2025 ESC指南：心肌炎和心包炎的管理

指南心血管内科· 心力衰竭 · 2025

Tables of Recommendations

evaluation of myocarditis and pericarditis(see Evidence Table 1) $\ldots$ 28

Recommendation Table 2- Recommendations for genetic testing

(see Evidence Table 2) $\ldots$ 30

ESC Guidelines

Recommendation Table 3-Recommendations for the use of cardiovascular magnetic resonance imaging(see Evidence Table 3)... 32 Recommendation Table 4-Recommendations for computed tomography(see Evidence Table 4)32 Recommendation Table 5-Recommendations for nuclear medicine(see Evidence Table 5)33.Recommendation Table 6-Recommendations for endomyocardial biopsy(see Evidence Table 6)42 Recommendation Table 7-Recommendations for autopsy (see Evidence Table 7)35 Recommendation Table 8-Recommendations for electro-anatomical mapping(see Evidence Table 8)36 Recommendation Table 9-Recommendations for medical therapy in myocarditis(see Evidence Table 9)39 Recommendation Table 10-Recommendations for medical therapy in pericardits(see Evidence Table 10)42 recommendation Table 11-Recommendations for interventions techniques including circulatory support in myocarditis(see Evidence Table 11)42 recommendation Table 12-Recommendations for interventional techniques in pericardits(see Evidence Table 12)43 Recommendation Table 13-Recommendations for surgical therapy(see Evidence Table 13)44 Recommendation Table 14-Recommendations for management of arrhythmias and prevention of sudden cardiac death in myocarditis(see Evidence Table 14)45 recommendation Table 15-Recommendations for risk stratification, complications, and outcomes of inflammatory mypericarditis(see Evidence Table 15)47 Recommendation Table 16-Recommendations for giant-cell myocarditis(see Evidence Table 16)51 Recommendation Table 17-Recommendations for myocarditis in sarcoidosis(see Evidence Table 17)52 Recommendation Table 18-Recommendations for immune checkpoint inhibitor-associated myocarditis(see Evidence Table 18)55 Recommendation Table 19-Recommendations for inflammatory cardiomyopathy(see Evidence Table 19)56 Recommendation Table 20-Recommendations for tuberculous pericarditis(see Evidence Table 20)57 Recommendation Table 21-Recommendations for neoplastic pericardial involvement(see Evidence Table 21)58 Recommendation Table 22- Recommendations for post-cardiac injury syndrome(see Evidence Table 22)59 Recommendation Table 23- Recommendations for purulent pericarditis(see Evidence Table 23)60 Recommendation Table 24-Recommendations for constrictive pericarditis(see Evidence Table 24)64 Recommendation Table 25- Recommendations for pregnancy,lactation, and reproductive issues(see Evidence Table 25)65 Recommendation Table 26-Recommendations for physical activity and myocarditis/pericardits(see Evidence Table 26)65 Recommendation Table 27- Recommendations for multidisciplinary teams in mypericardial syndromes(see Evidence Table 27)66

List of tables

Table 1 Classes of recommendations 7 Table 2 Levels of evidence 8

Table 3 Terminology and stages $\ldots$ 11

Table 4 Diagnostic criteria and classification for inflammatory myopercidial syndrome 13

Table 5 Histopathological criteria for myocarditis 13

Table 6 Red flags for the clinical diagnosis of myocarditis and pericarditis

Table 7 Clinical risk stratification to guide work-up in inflammatory mypericardial syndrome 16

Table 8 Causes of cardiac tamponade 25

Table 9 Basic and advanced level assessment. 29

Table 10 Classification of pericardial effusion 31

Table 11 Parameters for reporting by endomyocardial biopsy 35

Table 12 Therapy for specific forms of myocarditis 37

Table 13 Specific initial dosing and duration of therapy for acute and recurrent pericarditis 40

Table 14 Tapering of corticosteroids 40

Table 15 Follow-up in inflammatory mypericarditis syndrome after discharge $\ldots$ 47

