.6. Delivery in women on anticoagulants 26
4.5.6.1. Planned delivery 26
4.5.6.2. Urgent delivery on therapeutic anticoagulation 26
4.5.6.2. Delivery on vitamin K antagonists 26
4.5.6.2.2. Delivery on heparin
4.5.6. Restarting anticoagulation after delivery 26
4.5.7. Endocarditis prophylaxis for delivery 26
4.6. Post-partum monitoring and complications. 28
4.6.1. Monitoring
4.6.2. Breastfeeding and lactation.28
4.6.3. Complications
4.6.3.1. Haemorrhage
4.6.3. Psychological reactions, post-partum depression
ESC Guidelines
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5. Drugs during pregnancy and lactation\longdots28
5.1. General principles 28
5.1. Pharmacokinetics and pharmacodynamics in pregnancy...
5.1.2. Pharmacogenetics 28
5.1. Newborn drug exposure in breast milk $\ldots$ 28
5.2. Drug classes in pregnancy 28
5.2. Anticoagulants 28
5.2.1. Vitamin K antagonists 29
5.2.1.2. Low-molecular-weight heparins $\boxed{30}$
5.2.1.2.1. Low-molecular-weight heparin dosing 30
5.2.1.2. Once-daily vs twice-daily administration.30
5.2.1.3. Unfractionated heparin 30
5.2.1.4.Fondaparinux 30
5.2.1.5. Direct oral anticoagulants 30
5.2.2. Antiplatelet treatment 31
5.2.3. Diuretics and SGLT2 inhibitors 31
5.2.4. Pulmonary hypertension 31
5.2.5. Anti-arrhythmic agents 31
5.2.6. Calcium channel blockers $\boxed{31}$
5.2. Renin-angiotensin-aldosterone system inhibitors 32
5.2.8. Lipid-lowering agents 32
5.2.9. Beta-adrenergic blocking agents 32
5.2.10.Immunospressants 32
5.2.11.Neuroactive drugs 32
5.2.12. Obstetric drugs in patients with cardiovascular disease..32
5.3. Internet databases $\ldots$ 32
5.4. List of drugs 32
6. Pregnancy in women with cardiomyopathies and primary
arrhythmia syndromes $\longdots$
6.1. Cardiomyopathies $\underline{34}$
6.1. Cardiomyopathies 34
6.1.2. Arrhythmogenic right ventricular cardiomyopathy
6.1.3. Hypertrophic cardiomyopathy $\boxed{34}$
6.1.3.1. Treatment of hypertrophic cardiomyopathy in pregnancy 34
6.1.3.2. Left ventricular outflow tract obstruction 34
6.1.4. Hypertrabeculation of the left ventricle 35
6.1.5. Labour and delivery in cardiomyopathies 35
6.2. Primary arrhythmia syndromes 35
6.2.1. Long QT syndrome 35
6.2.2. Brugada syndrome 36
6.2.3. Catecholaminergic polymorphic ventricular
tachycardia $\longdots$ 36
6.2.4. Short QT syndrome 36
6.2.5. Labour and delivery in primary arrhythmia syndromes....36
7. Peripartum cardiomyopathy
7. Epidermiology 37
7. Mechanisms
7.3. Diagnosis and clinical interventions 37
7.4. Outcomes
8. Pregnancy in women with aortopathies 39
8.1. Women with hertablethar thoracic actic disease 39
8.1.1. Marfan syndrome 40
8.1.2. Loeys-Dietz syndrome 40
8.1.3. Vascular Ehlers-Danlos syndrome 40
8.1.4. Non-syndromic heretthetic thoracic aic diseases.40
8.1.5. Aortic disease with no identifiable(likely) pathogenic
variant $\longdots$ 40
8.2. Turner syndrome...40
8.3. Bicuspid aortic valve disease 40
8.4. Aortic aneurysms other than root or ascending aorta $\boxed{41}$
8.5. Aortic dissection $\ldots$ 41
8.6. Management $\ldots$ 41
8.7. Cardiac surgery during pregnancy 42
9. Pregnancy in women with known congenital heart disease 43
10.Pregnancy in women with pulmonary arterial hypertension $\boxed{47}$
10.1. Pre-existing pulmonary arterial hypertension $\boxed{47}$
10.1. Matalm and foetal risk 47
10.1.2. Counselling and contraception 47
10.1.3. Management during pregnancy 47
10.2. New diagnosis in pregnancy $\longdots$ 48
10.3. Delivery in women with pulmonary arterial hypertension...
10.3.1. Peri- and post-partum monitoring $\longdots$
11.Venous thromboembolism in pregnancy and post-partum 48
11. Epidemiology and maternal risk 48
11.2. Risk factors for pregnancy-related venous thromboembolism 48
11.3. Prevention of venous thromboembolism. 49
11.3. Pregnancy women with no prior indications for long-term
anticoagulation 49
11.3.2. Pregnant women with prior indication for long-term
anticoagulation $\longdots$ 49
11.4. Management of acute venous thromboembolism. 49
11.4.1. Clinical presentation and diagnosis 49
11.4.1.1. Deep vein thrombosis 49
11.4.1.2. Pulmonary embolism $\ldots$ 50
11.4.1. Treatment of venous thromboembolism in pregnancy...50
11.5. Management of delivery and the post-partum period 52
12.Pregnancy in women with acquired heart disease 52
12.1. Acute chest pain in pregnancy $\ldots$ 52
12.2. Coronary artery disease 52
12.2.1. Acute coronary syndrome $\ldots$ 52
12.2.1.1. Coronary artery disease epidemiology and aetiology
12.2.1. Presentation and diagnosis 52
12.2.1.3. Pregnancy-associated spontaneous coronary artery
dissection $\boxed{54}$
12.2.2. Coronary artery interventions $\longdots$
12.2.3. Chronic coronary syndromes in pregnancy $\ldots$ 54
12.2.4. Management and delivery $\longdots$ 54
12.3. Hypertensive disorders 55
12.3.1. Definition and classification of hypertension in pregnancy
13.2.1.1. Pre-eclampsia/eclampsia 56
12.3.2. Diagnosis and risk assessment.56
12.3.2.1. Blood pressure measurement 56
12.3.2.2. Laboratory tests 56
12.3.3. Management of hypertension in pregnancy 56
12.3.3.1. Non-pharmacological management $\boxed{56}$
12.3.3.2. Pharmacological treatment $\boxed{57}$
12.3.3.2.1.Mild hypertension (BP 140/90-159/109 mmHg)
13.2.3.2. Pre-eclampsia 57
12.3.3.2.3. Severe hypertension (BP≥160/110 mmHg) $\ldots$ 60
12.3.4. Hypertension and delivery $\longdots$ 60
12.4. Arrhythmias $\longdots$ 61
12.4.1. Supraventricular arrhythmias $\longdots$ 61
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ESC Guidelines
12.4.1.1. New-onset narrow QRS tachycardia 61
12.4.1.2. Atrial fibrillation including anticoagulation 62
12.4.1. Pre-existing supentraventricular tachycardia 63
12.4.2. Ventricular arrhythmias 64
12.4.3. Cardioversion, ablation, and device implantation, and
implantable cardioverter defibrillator management 64
12.4.3.1. Electrical cardioversion 64
12.4.3. Catheter ablation 64
12.4.3. Device implantation 65
12.4.3. Implantable cardioverter defibrillator management.. 66
12.4. Cardiac arrest 68
12.4.5. Bradycardia 69
12.4.5.1. Sinus node dysfunction 69
12.4.5. Atriventricular block 69
12.4.5.3. Management of sinus node dysfunction and
atrioventricular block 69
12.5. Valvular heart disease 69
12.5.1. Stenotic native valve lesions 69
12.5.1.1. Mitral valve stenosis 70
12.5.1.1. Management 70
12.5.1.1.2. Interventions
12.5.1.1.3. Delivery 70
12.5.1.1. Post-partum 70
12.5.1.2. Valvular aortic stenosis 70
12.5.1.2. Management 70
12.5.2. Regurgitant native valve lesions 70
12.5.2.1. Mitral and aortic valve regurgitation 70
12.5.2.1.1. Management 70
12.5.2.2. Arrhythmogenic mitral valve prolapse 71
12.5.2.3. Tricuspid regurgitation 71
12.5.3. Prosthetic valves 72
12.5.3.1. Bioprosthetic valves 72
12.5.3.2. Mechanical valves 72
12.5.3.1. Anticoagulation during pregnancy 73
12.5.3.2. Mechanical valve thrombosis 73
12.5.3.2. Anticoagulation during delivery in women with
mechanical heart valves 73
12.5.4. Endocarditis prophylaxis 75
12.6. Heart failure 75
12.6.1. Chronic heart failure 75
12.6.2. Acute heart failure(including cardiogenic shock) 75
12.7. Special populations 77
12.7.1. Heart transplantation 77
12.7.2. Cardio-oncology 77
12.7.2.1 Gestational cancer 77
12.7.2.2 Pregnancy in cancer survivors 78
13. Adverse pregnancy outcomes and long-term management
13.1. Adverse pregnancy outcomes 78
13.1. Post-partum hypertensive disorders
13.1.2. Gestational diabetes mellitus 78
13.1.3. Pre-term birth 78
13.1.4. Small for gestational age 78
13.1.5. Pregnancy loss and placental abruption 78
13.2. Breastfeeding 78
13.3. Women's Heart Clinics 79
14. Key messages 81
15. Gaps in evidence 82
16. What to do' and'what not to do' messages from the Guidelines
17. Evidence tables 83
18. Data availability statement 83
19. Author information 88
20. Appendix 88
21. References 89
Tables of Recommendations
Recommendation Table 1-Recommendations for counselling,nregnancy risk assessment,contraception,assisted reproductive technology, and the involvement of a Pregnancy Heart Team(see Evidence Table 1)
Recommendation Table 2-Recommendations for diagnostic methods in pregnancy(see Evidence Table 2)24
Recommendation Table 3-Recommendations for timing and mode of delivery(see Evidence Table 3)26
Recommendation Table 4-Recommendation for direct oral anticoagulants and pregnancy 31
Recommendation Table 5-Recommendations for
cardiomyopathies and pregnancy 35
Recommendation Table 6-Recommendations for primary
arrhythmia syndromes and pregnancy(see Evidence Tables 4-6) $\ldots$ 36
cardiomyopathy(see Evidence Table 7)39
cardiac surgery, and pregnancy 42
Recommendation Table 9-Recommendations for congenital
heart disease and pregnancy(see Evidence Table 8)47
Recommendation Table 10-Recommendations for pulmonary
arterial hypertension and pregnancy 48
Recommendation Table 11-Recommendations for venous
thromboembolic diseases and pregnancy(see Evidence Tables 9 and
10)52
Recommendation Table 12-Recommendations for coronary
artery disease and pregnancy(see Evidence Table 11)55
Recommendation Table 13-Recommendations for hypertensive
disorders and pregnancy(see Evidence Tables 12-17) $\boxed{60}$
Recommendation Table 14-Recommendations for
supraventricular tachycardia and pregnancy 64
Recommendation Table 15-Recommendations for ventricular
tachycardia, device implantation, catheter ablation, and pregnancy....67
Recommendation Table 16-Recommendations for cardiac arrest
and pregnancy 69
Recommendation Table 17- Recommendation for congenital
atrioventricular block and pregnancy 69
Recommendation Table 18- Recommendations for native valve
disease and pregnancy 72
Recommendation Table 19- Recommendations for prosthetic
valves and pregnancy(see Evidence Table 18)73
Recommendation Table 20)-Recommendations for chronic and
acute heart failure and pregnancy(see Evidence Table 19)75
Recommendation Table 21-Recommendations for heart
transplantation and pregnancy 77
Recommendation Table 22-Recommendations for
cardio-oncology and pregnancy 78
Recommendation Table 23- Recommendations for
long-term effects of adverse pregnancy outcomes(see Evidence
Tables 20 and 21)81
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List of tables
Table 1 Classes of recommendations $\boxed{7}$
Table 2 Levels of evidence $\ldots$ 8
Table 3 Updates of the 2025 Guidelines on cardiovascular disease
and pregnancy 9
Table 4 New recommendations $\boxed{9}$
Table 5 Revised recommendations 11
Table 6 Modified World Health Organization 2.0 classification of
maternal cardiovascular risk.16
Table 7 Pre-implantation and pre-natal options and implications
Table 8 Overview of benefits and risks of different methods of contraception in women with cardiovascular disease 21
Table 9 Predictors of neonatal events in pregnancies of women with cardiovascular disease.
Table 10 List of anticoagulation regimens and disease entities in which they are indicated $\ldots$ 29
Table 11 Dosing regimens for the commonly used
low-molecular-weight heparins 30
Table 12 Risks, monitoring, and management during pregnancy and delivery in women with congenital heart disease 44
Table 13 Reasons for antepartum/post-partum thrombophylaxis 49
Table 14 Hypertensive disorders of pregnancy 55
Table 15 Risk factors for pre-eclampsia. 56
Table 16 'What to do' and 'what not to do' 83
List of figures
Figure 1 Physiology of haemodynamic changes, and changes in
Figure 2 Central illustration. Role of Pregnancy Heart Team in pregnancy pathway. 15
Figure 3 Composition of the core and expanded case-based
Pregnancy Heart Team. 19
Figure 4 Pre-conception counselling and genetic aspects 20
Figure 5 Management of urgent delivery in women under
Anticoagulants 27
Figure 6 Choice of medication during pregnancy (left) and during
<EndOfPara>lactation and breastfeeding (right)
Figure 7 Risk factors and management of peripartum cardiomyopathy
Figure 8 Thresholds for prophylactic surgical treatment prior to pregnancy of aortic root/ascending aneurysm (above the line) and
recommended mode of delivery according to aortic diameter(below the line) 41
Figure 9 Algorithm for the diagnosis and treatment of deep vein thrombosis during pregnancy 50
Figure 10 Algorithm for the diagnosis and treatment of pulmonary embolism in pregnancy in stable (A) and unstable women (B). 51
Figure 11 Management of chest pain during pregnancy and within 6 months post-partum
Figure 12A Management of hypertension and pre-eclampsia in the emergency ward
Figure 12B Proteinia assessment and diagnosis of pre-eclampsia... 58
Figure 12C Monitoring and treatment of hypertension and pre-ecampsia
Figure 13 Arrhythmogenesis in pregnant women
Figure 14 Management of narrow QRS tachycardia in pregnant women
Figure 15 Management of atrial fibrillation and atrial flutter in pregnancy 63
Figure 16 Management of ventricular tachycardias in pregnancy $\ldots$ $\ldots$ $\ldots$ $\ldots$ $\ldots$ $\ldots$ $\ldots$ $\ldots$ $\ldots$ $\ldots$ $\ldots$
Figure 17 Management of pacemaker and implantable cardioverter
defibrillator and pregnancy $\ldots$ 66
Figure 18 Management of implantable cardioverter defibrillator
shocks in pregnancy $\ldots$ 67
Figure 19 Management of cardiac arrest in pregnancy 68
Figure 20 Valvular heart disease and pregnancy 71
Figure 21 Management of anticoagulants during the different stages of pregnancy in women with mechanical heart valves. 74
Figure 22 Management of acute heart failure and cardiogenic shock
in pregnancy and up to 6 months post-partum $\boxed{76}$
Figure 23 Multidisciplinary approach of adverse pregnancy outcomes 79
Figure 24 Algorithm for the management of new-onset post-partum
Figure 25 Algorithm for the management of adverse pregnancy
outcomes $\ldots$ 80
Abbreviations and acronyms
ACE-(I) Angiotensin-converting enzyme(-inhibitor)
ACHD Adult congenital heart disease
ACS Acute coronary syndrome
ADR Adverse drug reaction
AF Atrial fibrillation
AFL Atrial flutter
AHF Acute heart failure
AHT Aralid hypertension
ALARA As low as reasonably achievable
ALT Alyanine transaminase
AMVP Arritymic mitral valve prolapse
APOA adverse pregnancy outcomes
aPTT Activated partial thromboplastin time
ARB AGiotensin receptor blocker
ARNI Angiotensin receptor/neprilysin inhibitor
ARVC Arrhythmogenic right ventricular
cardiomyopathy
ASA ASCVD Ateriosclyalic acid
ASCVD
Atherosclerotic cardiovascular disease
AS
�rial septal defect
ASI
AST
AST
ASpartate aminotransferase
AV
Atrioventricular
AV(N)RT
Atriventricular (nodal) re-entry tachycardia
AVSD
Atrioventricular septal defect
BA.
Bicuspid aortic valve
B-blocker
Beta-blocker
b.i.
Bis in die (twice a day)
BMI
Bryod mass index
BNP
B-type natriuretic peptide
B
Bood pressure
b.p.m.
B.p.m.
BrS
Brugada syndrome
CAB
CABG Coronary artery bypass graft
CAD
Coronary artery disease
CARP GREG
Cardiac Disease in Pregnancy study II
Calcium channel blocker
CCB
CCB
Confidence interval
CMP
Cardiomyopathy
Cardiovascular magnetic resonance
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ESC Guidelines
Cardiac output
COR
Class of recommendation
CPG
Clinical Practice Guidelines
Cardiopulmonary resuscitation
CPVT
Catecholaminergic polymorphic ventricular
cTachycardia
CT
Computed tomography
cTnI
Cardiac troponin I
cTnT
Cardiac troponin T
CTPA
Computed tomography pulmonary angiography
CTRCD
Cancer-therapy-related cardiac dysfunction
Cardiovascular disease
DAPT
Dual antplatelet therapy
DCM
Dilated cardiomyopathy
DOAC
Direct oral anticoagulant
DVT
Deep vein thrombosis
ECG
Electrocardiogram
ECMO
Extracorporeal membrane oxygenation
EF
Ejection fraction
ER
EURObservational Research Programme
ERA
Endothelin receptor antagonist
ESC
European Society of Cardiology
ESH
European Society of Hypertension
FAT
Focal atrial tachycardia
FDA
Food and Drug Administration
FP
Fresh frozen plasma
GDM
Gestational diabetes mellitus
HCM
Hypertrophic cardiomyopathy
HELLP
Haemolysis, elevated liver enzymes, low platelet
count
count
HF
Heart failure
HF FrEF
Heart failure with reduced ejection fraction
HLA
Human leucocyte antigen
HR
Heart rate
HTAD
Heritable thoracic aortic disease
ICD
Implantable cardioverter defibrillator
INR
International normalized ratio
IU
International unit
IUGR
Intrauterine growth restriction
IU
Intrauterine device
i.v.
Intravenous
IVF
In vitro fertilization
LA
Left artery
LDL
Low-density lipoprotein
LDS
Loeys-Dietz syndrome
LMWH
Low-molecular-weight heparin
LQT1/2/3
Long QT syndrome type 1,2, or 3
LQTS
Long QT syndrome
LV
Left ventricle
LVAD
Left ventricular assist device
LVEDD
Left ventricular end-diastolic diameter
LVEF
Left ventricular ejection fraction
LV
Left ventricular hypertrophy
LVOT(O)
Left ventricular outflow tract (obstruction)
MACE
Major adverse cardiovascular events
MFS
Marfan syndrome
MHV
Mechanical heart valve
MINOCA
Myocardial infarction with non-obstructive
coronary arteries
MR
MRA
mWHO
NA
NDLVC
NP
NSAID
nsHTAD
NSTE ACS
NT-proBNP
NYHA
o.d.
oTTG
OR
PAH
PAP
PASP
PCI
PE
pH
p.o.
PPCM
pH
PREM
PROM
PV
QRS
RBC
RID
ROPAC
ROSC
RV
RVEF
RVH
RVOT(O)
RVOT-VT
Tachycardia
SBP
SCAD
SGA
SGLT2
SPAP
SpO2
SQS T
STEMI
SVT
TAD
TAVI
TGA
TVO
TPVI
TR
TS
TTE
UACR
UFH
Mital valve regurgitation
Mineralocorticoid receptor antagonist
Millunit
modified World Health Organization
Not applicable
Non-dilated left ventricular cardiomyopathy
Natriuretic peptide (NT-proBNP and BNP)
Non-steroidal anti-inflammatory drug
Non-syndromic heritable thoracic aortic disease
Non-ST-Elevation acute coronary syndrome
N-terminal pro-brain natriuretic peptide
New York Heart Association
Omni die (once a day)
Oral glucose tolerance test
Odds ratio
Pathogenic/likely pathogenic
Pulmonary arterial hypertension
Pulmonary arterial pressure
Pulmonary arterial systolic pressure
Percutaneous coronary intervention
Pulmonary embolism
Pulmonary hypertension
Placental growth factor
Per os(by mouth)
PPCM
Post-partum haemorrhage
Patient-reported experience measure
Patient-reported outcome measure
Pulmonary valve
Q,R,and S waves
Red blood cell
Relative infant dose
Registry of Pregnancy and Cardiac Disease
Return of spontaneous circulation
Right ventricle
Right ventricular ejection fraction
Right ventricular hypertrophy
Right ventricular outflow tract (obstruction)
Right ventricular outflow tract ventricular
tachycardia
Systolic blood pressure
Spontaneous coronary artery dissection
Small for gestational age
Sodium-glucose co-transporter-2
Systolic pulmonary artery pressure
Oxyen saturation
Short QT syndrome
ST-elevation myocardial infarction
Supraventricular tachycardia
Thoracic aortic disease
Transcatheter aortic valve implantation
Transposition of the great arteries
Tetralogy of Fallot
Transcatheter pulmonary valve implementation
Tricuspid regurgitation
Turner syndrome
Transthoracic echocardiogram
Urine albumin-creatinine ratio
UHRine albumin-creatinine ratio
ESC Guidelines
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VA-ECMO
VF
Veno-arterial extracorporeal membrane oxygenation
Ventricular fibrillation
VHD
Valvular heart disease
VKA
Vitamin K antagonist
VSD
Ventricle septal defect
VT
Ventricular tachycardia
VTE
Venous thromboembolism
WCD
Wearable cardioverter defibrillator
WHO
World Health Organization
WPW
Wolff-Parkinson-White
1. Preamble
Guidelines evaluate and summarize available evidence with the aim of assisting health professionals in proposing the best diagnostic or therapeutic approach for an individual patient with a given condition.European Society of Cardiology (ESC) Guidelines are intended for use by health professionals but do not override their individual re-sponsibility to make appropriate and accurate decisions in consider-ation of each patient's health condition and in consultation with the patient or the patient's caregiver where appropriate and/or neces-sary. It is also the health professional's responsibility to verify the rules and regulations applicable in each country to drugs and devices at the time of prescription 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. European Society of Cardiology
Policies and Procedures for formulating 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 2018.This Task Force was selected by the ESC to include professionals involved with the medical care of patients with this pathology and to in-clude patient representatives and methodologists. The selection proced-ure included an open call for authors and aimed to include members from across the whole of the ESC region and from relevant ESC Subspecialty Communities. Consideration was given to diversity and inclusion.
Guidelines Task Forces perform a critical review and evaluation of the published literature on diagnostic and therapeutic approaches including assessment of the risk-benefit ratio. Recommendations are based on major randomized trials and relevant systematic re-views and meta-analyses, when available. Systematic literature searches are conducted in cases of controversy or uncertainty to ensure that all key studies were considered. For recommendations related to diagnosis and prognosis, additional types of evidence are included, such as diagnostic accuracy studies and studies focused on the development and validation of prognostic models. The strength of each recommendation and the level of evidence support-ing it are weighed and scored according to predefined criteria as outlined in Tables 1 and 2. Patient-reported outcome measures(PROMs) and patient-reported experience measures (PREMs) are also evaluated when available as the basis for recommendations and/or discussion in these guidelines.
Evidence tables summarizing key information from relevant studies are generated to facilitate the formulation of recommendations, to en-hance comprehension of recommendations after publication, and to
Table 1 Classes of recommendations
 ESC Guidelines
Table 2 Levels of evidence
Level of evidence A
Data derived from multiple randomized clinical trials or meta-analyses.
evidence B
Data derived from a single randomized clinical trial or large non-randomized studies.
evidence C
Consensus of opinion of the experts and/or small studies,retrospective studies, registries.
reinforce transparency in the guidelines' development process. The ta-bles are published in their own section of ESC 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 re-view. A second Task Force vote on all recommendations is conducted after the final round of review and revision. For each vote, the Task Force follows ESC voting procedures and all recommendations require at least 75% agreement among voting, members to be approved.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.escardio.org/doi) and are compiled in a report published in a supplementary document with the guidelines. Funding for the development of ESC Guidelines is derived en-tirely from the ESC with no involvement of the healthcare industry.
The CPG Committee supervises and coordinates the preparation of new guidelines and approves their publication. In addition to review by the CPG Committee, ESC Guidelines undergo multiple rounds of double-blind peer review on a dedicated online review platform. The re-view is conducted by topic experts, including members from ESC National Cardiac Societies and from relevant ESC Subspecially Communities. Guideline Task Forces consider all review comments and are required to respond to all those classified as major. After appro-priate revisions, the Task Force and the CPG Committee members ap-prove the final document for publication in the European Heart Journal.
Unless otherwise stated, ESC Guidelines content refers to sex,understood 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
2.1. Why we need new Guidelines on cardiovascular disease and pregnancy
Since the previous version of these Guidelines was published in 2018,new evidence has emerged, and clinical focus has changed in various as-pects, requiring an updated discussion. These include the importance of the Pregnancy Heart Team, the modalities for pre-pregnancy counsel-ling and risk stratification, and drugs during pregnancy, lactation and/or breastfeeding, and post-partum stages.In Table 3, the most relevant up-dates are listed with their respective rationale.
2.2. Why these Guidelines are important
Cardiovascular disease(CVD) is a major cause of maternal mortality and morbidity. With these new Guidelines we wish to provide updated evidence-based guidance for patients and caregivers. Reducing maternal mortality and morbidity is a key priority of the World Health Organization(WHO).
In managing maternal and foetal health, it is essential to balance the risks and benefits of maternal and foetal therapeutic needs. Due to the scarcity of prospective or randomized studies within this field,which often cannot be performed for ethical reasons, most recommen-dations in these Guidelines are based on evidence level C. Consequently, there is an ongoing need for more registries, such as the Registry of Pregnancy and Cardiac Disease(ROPAC) and the European Surveillance of Congenital Anomalies network, and pro-spective studies to enhance our understanding in this area.
2.3. What is new
As mentioned in Section 2.1, this new version of the guidelines not only includes an update to several recommendations(Table 4) but also in-troduces a structural revision. See Supplementary data online(Table S1) for a detailed overview of the new recommendations.
Below we discuss the key updates per section, highlighting a selection of new and revised recommendations along with their rationale.
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Table 3 Updates of the 2025 Guidelines on cardiovascular disease and pregnancy
|Topic|New information|Rationale| |---|---|---| |Pregnancy Heart Teamα|Broader acceptance, dedicated section|Ensure comprehensive care throughout reproductive stagesb| |Risk stratification a.c|mWHO 2.0 classification, refined and expanded clinical categories|More data have emerged, necessitating more nuanced risk assessment for patient counselling1,2| |Clinical data and research|ROPAC3-12 and PPCM13-17 registries Cardiomyopathies Primary arrhythmia syndromes|New or updated clinical management| |Clinical scenarios|Algorithms for management of clinical situations in pregnant women|Provide practical information for the clinical cardiologist| |Genetic testing and counselling|Advancements in testing and pre-implantation procedures|Incorporation of latest management of genetic testing and counselling| |Revision of contraindications (COR III) for pregnancy in women classified as mWHO class IV|Emphasis on the critical role of comprehensive counselling by the Pregnancy Heart Team (COR I) Reproductive choices|Recognition of a woman's autonomy in making reproductive choices Promoting a detailed and transparent dialogue about the heightened risks and encouraging shared decision-making| |Adverse pregnancy outcomes (APO)|Increased focus on long-term outcomes|Evidence supports the need for thorough discussion and management of APOs ${}^{18}$|
COR, class of recommendation; mWHO, modified World Health Organization; PPCM, peripartum cardiomyopathy; ROPAC, Registry of Pregnancy and Cardiac Disease.
aSee Section 4.
bSee Figure 2.
$cSee Table 6$ .
Table 4 New recommendations
|Recommendations|Recommendations|Recommendations|Recommendations| |---|---|---|---| ||||| |Section 4. The Pregnancy Heart Team|||| |Although the concept of the Pregnancy Heart Team was previously part of the general principles, it has now been given its own dedicated section, which covers all aspects from pre-conception through to the postpartum period.|||| |A discussion by the Pregnancy Heart Team|||| |recommended for women with mWHO 2.0 class IV conditions, including a shared decision-making process for pregnancy operations,involving psychological support.|||I| |It is recommended that women with CVD of mWHO 2.0 class II-III and above are evaluated and managed by a Pregnancy Heart Team from pre-pregnancy onwards through pregnancy and post-partum.||I|C| |Measurement of BNP and NT-proBNP levels should be considered prior to pregnancy in women with HF of any aetiology, including previous PPCM, cardiomyopathy,ACHD,and PAH,and be monitored during pregnancy according to the underlying disorder and in case of new-onset or worsening symptoms.||IIa|B| |Section 5. Drugs during pregnancy and lactation|||| |Given the importance of medication use throughout this document, this section has been brought forward and revised. The former comprehensive medication table has been moved to the Supplementary data online, and we provide a summary figure(Figure 6) listing the(contra)indicated medications.|||| |Section 6. Pregnancy in women with cardiomyopathies and primary arrhythmia syndromes|||| |This section has been expanded since 2018 for advice in specific cardiomyopathies and primary arrhythmias. Vaginal delivery is recommended in most women with CMPs, unless there are obstetric indications for casarean section, severe HF (EF<30% and/or NYHA class III/IV), uncontrolled arrhythmias, or severe outflow obstruction(≥50 mmHg) in women with HCM, or in women presenting in labour on VKAs.|||| |In women with DCM and worsening of EF during pregnancy, counselling on the risk of recurrence during a subsequent pregnancy is recommended in all cases, even after recovery of LV function.|||| |It is recommended that women with HCM with symptomatic LV dysfunction(EF<50%) and or severe LVOTO(≥50 mmHg) wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.|||| |Myosin inhibitors are not recommended in women during pregnancy due to lack of safety data.||||
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|||||| |---|---|---|---|---| |Beta-blockers, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy in women with LQTS.|1|B||| |It is recommended to continue beta-blocker therapy during lactation in women with LQTS to reduce arrhythmic risk.|1|I|B|| |Pre-pregnancy dose beta-blockers of nadolol or propranolol is recommended in patients with LQT2, particularly in the post-partum period, which represents a high-risk period for life-threatening arrhythmias.|1|I|B|| |Beta-blockers, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy and lactation in women with CPVT.|1|I|C|| |Flecanide, in addition to beta-blockers, is recommended in women with CPVT who experience cardiac events, such as syncope, VT, or cardiac arrest during pregnancy.|1|I|C|| |Section 7. Peripartum cardiomyopathy||||| |We have provided a separate section on PPCM in these guidelines.||||| |Genetic counselling and testing should be considered in women with PPCM.||lla|C|| |When a reversible course of HF is assumed,treatment in accordance with HF guidelines should be considered for at least 12 months after complete LV recovery (normalization of LV volumes and EF).|lla|C||| |Section 8. Pregnancy in women with a orortopathies Since 2018, significant evidence has emerged in the context of heritable thoracic aortic disease(HTAD), supporting a more gene- and variant-based approach, which has been incorporated in this version of the guidelines. It is recommended that women with a history of aortic dissection or-surgery have pre-pregnancy counselling about the high risk by an extended Pregnancy Heart Team considering the presence and type of genetic variant, aortic morphology, growth rate, and aetiology of aortic dissection.|I|C||| |Section 9. Pregnancy in women with known congenital heart disease This section has undergone a major update based on recent reports, which have been summarized in a clear and concise table. It is recommended that all women with Fontan circulation who wish to become pregnant receive counselling from the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.|I|C||| |Section 10. Pregnancy in women with pulmonary arterial hypertension||||| |This subject is now covered in a separate section in these guidelines, in line with growing insights into management. It is recommended that women of childbearing potential with PAH wishing to become pregnant are counselled by a multiop the very high risk of pregnancy-related adverse events, encouraging a shared decision-making process about whether to become pregnant.||I|C|| |Section 11. Venous thromboembolism in pregnancy and post-partum Guidance on the involvement of an expert team and more prompt initiation of treatment are now provided in dedicated flowcharts and recommendations.In pregnant women or women in the post-partum period with suspicion of venous thromboembolism(VTE)[deep vein thrombosis(DVT) and/or PE], an immediate formal diagnostic assessment with validated methods is recommended and should not be postponed.|I|B||| |Section 12. Pregnancy in women with acquired heart disease Recommended for emergency situations are provided for acquired heart diseases in addition to the new sections on cardio-oncology and heart transplantation.||||| |Recommendations for coronary artery disease and pregnancy||||| |In pregnant women with chest pain, it is recommended to exclude life-threatening cardiovascular conditions, including PE,ACS(including SCAD), and acute aortic syndrome.|1|I|C|| |The duration of DAPT(aspirin and clopidogrel) in pregnant women undergoing coronary stent implantation is recommended to be the same as in non-pregnant women, with an individual approach considering ischaemic risk and delivery-related bleeding risks. Continuation of statins may be considered during pregnancy in women with established ASCVD.|1|I|C|| |Recommendations for hypertensive disorders and pregnancy||||| |It is recommended to aim for systolic BP<140 mmHg and diastolic BP<90 mmHg in pregnant women. It is recommended to aim for systolic BP<140 mmHg and diastolic BP<90 mmHg in pregnant women. In severe hypertension, drug treatment with i.v.labetalolur, upapidil,nicardipine, or oral short acting nifedipine or methyldopa is recommended for acute reduction in blood pressure. Intravenous hydralazine is a second-line option.||||| |Recommendations for supraventricular tachycardia and pregnancy Thererate of supraventricular tachycardia and pregnancy Thererate of acute reduction in blood pressure. Intravenous hydrahaline is a second-line option.||||| |Therapeutic anticoagulation with LMWH is recommended for pregnant women with persistent or permanent AF at elevated thrombobolic risk.||||| |Flecanide, in addition to beta-blockers, should be considered for long-term AF rhythm control in pregnancy.||||| |Recommendation for ventricular tachycardia, device implantation and catheter ablation and pregnancy||||| |When performing catheter ablation during pregnancy, the use of non-fluoroscopic mapping and navigation systems should be considered.|||||
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|Recommendations for cardiac arrest and pregnancy|||| |---|---|---|---| |Continuous manual left uterine displacement during CPR in pregnant women (≥20 weeks) with cardiac arrest is recommended to relieve|||| |aortocaval compression.|||| |It is recommended to establish i.v.access above the diaphragm to ensure that the i.v. therapy is not obstructed by the gravid uterus.|||| |It is recommended that no drugs are withheld in pregnant women with cardiac arrest due to concerns of teratogenicity.|||| |Recommendation for congenital atrioventricular block and pregnancy|||| |In pregnant women with asymptomatic congenital AV block,normal cardiac anatomy and function,a narrow QRS complex,and ventricular|||| |rate(≥50 b.p.m.) a prophylactic temporary pacemaker during delivery is not recommended.|||| |Recommendation for native valve disease and pregnancy|||| |Valve surgery during pregnancy should only be considered when there is a maternal mortality risk and other treatment options have failed.|||| |Recommendation for prosthetic valves disease and pregnancy|||| |It is recommended that a care plan documenting the agreed anticoagulant strategy (including the decision to continue VKAs or converting to therapeutic-dose LMWH in the first trimester) is in place for women of childbearing age with a MHV prior to pregnancy or as soon as pregnancy is recognized.|||| |Recommendations for chronic and acute heart failure and pregnancy|||| |Inotropes and/or vasopressors are recommended in pregnant women with cardiogenic shock with levosimandan, dobutamine, and milrinone as recommended agents.|||| |ACE-Is,ARBs,ARNIs,MRAs,ivabradine,and SGLT2 inhibitors are not recommended during pregnancy due to adverse foetal effects.|||| |Recommendations for heart transplantation and pregnancy|||| |It is recommended to postpone pregnancy until at least 1 year after heart transplantation, taking individual risk factors into account.|||| |In women with a heart transplant, it is recommended that immunosuppression serum drug levels are monitored during pregnancy every 4 weeks until the 32nd week, then every 2 weeks until the 36th week, then weekly until delivery and for 6-12 months after delivery to guide dosing.|||| |Recommendation for cardio-oncology and pregnancy|||| |It is recommended that pregnant women with cancer who require cardiotoxic cancer therapy are jointly managed by the Pregnancy Heart Team and the cardio-oncology team.|||| |Section 13. Long-term effects of adverse pregnancy outcomes|||| |This is a completely new section in the guidelines, reflecting the growing recognition of the importance of APOs.|||| |It is recommended to undertake a cardiovascular risk assessment in women with APOs, to recognize and document APOs when CVD risk is evaluated in women, and to provide counselling on the importance of healthy lifestyle choices that optimize cardiovascular health.||||
ACE-I, angiotensin-converting enzyme inhibitor; ACHD, adult congenital heart disease; ACS, acute coronary syndrome: AF, atrial fibrillation; APO, adverse pregnancy outcomes; ARB,angiotensin receptor blocker; ARNI, angiotensin receptor/nepriynisil inhibitor; ASCV, Atherosclerotic cardiovascular; AV, atrioventricular; BNP, brain natriuretic peptide; BP,blood pressure; CMP; cardiomyopathy; CPR, cardiopulmonary resuscitation; CPVT, catecholaminergic polymorphic ventricular tachycardia; CVD, cardiovascular disease; DAPT, dual antipletate therapy; DCM, dilated cardiomyopathy; DVT, deep vein thrombosis; EF, ejection fraction; HCM, hypertrophic cardiomyopathy; HF, heart failure; HTAD, heritable thoracic aortic disease; iv, intravenous; LMWH, low-molecular-weighter heparin; LQT2, long QT syndrome type 2; LQTS, long QT syndrome; LV, left ventricle; LVOTO, left ventricular outflow tract obstruction; MHV, mechanical heart valve; MRA, mineralocorticoid receptor antagonist; mWHO, modified World Health Organization; NT-proBNP, N-terminal pro-brain natriuretic peptide; NYHA, New York Heart Association; PAH, pulmonary arterial hypertension; PE, pulmonary embolism; PPCM, peripartum cardiomyopathy; SCAD, spontaneous coronary artery dissection; SGLT2, sodium-glucose co-transporter; VKA, vitamin K antagonist; VT, ventricular tachycardia; VTE, venous thromboembolism.
${}^{a}$ Class of recommendation.
${}^{a}$ Level of evidence.
<EndOfPara>of cardiovascular diseases during pregnancy. See Supplementary data online (Table S2) for a detailed overview of all modified recommendations.
2.4. What has changed
Table 5 lists the recommendations with a revised Class of Recommendation since the 2018 Guidelines for the management
Table 5 Revised recommendations
|Recommendations in 2018|Classa|Recommendations in 2025|Classa|Levelb|| |---|---|---|---|---|---| |Section 4. The Pregnancy Heart Team|||||| |Prophylactic antibiotic therapy to prevent endocardits during delivery is not recommended.|III|C|Systemic antibiotic phosphoryaxis may be considered for delivery in women at high risk.|IIb|C| |Section 6. Recommendations for cardiomyopathies and pregnancy|||||| |In patients with HCM, it is recommended that beta-blockers are continued in women who used them before pregnancy.|I|C|Continuation of beta-blockers should be considered during pregnancy in women with CMPs, with close|IIa|C|
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Section 8. Recommendations for aortopathies, cardiac surgery, and pregnancy
Pregnancy is not recommended in patients with vascular Ehlers-Danlos syndrome.
III
It is recommended that women with vascular Ehlers-Danlos syndrome wishing to become pregnant are counselled regarding the very high risk of pregnancy-related adverse events by a multidisciplinary team, considering family history, genetic variant, and previous vascular events.
Beta-blocker therapy throughout pregnancy should be considered in women with Marfan syndrome and other heritable thoracic aortic diseases.
Ila
Beta-blocker therapy throughout pregnancy and in the post-partum period is recommended in women with MFS and other HTADs.
Section 9. Recommendations for congenital heart disease and pregnancy
Patients with a systemic right ventricle(Mustard/Senning or congenitally corrected TGA), in NYHA class III/IV, systemic ventricular dysfunction(EF<40%), or severe TR should be advised against pregnancy.
Ila
It is recommended that women with a systemic RV(Mustard/Senning or congenitally corrected TGA), in NYHA class III/IV, systemic ventricular dysfunction(EF<40%), or severe TR wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.
Section 12. Recommendations for acquired heart disease and pregnancy
An invasive management strategy should be considered for NSTE ACS with high-risk criteria.
Ila
It is recommended to manage pregnant women with ACS in the same way as non-pregnant women, including diagnostic investigations and interventions.
C
Catheter ablation with electro-anatomical systems should be considered in experienced centres in cases of drug-refractory and poorly tolerated SVT.
Ila
women with recurrent, long symptomatic SVT or with contraindications to pharmacological therapies.
Balloon aortic valuloplasty should be considered during pregnancy in patients with severe aortic stenosis and severe symptoms.
Ila
In very selected symptomatic pregnant women with severe aortic stenosis not responding to medical therapy,non-surgical options such as balloon valvuloplasty or TAVI may be considered.
A bioprosthesis should be considered in young women contemplating pregnancy.
Ila
A bioprosthetic valve is recommended(over a mechanical valve) in young women contemplating pregnancy requiring a valve prosthesis.
During the second and third trimesters, LMWH with anti-factor Xa level monitoring and dose adjustment(see separate recommendations) may be considered in women who need a high dose of VKA after patient information and consent.
During the second and third trimesters until the 36th week, continuing VKAs should be considered in women with prosthetic heart valves at higher risk of thrombosis.
ACS,acute coronary syndrome;CMP, cardiomyopathy;EF,ejection fraction;HCM,hypertrophic cardiomyopathy;HTAD,heritable thoracic aortic disease;LMWH,low-molecular-weight heparin;MFS,Marfan syndrome;NSTE ACS,non-ST-elevation myocardial infarction;NYHA,New York Heart Association;RV,right ventricle;SVT,supraventricular tachycardia;TAVI,transcatheter aortic valve implantation; TGA,transposition of the great arteries; TR,tricuspid regurgitation; VKA, vitamin K antagonist.
bLevel of evidence.
3. General considerations
3.1. Epidemiology
Within high-income countries the number of pregnancies and deliveries in women with acquired, congenital, or inherited CVD is growing significant-ly.19-21 This trend originates from several factors: higher maternal age at first pregnancy, a growing number of women with congenital heart disease reaching childbearing age, and a rising prevalence of cardiovascular co-morbidities.19-21 Globally, up to 4% of pregnancies are complicated by CVD, rising to 10% when including hypertensive disorders.22-25 Maternal CVD is now the leading cause of non-obsterotic mortality in preg-nant women24,26, accounting for 33% of pregnancy-related deaths world-wide.25,27,28 In women with pre-existing CVD, up to 16% of pregnancies are complicated by CVD.29-32 Notably,68% of pregnancy-related deaths
caused by CVD are preventable.33 Women with CVD during pregnancy face higher risk of cardiac events later in life, making secondary prevention crucial.25 Adverse neonatal outcomes occur in~25% of these pregnancies in women with CVD34,35 with high rates of obstetric complications(17%)and maternal mortality/morbidity(11%).34.35 Of note, recent research in-dicates that pre-existing CVD in the mother is associated with an in-creased risk of CVD in her children, and this association is unlikely to be explained by unmeasured familial or genetic factors.36
3.2. Physiology of pregnancy
Pregnancy induces physiological logical changes in the cardiovascular system to meet the increased metabolic needs of the mother and foetus(Figure 1).These changes occur from the early stages of pregnancy onward. Starting at 6 weeks of gestation, stroke volume and cardiac output(CO) increase
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 Figure 1 Physiology of haemodynamic changes, and changes in electrocardiogram and echocardiography during and post pregnancy. BP, blood pressure;ECG, electrocardiogram; LA, left atrium; LV, left ventricle; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; RV, right ventricle; RVEF, right ventricular ejection fraction; SPAP, systolic pulmonary artery pressure.
by 30%-50%, and heart rate increases by 10-20 beats per minute.Peripheral vascular resistance decreases by 20%-50%.37
Left and right atrial and ventricular diameters and volumes increase while ventricular function is preserved.38 Blood pressure and CO in-crease during labour.39 After delivery, the uterus contracts, and CO drops rapidly to~15%-25% above normal. A gradual decrease of CO follows over the next 3-4 weeks and reaches pre-pregnancy levels at~6 weeks post-partum.
In women with heart disease, left and right ventricular adaptation to pregnancy can be suboptimal and can lead to heart failure(HF) and
atrial and ventricular tachyarrhythmias. Atrial arrhythmias may develop in response to cardiac stretch and hormonal changes in pregnancy and may not be well tolerated in women with CVD. The haemodynamic and hormonal changes during pregnancy are risk factors for aortic dis-section in women with a orthopathy.40 Pregnancy is a hypercoagulable state associated with an increased risk of thromboembolism.41 Increased activity of gastrointestinal-hepatic metabolism, liver enzyme systems, glomerular filtration rate and plasma volume, changes in pro-tein binding, and decreased serum albumin levels all contribute to changes in the pharmacokinetics of many drugs.42
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4. The Pregnancy Heart Team
4.1. Concept and requirements
The central role of the Pregnancy Heart Team is illustrated in Figure 2. The concept of the Pregnancy Heart Team was first intro-duced in the 2018 ESC Guidelines for the management of cardiovas-cular diseases during pregnancy. It has become an established component in the care of women with CVD or those who develop cardiovascular problems during pregnancy. 44-49 This care provision commences prior to pregnancy and persists through the post-partum period. Research has shown that management by a Pregnancy Heart Team is associated with favourable maternal, foetal and healthcare services outcomes, including lowered maternal mor-tality and readmission rates and subsequently improved patient safety.50 Institutional Pregnancy Heart Teams should be established in referral hospitals, taking into account the geographical regions,disciplines represented, and numbers of births, as well as sociocul-tural aspects.44,45,47-49 Maintaining a balance between the need for follow-up by such teams and the workload on these teams is crucial,emphasizing the importance of carefully selecting women who should be directed to a Pregnancy Heart Team. Patient selection is best ac-complished by a risk assessment using the modified World Health Organization(mWHO) 2.0 classification(Table 6). The Pregnancy Heart Team should encompass a core team that can be expanded with other experts(see Figure 3), tailored to women's physical and mental health or emerging complications. ${}^{53}$
The primary responsibilities of the Pregnancy Heart Team encompass risk assessment, collaborative care plan development, continuous progress monitoring, coordination, patient education, and psycho-logical counselling. A staged approach is recommended, from pre-conception and pregnancy through to labour, delivery, and post-partum care. Promoting shared decision-making is essential at all stages. Not every hospital needs to establish a dedicated Pregnancy Heart Team, but each hospital should establish commu-nication and collaboration with nearby expert teams, optimizing emergency and elective referral pathways within a shared-approach care model.
4.2. Pre-pregnancy counselling and family planning
Women should receive pre-pregnancy counselling and education about the maternal, foetal, and transmission risk(s). In adolescents diagnosed with congenital or inherited heart disease, tailored discussions about re-productive health should start early, ideally from menarche. Girls and wo-men with congenital heart disease may not demonstrate appropriate understanding of safe contraception and pregnancy risk. High rates of un-intended pregnancies(up to 45%) have been reported in adolescents with congenital heart disease.55 Transition programmes showed im-proved disease-related knowledge levels in adolescents with congenital heart disease.56-58
4.2.1. Risk assessment
A personalized pregnancy-related risk assessment is needed in all wo-men with CVD and should encompass the specific cardiovascular diag-nosis, functional status, and medication regimen, as well as non-cardiac risk factors such as maternal age, smoking history, comorbidities, body mass index(BMI), obstetric history, logistical care aspects, maternal ethnicity, and socioeconomic status. It is also crucial to integrate foetal and obstetric outcomes with specific cardiovascular considerations.
Maternal preferences should be thoroughly explored as part of the shared decision-making process.
4.2.1. Maternal risk assessment
Depending on the diagnosis, a cardiovascular assessment may include im-aging, biomarker-level assessment, and functional testing. Cardiopulmonary exercise testing can be useful for pre-pregnancy risk stratification. ${}^{59,60}$ Assessment may include re-evaluation after discontinuation of teratogenic medications and whether pre-pregnancy intervention is required.
Various scoring systems are available to assess maternal risk and foetal risk.These do not fully explore the interaction with non-cardiac risk factors,only focus on maternal cardiac events, and have mainly been validated in higher-income countries. Further adaptation and validation in other coun-tries may be required.51 Despite these limitations, disease-specific risks can be effectively assessed using the mWHO classification, validated as the best-available risk assessment model.1.61 However, the mWHO classifica-tion is oriented towards adult congenital heart disease(ACHD) and iden-tifying those at the highest risk. Therefore, the mWHO 2.0 classification has now been expanded with other CVDs and refined by integrating the Cardiac Disease in Pregnancy study(CARPREG) II(Table 6).52 Specific ex-pertise and collaborative management by a Pregnancy Heart Team is man-datory for all women with a condition of mWHO 2.0 class II-III or above.
4.2.2. Genetic counselling
Several CVDs have a genetic basis, including heritable cardiac conditions such as some aortopathies, channelopathies, cardiomyopathies, congenital heart disease, and subsets of pulmonary arterial hypertension(PAH) and thromboembolic disease. Most show autosomal dominant inheritance with a 50% transmission risk. Knowledge of an underlying pathogenic/likely pathogenic(P/LP) variant(adjusted terminology for mutation) is of increas-ing importance to better assess pregnancy-related outcomes and to adjust management(Figure 4).62.63 Therefore, it is recommended that genetic testing for CVD is performed pre-pregnancy in a specialized cardiogenetic centre or a network model with access to a multidisciplinary team, involv-ing appropriately trained professionals with expertise in genetic testing methodology, sequence variant interpretation, clinical application of genet-ic testing, and pre- and post-testing genetic counselling about the transmis-sion risk and the variable expression of an inherited genetic condition.64,65
4.2.2.1. Pre-natal and pre-implantation diagnosis
A timely discussion about pre-implantation(or pre-gestational) genetic testing and pre-natal testing should be offered to every woman and/or couple when there is a known parental monogenic or chromosomal ab-normality. Pre-implantation genetic testing requires in vitro fertilization(IVF).The modalities of pre-natal and pre-implantation testing,including precautions, are summarized in Table 7. The decision whether to pur-sue pre-implantation or pre-natal genetic testing should include consid-eration of a spectrum of aspects related to the disease, including cultural, religious, and legal issues, but also accessibility of required tech-niques and expertise.67 Counselling should be provided at an experi-enced centre with an expert multidisciplinary team. An individualized approach is required to ensure autonomous choice and informed decision-making within the local ethical and legal framework. Several of these options take time and require early referral.