Table 16 Indicators of non-wiral aetologies and complications

(high-risk features or red flags in acute pericarditis)48

Table 17 Echocardiographic signs of cardiac tamponade 62

Table 18 Definitions and therapy of main constructive pericardial

syndromes 63

Table 19'What to do' and'What not to do' $\ldots$ 69

List of figures

Figure 1 Central illustration of the ESC guidelines on myocarditis and

pericarditis $\ldots$ 9

Figure 2 Paradigm change in the clinical diagnosis of myocarditis 12

Figure 3 Stages of inflammatory myopericardial syndrome $\longdots$ 12

Figure 4 Diagnostic criteria by cardiovascular magnetic resonance

based on the updated Lake Louise criteria 14

Figure 5 Diagnostic algorithm and triage for inpatient myocarditis $\longdots$ 17

Figure 6 Diagnostic algorithm and triage for outpatient myocarditis 18

Figure 7 Diagnostic algorithm and triage for pericarditis

Figure 8 Spectrum of myocarditis presentations and outcomes $\ldots$ 20

Figure 9 Diagnostic algorithm for acute chest pain presentation 21

Figure 10 Diagnostic algorithm for acute heart failure presentation.. 23

Figure 11 Diagnostic algorithm for arrhythmia presentation 24

Figure 12 Management of cardiac tamponade 26

Figure 13 Management of constriction 27

Figure 14 The different courses of inflammatory myopericardial syndrome and the interplay between genetic background

inflammation and autoimmunity beyond the initial infectious trigger. 31

Figure 15 Histopathological findings in myocarditis 34

Figure 16 Proposed algorithm of medical therapy for pericarditis in adults(not including interventional therapies and pericardiectomy).. 41

Figure 17 Follow-up and risk stratification after acute myocarditis with arrhythmic presentation 48

Figure 18 Stages of tuberculosis pericarditis 57

Figure 19 Triage and management of pericardial effusion $\ldots$ 61

Figure 20 Multidisciplinary teams for inflammatory myopericardial

syndrome 67

Abbreviations and acronyms

ACC 7

ACS Acute coronary syndrome

ESC Guidelines

ADA

Adenosine deaminase

Atrial fibrillation

Acute myocardial

Acute myocardial infarction

Acute pericarditis

ARVC

Arrhythmogenic right ventricular cardiomyopathy

ATG

Anti-thymocyte globulin

AVB

Atrioventricular block

B19V

Parvovirus B19

CAD

Coronary artery disease

Chagas disease

Confidence interval

Creatinine kinase

CK-MB

Creatinine kinase muscle-brain type

CMP

Cardiomyopathy

CMR

Cardiovascular magnetic resonance

CMV

Cytomegalovirus

COVID-19

Coronavirus disease 2019

Constrictive pericarditis

Cardiopulmonary bypass

CRT

Cardiac resynchronization therapy

Cardiac sarcoidosis

Computed tomography

CTLA-4

Cytotoxic T-lymphocyte antigen 4

CTP

Cardiac tamponade

DCM

Dilated cardiomyopathy

DNA

Deoxyribonucleic acid

DSP

Desmoplakin

EAM

Electro-anatomical mapping

EBV

Epstein-Barr virus

ECG

Electrocardiogram

ECP

Effusive-constrictive pericarditis

ECV

Extracellular volume

Ejection fraction

EGPA

Eosinophilic granulomatosis with polyangitis

Eosinophilic myocarditis

Endomyocardial biopsy

European Society of Cardiology

ESR

Erythrocyte sedimentation rate

FDG-PET

Fluorodeoxyglucose positron emission

tomography

Fulminant myocarditis

Familial Mediterranean fever

GCM

Giant-cell myocarditis

GDMT

Guideline-directed medical therapy

GLS

Global longitudinal strain

HAART

Highly active antiretroviral therapy

HCM

Hypertrophic cardiomyopathy

HCV

Hepatitis C virus

HES

Hypereosinophilic syndrome

Heart failure

HHV-6

Human herpesvirus 6

HIV

Human immunodeficiency virus

Hazard ratio

hs-Tnl

High-sensitivity troponin I

hs-TnT

High-sensitivity troponin T

Heart transplantation

IABP

Intra-aortic balloon pump

ICD

Implantable cardioverter-defibrillator

ICI

ICL

IFN

IL-1

IL-1RA

IL-1RL1

IMPS

i.v.