4.2.3. Reproductive technology
Infertility rates in most women with CVD are similar to those in the general population, but managing infertility and medically assisted reproductive treatment is more complex. ${}^{68}$
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Pregnancy Heart Team
Extended with specific multidisciplinary teams if indicated
Pre-conception
•Risk assessment mWHO 2.0
•Genetic counselling
●Lifestyle counselling
•Reproductive technology
•Drug review
•Clinical optimization
•Contraception
Pregnancy
Disease-specific
•Regular follow-up and risk assessment
•Regular foetal assessment
•Documented delivery plan
Delivery (plan)
Congenital heart disease
 lschaemic heart disease
Ischaemic heart disease
•Timing and mode of delivery
●Foetal and maternal monitoring
•Anaesthesia and pain relief methods
●Drug management and bleeding control
•Device management
Peripartum CMP
Cardiac channelopathies
Cardiac channelopathies
Cardiac channelopathies
   Heart failure
Valvular heart disease
 Cardiomyopathies
Post-partum
• Breastfeeding and lactation
•Contraception
•Maternal cardiac follow-up
Long term
●Identify adverse pregnancy outcome
• Women's Heart Clinic
• Cardiovascular risk factor screening
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Table 6 Modified World Health Organization 2.0 classification of maternal cardiovascular risk
||mWHO 2.0 I|mWHO 2.0 II|mWHO 2.0 II-III|mWHO 2.0 III|mWHO 2.0 IV| |---|---|---|---|---|---| |Diagnosis|Ventricular (dys)function + pulmonary hypertension||||| |Diagnosis|Mild left ventricular impairment: EF>45%. Significantly impaired, Sificantly impaired RV(subpulmonary) function.|Moderate left ventricular impairment: EF<30% EF 30%-45%. Previous PPCM with not more than mild residual left ventricular impairment.|||| |Diagnosis|Arrhythmias|Arrhythmias|Arrhythmias|Arrhythmias|| |Diagnosis|Atrial or ventricular ectopic beats, isolated.|Most supraventricular arrhythmias. Bradycardia requiring pacemaker.|Low-risk LQTS: no previous events+ on full dose beta-blocker therapy. Low-risk CPVT: well controlled by medical therapy. BrS with no previous events.|Sustained ventricular tachycardia from any aetiology. LQT2(post-partum). Symptomatic CPVT and LQTS not adequately controlled by therapy. BrS with previous events.|| |Cardiomyopathy|Cardiomyopathy|Cardiomyopathy|Cardiomyopathy||| |HCM: genotype-positive + phenotype-negative.||Low-risk ARVC: genotype-positive+ no or mild phenotype. HCM without complications. DCM/NDLVC with normal or mild left ventricular impairment: EF>45%.|ARVC with moderate/ severe disease. HCM with arrhythmic and/or moderate haemodynamic complications. DCM/NDLVC with moderate left DCM/NDLVC with moderate left ventricular impairment: EF 30%-45%.|DCM/NDLVC with severe left ventricular impairment: EF<30% or NYHA class IIIIV. HCM with symptomatic severe outflow tract obstruction: 50 mmHg. HCM with severely symptomatic LV dysfunction(EF<50%)|| |Congenital heart disease|||||| ||Successfully repaired uncomplicated nitrical or ventricular atrioventricular septal defects. $$\text{ sptel defect.}$$ Repaired tetralogy significant residual lesions. Uncomplicated|Unpaired cyanotic heart disease(not Eisennenger). Systemic RV with good or mildly decreased ventricular function.|||| ||patent ductus arteriosus, anomalous pulmonary venous drainage.|significant residual haemodynamic/ arrhythmic lesions. Transposition of the great arteries with arterial switch without significant residual lesions.|Uncomplicated Ebstein anomaly: mild to moderate TR, no tricuspid stenosis, no|Uncomplicated Fontan correlation: good ventricular function, no significant valve disease or arrhythmias, good exercise tolerance, and normal arterial saturations. Ebstein anomaly with any complication.|Sistemic RV with moderate or severely decreased ventricular function. Fontan with any complication. Eisenmenger syndrome.|
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||mWHO 2.0 I|mWHO 2.0 II|mWHO 2.0 II-III|mWHO 2.0 III|mWHO 2.0 IV|| |---|---|---|---|---|---|---| ||Valvular heart disease|||||| ||Small or mild ●pulmonary stenosis ●mitral valve prolapse without significant regurgitation.|Native, homograft or tissue valve disease not considered mWHO 2.0 I or IV: mild mitral stenosis, moderate aortic stenosis. Moderate valvular regurgitation.|Uncomplicated mechanical valve with stable well controlled INRs. Moderate mitral stenosis. Severe asymptomatic aortic stenosis. Severe left-sided valvular regurgitation.|Severe mitral stenosis. Severe symptomatic aortic stenosis.||| ||Aortopathy|Aortopathy||||| ||Non-HTAD mild aortic dilatation(<40 mm).|Turner syndrome without cardiovascular features (BAV, coarctation,AHT,aortic dilatation).|Marfan or other HTAD syndrome without aortic dilatation. Aorta<45 mm in BAV pathology.|Moderate aortic dilatation:40-45 mm in Marfan syndrome or other HTAD; 45-50 mm in BAV, Turner syndrome ASI 20-25 mm/m2, other aortic dilatation <50 mm. Marfan with previous aortic root replacement. Previous aortic dissection with stable diameter.|Severe aortic dilatation:45 mm in Marfan syndrome or other HTAD, >50 mm ASI>25 mm/m2 in Turner syndrome, other aortic dilatation >50 mm. Vascular Ehlers- Danlos syndrome. Severe(re)coarctation. Previous aortic dissection with stable|| ||Acquired+ coronary heart disease + other|||||| ||||||Prior SCAD. Prior ischaemic cardiac event (STEMI/NSTE ACS). Prior adverse pregnancy outcome requiring hospitalization. Prior adverse cardiovascular effects of cancer treatment.|| |Risk|Risk|No detectable increased risk of maternal mortality and no/mild increased risk in morbidity.|Small increased risk of maternal mortality or moderate increase in morbidity.|Intermediate increased risk of maternal mortality or severe morbidity.|Significantly increased risk of maternal mortality or severe morbidity.|| |Average maternal cardiac events|Van Hagen et al. (2016)51|9.9%|7.7%|17.7%|28.9%|| |event rates|Silversides et al. (2018)52|3.1%|21.7%|12.8%|21.1%|35.6%|
Individualize each maternal risk with the modifiers below( derived from CARPREG II)
CARPREG II score: 1 point
CARPREG II score: 2 points
CARPREG II score: 3 points
● Prior cardiac event or arrhythmias
● No prior cardiac intervention indicated
● Ventricular dysfunction
● Baseline NYHA III/IV or cyanosis
● High-risk left-sided valve disease or outflow tract obstruction
● Mechanical valve
● Pulmonary hypertension
● Coronary artery disease
• High-risk aortopathy
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||mWHO 2.0 I|mWHO 2.0 II|mWHO 2.0 II-III|mWHO 2.0 III|mWHO 2.0 IV| |---|---|---|---|---|---| |Involvement of the Pregnancy Heart Team|No|No|Yes|Yes|Yes| |Counselling|Yes(by regular healthcare professional)|Yes(by regular healthcare professional)|Yes: expert counselling by Pregnancy Heart Team is required|Yes: expert counselling by Pregnancy Heart Team is required|Yes: expert counselling by Pregnancy Heart Team is required| |Obstetric and cardiac care during pregnancy|Local hospital|Local hospital|Shared care with local hospital+ Pregnancy Heart Team|Expert centre, care led by Pregnancy Heart Team|Care led by Pregnancy Heart Team| |Location of delivery|Local hospital|Local hospital|Shared care with local hospital+ Pregnancy Heart Team. Location depends on CV status and evolution of pregnancy|Expert centre, care led by Pregnancy Heart Team|Expert centre, care led by Pregnancy Heart Team|
AHT,arterial hypertension;ARVC,arrhythmogenic right ventricular cardiomyopathy;ASI,aortic size index;BAV,bicuspid aortic valve;BrS,Brugada syndrome;CARPREG II,Cardiac Disease in Pregnancy study;II:CPVT,catecholaminergic polymorphic ventricular tachycardia;CV,cardiovascular;DCM,dilated cardiomyopathy;EF,ejection fraction;HCM,hypertrophic cardiomyopathy;HTAD,heritable thoracic aortic diseases;INR,international normalized ratio;LQTS,longQT syndrome;LQT2, long QT syndrome type 2;LV,left ventricle;mWHO,modified World Health Organization; NDLVC, non-dilated left ventricular cardiomyopathy; NSTE ACS, non-ST-elevation acute coronary syndrome; NYHA, New York Heart Association;PAH,pulmonary arterial hypertension;PPCM,peripartum cardiomyopathy;RV,Right ventricle;SCAD,spontaneous coronary artery dissection;STEMI,ST-elevation myocardial infarction;TR,tricuspid regurgitation.
aDefinition of cardiac events: cardiac arrest, cardiac death, arrhythmia requiring treatment, left/right heart failure, thromboembolic event, aortic dissection, acute coronary syndrome, or hospitalization for cardiac reason. Endocarditis only in van Hagen et al. ${}^{51}$
 BEstimation of maternal adverse cardiac event rate with integration of CARPREG ll score. Reprinted from Silversides et al.52 with permission from Elsevier.
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 Figure 3 Composition of the core and expanded case-based Pregnancy Heart Team. MDT, multidisciplinary team.
Nevertheless, women with CVD requesting reproductive treatment should not be turned down based on assumed cardiovascular risk un-til their case has been discussed in a multidisciplinary setting involving the Pregnancy Heart Team.
Assisted reproduction has added risks above those of pregnancy alone; superovulation is pro-thrombotic and can be complicated by ovar-ian hyperstimulation syndrome, with marked fluid shifts and a high thrombosis risk. All women with CVD who are embarking on fertility treatment should have an individual risk assessment for venous thrombo-embolism(VTE) given the risk associated with these techniques. ${}^{69}$ The
risk of ovarian hyperstimulation syndrome can be reduced by careful cy-cle monitoring, using a low-dose follicle-stimulating hormone in combin-ation with a gonadotropin-releasing hormone antagonist. Transferring a single embryo is strongly advised in women with CVD, as carrying multiple gestations is associated with greater cardiovascular changes and more maternal and foetal complications. ${}^{70,71}$
In women with mWHO 2.0 class III conditions or those who are an-ticoagulated(Table 6), the risk of complications from superovulation is very high. It is therefore recommended that these women have a full pre-pregnancy assessment by a Pregnancy Heart Team prior to the
 |Pre-implantation genetic diagnosis|IVF procedure followed by biopsy and genetic testing of a single cell of the embryo. Embryo transfer with success rate of 25%-30%(dependent on mother's age and fertility).| |---|---| ||Risks to mother and offspring of IVF, such as multiple birth, premature labour and low birth weight, as well as side effects of hormonal treatment. Availability, expense and methods differ across countries.| |Chorionic villus sampling|Transcervical or transabdominal sampling of the chorionic villi at the end of the first trimester. Procedure-related foetal loss rate~0.2%.66| |Amniocentesis|Direct sampling of amniotic fluid after 15 weeks of gestation. Procedure-related foetal loss rate~0.1%.66|
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procedure, including an evaluation of the risk of hormonal treatment.The option of natural cycle IVF should be considered. Hysteroscopy and laparoscopy can be life-threatening procedures in women with spe-cific cardiac conditions, such as a Fontan circulation, and should only be undertaken in an experienced centre with appropriate support.
Fertility treatment should be avoided in women with mWHO 2.0 class IV conditions.
4.2.4. Contraception
To ensure informed decision-making about pregnancy, accurate counselling about contraception should be provided to all girls and women of childbearing age with CVD, starting from menarche,to prevent unplanned pregnancies. An overview of the benefits and risks of different types of contraception in women with CVD is pro-vided in Table 8.
4.2.5. Termination of pregnancy including psychological support
It is strongly recommended to consider and discuss termination of pregnancy with women whose risk is classified as mWHO 2.0 class IV due to the exceptionally elevated risk of maternal foal mor-tality or severe morbidity.83 Efforts should be made to minimize de-lays for women seeking pregnancy termination because the risk of procedure-related complications increases as gestational age ad-vances. Surgical methods are often preferred, but pharmacological methods remain an option until the ninth week of pregnancy.83 Given the emotional and psychological impact of pregnancy termin-ation, it is crucial to provide professional psychosocial support, which plays a significant role in reducing adverse mental health outcomes.89 At the same time a discussion should be held regarding appropriate contraception.
Table 8 Overview of benefits and risks of different methods of contraception in women with cardiovascular disease
|Method|Benefits|Cardiovascular riskss|Cautious use and contraindications|Contraceptive efficacy| |---|---|---|---|---| |Hormonal oral contraceptives||||| |Progestin-only oral contraceptives|Minimal/no impact on coagulation factors Safe CV risk profile 72,73|Mild fluid retention|LQTS not on beta-blockers|++(general) $$\text{+++(for}$$ drospirenone)"73| |Combined oral contraceptives 76,77|Regular menstruation with reduced blood loss|VTE,hypertension and altered lipid|Known dyslipidaemia78 Pre-existing hypertension79 Obesity80 Cyanosis MHV Fontan circulation Risk factors for ACS81|+++| |Long-acting reversible contraceptives||||| |Levonorgestrel-releasing IUD|↓ Menstrual bleeding and iron loss|None specified|Vasovagal responses on insertion and removal(done by gynaecologist)→caution and monitoring with availability of anaesthesiologist recommended in PAH and Fontan circulation82|Safest and most effective option +++| |Smaller levonorgestrel IUD|↓ Menstrual bleeding and iron loss Easier to insert ↓ Risk of vasovagal responses|None specified||+++| |Copper IUD|↓Cost|-|↑ Intensity of menstrual bleeding|+++| |Etonogestrel-releasing subcutaneous implants|No pelvic infection risk|None specified|Surgical subcutaneous insertion(in the forearm with local anaesthesia-outpatient procedure)|+++| |Depot medroxyprogesterone acetate injection83|Lighter menses|Increased VTE risk, weight gain|Irregular bleeding|++| |Barrier methods +1 Pelvic infection risk84 - None specified +|||||
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|Permanent sterilization||||| |---|---|---|---|---| |Tubal ligation Vasectomy|Permanent|Anaesthetic and procedural risks|Non-reversible|+++| |Emergency contraception||||| |Oral contraceptive pills to delay ovulation||||| |Uilpristal acetate|↑Effectiveness than levonorgestrel|No↑ thrombosis risk85-87|None specified|+++(only if taken before ovulation)| |Levonorgestrel single dose of 1.5 mg <72 h after unprotected intercourse|-|No↑ thrombosis risk|None specified|++(only if taken before ovulation)| |Contractive device|Contractive device|Contractive device|Contractive device|Contractive device| |Copper IUD <120 h after unprotected intercourse|-|-|None specified|+++(in addition to ongoing contraception) 85-88|
ACS,acute coronary syndrome;CV,cardiovascular;IUD,intrauterine device;LQTS,long QT syndrome;mg,milligram;MHV:mechanical heart valve;PAH,pulmonary arterial hypertension;VTE, venous thromboembolism.
† increase ↓ decrease.
^{4} Higher in combined oral contraceptive pills containing ethyniloestradiol compared to natural oestriodol or oestretol.
Recommendation Table 1-Recommendations for counselling, pregnancy risk assessment, contraception, assisted re-productive technology, and the involvement of a Pregnancy Heart Team(see Evidence Table 1)
|Recommendations|Recommendations|Recommendations|Recommendations|Recommendations|Classa|Levelb| |---|---|---|---|---|---|---| |Maternal risk assessment||||||| |It is recommended to perform a risk assessment in all women with CVD of childbearing age using the mWHO 2.0 classification|44,45,47-49,54|44,45,47-49,54|44,45,47-49,54|1|C|| |A discussion by the Pregnancy Heart Team about the high risk of maternal mortality or morbidity and the related high foetal risk is recommended for women with mWHO 2.0° class IV conditions, including a shared decision-making process for pregnancy termination,involving psychological support. ${}^{65}$|1|1|1|1|C|| |It is recommended that women with CVD of mWHO 2.0° class II-III and above are evaluated and managed by a Pregnancy Heart Team from pre-pregnancy onwards through pregnancy and post-partum. 44,45,47-49,54|1|1|1|1|C|| |Methods of contraception||||||| |It is recommended that women with CVD of mWHO 2.0° class II and above, or those at risk of developing CVD, receive individualized advice to determine the most suitable contraception method, including emergency contraception. ${}^{90,91}$|1|1|1|C||| |Progestin-only treatment, contraceptive implants, and/or levonorgestrel IUDs should be considered when there is any risk of thrombboembolic events.73,92-94|||B|||| |Genetic counselling|Genetic counselling|Genetic counselling||||| |Assessment by a clinical geneticist prior to pregnancy is recommended in women fulfilling diagnostic criteria for inherited cardiovascular disease to guide risk stratification and pre-natal genetic testing.63,95|||I|C||| |Pre-conception genetic counselling is recommended in couples with heritable CVD, whether genetic testing is being considered or not. It is recommended that this counselling is provided by an appropriately trained healthcare professional within a multidisciplinary team that offers psychological support and education to encourage decision-making.63,95||||||| |Reproductive technology||||||| |It is recommended that single embryo transfer is performed in women with CVD.70,71|||I|C||| |Pregnancy termination||||||| |It is recommended to offer women with CVD access to termination of pregnancy that is tailored to their cardiac condition to minimize the risks of the procedure.83||I|C||||
CVD,cardiovascular disease; IUD, intrauterine device; mWHO, modified WHO.
${}^{3}$ Class of recommendation.
$^{b}$ Level of evidence.
${}^{c}$ The mWHO 2.0 classification is the updated mWHO classification from the 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy ${}^{43}$ and described in Table 6.
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4.3. Diagnostic methods in pregnancy
The pros and cons of the primary cardiovascular diagnostic methods for diagnosing cardiovascular disease in pregnancy are described here.Pre-pregnancy evaluation is covered in the risk assessment section(Section 4.2.1).
4.3.1. Electrocardiogram, including mobile rhythm devices
Pregnant women may present changes in their surface electrocardio-gram(ECG), including increased heart rate, minor leftward QRS axis shift(15-20 degrees), slightly decreased(20 ms) PR interval, prominent Q waves in II,III, and aVF, and flat or inverted T-waves in III, aVF, V1, V2,and V3(Figure 1). 96-98
A 12-lead ECG is part of the standard evaluation of pregnant women presenting with new-onset cardiac signs or symptoms or suspected ar-rhythmia. In pregnant women presenting with syncope or palpitations,long-term Holiter monitoring or implantable loop recorders should be considered as additional diagnostic tools. As pregnant women are more prone to arrhythmias, the threshold to perform long-term ambulatory rhythm monitoring should be low.
4.3.2. Echocardiography
Tranthoracic echocardiography(TTE) is the first-line imaging method used in pregnancy. Physiological changes in cardiac geometry and functioning are expected during pregnancy(Figure 1).99,101-103 These are greatest early in the third trimester and resolve early post-partum.Agitated saline contrast should not be used during pregnancy, given the risk of placental infarction due to microbubble embrolism, resulting in foetal distress. ${}^{99,104}$ Relevant foetal exposure to intravenous(i.v.)echocardiographic contrast agents is not expected due to their very short half-life.105 Nevertheless, these agents should only be used select-ively because studies during pregnancy or lactation are lacking.99 Transoesophageal echocardiography is relatively safe, but the potential risks and benefits must be weighed individually, including the risk of em-esis/aspiration and sudden increase in intra-abdominal pressure.Speckle-tracking echocardiography is a useful method to detect subclin-ical myocardial abnormalities in pregnancy.106,107
4.3.3. Cardiopulmonary exercise testing
If there is suspicion of new-onset CVD during pregnancy, submaximal exercise testing(at 80% of predicted maximal heart rate) can be useful to assess cardiovascular response to exercise. There is no evidence that exercise testing increases the risk of spontaneous miscarriage.108,109 Stress echocardiography using bicycle ergometry may improve diagnos-tic specificity.The use of pharmacologic stress agents(e.g. dobutamine)should be avoided. ${}^{99,110}$ There is no evidence supporting a preference for treadmill over bicycle exercise testing during pregnancy. The choice should be based on women's individual risk factors, contraindications,pregnancy stage, and local availability of testing and expertise.
4.3.4. Biomarkers
Throughout pregnancy and the early post-partum stages, natriuretic peptide[NP: B-type natriuretic peptide(BNP) and N-terminal pro-brain natriuretic peptide(NT-proBNP)] values within the normal range have a strong negative predictive value for heart failure whereas the positive predictive value tends to be lower. ${}^{11,112}$ In women with pre-existing cardiomyopathy,ACHD, or valvular heart disease, baseline as a
minimum and serial NP measurements on an individualized basis should be considered to diagnose cardiac complications during pregnancy and post-partum.113-118
Although cardiac troponin I(cTnI) and cardiac troponin T(cTnT) are essential in diagnosing myocardial ischaemia, standardized values in preg-nancy and post-parton part have not been established.112,119 Therefore, rou-tine use of troponins alone during pregnancy is not recommended.
D-dimer testing has relevance in the diagnosis of VTE(see Section 11), taking into account the physiological increase during pregnancy,particularly in the third trimester.
4.3.5. Ionizing radiation exposure
Risks of ionizing radiation exposure are highest during organogenesis and decrease with time. ${}^{120,121}$ Exposing the foetus to radiation doses>150-200 mGy may result in intrauterine growth restriction(IUGR),congenital malformations(in particular of the central nervous system),and malignancies. If possible, procedures should be delayed at least until the completion of major organogenesis(>12 weeks of gestation).However, the safety of the woman is important and should guide the clinical decision. All radiation doses to the foetus must be kept‘as low as reasonably achievable'(ALARA)(preferably<50 mGy) and should be clearly documented. Manoeuvres to minimize radiation are:(i) use echo guidance when possible;(ii) place the source as far and the receiver as close as possible to the patient;(iii) use only low-dose fluoroscopy(7.5 frames per second or lower);(iv) favour anteroposter-ior projections;(v) avoid direct radiation of the abdominal region(ab-dominal shielding is of limited benefit due to internal scatter from thoracic tissues rather than direct foetal irradiation);(vi) collimate as tightly as possible to the area of interest;(vii) minimize fluoroscopy time; and(viii) ensure the procedure is performed by an experienced cardiologist.122-126 lodinated contrast can cross the placenta, but has not been reported to have teratogenic effects.127 The potential risk of congenital hypothyroidism is unclear but no abnormalities of foetal thyroid function after application have been reported.122,128,129
4.3.5.1. Chest radiography
The chest radiograph is a practical and readily available diagnostic tool for evaluating cardiopulmonary diseases. The foetal dose from chest radiography is<0.01 mGy. Nevertheless, it should only be performed in symptomatic women if other methods fail to clarify the cause of the symptoms.
Lung ultrasound is a valuable tool for diagnosing pleural effusion, pul-monary oedema, pneumothorax, and pneumonia. However, there is currently a lack of data about the regular ultrasound pattern during pregnancy,130,131 and lung ultrasound is therefore not recommended as an alternative to chest radiography.
Protection of the foetus is governed by radiological standards. Both the technician and the radiologist should act accordingly.
4.3.5.2. Computed tomography and nuclear medicine imaging
The radiation dose to the foetus from a chest computed tomography(CT) or pulmonary CT angiography is estimated at 0.02 mGy.121 Technetium-99m, used for ventilation-perfusion lung scanning for de-tection of pulmonary metabolism, results in an embryonic or foetal ex-posure of<5 mGy, which is considered a safe dose in pregnancy.Computed tomography or nuclear medicine techniques are generally
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not recommended during pregnancy. However, if such techniques are necessary because other diagnostic tools are insufficient or not readily available for the diagnosis in question, they should not be withheld from a pregnant patient. 100,132
4.3.5.3. Cardiac catheterization
Cardiac catheterization is seldom needed during pregnancy but may be necessary for specific diagnostic and interventional purposes.Foetal compromise decreases with gestational age. The highest risk is<20 weeks gestation and is proportional to the radiation dose, with no re-ports of foetal anomalies or loss when exposure is<50 mGy.133,134 Most coronary procedures can be performed within these dose limits and radiation exposure to the foetus itself is estimated to be lower than 20%.The radial approach by an experienced operator is preferable and every effort to reduce radiation exposure should be made.
4.3.6. Cardiovascular magnetic resonance
Cardiovascular magnetic resonance(CMR) is advised if other non-invasive diagnostic measures are insufficient to provide a clinical diagnosis and is preferable to radiation-based imaging modalities. 99,100,135 It seems prudent to avoid a scanner strength higher than 1.5 tesla due to the greater energy deposition in tissue. Evidence regarding gadolinium-based contrast in preg,nancy is controversial and its use should be avoided unless absolutely ne-cessary. ${}^{135-137}$ Excretion of gadolinium-based agents into breast milk is limited(<0.04% of an i.v. dose within the first 24 h, with 1%-2% absorp-tion). ${}^{138}$ Lactating women receiving intravascular gadolinium should dis-continue lactation for 24 h. ${}^{133,138,139}$
4.4. Foetal assessment
4.4. Foetal/obstetric complications
The typical increase in CO during pregnancy may not occur optimal-ly in some women with CVD, potentially affecting uteroplacental blood flow. These and other cardiovascular risk factors contribute to an increased risk of obstetric and foetal complications, including foal loss,still birth, pre-term birth, pre-eclampsia, and IUGR. ${}^{140}$ Furthermore, the severity of obstetric and foetal outcomes varies depending on the maternal risk as defined in the mWHO 2.0 classi-fication. Adverse outcomes are more frequent in women with a higher mWHO 2.0 classification, emphasizing the importance of risk stratification, comprehensive counselling, and multidisciplinary management, including neonatology expertise.2,134,140 Notably, pul-monary hypertension(PH) represents one of the highest risks for obstetric and foetal complications.141 The main predictors of neo-natal complications are indicated in Table 9.
4.4.2. Screening for congenital heart disease in the foetus
Foetal echocardiography should routinely be offered at 18-22 weeks when parents have congenital heart disease. This will detect up to 80% of significant congenital cardiac defects.142-144
4.4.3. Assessing foetal well-being
Detailed anatomical foetalassment is required in women using cardiac medication with teratogenic effects(see Section 5 for more details).145
Recommendation Table 2- Recommendations for diagnostic methods in pregnancy(see Evidence Table 2)
|Recommendations|Table 2- Recommendations for diagnostic methods in pregnancy(see Evidence Table 2)| |---|---| |Echocardiography|| |Transthoracic echocardiography is recommended as first-line imaging tool in any pregnant woman with unexplained or new cardiovascular signs or symptoms. ${}^{99}$|I C| |Biomarkers|| |Measurement of BNP and NT-proBNP levels should be considered prior to pregnancy in women with HF of any aetiology, including previous PPCM, cardiomyopathy,ACHD,and PAH,and be monitored during pregnancy according to the underlying disorder and in case of new-onset or worsening symptoms. ${}^{114}$|IIa B| |Ionizing radiation|| |It is recommended to limit exposure to all medical ionizing radiation doses to ALARA levels. ${}^{121}$|I C| |It is recommended to keep the radiation dose to the foetus as low as possible(preferably<50 mGy),particularly if the foetus is in the field of view. ${}^{120,121}$|I C| |A CT scan should be considered for PE when clinical benefits outweigh the risks to the mother and foetus.|100,121,132| |A chest radiograph may be considered as a first-line imaging tool if other methods are not successful in clarifying the cause of dyspnoea.|IIb C| |Coronary angiography with minimal radiation may be considered during pregnancy if potential benefits outweigh the risks.|I b C| |Cardiovascular magnetic resonance|| |Discontinuation of lactation for 24 h should be considered in women in whom i.v. gadolinium is required. 133,139|IIa C| |CMR imaging without gadolinium contrast should be considered for a definitive, clinically relevant diagnosis during pregnancy,if other non-invasive diagnostic measures are not sufficient. 135,136|IIa C|
ACHD, adult congenital heart disease; ALARA, as low as reasonably achievable; BNP, B-type natriuretic peptide; CMR, cardiovascular magnetic resonance; CT, computed tomography; HF,heart failure; i.v., intravenous; NT-proBNP, N-terminal pro-brain natriuretic peptide; PAH, pulmonary arterial hypertension; PE, pulmonary embolism; PPCM, peripartum cardiomyopathy. ${}^{13}$ Class of recommendation.
bLevel of evidence.
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Table 9 Predictors of neonatal events in pregnant-cies of women with cardiovascular disease
Predictors of neonatal events
|NYHA class III/IV or cyanosis during baseline pre-natal visit|| |---|---| |Maternal left heart obstruction|| |Low maternal oxygen saturation(<90%)|| |Multiple gestations|| |Use of anticoagulants|| |Cardiac medication before pregnancy|| |Mechanical valve prosthesis|| |Maternal cardiac event during pregnancy|| |Maternal decline in CO during pregnancy||
Derived from the 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy.43 CO,cardiac output;NYHA,New York Heart Association.
In women with beta-blocker exposure, higher small for gestational age(SGA) rates and, more rarely, bradycardia have been reported, indicat-ing the need for appropriate foetal monitoring.12,146 Foetal ductus ven-osus Doppler velocity is a useful adjunct to evaluate foetal well-being and determine the time to delivery in cases of increased risk of IUGR.147
4.4.4. Foetal assessment of heritable primary arrhythmias
In families with primary arrhythmia, the foetus may present with arrhyth-mias. Therefore, the foetal heart rate should be assessed at baseline and during each pre-natal visit and compared against gestation-specific norms. In pregnancies complicated by suspected primary arrhythmia-related foetal arrhythmias, complete foetal echocardiography, typically performed at 20-22 weeks, is recommended to evaluate heart anatomy,ventricular function, and the arrhythmia mechanism.148 Foetal magneto-cardiography, if available, offers valuable insights into arrhythmia type and severity and monitors anti-arrhythmic drug therapy, as it captures all car-diac time intervals(P,QRS,T-wave) between 17 and 24 weeks of gesta-tion. It is currently the only method to detect repolarization abnormalities, such as QT interval prolongation. 149
4.5. Timing and mode of delivery
An individualized delivery plan should be made that covers the needs for induction of labour, labour management, delivery, and post-partum surveillance, in shared decision-making with the pregnant women.This delivery plan should be widely accessible to the patient, her partner, and relevant health professionals, and should be placed in the patient's(electronic) health record.
4.5.1. Timing of delivery
Pregnant women with CVD are more likely to have comorbidities and experience adverse events during delivery than those without CVD,and require additional monitoring and care.150 Any maternal benefit of early term delivery(from 37 weeks 0 days to 38 weeks 6 days of ges-tation) should be weighed against the increased likelihood of adverse foetal outcomes.151 Induction of labour between 39 and 40 weeks re-duces the risk of emergency caesarean section by 12% and the risk of stillbirth by 50% in women without CVD. The benefit is likely to be greater for women with CVD who have higher rates of obstetric com-plications.152,153 In the absence of maternal or foetal indications for
early birth, induction of labour before 39 weeks should be reserved for obstetrical indications.154
4.5.2. Induction of labour
Mechanical methods, prostaglandin E1 analogue(misoprostol),slow-release formulation of 10 mg prostaglandin E2(dinoprostone),oxytocin, and artificial rupture of membranes are all considered safe to induce labour.4,155,156 High-dose(600 mg) misoprostol does not af-fect cardiac parameters in women without heart disease, although there remains a theoretical risk of coronary vasospasm and arrhyth-mias.155 Dinoprostone may cause profound hypotension, but only when injected blindly into the myometrium, and this route of adminis-tration should be avoided.15 The use of an additional 2 IU of oxytocin for the management of the third stage in women with CVD has no car-diac consequences and is associated with significantly lower blood loss.15 In women at high risk(mWHO 2.0 classes III-IV), oxytocin is generally considered as a first-line uterotonic, misoprostol and carbo-proast are second line(see Supplementary data online, Table S3).159
Mechanical methods such as a cervical ripening balloon might be pref-erable in women where a drop in systemic vascular resistance would be detrimental.160 If membranes are ruptured, augmentation of labour should be immediate to reduce the risk of infection and should be under-taken with oxytocin to minimize the number of vaginal examinations.
4.5.3. Vaginal or caesarean delivery
Vaginal delivery is associated with less blood loss and lower risk of in-fections and venous thromboembolism and should be advised for most women.161 Planned caesarean section does not confer any advan-tage over planned vaginal delivery in terms of maternal outcomes and may be associated with adverse foetal outcomes.
Caesarean section is the preferred mode of delivery for obstetric in-dications and for women presenting in labour who use or have used vitamin K antagonist(VKA) within the past 2 weeks, with high-risk aor-topathy(mWHO 2.0 class III), with hypertrophic cardiomyopathy(HCM) and severe left ventricle outflow tract obstruction, or in acute intractable HF.43
4.5.4. Haemodynamic monitoring during delivery
Pulse oximetry, blood pressure monitoring, and continuous ECG mon-itoring may help detect early signs of decompensation, arrhythmias, and ischaemia in women with significant CVD and identify those in whom delivery should be expedited.164 Arterial lines should be reserved for those women who have haemodynamic instability or are at risk of it.A right-heart catheter is of uncertain benefit, is associated with compli-cations, and should be avoided in most cases. Minimally invasive CO monitoring is preferable.110
4.5.5. Anaesthesia/analgesia
Analgesia is crucial for labour in pregnant women with CVD to reduce physical stress. Neuxarial methods are very effective analgesic blocks.The onset of conventional epidural analgesia is relatively slow(±15 min)and allows for careful titration of a local anaesthetic-opioid mix.165 Spinal analgesia is suitable for women with high-risk CVD, where a faster onset of symphetic block is desirable.166 Combined spinal-epidural analgesia typically has a faster onset time(±5 min). However, adverse effects such as hypotension and foetal heart rate abnormalities occur more quickly and are more pronounced. Different techniques for admin-istering low-concentration, high-volume local anaesthetic-opioid regi-mens allow maintenance of epidural analgesia through the epidural
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catheter. Whenever an epidural catheter is in situ in a high-risk woman,higher doses can be administered for conversion to caesarean section,avoiding airway and other complications of general anaesthesia. In women at risk of dural ectasia, including Marfan syndrome, extra caution and man-agement in an expert centre is essential. Furthermore, a pre-delivery con-sultation with the anaesthesia team is needed.167 When neuraxial analgesia is contraindicated due to conditions such as systemic anticoagulation or spinal deformities, opioids(i.v. remiferrant) are an alternative despite the risk of hypoventilation and apnoea.168,169 Single-shot spinal analgesia is common in caesarean delivery for its simplicity and effectiveness.167
4.5.6. Delivery in women on anticoagulants
4.5.6.1. Planned delivery
In women with mechanical heart valves(MHVs) taking VKAs, suspen-sion of VKAs and bridging with heparin[either therapeutic-dose low-molecular-weight heparin(LMWH) or i.v. unfractionated heparin(UFH)] is recommended at least 2 weeks before planned delivery(see also Section 5 and Section 12). This is because of the slow metab-olism of VKA in the foetus. If therapeutic-dose LMWH is used, one strategy is to switch to i.v. therapeutic UF at least 36 h before planned delivery.170 In these settings the target activated partial thromboplastin time(aPTT) is≥2 times control values. UFH can then be stopped 4-6 h before surgery(in case of caesarean section) or before insertion of re-gional anaesthesia or anticipated vaginal delivery. For women who are on therapeutic-dose LMWH for non-MHV indications, dosing can be omitted for 24 h prior to caesarean section or anticipated vaginal deliv-ery with no need for bridging. In women with MHVs who are on LMWH and aspirin in combination, consideration should be given to stopping aspirin 4 days before delivery.170
4.5.6.2. Urgent delivery on therapeutic anticoagulation
Managing women who are anticoagulated during delivery is complex and needs an individualized approach. Figure 5 gives an overview, but again each scenario may need a more tailored solution.
4.5.6.2.1. Delivery on vitamin K antagonists. If women require ur-gent delivery and have been taking VKAs within the last 2 weeks,then delivery by caesarean section is recommended to reduce the risk of foetal intracranial bleeding. When urgent delivery is required,preventing bleeding complications with administration of i.v.four-factor prothrombin complex concentrate(4F-PCC), depending on the inter-national normalized ratio(INR)(25 U/kg for a therapeutic INR range of 2-4) is the preferred method for rapid INR normalization. If necessary,
vitamin K should be given. ${}^{171,172}$ If 4F-PCC is not available, fresh frozen plasma(FFP) is an alternative, but it takes longer to reverse an elevated INR and requires a larger fluid challenge. ${}^{171,173}$ . The involvement of an expert haematologist in these scenarios is essential, in addition to the Pregnancy Heart Team.The foetus may remain anticoagulated for 8-10 days after discontinuation of maternal VKAs, and may need to be gi-ven FFP and higher doses of vitamin K.170
4.5.6.2.2. Delivery on heparin. If delivery occurs after recent adminis-tration of heparin(e.g. within 4-6 h of UFH, with non-normalized aPTT,or within 12 h of therapeutic LMWH) protamine sulfate should be given.Neutralization of LMWH varies between products and may be less ef-fective.174 Proamine dosage depends on timing after the last dose of LMWH(1 mg/1 mg enoxaparin<8 h; 0.5 mg/1 mg enoxaparin>8 h).For UFH,1 mg of protamine per 100 units of heparin is needed.175
In addition to the level of anticoagulation, the decision to reverse an-ticoagulation should also be related to the bleeding risk, which is higher with conditions such as placental abruption, placenta previa, and mul-tiple previous caesarean sections.
4.5.6.3. Restarting anticoagulation after delivery
The decision to restart anticoagulation post-delivery is challenging and must balance risk of bleeding and risk of thrombosis. Anaesthetic, cardiac,haematology, and obstetric teams may have different priorities, but all need to be actively involved in decision-making, which should also involve the patient. Late obstetric bleeding(>24 h) is common,176 as was also confirmed in recent data from the ROPAC III trial177(bleeding on mean post-partum day 3.6), suggesting that these events occur at a time when heparin is being used at the same time as the VKA is being re-introduced. Restarting UHF(aPTT levels≥2 times the control) or low/intermediate doses of LMWH are all valid options.170 Techniques to re-duce bleeding risk include active management of the third stage of labour with oxytocin.Recently,the effect of adding 2 IU oxytocin over 10 min to a standard treatment of low-dose infusion for 4 h[10 IU of oxytocin in 500 mL of normal saline given i.v. at 36 mL/h for 4 h(12 mL/min)] was analysed. The addition of 2 IU of oxytocin was not associated with any greater derangement in cardiovascular measures, but with a significantly lower volume of blood loss.158 VKA should only be started 7-14 days or later post-partum to reduce the risk of late bleeding.170
4.5.7. Endocarditis prophylaxis for delivery
Systemic antibiotics according to the 2023 ESC Guidelines for the man-agement of endocarditis may be considered for delivery in women at high risk of endocarditis. ${}^{178}$
Recommendation Table 3- Recommendations for timing and mode of delivery(see Evidence Table 3)
|Recommendations||Classa|Levelb| |---|---|---|---| |Timing and mode of delivery|||| |Vaginal delivery is recommended in most women with CVD.161-163||I|B| |Systemic antibiotic prophylaxis may be considered for delivery in women at high risk ${}^{c}$ 178||IIb|C| |Routine induction of labour prior to 39 weeks is not recommended in women with stable CVD.44,154||III|C| |Delivery in women on anticoagulants|||| |It is recommended that the timing of delivery is planned to ensure safe and effective peripartum anticoagulation.||I|C| |It is recommended to discontinue VKAs and start therapeutic-dose LMWH or adjusted-dose iv. UFH at the 36th week of gestation or 2 weeks before the planned delivery. ${}^{179}$||I|C| |In women at low risk ${}^{d}$ on therapeutic-dose LMWH, neuraxial anaesthesia and vaginal delivery(or caesarean section for obstetric||I|C| |indications) is recommended 24 h after the last dose of LMWH.180||||
Continued
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In women at high risk, it is recommended to convert LMWH to i.v. UF at least 36 h prior to delivery and stop the UFH infusion 4-6 h prior to anticipated delivery. The APTT should be normal before regional anaesthesia. 180
If women at high risk, it is recommended to convert LMWH to i.v. UF at least 36 h prior to delivery and stop the UFH infusion 4-6 h prior to anticipated delivery. The APTT should be normal before regional anaesthesia. 180
Post-delivery,it is recommended that the decision to restart LMWH or UFH is made after discussion with the Pregnancy Heart Team and the woman who gave birth. 170
It is recommended to postpone the switch from heparin back to oral anticoagulants until 7-14 days post-partum when the wound area has healed, in consultation with the Pregnancy Heart Team. 177
In women on therapeutic-dose LMWH, planned delivery should be considered at around 39 weeks to avoid the risk of spontaneous labour while fully anticoagulated.
In women who are on antenatal anticoagulation, active management of the third stage of labour with oxytocin should be considered.158
aPTT,activated partial thromboplastin time;CVD,cardiovascular disease;i.v.,intravenous;LMWH,low-molecular-weight heparin;UFH,unfractionated heparin;VKA,vitamin K antagonist.S°Class of recommendation.
'scend Table 10.
 Figure 5 Management of urgent delivery in women under anticoagulants. aPTT, activated partial thromboplasma time; FFP, fresh frozen plasma; INR, inter-national normalized ratio; i.v., intravenous; LMWH, low-molecular-weight heparin; 4F-PCC, four-factor thrombin complex concentrate; N, no; PPH, post-partum haemorrhage; RBC, red blood cell; UFH, unfractionated heparin; VKA, vitamin K antagonist; Y, yes.
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4.6. Post-partum monitoring and complications
4.6.1. Monitoring
The post-partum period is associated with significant haemodynamic changes and fluid shifts. Hence, women are at risk of adverse outcomes,such as hypertension, HF, or stroke. 181,182 Post-partum management must be individualized and depends on the woman's underlying CVD,risk or presence of arrhythmias and HF symptoms, and the course dur-ing pregnancy and delivery. For women at the highest HF risk or with HF symptoms during pregnancy or delivery, admission to an intensive(cardiac) care unit during the first 24-48 h for haemodynamic monitor-ing should be considered.183 Early ambulation is important to reduce the thromboembolism risk.
In women with hypertensive disorders of pregnancy, blood pressure should be monitored in hospital(or with an equivalent level of out-patient surveillance) for 72 h after birth and checked again 7-10 days post-partum. Optimizing blood pressure levels from the immediate post-partum period until the first post-natal months could help prevent the development of hypertension and improve long-term cardiovascular-har lather.184
4.6.2. Breastfeeding and lactation
Throughout these Guidelines, the term'lactation'(including not only breastfeeding but also other methods such as pumping) is used as the default term in most sections, especially where it encompasses a broad-er scope, such as in medication-related contexts. We use“breastfeed-ing' specifically in sections where the focus is on the act of nursing or direct feeding at the breast, particularly when discussing its physiological and long-term health outcomes.
Breastfeeding is a global priority because interruption of lactation is associated with adverse health outcomes for the woman and her child,including higher maternal risks of breast cancer, ovarian cancer, dia-betes, and hypertension, and greater infant risks of infectious and meta-bolic disease.185,186
Inhibition of lactation can be obtained with standard doses of cabergo-line in general, or bromocriptine in peripartum cardiomyopathy(PPCM).
Several drugs are contraindicated during lactation(see Figure 6 in Section 5 and Supplementary data online, Table S4).
4.6.3. Complications
4.6.3.1. Haemorrhage
Post-partum haemorrhage(PPH) is more frequently reported in wo-men with CVD.187 To reduce the risk of PPH, an active third stage of labour with early cord clamping and administration of oxytocin to de-liver the placenta should be pursued. Maternal anaemia is a known risk factor for PPH, so anaemia should be managed aggressively in the ante-natal period.
At the time of delivery, a slow i.v. infusion of 2 IU oxytocin over 10 min immediately after birth, followed by 12 mU/min for 4 h, reduces the PPH risk and has a minimal impact on cardiovascular parameters.158 In cases of PPH that are refractory to medical treatment, additional de-vices may be used, such as the Bakri intrauterine balloon, uterine com-pression sutures, or further haemostatic measures including uterine artery embolization or hysterectomy.
4.6.3.2. Psychological reactions, post-partum depression
Although the general risk of post-partum depression among new mothers in the general population is~10%-20%, this risk increases
with underlying health conditions such as CVD, where~1 in 3 mothers have reported symptoms of depression in the post-partum period.188 Those with PPCM are particularly vulnerable to depression.189-191 These findings emphasize the critical need for early detection, regular mental health screening and the necessity of holistic care models with psychological support and tailored interventions.191,192
5. Drugs during pregnancy and lactation
5.1. General principles
5.1.1. Pharmacokinetics and pharmacodynamics in pregnancy
Physiological adaptation of maternal organ systems to pregnancy affects the pharmacokinetics and pharmacodynamics of potentially all medical treatments, including cardiovascular drugs(see Section 3.2).146,193,194
5.1.2. Pharmacogenetics
An overlap between individual genotypes associated with drug effects and pregnancy-induced modifications(e.g. liver enzymes) may unmask adverse effects or require careful titration, in particular for drugs that lead to severe adverse drug reactions(ADRs). As an example, war-farin can cause severe ADR at the maternal(bleeding, thrombosis)and/or foetal level(embryotoxicity, teratogenesis).195 The most not-able cases refer to the polymorphisms of CYP2D6, associated with dif-ferent phenotypes(extensive, ultrarapid or poor metabolizers),leading to diverse pharmacokinetics/pharmacodynamics of drugs used in pregnancy such as beta-blockers(e.g. labelatol, metoprolol),antidepressants(e.g. fluoxetine, paroxetine), and analgesic drugs(e.g.tramadol,codeine).194 Poor and ultrarapid metabolizers may ex-perience extreme variations in drug plasma level and bioavailability,and hence in their effects.195
5.1.3. Newborn drug exposure in breast milk
The exposure of the newborn to maternal drugs via breast milk is ex-pressed as a percentage value, calculated as the dose taken by the in-fant compared either to the therapeutic dose of the same drug(often unknown for newborns) or the maternal weight-adjusted dose.196 The‘relative infant dose’(RID) depends on the relative amount of drug secreted in the milk(milk-to-plasma concentration ratio) and the quantity of milk intake(the standard is 150 mL/kg/day) on a body weight basis.196 The dose per kg of the infant is compared to the maternal dose per kg over the same period. A RID lower than 5%-10% is generally considered safe(see Figure 6; Supplementary data online; Table S4; and LactMed database).197
5.2. Drug classes in pregnancy
5.2. Anticoagulants
The use of anticoagulants during pregnancy represents a complex balance of risks and benefits, influenced by specific indications,and hampered by low-quality evidence. Indications for anticoagula-tion in pregnancy are diverse and covered in different sections in these Guidelines. In this section, we cover drug-specific aspects and dosing regimens that explicitly pertain to the setting of pregnancy.
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Table 10 List of anticoagulation regimens and disease entities in which they are indicated
|Indication|Type of anticoagulant|Dosing|Timing| |---|---|---|---| |Low thrombosis risk|Low thrombosis risk|Low thrombosis risk|Low thrombosis risk| |VTE prevention/no indication for oral anticoagulationa|LMWH|Prophylactic dose|o.d.| |Uncomplicated Fontan circulationb|LMWH|Prophylactic dose|o.d.| |Intermediate thrombosis risk|||| |VTE(DVT/PE) during pregnancy a|LMWH|Therapeutic dose|o.d.or b.i.d.| |Persistent/permanent AF at elevated thromboembolic risk c|LMWH|Therapeutic dose|o.d.or b.i.d.| |Decreased ventricular function(EF<35%) and/or intracardiac thrombus|LMWH|Therapeutic dose|o.d.or b.i.d.| |High thrombosis risk|High thrombosis risk|High thrombosis risk|High thrombosis risk| |Mechanical heart valves e|||| |1.First trimester|||| |Low VKA dose to achieve required INR|First trimester: VKA or|INR: weekly to every 2 weeks|| |Low VKA dose to achieve required INR|LMWH|dose adjusted to peak anti-factor Xa level|b.i.d.| |High VKA dose to achieve required INR|Switch to LMWH|Dose adjusted to peak anti-factor Xa level(weekly until threshold, every 2-4 weeks thereafter)|b.i.d.| |2.From week 13: shared decision|||| |(a) Continue/switch to VKA with weekly to every 2 weeks INR|||| |(b) Continue LMWH with dose adjustment as above|||| |Delivery: refer to Section 4.5.6.2.(for urgent delivery) and Section 4.5.6.1(for planned delivery)||||
AF,atrial fibrillation; b.i.d, is in die (twice a day).DVT, deep vein thrombosis;EF, ejection fraction; INR, international normalized ratio; LPMWH, low-molecular-weight heparin; o.d., omni die(once a day);PE,pulmonary embolism; VKA, vitamin K antagonister; VTE, venous thromboembolism.
aRefer to Section 11 Venous thromboembolism.
bRefer to Section 9 Pregnancy in women with congenital heart disease.
Refer to section 12.4.1. Atrial fibrillation including anticoagulation.
rRefer to section 12.6 Heart failure.
"Refer to Section 12.5.3.2 Mechanical heart valves.
'≤5 mg of warfarin;≤2 mg/day acocoumarol,≤3 mg/day phenprocoumon.43
Low-molecular-weight heparin treatment regimen glossary
To ensure consistency throughout these Guidelines, we apply the fol-lowing wording about LMWH treatment-any deviations from these standards are clearly indicated in the specific sections:
● Prophylactic-dose LMWH refers to low fixed doses with adjustment for extremes of body weight.198
● Therapeutic-dose LMWH refers to high doses typically reserved for treatment of VTE(Section 11) and thrombosis prevention in MHVs(Section 12).
An individualized shared decision-making approach with careful con-sideration of maternal thrombosis risk vs foetopathy is needed, and strategies will vary from prophylactic dosing of LMWH to correctly dosed VKAs. Regional differences, also related to lower availability of anti-factor Xa level monitoring in low- and middle-income countries as indicated by the ROPAC III study, also need to be taken into account.Interestingly, this study shows that despite higher monitoring and bet-ter resource availability, the risk of thrombosis was higher in high-income countries, specifically due to higher use of treatment regimens with therapeutic LMWH.177 Haemorrhagic complications in the mother can occur with all regimens.199 Table 10 lists the regimens and disease entities in which anticoagulants are indicated.
5.2.1.1. Vitamin K antagonists
Vitamin K antagonists cross the placenta and are associated with em-bryopathy and footopathy risk, even at low doses. They will therefore be switched to LMWHs in most pregnant women, with the only excep-tion being women with atrial fibrillation(AF) in the context of moder-ate to severe mitral valve stenosis or MHVs, given the lower thrombosis risk with VKAs compared to LMWH in the latter(see Section 12). 179,200 Women receiving chronic VKAs who are contemplating pregnancy need counselling regarding avoidance of the potential teratogenic ef-fects. When switching(usually to LMWH) is desired, this should take place as soon after conception as possible.
Vitamin K antagonistly is thought to be related to inter-ference with embryonic justification.201,202 Adverse impact is highest in the first trimester(0.6%-12% of embryopathy) and much lower but persisting in later stages of pregnancy(0.7%-2% risk of footopathy,e.g. central nervous anomalies, intracranial haemorrhage).200,203,204 The risk of embryopathy in the first trimester depends on the VKA dose.The risk was 0.45%-0.9% in pregnancies with low-dose warfarin according to two systematic reviews.199,205 In this setting, low-dose re-fers to the dose necessary to maintain the appropriate INR(according to current guidelines this equals doses of≤5 mg of warfarin,≤2 mg/day acenocoumarol,≤3mg/day phenprocoumon).43 This approach may be seen as a reasonable balance between the risks to the mother with
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Table 11 Dosing regimens for the commonly used low-molecular-weight heparins
||Anoxaparin|Dalteparin|Tinzaparin|Target| |---|---|---|---|---| |Prophylactic LMWH Body weight 50-100 kg|4000 IU o.d.|5000 IU o.d.|4500 IU o.d.|NA| |Therapeutic LMWH (non-MHV)|150 IU/kg o.d.|200 IU/kg o.d.|175 IU/kg o.d.|NA| |Therapeutic LMWH MHz|125 IU/kg b.i.d.(starting dose) then 100 IU/kg b.i.d.|125 IU/kg(starting dose) b.i.d. then 100 IU/kg b.i.d.|250 IU/kg(starting dose) then 175 IU/kg o.d.|0.8-1.2 U/mL anti-factor Xa (4-6 h post administration)|
b.i.d.,bis in die(twice a day);IU,international units;LMWH,low-molecular-weight heparin;MHV,mechanical heart valve;NA,not applicable;o.d.,omni die(once a day).
MHV and the foetus. ${}^{170,200,204,206,207}$ Due to incomplete development of liver metabolism, the INR takes longer to normalize in the foetus and neonate than in the mother, which is why VKA should be discontinued 2 weeks before delivery(see Section 4).
If the indication of anticoagulation is non-MHV, such as pregnancy-related VTE, VKAs are not recommended. In case of pre-existing VKA or direct oral anticoagulant(DOAC) therapy due to pre-vious VTE, VKAs and DOACs should be replaced by LMWH when pregnancy is planned or at recognition of pregnancy.208
Vitamin K antagonists are safe during lactation 209 mended in all women with MHVs given their superior anticoagulant properties in avoiding valve thrombosis.179,200
5.2.1.2. Low-molecular-weight heparins
Embryopathy or footetaply has not been reported with LMWHs, even in therapeutic doses, but thromboembolic complications in women with MHVs are higher than with VKAs(8.7%, 5.8%, and 2.7% for LMWH, UFH, and VKA, respectively).179,200 LMWHs appear less likely to induce heparin-induced thrombocytopenia compared with UFH, al-though this has not been studied in pregnancy.210
Data on optimal dosing and frequency of administration in pregnancy are scarce and mostly limited to the setting of VTE and MHV.
5.2.1.2.1. Low-molecular-weight heparin dosing. In women with MHVs, slightly higher starting doses are suggested to ensure minimal delay in reaching the target range(See Table 11).
For prophylactic-dose LMWH, a fixed low-dose LMWH regimen can be used in most cases.207 In women with acute VTE requiring thera-peutic LMWH dose, routine anti-factor Xa monitoring has not been shown to affect clinical outcomes despite fluctuations of anti-factor Xa levels during pregnancy, and should only be considered in women with renal insufficiency or obesity, where adjustment for body weight may result in overdosing. 211-213 Underweight patients show a low prevalence of antepartum or post-partum VTE214 and do not require specific recommendations compared to patients with normal weight. 215
Monitoring of anti-factor Xa levels is essential in women with MHVs on therapeutic-dase LMWH: at least weekly until target level is achieved or when there is a below target level at any stage, and regular monitoring thereafter(e.g. every 2-4 weeks depending on stability)(see Section 12.5.3.2). Recommended peak anti-factor Xa levels should be individualized based on type and location of the valve(between 1.0 and 1.2 U/mL) and additional trough level measurement may be indi-cated in selected cases with increased thrombosis risk(see Section 12.5.3.2).216
5.2.1.2.2. Once-daily vs twice-daily administration. In pregnant wo-men with confirmed acute VTE, no clear benefit of a twice-daily LMWH administration vs a once-daily administration has been demon-strated.217,218 Thus, either using a once- or twice-daily regimen, each one resulting in a therapeutic dose, is reasonable.
Twice-daily administration at slightly higher doses is the usual thera-peutic dosing regimen for pregnant women with MHVs.177 There is in-sufficient evidence for the use of LMWH injections more frequently than twice daily.
5.2.1. Unfractionated heparin
Intravenous UFH, although not crossing the placenta, is associated with higher risks of thrombocytopenia and osteoporosis compared with LMWH. The risk of valve thrombosis during pregnancy with subcutane-ous UFH is unacceptably high and its use is not recommended.
In women with MHVs in whom VKAs cannot be continued, intraven-ous UFHs is only indicated when anti-factor Xa monitoring is not pos-sible during the first trimester and at the time of delivery(see Section 4.5.6). However, intravenous heparin dosing is challenging, requiring hospitalization and multiple daily blood tests to achieve an aPTT≥2 times control values.
5.2.1.4. Fondaparinux
In women requiring prophylaxis of VTE, good outcomes with subcuta-neous fondoparnux were reported in an observational study of 65 pregnancies and a retrospective analysis in 84 women with one or more previous pregnancies.220,221 Its use can be considered if there is an allergy or adverse response to LMWH(prophylactic dose: 2.5 mg daily) thereafter. therapeutic dose: up to 10 mg daily)221-223(see Section 11).
5.2.1.5. Direct oral anticoagulants
Direct oral anticoagulants have shown better bleeding profiles than a LMWH or VKA regimen across indications in non-pregnant po-pulations. Outcome data on their use in pregnancy are scarce and in-consistently captured in pharmacovigilance databases, indicating a need for a more robust system of reporting. ${}^{224,225}$ The foetal effects of DOACs are controversial. ${}^{226,227}$ Animal and in vitro studies showed that dibagtran, rivaraboxan, and apixaban crossed the placenta. ${}^{228-230}$ Prescription information based on these data reported variable adverse effects in pregnant rodents and rabbits: post-implantation loss, mater-nal bleeding, or malfunction at>4 times the recommended maternal doses(see Supplementary data online, Table S4). Counselling women on DOACs who are planning a pregnancy is advised, considering the complexity of pre- and post-conceptional switches to alternative
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regimens(LMWH, VKA) and the risk of VTE recurrence. ${}^{227}$ DOACs may have an edge over VKAs, such as rapid reversal in case of prema-ture delivery and a short antepartium interruption period, due to their reversible inhibition of procoagulant factors. The oral route is an advan-tage over LMWHs. However, evidence of safety is lacking for specific DOAC antidotes(andexanet alfa, adirucumazib) in pregnant women and can only be inferred from pre-clinical studies. After uncertain initial reports on foetotoxicity, 224 a recent retrospective cohort study(main-ly in women exposed to rivaroxaban) does not support a high risk of embryotoxicity.231 It should be highlighted that despite promising stud-ies, clinical evidence on the benefits and risks of DOACs for the mother and foetus is scarce and needed, and their foetal safety over VKAs dur-ing the second and third trimesters has not been established. DOACs are not recommended in pregnancy and they should only be used in the absence of any other option in consultation with the Pregnancy Heart Team and the haematology team. Based on current data there is no ab-solute indication to interrupt pregnancy in the case of accidental exposure. ${}^{227,232}$
During lactation, alternative drugs should be preferred to DOACs due to the paucity of data. However, there are relevant differences be-tween the agents. In studies on lactating women treated with apiban,the concentration in milk was significantly higher than that of rivarova-ban: the milk-to-plasma ratio was>12%, 233 and the weight-adjusted in-fant doses 14%-20%.34 Dabigatran etexilate mesylate, the orally available prodrug, is poorly excreted to the milk after biotransforma-tion to dibagtran, and its oral absorption by the neonatal gastrointes-$$\text{tinal tract is likely negligible. In two breastfed neonates of women}$$receiving dibagtran, the maximum drug concentrations in the neo-nates' plasma were 100 000 times below the levels that would have a significant effect on coagulation indices.235 In lactating women treated with 15-20 mg/day rivaroxaban, the breastfed infant would receive a low dose, corresponding to 1.3%-5% of the maternal weight-adjusted dosage.233,236-238 Therefore, dibagtran and rivaroxaban may be taken cautiously during lactation. Signs of bleeding should be monitored in neonates of lactating mothers taking dibagtran.
Recommendation Table 4-Recommendation for dir-ect oral anticoagulants and pregnancy
|Recommendation|Classa|Levelb| |---|---|---| |DOACs are not recommended during pregnancy.|III|C|
DOAC, direct oral anticoagulants.
aClass of recommendation.
bLevel of evidence.
5.2.2. Antiplatelet treatment
No teratogenic effect is reported for aspirin doses up to 300 mg daily.Clopidogrel is considered safe if dual antiplatelet therapy(DAPT) is needed for the shortest possible duration.239,240 Ticagrelor is contrain-dicated due to embryotoxicity. Prasugure may be considered during pregnancy in special populations including poor metabolizers in whom the prodrug coploidogrel has limited effect.241,242 The use of glycoprotein IIb/lla inhibitors(epitfibatide and tirofiban) should only be used in pregnancy if strictly necessary.240
5.2.3. Diuretics and SGLT2 inhibitors
Diuretics may be used in pregnancy to treat systemic hypertension es-pecially in emergencies or HF-related volume overload conditions.
Care must be taken to monitor for reduction in plasma volume or CO, and decrease in placental perfusion.
Pre-clinical data on SGLT2 inhibitors showed that they cross the pla-centa243 and exposure to these drugs may cause foetal damage in ro-dents, especially during the second and third trimesters.244 SGLT2 inhibitors should be stopped before pregnancy and during lactation.
5.2.4. Pulmonary hypertension
Parenteral prostaglanding analogues(i.v.eprostenol, treprostinil) can be used in pregnant women with significant right ventricle(RV) dysfunc-tion, while recognizing that these agents may interfere with platelet ag-gregation and may promote bleeding.245 Oral phosphodiesterase 5 inhibitors(e.g. sildenafil, tadalfl) can also be used, while recognizing the potential side effects of pre-term delivery and SGA babies.246 Combination therapy with sildenafil and inhaled iloprost has also been reported.247 Calcium channel blockers should be continued dur-ing pregnancy for women with vasodilator-responsive PAH and normal RV function. Endothelin receptor antagonists(ERAs,e.g. bosentan, am-brisentan, macientan) should not be used in pregnancy due to their teratogenic potential. There are few data on the safety of agents such as bosentan and sildenafil in the post-partum period for lactating mothers; however, successful cases have been reported.248,249
5.2.5. Anti-arrhythmic agents
For women without structural heart disease, anti-arrhythmic drugs(such as flacinide, sotalol, and ibutilide) can be used for the prevention or ter-mination of AF and atrial flutter(AFL).250,251 Beta-blockers are consid-ered safe, especially lipophilic compounds(labelalol, metoprolol, and propranolol). In pregnant women with AF and concomitant congestive HF,digoxin may be an alternative option for rate control. Amiodarone can cause foetal abnormalities, bradycardia, and thyroid dysfunction,and its routine use is contraindicated during pregnancy, but may be used as single dose in emergencies like ventricular tachycardia(VT)storm.There are no restrictions on amiodarone use in cardiac arrest.252
5.2.6. Calcium channel blockers
The safety and efficacy of nifedipine[the originator of dihydropyridine calcium channel blockers(CBs)] as an antihypertensive in pregnancy has largely been proved in comparison with other antihypertensive treatments(see Section 12.3). A meta-analysis of 22 randomized con-trol trials with 2595 participants found that nifedipine was significantly more effective at reducing patients' high blood pressure compared with other antihypertensive drugs(labetalol, hydralazine, methyldopa)in hypertensive patients.253 Foetal, neonatal, and maternal safety outcomes were not statistically different between nifedipine and com-parators, except for maternal headache and flushing.253 A randomized controlled trial compared oral regimens with nifedipine, labetalol,or methyldopa in women requiring antihypertensive therapy due to severe hypertension. It found that the primary outcome of blood pres-sure control within 6 h with no adverse outcome was more common with nifedipine or labelal than with methyldopa254. Amlodipine showed safety and efficacy similar to nifedipine.255 Studies on the non-dihydropyridine CCB diltiazem are inadequate and significant potential teratogenic effects have been demonstrated in rodents and rabbits.The drug passes in milk, reaching relevant infant concentrations.Therefore, diltiazem is not recommended in pregnancy and lactation.Oral verapamil is considered safe; no teratogenicity has been observed.The drug is excreted at low levels in milk,<1% of the mother's weight-adjusted dosage.
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5.2.7. Renin-angiotensin-aldosterone system inhibitors
Angiotensin-converting enzyme inhibitors(ACE-Is), angiotensin re-ceptor blockers(ARBs), angiotensin receptor/neprilynsin inhibitors(ARNIs), and renin inhibitors can cause foetal malformations,IUGR and death, and are contraindicated in pregnancy. Caution should be recommended to childbearing women, especially in the absence of effective contraception. Captopropil, enalapril, and benaze-pril are safe during lactation,146 whereas ARBs are not recom-mended. Candesartan may be an exception.256 Aldostone antagonists, canrenone, and spironolactone can have anti-androgenetic effects and are contraindicated in pregnancy.Spironolactone is considered safe during lactation because of exten-sive metabolism to canrenone, thus the infant would receive less than 1% of the mother's daily dosage of canrenone.257 Case reports of elperoneen in pregnant women with resistant hypertension iden-tified no adverse effects.258-261
5.2.8. Lipid-lowering agents
Diagnosis of maternal hypercholesterolaemia at the first trimester or familial hypercholesterolaemia have adverse consequences for both foetus and mother.262 Low-density lipoprotein(LDL) levels increase by~30%-50%, high-density lipoprotein cholesterol by 20%-40%,and triglycerides by 50%-100% during pregnancy262, so referring to reference range as for routine testing is of limited clinical use.Previously,lipid-lowering treatment was usually discontinued pregnancy because of limited safety data.43 Having been contraindi-cated in pregnancy since 1987, statins now remain contraindicated only during lactation. In July 2021 the United States Food and Drug Administration(FDA)263 stated that the evidence was insuffi-cient to conclude that a risk of miscarriage is increased with statins and requested removal of the contraindication.264 Continuing with statins may therefore be considered during pregnancy in wo-men with familial hypercholesterolaemia or established atheroscler-otic cardiovascular disease(ASCVD)(see Section 12.2).265 Furthermore, inadvertent conception during statin therapy does not require pregnancy termination but should prompt close follow-up. Bile acid binding sequestrants265 and LDL apheresis265 can be considered in women with familial hypercholesterolaemia. PCSK9 inhibitors and exetizibe are not recommended during pregnancy due to lack of clinical data.266 Bempedoic acid has a strong contra-indication and therefore women are recommended contraception during its use.
5.2.9. Beta-adrenergic blocking agents
Beta-blocker use during early pregnancy has not been associated with an increased risk of congenital malformations. ${}^{250,267,268}$ Recent data from ROPAC indicate higher SGA rates in women with beta-blocker exposure(15.3% vs 9.3%,P<.001). With metoprolol as reference, la-betalol(0.2, 95% CI 0.1-0.4) was the least likely to cause SGA, and atenolol(2.3, 95% CI 1.1-4.9) the most.12 Labetalol and lipophilic drugs(metoprolol, propranolol, carvedilol) are preferred due to high first-pass metabolism, as well as beta-1-selective drugs(bisopro-lol, metoprolol), which reduce the risk of hypoglycaemia in addition to
reduced IUGR. Nadolol and pindolol are also safe in the case of ar-rhythmic events in cardiomyopathies and channelopathies(see Section 6).269-271 Of note, the metabolism of metoprolol(and perhaps other oral lipophilic beta-blockers) was significantly higher in mid and late pregnancy than post-partum, likely due to enzymatic induction during pregnancy.272 Changes in dosage(dose and frequency) are like-ly required if inadequate clinical responses are encountered.272
Atenolol causes severe growth restriction, bradycardia, and hypogly-caemia and is not recommended.250,268,272,273
Propranolol, metoprolol(combined with hydralazine), and labelalol had the lowest and solatone, the highest risk of neonatal bradycardia dur-ing lactation.274 For the lipophilic beta-blockers, milk level was<1% of the maternal weight-adjusted dose, thus reducing the risks associated with neonatal exposure during lactation.272
5.2.1. Immunosuppressants
The balance between maternal and foetal safety is challenging for im-munosuppressant therapy, especially for women with heart trans-plantation. Medication can pass to the milk and expose neonates and infants to adverse drug effects. Changes in maternal physiology impact the pharmacokinetics of immunosuppressant drugs(see Section 3.2).275 Calcineurin inhibitors(e.g. cyclosporine, tacrolimus),mammalian target of rapamycin inhibitors(e.g. everolimus, sirolimus),and aziathoprine are the drugs of choice during pregnancy and lacta-tion, which should not be discouraged. Mycophenolate derivatives in-crease the risk of miscarriage and foetal malformations especially during the first trimester and should be discontinued at least 6 weeks before conception. ${}^{276,277}$ and should be discontinued at least 6 weeks
5.2.11. Neuroactive drugs
Selective serotonin reuptake inhibitors, including sertraline, can be ta-ken safely during pregnancy and lactation.278 Zuranolone, a synthetic form of the neurotroidal allopregnanolone, has recently been ap-proved for the treatment of post-partum depression. No information is available on its safety in patients with CVD. Zuranolone is excreted in the milk and lactation should be avoided in the absence of safety data. ${}^{279}$
5.2.12. Obstetric drugs in patients with cardiovascular disease
Drugs for inducing ovulation,including follicle-stimulating hormone and luteinizing hormone or combinations, are associated with an increased risk of deep vein thrombosis(DVT) and PE, due to the sharp rise in oes-trogen levels during follicle recruitment,280 but no other immediate car-diovascular side effects are known.
5.3. Internet databases
See Supplementary data online, Internet databases.
5.4. List of drugs
See Supplementary data online, Table S4.
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33
 Figure 6 Choice of medication during pregnancy(left) and during lactation and breastfeeding(right). ACE-I, angiotensin-converting enzyme inhibitor; ARB,angiotensin receptor blocker; ARNI, angiotensin receptor/repinysin inhibitor; ASA, acetylsalicylic acid; ASCVD, atherosclerotic cardiovascular disease; DOAC,direct oral anticoagulant; LMWH, low-molecular-weight heparin; MRA, mineralocorticoid receptor antagonist; PCSK9-I, proprotein convertase subtilisin/kexin type 9 inhibitor; SGLT2-L, sodium-glucose co-transporter-2 inhibitors; UFH, unfractionated heparin; VKA, vitamin K antagonist; wk, week.
++ First/safest choice in pregnancy, lactation and breastfeeding. Second choice in pregnancy, lactation, and breastfeeding. x Evidence of foetal or infant toxicity or no data on safety. ${}^{8}$ except candesartan. ${}^{8}$ See text for details.
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ESC Guidelines
6. Pregnancy in women with cardiomyopathies and primary arrhythmia syndromes
6.1. Cardiomyopathies
Cardiomyopathies are characterized by disease-specific structural ab-normalities and increased risk of ventricular and supraventricular ar-rhythmias. The risk associated with pregnancy in a woman with cardiomyopathy can be estimated using the mWHO 2.0 classification(Table 6). Pre-pregnancy, women with cardiomyopathies should be clinically evaluated to optimize treatment, avoid contraindicated drugs,and assess the risk of heart failure and arrhythmias. Indicated proce-dures, including implantable cardioverter defibrillator(ICD) implant-ation, should be performed before pregnancy. 60
Genetic counselling is recommended before pregnancy to explain the probability of genetic transmission, risks for the mother, foetus,and child, and the possibilities of pre-implantation and pre-natal genetic testing(Table 7).60,281 Women with cardiomyopathies should be man-aged by the Pregnancy Heart Team, including a cardiologist with ex-pertise in cardiomyopathies and arrhythmias.
6.1.1. Dilated cardiomyopathy and non-dilated left ventricular cardiomyopathy
In women with dilated cardiomyopathy(DCM) and non-dilated left ven-tricle(LV) cardiomyopathy(NDLVC), severe systolic LV dysfunction,New York Heart Association(NYHA) functional class III/IV, RV failure,sustained ventricular arrhythmias,AF,and/or severe mitral valve regurgi-tation(MR) are high-risk criteria for major adverse cardiovascular events during pregnancy.282 In contrast, women with mild LV dysfunction, good functional status, no arrhythmias, and no history of cardiac events are likely to have an uncomplicated pregnancy.282
Therapy should be modified before pregnancy. ACE-Is, ARBs,mineralocorticoid receptor antagonists(MRAs), sactrihit/valsartan, and SGLT2 inhibitors are all contraindicated during pregnancy. Pre-pregnancy risk stratification should include temporary withdrawal of contraindicated medication with close monitoring(see Section 12.6 Heart failure.Beta-blockers should be continued with close monitoring of foetal growth.If anticoagulation is needed for AF or evidence of an intracardiac thrombus.LMWH should be used(see Section 5 for dosing regimens).
Data about genotype-specific management during pregnancy are scarce but one study evaluated the risk of pregnancy and progression of cardiomyopathy in women with lamin A/C(LMNA) P/LP variants.283 A small subset of women experienced arrhythmias during pregnancy al-though a history of pregnancy was not associated with long-term ad-verse disease progression.283
More information is included in Sections 7, 12.4, and 12.6.
6.1.2. Arrhythmogenic right ventricular cardiomyopathy
Several observational studies and registries have shown that pregnant-cies in women with arrhythmogenic right ventricular cardiomyopathy(ARVC) are generally well tolerated with good foetal outcomes and no cardiac mortality when receiving optimal surveillance and ther-apy. 284,285 Delivery was usually vaginal and appeared safe. Sustained ventricular arrhythmias were reported in 5% of pregnancies and HF in 13%. Neither increased arrhythmia burden or ICD shocks were ob-served.284 Beta-blocker therapy should be continued during pregnancy(with the exception of atenolol) or could be started in pregnancy if
needed. The two most used anti-arrhythmic drugs in previous studies,beside beta-blockers, were flecainide and sotalol. Both drugs have a long record of safety. However, sotalol should be used with caution in women with reduced ejection fraction(EF) and with careful cor-rected QT interval(QTc) monitoring. ${}^{60}$ Sotalol also has a beta-blocker effect, necessitating monitoring of foetal growth. ${}^{286,287}$ Amiodarone is contraindicated in pregnancy. In women at high arrhythmic risk, an ICD should be implanted, preferably before pregnancy(see Section 12.4).
Two large studies of women with ARVC showed that pre-pregnancy phenotypical severity, rather than pregnancy itself, was the primary risk factor. Pregnancy was uneventful in the overwhelming majority. 288,289 AprCVC phenotype. 288
6.1.3. Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy 290 is the most common inherited cardiomy-opathy and is often caused by variants in sarcomeric genes. Phenocopies such as Anderson-Fabry disease and Danon disease 290 are X-linked and therefore the cardiopic phenotype tends to be milder and occurs later in life in females than males, making pregnancy usually uneventful.291-293
Despite higher maternal mortality in women with HCM compared with the general population, absolute maternal mortality is low(0.5%)and confined to women at particularly high risk(Table 6).294,295 Data from the ROPAC registry showed that despite overall good outcomes,23% of pregnant women with HCM developed major cardiac events,in-cluding VT(10%) and AF(1.7%), mostly in women already identified as high risk prior to pregnancy.296 A recent systematic review including 1624 women confirmed low neonatal mortality(0.2%) and stillbirths(1%) in pregnant women with HCM.297 A study including 242 women with HCM found that pregnancy was not a modifier of the long-term outcomes and pregnancy was well tolerated.298 Risk factors for ma-jor adverse cardiovascular events were advanced NYHA class and higher age at diagnosis.298 Left atrium diameter as a risk factor has been reported with conflicting results.298,299
1.3.1. Treatment of hypertrophic cardiomyopathy in pregnancy
Ongoing beta-blocker therapy should be continued during pregnancy.Atenolol should be replaced before pregnancy(Section 5.2.6). Atrial fib-rillation is poorly tolerated in HCM patients in general due to the risk of haemodynamic decompensation, and medical or electrical cardiover-sion of AF during pregnancy should be considered. Beta-blockers should be started during pregnancy when new symptoms occur[e.g.cue to left ventricular outflow tract obstruction(LVOTO)], for rate control in AF, and to suppress ventricular arrhythmias. Verapamil is the second choice of drug when beta-blockers are not tolerated.
1.3.2. Left ventricular outflow tract obstruction
Left ventricular outflow tract(LVOT) gradients may increase slightly during pregnancy and were previously associated with increased car-diac events including arrhythmias and HF.300 However, subsequent studies have not confirmed this association. ${}^{296,298}$
In women with obstructive HCM, it is recommended to evaluate gra-dient in basal condition, with exercise and the Valsalva manoeuvre, be fore pregnancy and with only the medications allowed during pregnancy, to identify those needing septal reduction therapy before pregnancy.60 Disopyramide may cause uterine contractions and is not recommended in pregnancy and should be discontinued unless the ben-efits outweigh foetal risk. Data on the safety of alcohol septal ablation during pregnancy are limited to a few case reports. ${}^{60,301,302}$
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Myosin inhibitors(e.g. mavacamten) have not been tested in preg-nancy and animal studies have shown foetal toxicity. ${ }^{303}$ Therefore,contraception is recommended while on this treatment. Mavacamten may interact with hormonal contraception and therefore adding intra-uterine or barrier contraception to hormonal contraception may be considered. Myosin inhibitor treatment should be discontinued at least 6 months before planning pregnancy ${ }^{304}$ (see Supplementary data online, Table S4).
6.1.4. Hypertrabeculation of the left ventricle
Hypertrabeculation in isolation identified during pregnancy can be the simple consequence of an increased preload, can resolve after preg-nancy, and cannot be used to make a diagnosis of cardiomyopathy.60 Patients with hypertrabeculation and associated HCM, DCM, or NDLVC should follow the same recommendation as patients with the specific cardiomyopathy.60
6.1.5. Labour and delivery in cardiomyopathies
Labour and delivery may be associated with acute pain, adrenaline re-lease, and need for urgent administration of anaesthetic drugs, and therefore haemodynamic monitoring and continuous telemetry moni-toring during and after delivery is often warranted. In the absence of ob-stetric contraindications, vaginal delivery is generally recommended.Neuraxial anaesthesia reduces pain and therefore reduces adrenergic activation and arrhythmic risk.
In HCM, peripheral vasodilation is poorly tolerated in women with severe LVOT obstruction(LVOTO) and therefore epidural and spinal anaesthesia should be applied cautiously. Low-risk LVOTO cases may have a spontaneous labour and vaginal delivery.Caesarean section may be the preferred option in women with severe LVOTO.
Recommendation Table 5- Recommendations for cardiomyopathies and pregnancy
|Recommendations|Classa|Levelb| |---|---|---| |Clinical cardiological surveillance (ECG, echocardiogram, and Holter ECG monitoring) is recommended during pregnancy in women with CMPs, depending on individual risk.|1|C| |Vaginal delivery is recommended in most women with CMPs, unless there are obstetric indications for caesarean section, severe HF(EF<30% and/or NYHA class III/IV), uncontrolled arrhythmias, or severe outflow obstruction(≥50 mmHg) in women with HCM, or in women presenting in labour on VKAs. ${}^{60}$|1|C| |Continuation of beta-blockers should be considered during pregnancy in women with CMPs, with close follow-up of foetal growth. ${}^{60}$|lla|C| |Dilated cardiomyopathy||| |In women with DCM and worsening of EF during pregnancy, counselling on the risk of recurrence during a subsequent pregnancy is recommended in all cases, even after recovery of LV function. ${}^{43}$|I|C|
Arrhythmogenic right ventricular cardiomyopathy
|Arrhythmogenic right ventricular cardiomyopathy|| |---|---| |Flecainide, in addition to beta-blockers, should be considered as the anti-arrhythmic drug of choice in pregnant women with ARVC. ${}^{148}$|lla| |Sotalol may be considered as an anti-arrhythmic drug in pregnant women with ARVC, with careful evaluation of QTc and while monitoring for foetal bradycardia and foetal growth and neonate|llb| |hypoglycaemia.||
#
It is recommended to use the same risk stratification protocol for ventricular arrhythmias in pregnant women with HCM as for non-pregnant women with HCM.43
It is recommended to start beta-blockersc in women with HCM who develop symptoms due to outflow tract obstruction or arrhythmia during pregnancy.
It is recommended that women with HCM with symptomatic LV dysfunction(EF<50%) and or severe LVOTO(≥50 mmHg) wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.294,295
Cardioversion for AF should be considered in pregnant women with HCM.43,305 Disopyramide may be considered in pregnant women with HCM only when the potential benefits outweigh the risk of uterine contractions.305,306 Myosin inhibitors are not recommended in women during pregnancy due to lack of safety data.303,304
Myosin inhibitors are not recommended in women during pregnancy due to lack of safety data.303,304
AF,atri fibrillation; ARVC, arrhythmogenic right ventricular cardiomyopathy; CMP,diversityopathy; DCM, dilated cardiomyopathy; ECG, electrocardiogram; EF, ejection fraction; HCM, hypertrophic cardiomyopathy; HF, heart failure; LV, left ventricular;LVOTO, left ventricular outflow tract obstruction; NYHA, New York Heart Association; QTc, corrected QT interval; VKA, vitamin K antagonist.
bLevel of evidence.
6.2. Primary arrhythmia syndromes
In general, women with primary arrhythmia syndromes tolerate pregnancy, will. Genetic counselling is recommended before pregnancy,as discussed in Section 6.1. A complete clinical re-evaluation, optimiza-tion of treatment, and ICD evaluation should be undertaken prior to pregnancy.252 Indicated treatment should be continued throughout pregnancy and in the post-partum period.
6.2.1. Long QT syndrome
Long QT syndrome(LQTS) is the most common channelopathy.307 All pa-tients with LQTS should take beta-blockers, with propranolol and nadolol being the most effective.308 Additional therapies include left cardiac sympa-thetic denervation309 and methixeline for LQT3252 and LQT2.310,311 The foetal risk of methixet treatment is unknown, and decisions on treatment during pregnancy should be a shared decision with the woman.
Retrospective studies ${}^{312-316}$ show that women with LQTS were not at higher risk of cardiac events during pregnancy itself, but had an increased risk
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ESC Guidelines
in the post-partum period(up to 12 months), especially for those with LQT2. Beta-blocker therapy was associated with risk reduction in all the studies. Women with LQTS should therefore start beta-blockers at preg-nancy or continue beta-blockers at pre-pregnacy dose, with propranolol or nadolol as drugs of choice. Beta-blockers should be continued in the post-partum period, particularly in the case of women with LQT2 due to the in-creased arrhythmic risk. It should be noted that nadolol has a higher excre-tion in breast milk than propranolol, with a relative infant dose of 4%-7%.317 Therefore, nadolol is generally not the preferred beta-blocker during lacta-tion.However, arrhythmik can be high in LQT5, and nadolol is one of the drugs of choice; therefore, a careful weighting of benefit against harm is ap-propriate.Change of beta-blocker therapy after delivery should be avoided,as this is a vulnerable phase. Therefore, a change from nadolol to propran-olol should ideally be evaluated before pregnancy. High dosages of radolol during lactation may require monitoring of the infant for bradycardia.
Women with LQTS should always avoid QT-prolonging drugs(see www.crediblems.org)318. Women with LQTS should be promptly treated for hypokalaemia and hypomagnesemaia, which is relevant in pregnancy-related hypermeesis, causing electrolyte disturbances and failure to absorb oral medications. All anti-emetic medications are QT-prolonging. Electrocardiogram monitoring should be performed if anti-emetic therapy is absolutely required.
Long QT syndrome can manifest very early in life, even during the foe-tal period, and can be a cause of stillbirth 319,320(Section 4.5.1). A neonatal ECG should be performed post-delivery and after 2 weeks to avoid over-diagnosis due to transiently prolonged QT interval during the first 7-10 days of life.321 Genetic screening for familiar genetic variants should be performed as soon as possible(e.g. from chordal blood). If the newborn is affected by LQTS, beta-blocker therapy should be started immediately.
6.2.2. Brugada syndrome
Men with Brugada syndrome(BrS) are more often symptomatic than women.322 The only retrospective study on pregnant women with BrS did not show an increased risk of cardiac events during pregnancy and the post-partum period.323 All patients with BrS should avoid con-traindicated drugs(see www.brugadadugs.org),324 large meals, or ex-cess alcohol, and promptly treat fever and its causes.325 If there are symptoms during pregnancy, quinidine therapy should be considered with monitoring of hepatic function and blood count in the mother.
6.2.3. Catecholaminergic polymorphic ventricular tachycardia
Catecholaminergic polymorphic ventricular tachycardia mainly caused by P/LP in the RYR2 gene. ${}^{252}$ The only retrospective
study published, involving 96 women and 228 pregnancies, did not show an increased risk of cardiac events during pregnancy and the post-partum period.326
Beta-blockers are the mainstay of therapy, with additive flecainide if needed.322,327 Nadolol and propranolol are beta-blockers of choice and should be continued during pregnancy and lactation. As in LQTS, the higher excretion of nadolol in breast milk should be noted(Section 6.2.1). Left cardiac sympathetic denervation is a valuable anti-arrhythmic option that should be performed in experienced centres before pregnancy if indicated.328 Implantable cardioverter defibrillators are indicated in a minority of patients with CPVT.
6.2.4. Short QT syndrome
Short QT syndrome(SQTS) is a rare channelopathy characterized by short QT and increased risk of life-threatening arrhythmias and AF.329 There are no case reports or studies published on pregnancy in women with SQTS. When choosing an anti-arrhythmic drug during pregnancy, quinidine is the best option in the absence of more robust data. 330
6.2.5. Labour and delivery in primary arrhythmia syndromes
In all primary arrhythmia syndromes, delivery should be planned with heart rhythm monitoring, electrolyte control, and post-operative ECG monitoring until all anaesthetic drugs have been eliminated.
Labour and delivery may be associated with acute pain, adrenaline release, and urgent administration of anaesthetic drugs, and therefore continuous telemetry monitoring is often warranted. In the absence of obstetric contraindications, vaginal delivery is generally recom-mended. Neuraxial anaesthesia reduces pain and therefore adrenergic activation which is specifically important in LQTS and CPVT. Women with LQTS and CPVT should continue beta-blocker therapy during la-bour and delivery. In women with CPVT, it is reasonable to keep the heart rate under the threshold for premature ventricular contrac-tion onset during delivery, typically 100-110 b.p.m.331,332 Anaesthetic drugs for LQTS should be selected according to the CredibleMeds website(www.credibleeds.org).
In BrS, propofol and local anaesthetics with sodium-blocking agents(e.g. lidocaine) carry a theoretical risk of triggering arrhythmias. Case reports have indicated unconventional delivery with unaxial anaesthesia in women with BrS. ${}^{333}$ Thiopental and inhalation anaesthesia have so far not been associated with adverse events. ${}^{324,333}$ Anaesthetic drugs should be chosen according the BrugadaDrugs website(www.brugadadrugs.org).
Recommendation Table 6- Recommendations for primary arrhythmia syndromes and pregnancy(see Evidence Tables 4-6)
|Recommendations|Classa|Levelb| |---|---|---| |Monitoring and treatment of hypokalemaa and hypomagnesmaia is recommended in pregnant women with primary arrhythmia|I|C| |syndromes suffering from hyperemesis.334||| |Long QT syndrome||| |Beta-blockersc, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy in women with LQTS. ${}^{312-316,335}$|$1$|B| |It is recommended to continue beta-blocker therapy during lactation in women with LQTS to reduce arrhythmia risk.|${}^{148,336}$ I|B| |Pre-pregnancy beta-blocker dose of nadolol or propranolol, is recommended in women with LQT2, particularly in the post-partum period, which represents a high-risk period for life-threatening arrhythmias.|$1$|B|
Continued
<FIGTEXT=></FIGTEXT>
ESC Guidelines
37
In women carrying a LQTPS P/LP variant and who are phenotype-negative, use of beta-blockersc during pregnancy, post-partum, and lactation should be considered.148 Left cardiac sympathetic denervation should be considered before pregnancy in high-risk woman with LQTS who are not adequately protected by pharmacological therapies or who have appropriate ICD shocks despite optimal medical therapy.252 Brugada syndrome Quinidine therapy should be considered in pregnant women with BrS who have arrhythmic events during pregnancy.337,338 C Catecholaminergic polymorphic ventricular tachycardia Beta-blockersc, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy and lactation in women with CPVT. 43,148,252 lFecainide, in addition to beta-blockers, is recommended in women with CPVT who experience cardiac events such as syncope, VT, or cardiac arrest during pregnancy.It is recommended that women with CPVT who are stable on beta-blockers(nadolol or propranolol as drugs of choice) and flecainide before pregnancy continue both drugs during pregnancy and post-partum.The use of beta-blockersc during pregnancy and lactation should be considered in phenotype-negative women with a CPVT P/LP variant.148 Ia C Left cardiac sympathetic denervation should be considered before pregnancy in high-risk women with CPVT who are not adequately protected by pharmacological therapies or with appropriate ICD shocks despite optimal medical therapy.252
BrS,Brugada syndrome;CPVT,catchelaminergic polymorphic ventricular tachycardia;ICD,implableardioverter defibrillar;LQTS,long QT syndrome, LQT2, long QT syndrome type 2:P/LP,pathogenic/likely pathogenic;SQTS,short QT syndrome;VT,ventricular tachycardia.
${}^{a}$ Class of recommendation.
{Except for atenolol.
7.Peripartum cardiomyopathy
7.1. Epidemiology
Peripartum cardiomyopathy is a potentially life-threatening condition defined as HF with reduced left ventricular ejection fraction(LVEF)<45%, without any other cause of HF, that occurs mainly during the peripartum period or in the months following delivery, termination,or miscarriage.339 Peripartum cardiomyopathy is essentially a diagnosis of exclusion and requires urgent management.
Worldwide, PPCM is a complication of 1 of 2000 births, ${}^{340}$ but inci-dence rates vary depending on the geographical region, ethnicity, and socioeconomic factors, with an incidence of 1-4/1000 births in the United States of America ${}^{341,342}$ and 10/1000 births in the north-western region of Nigeria. ${}^{343}$ Recent data from 49 countries showed that most women presented with PPCM in the post-partum stage. ${}^{344-346}$ Risk factors for PPCM are shown in Figure 7.
7.2. Mechanisms
Recent trials suggest a'multiple hit theory for developing PPCM, with an accumulation of genetic and environmental risk factors(Figure 7). An overrepresentation of genetic variants in TTN,FLNC,BAG3, and DSP genes have been found in up to 15% of women with PPCM, with TTN truncating variants being the most common.347,348 The prevalence of these four genes in women with PPCM was comparable to the prevalence in DCM cohorts, supporting the similarity between PPCM and DCM. Genetic testing should therefore be considered in women with PPCM.
There is growing evidence that several pathophysiological mechan-isms in PCM converge on a common pathway, which involves inflam-mation, unbalanced oxidative stress, and the generation of the anti-angiogenic 16 kDa prolactin. The 16 kDa prolactin induces
endothelial dysfunction and damage, and subsequently leads to HF.Blocking prolactin with the dopamine and dopamine D2 receptor agonist bromocrip-tine has emerged as a potential disease-specific therapy for PCMC.344,349-352 Additionally, the systemic or local increase in other anti-angiogenic factors, such as the soluble fms-like tyrosine kinase-1(sFt-1) receptor, contributes to both local and widespread vascular dysfunction.353
7.3. Diagnosis and clinical interventions
Peripartum cardiomyopathy may present as subtle manifestations but most women with PPCM present with acute heart failure(AHF) with severe symptoms(NYHA III/IV). Mild to moderate symp-tomatic cases of PPCM are often mistaken for physiological changes associated with pregnancy, especially in the post-partum period.Myocarditis is a differential diagnosis and should be excluded by CMR.354 Women with PPCM and pre-eclampsia had a higher risk of adverse neonatal outcome but also a higher likelihood of left ven-tricular recovery(LVEF≥50%).15 Diagnostic measures in a woman with suspected PPCM should include ECG, NPs, and echocardiog-raphy. The management strategy should be discussed within the Pregnancy Heart Team, considering maternal and foetal outcomes(Figure 7). Foetal mortality and low birth weight are common in mothers with PPCM, and children of these mothers have a 3.4 times higher incidence of cardiovascular disease and 5 times higher mortality. ${}^{355}$
Treatment of AHF caused by PPCM follows the main principles of AHF management during and after pregnancy(Section 12.6).Mechanical circulatory support should be considered in women with persistent cardiogenic shock despite medical treatment. ${}^{356,357}$
Most medications used in the management of HF are foetotoxic and thus contraindicated during pregnancy(i.e. ACE-Is, ARBs, MRAs, and SGLT2 inhibitors).339 In the post-partum period, full HF treatment
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ESC Guidelines
Peripartum cardiomyopathy (PPCM)
Definition
Symptoms and signs of heart failure with reduced LVEF<45% without any other explainable cause that occur during the peripartum period or in the months following delivery, termination or miscarriage
Risk factors
● Malnutrition
● Geographical region
● Family history
● Multiparity,multiple pregnancies
● Genetic P/LP variants in DCM genes
● Fertility-assisted treatments
•Previous PPCM
● Smoking
● Age<20 or>40 years
● Diabetes, hypertension, pre-eclampsia
● Ethnicity
● Prolonged use of tocolytic beta-agonists
Investigations
 Physical exam
 Electrocardiogram
 Natriuretic peptide
 X-ray
 Echocardiography
 CMRa
Management by Pregnancy Heart Team
Pregnancy
● Adjusted acute HF treatment
Post-partum
● If no reversible cause is found, continue HF treatment
● Bromroptinine in addition to optimal HF treatment(Class IIb)
● Prophylactic anticoagulation if bromocriptine given(Class IIa)
Outcomes
● 25-60% of women show LVEF recovery by 6 months
● Substantial variation according to ethnic background and geographical region with worse outcome in Black women in the United States and among women in less developed countries worldwide
 Figure 7 Risk factors and management of peripartum cardiomyopathy. CMR, cardiac magnetic resonance imaging; HF, heart failure; LVEF, left ventricular ejection fraction; P/LP, pathogenic/likely pathogenic; PPCM, peripartum cardiomyopathy. In specific cases.
<BeginOfPara>can be initiated, except if lactation and breastfeeding are necessary for nutritional reasons, in which case ARBs and SGLT2 inhibitors should be avoided. Spironolactone is considered safe(see Section 5.2.7 and Figure 7).
In addition to HF treatment, the prolactin production suppressing agent bromocritine may be considered in women with PPCM(Figure 7). ${}^{358-360}$ A secondary effect of bromocritine is stopping
lactation, which enables the possibility of full HF treatment of the mother that is not breeding. The downsides of stopping lactation as PPCM treatment include psychological implications for the mother and the source of nutrition for the infant. These considerations indicate that women with moderate and severe HF in PPCM are the preferred candidates for bromocriptine treatment. A recent multi-centre rando-mized study comparing two different bromocriptine dosages in women
ESC Guidelines
39
with severe PPCM(2.5 mg daily for 1 week vs 5 mg daily for 2 weeks followed by 2.5 mg daily for 6 weeks) observed a high LV recovery rate at 6 months. No significant differences were observed between treatment over 1 week and 8 weeks, suggesting that a 1 week addition of bromocritine to standard heart failure treatment would be benefi-cial.358 There are limited data on the use of bromocritine in pregnant women with PPCM and cardiogenic shock.339,361 Personalized bromo-critine treatment, with dose adjustments to effectively suppress pro-lactin, may be a viable therapeutic option in these specific cases. Adding LMWH(in prophylactic doses at a minimum) to bromocritine should be considered to reduce the thromboembolic risk.362
7.4. Outcomes
Risk stratification is crucial to determine the appropriate level of care for women diagnosed with PPCM(Figure 7). Key indicators to identify indi-viduals at risk of complications include LVEF<30%, LV end-diastolic diameter>60 mm,biventricular dysfunction,ECG QT interval prolonga-tion, delayed diagnosis, and Middle Eastern or African ethnicity and/or geography.344 Additional parameters such as age(>40 or<20 years),antepartum diagnosis, haemodynamic parameters at presentation, and cardiac biomarkers can further refine risk stratification.
PPCM may cause ventricular tachyarrhythmias and patients should therefore be monitored.363,364 As~50% of women with PPCM recover within 1 year after delivery, a wearable cardioverter with cryptor (WCD)for pregnant women with LVEF<35% at risk of sudden cardiac death may be considered to provide bridging therapy to recovery.
Myocardial recovery after PPCM, defined as LVEF>50%, has been shown to occur in 46%(25%-62% according to geographical region)of women at 6 months.16 Full Hf treatment should be given during the first year after complete LV function recovery. Stepwise discontinuation of HF therapy may be considered after 1 year if complete myocardial re-covery is achieved, assuming that no genetic predisposition has been identified.339,367 However, recent data indicated higher risk of LVEF re-lapse during subsequent pregnancies in PPCM women who had discon-tinued their HF medication.368 Left ventricular assist device(LVAD) or heart transplantation have been reported in up to 10% of PPCM cases,with inferior survival rates compared to other age-adjusted heart trans-plant recipients.340
Outcomes after PPCM differ globally.344 The Eurobservational Research Programme's(EORP) PPCM registry reported low mortality rates369 of 2.4% 1 month after diagnosis.370 However, the mortality rate at 6 months was 6%, with HF and cardiac arrest as the more freestu quent causes of death.16 At 1 year follow-up, death from any cause oc-curred in 8% of women, with regional variations(Europe 5%, Africa 6%,Asia-Pacific 9%, Middle East 19%; P<.001).
Women with a previous PCM diagnosis a notably elevated risk of poor outcomes. In the most recent EORP paper following women with subsequent pregnancies after PPCM, risk of maternal mortality was lower than in previous reports, at 2% at 198 days after delivery.368 More than mild LV dysfunction before a new pregnancy increases the risk of LVEF deterioration, but also women with recovered LV functions re-mained at risk of relapse.368 In women planning a new pregnancy after a previous PPCM and with only mild LV dysfunction, stress echo without contraindized HF medication may be helpful to further stratify risk.Having a good contractile reserve after HF medication has been dis-contined may be an encouraging prognostic sign.371 If planning a new preg-nancy after PPCM, discontinuation of beta-blocking therapy may not be advisable, and restarting beta-blocking therapy may be beneficial at a sub-sequent pregnancy, irrespective of baseline LV systolic function.368
Recommendation Table 7- Recommendations for peripartum cardiomyopathy(see Evidence Table 7)
|Recommendations|Classa|Levelb| |---|---|---| |Counselling for women with PPCM about the risk of recurrence during a subsequent pregnancy and about contraception is recommended in all cases, even after recovery of LV function(LVEF>50%).355,369||C| |Adding at least prophylactic LMWH treatment to bromoriptine treatment in women with PPCM should be considered.358,362,372,373|lla|C| |Genetic counselling and testing should be considered in women with PPCM.60|lla|C| |When a reversible course of HF is assumed, treatment in accordance with HF guidelines should be considered for at least 12 months after complete LV recovery(normalization of LV volumes and EF).339,345,368,374|lla|C| |Bromoriptine treatment may be considered in addition to optimal HF treatment to enhance recovery of LV function in women with PPCM.358- 360,366,375,376|lb|B| |The use of a WCD may be considered in women with PPCM and LVEF<35%.377|lb|C|
EF,ejection fraction;HF, heart failure; LMWH, low-molecular-weight heparin; LV, left ventricle; LVEF, left ventriclear ejection fraction; PPCM, peripartum cardiomyopathy;WCD, wearable cardioverter defibrillator.
8. Pregnancy in women with aortopathies
Acute arterial dissection during pregnancy occurs in 5.5/100 000 live births, with the aorta being the third most frequent location(19.8%)after coronary artery dissection(38.2%) and vertebral artery dissection(22.9%).378 A large cohort study reported an aortic dissection rate of 5.5 per million women during pregnancy and post-partum, compared with 1.4 per million during the equivalent period 1 year later.40 Although rare, acute aortic syndromes carry high foetal and maternal morbidity and mortality risks.378,379 Arterial dissections occur ante-natally in 15%, intrapartum in 23%, and post-partum in 62% of cases.378 Most pregnancy-related aortic dissections occur in women who are un-aware of their underlying aortic disease380 and events rarely occur in women who have been monitored according to guidelines. The risk of peripartum dissection in more distal aortic segments remains after prior aortic root replacement.381 The mechanism for dissection during pregnancy is unclear. Given the high post-partum prevalence, haemo-dynamic changes alone do not fully explain the increased risk and hor-monal influences are likely involved.
8.1. Women with heritable thoracic aortic disease
The number of genes associated with heritable thoracic aortic disease(HTAD) is steadily increasing. Although there is clear evidence for an increased risk of aortic dissection in HTAD, recent data from the
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ROPAC III study showed that the aortic dissection incidence rate(3.5%)in pregnant women with HTAD was lower than previously reported.382 Phenotypes and outcomes between different genes and variants vary,are of clinical importance, and impose differences in management with regard to the extent of imaging, surveillance, and referral for sur-gery.62,383 Clinical and genetic entities for which data are available are discussed below and included in Figure 8.
8.1.1. Marfan syndrome
Marfan syndrome(MFS) is caused by P/LP variants in FBN1.Pregnancy-associated cardiovascular events include aortic and coronary artery dissection as well as rapid aortic growth necessitating surgery.384 Aortic event rates can reach up to 10%. Although type A dissections mainly occur in undiagnosed women, often with aortic diameters ex-ceeding surgical thresholds,389 type B dissections remain unpredictable and can occur even after prophylactic root replacement.390 Women di-agnosed earlier in life have a lower risk of dissection.391 More dissections occur during the post-partum period than during pregnancy or at deliv-ery.384,392 Event rates and overall maternal mortality are low in women under guidelines-based follow-up.7,390 Studies have shown stable aortic root diameters during pregnancy in women with diameters between 40 and 45 mm.384,393 No significant difference in aortic events is noted be-tween ever-pregnant and never-pregnant women,384,392 but most data come from patients in highly controlled environments.
8.1.2. Loeys-Dietz syndrome
Loeys-Dietz syndrome(LDS) is linked to P/LP variants in six genes:TGFBR1,TGFBR2,SMAD2,SMAD3,TGFB2,and TGFB3,Aortic outcomes in LDS vary by gene and variant, leading to gene-specific recommenda-tions for aortic root surgery thresholds.62,383,388 Planned pregnancy is a known risk factor, but data on dissection risk during pregnancy, including diameters at dissection, are limited. Cases of type B dissection after aortic root replacement have been reported.394 A higher incidence of haemor-rhagic events, reported in earlier studies, ${}^{395}$ was not corroborated in a recent ROPAC III study.382 Although pregnancy data for women with LDS are sparse, recent reports suggest favourable maternal and foetal outcomes with appropriate counselling and surveillance.395 The lack of data about aortic diameters at dissection during pregnancy limits high-level recommendations for prophylactic aortic root surgery thresholds.
8.1.3. Vascular Ehlers-Danlos syndrome
With a reported pregnancy-related mortality rate of 5% and life-threatening vascular events in up to 10% of pregnancies, women with vascular Ehlers-Danlos syndrome undeniably have high-risk pregnan-cies.396 Pregnancy-related complications include vascular dissection or rupture, uterine rupture, perineal tears, haemorrhage, and prema-ture birth. However, pregnancy and delivery do not seem to affect overall survival rates in women with vascular Ehlers-Danlos syn-drome. ${}^{397}$ The risk may be lower for some women with specific genetic variants,null mutations,and normal vascular imaging. ${}^{398,399}$ 慕eliprol is recommended(also in normotensive women), given the very high risk of dissections and the benefit demonstrated in non-pregnant popula-tions. ${}^{7}$ Shared decision-making is crucial for these women. A ROPAC study included four women with vascular Ehlers-Danlos syndrome who experienced pregnancy without adverse maternal events. ${}^{7}$ Based on data from a recent systematic review, caesarean section at 37 weeks should be scheduled to avoid obstetrical complications. ${}^{400}$ Women
with vascular Ehlers-Danlos syndrome should be counselled on preg-nancy risk and monitored by a Pregnancy Heart Team.
8.1.4. Non-syndromic heritable thoracic aortic diseases
The number of genes linked to non-syndromic heritable thoracic aortic diseases(nsHTAD) is growing, including those rarely associated with extra-aortic features such as MYLK, ACTA2, MYH11, and PRKG1. 401,402 For most cases, specific pregnancy management recommendations are limited. Pragmatically, prophylactic surgery in nsHTAD is recommended at a diameter>45 mm. In women with variants in PRKG1, certain ACTA2 variants, or additional risk factors that carry a high dissection risk at small diameters, such as hypertension or family history of dissection at smaller diameters, surgery may be considered at lower diameters(>40 mm).386
8.1.5. Aortic disease with no identifiable(likely)pathogenic variant
It is unclear whether young women with known aortic disease in whom genetic screening fails to identify a P/LP variant truly have a lower dis-section risk than those with a known variant. The term'sporadic aneur-ysm' is discouraged, as an aneurysm may stem from a heritable disorder even without a family history. Recent data from a large cohort of type A aortic dissection patients<30 years of age showed a near dichotomy between HTAD and unknown hypertension as probable dissection causes.403
8.2. Turner syndrome
Approximately 50% of women with Turner syndrome(TS) have cardiovascular manifestations, including aortic dilatation, bicuspid aortic valve(BAV), aortic coarctation, elongated aortic arch, and partial ab-normal pulmonary venous return.404,405 All women with TS present a generalized arteriopathy and TS itself is an independent risk factor for thoracic aortic dilatation. Aortic dissection risk(85% type A and 15% type B increases with increasing diameters and can be reduced by following treatment guidelines.406-409 Risk factors include hyperten-sion,BAV, and coarctation. In women with TS and an aortic size index(ASI)≥25 mm/m2, aortic height index≥25 mm/m or a z-score>4, the increased dissection risk and the option of surgery before pregnancy should be discussed with the patient and the Pregnancy Heart Team,taking the other risk factors into account. 410-412 Spontaneous preg-nancy can occur in women with mosaic TS, but assisted fertility tech-niques are now more common. Timely cardiovascular evaluation before fertility treatment is very important. Higher rates of adverse events during pregnancy and post-partum have been reported including hypertensive disease, gestational diabetes, haemorrhage, and SGA babies. 413,414 Caesarean section rates of up to 67% have been reported.414
8.3. Bicuspid aortic valve disease
Available data for patients with BAV indicate a low risk of aortic events if the aorta is<45 mm. Data on pregnancy in women with diameters of 45-50 mm are limited.7,415 Recent data on patients with BAV demon-strate a higher risk of dissection in those with a'root phenotype' com-pared to those with a primarily ascending aorta involvement. 416,417 When counselling these patients, it is important to note that BAV does not exclude the possibility of nsHTAD.
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8.4. Aortic aneurysms other than root or ascending aorta
Currently there are no recommendations for prophylactic surgery be-fore conceiving except for the aortic root and ascending aorta. Recently published guidelines recommended surgery for the undissected aortic arch, descending and abdominal aorta at 50 mm in patients with Marfan syndrome, ${ }^{62}$ but no specific guidelines for management in preg-nancy are available.
8.5. Aortic dissection
Data about pregnancy in women with a history of aortic dissection are scarce. ROPAC II and III included 11 and 9 women,respectively, with a previous dissection and reported no maternal mortality. However, two women in ROPAC III had a recurrent aortic event. ${}^{7,382}$ Adverse events are likely low in women with a history of traumatic or iatrogenic dissec-tion and probably also for those with a maximum aortic diameter of<40 mm and documented stable follow-up. Obviously there is a selec-tion bias, as many women with complex aortic disease choose not to have children independent of the risk of progression of aortic disease.
8.6.Management
Women with aortic disease should be managed by a multidisciplinary team with experts from both the Pregnancy Heart Team and the aor-tic team who are experienced in diagnostic pathways, medical and sur-gical management of aortopathies in the ante-, peri-, and post-partum periods. Institutional protocols for the management of pregnancy-related aortic events should be available and a shared-decision model needs to be applied. Imaging of the entire aorta (CT or CMR) in wo-men with known or suspected aortic disease is recommended and can reasonably be performed for most clinical scenarios within the 6 months prior to pregnancy. CMR without gadolinium is recom-mended in pregnant women with known aortopathy, without pre-pregnancy imaging. In all women with aortic disease, strict blood pressure control is recommended. Specific target values for this spe-cific situation have not been studied-in the general population it is recommended that treated systolic blood pressure values be tar-geted to 120-129 mmHg to reduce CVD, provided the treatment is well tolerated. 388,418 In women with genetic aortopathies, treatment with beta-blockers throughout pregnancy should be considered with foetal growth monitoring. Women who used beta-blockers
 Figure 8 Thresholds for prophylactic surgical treatment prior to pregnancy of aortic root/ascending aneurysm(above the line) and recommended mode of delivery according to aortic diameter(below the line). BAV, bicuspid aortic valve; LDS, Loeys-Dietz syndrome;MFS, Marfan syndrome, nsHTAD, non-syndromic heritable thoracic aortic disease; P/LP, pathogenic/likely pathogenic; TAD, thoracic aortic disease; w/o, without.3aRisk factors: family history of dissection, rapid aortic growth(≥3 mm/year), uncontrolled hypertension. bRoot phenotype to be added to the other risk factors. Based on Narula et al.,385 Wallace et al.,385 Regalado et al.,386 Jonadeu et al.,387 Mazzolai et al.,388 and Isellbacher et al.62.
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throughout pregnancy in the ROPAC III study gave birth to infants with a significantly lower birth weight than women who did not. ${}^{382}$ Specific thresholds for pre-conception aortic root surgery are illu-strated in Figure 8.
The mode of delivery needs to be informed by the patient's history,presence and type of gene/variant, and aortic diameter. The primary aim of intrapartum management in women with aortic disease is to re-duce the cardiovascular stress of labour and delivery. Caesarean section may be considered in women with a maximum diameter of>45 mm and those with a history of dissection. In women with an aortic diam-eter<40 mm, vaginal delivery is recommended. In women with MFS,LDS, and vascular Ehlers-Danlos syndrome, pre-delivery anaesthi-ology consultation is recommended to consider precautions for dural ectasia and scoliosis(including possible previous surgery). 419 In general,an individualized approach is favoured.383 Given the peak risk of a dis-section at day 6 post-partum, it may be appropriate for women to stay in hospital for 1 week post-partum.420
8.7. Cardiac surgery during pregnancy
Prophylactic cardiac surgery in women who are planning a pregnancy is far more common than urgent or emergency surgery during pregnancy.Aortic surgery is the most frequently performed procedure during preg-nancy, followed by surgery for aortic and mitral valve disease. Key pregnancy-related pathologies include prosthetic valve thrombosis and endocarditis. The decision to perform surgery with extracorporeal circula-tion and cardioplegic arrest during pregnancy is highly individualized with no specific guidelines available. A recent meta-analysis 421 reported a maternal mortality rate of 7.3% consistent across trimesters, and no difference in ma-ternal mortality if caesarean section was performed. Overall foetal mortal-ity was 26.5%, lowest during third trimester surgeries(10.3%). Caesarean section before surgery significantly reduces foetal mortality. The decision to perform a caesarean section prior to surgery should be based on foetal viability and the level of medical care available rather than on a fixed gesta-tional age. This is particularly crucial in acute type A aortic dissection.Hypothermic distal circulatory arrest increases foetal mortality. ${}^{422}$
Recommendation Table 8-Recommendations for aortopathies, cardiac surgery, and pregnancy
|Recommendations|Classa|Levelb| |---|---|---| |Counselling||| |It is recommended that women with aortic disease have counselling about the risk of aortic dissection in pregnancy and the post-partum period. 404,423|I|C| |It is recommended that women with a history of aortic dissection or-surgery have pre-pregnancy counselling about the high risk by an extended Pregnancy Heart Team' considering the presence and type of genetic variant, aortic morphology, growth rate, and aetiology of aortic dissection. 7,381,424|I|C| |It is recommended that women with vascular Ehlers-Danios syndrome wishing to become pregnant are counselled regarding the very high risk of pregnancy-related adverse events by a multidisciplinary team, considering family history, genetic variant, and previous vascular events. 7,396,397,425|I|C| |Imaging||| |Imaging of the entire aorta d(CT or CMR) is recommended before pregnancy in women with known or suspected aortic disease. 390,424,426|I|C| |In women with aortic dilatation related to BAV, imaging(with TTE, and CMR/CT if needed) of the aortic root, ascending aorta, and descending aorta(to rule out coarctation) is recommended before pregnancy. 427,428|I|C| |In women with low-risk aortic disease(mWHO 2.0 classes II and II-III), one-time echocardiographic imaging between 20 and 30 weeks of gestation and imaging at 6 months post-partum is recommended. 393,429|I|C| |In women with moderate to high-risk aortic disease(mWHO 2.0 classes III and IV), repeated echocardiographic imaging every 4-12 weeks (depending on diagnosis and severity of dilatation) is recommended during pregnancy and until 6 months post-partum. 393,429,430|I|C| |CMR (without gadolinium) imaging of the entire aorta is recommended in pregnant women at risk of or with known aortic dilatation who have not had recent pre-pregnancy cross sectional imaging. 135|I|C| |Treatment-medical||| |When a woman with known aortic dilatation, history of dissection, or P/LP variant associated with aortic disease becomes pregnant, strict and individualized BP control is recommended. 431,432|I|C| |Beta-blocker therapy e throughout pregnancy and in the post-partum period is recommended in women with MFS and other HTADs. 433|I|C| |Celiprolol is recommended in women with vascular Ehlers-Danios syndrome during pregnancy and lactation. 434|I|C| |Treatment-intervention/surgical||| |It is recommended that indications for pre-pregnancy aortic root and/or ascending aortic surgery are guided by aortic morphology, underlying pathology, family history, genetic variant, previous vascular events, and patient's preference. 62,383|I|C| |It is recommended that centres managing pregnancies in women with moderate to high-risk aortic disease (mWHO 2.0 class III/IV) can provide cardiovascular surgery in case of peripartum adverse events. 435,436|I|C| |Specific conditions||| |In women with MFS and aortic root diameters>45 mm, surgery before pregnancy is recommended. 380,424|I|C| |In women with LDS with P/LP variants in TGFBR1,TGFBR2, and aortic root diameters≥45 mm, surgery before pregnancy is recommended. 437-439|I|C|
Continued
<FIGTEXT=></FIGTEXT>
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|In women with nsHTAD with P/LP variants in MYH11, ACTA2, PRKG1, or MYLK, and aortic root diameters≥45 mm, surgery before pregnancy is recommended. ${}^{385,386,440}$|I|C| |---|---|---| |In women with BAV and aortic root or ascending aortic diameter≥50 mm, surgery before pregnancy is recommended.|1|C| |In women without an identifiable P/LP variant with aortic root or ascending aortic diameters≥50 mm, surgery before pregnancy is recommended.|I|C| |In women with HTAD and aortic arch, descending aortic, or abdominal aortic diameters≥50 mm, surgery before pregnancy should be considered. ${}^{392,443}$|lla|C| |In women with LDS with P/LP variants in TGFβ2,TGFβ3, SMAD2, and SMAD3, and aortic root diameters≥45 mm, surgery before pregnancy should be considered. ${}^{437,439}$|lla|C| |In women with BAV and root phenotype or family history of aortic aneurysm or dissection, surgery before pregnancy should be considered if the aorta is≥45 mm.|lla|C| |In women without an identifiable P/LP variant with aortic root or ascending aortic aneurysm≥45 mm, surgery before pregnancy should be considered in the presence of a family history of aortic aneurysm, aortic dissection, uncontrolled arterial hypertension, or on patient's preference.|lla|C| |In women with MFS and aortic root diameters between 40 and 45 mm, surgery before pregnancy may be considered if risk factors(growth >3 mm/year, family history of aortic dissection) are present. ${}^{444}$|llb|C| |In women with LDS with P/LP variants in TGFβFR1 or TGFβ2 and aortic root diameters≥40 mm,surgery before pregnancy may be considered. ${}^{387,437,445,446}$|llb|C| |In women with nsHTAD and aortic root diameters≥40-44 mm, surgery before pregnancy may be considered in the genetic variant, family history, and aortic growth rate. ${}^{385,386,440}$|llb|C| |Delivery|I|C| |In women with a aorta <40 mm, vaginal delivery is recommended.|I|C| |In women with vascular Ehlers-Danlos syndrome, caesarean section at 37 weeks is recommended for obstetrical reasons.|I|C| |In women with a aorta 40-45 mm, vaginal delivery with epidural anaesthesia and an expedited second stage should be considered.|lla|C| |In women with an aorta≥45 mm, caesarean section should be considered.|lla|C| |In women with a aorta 40-55 mm, caesarean section may be considered.|llb|C| |The use of ergometrine post-delivery is not recommended in women with aortomy.|III|C| |Cardiac surgery during pregnancy||| |Delivery before cardiac surgery should be considered as soon as the foetus is viable, taking gestational age, comorbidities, and the available level of neonatal care into account. ${}^{163,421,435,447}$|lla|C| |Cardiac surgery may be considered during pregnancy when conservative and medical therapy has failed, and in situations that threaten the mother's life or that are not amenable to percutaneous treatment.|llb|C|
BAV, bicuspid aortic valve; BP, blood pressure; CMR, cardiovascular magnetic resonance imaging; CT, computed tomography; HTAD, heritable thoracic aortic disease; LDS, Loeys-Dietz syndrome; MFS, Marfan syndrome; mWHO, modified World Health Organization; nsHTAD, non-syndromic heritable thoracic aortic disease; P/LP, pathogenic/likely pathogenic; TTE,transthoracic echocardiogram.
Class of recommendation.
bLevel of evidence.
‘Extended Pregnancy Heart Team: regular team+ multidisciplinary aortic team-see also Section 4.1.
In women with vascular Ehlers-Danlos syndrome and LDS, imaging should encompass the entire aorta, including supra-aortic vessels as well as iliac and femoral arteries.
See Section 5.2.9 for beta-blocker choice.
9. Pregnancy in women with known congenital heart disease
Congenital heart disease is present in 0.8%-0.9% of live births, with signifi-cant geographical variation.448,449 Nowadays, most children born with con-genital heart disease reach fertile age, even those with complex lesions,making adult congenital heart disease(ACHD) one of the most frequent CVDs during pregnancy.450 Discussions about family planning, contracep-tion, pregnancy risk(mWHO 20-see Table 6), and life expectancy are es-sential and should start early, preferably during the transition to adult life.2
In the prospective ROPAC registry, most women with ACHD(n=3295) had a relatively favourful pregnancy outcome, with an overall mortality rate of 0.2% and trends improving from 2007 to 2017.2 Heart failure rates were low in ROPAC, with differences according
to disease complexity(13% in severe, 5%-6% in less-complex lesions).Arrhythmia rates were low overall(2%). Women with uncorrected ACHD more often have maternal and foetal complications.451 Women with ACHD experiencing complications during pregnancy and post-partum may also be at higher risk of late cardiac events.451
Pre-pregnancy evaluation should at least include routine blood tests,ECG,TTE, and cardiulmonary exercise testing. As mentioned in Section 4, the increased transmission risk should be discussed, and gen-etic counselling should be offered.452 The level and timing of the pre-pregnancy cardiovascular evaluation and follow-up during pregnancy depend on the mWHO 2.0 class(see Table 6), taking the anatomical and functional status into account.
Optimization of cardiac status and any comorbidities should take place prior to pregnancy. This includes guideline-directed elective surgery or/and
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intervention of significant haemodynamic lesions(native or residual),21 as well as optimizing medical therapy and healthy lifestyle choices.
The timing and mode of delivery should be decided by the Pregnancy Heart Team, for all women with a condition of mWHO 2.0 class II-III or above. In general, vaginal delivery is the preferred de-livery mode in women with ACHD.163 Post-partum monitoring should be individualized based on the woman's underlying ACHD, risk or presence of arrhythmias and/or HF, and the course during pregnancy
and delivery. High-risk women or those with HF symptoms during pregnancy or delivery should be considered for intensive(cardiac)care admission for haemodynamic monitoring.183 For more details about managing the various delivery stages, including post-partum,see Sections 4.5 and 4.6.1.
A summary of relevant disease-specific considerations, maternal and foetal complications, monitoring, and management during pregnancy are listed in Table 12.
Table 12 Risks, monitoring, and management during pregnancy and delivery in women with congenital heart disease
|ACHD|Maternal Risk|Obstetric and foetal risk|Monitoring|Pregnancy management and delivery| |---|---|---|---|---| |Left ventricular outflow tract obstruction(LVOTO)||||| |Coarctation of the aorta|●↑ Complication risk if residual obstruction (gradient >20 mmHg, aortic lumen <12 mm), clinical signs of HF, LVEF<40%, NYHA class>1° ●↑ Risk of aortic dissection (if aneurysm present) ● Uncontrolled hypertension|●↑ Miscarriage rate453 ● Pre-term birth and low birth weight in 99°|● Close BP monitoring -also early post-partum ● Pre-pregnancy CMR and treatment of residual lesions 454|●Treat hypertensiona ● Consider bed rest, hospital admission and stenting in case of severe symptomatic (re)coarctation (including refractory hypertension or maternal/foetal compromise) 455 ● Vaginal delivery preferred unless aneurysm,HF,severe hypertension|
Shunt lesions
|ASD|● Low risk in(un)repaired ASD (if no PAH) 157 Unrepaired ASD: ●↑ Risk of arrhythmia(4%)457 ● Paradoxical embolism (2%-5%)457,458|● Rare ${}^{457}$ ● Unrepaired ASD: ●SGA(21%) ● Foetal/perinatal mortality(2%-3%) ● Pre-eclampsia(7%)|Unrepaired and uncomplicated ASD: consider TTE at 28-32 weeks|● Large and/or haemodynamically significant ASD: closure pre-pregnancy21 ● Unrepaired ASD: ● Consider ASA or prophylactic LMWHd for paradoxical embolism prevention ● Consider device closure in pregnancy only for recurrent stroke on medical therapy| |---|---|---|---|---| |VSD and patent ductus arteriosus|Low risk in small or repaired lesions with normal LV and no PAH°|No evidence for↑ risk|Unrepaired and uncomplicated VSD: consider TTE at 28-32 weeks|Vaginal delivery is preferred| |AVSD|● Low risk in repaired AVSD without significant residual lesions|● Offspring mortality in 6% primarily due to recurrence of the congenital heart|Unrepaired and uncomplicated AVSD: consider TTE at 28-32 weeks|● Residual shunt: see ASD and/or VSD ●↑ AV valve regurgitation and/or HF ● PAH°| ||regurgitation and HF if residual left AV valve regurgitation 459,460|disease 459|↑ FU frequency in significant valve regurgitation, PAH,↓ ventricular function, or↑|● Delivery: see ASD and VSD| ||●Paradoxical emboli risk in unoperated(partial) AVSD|||| |Pulmonary valve and RVOT disease||||| |RVOTO/PV stenosis|● Mild to moderate: low risk ● Severe: RV failure and arrhythmia21|● Very low complication: risk 462,463|● Mild to moderate: ● TTE at 28-32 weeks ● Severe stenosis:|Pre-pregnancy severe RVOTO(Doppler peak gradient>64 mmHg) or/and any signs of right HF:| |||||Continued|
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||||● (Bi)monthly TTE (focused on RV function)|● Intervention (at any level of the RVOT) $^{21}$ Severe symptomatic PV stenosis (not responding to bed rest and conservative management): ● Consider transcatheter balloon valvotomy 21 Consider caesarean section in severe RVOTO/PV stenosis 463| |---|---|---|---|---| |PV regurgitation|●↑ Risk when impaired RV function462|● Premature birth463|Bimonthly TTE if severe PV regurgitation and↓ RV function|| |Post pulmonary valve replacement (surgical or transcatheter without severe stenosis/regurgitation)|● Low risk463-466|● Very low complication risk462,463|TTE at 28-32 weeks|Vaginal delivery is preferred| |Repaired TOF||||| ||● Low risk if no residual lesions467 ●↑ Risk of arrhythmia and HF (7%-10%) if pulmonary regurgitation,↓ RV function, severe RVOTO467,468|● 15% risk of foetal and obstetric complications, mainly pre-term delivery and low birth weight467 ● Low foetal mortality (0.7%)467 ● Recurrence risk in the offspring in 22q11 deletion syndrome: 50%|● First trimester and at 28-32 weeks FU with TTE(increase FU depending on functional status)|● RV failure management: Bed rest and diuretics ● Arrhythmia management8 ● Severe PV stenosis/regurgitation: see above ● Vaginal delivery is preferred| |Ebstein anomaly|Ebstein anomaly|Ebstein anomaly|Ebstein anomaly|| ||● Overall MACE rate in ROPAC 9.9%|● Foetal risk is related to↓ maternal CO and cyanosis ${}^{3,469}$ : ● Miscarriage ●(Very) high risk when pre-pregnancy HF,cyanosis due to atrial shunt ●↑ Arrhythmia risk due to accessory pathways469|● Mild to moderate: baseline and 28-32 weeks assessment with TTE and ECG ● Severe: monthly/ bimonthly TTE& ECG binomally TTE& ECG|● Severe tricuspid regurgitation with HF can usually be managed medically ● Treat arrhythmias promptly ● Appropriate pre-pregnancy counselling about very high risk of MACE when HF and/or cyanosis| |Transposition of the great arteries||||| |TGA after atrial switch (Mustard or Sening) and CCTGA|● High pregnancy risk—MACE rate up to 28% in retrospective series470- lower risk in ROPAC6: Atrial and ventricular arrhythmias in 6.7%,HF in 10% ● Atrial arrhythmias often poorly tolerated ● Baffle leaks may lead to desaturation and paradoxical embolism471 ● Predictors of MACE: symptoms of HF before pregnancy and systemic RV EF <40%6|● Foetal risks associated with maternal CO and saturation ● Pre-term birth (21%) ● Low birth weight (18%-21%)6,472,473 ● Rare foetal and neonatal death (1%)474 ● PPH(7%)6|● According to anatomical and functional status: TTE every 1-3 months and serial NP ● Holter monitoring if palitations|● Pre-pregnancy counselling about very high risk if NYHA class III/IV, systemic RV EF <40%, more than moderate tricuspid regurgitation, or treated HF472,473,475 ● Treat HF primarily with medical therapy ● Promptly treat arrhythmia8 ● Consider prolonged post-partum monitoring (48-72 h) and early post-partum FU given the ↑ risk of post-partum HF No clear evidence for long-term deterioration or ↑ cardiovascular events associated with pregnancy 6,476| |TGA with arterial switch|● Low risk ● Ventricular arrhythmias (2.5%-7%),HF(2%-4%)8|● Low rate of prematurity or foel total loss ${}^{47,47}$|● Consider TTE at 20 weeks ● Intensify if ↓ ventricular function, $\uparrow$ aortic|● Vaginal delivery is preferred ● Surgery before pregnancy when the neo-aortic root is >55 mm ${}^{21,478}$ or if severe AR ${}^{f}$|
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||||regurgitation and ↑||| |---|---|---|---|---|---| |Single ventricle physiology palliated with Fontan circulation|||||| ||High pregnancy risk CV events ${}^{479}$ :|↑Very high foetal complication risk. ${}^{479-483}$|● According to anatomical and functional status: TTE|● Pre-pregnancy counselling about very high risk especially if any risk factor(see maternal risk)|| ||● Supraventricular arrhythmias (8%-11%)|● Low live birth rate(56%) ● Miscarriages (45%-54%)|● Miscarriages (45%-54%)|●Pregnancy may be well tolerated and successful in a subset of women with single ventricle and Fontan circulation without complications479,480,485-487|| ||● HF(4%-14%)|● SGA(20%-55%)|● SGA(20%-55%)||| ||Risk factors. ${}^{479}$|● Premature birth(59%- 72%)|● FU in specialized||| ||● Oxygen saturations<85%||ACHD centre|Fontan circulation without complications479,480,485-487|| ||● ↓ Ventricular function|● Neonatal death(5%-|||| ||● Arrhythmias|18%)||● ASA and/or LMWH(depending on the presence of complications)|| ||● Significant valvular disease|Obstetric risk:|||| ||● NYHA class III/IV|● Hypertension(14%)||should be considered in shared decision ${}^{484}$|| ||● FALD|● PPH(13%)||● Atrial tachyarrhythmias should be promptly treated with maternal oxygen|| |Labourlo delivery with preload dependent|||||| |EF, ejection fraction; FALD, Fontan-associated liver disease; FU, follow-up; HF, heart failure; iv., intravenous; LMWH, low-molecular-weight heparin; LV, left ventricle; LVEF, left ventricular ejection fraction; LVOTO, left ventricular outflow obstruction; MACE: major adverse cardiovascular events; NP, natriuretic peptide; NYHA, New York Heart|||||| |Association; PAH, pulmonary arterial hypertension; PPH, post-partum haemorrhage; PV, pulmonary valve; ROPAC, Registryry of Pregnancy and Cardiac Disevorticle, RVOT, right ventricle outflow tract obstruction; SGA, small for gestational age; TGA, transposition of the great arteries; TOF, tetralogy of Fallot; TTE, transthoracic echocardiogram; VSD, ventricle septal defect.|||||| |↑ increase ↓ decrease.|||||| |${}^{2}$ Refer to Section 12.3 Hypertensive disorders.|||||| |${}^{2}$ Refer to Section 12.5.1 Stenotic native valve lesions.|||||| |${}^{2}$ Refer to Section 8.3 Bicuspid aortic valve disease.|||||| |${}^{2}$ Refer to Section 5 Drugs during pregnancy and lactation.|||||| |${}^{2}$ Refer to Section 10 Pregnancy in women with pulmonary arterial hypertension,"Refer to Section 12.52 Regurgitant native valve lesions.|||||| |${}^{2}$ Refer to Section 12.4 Arrhythmias.|||||| |${}^{2}$ Refer to Section 12.6 Heart failure.|||||| |${}^{2}$ Refer to Section 12.4.3 Cardioversion, ablation, and device implantation and implantable cardioverter defibrator management.||||||
ACHD, adult congenital heart disease; ASA, acetylsalicylic acid; ASD, atrial septal defect; AV, atrioventricular; AVSD, atrioventricular septal defect; BAV, bicuspid aortic valve; BP, blood pressure; CCTGA, congenitally corrected transposition of the great arteries; CMR, cardiovascular magnetic resonance; CO, cardiac output; CV, cardiovascular; ECG, electrocardiogram;EF, ejection fraction; FALD, Fontan-associated liver disease; FU, follow-up; HF, heart failure; iv., intravenous; LMWH, low-molecular-weight heparin; LV, left ventricle; LVEF, left ventricular ejection fraction; LVOTO, left ventricular outflow tract obstruction; MACE: major adverse cardiovascular events; NP, natriuretic peptide; NYHA, New York Heart Association; PAH, pulmonary arterial hypertension; PPH, post-partum haemorrhage; PV, pulmonary valve; ROPAC, Registry of Pregnancy and Cardiac Disease; RV, right ventricle,RVOTO, right ventricle outflow tract obstruction; SGA, small for gestational age; TGA, transposition of the great arteries; TOF, tetralogy of Fallot; TTE, transthoracic echocardiogram;VSD, ventricle septal defect.
↑ increase↓ decrease.
Refer to Section 12.3 Hypertensive disorders.
bRefer to Section 12.5.1 Stenotic native valve lesions.
Refer to Section 8.3 Bicuspid aortic valve disease.
Referto in Section 5 Drugs during pregnancy and lactation.
Refer to Section 10 Pregnancy in women with pulmonary arterial hypertension.
Refer to Section 12.5.2 Regurgitant native valve lesions.
Refer to Section 12.4 Arrhythmias.
"Refer to Section 12.6 Heart failure.
'Refer to Section 12.4.3 Cardioversion, ablation, and device implantation and implantable cardioverter defibrillator management.
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Recommendation Table 9- Recommendations for congenital heart disease and pregnancy(see Evidence Table 8)
|Recommendations|Classa|Levelb| |---|---|---| |Vaginal delivery is recommended in most women with ACHD.161,163|I|B| |It is recommended that all women with Fontan circulation who wish to become pregnant receive counselling from the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.479,480,484,486,487|I|C| |It is recommended that women with a systemic RV (Mustard/Senning or congenitally corrected TGA), in NYHA class III/IV, systemic ventricular dysfunction (EF <40%), or severe TR wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.473-475|I|C| |In women with significant haemodynamic lesions, discussion about guideline-directed interventions is recommended prior to pregnancy.|I|C|
ACHD, adult congenital heart disease; EF, ejection fraction; NYHA, New York Heart Association; RV, right ventricle; TGA, transposition of the great arteries; TR, tricuspid regurgitation.
${}^{a}$ Class of recommendation.
bLevel of evidence.
10. Pregnancy in women with pulmonary arterial hypertension
Pulmonary hypertension(PH) is defined as a mean pulmonary arterial pressure>20 mmHg, derived from invasive right-heart cath-eterization, and is classified by aetiology and pathophysiology.490 Pulmonary arterial hypertension(PAH) is pre-capillary PH character-ized by a pulmonary vascular resistance>2 Wood units and pulmon-ary arterial wedge pressure≤15 mmHg. Untreated, idiopathic PAH results in death within a median of 2.8 years, but with PAH therapies,median survival extends to over 7 years.491,492 There is a preponder-ance of females in the incidence of PAH, and this includes women of childbearing age. The first clinical manifestations may be seen in pregnancy.493
Women with PAH should be managed by a Pregnancy Heart Team,and a PH expert experienced in diagnostic pathways, medical treat-ment, and anticoagulation management from the ante- to the peri-and post-partum period.
10.1. Pre-existing pulmonary arterial hypertension
In women with PAH, maternal and foetal outcomes vary according to the PAH subset. With improved treatment of PAH and a multidisciplinary approach during pregnancy and the peri-partum period, maternal mor-tality has declined but remains high,ranging from 11% to 25%.2,490,494,495
10.1.1. Maternal and foetal risk
Although there is no safe cut-off for elevated pulmonary artery pres-sure and risk, pregnancies with mild PAH and vasoreactive PAH seem to have better maternal and foetal outcomes than those with moderate to severe PAH.141,496-498 Women with severe PAH, non-vasoreactive idiopathic PAH,and Eisenemenger syndrome have the high-est risk of maternal and foetal mortality.496,497,499-502 As the clinical course of PAH during pregnancy remains associated with unforesee-able risks and pregnancy may accelerate PAH progression, all women with PAH496 wishing to become pregnant should be counselled by a multidisciplinary team regarding the very high risk of pregnancy-related adverse events.
Women with Eisenmenger syndrome are unlikely to tolerate preg-nancy due to additional risks of RV failure and paradoxical emboli.Chronic cyanosis may worsen due to systemic vasodilatation during pregnancy, an increased right-to-left shunt, and decreased pulmonary blood flow.
Foetal and neonatal mortality risk is high in women with PAH,main-ly related to pre-term delivery,reduced maternal CO,and/or hypox-aemia.503 Miscarriage is common. If oxygen saturation is>90%, there is usually a better foetal outcome(10% foetal loss). If oxygen satur-ation is<85%, miscarriage, IUGR, prematurity, and foetal death are common(live birth rate of only 12%).504,505
10.1.2. Counselling and contraception
Women of childbearing potential with PAH should be counselled at the time of diagnosis about the very high risk and uncertainties as-sociated with becoming pregnant. Clear advice against becoming pregnant, including referral for psychological support if needed,and clear contraceptive advice are required, taking into account the woman's individual needs. Reduced efficacy of hormonal contracep-tives should be carefully considered and discussed with women trea-ted with ERAs, as well as the addition of barrier methods for contraception.490,493
10.1.3. Management during pregnancy
When pregnancy occurs, termination should be discussed. Rigorous planning with the optimization of targeted PAH therapies and close monitoring are key in managing women with PAH who wish to con-tinue with the pregnancy after appropriate counselling on the high ma-ternal and foetal risks.
Bed rest may be required in symptomatic women, and it may be ap-propriate to avoid additional risk factors(such as air travel). Right-heart catheterization can be performed to assist management in women showing deterioration.
Diuretics may be needed in women with HF, and iron deficiency should be treated.43 It is recommended to stop ERAs,ricuogiat,and selezipag because of potential or unknown teratogenicity.43,490 PAH therapies that can be used during pregnancy include phosphodiesterase-5 inhibitors and prostacyclin analogues. Sildenafil is used in the vast majority of women and is combined with a prosta-cyclin analogue depending on the disease severity. The subset of wo-men with true vasodilator responsiveness who are well controlled on CCB therapy should continue taking this during pregnancy.43,490,506
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In women with Eisenmenger syndrome, caution is warranted when administering drugs that may lead to sudden systemic vasodilation or a risk of paradoxical air embolism(i.v. line filters should be used for i.v. therapies). Thromboembolism is a major risk, and anticoagulation regimens(type and dosage) should be considered individually, balan-cing the risk of bleeding vs VTE at each stage of pregnancy. LMWH is most commonly used. Regular follow-up is advisable, initially every 2-4 weeks and then weekly in the third trimester. Women need to be monitored for increasing hypoxaemia and symptoms of HF, including breathlessness, syncope, and congestion. Regular echocardiography and blood testing, including NP levels, can provide evidence of HF where appropriate.
10.2. New diagnosis in pregnancy
The usual diagnostic algorithm as per the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension should be followed in a pregnant woman with suspected PAH. Right-heart catheterization should be considered if there is diagnostic uncer-tainty in identifying de novo PAH in pregnancy and to assist with im-portant therapeutic decisions. ${}^{490}$ If this is required, it should be performed in a specialized centre. An individualized approach is re-quired for starting PAH therapies. Many centres start therapy with oral sildenafil. Close follow-up by an experienced Pregnancy Heart Team with a PH expert is needed and prompt escalation of PAH therapy, usually with i.e. eprostopenol, is indicated depending on the disease severity.
10.3. Delivery in women with pulmonary arterial hypertension
A detailed delivery plan, including the optimal mode and timing of de-livery, should be provided on a timely basis by the Pregnancy Heart Team with a PH expert. Early delivery, with careful tracking of foetal growth, is often required in women with progressive, decompensated HF not responding to PAH therapies and to reduce the risk of an un-planned birth outside an expert centre. 245 Therapeutic LMWH should be stopped 24 h prior to any mode of delivery to reduce the risk of maternal haemorrhage. Caesarean section providing for a more controlled delivery may be preferred over vaginal deliv-ery.494,507 Regional anaesthesia is usually favoured over general anaesthesia.
10.3.1. Peri- and post-partum monitoring
Due to the rapid changes in haemodynamics, the post-partum period is particularly high risk, with the majority of maternal mortality occurring after delivery.245 During delivery and post-delivery, women should be monitored in the intensive care setting with ECG, pulse oximetry,CO monitoring, meticulous fluid balance with central venous pressure monitoring, and optimization of RV function all important determinants of a good outcome. Women remain at high risk for many months after delivery, and individualized counselling is required to discuss the need for ongoing therapies and the avoidance of future pregnancies. In wo-men with severe PAH and those who had complications during preg-nancy and/or delivery, optimization of PAH therapies should be prioritized over lactation.
Recommendation Table 10- Recommendations for pulmonary arterial hypertension and pregnancy
|Recommendations|Classa|Levelb| |---|---|---| |It is recommended that women of childbearing potential with PAH wishing to become pregnant are counselled by a multidisciplinary team regarding the very high risk of pregnancy-related adverse events, encouraging a shared decision-making process about whether to become pregnant. 490|1|C| |It is recommended to provide clear contraceptive advice to women of childbearing potential with PAH:490|1|C| |For women with PAH requiring pregnancy termination, it is recommended to perform this in PH centres. 490|1|C| |Right-heart catheterization should be considered during pregnancy if there is diagnostic uncertainty or to assist with important therapeutic decisions. 490|11|C| |Endothelin receptor antagonists, riocguat, and selexipag are not recommended during pregnancy. 490,508,509|III|C|
PAH, pulmonary arterial hypertension; PH, pulmonary hypertension.
aClass of recommendation.
bLevel of evidence.
11. Venous thromboembolism in pregnancy and post-partum
11.1. Epidemiology and maternal risk
Venous thromboembolism includes PE and DVT. The pooled incidence of pregnancy-related VTE(including post-partum) is 1.2 per 1000 deliver-ies ${}^{510}$ , and it is a major cause of pregnancy-related morbidity and mortal-ity.510 Pregnancy-related VTE has a fatality rate of 0.68% and a recurrence rate(during pregnancy and post-partum) of 4.27%, which is higher post-partum.510 A documented assessment of VTE risk factors is recom-mended before or in early pregnancy. The VTE risk is highest in the third trimester and in the first 6 weeks post-partum. 510 Mortality in pregnancy-related VTE is associated with CVD, hypertension, twin gesta-tion, pre-term birth, caesarean section, transfusion, and black ethnicity.511
11.2. Risk factors for pregnancy-related venous thromboembolism
Pregnancy is accompanied by physiological changes leading to an increased VTE risk. First, increased procoagulant activity as well as de-creased physiological anticopagulant and fibrinolytic activity result in a hy-percoagulable state.512,513 Second, the expanding uterus causes mechanical compression of the inferior vena cava and the pelvic veins,leading to impeded venous flow.512,513 In addition, non-pregnancy-related and pregnancy- or delivery-related conditions may modify the in-dividual VTE risk(see Supplementary data online, Table S5).
In pregnancy, as well as in the early post-partum period, an emerging suspicion of VTE requires immediate diagnostic clarification.
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11.3. Prevention of venous thromboembolism
Thrombobropylaxis follows an individualized risk assessment weighing the VTE risk against the bleeding risk ante- and post-partum.
11.3.1. Pregnant women with no prior indications for long-term anticoagulation
If prevention and treatment of VTE are initiated in the antepartum per-iod, continuation for up to 6 weeks post-partum should be considered.In women with low-risk thrombophila without a history of VTE, rou-tine antepartum thrombophylaxis is not required.514 in women with a history of VTE or a high-risk thrombophilia, medical thrombo-prophylaxis is recommended(Table 13). In women with ovarian hyper-stimulation syndrome after in vitro fertilization, thrombophylaxis is recommended during the first trimester.515,516
The drug class of choice for the prevention and treatment of pregnancy-related VTE is LMWH.517,518 Fondaparux may be consid-ered as an alternative. A randomized controlled trial comparing a weight-adjusted intermediate-dose LMWH with a fixed low-dose LMWH regimen found that weight adjustment did not reduce the risk of recurrent VTE in the combined ante- and post-partum peri-ods.519 Post-hoc analyses suggested a higher efficacy of weight-adjusted intermediate-dose LMWH in the post-partum period only, but this
<EndOfPara>needs to be confirmed by future studies. In morbidly obese women,weight-based prophylactic dosing(considering anti-factor Xa measure-ment) instead of fixed dosing might be more appropriate. ${ }^{198}$
11.3.2. Pregnant women with prior indication for long-term anticoagulation
In case of pre-existing oral anticoagulation therapy due to previous VTE, oral anticoagulation (DOAC or VKA) should be replaced by LMWH at recognition of pregnancy.517
11.4. Management of acute venous thromboembolism
11.4.1. Clinical presentation and diagnosis
11.4.1.1. Deep vein thrombosis
The expanding uterus potentially reduces the blood flow in the iluliacoal veins. In addition, a constitutional narrowing of the left-sided common iliac vein between the spine and the crossing artery could contribute to an increased risk of left-sided ilioemoral thrombosis. ${}^{520}$ The clinical LEFT criteria(L= Left, symptoms in the left leg; E= Edema, calf circum-ference difference $\geq 2$ cm; Ft= First trimester of presentation) may be used to identify low risk of pregnancy-related DVT.521,522 In pregnant women with suspicion of acute DVT, immediate diagnostic clarification is indicated (Figure 9).
Table 13 Reasons for antepartum/post-partum thrombophylaxis
|Medical conditions|Antepartum thrombophylaxis|Post-partum thrombophylaxis| |---|---|---| |History of unprovoked VTE||| |History of hormone-associated VTE||| |Homozygous factor V Leiden mutation||| |Heterozygous factor V Leiden mutation||| |Homozygous prothrombin gene mutation||| |Heterozygous prothrombin gene mutation||| |Antithrombin deficiency||| |Antiphospholipid syndrome||| |Protein C or S deficiency||| |Combined thrombophilia|||
Adapted from Nichols et al.213 under the terms of the Creative Commons Attribution-NonCommercial-No Derivatives License(CC BY NC ND).VTE, venous thromboembolism.
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 Figure 9 Algorithm for the diagnosis and treatment of deep vein thrombosis during pregnancy.DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin,MR,magnetic resonance.Adapted from Chan et al. ${}^{523}$
11.4.1.2. Pulmonary embolism
Clinical signs and symptoms of PE in pregnancy do not differ from those of PE in non-pregnant women. The diagnostic approach in haemodynamically stable pregnant women with suspicion of PE aims to reduce the need for computed tomography pulmonary angiography(CTPA) by implementing additional diagnostic strategies, such as clinical features, D-dimer, and ven-ous ultrasound. Levels of D-dimer increase physiologically up to 39% per trimester. ${}^{524}$ A multinational study demonstrated the efficiency of a diag-nostic strategy involving clinical probability, D-dimer measurements(threshold<500μg/L), and peripheral venous compression ultrasound to reduce the need for CTPA. ${}^{525}$ Using both the YEARS criteria(1, clinical signs of acute DVT; 2, haemoptysis; 3, PE is the most likely diagnosis) and adapted D-dimer thresholds allows a further reduction in the need for CTPA(D-dimer threshold if YEARS criteria present<500μg/L, if
YEARS criteria absent<1000μg/L). ${}^{526}$ Another meta-analysis confirmed the value of including D-dimer in a diagnostic algorithm to rule out PE in pregnant women with suspicion of PE(Figure 10).
11.4.2. Treatment of venous thromboembolism in pregnancy
In pregnant women with a suspicion of VTE, anticoagulation with thera-peutic LMWH should be commenced immediately, even before imaging,until the diagnosis of VTE is either excluded or confirmed. In pregnant wo-men with confirmed acute VTE, therapeutic anticoagulation with weight-adjusted LMWH based on early pregnancy weight is recommended by using either a twice-daily or a once-daily regimen, each one resulting in a therapeutic daily dose ${}^{518}$ (see also Section 5.2.1). Currently, there is in-sufficient evidence to favour once- or twice-daily regimens. ${}^{217,218,518}$
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 Figure 10 Algorithm for the diagnosis and treatment of pulmonary embolism in pregnancy in stable(A) and unstable women(B).CTPA, computed tom-ography pulmonary angiography; DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin; PE, pulmonary embolism; RV, right ventricle; TTE, transthoracic echocardiogram; UFH, unfractionated heparin. Adapted from Barrosi et al. $^{528}$ with permission from Elsevier.
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Despite fluctuations of anti-factor Xa levels during pregnancy, routine anti-factor Xa monitoring does not affect clinical outcomes and should only be considered in women with renal insufficiency or obesity.211-213 Fondaparinux may be considered as an alternative. In unstable pregnant women with PE, UFH may be used in the initial phase of therapeutic anticoagulation.
After delivery, therapeutic-dose anticoagulation should be administered for a minimum of 6 weeks, up to an overall duration of 3 months, except for cases in which an indefinite duration of anticoagulation is indi-cated.510,529 LMWH or VKAs may be given during lactation. A more de-tailed discussion of anticoagulants in the lactation period can be found in Section 5. Thrombolytic or interventional treatment of PE is not recom-mended in the peripartum period and should only be considered in women with high-risk PE after consultation with a specialized multidisciplinary team. In pregnant women with acute iliofemoral DVT, interventional thrombus removal should not routinely be performed. Data on the effect-iveness and risks of the placement of temporary inferior vena cava filters for the prevention of PE in pregnant women are limited but appear to be comparable to non-pregnant women. Due to limited data and potential complications associated with the inferior vena cava filters, their placement should be limited to recurrent VTE despite appropriate anticoagulation or contraindication to therapeutic-dose anticoagulation therapy. 530,531
11.5. Management of delivery and the post-partum period
For pregnant women receiving a prophylactic dose of anticoagulation,there is no specific need for a planned delivery. However, pregnant wo-men receiving a therapeutic dose of anticoagulation need a planned de-livery with prior discontinuation of LMIVWH to prevent spontaneous delivery in a period of full anticoagulation. Details for the management of anticoagulation during pregnancy and delivery,including for VTE,are provided in Sections 4.5.6. and 5.2.1.
12. Pregnancy in women with acquired heart disease
12.1. Acute chest pain in pregnancy
Diagnostic evaluation for chest pain in pregnant women follows the same protocol as in non-pregnant women, including clinical examination, ECG, biomarkers and echocardiography(Figure 11).207,537,538 Importantly, spontaneous coronary artery dissection(SCAD) is a more prevalent cause of chest pain during pregnancy and in the early post-partum period than in non-pregnant women.539
Treatment and management of the specific differential diagnoses should follow established respective guidelines. The specificity of D-dimer is reduced during pregnancy 540,541 and women should not undergo chest CT based solely on D-dimer levels(Section 11). In sus-pected acute aortic syndromes, there should be a low threshold for aortic CT and consultation with the aortic team in emergencies(Section 8).
12.2. Coronary artery disease
12.2.1. Acute coronary syndrome
12.2.1.1. Coronary artery disease epidemiology and aetiology
Acute coronary syndromes(ACS) are a major cause of maternal death in developed countries, accounting for 20% of cardiovascular deaths. ${}^{543}$ The risk of ACS is three to four times higher in pregnant women than in non-pregnant women of reproductive age,544 and mortality is estimated at 5%.5%.5. Because the age at giving birth is increasing overall, ACS in pregnancy may become more com-mon.546 Although ACS can occur at any stage of pregnancy, it is more common in the third trimester or post-partum.544 Classic ASCVD risk factors are associated with ACS during pregnancy.
Recommendation Table 11- Recommendations for venous thromboembolic diseases and pregnancy(see Evidence Tables 9 and 10)
|Recommendations||Classa|Levelb| |---|---|---|---| |For pregnant or post-partum women at high risk of VTE, a prophylactic fixed dose of LMWH is recommended over a higher weight-adjusted dose to reduce the risk of VTE. ${}^{519}$|||| |In pregnant women or in women in the post-partum period with suspicion of VTE(DVT and/or PE), an immediate formal diagnostic assessment with validated methods is recommended and should not be postponed. ${}^{525,526}$|||B| |In pregnant women or women in the post-partum period with newly diagnosed VTE(DVT and/or PE), the involvement of the Pregnancy|||| |Heart Team,including a vascular specialist and a haematologist, is recommended.||I|C| |In pregnant or post-partum women with a diagnosis of VTE without haemodynamic instability, anticoagulation is recommended by using therapeutic-dose LMWH based on early pregnancy body weight. ${}^{212,532}$|||| |In pregnant women or women in the post-partum period with a strong clinical suspicion of VTE, initiation of treatment with a therapeutic-dose of LMWH should be considered until the presence of VTE has been ruled out or confirmed.||lla|C| |In pregnant or post-partum women with a diagnosis of acute high-risk PE,d catheter-based reperfusion strategy or systemic thrombolysis should be considered. ${}^{533-535}$||lla|C| |In pregnant or post-partum women with a diagnosis of acute high-risk PE,d surgical thrombectomy may be considered as an alternative to a catheter-based approach or systemic thrombolysis. ${}^{533-535}$||Ib|C|
DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin; PE, pulmonary embolism; VTE, venous thromboembolism.
aClass of recommendation.
bLevel of evidence.
See Supplementary data online, Table S5 for VTE risk factors.
${}^{d}$ According to the Pulmonary Embolism Severity Index from the 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism. ${}^{536}$
<FIGTEXT=></FIGTEXT>
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 Figure 11 Management of chest pain during pregnancy and within 6 months post-partum. ASCVD, atherosclerotic cardiovascular disease; B-blocker, beta-blocker;CABG,coronary artery bypass graft,CAD,coronary artery disease;CT,computed tomography;DVT,deep venous thrombosis; ECG, electrocar-diogram;EF,ejection fraction;hs-cTn,high sensitivity cardiac troponin;i.v.,intravenous;MINOCA,myocardial infarction with non-obstructive coronary ar-teries; o.d., once a day; PCI, percutaneous coronary intervention; PE, pulmonary embolism; SCAD, spontaneous coronary artery dissection; TTE,transthoracic echocardiogram.3In patients without very high or high-risk features and a low index of suspicion for unstable angina.bDual anti-platelet therapy:clopidogrel:loading dose of 300-600 mg orally, followed by an oral maintenance dose of 75 mg o.d. Aspirin:loading dose of 150-300 mg orally or 75-250 mg i.v.if oral ingestion is not possible, followed by an oral maintenance dose of 75-100 mg o.d.
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Additional risk factors are pre-eclamphia, thrombophilia, transfu-sion, post-partum infection, multiparity, and PPH. Pregnancies that required fertility treatment have not been shown to have an increased risk of ACS.547
Pregnancy-associated SCAD is the single most frequent cause of ACS during pregnancy and post-partum(43%), followed by atherosclerotic lesion(27%), coronary embolism(17%), and vasospasm(2%).239 Coronary thromboembolism may be due to pregnancy-related hyper-coagulability and paradoxical embolization.549 Vasospasm has been asso-ciated with the use of ergot derivatives prescribed for lactation suppression or to treat PPH.
12.2.1.2. Presentation and diagnosis
Clinical presentation of ACS in pregnancy is the same as in the non-pregnant population. However, pregnant women with SCAD tend to have a more severe clinical presentation than women with non-SCAD ACS.550-553
An ACS in pregnancy should be suspected in women presenting with cardiac arrest, acute onset chest pain, dyspnoea, ischaemic changes on ECG, or elevated cardiac biomarkers. ${}^{551,554}$ Diagnostic evaluation should follow ACS strategies(Figure 11). ${}^{555-557}$ Major ischaemic ECG changes due to pregnancy itself are not expected(Figure 1).
Invasive coronary angiography during pregnancy should be reserved for those with ACS, or when other diagnostic methods are inappropri-ate. ECG changes, such as transient-ST-segment depression and T-wave inversion can be normal during pregnancy, but a serum troponin rise suggests myocardial injury as in non-pregnant women. ST elevation is not normal in pregnancy and warrants urgent attention. ${}^{558}$ ST-elevation myocardial infarction(STEMI) in pregnant women in-volves the anterior wall in 70%-80% of cases.239,558 In more than half the cases, a reduction of LVEF<40% is observed, leading to a high in-cidence of complications.20 Myocardial infarction with non-obstructive coronary arteries(MINOCA) should be considered a working diagnosis warranting further investigation. ${}^{559}$
12.2.1.3. Pregnancy-associated spontaneous coronary artery dissection
Pregnancy-associated SCAD affects 1.81 per 100 000 pregnancies ${}^{560}$ and may occur at any time during or after pregnancy, although>70%occur early post-partum, most commonly within the first week.550 Multiple predisposing factors have been described, including oestrogen and progesterone surges causing structural changes to the coronary tu-nica media. SCAD predominantly occurs in the left-sided coronaries,with multivessel involvement. ${}^{561}$
Percutaneous coronary intervention(PCI) in SCAD is associated with an increased risk of complications, particularly atrogenic disec-tion and haematoma extension.562 For this reason, a conservative ap-proach to revascularization is advised in clinically stable women with SCAD without active or ongoing ischaemia. 539.563 If SCAD involves the left main coronary artery or proximal vessels, a coronary artery by-pass graft(CABG) may be considered depending on technical consid-erations and local expertise.539 A multidisciplinary team should decide whether the patient is a candidate for PCI or CABG.
Optimal medical management following SCAD is unknown but is currently being investigated in an ongoing clinical trial.562 Limited obser-vational data suggest that beta-blockers(e.g. labelatol) and avoiding hypertension may be associated with a lower risk of recurrent SCAD.564.565 The role of antiplatelet therapies in conservatively mana-ged SCAD has been controversial, with evidence favouring single
antiplatelet therapy with aspirin.563,566 Women with a history of SCAD should be carefully counselled regarding the risk of recurrent events in subsequent pregnancy.567,568
12.2.2. Coronary artery interventions
The indications for acute revascularization are comparable to those for non-pregnant women. In patients with high or very high-risk ACS,immediate coronary angiography and PCI, if indicated, are recom-mended.557 Moreover, an early invasive strategy with coronary angiog-raphy is recommended for pregnant women with a confirmed or a working diagnosis of non-ST-elevation ACS(NSTE ACS) and with a high index of suspicion for unstable angina. In atherosclerotic lesions557 PCI is indicated when there is ongoing or recurrent chest pain, haemo-dynamic instability, or ongoing ischaemia due to functionally significant coronary stenoses or acute occlusions.122
The choice of coronary stents should not be different from that for non-pregnant women. Duration of DAPT should follow recommenda-tions for non-pregnant patients with an individual approach considering is-chaemic and delivery-related risks, including bleeding risk during delivery and neuraxial anaesthesia. Stents approved for short DAPT may be pre-ferred during pregnancy in specific cases according to gestational age and timing of delivery. In the case of coronary embolism, thrombo-aspiration and/or a simple angioplasty can be performed.43,569 Invasive procedures should follow the ALARA Principle(see Section 4.3.5).
Systemic thrombolysis may be an alternative reperfusion strategy if timely PCI is not available. Recombinant tissue plasminogen activator does not cross the placenta but can induce bleeding complications, in-cluding subplacental.
12.2.3. Chronic coronary syndromes in pregnancy
Pregnant women with chronic coronary syndromes(CCS) are at high risk of adverse maternal and foetal outcomes: 32% have cardiovascular complications(including 9% with ischaemic cardiovascular complica-tions) and there is 2% maternal mortality.570 The CARPREG II score,now also included in the mWHO 2.0 classification(Table 6, Section 4), highlights the high risk of CCS as a predictor of maternal complica-tions. When counselling women with CCS, pregnancy can preferably be considered when there is no residual ischaemia or LV dysfunction 12 months after an index event.
12.2.4. Management and delivery
Women with ACS or CCS should be managed by a Pregnancy Heart Team. Treatment should be tailored to the underlying pathophysiology,although foetal considerations may affect the choice of therapy. ${}^{50,571}$ All pregnant women with ACS and their foetus should be monitored at an intensive cardiac care unit.
The mode of delivery in a patient with gestational ACS or CCS should be determined by obstetric considerations and the clinical status of the mother. A vaginal delivery is indicated in most women with ob-structive coronary artery disease(CAD). Vaginal delivery eliminates the potential risks associated with general anaesthesia and a major surgical procedure. Clopidogrel must be withheld a minimum of 5 days before neuraxial anaesthesia to reduce the risk of epidural hematoma. ${}^{572}$ An elective caesarean section avoids a long or stressful labour and allows better control of the time of delivery. A plan for emergency delivery of a potentially viable foetus in case of sudden maternal deterioration should also be established. An arbitrary minimum time to delivery in stable women is at 2 weeks after ACS.18
Lipid-lowering and antiplatelet therapy are described in Section 5.
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Recommendation Table 12- Recommendations for coronary artery disease and pregnancy(see Evidence Table 11)
|Recommendations|Classa|Levelb| |---|---|---| |In pregnant women with chest pain, it is recommended to exclude life-threatening cardiovascular conditions, including PE,ACS(including SCAD), and acute aortic syndrome. ${}^{538,539}$||C| |It is recommended to manage pregnant women with ACS in the same way as non-pregnant women, including diagnostic investigations and interventions. ${}^{557}$|I|C| |Low-dose ASA is recommended as the antiplatelet treatment of choice during pregnancy and lactation when single antiplatelet treatment is indicated. ${}^{573-579}$|I|B| |If DAPT is required, clopidogrel is recommended as the P2Y12 inhibitor of choice during pregnancy. ${}^{239}$|I|C| |The duration of DAPT(aspirin and clopidogrel) in pregnant women undergoing coronary stent implantation is recommended to be the||| |same as in non-pregnant women, with an individual approach considering ischaemic risk and delivery-related bleeding risks. ${}^{239}$||| |A vaginal delivery should be considered in most pregnant women with ACS, depending on LV function and clinical symptoms.|IIa|C| |Continuation of statins may be considered during pregnancy in women with established ASCVD. ${}^{580-582}$|IIb|C|
ACS,acute coronary syndrome;ASA,acetylsalicylic acid;ASCVD,atherosclerotic cardiovascular disease;DAPT,dual antiplatelet therapy;LV,left ventricular;PE,pulmonary embolism;SCAD,spontaneous coronary artery dissection.
aClass of recommendation.
bLevel of evidence.
12.3. Hypertensive disorders
Hypertensive disorders of pregnancy are the second most common med-ical complications(after PPH), affecting 5%-15% of pregnancies world-wide, and are a major cause of maternal, foetal, and neonatal morbidity and mortality.583 Hypertensive disorders in pregnancy include pre-existing
hypertension(chronic hypertension), gestational hypertension, and pre-eclampsia(Table 14). Over recent years an upward incidence trend has been observed due to older age at first childbirth and rising prevalence of obesity.586,587 Maternal risks include placental abruption, stroke,multiple organ failure, and disseminated intravascular coagulation.
Table 14 Hypertensive disorders of pregnancy
A. Pre-existing(chronic) hypertension
Hypertension which either precedes pregnancy or develops before 20 weeks gestation, usually persisting>6 weeks post-partum, and which may be associated with proteinuria.
(1) Primary hypertension
(2)Secondary hypertension
(3)White-coat hypertension
(4)Masked hypertension
B. Gestational hypertension
Hypertension which develops after 20 weeks gestation and usually resolves within 6 weeks post-partum.
Transient gestational hypertension
Usually detected in the clinic but then settles with repeated BP measurements taken over several hours; associated with a 40% risk of developing true gestational hypertension or eclampsia in the remainder of the pregnancy, thus requiring careful follow-up.
C. Pre-eclampsia
Gestational hypertension accompanied by one or more of the following new-onset conditions at or after 20 weeks gestation:
●Proteinuria [urinary albumin excretion in a 24 h urine sample>0.3 g/day or UACR in a random spot urine sample>30 mg/mmol(0.3 mg/mg)]
● Other maternal organ dysfunction including:
●Acute kidney injury(serum creatinine≥90μmol/L;1 mg/dL)
● Liver dysfunction(elevated ALT or AST>40 IU/L;>0.67μkat/L with or without right upper quadrant or epigastric abdominal pain)
●Neurological complications(e.g.eclampsia/convulsions, altered mental status, blindness, stroke, clonus,severe headaches, persistent visual scotomata)
●Haematological complications(platelet count<150 000μL, disseminated intravascular coagulation, haemolysis)
●Uteroplacental dysfunction(IUGR, abnormal umbilical artery Doppler waveform analysis, or stillbirth).
D. Pre-existing hypertension+ superimposed pre-eclampsia
Pre-existing hypertension associated with any of the above maternal organ dysfunctions consistent with pre-eclampsia or a further increase in BP with new-onset proteinuria.
E. Antenatally unclassifiable hypertension
When BP is first recorded after 20 weeks gestation and hypertension is diagnosed, reassessment is necessary at or after 6 weeks post-partum. If hypertension resolves, it should be reclassified as gestational hypertension, whereas if hypertension persists, it should be reclassified as pre-existing/chronic hypertension.
Based on Mancia et al.584 and McEvoy et al.
ALT,alanine transaminase;AST,aspartate aminotransferase;BP,blood pressure;IUGR,trauterine growth restriction;UACR,urine albumin-creatinine ratio
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The foetus is at high risk of IUGR prematurity, and intrauterine death(25%,27%,and 4%,respectively,in cases of pre-eclampsia).589
12.3.1. Definition and classification of hypertension in pregnancy
Hypertension in pregnancy is typically defined as systolic blood pres-sure(BP) of≥140 mmHg and/or diastolic BP of≥90 mmHg,585 measured using repeated BP readings in the office or hospital on two separate occasions or≥15 min apart in severe hypertension(≥160/110 mmHg).584,590
12.3.1.1. Pre-eclampsia/eclampsia
Pre-eclampsia is defined as gestational hypertension complicated by new onset of the laboratory or clinical changes reported in Table 14 at or after 20 weeks. Eclampsia is defined as the new onset of seizures or coma in a pregnant woman with pre-eclampsia. ${}^{584,585}$
The combination of haemolysis, thrombocytopenia, and elevated transaminases defines HELLP syndrome, which is usually considered to be a variant of pre-eclampsia.43 Risk factors for pre-eclampsia are de-scribed in Table 15.
Table 15 Risk factors for pre-eclampsia
High risk factors for pre-eclampsia
Hypertensive disorders during a previous pregnancy
Chronic hypertension
Chronic kidney disease
Type 1 or type 2 diabetes mellitus
Autoimmune diseases such as systemic lupus erythematosus or
antiphospholipid syndrome
Assisted reproductive therapy in the current pregnancy
Moderate risk factors for pre-eclampsia
Nulliparity
Age≥40 years
Pregnancy interval of more than 10 years
BMI≥35 kg/m2 at the first visit
Family history of pre-eclampsia
Multi-foetal pregnancy
Based on Mancia et al.584 and McEvoy et al.585
BMI, body mass index.
12.3.2. Diagnosis and risk assessment
12.3.2.1. Blood pressure measurement
Maternal BP should be assessed at each encounter and should be measured in the sitting position(or the left lateral recumbent position during labour)with an appropriately sized arm cuff at heart level and using Korotkoff V for diastolic BP. Mercury syphymanomometers remain the gold standard for BP measurement in pregnancy as automatic devices tend to under-record BP and are unreliable in severe pre-eclampsia. Only automatic devices specific-ally validated for pregnancy should be used.584,591
The diagnosis of hypertension in pregnancy by ambulatory BP mon-itoring is superior to office BP measurements or home BP monitoring for the prediction of pregnancy outcomes.584,592 Ambulatory BP mon-itoring avoids unnecessary treatment of white-coat hypertension, and is
useful in the management of high-risk pregnant women with hyperten-sion and those with diabetic or hypertensive nephropathy.593,594 Either home BP monitoring or office BP measurements may be used alterna-tively or complementarily to diagnose hypertensive disorders during pregnancy in women at risk of pre-eclampsia.
However, among pregnant women with pre-existing or gestational hypertension, home BP monitoring is not associated with better BP control compared with scheduled office BP measurements.584,595,596 Either can be used for BP monitoring.
12.3.2.2. Laboratory tests
Basic laboratory investigations recommended for monitoring hyperten-sive disorders of pregnancy include urinalysis, blood count, haemato-crit, liver enzymes, serum creatinine, and serum uric acid. All pregnant women should be assessed for proteinuria in early pregnancy to detect pre-existing renal disease and, in the second half of pregnancy,to screen for pre-eclampsia. 43
In addition to basic laboratory tests, the following investigations may be considered:
● Ultrasound of the adrenals, and plasma and urinary fractionated me-tanephrine assays.
● Doppler ultrasound of uterine arteries(after 20 weeks of gestation). ${}^{597}$
● A ratio of soluble fms-like tyrosine kinase-1(sFlt-1) to placental growth factor(PIGF) of<38 can be used to reliably exclude the de-velopment of pre-eclampsia over the next 7 days when clinically suspected. 43,598
If women with chronic hypertension are suspected of developing pre-eclampsia, testing for PIGF may help rule out pre-eclampsia be-tween 20 and 36 weeks. ${}^{59,600}$
12.3.3. Management of hypertension in pregnancy
Management of hypertension in pregnancy depends on the woman's BP and gestational age, and the presence of associated maternal and foe-tal risk factors.601,602 In pregnant women with BP>160/110 mmHg,hos-pital admission is recommended ${}^{603}$ (Figure 12A). If BP is≥140-159/90-99 mmHg,BP control is mandatory with a BP target of<140/90 mmHg.
In two large trials, ${}^{583,604}$ tight diastolic BP control(<85-90 mmHg) in women with pre-existing hypertension was superior to less tight dia-stolic BP control(<100-105 mmHg) and caused no harm.
In pregnant women with diagnosed hypertension, blood tests, clinical examination, and assessment of proteinuria are mandatory and should be repeated regularly. ${}^{599}$ If a urine dipstick is positive or borderline for proteinuria, and symptoms and laboratory tests(including biomarker assessment) are indicative of pre-eclampsia, the diagnosis of pre-eclampsia can be made and hospital admission is recommended where there are clinical concerns.
12.3.3.1. Non-pharmacological management
Pregnant women with hypertension should be advised to follow a healthy lifestyle including physical activity, smoking cessation, a healthy diet, and control of body weight. Lifestyle changes before and during pregnancy may ameliorate both maternal and foetal risks.605 Salt re-striction is not advised to reduce hypertensive disorders during preg-nancy, but it is reasonable for women with pre-existing hypertension to continue with a low sodium diet. ${}^{584}$ Unless contraindicated, aerobic exercise should be recommended in pregnant women with hyperten-sion to maintain ideal body weight and reduce adverse pregnancy
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outcomes. ${}^{606}$ Obese women are advised to avoid an increase in weight of more than~7 kg from pre-conception. ${}^{601}$
Calcium supplements are recommended for the prevention of pre-eclampsia in women with a low dietary intake of calcium(<600 mg/day),607 where low-dose calcium supplementation(<1 g/day) has been shown to be as effective as high-dose(≥1 g/day). 608
12.3.3.2. Pharmacological treatment
12.3.3.2.1. Mild hypertension(PB 140/90-159/109 mmHg). In mild gestational hypertension it seems reasonable to initiate treatment at BP values of 140/90 mmHg,583,609 whereas a diastolic BP reduction to<80 mmHg is not recommended.
Methyldopa, beta-blockers(most data are available for labelatol),and dihydropyridine CCBs(most data are available for nifedipine)are the drugs of choice for mild gestational and pre-existing hypertension.584
ACE-Is, ARBs, and direct rein inhibitors are strictly contraindicated-Duiretics are not advised in gestational hypertension and pre-eclampsia,due to the reduction of intravascular volume and reduction of uteropla-cent perfusion and thereby possible foetal adverse effects.
12.3.3.2.2. Pre-eclampsia. Pre-eclampsia may require hospital admis-sion, but not all women will require ongoing hospitalization and care should be individualized(Figure 12B and Figure 12C). Women with at least one high-risk factor or two moderate-risk factors for pre-eclampsia(Table 15) should be advised to take 75-150 mg aspirin daily at bedtime from week 12 to week 36/37. ${}^{599,610}$ We advise discontinu-ation of low-dose aspirin at week 36/37 when the aspirin indication is pre-eclampsia.
Pre-eclampsia with severe features(severe hypertension with or without proteinuria, any hypertension grade with neurological, haem-atological, or cardiovascular complications, liver dysfunction, or renal dysfunction) should be managed with a magnesium sulfate infusion to prevent eclampsia, in addition to early delivery.43,611 Magnesium toxicity can present with cardiac effects, including ECG interval changes(prolonged PR, QRS, and QT intervals) at magnesium levels of 2.5-5 mmol/L, and can progress to atrioventricular(AV) nodal con-duction block, bradycardia, hypotension, and cardiac arrest at levels of 6-10 mmol/L. If magnesium toxicity is suspected, it is recommended to stop the magnesium infusion and give 30 mL i.v. calcium gluco-nate. ${}^{612-614}$
 Figure 12A Management of hypertension and pre-eclampsia in the emergency ward. BP, blood pressure; N,no;Y,yes.
a See Figure 12B.
${}^{b}$ See Figure 12C.
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 Figure 12B Proteinuria assessment and diagnosis of pre-eclampsia. BP, blood pressure; PIGF, placental growth factor; sFLt-1, soluble fms-like tyrosine kinase-1.
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 Figure 12C Monitoring and treatment of hypertension and pre-eclampsia. Mg, magnesium; PlGF, placental growth factor; p.o., per oral.$$\text{ a}\text{ Labetalol 100 mg p.o. b.i.d. bMetoprolol 100 mg p.o. b.i.d. c.Methyldopa 250 mg p.o. b.i.d./t.i.d. d.Nifedipine 5-10 mg p.o. if> 160/110 mmHg}$$
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12.3.3.2.3. Severe hypertension(BP≥160/110 mmHg). In severe hypertension, assessment and gradual BP reduction to<160/110 mmHg is mandatory in a hospital setting. Continuous cardiotoco-graphic monitoring is also compulsory. The selection of antihyperten-sive drugs and the route of administration depend on initial diagnosis,expected delivery time, presence or absence of pre-eclampsia, and the preferences and experience of the attending physicians. 43,611 Recent comprehensive meta-analyses comparing commonly used anti-hypertensive drugs(e.g. oral nifedipine, labetalol, methyldopa)(Figure 12C) showed they had similar efficacy in lowering BP in severe hypertension in pregnancy, with nifedipine showing superiority in some studies(see Section 5.2.6).43,253,254,611,615 Nifedipine also has the advan-tage of wider distribution, availability, and lower pricing. Available data showed that hydralazine is less effective than other drugs and is asso-ciated with more side effects.616 Hydralazine is therefore a second-line option to be used only if other drugs are not available.
In cases of pre-eclampsia with severe features, persistent severe hypertension, or recurrent severe hypertension despite orally admi-nistered agents, i.v. administration of labelatolol(or nicardipine) is ad-vised. Intravenous urapilid can also be used but may not be available in all countries.611,617,618 Sodium nitroprusside is the drug of last re-sort because prolonged treatment is associated with an increased risk of foetal cyanide poisoning.619 The drug of choice when pre-eclampsia is associated with pulmonary oedema is nitroglycerine(glyceryl trinitrate), given as an i.v. infusion of 5μg/min, gradually
increasing every 3-5 min to a maximum dose of 100μg/min, in com-bination with diuretics. 43,611
12.3.4. Hypertension and delivery
A recent randomized controlled trial from the United Kingdom found that once a diagnosis of pre-eclampsia was made in women with late pre-term pre-eclampsia(34-37 weeks), there was a lower rate of ma-ternal morbidity and less severe maternal hypertension when delivery was planned to occur within the next 48 h.620 However, a greater pro-portion of neonates were admitted to the neonatal intensive care unit compared to mothers who were managed from an earlier stage.Decisions around timing of delivery should be individualized considering both maternal and foetal well-being. If well managed hypertension alone, delivery should be planned around 39 weeks of gestation.
When choosing the mode of delivery, the clinical scenario should take into consideration the current gestational age and a full foetal as-sessment, as well as the preference of the mother. If induction of la-bour is to be considered, continuous foetal monitoring is required.Women with severe pre-eclampsia benefit from neuraxial anaesthesia to reduce the hypertensive response to pain. Additionally, an epidural will provide adequate anaesthesia should a caesarean delivery be required.
After delivery, methyldopa should be avoided due to the risk of post-partum depression. Methyldopa should be stopped within 2 days after delivery and changed to an alternative treatment.
Recommendation Table 13- Recommendations for hypertensive disorders and pregnancy(see Evidence Tables 12-17)
|Recommendations||Classa|Levelb| |---|---|---|---| |It is recommended to aim for systolic BP<140 mmHg and diastolic BP<90 mmHg in pregnant women.|583,585,609||B| |Systolic BP≥160 mmHg or diastolic BP≥110 mmHg in a pregnant woman is an emergency, and treatment in a hospital setting is recommended.|||C| |Low-dose aspirin(75-150 mg daily) is recommended in women at moderate or high risk of pre-eclampsia(i.e.at least one high-risk factor or two moderate-risk factors for pre-eclampsia) from weeks 12 to 36/37.610,621,622||I|A| |In women with gestational hypertension, initiation of drug treatment is recommended at systolic BP≥140 mmHg or diastolic BP||I|B| |$\geq 90 mmHg$|||| |Methyldopa is recommended for the treatment of hypertension in pregnancy.|623,624|I|B| |Labetalol, metoprolol, and dihydropyridine CCBs are recommended for the treatment of hypertension in pregnancy. ${}^{623}$||I|C| |In severe hypertension, drug treatment with i.v. labelatol, urapidil, nicardipine, or oral short acting nifedipine or recommended for acute reduction in blood pressure. ${}^{625,626}$ Intravenous hydralazine is a second-line option.||I|C| |In pre-eclampsia associated with pulmonary oedema, nitroglycerine given as an i.v. infusion is recommended. ${}^{627}$||I|C| |In women with pre-eclampsia without severe features, delivery is recommended at 37 weeks. ${}^{620,628}$||I|B| |It is recommended to expedite delivery in women with pre-eclampsia associated with adverse markers such as haemostatic disorders.|${}^{629}$||C| |In women with gestational hypertension, delivery is recommended at 39 weeks. ${}^{620,628}$||I|B| |Ambulatory BP or home BP monitoring should be considered to exclude white-coat and masked hypertension, which are common in pregnancy.|lla|C|| |Home BP monitoring may be considered as an adjunct to office BP measurements in pregnant women to detect new-onset hypertension or for monitoring BP control. ${}^{595,596}$||Illb|B|
BP,blood pressure;CBC,calcium channel blocker;iv,intravenous
Class of recommendation.
bLevel of evidence.
````C`Office BP measurements.
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 Figure 13 Arrhythmogenesis in pregnant women. CV; cardiovascular.
12.4. Arrhythmias
The number of pregnant women presenting with arrhythmia is rising due to increasing age at pregnancy and cardiovascular risk factors such as obesity, hypertension, diabetes, and CAD in pregnant wo-men.630 Haemodynamic, metabolic, and hormonal changes,and changes in autonomic function may contribute to increased arrhythmio-genesis during pregnancy and women with prior history of arrhythmia may experience worsening of symptoms during pregnancy(Figure 13). ${}^{630}$ Arrhythmia may have serious effects on the health of both the mother and the foetus and should be treated similarly to ar-rhythmias in non-pregnant women.
12.4.1. Supraventricular arrhythmias
12.4.1.1. New-onset narrow QRS tachycardia
New-onset narrow QRS(<120 ms) tachycardias in pregnancy are treated according to haemodynamic stability. In all cases with haemodynamic instability caused by any supraventricular tachycardia(SVT) including AF and AFL, synchronized, direct current cardiover-sion is indicated(Figure 14). ${}^{631}$ The foetal heart rate should be closely monitored after cardioversion. ${}^{632}$ In haemodynamically stable nar-row QR STS cachardias, the use of vagal manoeuvres(modified Valsalva manoeuvre, carotid sinus massage) may terminate an atrio-ventricular(nodal) re-entry tachycardia(AV(N)RT) arrhythmia.
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 Figure 14 Management of narrow QRS tachycardia in pregnant women.i.v.,intravenous;SVT, supraventricular tachycardia.aAdenosine 6-18 mg bolus.bAtenolol contraindicated.‘Metoprolol.2-5.15 mg.dVerapamil 2.5-10 mg bolus over 5.min.
If these manoeuvres fail, i.v. adenosine(6-18 mg bolus) is recom-mended for termination of AV(N)RT. Intravenous beta-1-selective blockers(preferably metoprolol) can be administered for all SVTs,which either terminate the SVT or slow AV conduction and thereby the ventricular rate. ${}^{634}$ Intravenous beta-1-selective blockers(meto-prol), non-dihydropyridine CCBs(verapamil), and digoxin can be used safely. ${}^{635}$ In stable patients without structural heart disease, fle-cainide and ibutilide may be considered for termination of AF and AFL(Figure 15). In patients with congenital disease, synchronized,direct current cardioversion may be preferred.
12.4.1.2. Atrial fibrillation including anticoagulation
The incidence of arrhythmias among pregnant women is increasing,with AF being the most clinically relevant.252,271,636 Atrial enlargement during pregnancy is accompanied by increased atrial function and both size and function of the left atrium reverse after normal pregnancy.Atrial fibrillation is more frequent in pregnant women at older age, with high BMI638,with ACHD,or with predisposing acquired conditions(e.g.hypertension, HF).637 Compared to women<25 years of age, the odds ratio(OR) of AF episodes was 5.2 in women aged≥40, and the OR was higher in the third compared to the first trimester.638 Rapid
atrioventricular conduction of AF may have serious haemodynamic consequences for both mother and foetus. Atrial fibrillation during pregnancy is associated with increased maternal death. 639 Atrial flutter in pregnant women most often occurs in the presence of ACHD or valvular heart disease(VHD) and in metabolic disturbances such as thyrotoxisosis or electrolyte disturbances.
Direct current cardioversion in pregnancy is required in haemo-dynamically unstable patients with monitoring of foetal heart rate(Figure 15).250,268,271 Rhythm control is the preferred AF treatment strategy during pregnancy. For women with structurally normal hearts,anti-arrhythmic drugs(e.g. flecanide and sotalol, see Section 5.2.5) are not associated with foetal harm, although sotalol's beta-blocker effect necessitates monitoring of foetal growth. 250,268,271 There are minimal data on the use of propafenone during pregnancy, but this sodium chan-nel blocker may be considered if flecanide is not available. Intravenous ibitulide or flecanide may be considered for termination of AFL and AF in haemodynamically stable patients.640
The indication for anticoagulation with LMWH before cardioversion or the need for transoesophageal echocardiography should be evalu-ated as in non-pregnant women and be maintained for at least 4 weeks after cardioversion. 636,641
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![Management of atrial fibrillation and atrial flutter in pregnant women\nHaemodynamically unstable AF/AFL\nAF/AFL with pre-excitation and high ventricular rates\nHaemodynamically unstable AF/AFL\nPharmacological cardioversion\nSevere structural heart disease\nAcute rate control\niv.b-beta-blockersa e.g.metoprololb (Class I)\ni.v.\niv.v. verapamilc\n(i.v. flecainidee\n(Class Ila)\nOR\nOR\niv.v. flecainide\n(Class IIb)\nOR\niv.digoxind\nAvoid amiodarone or\n(i.v. ibutilidef\n(Class IIla)\nESC\nAtrial fibrillation and atrial flutter in pregnancy. AF, atrial fibrillation; AFL, atrial flutter; i.v., intravenous; N,no; SVT, supraven-\ntricular tachycardia; Y,yes.a'Anolenol: contraindicated.bMetoprolol: 2.5-15 mg. Verapamil: 2.5-1 mg bolus over 5 min.dDigoxin: 0.5 mg bolus, 0.75-1.5 mg over 24 h in divided doses.°Flecainide:2 mg/kg over 10 min.fibutilde:<60 kg:0.01 mg/kg over 10 min,repeated after 10 min if necessary;≥60 kg:1mg over 10 min, repeated after 10 min if necessary.\nFig 15 Management of atrial fibrillation and atrial flutter in pregnancy. AF, atrial fibrillation; AFL, atrial flutter; i.v., intravenous; N,no; SVT, supraven-tricular tachycardia;Y,yes.a'Anolenol: contraindicated.bMetoprolol:2.5-15 mg. Verapamil:2.5-1 mg bolus over 5 min.dDigoxin: 0.5 mg bolus,0.75-1.5 mg over 24 h in divided doses.c.Flecainide:2 mg/kg over 10 min.fibutilde:<60 kg:0.01 mg/kg over 10 min,repeated after 10 min if necessary;≥60 kg:1mg over 10 min, repeated after 10 min if necessary.\ni.v.flecainide\nin\nof\nprregnation.\nWhen a rate control strategy is needed in the case of(long-standing)\npresent or permanent AF, beta-blockers, verapamil, or digoxin should be used, also in combination, taking into consideration the con-\ncomitant conditions affecting the mother. ${}^{271,642}$ \nAtrial fibrillation is a strong risk factor for cardioembolic events,\nand the hypercoagulable state of pregnancy may increase this risk. In\npregnant women with persistent or permanent AF, the decision to an-\nticoagulate is the same as in non-pregnant women and depends on the\nrisk of thromboembolic events according to the CHA2DS2-VA score\nand focal atrial tachycardia(FAT), chronic oral prophylaxis can be\nfor thromboembolic events according to the CHA2DS2-VA score\nwith drug-refractory SVT or who have a contraindication to these\nstroke(doubled), vascular disease, age 65-74]. The CHA2DS2-VA\nnone if flecainide is not available.\n](2/aj0YEe4oUhYkBdfpda0fYP/figure6027546bfb924207b3bf738d18bf8199_0_2.png) Figure 15 Management of atrial fibrillation and atrial flutter in pregnancy. AF, atrial fibrillation; AFL,atrial flutter; i.v.,intravenous;N,no;SVT,praven-tricular tachycardia;Y,yes.a'Atenolol: contraindicated.bMetoprolol:2.5-15 mg.Verapamil:2.5-1 mg bolus over 5 min.dDigoxin:0.5 mg bolus,0.75-1.5 mg over 24 h in divided doses。cFlecanide:2 mg/kg over 10 min.fibutilde:<60kg:0.01mg/kg over 10min,repeated after 10 min if necessary;≥60kg:1mg over 10 min, repeated after 10 min if necessary.
When a rate control strategy is needed in the case of(long-standing)persistent or permanent AF, beta-blockers, verapamil, or digoxin should be used, also in combination, taking into consideration the con-comitant conditions affecting the mother. ${}^{271,642}$
Atrial fibrillation is a strong risk factor for cardioembolic events,and the hypercoagulable state of pregnancy may increase this risk. In pregnant women with persistent or permanent AF, the decision to an-ticoagulate is the same as in non-pregnant women and depends on the risk of thromboembolic events according to the CHA2DS2-VA score[congestive heart failure, hypertension, age≥75(doubled), diabetes,stroke(doubled), vascular disease, age 65-74]. The CHA2DS2-VA score threshold of≥2 to anticoagulate has not been validated in
pregnancy.643,644 DOACs are contraindicated in pregnancy. The pres-ence of mechanical valves or moderate to severe mitral stenosis require VKA(see Section 5.2.1 and Section 12.5).
12.4.1.3.Pre-existing supraventricular tachycardia
In women with AVNRT, atrioventricular re-entry tachycardia(AVRT),and focal atrial tachycardia(FAT), chronic oral prophylaxis can be achieved with beta-blockers(metoprolol) or verapamil. For women with drug-refractory SVT or who have a contraindication to these drugs, flacinide or solatol are reasonable alternatives, as is propafe-none if flecanide is not available.
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In pregnant women with AVRT and Wolff-Parkinson-White(WPW)syndrome, arrhythmia episodes can be prevented by using oral fleacinide,or propafenone when fleacinide is not available. When AV-nodal blocking agents are used in WPWP syndrome and AF occurs, the risk of rapid ven-tricular rates is increased. However, in pregnant women without docu-
mented AF, with known orthodromic AVRT, and with intermittent pre-excitation, long-term AV blockade is acceptable for prevention.
If catheter ablation treatment is necessary, it should be performed by experienced operators in a centre equipped with non-fluoroscopic mapping techniques(Section 12.4.3.2).
Recommendation Table 14- Recommendations for supraventricular tachycardia and pregnancy
|Acute management of SVT and AF|Classa|Levelb| |---|---|---| |Immediate electrical cardioversion is recommended for acute treatment of SVT with haemodynamic instability.|1|C| |Vagal nanoeurans and iv.e. adenosine are recommended for conversion of haemodynamically stable supraventricular tachycardias.645|1|C| |Intravenous beta-blockersc(e.g. metoprolol) are recommended as the first-line option for acute rate control in pregnant women with AF or AF with preserved LVEF and rapid ventricular rate.646|1|C| |Intravenous digoxin or verapamil(if preserved LVEF) should be considered as a second-line option for initial rate control in pregnant women with AF or AFL and rapid ventricular rate.635|1|C| |lbutilide or fleacinide may be considered for termination of AF and AFL in pregnant women without structural heart disease.640,647|116|C| |Long-term management of SVT and AF||| |Therapeutic anticoagulation with LMWH is recommended for pregnant women with persistent or permanent AF at elevated|1|C| |thromboembolic risk.636,641||| |Beta-1-selective blockersc are recommended for rate control in pregnant women with AF,AFL,or FAT.|146,271,648|1| |Beta-1-selective blockersc or verapamil are recommended for the prevention of SVT in women without pre-excitation on resting|1|C| |ECG.146,268,649||| |Fleacinide or proaphenone are recommended for the prevention of arrhythmias in pregnant women with WPW syndrome.|1|C| |Digoxin or verapamil should be considered for rate control in pregnant women with AF,AFL,or FAT when beta-blockers fail or are not tolerated.146,271,645|114|C| |Fleacinide, in addition to beta-blockers, should be considered for long-term AF rhythm control in pregnancy.250,268,271,640|114|C| |Sotalol may be considered for rhythm management of AF and AFL with controlling for pro-arrhythmic risk factors as in non-pregnant women.651|116|C| |Catheter ablation may be considered in pregnant women with recurrent, long symptomatic SVT, or with contraindications to pharmacological therapies.|116|C|
AF,atrial fibrillation; AFL,atrial flutter;ECG,electrocardiogram;FAT,focal atrial tachycardia;iv.,intravenous;LMWH,low-molecular-weight heparin;LVEF,left ventricular ejection fraction;SVT,supraventricular tachycardia;WPW,Wolff-Parkinson-White.
Class of recommendation.
bLevel of evidence.
‘Except for atenol.
12.4.2. Ventricular arrhythmias
New-onset VT and ventricular fibrillation(VF) arising during pregnancy are rare(18 per 10000 pregnancy-related hospitalizations). ${}^{652}$ The most common type of VT in pregnant women is idiopathic VT originating from the right ventricular outflow TROV(T) Figure 16). When new-onset VT develops during the last 6 weeks of pregnancy or during the first month post-partum, underlying PCM should be excluded.370
The use of amiodarone is not recommended in pregnancy and should be limited to women with refractory or life-threatening arrhyth-mias that cannot be controlled with any other anti-arrhythmic therapy.If administered, it requires close monitoring for potential side effects in the foetus, such as bradycardia or IUGR.
In women with known underlying substrates for VT, beta-blockers are recommended for prevention of VT.148,252 In case of refractoriness or contraindications to beta-blockers, anti-arrhythmic therapy with fle-cainide, solal, or quindidine is recommended, with the choice of drug based on the underlying cardiac substrate(Figure 16).148,252 Idiopathic RVOT-VT can be prevented with beta-blockers or verapamil.653 When this is ineffective, flecainide 654 or solatol ${}^{650,655-659}$ are safe op-tions to consider for prophylaxis of idiopathic RVOT-VT.
Recommendations on the acute management of ventricular arrhyth-mia during pregnancy are described in the 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the preven-tion of sudden cardiac death, and are depicted in Figure 16. ${}^{252}$
12.4.3. Cardioversion, ablation, and device implantation, and implantable cardioverter defibrillator manage
12.4.3.1. Electrical cardioversion
Electrical cardioversion is safe and effective in all pregnancy phases as it does not affect foetal circulation or induce foetal arrhythmia. In preg-nancy there are no changes in transthoracic impedance compared to non-pregnant women,660 and shock energies delivered should there-fore be the same as in non-pregnant patients. The foetal heart rate should be monitored after cardioversion. ${}^{631,632,661,662}$
12.4.3.2. Catheter ablation
Catheter ablation in pregnant women should preferably be performed after the first trimester in a centre with experience in non-fluoroscopic
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electro-anatomical mapping and catheter navigation systems.663-665 Catheter ablation for drug-refractory and poorly tolerated VT or for recurrent drug-refractory AVNRT,AVRT,FAT,cavorticuspid isthmus-dependent AFL, and certain benign right-sided VTs may be considered to avoid potentially harmful anti-rarrhythmic drug effects during preg-nancy, although it has no role in AF.664,666
12.4.3.3. Device implantation
An ICD is indicated in pregnant women who are at high risk of sudden cardiac death. ${}^{252}$ Implantation of a device is not associated with a high-er risk of major complications and can be performed safely, ${}^{667,668}$ par-ticularly after 8 weeks of gestation. During implantation, radiation exposure should be minimized following the ALARA principle(see
 Figure 16 Management of ventricular tachycardias in pregnancy. CPVT, catecholaminergic polymorphic ventricular tachycardia; i.v., intravenous; N, no;RVOT, right ventricular outflow tract; VF, ventricular fibrillation; VT, ventricular tachycardia; Y, yes. See Supplementary data online(Table S6) for medication dosages. Adapted from Zeppenfeld et al. ${}^{252}$ .
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Section 4.3.5) or with non-fluoroscopic imaging techniques.669 Women with an ICD should maintain their regular ICD care through-out pregnancy. ${}^{669}$
12.4.3.4. Implantable cardioverter defibrillator management
Routine ICD interrogation and guidance are recommended prior to de-livery. Management of pregnant women with an ICD or pacemaker is summarized in Figures 17 and 18.
Women with structural heart disease are at higher risk of atrial and ventricular tachyarrhythmias during pregnancy.670 Consequently,preg-nant women with ICDs may present with either an inappropriate shock(due to e.g. lead defects, new-onset supraventricular tachyarrhythmias,or technical issues such as T-wave oversensing or noise sensing) or an
appropriate ICD shock caused by ventricular tachyarrhythmias. In case of tachyarrhythmias, triggering events such as HF, electrolyte abnormal-ities, ischaemia, or infectious disease should be ruled out, as with non-pregnant women. Depending on the underlying cause, therapy consists of device reprogramming or initiating or adapting anti-arrhythmic drug therapy. In the case of drug-refractory arrhythmias or serious anti-arrhythmic drug side effects, catheter ablation may be considered in ex-perienced centres.
Most data indicate that maternal ICD shocks do not have major foe-10al adverse effects. ${ }^{668,671}$ The approach to pregnant women presenting with ICD shocks is no different from non-pregnant women(Figure 18). ${ }^{252}$
A WCD may be considered when pregnant women have an ICD in-dication from reversible conditions.365,672-674
 Figure 17 Management of pacemaker and implantable cardioverter defibrillator and pregnancy. b.p.m., beats per minute; ICD, implantable cardioverter defibrillator; VF, ventricular fibrillation; VT, ventricular tachycardia. ${}^{a}$ Patients with an increase in arrhythmias during pregnancy, history of ventricular tachyar-rhythmias. ${}^{b}$ Single zone configuration: VT detection at 250 b.p.m., prolonged detection duration, e.g. 30 out of 40 beats.
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 Figure 18 Management of implantable cardioverter defibrillator shocks in pregnancy. ICD, implantable cardioverter defibrillator; N,no;SVT, supraven-tricular tachycardia; VF, ventricular fibrillation; VT, ventricular tachycardia; Y, yes.
Recommendation Table 15- Recommendations for ventricular tachycardia, device implantation, catheter ablation, and pregnancy
|Recommendations|Classa|Levelb| |---|---|---| |Immediate electrical cardioversion is recommended for both unstable and stable ventricular tachycardias. 252|1|C| |Beta-blockers or verapamil are recommended for the prevention of idiopathic sustained VT.|1|C| |If an ICD, pacemaker, or resynchronization therapy device is indicated during pregnancy, implantation is recommended with optimal radiation protection. 667,675|1|C| |In idiopathic RVOT-VT, flecanide should be considered if beta-blockers fail, to prevent recurrence.|lla|C|
For acute conversion of haemodynamically stable sustained VTs during pregancy, i.v. beta-blocker,adenosine(idiopathic RVOT-VT), verapamil(fascicular VT), procanimide, or overdrive ventricular pacing(ICD lead) should be considered. ${}^{252,653,676-678}$
When performing catheter ablation during pregnancy, the use of non-fluoroscopic mapping and navigation systems should be considered. ${ }^{663-665}$ C Catheter ablation with electro-anatomical mapping systems may be considered in experienced centres in the case of sustained drug-refractory, recurrent, and/or poorly tolerated VT if there are no other alternatives.
llb C
ICD, implantable cardioverter defibrillator; i.v., intravenous; RVOT, right ventricular outflow tract; VT ventricular tachycardia.
${}^{B}$ Level of evidence.
C
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12.4.4. Cardiac arrest
Maternal cardiac arrest occurs in 8/100 000 hospitalizations in the United States of America $^{679}$ and 7.6/100 000 pregnancies in the Netherlands. $^{680}$ Haemorrhage and anaesthetic complications are the most common overall causes of cardiac arrest, $^{681}$ and HF, ACS, arrhythmias, aortic dis-section, and PE are the most common cardiovascular causes of cardiac arrest. $^{682,683}$
Because most of the underlying causes of cardiac arrest in pregnancy tend to be reversible, pregnant women have better outcomes than non-pregnant women. ${}^{684}$ Basic cardiac arrest resuscitation principles apply to pregnant women, although some differences should be consid-ered. ${}^{684}$ If cardiac arrest occurs beyond 20 weeks of pregnancy, left lat-eral manual displacement of the uterus or left lateral position of the woman is indicated to avoid aortocaval compression(Figure 19).Chestcomplications·Bleeding·Pulmonary embolism·
 Figure 19 Management of cardiac arrest in pregnancy.i.v.,intravenous;ROSC,return of spontaneous circulation.30mL calcium gluconate 10% solution.
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In post-arrest care, the full left lateral decubitus position is recom-mended. The use of device-assisted chest compressions in pregnancy is currently not recommended due to lack of data. ${}^{684}$ Importantly, no drugs should be withheld because of concerns about teratogen-icity. ${}^{614,686}$ Foetal monitoring after cardiac arrest is mandatory.
Emergency casarean section should be immediately prepared for and considered when initial resuscitation fails. ${}^{682}$ If this is not feasible,rapid maternal transfer is advised to an appropriate clinical setting with uninterrupted resuscitation.
Recommendation Table 16- Recommendations for cardiac arrest and pregnancy
|Recommendation|Classa|Levelb| |---|---|---| |Continuous manual left uterine displacement during CPR in pregnant women (≥20 weeks) with cardiac arrest is recommended to relieve aortocaval compression. 614|I|C| |It is recommended to establish i.v.access above the diaphragm to ensure that the i.v. therapy is not obstructed by the gravid uterus. 614|I|C| |It is recommended to perform the same chest compressions and defibrillation protocols in pregnant as in non-pregnant women. 554,614,687|I|C| |Anterolateral defibrillator pad placement is recommended with the lateral pad placed under the breast. 614,660|I|C| |It is recommended that no drugs are withheld in pregnant women with cardiac arrest due to concerns of teratogenicity. 686|I|C| |Immediate casearan sea in the site of the arrest should be considered and immediately prepared if ROSC has not been achieved in the mother after 4 min of resuscitative efforts and if the foetus is viable,taking gestational age, comorbidities, and the available level of medical care into account. 614,688,689|lla|C|
CPR, cardiopulmonary resuscitation; iv, intravenous; ROSC, return of spontaneous circulation.
${}^{2}$ Class of recommendation.
Ⓑ Level of evidence.
12.4.5. Bradycardia
12.4.5. Bradycardia
Sinus bradycardia due to sinus node dysfunction is uncommon in pregnant women who do not have structural heart disease. In the second trimester, symptomatic bradycardia may occur as a re-sult of a reduction in systemic resistance, but this rarely requires treatment. Symptomatic bradycardia during pregnancy may be caused by the supine hypotensive syndrome, defined as a systolic BP decrease of>15 mmHg due to compression of the inferior vena cava by the uterus.690 Management depends on the underlying cause, severity of symptoms, and potential risks to both the mother and the foetus.
12.4.5.2. Atrioventricular block
Mobitz type I AV block is common in pregnant women and rarely progresses during pregnancy.691 There are no data on progression of congenital AV conduction block during pregnancy and vaginal delivery does not cause extra risk for mothers who are asymp-tomatic, haemodynamically stable, and have a normal cardiac anat-omy and function.691 Prophylactic placement of temporary pacemaker wires is not usually indicated but is an individualized decision.
12.4.5.3. Management of sinus node dysfunction and atrioventricular block
In acute, life-threatening settings,bradycardia should be treated as in non-pregnancy. Isoproterenol can be used when benefits outweigh risks.It is not known if it is excreted in human milk. Pacing indications(temporary and permanent) do not differ between pregnant and non-pregnant women and can be found in the 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization ther-apy.692 Pacemakers can be implanted safely during pregnancy using standard methods with minimal fluoroscopy or non-fluoroscopic methods.675,693-695
Recommendation Table 17- Recommendation for congenital atrioventricular block and pregnancy
|Recommendation|Classa|Levelb| |---|---|---| |In pregnant women with asymptomatic congenital||| |AV block,normal cardiac anatomy and function,a narrow QRS complex,and ventricular rate||| |(≥50 b.p.m.),a prophylactic temporary pacemaker during delivery is not recommended.691|||
AV, atrioventricular; b.p.m.,beats per minute; QRS,Q,R,and S waves.
${}^{a}$ Class of recommendation.
Ⓑ Level of evidence.
12.5. Valvular heart disease
During childbearing years VHD is usually either congenital or rheumatic in cause. Complications during pregnancy include new-onset AF, which can lead to deterioration in cardiac function, an increased risk of thromboembolic events, and heart failure.696,697 Women with valve disease should have access to pre-conception counselling and their car-diac condition should be optimized. This may include pre-pregnancy intervention or surgery for those with symptoms or severe disease(Figure 20), in keeping with the 2021 ESC/EACTS Guidelines for the management of valvular heart disease.698 Dedicated tools for risk strati-fication may be needed in the setting of rheumatic heart disease.697
12.5.1. Stenotic native valve lesions
Stenotic valve lesions limit the ability to increase CO during pregnancy.The result of this may be presentation with symptoms for the first time during pregnancy. Serial TTE in pregnancy will usually demonstrate an increase in valve gradient of up to 50% due to the normal pregnancy-related increase in CO. ${}^{699}$
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12.5.1.1. Mitral valve stenosis
Mitral valve stenosis is a common cause of HF during pregnancy. ${}^{11}$ Mild stenosis is usually well tolerated. ${}^{11}$ However, symptoms may occur if the valve area is<1.5 cm2. Maternal mortality in mitral stenosis is higher in those with NYHA>II, systolic pulmonary arterial pressure(PAP)>30 mmHg, severe stenosis, older age, and in low-income coun-tries ${}^{11,696,700}$ (Figure 20). Foetal risks include increased rates of prema-ture delivery, IUGR, and foetal death, especially in highly symptomatic mothers(NYHA III/IV).701
12.5.1.1. Management. Diagnosis is as per usual criteria.698 During pregnancy, valve area by 2D-planimetry is thought to be more reliable than flow-dependent measures, because higher stroke volume and tachycardia will increase the measured gradient across the valve.702 Mitral valve anatomy, especially the presence of subval-var involvement or the presence of MR, is important if considering intervention.
If signs or symptoms of PH are present, activity restriction should be suggested, and beta-blockers and/or diuretics should be started.Anticoagulation regimens should be individualized. Therapeutic antic oagulation with full therapeutic-dose LMWH or VKA(see Section 5)is indicated in those with AF, left atrial clot, or a previous embolism.Anticoagulation should be considered in those with significant mitral stenosis, spontaneous echo contrast in the left atrium, dilated left at-rium with left atrial volume index>60 mL/ml2, or those in HF.
12.5.1.1.2. Interventions. Pre-pregnancy intervention should be con-sidered in those with significant stenosis(valve area<1.5 cm2). Before and during pregnancy, percutaneous mitral balloon commisrotoromy is the primary intervention in those who remain in NYHA III/IV or with severe PAP elevation despite medical therapy.703 Balloon techniques are highly successful during pregnancy unless there is complex subvalvar involvement. Closed commissorutomy is rarely used but is an alterna-tive. Open valve surgery should only be used when there is a risk to ma-ternal life and other options are not possible or have failed. ${}^{704}$
12.5.1.1.3. Delivery. Vaginal delivery is the preferred option.Caesarean section is preferred in cases of severe mitral stenosis and for those with refractory HF. Delivery is a time of increased risk of HF and thrombotic events. ${}^{182}$
12.5.1.1.4. Post-partum. Close monitoring is needed in the days follow-ing delivery and diuretics may be required to treat fluid overload. The long-term outcome depends on the risk of valve progression and the success of commissorotomy if performed. Lifelong follow-up is required.
12.5.1.2. Valvular aortic stenosis
Bicuspid aortic valve disease is a common cause of valvular aortic stenosis in women of childbearing age. The outcome is related to the baseline severity of the stenotic lesion. Women with severe stenosis and those with symp-toms prior to pregnancy have a 1 in 4 risk of developing HF during preg-nancy. ${}^{703}$ Exercise testing and measurement of NP can be used to stratify risk prior to pregnancy. Those with symptomatic severe aortic sten-osis should be offered intervention prior to pregnancy. Risk-stratifying those with asymptomatic aortic stenosis is more challenging. Left ventricu-lar systolic dysfunction, or effort limitation on exercise testing, indicate that intervention before pregnancy should be considered. ${}^{698}$
Women with severe aortic stenosis contemplating pregnancy should be counselled regarding the risks and offered surgery if they prefer.
Despite this, maternal mortality is rare for those under expert care.703 The risk of sudden death in those with severe stenosis is in-creased but difficult to quantify. BAV-associated aortopathy is dis-cussed in Section 8.3.
12.5.1.2.1. Management. Medical therapy has a limited role in symptomatic aortic stenosis. Diuretics may help those with HF or high filling pressures, but caution should be exercised. In women with severe symptomatic stenosis, rest and possibly hospital ad-mission should be considered. Intervention should be considered in women with persisting symptoms including angina or with new ST changes on ECG.In symptomatic pregnant women with severe aortic stenosis not responding to medical therapy, non-surgical options such as balloon valuloplasty or transcatheter aortic valve implantation(TAVI) may be considered during pregnancy.705,706 Procedures should be performed in an experienced valve centre. If no catheter-based options are available, surgical valve replacement or repair is re-commended. If the foetions is at a viable gestation, taking account of other comorbidities and the available level of neonatal care, delivery should occur prior to valve intervention. These complex decisions should be discussed with the full Pregnancy Heart Team."707 Cardiac surgery with cardiopulmonary bypass is associated with at least a 20% risk of foetal loss.
Vaginal delivery is the preferred mode of delivery for the majority of women. In those with severe symptomatic aortic stenosis, caesarean delivery should be considered. Early post-partum HF may develop.
For pulmonary stenosis, see Section 9 on congenital heart disease.
12.5.2. Regurgitant native valve lesions
Valve regurgitation is generally better tolerated than valve stenosis in pregnancy. Increased maternal and foetal event rates can be seen in those with severe regurgitation. ${}^{709}$
12.5.2.1. Mitral and aortic valve regurgitation
Women with valve regurgitation and either symptoms or LV dysfunction incur an increased risk of HF, occurring in 20%-25%of those with at least moderate regurgitation. ${}^{182,710}$ Acute regurgitant lesions are often less well tolerated than chronic regurgitation.
12.5.2.1.1. Management. Diuretics can be used in those with severe symptomatic mitral or aortic regurgitation. Cardiac surgery is rarely re-quired during pregnancy. Vaginal delivery is preferred unless the mother is in refractory HF.
12.5.2.2. Arrhythmogenic mitral valve prolapse
Arrhythmic mitral valve prolapse(AMVP) is defined as the presence of mitral valve prolapse and arrhythmia symptoms or signs, such as fre-quent ventricular premature contractions or complex ventricular ar-rhythmias.711 The arrhythmias may arise from myocardial fibrosis resulting from prolonged and increased stretch of papillary muscles and of the inferolateral LV wall by the prolapsing valves.
Several reports have included female sex as a risk factor for severe arrhythmic events.711 Other risk factors include syncope, the pres-ence of mitral annular disjunction, late gadolinium enhancement on CMR, complex ventricular arrhythmias, including non-sustained ventricular tachyocardia, syncope, T-wave inversions in the inferolat-eral ECG leads, bi-leaflet mitral valve prolapse, and reduced LVEF.Little is known about the effect of pregnancy in women with AMVP,but altered loading conditions may lead to increased tension in mitral
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valve apparatus and thereby increased risk of ventricular arrhythmias.A recent publication indicated increased arrhythmic risk during preg-nancy in women with AMVP and life-threatening ventricular arrhythmias.712
<BeginOfPara>It is recommended that women with AMVP undergo pre-conception counselling and optimization of medication. Medical treatment includes anti-arrhythmic therapy with, for example, beta-blockers and/or flecai-nide.713 If started pre-pregnancy, treatment should continue during preg-nancy with close follow-up and arrhythmic monitoring. A pregnant woman with AMVP should be monitored during pregnancy at a tertiary
centre with experience in AMVP and with periodic Holter monitoring to identify a potential increase in arrhythmic burden. ${}^{711}$ Risk stratification for ICD implantation should follow the consensus for AMVP in general. ${}^{711}$
12.5.2.3. Tricuspid regurgitation
Medical treatment for tricuspid regurgitation is usually not required but during pregnancy diuretics and medication for rhythm manage-ment may be needed. Surgery for isolated TR in pregnancy is rarely indicated except for the setting of endocarditis.
 Figure 20 Valvular heart disease and pregnancy.ECG,electrocardiogram;LV,left ventricle;LVH,left ventricle/HPUH,left ventricle;PASP,pulmonary arterial systolic pressure;RV,right ventricle;RVH, right ventricular hypertrophy.Red flags indicate high-risk features.
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Recommendation Table 18- Recommendations for native valve disease and pregnancy
|Recommendations|Classa|Levelb| |---|---|---| |Intervention is recommended before pregnancy in symptomatic patients with severe aortic stenosis. ${}^{698}$||C| |Intervention is recommended before pregnancy in women with mitral stenosis and a valve area<1.5 cm2. ${}^{698,701,714}$||C| |In pregnant women with symptomatic mitral stenosis or pulmonary hypertension, restricted activities and beta-blockers are recommended. ${}^{20}$||C| |In pregnant women with mitral stenosis, diuretics are recommended when congestive symptoms persist despite beta-blockers. ${}^{20}$||C| |Full therapeutic-dose anticoagulation is recommended in women with mitral stenosis complicated by AF, left atrial thrombus, or prior embolism.||| |Surgical treatment is recommended before pregnancy in women with severe aortic or mitral regurgitation with symptoms, impaired ventricular function, or marked ventricular dilatation.||| |Diuretics are recommended in pregnant women with regurgitant lesions when symptoms or signs of congestion occur.||C| |Intervention should be considered before pregnancy in those with asymptomatic severe aortic stenosis after counselling on the risks and benefits. ${}^{698}$||C| |Percutaneous mitral commissorotomy for mitral stenosis should be considered in pregnant women with severe symptoms or systolic pulmonary artery pressure>50 mmHg despite medical therapy. ${}^{698}$|lla|C| |Valve surgery during pregnancy should only be considered when there is a maternal mortality risk and other treatment options have failed. ${}^{421}$|lla|C| |In very selected symptomatic pregnant women with severe aortic stenosis not responding to medical therapy, non-surgical options such as balloon valuloplasty or TAVI may be considered. ${}^{716}$|Ib|C|
AF,atrial fibrillation; TAVI, transcatheter aortic valve implantation.
Class of recommendation.
bLevel of evidence.
12.5.3. Prosthetic valves
When a woman of childbearing age or a girl requires valve surgery,careful consideration should be given to the possibility of future preg-nancies. When appropriate, the discussion regarding valve choice should involve the Pregnancy Heart Team. In general, valve repair,valve-in-valve, or non-mechanical valves are preferable, avoiding the need for anticoagulation. Data from the ROPAC III study, focusing on prosthetic valves, show that the chance of an uncomplicated preg-nancy with a live birth in women with a MHV was 54%, compared to 79% in women with a tissue valve.177 Regional differences, especially be-tween high-income and low- and middle-income countries, need to be acknowledged, as also indicated in a recent study from Madras in India(M-PAC registry) describing pregnancy outcomes in 70 women with a prosthetic heart valve.717 A very high foetal death rate and major ad-verse cardiovascular events(MACE) rate(40% and 34%, respective-ly),717 including a high number of valve thromboses, is believed to relate not only to differences in organization of care, but also to under-lying valvular disease, with more rheumatic heart disease in low- and middle-income countries. The Ross procedure in aortic valve disease is an alternative option to be considered. In the absence of aortic dila-tation, pregnancy risk is low after the Ross procedure. ${}^{718}$
12.5.3.1. Bioprosthetic valves
Prior to pregnancy, a full assessment of valve function should be performed. Many women are on lifetime low-dose aspirin treatment,and this should be continued during pregnancy unless there is a contra-indication. If there is severe valve dysfunction prior to pregnancy,reintervention should be considered. However, in this setting the risk of pregnancy with the current valve dysfunction should be ba-lanced against the risk of the new valve being proposed. Mechanical
valve implantation should be avoided when possible. Transcatheter valve-in-valve intervention may have a role in extending the lifespan of a failing bioprosthetic valve in a young woman contemplating preg-nancy. In a recent retrospective study of CARPREG data, 215 pregnant-cies in 101 women who had implanted bioprosthetic valves prior to pregnancy were described. More than a quarter had some degree of valvar dysfunction, although the time since the last valve replacement surgery was only 6±3 years on average. Bioprosthetic valve dysfunc-tion was more than twice as common in women with left-sided as op-posed to right-sided valves. ${}^{719}$
The chance of pregnancy without serious adverse events and a live birth in women with a bioprosthetic valve is 79%.177 When significant bioprosthetic dysfunction is present, the risk of complications can be significant, especially if associated with severe stenosis or ventricular dysfunction. There is no compelling evidence that pregnancy is asso-ciated with accelerated valve deterioration.
12.5.3.2. Mechanical valves
Pregnant women with MHVs are exposed to a high risk of complica-tions(mWHO 20. risk classification≥III). The chances of an event-free pregnancy with a live birth were only 58% in the initial ROPAC ll study and showed no improvement after 8 years in the ROPAC III study(54%).177,204 Thrombotic complications occur in 9%-24% and bleeding complications in 20%-30% of the cases in the ROPAC III and a United Kingdom study, respectively.176,177 Women with a mechanical valve in the mitral position are especially at risk of adverse outcomes, including mortality.177
All women with MHVs should be fully counselled pre-pregnancy re-garding the risks and benefits of the various anticoagulation regimens.When planning the optimal anticoagulation strategy, logistical issues,
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such as access to timely anti-factor Xa level testing and maternal ability to adhere to treatment regimens, need to be considered.
12.5.3.2.1. Anticoagulation during pregnancy. The most effective regimen in preventing maternal thrombotic complications is the con-tinuous use of VKAs. Thrombotic events not only compromise the mother but also jeopardize the baby. 170,200,204,206,720,721 However,there remain concerns about the foetal impact of VKAs. Data from the ROPAC III study indicated a higher risk of miscarriage in VKA users.177 As discussed in Section 5, the foetal risk of VKAs is in part dose-related. Although there is no safe dose for the foeta, event rates are reduced when lower doses of VKA are used.200 For these reasons,continuation of VKAs should be considered when the risk of throm-bosis is high and the dose required to achieve the target INR is low(see Section 5). Target INRs are unchanged from non-pregnant va-lues.698 INR monitoring should be weekly or every 2 weeks(see Section 5).
The alternative strategy is switching to therapeutic-dose LMWH(twice daily) until the 12th week of pregnancy with a monitoring plan. The target peak levels of anti-factor Xa should be discussed in-dividually and vary between 1 and 1.2 IU/mL. The value of trough anti-factor Xa levels is less clear. Adjusting dosing to obtain levels of>0.6 IU/mL has been suggested, however, with little evidence.170,216 Dosing regimens for therapeutic LMWH are provided in Section 5.In women with a very high thrombotic risk, the addition of low-dose acetylsalicylic acid(ASA) should be considered.170 In rare circum-stances, such as the unavailability of anti-factor Xa level testing, i.v.UFH can be used.Targeted a PTT levels with a prolongation of≥2 times the control can be challenging to achieve and may require multiple ad-justments of dosing and prolonged inpatient care. In the majority of cases, VKAs will be the favoured therapy in the second and third tri-mesters to minimize the maternal risks after the period of embryo-genesis.176,204 Despite this, some women will choose to remain on
therapeutic-dose LMWH throughout pregnancy. The management of anticoagulants during pregnancy in women with MHVs is summar-ized in Figure 21.
12.5.3.2.2. Mechanical valve thrombosis. Regular maternal cardiac ultrasound should be performed during pregnancy to assess valve func-tion and rule out valve thrombosis. Imaging once per trimester will usu-ally suffice unless there is pre-existing valve dysfunction or HF. Changes in valve gradient that exceed the usual increase due to changing cardiac output should be investigated. Symptoms such as new HF, embolic event, or syncope ne urgent assessment. Changes in valve clicks and new murmurs should also trigger investigation. Transthoracic and transoesophageal echocardiography, fluoroscopy, and CT can all be used to assess MHV leaflet movement.
Valve thrombosis has a high maternal mortality. Its management is comparable with management in non-pregnant women. In a subacute setting, optimizing anticoagulation with UFH and re-establishing a therapeutic INR with VKA may be sufficient. Thrombolysis may be con-sidered, especially in non-critically ill women, when surgery is not imme-diately available for critically ill women, and in right-sided prosthetic valve thrombosis.698 Urgent intervention is often required in acute thrombosis with obstruction or severe regurgitation.722 This is asso-ciated with high maternal and foetal risks. There is a clear survival bene-fit for the foetus without increasing maternal mortality if cardiac surgery is performed after caesarean section. Therefore, the optimal treatment strategy, as determined by the Pregnancy Heart Team, will depend on type of valve caesarean section. Therefore, the optimal mother, and gestational age. 421
12.5.3.2.3. Anticoagulation during delivery in women with mechan-ical heart valves. The management of delivery for women with MHV is discussed in Section 4.5.6. These are high-risk deliveries with sig-nificant bleeding complications.
Recommendation Table 19-Recommendations for prosthetic valves and pregnancy(see Evidence Table 18)
|Recommendations|Classa|Levelb| |---|---|---| |A bioprosthetic valve is recommended (over a mechanical valve) in young women contemplating pregnancy requiring a valve prosthesis. 177|I|B| |It is recommended that the type of valve surgery or intervention for a woman contemplating pregnancy is chosen in consultation with the Pregnancy Heart Team.|I|C| |Women with mechanical heart valves||| |It is recommended that a care plan documenting the agreed anticoagulant strategy(including the decision to continue VKAs or converting to therapeutic-dom MHW in the first trimester) is in place for women of childbearing age with an MHV prior to pregnancy or as soon as pregnancy is recognized. 170|I|C| |It is recommended that pregnant women with an MHV are managed by the Pregnancy Heart Team. 170|I|C| |In pregnant women on VKAs, it is recommended to perform INR monitoring weekly or at a minimum every 2 weeks.|I|C| |In pregnant women with MHVs on therapeutic-dose LMWH, it is recommended to check peak anti-factor Xa levels and to target levels according to individualized risk.|1|C| |During the second and third trimesters until the 36th week, continuing VKAs should be considered in women with prosthetic heart valves at higher risk of thrombosis.|IIa|C| |During the second and third trimesters, continuing LMWH with anti-factor Xa level monitoring and dose adjustment may be considered in women at lower risk of thrombosis.|IIb|C| |LMWH is not recommended when anti-factor Xa level monitoring is not available.|III|C|
INR, international normalized ratio; LMWH, low-molecular-weight heparin; MHV, mechanical heart valve; VKA, vitamin K antagonist.
${}^{b}$ Level of evidence.
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Figure 21 Management of anticoagulants during the different stages of pregnancy in women with mechanical heart valves. INR,international normalized ratio; i.v., intravenous; LMWH, low-molecular-weight heparin; LV,left ventricle; N,no; UFH, unfractionated heparin; VKA, vitamin K antagonist; Y, yes. ${}^{a}$ See Table 10. ${}^{\text{b}}$ See Figure 5 and Section 4.5.7.
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12.5.4. Endocarditis prophylaxis
Infective endocarditis during pregnancy is a rare yet severe event as-sociated with maternal and foetal morbidity and mortality. An increas-ing risk factor is represented by i.v. drug abuse associated with the opioid epidemic in the United States of America.723 The most com-mon pathogens are Staphylococcus(74%) and Serratia(13%).724 A re-cent comparison across antepartum, delivery, and post-partum maternity-associated infective endocarditis showed the 60-day mor-tality rate was highest in the delivery subgroup and the rate of valve replacements was highest in post-partum cases.725 Antibiotics should be given according to guidelines, 178,726 laboratory data on culture and antibiotic sensitivity, and the differential foetal toxicity of antibiotics(see Section 5).
12.6. Heart failure
12.6.1. Chronic heart failure
Heart failure complicates 11% of pregnancies in women with pre-existing heart disease and has an in-hospital maternal mortality rate of 9%2.Specific pre-pregnancy counselling is needed for women with ventricular dysfunction irrespective of the cause. As many HF medications are contra-indicated in pregnancy(see Section 5), modifying the drug regimen pre-pregnancy should be part of pregnancy risk stratification, with reassessment after at least 3 months. ${}^{727}$ Contractile reserve off HF therapy, measured by stress echocardiography, can be used for reassessing ventricular function.371
Two peaks of HF deterioration occur in pregnancy: at 23-30 weeks and peri-delivery.182 Pre-conception counselling should include a discussion of management if there is a clinical deterioration during the first peak. Early de-livery due to maternal cardiac deterioration will impact fetal outcomes.
Patients with mild ventricular dysfunction may tolerate pregnancy with no increase in symptoms. However, those with worse than mild ventricu-lar dysfunction(mWHO 2.0 class>ill)(Table 6) require expert care from the Pregnancy Heart Team, with additional input from the advanced HF team including transplant and mechanical circulatory support experts.
Women with pre-existing severe HF(LVEF<30%,mWHO 2.0 class IV) are at high risk of maternal morbidity and mortality, and account for up to 15% of maternal deaths globally.2,728
Assessment of patients with pre-existing HF includes regular assess-ment of symptoms, echocardiography, and NP at intervals determined by the severity of HF and other non-cardiac issues.
12.6.2. Acute heart failure(including cardiogenic shock)
Acute heart failure can develop in women without pre-existing heart disease as can be the case in PPCM(Section 7), or secondary in women with known cardiac disease such as cardiomyopathy, ischaemic heart disease,ACHD,and severe VHD.The diagnosis can be challenging be-cause the symptoms and signs of AHF can be misinterpreted as changes due to pregnancy(Figure 22).349,729 Pregnant women presenting with AHF require urgent hospital admission. These patients should be re-ferred to an expert centre with established advanced HF care, including on-site surgery and mechanical circulatory support or even a transplant programme as backup.In case of cardiogenic shock, recommended inotropic agents include le-
In case of cardiogenic shock, recommended inotropic agents include le-vosimendan, ${}^{730}$ dobutamine, and mirilone(Figure 22). Levosimendan is administered as a continuous infusion without an intial loading dose.Dobutamine is an option, whereas adrenaline should be avoided.Milirone may be an alternative if benefits outweigh the risk, due to placental transfer(see Supplementary data online, Table S2). Mechanical circulatory support[preferably veno-arterial extracorporeal membrane oxygenation(VA-ECMO) ${}^{731}$ ] should be considered in case of severe
refractory cardiogenic shock.339 In cardiogenic shock, urgent delivery by caesarean section with combined spinal/epidural analgesia or general an-esthesia is recommended.732-734
Milder cases of acute HF can be treated with oral diuretics,b1-selective beta-blockers(bisopropol, metoprolol succinate), hydrala-zine, and oral nitrates. Diuretics(loop diuretics and thiazides if re-quired) should be used with caution due to a potential reduction in uterine blood flow, but may be necessary in pulmonary congestion or echocardiographic signs of high LV end-diastolic pressure.
Recommendation Table 20- Recommendations for chronic and acute heart failure and pregnancy(see Evidence Table 19)
|Chronic heart failure||$$\text{Level}^{\text{b}}$$| |---|---|---| |It is recommended that women with HFREF are advised about the risk of deterioration of cardiac function during pregnancy and peripartum. ${}^{34}$||C| |In pregnant women with HFREF, it is recommended that non-selective beta-blockers are switched to beta-1-selective blockers(metoprolol, bisoprolol) with close maternal and foetal monitoring. ${}^{733,734,738,739}$||C| |Anticoagulation with therapeutic doses of LMWH is recommended in pregnant women with intracardiac thrombus or decreased LV function with EF<35%.216||| |It is recommended to optimize HF guideline-directed medical therapy after delivery,taking contraindicated drugs during lactation into account. ${}^{339,734}$|l|C| |Due to the high metabolic demands of lactation, avoiding lactation may be considered in women with severe HF.360,733|llb|C| |ACE-Is,ARBs,ARNIs,MRAIs,ivabradine,and SGLT2 inhibitors are not recommended during pregnancy due to adverse foetal effects.||| |Acute heart failure||C| |Inotropes and/or vasopressors are recommended in pregnant women with cardiogenic shock with levosimendan, dobutamine, and mirinone as recommended agents. ${}^{730}$|l|C| |Urgent delivery with caesarean section is recommended in pregnant women with cardiogenic shock as soon as the foetus is viable, taking gestational age, comorbidities, and the available level of medical care into account. ${}^{689}$||C| |Early transfer of pregnant women in cardiogenic shock to a facility providing mechanical circulatory support should be considered. ${}^{345,740}$|lla|C| |Preventing lactation may be considered in women with severe HF due to the high metabolic demands of|llb|B|
ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI,angiotensin receptor/repinolysin inhibitor; EF,ejection fraction;HF, heart failure; HF,heart failure with reduced ejection fraction; LMWH, low-molecular-weight heparin; LV, left ventricle;MRA, mineralocortic receptor antagonist; SGLT2, sodium-glucose co-transporter-2.
aClass of recommendation.
bLevel of evidence.
“See Figure 6 and Supplementary data online, Table S2.
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 Figure 22 Management of acute heart failure and cardiogenic shock in pregnancy and up to 6 months post-partum.ACE-I,angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; ARNI, angiotensin receptor/nepriolysin inhibitor; b.p.m., beats per minute; HF, heart failure; HR, heart rate;LMWH, low-molecular-weight heparin; LVAD, left ventricular assist device; MCS, mechanical circulatory support; MRA, mineralocorticoid receptor antag-onist; PPCM, peripartum cardiomyopathy; SGLT2-l, sodium-glucose co-transporter-2 inhibitor; SBP, systolic blood pressure; SpO2, oxygen saturation;VA-ECMO, veno-arterial extracorporeal membrane oxygenation. ${}^{2}$ Assessment of heart failure severity: SBP<90 mmHg; HR>130 b.p.m. or<45 b.p.m;respiratory rate>25/min; SpO2<90%; Blood lactate>2.0 mmol/L; low central-venous oxygen saturation<60%(if available); altered mental state; cold,clammy,mottled skin; oliguria<0.5 mL/kg/h.b.Rombroriptine: starting dose 2.5 mg twice daily with up-titrification if needed.
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Beta-blockers should be initiated and gradually up-titrated to the max-imum tolerated dose.345,357,732-734 ACE-Is, ARBs, ARNs, IMRAs, ivab-radine, SGLT2 inhibitors, and aenolol are contraindicated during pregnancy due to adverse effects on the foetus. Hydralazine and ni-trates appear safe.43,345,357,733,734
In the post-partum period, the use of invabradine to control the heart rate may be considered in addition to beta-blockers, or if there is a contraindication for beta-blockers.43,339,735,736 In HF with a reversible cause, HF treatment in accordance with guidelines should be recom-mended for at least 12 months after full LV recovery, followed by grad-ual tapering ${}^{350}$ (see also Section 7). Women with pregnancy-associated HF should be counselled about the risks of recurrence in subsequent pregnancies.737
12.7. Special populations 12.7.1. Heart transplantation
Successful pregnancies have been reported in women with heart transplantation, but these pregnancies carry a higher risk. Before transplantation and before a post-transplantation pregnancy, wo men should be counselled about maternal and foetal risks, includ-ing the risks of rejection, infection, graft dysfunction, and potential teratogenicity of drugs. Based on the individual risk factors, it is recommended to postpone pregnancy until at least 1 year after transplantation.275 Women with heart transplantation are at higher risk of experiencing cardiometabolic complications during pregnancy such as pre-eclampsia, gestational diabetes, hyperten-sion, decreased kidney function, and infections. 741-745 The risk of complications is lower in women with normal graft function and no signs of rejection. Pre-pregnancy evaluation should include standard assessments and, if clinically indicated, coronary angiog-raphy, right-heart catheterization, and endomyocardial bi-opsy.741-745
All drugs should be reviewed before pregnancy 275 and mycopheno-lic acid therapy 275,741 should be avoided due to the teratogenic risk.In cases where the father has the same human leucocyte antigen(HLA)as the donated heart, there is a risk of developing donor-specific anti-bodies. ${}^{746,747}$ Therefore, consideration should be given to performing paternal HLA testing before conception.
During pregnancy, changes in maternal metabolism can affect the serum drug levels of immunosuppression therapy.748 Close monitoring of serum drug levels is recommended.275 Echocardiographic evalua-tions are recommended to assess graft function during pregnancy.Foetal growth should be regularly evaluated due to the risk of lower birth weight.745 Vaginal delivery should be considered in stable patients.745
Close monitoring of cardiac function, immunosuppression,and donor-specific antibodies is necessary until 6-12 months after delivery due to the risk of post-pregnancy rejection. 275,741,749-751 Lactation may be possible in patients on immunosuppressive drugs,depending on the type of medication(see Section 5.2.10).
Recommendation Table 21- Recommendations for heart transplantation and pregnancy
|Recommendations|Classa|Levelb| |---|---|---| |It is recommended to postpone pregnancy until at least 1 year after heart transplantation,taking individual risk factors into account. 275,741||C| |In women with a heart transplant,it is recommended that immunosuppression serum drug levels are monitored during pregnancy every 4 weeks until the 32nd week, then every 2 weeks until the 36th week, then weekly until delivery,and for 6-12 months after delivery to guide dosing. 275||C| |It is recommended to perform weekly monitoring of donor-specific antibodies for at least 6-12 months after delivery. 275,741,749-751||C| |Paternal HLA testing prior to conception should be considered due to the risk of developing donor-specific antibodies. 746,747|lla|C| |Mycophenolic acid therapy is not recommended in pregnancy and should be discontinued 6 weeks before conception. 275,741|III|C|
HLA,human leucocyte antigen anci and of recommendation.bLevel of evidence.
12.7.2. Cardio-onology
12.7.2.1 Gestational cancer
Gestational cancer is defined as cancer that occurs during pregnancy or within 12 months after delivery.The occurrence is~1 in 1000 pregnant-cies,with a possible rise in incidence as maternal childbearing age in-creases.The most frequent cancers affecting pregnant women are breast cancer, cervical and ovarian cancer, lymphoma, leukaemia, colo-rectal cancer, and melanoma.752-754 Women diagnosed with cancer during pregnancy should be evaluated and considered by a multidiscip-linary team.Both the effect of pregnancy on the cancer and the effect of the cancer on the pregnancy should be evaluated. Patients should be followed in centres with neonatal units in case of premature delivery.
The baseline assessment prior to chemotherapy, and the monthly or bimonthly follow-up during chemotherapy, should include clinical history,physical examination,ECG,cardiac biomarkers, and TTE in the context of physiological haemodynamic changes during pregnancy.TNP serial measurements,756 and high-sensitivity cTn can be used for mon-itoring of cancer-therapy-related cardiac dysfunction(CTRCD).734,756
Chemotherapy given during the first trimester is associated with a high risk of malformation(up to 20%) and miscarriage. Chemotherapy is often avoided after 34 weeks of gestation to provide a≥3 week window be-tween the last chemotherapy and delivery. Cytotoxic chemotherapies provide different risk profiles during the second and third trimesters.752,754 The suggested chemotherapy treatments for pregnant women with can-cer are summarized in the 2022 ESC Guidelines on cardio-oncology. 757
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12.7.2.2 Pregnancy in cancer survivors
Improved cancer treatments have led to an increased number of wo-men with pregnancies after oncological therapy. Previous treatment with anthracycline chemotherapy or chest radiotherapy implies a 15-fold increased lifetime risk of developing HF. Furthermore, both the cancer and the cancer treatment have an impact on fertility, preg-nancy outcomes, and cardiovascular health. The major risk factors for cardiovascular events during pregnancy in cancer survivors include CTRCD(28%; 47.4 times higher odds), younger age at cancer diagno-sis,758,759 higher cumulative doses of anthracycline, and greater dur-ation between cancer treatment and first pregnancy.758,759
Recommendation Table 22- Recommendations for cardio-oncology and pregnancy
|Recommendations|Classa|Levelb| |---|---|---| |It is recommended that pregnant women with cancer||| |who require cardiotoxic cancer therapy are jointly||| |managed by the Pregnancy Heart Team and the||| |cardio-oncology team.||| |Cardiac troponin and NP measurements may be||| |considered at baseline and during anthracycline||| |chemotherapy in pregnant women with||| |cancer. 734,756|||
NP,natriuretic peptide.
aClass of recommendation.
bLevel of evidence.
13. Adverse pregnancy outcomes and long-term management
Adverse pregnancy outcomes(APO), including gestational hyperten-sive disorders, pre-eclampsia, gestational diabetes mellitus(GDM),small or large for gestational age babies, or pre-term birth are a group of interrelated disorders that share common pathways. ${}^{760}$ Placental dysfunction and oxidative stress in the context of cardiometabolic, gen-etic, or environmental risk factors may cause APOs. ${}^{761}$ A Multidisciplin-ary care approach is essential(Figure 23) ${}^{761,762}$ for optimizing modifiable cardiovascular risk factors after all APOs. ${}^{761,762}$
13.1. Adverse pregnancy outcomes
13.1. Post-partum hypertensive disorders
Hypertension in the post-partum period is most common in women with antental hypertensive disorders, but it can also develop de novo in the post-partum period. New-onset or de novo post-partum pre-eclampsia is increasingly recognized as an important contributor to ma-ternal morbidity and mortality in the post-partum period(Figure 24). ${}^{763}$
Women with pregnancy-related hypertensive disorders, most not-ably pre-eclampsia, have a higher incidence of several CVDs, including CAD,stroke, and HF.762,764 Treatment for uncomplicated post-partum hypertension(first 6 weeks after delivery) includes nifedine fide and labe-talol(metoprolol if labelatis is unavailable). ${}^{764}$ A small randomized con-trolled trial showed that administration of furosemide in the first 5 days post-partum in women with gestational hypertension and pre-eclampsia significantly reduced the prevalence of persistently elevated
BP at 7 days.765 Methyldopa should be avoided because of the risk of post-partum depression.602,766 Agents used for the management of acute, severe hypertension in the post-partum period are similar to those used during pregnancy and include labelatol, hydralazine, and ni-fedpine(see Sections 5 and 12).767 For women with persistent hyper-tension, antihypertensive therapy should be initiated with reference to lactating status following current guidelines(see Section 5).584,585,767
13.1.2. Gestational diabetes mellitus
Gestational diabetes mellitus is characterized by glucose intolerance that is first recognized during pregnancy. ${}^{768}$ Haemoglobin A1c testing may help to identify women at high risk. ${}^{768, 769}$ Women with GDM have a sharply increased risk of developing type 2 diabetes later in life and a significantly higher likelihood of experiencing adverse cardiovas-cular events. ${}^{770-772}$ Women with GDM are recommended to undergo a formal oral glucose tolerance test(oGTT) 6-12 weeks post-partum with a repeat assessment at 6-12 months(Figure 25). Thereafter, regu-lar annual follow-up with glucose tolerance monitoring is recom-mended. ${}^{773-775}$
13.1.3. Pre-term birth
Pre-term delivery occurs after 20 and before the completion of 37 weeks of gestation, regardless of birth weight. There are strong associa-tions between pre-term delivery(alone or with pregnancy-related hypertensive disorders), CVD,and mortality.771,772 Women with pre-term deliveries are more likely to have an increasing BP trajectory after pregnancy and to be affected by accelerated atherosclerosis independ-ent of traditional CVD risk factors.776,777 The earlier pre-term delivery occurs, the more strongly it is associated with hypertension and CVD in later life. The relationship of pre-term birth to type 2 diabetes mellitus and dyslipidaemia is inconsistent.
13.1.4. Small for gestational age
Delivering a SGA baby(weight<10th percentile) has not been consist-ently related to an increased CVD risk, but has been associated with hypertension and diabetes.761,771,772 Conversely, large for gestational age babies(weight>90th percentile) have been reported to increase maternal CVD risk, but the evidence is limited.761
13.1.5. Pregnancy loss and placental abruption
Placental abruption, spontaneous pregnancy loss or stillbirth, and foetal loss after 28 weeks of gestation have been associated with an increased risk of future CVD, with a particularly high risk of hypertension and type 2 diabetes mellitus.771,778 One or more terminations are associated with a higher CVD risk, however, with limited evidence.779
13.2. Breastfeeding fosters the recording
Breastfeeding fostering the recovery of maternal physiological systems to their pre-conception state. Breastfeeding women have a better cardiometabolic profile, and breastfeeding up to 12 months after childbirth has been shown to lower future risk of CVD and mortality,780-783 potentially due to lowered BP.784-787 Longer breastfeeding periods are associated with better CVD out-comes.782,784,788-790 The role of breastfeeding for women who experienced an APO is less clear, but it also appears to have beneficial effects.789,791,792 There is inconclusive evidence about the beneficial effects of breastfeeding on the cardiovascular health of older women(i.e. aged≥55 years).720,788,793,794
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 Figure 23 Multidisciplinary approach of adverse pregnancy outcomes. CAD, coronary artery disease; CVD, cardiovascular disease. ${}^{a}$ See Section 13.3 on Women's Heart Clinics.
13.3. Women's Heart Clinics
Post-partum care is often segmented and only carried out by obste-tricians. A longer duration of post-partum care, including cardiovas-cular risk assessment and counselling on CVD risk prevention,is likely to lower the long-term risk of CVD in women with an APO(Figure 25). ${}^{762,795}$ Pregnancy Heart Teams and the potential
establishment of Women's Heart Clinics focusing on women of all ages with CVD are necessary to span the care up to post-partum.Seamless communication between the various healthcare providers(e.g. obstetrician, cardologist, internist, family physician) and multi-disciplinary management of APOs is critical for long-term care and the woman's future health. ${}^{761,796,797}$
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Recommendation Table 23-Recommendations for long-term effects of adverse pregnancy outcomes(see Evidence Tables 20 and 21)
|Recommendations|Classa|Levelb| |---|---|---| |Its recommended to undertake a cardiovascular risk assessment in women with APOs, to recognize and document APOs when CVD risk is evaluated in women, and to provide counselling on the importance of healthy lifestyle choices that optimize cardiovascular health. 771,772|1|B| |In women with persistent post-partum hypertension beyond 6 weeks to 3 months post-partum, initiation of antihypertensive therapy with reference to lactating status is recommended following current guidelines. 584,602,798|1|B| |In cases where adoption of healthy lifestyle choices alone is inadequate to control post-partum glucose levels, initiation of pharmacotherapy following current guidelines. 773,774,799|1|C| |following current guidelines is recommended. 773,774,799|1|C| |It is recommended that women with a history of GDM undergo a formal oGTT 6-12 weeks post-partum with a repeat assessment at 6-12 months and regular annual follow-up visits to screen for diabetes. 773,774,800|1|C| |Nifedipine and labelatol (metoprolifol if labelatol is unavailable) are recommended as treatments for uncomplicated post-partum|1|C| |hypertension in the first 6 weeks after delivery. 602,766,767||| |In women with a history of any APO, cardiovascular risk assessment should be considered at 3 months post-partum with repeat assessment at 6-12 months after implementation of appropriate lifestyle interventions, and regular long-term follow-up thereafter. 761,795|1|C| |Breastfeeding may be considered in order to lower the future cardiovascular risk in women with APOs.|789,791,792|llb|
APO, adverse pregnancy outcomes; CVD, cardiovascular disease; GDM, gestational diabetes mellitus; oGTT, oral glucose tolerance test.
14. Key messages
● A Pregnancy Heart Team should be involved in the risk assess-ment, counselling and management of women in mWHO 2.0 class≥II-III from pre-conception to the late post-partum.Each woman should have a detailed delivery plan agreed in advance.
● ln women with known CVD, a complete clinical re-evaluation should take place pre-pregnancy to estimate risk, optimize treat-ment, consider and evaluate the removal of contraindicated drugs,and reduce the probability of complications.
● Women and their partner (if any) should be offered structured psychosocial support during the entire trajectory, especially for those at high risk and those considering pregnancy termination.
● Women with known heritable cardiovascular disorders should be counselled about the transmission risk, including the option for as-sisted reproductive technology.
● Management of women with CVD who are pregnant or wishing to become pregnant should be individualized and performed ac-cording to a shared decision-making model, respecting the woman's autonomy.
● Women in mWHO 2.0 class IV should be comprehensively counselled about the very high pregnancy risk, being careful to promote a detailed and transparent dialogue about the heightened maternal and foetal risks associated with pregnancy.A shared decision-making process is essential, allowing for in-formed choices, including the consideration of pregnancy ter-mination if necessary.
● Vaginal delivery is the first choice for the majority of women with CVD.
● In a life-threatening situation, treatments such as defibrillation, in-terventions, acute coronary revascularization, mechanical circula-tory support, and medication should be the same as in non-pregnant women, irrespective of contraindications.
● The use of non-invasive imaging tests with ionizing radiation during pregnancy should only be performed when the benefits clearly out-weigh the maternal and foetal risk, and if the result will significantly modify the medical management.
● In women with LQTS and CPVT, the continuation of beta-blockers throughout pregnancy with monitoring of foetal growth is recom-mended(atenolol is the only contraindicated beta-blocker).Beta-blockers of choice are propranolol and nadolol.
● In women with LQT2, post-partum is a distinct high-risk period,and therefore full dosage of beta-blockers is strongly recommended.
● Genetic testing should be considered in PPCM.
● In women with PPCM and DCM, subsequent pregnancy is not re-commended if LV function does not normalize.
● Genetic testing in women with aortic disease wishing to conceive is recommended and management should be based on the presence and type of P/LP variant.
● Women with the following ACHD lesions should be provided with expert counselling and education by a Pregnancy Heart Team, with clear and thorough discussion of the very high pregnancy risk and the need for a shared decision-making process:
o Systemic RV, in NYHA class III-IV, ventricular dysfunction(EF<40%), more than moderate TR, or treated HF;
o A Fontan circulation and oxygen saturation<85%, reduced ven-tricular function, severe arrhythmias, or in NYHA class III-IV.
● There is no safe cut-off value for elevated pulmonary artery pres-sure in pregnancy.
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● Women of childbearing potential with PAH should be counselled at the time of diagnosis about the risks and uncertainties associated with becoming pregnant.
•Any suspicion of VTE,including DVT and PE, requires an immediate formal assessment with validated diagnostic tests by a multidisclin-ary specialized team.
● LMWH is the agent of choice for prophylaxis and treatment of VTE in pregnancy.
● When treating women with HF during pregnancy, it should be noted that several drugs[ACE-ls, ARBs, direct reinin inhibitors, sa-cubitril-valsartan(ARNls), MRAs,and SGLT2 inhibitors] are not re-commended. When inotropes or more advanced treatment is necessary, referral to an expert centre is recommended.
● When possible, mechanical valves should be avoided in girls and wo-men of childbearing age.
● Methyldopa, labelatol, and CCBs are recommended for the treat-ment of hypertension in pregnancy.
● Women at high or moderate risk of pre-eclampsia should be ad-vised to additionally take 75-100 mg of ASA daily from weeks 12 to 36/37.
● After cardiac transplantation, it is recommended to postpone preg-nancy for at least 1 year, taking individual risk factors into account.
● Women with APOs should be informed about long-term risks and preventive strategies and offered appropriate follow-up, including psychosocial support(if necessary).
15. Gaps in evidence
Pre-pregnancy counselling and evaluation
● Data on the adverse effects of assisted reproductive treatment in women with CVD are lacking.
Diagnostic methods
● There is a lack of data on the safety of echocardiographic contrast agents during pregnancy or lactation.
● There are controversial data on the use of gadolinium-based con-trast agents in pregnancy.
● There are no clear cut-offs for NT-proBNP levels during pregnancy.
● There are no normative values of cTnl and cTnT in pregnancy and the post-partum period.
● There is a lack of data on normal lung ultrasound pattern during pregnancy.
Drugs during pregnancy and lactation
● Safety data of DOACs and antidotes(idarucizumab, andexanet alfa,cirapantag) in pregnancy are lacking.
● Safety data of newer anti-arrhythmic drugs and rate-controlling drugs(vernakalant, ivabradine, landiolol) in pregnancy are lacking.
Cardiomyopathy and primary arrhythmia syndromes
● The available data on gene-specific management during pregnancy in different cardiomyopathies and primary arrhythmia syndromes are limited.
Peripartum cardiomyopathy
● The potential for recovery of cardiac function in PPCM remains un-clear and the risks in subsequent pregnancies are not well defined.
Aortopathies
● More data are needed to correctly estimate the pregnancy risk in women with previous aortic dissection and/or aortic root surgery.
● Risk factors for aortic dissection in the post-partum period are poorly understood, making counselling about this difficult.
● It is unclear whether a distinction between root and ascending phenotype in women with BAV should lead to a different threshold for prophylactic surgery(as in non-pregnant women).
Congenital heart disease
● More data are needed to estimate the risk and the long-term effects of pregnancy(including multiple pregnancies), especially in women with a Fontan circulation or univentricular hearts.
● Risk factors for the development of heart failure and arrhythmias in pregnant women with(systemic) right-heart failure are poorly understood.
Pulmonary hypertension
● Defining the optimal timing to start or escalate PAH therapies in pregnancy complicated with PAH remains challenging.
Venous thromboembolism
● Data on risk stratification of VTE in pregnancy are limited, specific-ally in those with other pre-existing comorbidities.
● Data on the use of anticoagulant agents(other than LMWH) are limited, just as data on the efficacy and safety of inferior vena cava filters and catheter-based thrombectomy(in PE).
Acquired heart disease
● The foetal risks associated with the newer HF medications remain unclear, particularly regarding exposure during different trimesters.
● The optimal tools to stratify risk of recurrence for atherosclerotic and SCAD ACS are unknown.
● Physiopathological mechanisms of SCAD in pregnancy are unknown.
● Optimal treatment of SCAD during pregnancy is not well established.
● There is scarce evidence about the necessity of using statins during pregnancy in women with cardiovascular risk or established ASCVD.
● Optimal anticoagulation strategies for women with MHVs during pregnancy remain uncertain.
● The role of anti-factor Xa level monitoring needs to be determined.
Women's Heart Clinics
● Optimal strategies for surveillance and follow-up of women with APOs are unclear.
● It is unclear how social determinants of health(the environmental factors that affect how people live, learn, and work) affect APOs.
● There is a need for studies exploring models of post-natal care,starting from the initial antenatal visit through to the end of the post-partum period.
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● Further research is needed to identify risk factors for pregnancy-related depression and poor health behaviour engage-ment in women with CVD,enabling the development of tailored in-terventions to improve their health and quality of life.
16.‘What to do’ and‘what not to do’ messages from the Guidelines
Table 16 lists all Class I and Class III recommendations from the text alongside their level of evidence.
17. Evidence tables
Evidence tables are available at European Heart Journal online.
18. Data availability statement
No new data were generated or analysed in support of this research.
Table 16 'What to do' and‘what not to do'
|Recommendations|Classa|Levelb| |---|---|---| |4. The Pregnancy Heart Team||| |Counselling, pregnancy risk assessment, contraception, assisted reproductive technology, and the involvement of a Pregnancy Heart Team||| |It is recommended to perform a risk assessment in all women with CVD of childbearing age using the mWHO 2.0 classification.|1|C| |A discussion by the Pregnancy Heart Team about the high risk of maternal mortality or morbidity and the related high foetal risk is recommended for women with mWHO 2.0 class IV conditions, including a shared decision-making process for pregnancy termination, involving psychological support.|1|C| |It is recommended that women with CVD of mWHO 2.0 class II-III and above are evaluated and managed by a Pregnancy Heart Team from pre-pregnancy onwards through pregnancy and post-partum.|1|C| |It is recommended that women with CVD of mWHO 2.0 class II and above, or those at risk of developing CVD, receive individualized advice to determine the most suitable contraception method, including emergency contraception.|1|C| |Assessment by a clinical geneticist prior to pregnancy is recommended in women fulfilling diagnostic criteria for inherited cardiovascular disease to guide risk stratification and pre-natal genetic testing.|1|C| |Pre-conception genetic counselling is recommended in couples with heritable CVD, whether genetic testing is being considered or not. It is recommended that this counselling is provided by an appropriately trained healthcare professional within a multidisciplinary team that offers psychological support and education to encourage decision-making.|1|C| |It is recommended that single embryo transfer is performed in women with CVD.|1|C| |It is recommended to offer women with CVD access to termination of pregnancy that is tailored to their cardiac condition to minimize the risks of the procedure.|1|C| |Diagnostic methods in pregnancy||| |Tranthoracic echocardiography is recommended as first-line imaging tool in any pregnant woman with unexplained or new cardiovascular signs or symptoms.|1|C| |It is recommended to limit exposure to all medical ionizing radiation doses to ALARA levels.|1|C| |It is recommended to keep the radiation dose to the foetus as low as possible(preferably<50 mGy), particularly if the foetus is in the field of view.|1|C| |Timing and mode of delivery||| |Vaginal delivery is recommended in most women with CVD.|1|B| |Routine induction of labour prior to 39 weeks is not recommended in women with stable CVD.|III|C| |It is recommended that the timing of delivery is planned to ensure safe and effective peripartum anticoagulation.|1|C| |It is recommended to discontinue VKAs and start therapeutic-dose LMWH or adjusted-dose i.v. UFH at the 36th week of gestation or 2 weeks before the planned delivery.|1|C| |In women at low risk on therapeutic-dose LMWH, neuraxial anaesthesia and vaginal delivery(or caesarean section for obstetric indications)|1|C| |is recommended 24 h after the last dose of LMWH.|1|C| |In women at high risk, it is recommended to convert LMWH to i.v. UFH at least 36 h prior to delivery and stop the UFH infusion 4-6 h prior to anticipated delivery. The aPTT should be normal before regional anaesthesia.|1|C| |If delivery starts while the mother is on VKAs or<2 weeks after discontinuation of VKAs, caesarean section is recommended for foetal protection.|1|C| |Post-delivery, it is recommended that the decision to restart LMWH or UFH is made after discussion with the Pregnancy Heart Team and the woman who gave birth.|1|C|
Continued
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|It is recommended to postpone the switch from heparin back to oral anticoagulants until 7-14 days post-partum when the wound area has healed, in consultation with the Pregnancy Heart Team.|||| |---|---|---|---| |5. Drugs during pregnancy and lactation|||| |Direct oral anticoagulants and pregnancy|||| |DOACs are not recommended during pregnancy.|Ⅲ C|Ⅲ C|| |6. Pregnancy in women with cardiomyopathies and primary arrhythmia syndromes|||| |Cardiomyopathies and pregnancy|||| |Clinical cardiac surveillance (ECG, echocardiogram, and Holter ECG monitoring) is recommended during pregnancy in women with|1 C|1 C|| |CMPs, depending on individual risk.|1|C|| |Vaginal delivery is recommended in most women with CMPs, unless there are obstetric indications for caesarean section, severe HF (EF <30% and/or NYHA class III/IV), uncontrolled arrhythmias, or severe outflow obstruction (≥50 mmHg) in women with HCM, or in women presenting in labour on VKAs.|1|C|| |In women with DCM and worsening of EF during pregnancy, counselling on the risk of recurrence during a subsequent pregnancy is recommended in all cases, even after recovery of LV function.|1|C|| |It is recommended to use the same risk stratification protocol for ventricular arrhythmias in pregnant women with HCM as for non-pregnant women with HCM.|1|C|| |It is recommended to start beta-blockers in women with HCM who develop symptoms due to outflow tract obstruction or arrhythmia during pregnancy.|1|C|| |It is recommended that women with HCM with symptomatic LV dysfunction (EF <50%) and or severe LVOTO (≥50 mmHg) wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.|1|C|| |Myosin inhibitors are not recommended in women during pregnancy due to lack of safety data.|Ⅲ|C|| |Primary arrhythmia syndromes and pregnancy|||| |Monitoring and treatment of hypokalaemia and hypomagnesiaemia is recommended in pregnant women with primary arrhythmia syndromes suffering from hyperemesis.|||| |Beta-blockers, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy in women with LQTS.|||| |It is recommended to continue beta-blocker therapy during lactation in women with LQTS to reduce arrhythmic risk.|||| |Pre-pregnancy dose beta-blocker of nadolol or propranolol are recommended in women with LQT2, particularly in the post-partum period, which represents a high-risk period for life-threatening arrhythmias.|||| |Beta-blockers, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy and lactation in women with CPVT.|1|C|| |Flecanide,in addition to beta-blockers, is recommended in women with CPVT who experience cardiac events such as syncope, VT, or cardiac arrest, during pregnancy.|||| |It is recommended that women with CPVT who are stable on beta-blockers (nadolol or propranolol as drugs of choice) and flecanide before pregnancy, continue both drugs also during pregnancy and post-partum.|1|C|| |7. Peripartum cardiomyopathy|||| |Counselling for women with PPCM about the risk of recurrence during a subsequent pregnancy and about contraception is recommended in all cases, even after recovery of LV function (LVEF >50%).|||| |8. Pregnancy in women with aortopathies|||| |It is recommended that women with aortic disease have counselling about the risk of aortic dissection in pregnancy and the post-partum period.|||| |It is recommended that women with aortic disease have counselling about the risk of aortic dissection in pregnancy and the post-partum extended Pregnancy Heart Team considering the presence and type of genetic variant, aortic morphology, growth rate, and aetiology of aortic dissection.|||| |Aortic dissection.|Aortic dissection.|Aortic dissection.|Aortic dissection.| |It is recommended that women with vascular Ehlers-Danlos syndrome wishing to become pregnant are counselled regarding the very high risk of pregnancy-related adverse events by a multidisciplinary team, considering family history, genetic variant, and previous vascular events.|||| |Imaging of the entire aorta (CT or CMR) is recommended before pregnancy in women with known or suspected aortic disease.|||| |In women with aortic dilatation related to BAV, imaging (with TTE, and CMR/CT if needed) of the aortic root, ascending aorta, and descending aorta (to rule out coarction) is recommended before pregnancy.|||| |In women with low-risk aortic disease (mWHO 2.0 classes II and II-III), one-time echocardiographic imaging between 20 and 30 weeks of gestation and imaging at 6 months post-partum is recommended.||||
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|In women with moderate to high-risk aortic disease (mWHO 2.0 classes III and IV), repeated echocardiographic imaging every 4-12 weeks (depending on diagnosis and severity of dilatation) is recommended during pregnancy and until 6 months post-partum.|I|C| |---|---|---| |CMR (without gadolinium) imaging of the entire aorta is recommended in pregnant women at risk of or with known aortic dilatation who have not had recent pre-pregnancy cross-sectional imaging.|I|C| |It is recommended that centres managing pregnancies in women with moderate to high-risk aortic disease (mWHO 2.0 class III/IV) can provide cardiovascular surgery in case of peripartum adverse events.|I|C| |When a women with known aortic dilatation, history of dissection, or P/LP variant associated with aortic disease becomes pregnant, strict and individualized BP control is recommended.|I|C| |Beta-blocker therapy throughout pregnancy and in the post-partum period is recommended in women with MFS and other HTADs.Celiprolol is recommended in women with vascular Ehlers-Danlos syndrome during pregnancy and lactation.|I|C| |It is recommended that indications for pre-pregnancy aortic root and/or ascending aortic surgery are guided by aortic morphology, underlying pathology,family history,genetic variant,previous vascular events,and patient's preference.|I|C| |In women with MFS and aortic root diameters>45 mm,surgery before pregnancy is recommended.|I|C| |In women with LDS with P/LP variants in TGFBR1,TGFBR2,and aortic root diameters≥45 mm,surgery before pregnancy is recommended.|I|C| |In women with nhsHTAD with P/LP variants in MYH11, ACTA2, PRKG1, or MYLK, and aortic root diameters≥45 mm, surgery before pregnancy is recommended.|I|C| |In women without an identifiable P/LP variant with aortic root or ascending aortic diameters≥50 mm, surgery before pregnancy is recommended.|I|C| |In women with a aorta<40 mm, vaginal delivery is recommended.|I|C| |In women with vascular Ehlers-Danlos syndrome, caesarean section at 37 weeks is recommended for obstetrical reasons.|I|C| |The use of ergometrine post-delivery is not recommended in women with aortopathy.|III|C| |9. Pregnancy in women with known congenital heart disease||| |Vaginal delivery is recommended in most women with ACHD.|I|B| |It is recommended that all women with Fontan circulation who wish to become pregnant receive counselling from the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.|I|C| |It is recommended that women with a systemic RV (Mustard/Senning or congenitally corrected TGA), in NYHA class III/IV, systemic ventricular dysfunction(EF<40%), or severe TR wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.|I|C| |10. Pregnancy in women with pulmonary arterial hypertension|||
10. Pregnancy in women with pulmonary arterial hypertension
It is recommended that women of childbearing potential with PAH wishing to become pregnant are counselled by a multidisciplinary team regarding the very high risk of pregnancy-related adverse events, encouraging a shared decision-making process about whether to become pregnant.
It is recommended to provide clear contraceptive advice to women of childbearing potential with PAH.
I C
For women with PAH requiring pregnancy termination, it is recommended to perform this in PH centres.
C
Endothelin receptor antagonists, riocgiup, and selexipag are not recommended during pregnancy.
Ⅲ
11. Venous thromboembolism in pregnancy and post-partum
For pregnant or post-partum women at high risk of VTE, a prophylactic fixed dose of LMWH is recommended over a higher weight-adjusted dose to reduce the risk of VTE.
1 B
In pregnant women or women in the post-partum period with suspicion of VTE(DVT and/or PE), an immediate formal diagnostic assessment with validated methods is recommended and should not be postponed.
B
In pregnant women or women in the post-partum period with newly diagnosed VTE(DVT and/or PE), the involvement of the Pregnancy Heart Team, including a vascular specialist and a haematologist, is recommended.
C
In pregnant or post-partum women with a diagnosis of VTE without haemodynamic instability, anticoagulation is recommended by using
I C
12. Pregnancy in women with acquired heart disease
Coronary artery disease and pregnancy
In pregnant women with chest pain, it is recommended to exclude life-threatening cardiovascular conditions, including PE, ACS(including SCAD), and acute aortic syndrome.
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It is recommended to manage pregnant women with ACS in the same way as non-pregnant women, including diagnostic investigations and interventions.
Low-dose ASA is recommended as the antiplatelet treatment of choice during pregnancy and lactation when single antiplatelet treatment is indicated.
If DAPT is required, clopidogrel is recommended as the P2Y12 inhibitor of choice during pregnancy.
I $\boxed{1}$ C
The duration of DAPT(aspirin and clopidogrel) in pregnant women undergoing coronary stent implantation is recommended to be the same as in non-pregnant women, with an individual approach considering ischaemic risk and delivery-related bleeding risks.
$\boxed{1}$
Hypertensive disorders and pregnancy
It is recommended to aim for systolic BP <140 mmHg and diastolic BP <90 mmHg in pregnant women.
1
Systolic BP≥160 mmHg or diastolic BP≥110 mmHg in a pregnant woman is an emergency, and treatment in a hospital setting is recommended.
1
Low-dose aspirin(75-150 mg daily) is recommended in women at moderate or high risk of pre-eclampsia(i.e. at least one high risk factor or two moderate risk factors for pre-eclampsia) from weeks 12 to 36/37.
1 A
In women with gestational hypertension, initiation of drug treatment is recommended at systolic BP≥140 mmHg or diastolic BP≥90 mmHg.
1
Methyldopa is recommended for the treatment of hypertension in pregnancy.
$\boxed{1}$
Labetalol, metoprolol, and dihydropyridine calcium channel blockers are recommended for the treatment of hypertension in pregnancy.
C
In severe hypertension, drug treatment with i.v. labelatol, urapilid, nicardipine, or oral short-acting nifedipine or methyldopa is recommended for acute reduction in blood pressure. Intravenous hydralazine is a second-line option.
$\boxed{1}$ C
In pre-eclampsia associated with pulmonary oedema,nitroglycerine given as an i.v. infusion is recommended.
1 C
In women with pre-eclampsia without severe features, delivery is recommended at 37 weeks.
1
It is recommended to expedite delivery in women with pre-eclampsia associated with adverse markers such as haemostatic disorders.
C
In women with gestational hypertension, delivery is recommended at 39 weeks.
1
Supraventricular tachycardia and pregnancy
Immediate electrical cardioversion is recommended for acute treatment of SVT with haemodynamic instability.
I
Vagal manoeuvres and i.v. adenosine are recommended for conversion of haemodynamically stable supervarventicular tachycardias.
1
Intravenous beta-blockers (metoprool) are recommended as the first-line option for acute rate control in pregnant women with AF or AF with preserved LVEF and rapid ventricular rate.
1 C
Therapeutic anticoagulation with LMWH is recommended for pregnant women with persistent or permanent AF at elevated thromboembolic risk.
1 C
Beta-1-selective blockers are recommended for rate control in pregnant women with AF,AFL,or FAT.
1 C
Beta-1-selective blockers or verapamil are recommended for the prevention of SVT in women without pre-excitation on resting ECG.
C
Flecanide or propafenone are recommended for the prevention of arrhythmias in pregnant women with WPWP syndrome.
C
Ventricular tachycardia, device implantation, catheter ablation, and pregnancy
Immediate electrical cardioversion is recommended for both unstable and stable ventricular tachycardias.
I
Beta-blockers or verapamil are recommended for the prevention of idiopathic sustained VT.
$\boxed{1}$ C
If an ICD, pacemaker, or resynchronization therapy device is indicated during pregnancy, implantation is recommended with optimal radiation protection.
1 C
Cardiac arrest and pregnancy
Continuous manual left uterine displacement during CPR in pregnant women(≥20 weeks) with cardiac arrest is recommended to relieve aortocaval compression.
C
It is recommended to establish i.v. access above the diaphragm to ensure that the i.v. therapy is not obstructed by the gravid uterus.
C
It is recommended to perform the same chest compressions and defibrillation protocols in pregnant as in non-pregnant women.
Anterolateral defibrillator pad placement is recommended with the lateral pad placed under the breast.
It is recommended that no drugs are withheld in pregnant women with cardiac arrest due to concerns of teratogenicity.
Congenital atrioventricular block and pregnancy
In pregnant women with asymptomatic congenital AV block, normal cardiac anatomy and function, a narrow QRS complex, and ventricular rate(≥50 b.p.m.), a prophylactic temporary pacemaker during delivery is not recommended.
C
Native valve disease and pregnancy
Intervention is recommended before pregnancy in symptomatic patients with severe aortic stenosis.
Intervention is recommended before pregnancy in women with mitral stenosis and a valve area<1.5 cm2.
C
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|In pregnant women with symptomatic tstenosis or pulmonary hypertension, restricted activities and beta-blockers are recommended.|1|C| |---|---|---| |In pregnant women with mitral stenosis, diuretics are recommended when congestive symptoms persist despite beta-blockers.|I|C| |Full therapeutic-dose anticoagulation is recommended in women with mitral stenosis complicated by AF, left atrial thrombus, or prior embolism.|I|C| |Surgical treatment is recommended before pregnancy in women with severe aortic or mitral regurgitation with symptoms, impaired ventricular function, or marked ventricular dilatation.|I|C| |Diuretics are recommended in pregnant women with regurgitant lesions when symptoms or signs of congestion occur.|I|C|
Prosthetic valves and pregnancy
A bioprosthetic valve is recommended(over a mechanical valve) in young women contemplating pregnancy requiring a valve prosthesis.
It is recommended that the type of valve surgery or intervention for a woman contemplating pregnancy is chosen in consultation with the Pregnancy Heart Team.
It is recommended that a care plan documenting the agreed anticoagulant strategy(including the decision to continue VKAs or converting to therapeutic-dose LMWH in the first trimester) is in place for women of childbearing age with an MHV prior to pregnancy or as soon as pregnancy is recognized.
It is recommended that pregnant women with an MHV are managed by the Pregnancy Heart Team.
In pregnant women on VKAs, it is recommended to perform INR monitoring weekly or at a minimum every 2 weeks.In pregnant women with MHVs on therapeutic-dose LMWH, it is recommended to check peak anti-factor Xa levels and to target levels according to individualized risk.
LMWH is not recommended when anti-factor Xa level monitoring is not available.
Chronic and acute heart failure and pregnancy
It is recommended that women with HFErF are advised about the risk of deterioration of cardiac function during pregnancy in pregnant women with HFFrF, it is recommended that non-selective beta-blockers are switched to beta-1-selective blockers(metoprolol,bisoprolol) with close maternal and foetal monitoring.
Anticoagulation with therapeutic doses of LMWH is recommended in pregnant women with intracardiac thrombus or decreased LV function with EF<35%.
It is recommended to optimize HF guideline-directed medical therapy after delivery, taking contraindicated drugs during lactation into account.
Urgent delivery with caesarean section is recommended in pregnant women with cardiogenic shock as soon as the foetus is viable, taking gestational age, comorbidities, and the available level of medical care into account.
Inotropes and/or vasopressors are recommended in pregnant women with cardiogenic shock with levosimendan, dobutamine, and milrinone as recommended agents.
ACE-Is,ARBs,ARNs,MRAs,ivadramine,and SGLT2 inhibitors are not recommended during pregnancy due to adverse foetal effects.
Heart transplantation and pregnancy
It is recommended to postpone pregnancy until at least 1 year after heart transplantation, taking individual risk factors into account.In women with a heart transplant, it is recommended that immunosuppression serum drug levels are monitored during pregnancy every 4 weeks until the 32nd week, then every 2 weeks until the 36th week, then weekly until delivery, and for 6-12 months after delivery to guide dosing.
It is recommended to perform weekly monitoring of donor-specific antibodies for at least 6-12 months after delivery.
Mycophenolic acid therapy is not recommended in pregnancy and should be discontinued 6 weeks before conception.
Cardio-oncology and pregnancy
It is recommended that pregnant women with cancer who require cardiotoxic cancer therapy are jointly managed by the Pregnancy Heart Team and the cardio-oncology team.
13. Long-term effects of adverse pregnancy outcomes
It is recommended to undertake a cardiovascular risk assessment in women with APOs, to recognize and document APOs when CVD risk is evaluated in women, and to provide counselling on the importance of healthy lifestyle choices that optimize cardiovascular health.
In women with persistent post-partum hypertension beyond 6 weeks to 3 months post-partum, initiation of antihypertensive therapy with reference to lactating status is recommended following current guidelines.
In cases where adoption of healthy lifestyle choices alone is inadequate to control post-partum glucose levels, initiation of pharmacotherapy following current guidelines is recommended.
It is recommended that women with a history of GDM undergo a formal oGTT 6-12 weeks post-partum with a repeat assessment at 6-12 months and regular annual follow-up visits to screen for diabetes.
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Nifedipine and labelatol(metoprolifol if labelatol is unavailable) are recommended as treatments for uncomplicated post-partum hypertension in the first 6 weeks after delivery.
ACE-I,angiotensin-converting enzyme inhibitor; ACHD; congenital heart disease; ACS, acute coronary syndrome: AF, atrial fibrillation; AFL, atrial flutter; ALARA, as low as reasonably achievable; aPPT,activated partial thromboplastin time;APO, adverse pregnancy outcome;ARB, angiotensin receptor blocker; ARNl, angiotensin receptor/neprlysin inhibitor;ASA,acetylsallicic acid; AV, atrioventricular; BAV, bicuspid aortic valve; BP, blood pressure; CMP: cardiomyopathy; CMR, cardiovascular magnetic resonance; CPR, cardiopulmonary resuscitation; CPVT, catecholaminergic polymorphic ventricular tachycardia; CT, computed tomography; CVD, cardiovascular disease; DAPT, dual antiplatelet therapy; DCM, dilated cardiomyopathy; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; ECG, electrocardiogram;EF, ejection fraction; FAT, focal atrial tachycardia; GDM, gestational diabetes mellitus; HCM, hypertrophic cardiomyopathy; HF, heart failure; HFrF, heart failure with reduced ejection fraction; HTAD, heritable thoracic aortic disease; ICD, implantable cardiover deffibrator; IR, international normalized ratio; iv., intravenous; LDS, Loeys-Dietz syndrome; LMWH, low-molecular-weight heparin; LQT2, long QT syndrome type 2;LQTS, long QT syndrome; LV, left ventricle; LVEF, left ventricle ejection fraction; LVOTO, left ventricular outflow tract obstruction; MFS, Marfan syndrome; MHV, mechanical heart valve; MRA, mineralocorticocretor agonist; m'WHO, modified World Health; Organization; nsHTAD, non-dynromic heritable thoracic aortic disease; NYHA, New York Heart Association; oGTT, oral glucose tolerance test; PAH, pulmonary arterial hypertension; PE, pulmonary embolism; PH, pulmonary hypertension; P/LP, pathogenic/likely pathogenic; PPCM,peripartum cardiomyopathy; RV, right ventricle; SCAD, spontaneous coronary artery dissection; SGLT2, sodium-glucose co-transporter-2; SVT, supraventricular tachycardia; TGA,transposition of the great arteries; TR, tricuspid regurgitation; TTE, transthoracic echocardiogram; UFH, unfractionated heparin; VKA, vitamin K antagonist; VT, ventricular tachycardia;VTE,venous thromboembolism;WPW,Wolff-Parkinson-White.
aClass of recommendation.
bLevel of evidence.
19. Author information
Author/Task Force Member Affiliations: Nina Eide Hasselberg, Department of Cardiology, Oslo University Hospital,Rikshopitalet, Oslo, Norway, Michele de Hosson, Cardiology,Ghent University Hospital, Ghent, Belgium; Margarita Brida,Department of Rehabilitation and Sports Medicine, Faculty of Medicine, University of Rijeka, Rijeka, Croatia, and Adult Congenital Heart Disease Centre, Royal Brompton and Harefield Trust and Imperial College, London, United Kingdom; Silvia Castelletti,Cardiology Department, IRCCS Istituto Auxologico Italiano, Milan,Italy; Matthew Caudwell, Obstetrics, St George's Hospital,London, United Kingdom; Elisabetta Cerbai, Department of Neurosciences, Psychology, Drug Research and Child Health,University of Florence, Florence, Italy, and European Laboratory for Non-Linear Spectroscopy, LENS, Sesto Feortino, Italy; Lia Crotti,Department of Cardiology, Cardiomyopathy Unit, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS, Istituto Auxologico Italiano, Milan,Italy, and Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; Nasjaja M.S. de Groot, Unit Translational Electrophysiology, Department of Cardiology, Erasmus University Medical Center, Rotterdam, Netherlands; Mette-Elise Estensen, Department of Cardiology, Oslo University Hospital,Oslo, Norway; Eva S. Goossens, Centre for Research and Innovation in Care, Department of Nursing and Midwifery, Faculty of Medicine and Health Sciences, University of Antwerp,Belgium, and Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium, and Department of Patient Care, Antwerp University Hospital, UZA, Antwerp; Bernhard Haring, Klinik fur Innere Medizin III, Saarland University, Homburg, Germany; Donata Kurpas, Division of Research Methodology, Department of Nursing,Crowl Medical University, Wroclaw. Poland; Carmel M. McEniery, Department of Medicine, University of Cambridge,Cambridge, United Kingdom; Sanne A.E. Peters, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands, and The George Institute for Global Health, School of Public Health, Imperial College London, London,United Kingdom, and The George Institute for Global Health, University of New South Wales, Sydney, Australia; Amina Rakisheva, Cardiology Department, City Cardiology Center,Almaty, Kazakhstan; Antonia Sambola, Acute Cardiac Care Unit,
Department of Medicine II, Medical University of Vienna, Vienna,Asustria; Florian S. Schoenhoff, Department of Cardiac Surgery,Inselspital, University Hospital Bern, University of Bern, Bern,Switzerland; Tommas Simoncini, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Francoise Steinbach, ESC Patient Forum, Sophia Antipolis, France; Isabella Sudano, Cardiology, University Hospital Zurich University Heart Center, Zurich, Switzerland, and University of Zurich, Switzerland;Itraa Sotnach, Southern Hospital, Adult Congenital Cardiac Service, Golden Jubilee National Hospital, Glasgow, United Kingdom; Anne Marie Valente, Cardiology, Boston Children's Hospital, Boston, MA,United States of America, and Medicine, Brigham and Women's Hospital, Boston, United States of America, MA, and Medicine and Pediatrics, Harvard Medical School, Boston, MA, United States of America.
20. Appendix
ESC Scientific Document Group
Includes Document Reviewers and ESC National Cardiac Societies.Document Reviewers: Werner Budts(CPG Review Co-ordinator)(Belgium), Karen Sliwa(CPG Review Co-ordinator)(South Africa), Marianna Adamo(Italy), Elena Arbelo(Spain), Eloisa Arbustini(Italy), Giuseppe Boriani(Italy), Antonio Brucato(Italy),Sergio Bucherii(Sweden), Alessandra Bura Riviere(France), Pavel Calda(Czech Republic), G.-Andrei Dan(Romania), Konstantinos Dimopoulos(United Kingdom), Alexandra Frogoudaki(Greece),Estelle Gandjakhch(France), Eva Gerdts(Norway), Sofie A Gevaert(Belgium), Bruna Gigante(Sweden), Bettina Heidecker(Germany),Bora Jbanez(Spain), Stefan James(Sweden), Mark Johnson(United Kingdom), Peter Juni(United Kingdom), Jolanda Kluin(Netherlands),Lars Kober(Denmark), Konstantinos C. Koskinas(Switzerland), Greg Lip(United Kingdom), Emma F. Magavern(United Kingdom), Bill McEvoy(Ireland), Borislama Mihaylova(United Kingdom), Richard Mindham(United Kingdom), Inge Moelgaard(Denmark), Philip Moons(Belgium), Jens Cedisis Nielsen(Denmark), Ntobeko A. B. Ntusi(South Africa), Agnes A. Pasquet(Belgium), Tatjana Potpara(Serbia), Eva Prescott(Denmark), Bianca Rocca(Italy), Jolien Roos-Hesselink(Netherlands), Xavier Rosselló(Spain), Anna Sannino
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(Germany), Felix Tanner(Switzerland), Ulf Landmesser(Germany),Ilonca Vaartjes(Netherlands), Christiana Vrints(Belgium), Katja Zeppenfeld(Netherlands), Dayenne Zwaagman(Netherlands)
ESC National Cardiac Societies actively involved in the review process of the 2025 ESC Guidelines for the management of cardiovas-cular disease and pregnancy.
Albania: Albanian Society of Cardiology, Aurel Demiraj; Algeria:Albania Society of Cardiology, Nora Henine; Armenia; Armenian Cardiologists Association, Hamlet G. Hayrapetyan; Austria:Austrian Society of Cardiology, Noemi Pavo; Azerbaijan:Azerbaijan Society of Cardiology, Gulane Aghayeva; Belgium:Belgian Society of Cardiology, Agnes A. Pasquet; Bosnia and Herzegovina: Association of Cardiologists of Bosnia and Herzegovina, Milan Ghulovic; Bulgaria; Bulgarian Society of Cardiology, Nina Gotcheva; Czechia; Croatia: Croatian Cardiac Society,Bosko Skoric; Cyprus: Cyprus Society of Cardiology, Maria Karakyriou; Czechia; Czech Society of Cardiology, Zuzana Motovska; Denmark: Danish Society of Cardiology, Norte Gulld�n Nielsen: Egypt; Egyptian Society of Cardiology, Ghada Youssef; Estonia; Estonian Society of Cardiology, Majara Maser;Finland: Finnish Cardiac, Society, Sanna Laurila; France; French Society of Cardiology, Bernard lung; Georgia: Georgian Society of Cardiology, Khatina Jalabadze; Germany; German Cardiac Society,Stephanie Fichtner; Greece: Hellenic Society of Cardiology,Alexandra Frogoudkidung; Hungary: Hungarian Society of Cardiology,Olga Jhanikala Balint; Iceland: Icelandic Society of Cardiology, Pordis Jona Hfrankelsdottir; Ireland: Irish Cardiac Society, Paul F. Brennan;Israel: Israel Heart Society, Rafael Kuralpestein; Italy; Italian Federation of Cardiology, Gabriele Eidyigia Resenza; Kazakhstan: Kazakhstan;Association of Cardiologists of Kazakhstan: Kazakhstan: Krishnan Jusbekova;Kosovo(Republic of): Kosovo Society of Cardiology, Pranvera Ibrahim; Kyrgyzstan; Kyrgyzson; Cardiology, Saamay Abilova; Latvia; Latvia Society of Cardiology, Oskars Kalejs;Lebanon: Lebanon Society of Cardiology, Georges Saade; Libya;Libyan Cardiac Society, Hanan Hera Bugaigis; Lithuania:Zhaoian Society of Cardiology, Jatear Bysensitu; Luxembourg;Luxembourg Society of Cardiology, Rouguiatou Sow; Malta; Maltese Cardiac Society, Maryland are Macana; Moldova(Republic of):Moldavian Society of Cardiology, Lilia David; Morocco; Morocco Society of Cardiology, Afreti Bayyness; Netherlands: Netherlands Society of Cardiology, Anastasia D. Egorova; North Macedonia; National Society of Cardiology of North Macedonia, Marjan Bosevski; Norway; Norwegian Society of Cardiology, Elisabeth Religur; Poland: Polish Cardiac Society, Olga Trojnraska; Portugal:Portuguese Society of Cardiology, Rita Ilhao Moreira: Romania:Romanian Society of Cardiology, Ruxandra Jurct; San Marino: San Marino. Mario of Cardiology, Marco Zavata: Serbia: Modern China Cardiac; Ministry of Cardiology, Marco Zavata: Serbia: Cardiology Society of Society of Serbia, Aleksandra Llic, Slovakia: Slovak Society of Cardiology, Juraj Druval; Slovenia: Slovenia Society of Cardiology, Katja Prokseli; Spain: Spanish Society of Cardiology,Milagros Pedreira Pérez; Sweden: Swedish Society of Cardiology,Christina Christersson; Switzerland: Swiss Society of Cardiology, Matthiasa Gremuttian, Syrian Arab Republic; Syrian Cardiovascular Association, Elias Barakat; Tunisia: Tunisia Society of Cardiology and Cardiovascular Surgery, Meramis Drissa: Turkye;Turkish Society of Cardiology, Alev arat Ozkan; Ukraine: Ukrainian Association of Cardiology, Olena I Mitchenko; United Kingdom of Great Britain and Northern Ireland: British Cardiovascular Society, Dawn L. Adamson; Uzbekistan: Association of Cardiologists of Uzbekistan, Feruza Zakirova
ESC Clinical Practice Guidelines(CPG) Committee: Ulf Landmesser(Chairperson)(Germany), Stefan James(Co-Chairperson)(Sweden), Marianna Adamo(ltaly), Suleman Aktaa(United Kingdom),Fotl W. Benagls and Netherlands), Colin Baigent(United Kingdom),Michael A. Borger(Germany), Giuseppe Boriani(ltaly), Margarita Brida(Croatia), Robert A. Byrne(Ireland), Estelle Goldjarbkhch(France),Bettina Heidecker(Germany), Anja Henmenneth(Germany), Borja lbanee(Zspann), Peter Jini(United Kingdom), Gregory Y.H. Lip(United Kingdom), John William McEvoy(Ireland), Borislava Mihaylova(United Kingdom), Inge Moegard(Denmark), Lis Neubeck(United Kingdom),Eva Prescott(Denmark), Bianca Rocca (Italy), Xavier Rossello(Spain),Anna Sinnina(Germany), Felix C. Tanner(Switzerland), Wojtekowsi(Poland), Katja Zeppenfeld(Netherlands)
21. References
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2. Roos-Hesselink J, Baris L, Johnson M, De Backer J, Otto C, Marelli A, et al. Pregnancy outcomes in women with cardiovascular disease: evolving trends over 10 years in the ESC Registry Of Pregnancy and Cardiac disease(ROPAC). Eur Heart J 2019:40:384-55. https://doi.org/10.1093/eurheartj/ehz136
3. van der Zande JA,Tutarel O,Ramlakhan KP, van der Bosch AE, Bordese R, Zengin E,et al.Pregnancy outcomes in women with Ebstein's anomaly: data from the Registry Of Pregnancy and Cardiac disease(ROPAC). Open Heart 2023;10:e002406. https://doi.org/10.1136/openhrt-2023-002406
4.Wander G, van der Zander JA, Patel RR, Johnson MR, Roos-Hesselink J. Pregnancy in women with congenital heart disease: a focus on management and preventing the risk of complications. Expert Rev Cardiovasc Ther 2023;21:587-99. https://doi.org/10.1080/14779072.2023.2237886
5. Ramlankan KP, Malhamal I, Marelli A, Rutz T, Goland S, Franx A, et al. Hypertensive disorders of pregnant women with heart disease: the ESC EORP ROPAC registry.Eur Heart J 2022;43:3749-61.https://doi.org/10.1093/eurheart/ehac308
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96
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ESC Guidelines
References
| Topic | New information | Rationale |
|---|---|---|
| Pregnancy Heart Teamα | Broader acceptance, dedicated section | Ensure comprehensive care throughout reproductive stagesb |
| Risk stratification a.c | mWHO 2.0 classification, refined and expanded clinical categories | More data have emerged, necessitating more nuanced risk assessment for patient counselling1,2 |
| Clinical data and research | ROPAC3-12 and PPCM13-17 registries Cardiomyopathies Primary arrhythmia syndromes | New or updated clinical management |
| Clinical scenarios | Algorithms for management of clinical situations in pregnant women | Provide practical information for the clinical cardiologist |
| Genetic testing and counselling | Advancements in testing and pre-implantation procedures | Incorporation of latest management of genetic testing and counselling |
| Revision of contraindications (COR III) for pregnancy in women classified as mWHO class IV | Emphasis on the critical role of comprehensive counselling by the Pregnancy Heart Team (COR I) Reproductive choices | Recognition of a woman's autonomy in making reproductive choices Promoting a detailed and transparent dialogue about the heightened risks and encouraging shared decision-making |
| Adverse pregnancy outcomes (APO) | Increased focus on long-term outcomes | Evidence supports the need for thorough discussion and management of APOs ${}^{18}$ |
| Recommendations | Recommendations | Recommendations | Recommendations |
|---|---|---|---|
| Section 4. The Pregnancy Heart Team | |||
| Although the concept of the Pregnancy Heart Team was previously part of the general principles, it has now been given its own dedicated section, which covers all aspects from pre-conception through to the postpartum period. | |||
| A discussion by the Pregnancy Heart Team | |||
| recommended for women with mWHO 2.0 class IV conditions, including a shared decision-making process for pregnancy operations,involving psychological support. | I | ||
| It is recommended that women with CVD of mWHO 2.0 class II-III and above are evaluated and managed by a Pregnancy Heart Team from pre-pregnancy onwards through pregnancy and post-partum. | I | C | |
| Measurement of BNP and NT-proBNP levels should be considered prior to pregnancy in women with HF of any aetiology, including previous PPCM, cardiomyopathy,ACHD,and PAH,and be monitored during pregnancy according to the underlying disorder and in case of new-onset or worsening symptoms. | IIa | B | |
| Section 5. Drugs during pregnancy and lactation | |||
| Given the importance of medication use throughout this document, this section has been brought forward and revised. The former comprehensive medication table has been moved to the Supplementary data online, and we provide a summary figure(Figure 6) listing the(contra)indicated medications. | |||
| Section 6. Pregnancy in women with cardiomyopathies and primary arrhythmia syndromes | |||
| This section has been expanded since 2018 for advice in specific cardiomyopathies and primary arrhythmias. Vaginal delivery is recommended in most women with CMPs, unless there are obstetric indications for casarean section, severe HF (EF<30% and/or NYHA class III/IV), uncontrolled arrhythmias, or severe outflow obstruction(≥50 mmHg) in women with HCM, or in women presenting in labour on VKAs. | |||
| In women with DCM and worsening of EF during pregnancy, counselling on the risk of recurrence during a subsequent pregnancy is recommended in all cases, even after recovery of LV function. | |||
| It is recommended that women with HCM with symptomatic LV dysfunction(EF<50%) and or severe LVOTO(≥50 mmHg) wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events. | |||
| Myosin inhibitors are not recommended in women during pregnancy due to lack of safety data. |
| Beta-blockers, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy in women with LQTS. | 1 | B | ||
| It is recommended to continue beta-blocker therapy during lactation in women with LQTS to reduce arrhythmic risk. | 1 | I | B | |
| Pre-pregnancy dose beta-blockers of nadolol or propranolol is recommended in patients with LQT2, particularly in the post-partum period, which represents a high-risk period for life-threatening arrhythmias. | 1 | I | B | |
| Beta-blockers, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy and lactation in women with CPVT. | 1 | I | C | |
| Flecanide, in addition to beta-blockers, is recommended in women with CPVT who experience cardiac events, such as syncope, VT, or cardiac arrest during pregnancy. | 1 | I | C | |
| Section 7. Peripartum cardiomyopathy | ||||
| We have provided a separate section on PPCM in these guidelines. | ||||
| Genetic counselling and testing should be considered in women with PPCM. | lla | C | ||
| When a reversible course of HF is assumed,treatment in accordance with HF guidelines should be considered for at least 12 months after complete LV recovery (normalization of LV volumes and EF). | lla | C | ||
| Section 8. Pregnancy in women with a orortopathies Since 2018, significant evidence has emerged in the context of heritable thoracic aortic disease(HTAD), supporting a more gene- and variant-based approach, which has been incorporated in this version of the guidelines. It is recommended that women with a history of aortic dissection or-surgery have pre-pregnancy counselling about the high risk by an extended Pregnancy Heart Team considering the presence and type of genetic variant, aortic morphology, growth rate, and aetiology of aortic dissection. | I | C | ||
| Section 9. Pregnancy in women with known congenital heart disease This section has undergone a major update based on recent reports, which have been summarized in a clear and concise table. It is recommended that all women with Fontan circulation who wish to become pregnant receive counselling from the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events. | I | C | ||
| Section 10. Pregnancy in women with pulmonary arterial hypertension | ||||
| This subject is now covered in a separate section in these guidelines, in line with growing insights into management. It is recommended that women of childbearing potential with PAH wishing to become pregnant are counselled by a multiop the very high risk of pregnancy-related adverse events, encouraging a shared decision-making process about whether to become pregnant. | I | C | ||
| Section 11. Venous thromboembolism in pregnancy and post-partum Guidance on the involvement of an expert team and more prompt initiation of treatment are now provided in dedicated flowcharts and recommendations.In pregnant women or women in the post-partum period with suspicion of venous thromboembolism(VTE)[deep vein thrombosis(DVT) and/or PE], an immediate formal diagnostic assessment with validated methods is recommended and should not be postponed. | I | B | ||
| Section 12. Pregnancy in women with acquired heart disease Recommended for emergency situations are provided for acquired heart diseases in addition to the new sections on cardio-oncology and heart transplantation. | ||||
| Recommendations for coronary artery disease and pregnancy | ||||
| In pregnant women with chest pain, it is recommended to exclude life-threatening cardiovascular conditions, including PE,ACS(including SCAD), and acute aortic syndrome. | 1 | I | C | |
| The duration of DAPT(aspirin and clopidogrel) in pregnant women undergoing coronary stent implantation is recommended to be the same as in non-pregnant women, with an individual approach considering ischaemic risk and delivery-related bleeding risks. Continuation of statins may be considered during pregnancy in women with established ASCVD. | 1 | I | C | |
| Recommendations for hypertensive disorders and pregnancy | ||||
| It is recommended to aim for systolic BP<140 mmHg and diastolic BP<90 mmHg in pregnant women. It is recommended to aim for systolic BP<140 mmHg and diastolic BP<90 mmHg in pregnant women. In severe hypertension, drug treatment with i.v.labetalolur, upapidil,nicardipine, or oral short acting nifedipine or methyldopa is recommended for acute reduction in blood pressure. Intravenous hydralazine is a second-line option. | ||||
| Recommendations for supraventricular tachycardia and pregnancy Thererate of supraventricular tachycardia and pregnancy Thererate of acute reduction in blood pressure. Intravenous hydrahaline is a second-line option. | ||||
| Therapeutic anticoagulation with LMWH is recommended for pregnant women with persistent or permanent AF at elevated thrombobolic risk. | ||||
| Flecanide, in addition to beta-blockers, should be considered for long-term AF rhythm control in pregnancy. | ||||
| Recommendation for ventricular tachycardia, device implantation and catheter ablation and pregnancy | ||||
| When performing catheter ablation during pregnancy, the use of non-fluoroscopic mapping and navigation systems should be considered. |
| Recommendations for cardiac arrest and pregnancy | |||
|---|---|---|---|
| Continuous manual left uterine displacement during CPR in pregnant women (≥20 weeks) with cardiac arrest is recommended to relieve | |||
| aortocaval compression. | |||
| It is recommended to establish i.v.access above the diaphragm to ensure that the i.v. therapy is not obstructed by the gravid uterus. | |||
| It is recommended that no drugs are withheld in pregnant women with cardiac arrest due to concerns of teratogenicity. | |||
| Recommendation for congenital atrioventricular block and pregnancy | |||
| In pregnant women with asymptomatic congenital AV block,normal cardiac anatomy and function,a narrow QRS complex,and ventricular | |||
| rate(≥50 b.p.m.) a prophylactic temporary pacemaker during delivery is not recommended. | |||
| Recommendation for native valve disease and pregnancy | |||
| Valve surgery during pregnancy should only be considered when there is a maternal mortality risk and other treatment options have failed. | |||
| Recommendation for prosthetic valves disease and pregnancy | |||
| It is recommended that a care plan documenting the agreed anticoagulant strategy (including the decision to continue VKAs or converting to therapeutic-dose LMWH in the first trimester) is in place for women of childbearing age with a MHV prior to pregnancy or as soon as pregnancy is recognized. | |||
| Recommendations for chronic and acute heart failure and pregnancy | |||
| Inotropes and/or vasopressors are recommended in pregnant women with cardiogenic shock with levosimandan, dobutamine, and milrinone as recommended agents. | |||
| ACE-Is,ARBs,ARNIs,MRAs,ivabradine,and SGLT2 inhibitors are not recommended during pregnancy due to adverse foetal effects. | |||
| Recommendations for heart transplantation and pregnancy | |||
| It is recommended to postpone pregnancy until at least 1 year after heart transplantation, taking individual risk factors into account. | |||
| In women with a heart transplant, it is recommended that immunosuppression serum drug levels are monitored during pregnancy every 4 weeks until the 32nd week, then every 2 weeks until the 36th week, then weekly until delivery and for 6-12 months after delivery to guide dosing. | |||
| Recommendation for cardio-oncology and pregnancy | |||
| It is recommended that pregnant women with cancer who require cardiotoxic cancer therapy are jointly managed by the Pregnancy Heart Team and the cardio-oncology team. | |||
| Section 13. Long-term effects of adverse pregnancy outcomes | |||
| This is a completely new section in the guidelines, reflecting the growing recognition of the importance of APOs. | |||
| It is recommended to undertake a cardiovascular risk assessment in women with APOs, to recognize and document APOs when CVD risk is evaluated in women, and to provide counselling on the importance of healthy lifestyle choices that optimize cardiovascular health. |
| Recommendations in 2018 | Classa | Recommendations in 2025 | Classa | Levelb | |
|---|---|---|---|---|---|
| Section 4. The Pregnancy Heart Team | |||||
| Prophylactic antibiotic therapy to prevent endocardits during delivery is not recommended. | III | C | Systemic antibiotic phosphoryaxis may be considered for delivery in women at high risk. | IIb | C |
| Section 6. Recommendations for cardiomyopathies and pregnancy | |||||
| In patients with HCM, it is recommended that beta-blockers are continued in women who used them before pregnancy. | I | C | Continuation of beta-blockers should be considered during pregnancy in women with CMPs, with close | IIa | C |
| mWHO 2.0 I | mWHO 2.0 II | mWHO 2.0 II-III | mWHO 2.0 III | mWHO 2.0 IV | |
|---|---|---|---|---|---|
| Diagnosis | Ventricular (dys)function + pulmonary hypertension | ||||
| Diagnosis | Mild left ventricular impairment: EF>45%. Significantly impaired, Sificantly impaired RV(subpulmonary) function. | Moderate left ventricular impairment: EF<30% EF 30%-45%. Previous PPCM with not more than mild residual left ventricular impairment. | |||
| Diagnosis | Arrhythmias | Arrhythmias | Arrhythmias | Arrhythmias | |
| Diagnosis | Atrial or ventricular ectopic beats, isolated. | Most supraventricular arrhythmias. Bradycardia requiring pacemaker. | Low-risk LQTS: no previous events+ on full dose beta-blocker therapy. Low-risk CPVT: well controlled by medical therapy. BrS with no previous events. | Sustained ventricular tachycardia from any aetiology. LQT2(post-partum). Symptomatic CPVT and LQTS not adequately controlled by therapy. BrS with previous events. | |
| Cardiomyopathy | Cardiomyopathy | Cardiomyopathy | Cardiomyopathy | ||
| HCM: genotype-positive + phenotype-negative. | Low-risk ARVC: genotype-positive+ no or mild phenotype. HCM without complications. DCM/NDLVC with normal or mild left ventricular impairment: EF>45%. | ARVC with moderate/ severe disease. HCM with arrhythmic and/or moderate haemodynamic complications. DCM/NDLVC with moderate left DCM/NDLVC with moderate left ventricular impairment: EF 30%-45%. | DCM/NDLVC with severe left ventricular impairment: EF<30% or NYHA class IIIIV. HCM with symptomatic severe outflow tract obstruction: 50 mmHg. HCM with severely symptomatic LV dysfunction(EF<50%) | ||
| Congenital heart disease | |||||
| Successfully repaired uncomplicated nitrical or ventricular atrioventricular septal defects. $$\text{ sptel defect.}$$ Repaired tetralogy significant residual lesions. Uncomplicated | Unpaired cyanotic heart disease(not Eisennenger). Systemic RV with good or mildly decreased ventricular function. | ||||
| patent ductus arteriosus, anomalous pulmonary venous drainage. | significant residual haemodynamic/ arrhythmic lesions. Transposition of the great arteries with arterial switch without significant residual lesions. | Uncomplicated Ebstein anomaly: mild to moderate TR, no tricuspid stenosis, no | Uncomplicated Fontan correlation: good ventricular function, no significant valve disease or arrhythmias, good exercise tolerance, and normal arterial saturations. Ebstein anomaly with any complication. | Sistemic RV with moderate or severely decreased ventricular function. Fontan with any complication. Eisenmenger syndrome. |
| mWHO 2.0 I | mWHO 2.0 II | mWHO 2.0 II-III | mWHO 2.0 III | mWHO 2.0 IV | ||
|---|---|---|---|---|---|---|
| Valvular heart disease | ||||||
| Small or mild ●pulmonary stenosis ●mitral valve prolapse without significant regurgitation. | Native, homograft or tissue valve disease not considered mWHO 2.0 I or IV: mild mitral stenosis, moderate aortic stenosis. Moderate valvular regurgitation. | Uncomplicated mechanical valve with stable well controlled INRs. Moderate mitral stenosis. Severe asymptomatic aortic stenosis. Severe left-sided valvular regurgitation. | Severe mitral stenosis. Severe symptomatic aortic stenosis. | |||
| Aortopathy | Aortopathy | |||||
| Non-HTAD mild aortic dilatation(<40 mm). | Turner syndrome without cardiovascular features (BAV, coarctation,AHT,aortic dilatation). | Marfan or other HTAD syndrome without aortic dilatation. Aorta<45 mm in BAV pathology. | Moderate aortic dilatation:40-45 mm in Marfan syndrome or other HTAD; 45-50 mm in BAV, Turner syndrome ASI 20-25 mm/m2, other aortic dilatation <50 mm. Marfan with previous aortic root replacement. Previous aortic dissection with stable diameter. | Severe aortic dilatation:45 mm in Marfan syndrome or other HTAD, >50 mm ASI>25 mm/m2 in Turner syndrome, other aortic dilatation >50 mm. Vascular Ehlers- Danlos syndrome. Severe(re)coarctation. Previous aortic dissection with stable | ||
| Acquired+ coronary heart disease + other | ||||||
| Prior SCAD. Prior ischaemic cardiac event (STEMI/NSTE ACS). Prior adverse pregnancy outcome requiring hospitalization. Prior adverse cardiovascular effects of cancer treatment. | ||||||
| Risk | Risk | No detectable increased risk of maternal mortality and no/mild increased risk in morbidity. | Small increased risk of maternal mortality or moderate increase in morbidity. | Intermediate increased risk of maternal mortality or severe morbidity. | Significantly increased risk of maternal mortality or severe morbidity. | |
| Average maternal cardiac events | Van Hagen et al. (2016)51 | 9.9% | 7.7% | 17.7% | 28.9% | |
| event rates | Silversides et al. (2018)52 | 3.1% | 21.7% | 12.8% | 21.1% | 35.6% |
| mWHO 2.0 I | mWHO 2.0 II | mWHO 2.0 II-III | mWHO 2.0 III | mWHO 2.0 IV | |
|---|---|---|---|---|---|
| Involvement of the Pregnancy Heart Team | No | No | Yes | Yes | Yes |
| Counselling | Yes(by regular healthcare professional) | Yes(by regular healthcare professional) | Yes: expert counselling by Pregnancy Heart Team is required | Yes: expert counselling by Pregnancy Heart Team is required | Yes: expert counselling by Pregnancy Heart Team is required |
| Obstetric and cardiac care during pregnancy | Local hospital | Local hospital | Shared care with local hospital+ Pregnancy Heart Team | Expert centre, care led by Pregnancy Heart Team | Care led by Pregnancy Heart Team |
| Location of delivery | Local hospital | Local hospital | Shared care with local hospital+ Pregnancy Heart Team. Location depends on CV status and evolution of pregnancy | Expert centre, care led by Pregnancy Heart Team | Expert centre, care led by Pregnancy Heart Team |
| Pre-implantation genetic diagnosis | IVF procedure followed by biopsy and genetic testing of a single cell of the embryo. Embryo transfer with success rate of 25%-30%(dependent on mother's age and fertility). |
|---|---|
| Risks to mother and offspring of IVF, such as multiple birth, premature labour and low birth weight, as well as side effects of hormonal treatment. Availability, expense and methods differ across countries. | |
| Chorionic villus sampling | Transcervical or transabdominal sampling of the chorionic villi at the end of the first trimester. Procedure-related foetal loss rate~0.2%.66 |
| Amniocentesis | Direct sampling of amniotic fluid after 15 weeks of gestation. Procedure-related foetal loss rate~0.1%.66 |
| Method | Benefits | Cardiovascular riskss | Cautious use and contraindications | Contraceptive efficacy |
|---|---|---|---|---|
| Hormonal oral contraceptives | ||||
| Progestin-only oral contraceptives | Minimal/no impact on coagulation factors Safe CV risk profile 72,73 | Mild fluid retention | LQTS not on beta-blockers | ++(general) $$\text{+++(for}$$ drospirenone)"73 |
| Combined oral contraceptives 76,77 | Regular menstruation with reduced blood loss | VTE,hypertension and altered lipid | Known dyslipidaemia78 Pre-existing hypertension79 Obesity80 Cyanosis MHV Fontan circulation Risk factors for ACS81 | +++ |
| Long-acting reversible contraceptives | ||||
| Levonorgestrel-releasing IUD | ↓ Menstrual bleeding and iron loss | None specified | Vasovagal responses on insertion and removal(done by gynaecologist)→caution and monitoring with availability of anaesthesiologist recommended in PAH and Fontan circulation82 | Safest and most effective option +++ |
| Smaller levonorgestrel IUD | ↓ Menstrual bleeding and iron loss Easier to insert ↓ Risk of vasovagal responses | None specified | +++ | |
| Copper IUD | ↓Cost | - | ↑ Intensity of menstrual bleeding | +++ |
| Etonogestrel-releasing subcutaneous implants | No pelvic infection risk | None specified | Surgical subcutaneous insertion(in the forearm with local anaesthesia-outpatient procedure) | +++ |
| Depot medroxyprogesterone acetate injection83 | Lighter menses | Increased VTE risk, weight gain | Irregular bleeding | ++ |
| Barrier methods +1 Pelvic infection risk84 - None specified + |
| Permanent sterilization | ||||
|---|---|---|---|---|
| Tubal ligation Vasectomy | Permanent | Anaesthetic and procedural risks | Non-reversible | +++ |
| Emergency contraception | ||||
| Oral contraceptive pills to delay ovulation | ||||
| Uilpristal acetate | ↑Effectiveness than levonorgestrel | No↑ thrombosis risk85-87 | None specified | +++(only if taken before ovulation) |
| Levonorgestrel single dose of 1.5 mg <72 h after unprotected intercourse | - | No↑ thrombosis risk | None specified | ++(only if taken before ovulation) |
| Contractive device | Contractive device | Contractive device | Contractive device | Contractive device |
| Copper IUD <120 h after unprotected intercourse | - | - | None specified | +++(in addition to ongoing contraception) 85-88 |
| Recommendations | Recommendations | Recommendations | Recommendations | Recommendations | Classa | Levelb |
|---|---|---|---|---|---|---|
| Maternal risk assessment | ||||||
| It is recommended to perform a risk assessment in all women with CVD of childbearing age using the mWHO 2.0 classification | 44,45,47-49,54 | 44,45,47-49,54 | 44,45,47-49,54 | 1 | C | |
| A discussion by the Pregnancy Heart Team about the high risk of maternal mortality or morbidity and the related high foetal risk is recommended for women with mWHO 2.0° class IV conditions, including a shared decision-making process for pregnancy termination,involving psychological support. ${}^{65}$ | 1 | 1 | 1 | 1 | C | |
| It is recommended that women with CVD of mWHO 2.0° class II-III and above are evaluated and managed by a Pregnancy Heart Team from pre-pregnancy onwards through pregnancy and post-partum. 44,45,47-49,54 | 1 | 1 | 1 | 1 | C | |
| Methods of contraception | ||||||
| It is recommended that women with CVD of mWHO 2.0° class II and above, or those at risk of developing CVD, receive individualized advice to determine the most suitable contraception method, including emergency contraception. ${}^{90,91}$ | 1 | 1 | 1 | C | ||
| Progestin-only treatment, contraceptive implants, and/or levonorgestrel IUDs should be considered when there is any risk of thrombboembolic events.73,92-94 | B | |||||
| Genetic counselling | Genetic counselling | Genetic counselling | ||||
| Assessment by a clinical geneticist prior to pregnancy is recommended in women fulfilling diagnostic criteria for inherited cardiovascular disease to guide risk stratification and pre-natal genetic testing.63,95 | I | C | ||||
| Pre-conception genetic counselling is recommended in couples with heritable CVD, whether genetic testing is being considered or not. It is recommended that this counselling is provided by an appropriately trained healthcare professional within a multidisciplinary team that offers psychological support and education to encourage decision-making.63,95 | ||||||
| Reproductive technology | ||||||
| It is recommended that single embryo transfer is performed in women with CVD.70,71 | I | C | ||||
| Pregnancy termination | ||||||
| It is recommended to offer women with CVD access to termination of pregnancy that is tailored to their cardiac condition to minimize the risks of the procedure.83 | I | C |
| Recommendations | Table 2- Recommendations for diagnostic methods in pregnancy(see Evidence Table 2) |
|---|---|
| Echocardiography | |
| Transthoracic echocardiography is recommended as first-line imaging tool in any pregnant woman with unexplained or new cardiovascular signs or symptoms. ${}^{99}$ | I C |
| Biomarkers | |
| Measurement of BNP and NT-proBNP levels should be considered prior to pregnancy in women with HF of any aetiology, including previous PPCM, cardiomyopathy,ACHD,and PAH,and be monitored during pregnancy according to the underlying disorder and in case of new-onset or worsening symptoms. ${}^{114}$ | IIa B |
| Ionizing radiation | |
| It is recommended to limit exposure to all medical ionizing radiation doses to ALARA levels. ${}^{121}$ | I C |
| It is recommended to keep the radiation dose to the foetus as low as possible(preferably<50 mGy),particularly if the foetus is in the field of view. ${}^{120,121}$ | I C |
| A CT scan should be considered for PE when clinical benefits outweigh the risks to the mother and foetus. | 100,121,132 |
| A chest radiograph may be considered as a first-line imaging tool if other methods are not successful in clarifying the cause of dyspnoea. | IIb C |
| Coronary angiography with minimal radiation may be considered during pregnancy if potential benefits outweigh the risks. | I b C |
| Cardiovascular magnetic resonance | |
| Discontinuation of lactation for 24 h should be considered in women in whom i.v. gadolinium is required. 133,139 | IIa C |
| CMR imaging without gadolinium contrast should be considered for a definitive, clinically relevant diagnosis during pregnancy,if other non-invasive diagnostic measures are not sufficient. 135,136 | IIa C |
| NYHA class III/IV or cyanosis during baseline pre-natal visit | |
|---|---|
| Maternal left heart obstruction | |
| Low maternal oxygen saturation(<90%) | |
| Multiple gestations | |
| Use of anticoagulants | |
| Cardiac medication before pregnancy | |
| Mechanical valve prosthesis | |
| Maternal cardiac event during pregnancy | |
| Maternal decline in CO during pregnancy |
| Recommendations | Classa | Levelb | |
|---|---|---|---|
| Timing and mode of delivery | |||
| Vaginal delivery is recommended in most women with CVD.161-163 | I | B | |
| Systemic antibiotic prophylaxis may be considered for delivery in women at high risk ${}^{c}$ 178 | IIb | C | |
| Routine induction of labour prior to 39 weeks is not recommended in women with stable CVD.44,154 | III | C | |
| Delivery in women on anticoagulants | |||
| It is recommended that the timing of delivery is planned to ensure safe and effective peripartum anticoagulation. | I | C | |
| It is recommended to discontinue VKAs and start therapeutic-dose LMWH or adjusted-dose iv. UFH at the 36th week of gestation or 2 weeks before the planned delivery. ${}^{179}$ | I | C | |
| In women at low risk ${}^{d}$ on therapeutic-dose LMWH, neuraxial anaesthesia and vaginal delivery(or caesarean section for obstetric | I | C | |
| indications) is recommended 24 h after the last dose of LMWH.180 |
| Indication | Type of anticoagulant | Dosing | Timing |
|---|---|---|---|
| Low thrombosis risk | Low thrombosis risk | Low thrombosis risk | Low thrombosis risk |
| VTE prevention/no indication for oral anticoagulationa | LMWH | Prophylactic dose | o.d. |
| Uncomplicated Fontan circulationb | LMWH | Prophylactic dose | o.d. |
| Intermediate thrombosis risk | |||
| VTE(DVT/PE) during pregnancy a | LMWH | Therapeutic dose | o.d.or b.i.d. |
| Persistent/permanent AF at elevated thromboembolic risk c | LMWH | Therapeutic dose | o.d.or b.i.d. |
| Decreased ventricular function(EF<35%) and/or intracardiac thrombus | LMWH | Therapeutic dose | o.d.or b.i.d. |
| High thrombosis risk | High thrombosis risk | High thrombosis risk | High thrombosis risk |
| Mechanical heart valves e | |||
| 1.First trimester | |||
| Low VKA dose to achieve required INR | First trimester: VKA or | INR: weekly to every 2 weeks | |
| Low VKA dose to achieve required INR | LMWH | dose adjusted to peak anti-factor Xa level | b.i.d. |
| High VKA dose to achieve required INR | Switch to LMWH | Dose adjusted to peak anti-factor Xa level(weekly until threshold, every 2-4 weeks thereafter) | b.i.d. |
| 2.From week 13: shared decision | |||
| (a) Continue/switch to VKA with weekly to every 2 weeks INR | |||
| (b) Continue LMWH with dose adjustment as above | |||
| Delivery: refer to Section 4.5.6.2.(for urgent delivery) and Section 4.5.6.1(for planned delivery) |
| Anoxaparin | Dalteparin | Tinzaparin | Target | |
|---|---|---|---|---|
| Prophylactic LMWH Body weight 50-100 kg | 4000 IU o.d. | 5000 IU o.d. | 4500 IU o.d. | NA |
| Therapeutic LMWH (non-MHV) | 150 IU/kg o.d. | 200 IU/kg o.d. | 175 IU/kg o.d. | NA |
| Therapeutic LMWH MHz | 125 IU/kg b.i.d.(starting dose) then 100 IU/kg b.i.d. | 125 IU/kg(starting dose) b.i.d. then 100 IU/kg b.i.d. | 250 IU/kg(starting dose) then 175 IU/kg o.d. | 0.8-1.2 U/mL anti-factor Xa (4-6 h post administration) |
| Recommendation | Classa | Levelb |
|---|---|---|
| DOACs are not recommended during pregnancy. | III | C |
| Recommendations | Classa | Levelb |
|---|---|---|
| Clinical cardiological surveillance (ECG, echocardiogram, and Holter ECG monitoring) is recommended during pregnancy in women with CMPs, depending on individual risk. | 1 | C |
| Vaginal delivery is recommended in most women with CMPs, unless there are obstetric indications for caesarean section, severe HF(EF<30% and/or NYHA class III/IV), uncontrolled arrhythmias, or severe outflow obstruction(≥50 mmHg) in women with HCM, or in women presenting in labour on VKAs. ${}^{60}$ | 1 | C |
| Continuation of beta-blockers should be considered during pregnancy in women with CMPs, with close follow-up of foetal growth. ${}^{60}$ | lla | C |
| Dilated cardiomyopathy | ||
| In women with DCM and worsening of EF during pregnancy, counselling on the risk of recurrence during a subsequent pregnancy is recommended in all cases, even after recovery of LV function. ${}^{43}$ | I | C |
| Arrhythmogenic right ventricular cardiomyopathy | |
|---|---|
| Flecainide, in addition to beta-blockers, should be considered as the anti-arrhythmic drug of choice in pregnant women with ARVC. ${}^{148}$ | lla |
| Sotalol may be considered as an anti-arrhythmic drug in pregnant women with ARVC, with careful evaluation of QTc and while monitoring for foetal bradycardia and foetal growth and neonate | llb |
| hypoglycaemia. |
| Recommendations | Classa | Levelb |
|---|---|---|
| Monitoring and treatment of hypokalemaa and hypomagnesmaia is recommended in pregnant women with primary arrhythmia | I | C |
| syndromes suffering from hyperemesis.334 | ||
| Long QT syndrome | ||
| Beta-blockersc, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy in women with LQTS. ${}^{312-316,335}$ | $1$ | B |
| It is recommended to continue beta-blocker therapy during lactation in women with LQTS to reduce arrhythmia risk. | ${}^{148,336}$ I | B |
| Pre-pregnancy beta-blocker dose of nadolol or propranolol, is recommended in women with LQT2, particularly in the post-partum period, which represents a high-risk period for life-threatening arrhythmias. | $1$ | B |
| Counselling for women with PPCM about the risk of recurrence during a subsequent pregnancy and about contraception is recommended in all cases, even after recovery of LV function(LVEF>50%).355,369 | C | |
| Adding at least prophylactic LMWH treatment to bromoriptine treatment in women with PPCM should be considered.358,362,372,373 | lla | C |
| Genetic counselling and testing should be considered in women with PPCM.60 | lla | C |
| When a reversible course of HF is assumed, treatment in accordance with HF guidelines should be considered for at least 12 months after complete LV recovery(normalization of LV volumes and EF).339,345,368,374 | lla | C |
| Bromoriptine treatment may be considered in addition to optimal HF treatment to enhance recovery of LV function in women with PPCM.358- 360,366,375,376 | lb | B |
| The use of a WCD may be considered in women with PPCM and LVEF<35%.377 | lb | C |
| Counselling | ||
| It is recommended that women with aortic disease have counselling about the risk of aortic dissection in pregnancy and the post-partum period. 404,423 | I | C |
| It is recommended that women with a history of aortic dissection or-surgery have pre-pregnancy counselling about the high risk by an extended Pregnancy Heart Team' considering the presence and type of genetic variant, aortic morphology, growth rate, and aetiology of aortic dissection. 7,381,424 | I | C |
| It is recommended that women with vascular Ehlers-Danios syndrome wishing to become pregnant are counselled regarding the very high risk of pregnancy-related adverse events by a multidisciplinary team, considering family history, genetic variant, and previous vascular events. 7,396,397,425 | I | C |
| Imaging | ||
| Imaging of the entire aorta d(CT or CMR) is recommended before pregnancy in women with known or suspected aortic disease. 390,424,426 | I | C |
| In women with aortic dilatation related to BAV, imaging(with TTE, and CMR/CT if needed) of the aortic root, ascending aorta, and descending aorta(to rule out coarctation) is recommended before pregnancy. 427,428 | I | C |
| In women with low-risk aortic disease(mWHO 2.0 classes II and II-III), one-time echocardiographic imaging between 20 and 30 weeks of gestation and imaging at 6 months post-partum is recommended. 393,429 | I | C |
| In women with moderate to high-risk aortic disease(mWHO 2.0 classes III and IV), repeated echocardiographic imaging every 4-12 weeks (depending on diagnosis and severity of dilatation) is recommended during pregnancy and until 6 months post-partum. 393,429,430 | I | C |
| CMR (without gadolinium) imaging of the entire aorta is recommended in pregnant women at risk of or with known aortic dilatation who have not had recent pre-pregnancy cross sectional imaging. 135 | I | C |
| Treatment-medical | ||
| When a woman with known aortic dilatation, history of dissection, or P/LP variant associated with aortic disease becomes pregnant, strict and individualized BP control is recommended. 431,432 | I | C |
| Beta-blocker therapy e throughout pregnancy and in the post-partum period is recommended in women with MFS and other HTADs. 433 | I | C |
| Celiprolol is recommended in women with vascular Ehlers-Danios syndrome during pregnancy and lactation. 434 | I | C |
| Treatment-intervention/surgical | ||
| It is recommended that indications for pre-pregnancy aortic root and/or ascending aortic surgery are guided by aortic morphology, underlying pathology, family history, genetic variant, previous vascular events, and patient's preference. 62,383 | I | C |
| It is recommended that centres managing pregnancies in women with moderate to high-risk aortic disease (mWHO 2.0 class III/IV) can provide cardiovascular surgery in case of peripartum adverse events. 435,436 | I | C |
| Specific conditions | ||
| In women with MFS and aortic root diameters>45 mm, surgery before pregnancy is recommended. 380,424 | I | C |
| In women with LDS with P/LP variants in TGFBR1,TGFBR2, and aortic root diameters≥45 mm, surgery before pregnancy is recommended. 437-439 | I | C |
| In women with nsHTAD with P/LP variants in MYH11, ACTA2, PRKG1, or MYLK, and aortic root diameters≥45 mm, surgery before pregnancy is recommended. ${}^{385,386,440}$ | I | C |
|---|---|---|
| In women with BAV and aortic root or ascending aortic diameter≥50 mm, surgery before pregnancy is recommended. | 1 | C |
| In women without an identifiable P/LP variant with aortic root or ascending aortic diameters≥50 mm, surgery before pregnancy is recommended. | I | C |
| In women with HTAD and aortic arch, descending aortic, or abdominal aortic diameters≥50 mm, surgery before pregnancy should be considered. ${}^{392,443}$ | lla | C |
| In women with LDS with P/LP variants in TGFβ2,TGFβ3, SMAD2, and SMAD3, and aortic root diameters≥45 mm, surgery before pregnancy should be considered. ${}^{437,439}$ | lla | C |
| In women with BAV and root phenotype or family history of aortic aneurysm or dissection, surgery before pregnancy should be considered if the aorta is≥45 mm. | lla | C |
| In women without an identifiable P/LP variant with aortic root or ascending aortic aneurysm≥45 mm, surgery before pregnancy should be considered in the presence of a family history of aortic aneurysm, aortic dissection, uncontrolled arterial hypertension, or on patient's preference. | lla | C |
| In women with MFS and aortic root diameters between 40 and 45 mm, surgery before pregnancy may be considered if risk factors(growth >3 mm/year, family history of aortic dissection) are present. ${}^{444}$ | llb | C |
| In women with LDS with P/LP variants in TGFβFR1 or TGFβ2 and aortic root diameters≥40 mm,surgery before pregnancy may be considered. ${}^{387,437,445,446}$ | llb | C |
| In women with nsHTAD and aortic root diameters≥40-44 mm, surgery before pregnancy may be considered in the genetic variant, family history, and aortic growth rate. ${}^{385,386,440}$ | llb | C |
| Delivery | I | C |
| In women with a aorta <40 mm, vaginal delivery is recommended. | I | C |
| In women with vascular Ehlers-Danlos syndrome, caesarean section at 37 weeks is recommended for obstetrical reasons. | I | C |
| In women with a aorta 40-45 mm, vaginal delivery with epidural anaesthesia and an expedited second stage should be considered. | lla | C |
| In women with an aorta≥45 mm, caesarean section should be considered. | lla | C |
| In women with a aorta 40-55 mm, caesarean section may be considered. | llb | C |
| The use of ergometrine post-delivery is not recommended in women with aortomy. | III | C |
| Cardiac surgery during pregnancy | ||
| Delivery before cardiac surgery should be considered as soon as the foetus is viable, taking gestational age, comorbidities, and the available level of neonatal care into account. ${}^{163,421,435,447}$ | lla | C |
| Cardiac surgery may be considered during pregnancy when conservative and medical therapy has failed, and in situations that threaten the mother's life or that are not amenable to percutaneous treatment. | llb | C |
| ACHD | Maternal Risk | Obstetric and foetal risk | Monitoring | Pregnancy management and delivery |
|---|---|---|---|---|
| Left ventricular outflow tract obstruction(LVOTO) | ||||
| Coarctation of the aorta | ●↑ Complication risk if residual obstruction (gradient >20 mmHg, aortic lumen <12 mm), clinical signs of HF, LVEF<40%, NYHA class>1° ●↑ Risk of aortic dissection (if aneurysm present) ● Uncontrolled hypertension | ●↑ Miscarriage rate453 ● Pre-term birth and low birth weight in 99° | ● Close BP monitoring -also early post-partum ● Pre-pregnancy CMR and treatment of residual lesions 454 | ●Treat hypertensiona ● Consider bed rest, hospital admission and stenting in case of severe symptomatic (re)coarctation (including refractory hypertension or maternal/foetal compromise) 455 ● Vaginal delivery preferred unless aneurysm,HF,severe hypertension |
| ASD | ● Low risk in(un)repaired ASD (if no PAH) 157 Unrepaired ASD: ●↑ Risk of arrhythmia(4%)457 ● Paradoxical embolism (2%-5%)457,458 | ● Rare ${}^{457}$ ● Unrepaired ASD: ●SGA(21%) ● Foetal/perinatal mortality(2%-3%) ● Pre-eclampsia(7%) | Unrepaired and uncomplicated ASD: consider TTE at 28-32 weeks | ● Large and/or haemodynamically significant ASD: closure pre-pregnancy21 ● Unrepaired ASD: ● Consider ASA or prophylactic LMWHd for paradoxical embolism prevention ● Consider device closure in pregnancy only for recurrent stroke on medical therapy |
|---|---|---|---|---|
| VSD and patent ductus arteriosus | Low risk in small or repaired lesions with normal LV and no PAH° | No evidence for↑ risk | Unrepaired and uncomplicated VSD: consider TTE at 28-32 weeks | Vaginal delivery is preferred |
| AVSD | ● Low risk in repaired AVSD without significant residual lesions | ● Offspring mortality in 6% primarily due to recurrence of the congenital heart | Unrepaired and uncomplicated AVSD: consider TTE at 28-32 weeks | ● Residual shunt: see ASD and/or VSD ●↑ AV valve regurgitation and/or HF ● PAH° |
| regurgitation and HF if residual left AV valve regurgitation 459,460 | disease 459 | ↑ FU frequency in significant valve regurgitation, PAH,↓ ventricular function, or↑ | ● Delivery: see ASD and VSD | |
| ●Paradoxical emboli risk in unoperated(partial) AVSD | ||||
| Pulmonary valve and RVOT disease | ||||
| RVOTO/PV stenosis | ● Mild to moderate: low risk ● Severe: RV failure and arrhythmia21 | ● Very low complication: risk 462,463 | ● Mild to moderate: ● TTE at 28-32 weeks ● Severe stenosis: | Pre-pregnancy severe RVOTO(Doppler peak gradient>64 mmHg) or/and any signs of right HF: |
| Continued |
| ● (Bi)monthly TTE (focused on RV function) | ● Intervention (at any level of the RVOT) $^{21}$ Severe symptomatic PV stenosis (not responding to bed rest and conservative management): ● Consider transcatheter balloon valvotomy 21 Consider caesarean section in severe RVOTO/PV stenosis 463 | |||
|---|---|---|---|---|
| PV regurgitation | ●↑ Risk when impaired RV function462 | ● Premature birth463 | Bimonthly TTE if severe PV regurgitation and↓ RV function | |
| Post pulmonary valve replacement (surgical or transcatheter without severe stenosis/regurgitation) | ● Low risk463-466 | ● Very low complication risk462,463 | TTE at 28-32 weeks | Vaginal delivery is preferred |
| Repaired TOF | ||||
| ● Low risk if no residual lesions467 ●↑ Risk of arrhythmia and HF (7%-10%) if pulmonary regurgitation,↓ RV function, severe RVOTO467,468 | ● 15% risk of foetal and obstetric complications, mainly pre-term delivery and low birth weight467 ● Low foetal mortality (0.7%)467 ● Recurrence risk in the offspring in 22q11 deletion syndrome: 50% | ● First trimester and at 28-32 weeks FU with TTE(increase FU depending on functional status) | ● RV failure management: Bed rest and diuretics ● Arrhythmia management8 ● Severe PV stenosis/regurgitation: see above ● Vaginal delivery is preferred | |
| Ebstein anomaly | Ebstein anomaly | Ebstein anomaly | Ebstein anomaly | |
| ● Overall MACE rate in ROPAC 9.9% | ● Foetal risk is related to↓ maternal CO and cyanosis ${}^{3,469}$ : ● Miscarriage ●(Very) high risk when pre-pregnancy HF,cyanosis due to atrial shunt ●↑ Arrhythmia risk due to accessory pathways469 | ● Mild to moderate: baseline and 28-32 weeks assessment with TTE and ECG ● Severe: monthly/ bimonthly TTE& ECG binomally TTE& ECG | ● Severe tricuspid regurgitation with HF can usually be managed medically ● Treat arrhythmias promptly ● Appropriate pre-pregnancy counselling about very high risk of MACE when HF and/or cyanosis | |
| Transposition of the great arteries | ||||
| TGA after atrial switch (Mustard or Sening) and CCTGA | ● High pregnancy risk—MACE rate up to 28% in retrospective series470- lower risk in ROPAC6: Atrial and ventricular arrhythmias in 6.7%,HF in 10% ● Atrial arrhythmias often poorly tolerated ● Baffle leaks may lead to desaturation and paradoxical embolism471 ● Predictors of MACE: symptoms of HF before pregnancy and systemic RV EF <40%6 | ● Foetal risks associated with maternal CO and saturation ● Pre-term birth (21%) ● Low birth weight (18%-21%)6,472,473 ● Rare foetal and neonatal death (1%)474 ● PPH(7%)6 | ● According to anatomical and functional status: TTE every 1-3 months and serial NP ● Holter monitoring if palitations | ● Pre-pregnancy counselling about very high risk if NYHA class III/IV, systemic RV EF <40%, more than moderate tricuspid regurgitation, or treated HF472,473,475 ● Treat HF primarily with medical therapy ● Promptly treat arrhythmia8 ● Consider prolonged post-partum monitoring (48-72 h) and early post-partum FU given the ↑ risk of post-partum HF No clear evidence for long-term deterioration or ↑ cardiovascular events associated with pregnancy 6,476 |
| TGA with arterial switch | ● Low risk ● Ventricular arrhythmias (2.5%-7%),HF(2%-4%)8 | ● Low rate of prematurity or foel total loss ${}^{47,47}$ | ● Consider TTE at 20 weeks ● Intensify if ↓ ventricular function, $\uparrow$ aortic | ● Vaginal delivery is preferred ● Surgery before pregnancy when the neo-aortic root is >55 mm ${}^{21,478}$ or if severe AR ${}^{f}$ |
| regurgitation and ↑ | |||||
|---|---|---|---|---|---|
| Single ventricle physiology palliated with Fontan circulation | |||||
| High pregnancy risk CV events ${}^{479}$ : | ↑Very high foetal complication risk. ${}^{479-483}$ | ● According to anatomical and functional status: TTE | ● Pre-pregnancy counselling about very high risk especially if any risk factor(see maternal risk) | ||
| ● Supraventricular arrhythmias (8%-11%) | ● Low live birth rate(56%) ● Miscarriages (45%-54%) | ● Miscarriages (45%-54%) | ●Pregnancy may be well tolerated and successful in a subset of women with single ventricle and Fontan circulation without complications479,480,485-487 | ||
| ● HF(4%-14%) | ● SGA(20%-55%) | ● SGA(20%-55%) | |||
| Risk factors. ${}^{479}$ | ● Premature birth(59%- 72%) | ● FU in specialized | |||
| ● Oxygen saturations<85% | ACHD centre | Fontan circulation without complications479,480,485-487 | |||
| ● ↓ Ventricular function | ● Neonatal death(5%- | ||||
| ● Arrhythmias | 18%) | ● ASA and/or LMWH(depending on the presence of complications) | |||
| ● Significant valvular disease | Obstetric risk: | ||||
| ● NYHA class III/IV | ● Hypertension(14%) | should be considered in shared decision ${}^{484}$ | |||
| ● FALD | ● PPH(13%) | ● Atrial tachyarrhythmias should be promptly treated with maternal oxygen | |||
| Labourlo delivery with preload dependent | |||||
| EF, ejection fraction; FALD, Fontan-associated liver disease; FU, follow-up; HF, heart failure; iv., intravenous; LMWH, low-molecular-weight heparin; LV, left ventricle; LVEF, left ventricular ejection fraction; LVOTO, left ventricular outflow obstruction; MACE: major adverse cardiovascular events; NP, natriuretic peptide; NYHA, New York Heart | |||||
| Association; PAH, pulmonary arterial hypertension; PPH, post-partum haemorrhage; PV, pulmonary valve; ROPAC, Registryry of Pregnancy and Cardiac Disevorticle, RVOT, right ventricle outflow tract obstruction; SGA, small for gestational age; TGA, transposition of the great arteries; TOF, tetralogy of Fallot; TTE, transthoracic echocardiogram; VSD, ventricle septal defect. | |||||
| ↑ increase ↓ decrease. | |||||
| ${}^{2}$ Refer to Section 12.3 Hypertensive disorders. | |||||
| ${}^{2}$ Refer to Section 12.5.1 Stenotic native valve lesions. | |||||
| ${}^{2}$ Refer to Section 8.3 Bicuspid aortic valve disease. | |||||
| ${}^{2}$ Refer to Section 5 Drugs during pregnancy and lactation. | |||||
| ${}^{2}$ Refer to Section 10 Pregnancy in women with pulmonary arterial hypertension,"Refer to Section 12.52 Regurgitant native valve lesions. | |||||
| ${}^{2}$ Refer to Section 12.4 Arrhythmias. | |||||
| ${}^{2}$ Refer to Section 12.6 Heart failure. | |||||
| ${}^{2}$ Refer to Section 12.4.3 Cardioversion, ablation, and device implantation and implantable cardioverter defibrator management. |
| Recommendations | Classa | Levelb |
|---|---|---|
| Vaginal delivery is recommended in most women with ACHD.161,163 | I | B |
| It is recommended that all women with Fontan circulation who wish to become pregnant receive counselling from the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.479,480,484,486,487 | I | C |
| It is recommended that women with a systemic RV (Mustard/Senning or congenitally corrected TGA), in NYHA class III/IV, systemic ventricular dysfunction (EF <40%), or severe TR wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events.473-475 | I | C |
| In women with significant haemodynamic lesions, discussion about guideline-directed interventions is recommended prior to pregnancy. | I | C |
| It is recommended that women of childbearing potential with PAH wishing to become pregnant are counselled by a multidisciplinary team regarding the very high risk of pregnancy-related adverse events, encouraging a shared decision-making process about whether to become pregnant. 490 | 1 | C |
| It is recommended to provide clear contraceptive advice to women of childbearing potential with PAH:490 | 1 | C |
| For women with PAH requiring pregnancy termination, it is recommended to perform this in PH centres. 490 | 1 | C |
| Right-heart catheterization should be considered during pregnancy if there is diagnostic uncertainty or to assist with important therapeutic decisions. 490 | 11 | C |
| Endothelin receptor antagonists, riocguat, and selexipag are not recommended during pregnancy. 490,508,509 | III | C |
| Medical conditions | Antepartum thrombophylaxis | Post-partum thrombophylaxis |
|---|---|---|
| History of unprovoked VTE |  |  |
| History of hormone-associated VTE |  |  |
| Homozygous factor V Leiden mutation |  |  |
| Heterozygous factor V Leiden mutation |  |  |
| Homozygous prothrombin gene mutation |  |  |
| Heterozygous prothrombin gene mutation |  |  |
| Antithrombin deficiency |  |  |
| Antiphospholipid syndrome |  |  |
| Protein C or S deficiency |  |  |
| Combined thrombophilia |  |  |
| Recommendations | Classa | Levelb | |
|---|---|---|---|
| For pregnant or post-partum women at high risk of VTE, a prophylactic fixed dose of LMWH is recommended over a higher weight-adjusted dose to reduce the risk of VTE. ${}^{519}$ | |||
| In pregnant women or in women in the post-partum period with suspicion of VTE(DVT and/or PE), an immediate formal diagnostic assessment with validated methods is recommended and should not be postponed. ${}^{525,526}$ | B | ||
| In pregnant women or women in the post-partum period with newly diagnosed VTE(DVT and/or PE), the involvement of the Pregnancy | |||
| Heart Team,including a vascular specialist and a haematologist, is recommended. | I | C | |
| In pregnant or post-partum women with a diagnosis of VTE without haemodynamic instability, anticoagulation is recommended by using therapeutic-dose LMWH based on early pregnancy body weight. ${}^{212,532}$ | |||
| In pregnant women or women in the post-partum period with a strong clinical suspicion of VTE, initiation of treatment with a therapeutic-dose of LMWH should be considered until the presence of VTE has been ruled out or confirmed. | lla | C | |
| In pregnant or post-partum women with a diagnosis of acute high-risk PE,d catheter-based reperfusion strategy or systemic thrombolysis should be considered. ${}^{533-535}$ | lla | C | |
| In pregnant or post-partum women with a diagnosis of acute high-risk PE,d surgical thrombectomy may be considered as an alternative to a catheter-based approach or systemic thrombolysis. ${}^{533-535}$ | Ib | C |
| Recommendations | Classa | Levelb |
|---|---|---|
| In pregnant women with chest pain, it is recommended to exclude life-threatening cardiovascular conditions, including PE,ACS(including SCAD), and acute aortic syndrome. ${}^{538,539}$ | C | |
| It is recommended to manage pregnant women with ACS in the same way as non-pregnant women, including diagnostic investigations and interventions. ${}^{557}$ | I | C |
| Low-dose ASA is recommended as the antiplatelet treatment of choice during pregnancy and lactation when single antiplatelet treatment is indicated. ${}^{573-579}$ | I | B |
| If DAPT is required, clopidogrel is recommended as the P2Y12 inhibitor of choice during pregnancy. ${}^{239}$ | I | C |
| The duration of DAPT(aspirin and clopidogrel) in pregnant women undergoing coronary stent implantation is recommended to be the | ||
| same as in non-pregnant women, with an individual approach considering ischaemic risk and delivery-related bleeding risks. ${}^{239}$ | ||
| A vaginal delivery should be considered in most pregnant women with ACS, depending on LV function and clinical symptoms. | IIa | C |
| Continuation of statins may be considered during pregnancy in women with established ASCVD. ${}^{580-582}$ | IIb | C |
| Recommendations | Classa | Levelb | |
|---|---|---|---|
| It is recommended to aim for systolic BP<140 mmHg and diastolic BP<90 mmHg in pregnant women. | 583,585,609 | B | |
| Systolic BP≥160 mmHg or diastolic BP≥110 mmHg in a pregnant woman is an emergency, and treatment in a hospital setting is recommended. | C | ||
| Low-dose aspirin(75-150 mg daily) is recommended in women at moderate or high risk of pre-eclampsia(i.e.at least one high-risk factor or two moderate-risk factors for pre-eclampsia) from weeks 12 to 36/37.610,621,622 | I | A | |
| In women with gestational hypertension, initiation of drug treatment is recommended at systolic BP≥140 mmHg or diastolic BP | I | B | |
| $\geq 90 mmHg$ | |||
| Methyldopa is recommended for the treatment of hypertension in pregnancy. | 623,624 | I | B |
| Labetalol, metoprolol, and dihydropyridine CCBs are recommended for the treatment of hypertension in pregnancy. ${}^{623}$ | I | C | |
| In severe hypertension, drug treatment with i.v. labelatol, urapidil, nicardipine, or oral short acting nifedipine or recommended for acute reduction in blood pressure. ${}^{625,626}$ Intravenous hydralazine is a second-line option. | I | C | |
| In pre-eclampsia associated with pulmonary oedema, nitroglycerine given as an i.v. infusion is recommended. ${}^{627}$ | I | C | |
| In women with pre-eclampsia without severe features, delivery is recommended at 37 weeks. ${}^{620,628}$ | I | B | |
| It is recommended to expedite delivery in women with pre-eclampsia associated with adverse markers such as haemostatic disorders. | ${}^{629}$ | C | |
| In women with gestational hypertension, delivery is recommended at 39 weeks. ${}^{620,628}$ | I | B | |
| Ambulatory BP or home BP monitoring should be considered to exclude white-coat and masked hypertension, which are common in pregnancy. | lla | C | |
| Home BP monitoring may be considered as an adjunct to office BP measurements in pregnant women to detect new-onset hypertension or for monitoring BP control. ${}^{595,596}$ | Illb | B |
| Acute management of SVT and AF | Classa | Levelb |
|---|---|---|
| Immediate electrical cardioversion is recommended for acute treatment of SVT with haemodynamic instability. | 1 | C |
| Vagal nanoeurans and iv.e. adenosine are recommended for conversion of haemodynamically stable supraventricular tachycardias.645 | 1 | C |
| Intravenous beta-blockersc(e.g. metoprolol) are recommended as the first-line option for acute rate control in pregnant women with AF or AF with preserved LVEF and rapid ventricular rate.646 | 1 | C |
| Intravenous digoxin or verapamil(if preserved LVEF) should be considered as a second-line option for initial rate control in pregnant women with AF or AFL and rapid ventricular rate.635 | 1 | C |
| lbutilide or fleacinide may be considered for termination of AF and AFL in pregnant women without structural heart disease.640,647 | 116 | C |
| Long-term management of SVT and AF | ||
| Therapeutic anticoagulation with LMWH is recommended for pregnant women with persistent or permanent AF at elevated | 1 | C |
| thromboembolic risk.636,641 | ||
| Beta-1-selective blockersc are recommended for rate control in pregnant women with AF,AFL,or FAT. | 146,271,648 | 1 |
| Beta-1-selective blockersc or verapamil are recommended for the prevention of SVT in women without pre-excitation on resting | 1 | C |
| ECG.146,268,649 | ||
| Fleacinide or proaphenone are recommended for the prevention of arrhythmias in pregnant women with WPW syndrome. | 1 | C |
| Digoxin or verapamil should be considered for rate control in pregnant women with AF,AFL,or FAT when beta-blockers fail or are not tolerated.146,271,645 | 114 | C |
| Fleacinide, in addition to beta-blockers, should be considered for long-term AF rhythm control in pregnancy.250,268,271,640 | 114 | C |
| Sotalol may be considered for rhythm management of AF and AFL with controlling for pro-arrhythmic risk factors as in non-pregnant women.651 | 116 | C |
| Catheter ablation may be considered in pregnant women with recurrent, long symptomatic SVT, or with contraindications to pharmacological therapies. | 116 | C |
| Recommendations | Classa | Levelb |
|---|---|---|
| Immediate electrical cardioversion is recommended for both unstable and stable ventricular tachycardias. 252 | 1 | C |
| Beta-blockers or verapamil are recommended for the prevention of idiopathic sustained VT. | 1 | C |
| If an ICD, pacemaker, or resynchronization therapy device is indicated during pregnancy, implantation is recommended with optimal radiation protection. 667,675 | 1 | C |
| In idiopathic RVOT-VT, flecanide should be considered if beta-blockers fail, to prevent recurrence. | lla | C |
| Recommendation | Classa | Levelb |
|---|---|---|
| Continuous manual left uterine displacement during CPR in pregnant women (≥20 weeks) with cardiac arrest is recommended to relieve aortocaval compression. 614 | I | C |
| It is recommended to establish i.v.access above the diaphragm to ensure that the i.v. therapy is not obstructed by the gravid uterus. 614 | I | C |
| It is recommended to perform the same chest compressions and defibrillation protocols in pregnant as in non-pregnant women. 554,614,687 | I | C |
| Anterolateral defibrillator pad placement is recommended with the lateral pad placed under the breast. 614,660 | I | C |
| It is recommended that no drugs are withheld in pregnant women with cardiac arrest due to concerns of teratogenicity. 686 | I | C |
| Immediate casearan sea in the site of the arrest should be considered and immediately prepared if ROSC has not been achieved in the mother after 4 min of resuscitative efforts and if the foetus is viable,taking gestational age, comorbidities, and the available level of medical care into account. 614,688,689 | lla | C |
| In pregnant women with asymptomatic congenital | ||
| AV block,normal cardiac anatomy and function,a narrow QRS complex,and ventricular rate | ||
| (≥50 b.p.m.),a prophylactic temporary pacemaker during delivery is not recommended.691 |
| Recommendations | Classa | Levelb |
|---|---|---|
| Intervention is recommended before pregnancy in symptomatic patients with severe aortic stenosis. ${}^{698}$ | C | |
| Intervention is recommended before pregnancy in women with mitral stenosis and a valve area<1.5 cm2. ${}^{698,701,714}$ | C | |
| In pregnant women with symptomatic mitral stenosis or pulmonary hypertension, restricted activities and beta-blockers are recommended. ${}^{20}$ | C | |
| In pregnant women with mitral stenosis, diuretics are recommended when congestive symptoms persist despite beta-blockers. ${}^{20}$ | C | |
| Full therapeutic-dose anticoagulation is recommended in women with mitral stenosis complicated by AF, left atrial thrombus, or prior embolism. | ||
| Surgical treatment is recommended before pregnancy in women with severe aortic or mitral regurgitation with symptoms, impaired ventricular function, or marked ventricular dilatation. | ||
| Diuretics are recommended in pregnant women with regurgitant lesions when symptoms or signs of congestion occur. | C | |
| Intervention should be considered before pregnancy in those with asymptomatic severe aortic stenosis after counselling on the risks and benefits. ${}^{698}$ | C | |
| Percutaneous mitral commissorotomy for mitral stenosis should be considered in pregnant women with severe symptoms or systolic pulmonary artery pressure>50 mmHg despite medical therapy. ${}^{698}$ | lla | C |
| Valve surgery during pregnancy should only be considered when there is a maternal mortality risk and other treatment options have failed. ${}^{421}$ | lla | C |
| In very selected symptomatic pregnant women with severe aortic stenosis not responding to medical therapy, non-surgical options such as balloon valuloplasty or TAVI may be considered. ${}^{716}$ | Ib | C |
| A bioprosthetic valve is recommended (over a mechanical valve) in young women contemplating pregnancy requiring a valve prosthesis. 177 | I | B |
| It is recommended that the type of valve surgery or intervention for a woman contemplating pregnancy is chosen in consultation with the Pregnancy Heart Team. | I | C |
| Women with mechanical heart valves | ||
| It is recommended that a care plan documenting the agreed anticoagulant strategy(including the decision to continue VKAs or converting to therapeutic-dom MHW in the first trimester) is in place for women of childbearing age with an MHV prior to pregnancy or as soon as pregnancy is recognized. 170 | I | C |
| It is recommended that pregnant women with an MHV are managed by the Pregnancy Heart Team. 170 | I | C |
| In pregnant women on VKAs, it is recommended to perform INR monitoring weekly or at a minimum every 2 weeks. | I | C |
| In pregnant women with MHVs on therapeutic-dose LMWH, it is recommended to check peak anti-factor Xa levels and to target levels according to individualized risk. | 1 | C |
| During the second and third trimesters until the 36th week, continuing VKAs should be considered in women with prosthetic heart valves at higher risk of thrombosis. | IIa | C |
| During the second and third trimesters, continuing LMWH with anti-factor Xa level monitoring and dose adjustment may be considered in women at lower risk of thrombosis. | IIb | C |
| LMWH is not recommended when anti-factor Xa level monitoring is not available. | III | C |
| Chronic heart failure | $$\text{Level}^{\text{b}}$$ | |
|---|---|---|
| It is recommended that women with HFREF are advised about the risk of deterioration of cardiac function during pregnancy and peripartum. ${}^{34}$ | C | |
| In pregnant women with HFREF, it is recommended that non-selective beta-blockers are switched to beta-1-selective blockers(metoprolol, bisoprolol) with close maternal and foetal monitoring. ${}^{733,734,738,739}$ | C | |
| Anticoagulation with therapeutic doses of LMWH is recommended in pregnant women with intracardiac thrombus or decreased LV function with EF<35%.216 | ||
| It is recommended to optimize HF guideline-directed medical therapy after delivery,taking contraindicated drugs during lactation into account. ${}^{339,734}$ | l | C |
| Due to the high metabolic demands of lactation, avoiding lactation may be considered in women with severe HF.360,733 | llb | C |
| ACE-Is,ARBs,ARNIs,MRAIs,ivabradine,and SGLT2 inhibitors are not recommended during pregnancy due to adverse foetal effects. | ||
| Acute heart failure | C | |
| Inotropes and/or vasopressors are recommended in pregnant women with cardiogenic shock with levosimendan, dobutamine, and mirinone as recommended agents. ${}^{730}$ | l | C |
| Urgent delivery with caesarean section is recommended in pregnant women with cardiogenic shock as soon as the foetus is viable, taking gestational age, comorbidities, and the available level of medical care into account. ${}^{689}$ | C | |
| Early transfer of pregnant women in cardiogenic shock to a facility providing mechanical circulatory support should be considered. ${}^{345,740}$ | lla | C |
| Preventing lactation may be considered in women with severe HF due to the high metabolic demands of | llb | B |
| Recommendations | Classa | Levelb |
|---|---|---|
| It is recommended to postpone pregnancy until at least 1 year after heart transplantation,taking individual risk factors into account. 275,741 | C | |
| In women with a heart transplant,it is recommended that immunosuppression serum drug levels are monitored during pregnancy every 4 weeks until the 32nd week, then every 2 weeks until the 36th week, then weekly until delivery,and for 6-12 months after delivery to guide dosing. 275 | C | |
| It is recommended to perform weekly monitoring of donor-specific antibodies for at least 6-12 months after delivery. 275,741,749-751 | C | |
| Paternal HLA testing prior to conception should be considered due to the risk of developing donor-specific antibodies. 746,747 | lla | C |
| Mycophenolic acid therapy is not recommended in pregnancy and should be discontinued 6 weeks before conception. 275,741 | III | C |
| It is recommended that pregnant women with cancer | ||
| who require cardiotoxic cancer therapy are jointly | ||
| managed by the Pregnancy Heart Team and the | ||
| cardio-oncology team. | ||
| Cardiac troponin and NP measurements may be | ||
| considered at baseline and during anthracycline | ||
| chemotherapy in pregnant women with | ||
| cancer. 734,756 | ||
| Its recommended to undertake a cardiovascular risk assessment in women with APOs, to recognize and document APOs when CVD risk is evaluated in women, and to provide counselling on the importance of healthy lifestyle choices that optimize cardiovascular health. 771,772 | 1 | B |
| In women with persistent post-partum hypertension beyond 6 weeks to 3 months post-partum, initiation of antihypertensive therapy with reference to lactating status is recommended following current guidelines. 584,602,798 | 1 | B |
| In cases where adoption of healthy lifestyle choices alone is inadequate to control post-partum glucose levels, initiation of pharmacotherapy following current guidelines. 773,774,799 | 1 | C |
| following current guidelines is recommended. 773,774,799 | 1 | C |
| It is recommended that women with a history of GDM undergo a formal oGTT 6-12 weeks post-partum with a repeat assessment at 6-12 months and regular annual follow-up visits to screen for diabetes. 773,774,800 | 1 | C |
| Nifedipine and labelatol (metoprolifol if labelatol is unavailable) are recommended as treatments for uncomplicated post-partum | 1 | C |
| hypertension in the first 6 weeks after delivery. 602,766,767 | ||
| In women with a history of any APO, cardiovascular risk assessment should be considered at 3 months post-partum with repeat assessment at 6-12 months after implementation of appropriate lifestyle interventions, and regular long-term follow-up thereafter. 761,795 | 1 | C |
| Breastfeeding may be considered in order to lower the future cardiovascular risk in women with APOs. | 789,791,792 | llb |
| 4. The Pregnancy Heart Team | ||
| Counselling, pregnancy risk assessment, contraception, assisted reproductive technology, and the involvement of a Pregnancy Heart Team | ||
| It is recommended to perform a risk assessment in all women with CVD of childbearing age using the mWHO 2.0 classification. | 1 | C |
| A discussion by the Pregnancy Heart Team about the high risk of maternal mortality or morbidity and the related high foetal risk is recommended for women with mWHO 2.0 class IV conditions, including a shared decision-making process for pregnancy termination, involving psychological support. | 1 | C |
| It is recommended that women with CVD of mWHO 2.0 class II-III and above are evaluated and managed by a Pregnancy Heart Team from pre-pregnancy onwards through pregnancy and post-partum. | 1 | C |
| It is recommended that women with CVD of mWHO 2.0 class II and above, or those at risk of developing CVD, receive individualized advice to determine the most suitable contraception method, including emergency contraception. | 1 | C |
| Assessment by a clinical geneticist prior to pregnancy is recommended in women fulfilling diagnostic criteria for inherited cardiovascular disease to guide risk stratification and pre-natal genetic testing. | 1 | C |
| Pre-conception genetic counselling is recommended in couples with heritable CVD, whether genetic testing is being considered or not. It is recommended that this counselling is provided by an appropriately trained healthcare professional within a multidisciplinary team that offers psychological support and education to encourage decision-making. | 1 | C |
| It is recommended that single embryo transfer is performed in women with CVD. | 1 | C |
| It is recommended to offer women with CVD access to termination of pregnancy that is tailored to their cardiac condition to minimize the risks of the procedure. | 1 | C |
| Diagnostic methods in pregnancy | ||
| Tranthoracic echocardiography is recommended as first-line imaging tool in any pregnant woman with unexplained or new cardiovascular signs or symptoms. | 1 | C |
| It is recommended to limit exposure to all medical ionizing radiation doses to ALARA levels. | 1 | C |
| It is recommended to keep the radiation dose to the foetus as low as possible(preferably<50 mGy), particularly if the foetus is in the field of view. | 1 | C |
| Timing and mode of delivery | ||
| Vaginal delivery is recommended in most women with CVD. | 1 | B |
| Routine induction of labour prior to 39 weeks is not recommended in women with stable CVD. | III | C |
| It is recommended that the timing of delivery is planned to ensure safe and effective peripartum anticoagulation. | 1 | C |
| It is recommended to discontinue VKAs and start therapeutic-dose LMWH or adjusted-dose i.v. UFH at the 36th week of gestation or 2 weeks before the planned delivery. | 1 | C |
| In women at low risk on therapeutic-dose LMWH, neuraxial anaesthesia and vaginal delivery(or caesarean section for obstetric indications) | 1 | C |
| is recommended 24 h after the last dose of LMWH. | 1 | C |
| In women at high risk, it is recommended to convert LMWH to i.v. UFH at least 36 h prior to delivery and stop the UFH infusion 4-6 h prior to anticipated delivery. The aPTT should be normal before regional anaesthesia. | 1 | C |
| If delivery starts while the mother is on VKAs or<2 weeks after discontinuation of VKAs, caesarean section is recommended for foetal protection. | 1 | C |
| Post-delivery, it is recommended that the decision to restart LMWH or UFH is made after discussion with the Pregnancy Heart Team and the woman who gave birth. | 1 | C |
| It is recommended to postpone the switch from heparin back to oral anticoagulants until 7-14 days post-partum when the wound area has healed, in consultation with the Pregnancy Heart Team. | |||
|---|---|---|---|
| 5. Drugs during pregnancy and lactation | |||
| Direct oral anticoagulants and pregnancy | |||
| DOACs are not recommended during pregnancy. | Ⅲ C | Ⅲ C | |
| 6. Pregnancy in women with cardiomyopathies and primary arrhythmia syndromes | |||
| Cardiomyopathies and pregnancy | |||
| Clinical cardiac surveillance (ECG, echocardiogram, and Holter ECG monitoring) is recommended during pregnancy in women with | 1 C | 1 C | |
| CMPs, depending on individual risk. | 1 | C | |
| Vaginal delivery is recommended in most women with CMPs, unless there are obstetric indications for caesarean section, severe HF (EF <30% and/or NYHA class III/IV), uncontrolled arrhythmias, or severe outflow obstruction (≥50 mmHg) in women with HCM, or in women presenting in labour on VKAs. | 1 | C | |
| In women with DCM and worsening of EF during pregnancy, counselling on the risk of recurrence during a subsequent pregnancy is recommended in all cases, even after recovery of LV function. | 1 | C | |
| It is recommended to use the same risk stratification protocol for ventricular arrhythmias in pregnant women with HCM as for non-pregnant women with HCM. | 1 | C | |
| It is recommended to start beta-blockers in women with HCM who develop symptoms due to outflow tract obstruction or arrhythmia during pregnancy. | 1 | C | |
| It is recommended that women with HCM with symptomatic LV dysfunction (EF <50%) and or severe LVOTO (≥50 mmHg) wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events. | 1 | C | |
| Myosin inhibitors are not recommended in women during pregnancy due to lack of safety data. | Ⅲ | C | |
| Primary arrhythmia syndromes and pregnancy | |||
| Monitoring and treatment of hypokalaemia and hypomagnesiaemia is recommended in pregnant women with primary arrhythmia syndromes suffering from hyperemesis. | |||
| Beta-blockers, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy in women with LQTS. | |||
| It is recommended to continue beta-blocker therapy during lactation in women with LQTS to reduce arrhythmic risk. | |||
| Pre-pregnancy dose beta-blocker of nadolol or propranolol are recommended in women with LQT2, particularly in the post-partum period, which represents a high-risk period for life-threatening arrhythmias. | |||
| Beta-blockers, with pre-pregnancy dose and with nadolol and propranolol as drugs of choice, are recommended during pregnancy and lactation in women with CPVT. | 1 | C | |
| Flecanide,in addition to beta-blockers, is recommended in women with CPVT who experience cardiac events such as syncope, VT, or cardiac arrest, during pregnancy. | |||
| It is recommended that women with CPVT who are stable on beta-blockers (nadolol or propranolol as drugs of choice) and flecanide before pregnancy, continue both drugs also during pregnancy and post-partum. | 1 | C | |
| 7. Peripartum cardiomyopathy | |||
| Counselling for women with PPCM about the risk of recurrence during a subsequent pregnancy and about contraception is recommended in all cases, even after recovery of LV function (LVEF >50%). | |||
| 8. Pregnancy in women with aortopathies | |||
| It is recommended that women with aortic disease have counselling about the risk of aortic dissection in pregnancy and the post-partum period. | |||
| It is recommended that women with aortic disease have counselling about the risk of aortic dissection in pregnancy and the post-partum extended Pregnancy Heart Team considering the presence and type of genetic variant, aortic morphology, growth rate, and aetiology of aortic dissection. | |||
| Aortic dissection. | Aortic dissection. | Aortic dissection. | Aortic dissection. |
| It is recommended that women with vascular Ehlers-Danlos syndrome wishing to become pregnant are counselled regarding the very high risk of pregnancy-related adverse events by a multidisciplinary team, considering family history, genetic variant, and previous vascular events. | |||
| Imaging of the entire aorta (CT or CMR) is recommended before pregnancy in women with known or suspected aortic disease. | |||
| In women with aortic dilatation related to BAV, imaging (with TTE, and CMR/CT if needed) of the aortic root, ascending aorta, and descending aorta (to rule out coarction) is recommended before pregnancy. | |||
| In women with low-risk aortic disease (mWHO 2.0 classes II and II-III), one-time echocardiographic imaging between 20 and 30 weeks of gestation and imaging at 6 months post-partum is recommended. |
| In women with moderate to high-risk aortic disease (mWHO 2.0 classes III and IV), repeated echocardiographic imaging every 4-12 weeks (depending on diagnosis and severity of dilatation) is recommended during pregnancy and until 6 months post-partum. | I | C |
|---|---|---|
| CMR (without gadolinium) imaging of the entire aorta is recommended in pregnant women at risk of or with known aortic dilatation who have not had recent pre-pregnancy cross-sectional imaging. | I | C |
| It is recommended that centres managing pregnancies in women with moderate to high-risk aortic disease (mWHO 2.0 class III/IV) can provide cardiovascular surgery in case of peripartum adverse events. | I | C |
| When a women with known aortic dilatation, history of dissection, or P/LP variant associated with aortic disease becomes pregnant, strict and individualized BP control is recommended. | I | C |
| Beta-blocker therapy throughout pregnancy and in the post-partum period is recommended in women with MFS and other HTADs.Celiprolol is recommended in women with vascular Ehlers-Danlos syndrome during pregnancy and lactation. | I | C |
| It is recommended that indications for pre-pregnancy aortic root and/or ascending aortic surgery are guided by aortic morphology, underlying pathology,family history,genetic variant,previous vascular events,and patient's preference. | I | C |
| In women with MFS and aortic root diameters>45 mm,surgery before pregnancy is recommended. | I | C |
| In women with LDS with P/LP variants in TGFBR1,TGFBR2,and aortic root diameters≥45 mm,surgery before pregnancy is recommended. | I | C |
| In women with nhsHTAD with P/LP variants in MYH11, ACTA2, PRKG1, or MYLK, and aortic root diameters≥45 mm, surgery before pregnancy is recommended. | I | C |
| In women without an identifiable P/LP variant with aortic root or ascending aortic diameters≥50 mm, surgery before pregnancy is recommended. | I | C |
| In women with a aorta<40 mm, vaginal delivery is recommended. | I | C |
| In women with vascular Ehlers-Danlos syndrome, caesarean section at 37 weeks is recommended for obstetrical reasons. | I | C |
| The use of ergometrine post-delivery is not recommended in women with aortopathy. | III | C |
| 9. Pregnancy in women with known congenital heart disease | ||
| Vaginal delivery is recommended in most women with ACHD. | I | B |
| It is recommended that all women with Fontan circulation who wish to become pregnant receive counselling from the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events. | I | C |
| It is recommended that women with a systemic RV (Mustard/Senning or congenitally corrected TGA), in NYHA class III/IV, systemic ventricular dysfunction(EF<40%), or severe TR wishing to become pregnant are counselled by the Pregnancy Heart Team regarding the high risk of pregnancy-related adverse events. | I | C |
| 10. Pregnancy in women with pulmonary arterial hypertension |
| In pregnant women with symptomatic tstenosis or pulmonary hypertension, restricted activities and beta-blockers are recommended. | 1 | C |
|---|---|---|
| In pregnant women with mitral stenosis, diuretics are recommended when congestive symptoms persist despite beta-blockers. | I | C |
| Full therapeutic-dose anticoagulation is recommended in women with mitral stenosis complicated by AF, left atrial thrombus, or prior embolism. | I | C |
| Surgical treatment is recommended before pregnancy in women with severe aortic or mitral regurgitation with symptoms, impaired ventricular function, or marked ventricular dilatation. | I | C |
| Diuretics are recommended in pregnant women with regurgitant lesions when symptoms or signs of congestion occur. | I | C |
引用 / 出处
2025 ESC指南：心血管疾病和妊娠的管理. 2025.