IVIG

LAG-3

LGE

LVAD

LVEF

MACE

MCS

miRNAs

NDLVC

NLRP3

NSAID

NSVT

NT-proBNP

peptide

LP/PL

PaM

PCIS

PCR

PD-1

PD-L1

Peff

PPCM

PPS

PVS

RAP

RCM

RCT

RNA

SARS-CoV-2

SCD

SLE

SSc

TDI

TNF-α

TRAPS

TTE

uFN-y

Immune checkpoint inhibitor

Intensive care unit

Interferon

Interleukin-1 receptor antagonist

IL-1 receptor-like 1

Inflammatory myopericardial syndrome

Intravenous

Intravenous immunoglobulins

Jugular venous pressure

Left atrial

Lymphocyte activation gene 3

Lyme carditis

Late gadolinium enhancement

Lake Louise criteria

Lymphocytic myocarditis

Left ventricle

Left ventricular assist device

Left ventricular ejection fraction

Major adverse cardiac events

Mechanical circulatory support

MicroRNAs

Non-dilated left ventricular cardiomyopathy

NLR family pyrin domain containing 3

Non-steroidal anti-inflammatory drug

N-terminal prohormone of brain natriuretic

peptide

Odds ratio

Pathogenic/likely pathogenic

Pregnancy-associated myocarditis

Post-cardiac injury syndrome

Programmed cell death protein 1

Programmed death ligand 1

Pericardial effusion

Paritarmum cardiomyopathy

Post-pericardiomy syndrome

Programed ventricular stimulation

Rheumatoid arthritis

RAP Right

Restrictive cardiomyopathy

Randomized controlled trial

Ribonucleic acid

Recurrent pericarditis

Severe acute respiratory syndrome coronavirus 2

Sudden cardiac death

Systemic lupus erythematosus

Systemic sclerosis

Tuberculosis

Tissue Doppler imaging

Task Force

Tumour necrosis factor alpha

TRAPS our necrosis factor receptor-associated

periodic syndrome

TTE Transthoracic echocardiography

Unstimulated interferon gamma

Ventricular arrhythmias

ESC Guidelines

VA-ECMO

VAD

Veno-arterial extracorporeal membrane oxygenation

Ventricular assist device

Ventricular fibrillation

Ventricular tachycardia

WCD

Wearable cardioverter-defibrillator

Wall motion abnormalities

1. Preamble

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

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

This guideline updates and replaces the previous version of the ESC Guidelines on pericarditis from 2015. For the first time it also covers myocarditis. This Task Force was selected by the ESC to include profes-sionals involved with the medical care of patients with this pathology and to include patient representatives and methodologists. The selec-tion procedure included an open call for authors and aimed to include

members from across the whole of the ESC region and from relevant ESC Subspecialy 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 in-cluding assessment of the risk-benefit ratio. Recommendations are based on major randomized trials and relevant systematic reviews 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 diagno-sis 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 recommen-dation and the level of evidence supporting 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 reinforce transparency in the guidelines development process. The ta-bles are published in their own section of ESC Guidelines and reference specific recommendations tables.

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

Table 1 Classes of recommendations

![Functions of recommendations\nClass I\nClass I\nEvidence and/or general agreement\nIs recommended or is indicated\nClass I\nConflicting evidence and/or a divergence of opinion about the usefulness/\nclass II\neffacy of the given treatment or procedure.\nClass II\nClass Ila\nWeight of evidence/opinion is in favour of usefulness/efficacy.\nUsefulness/effacy is less well established by evidence/opinion.\nClass III\nEvidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases\nShould be recommended\nIvsan\n](2/aj0YEe4oUhYkBdfpda0fYP/figure4768659f507040c2923740ba76f4d83f_0_22.png) ESC Guidelines

Table 2 Levels of evidence

|Level of evidence A|Data derived from multiple randomized clinical trials or meta-analyses.| |---|---| |Level of evidence B|Data derived from a single randomized clinical trial or large non-randomized studies.| |Level of evidence C|Consensus of opinion of the experts and/or small studies, retrospective studies, registries.|

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 de-rived entirely from the ESC with no involvement of the healthcare industry.

The CPG Committee supervises and co-ordinates 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 review 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 ap-propriate revisions, the Task Force and the CPG Committee members approve 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

Myocarditis and pericarditis are inflammatory diseases of the myocar-dium and pericardium, respectively, with potential overlap. These are the first ESC clinical practice guidelines covering the whole spectrum of these diseases.

Herein, the Task Force(TF) introduces the term‘inflammatory myo-pericardial syndrome'(IMPS). IMPS is an umbrella term during the initial

diagnostic process until a final diagnosis is made(Figure 1). It reflects the possible myocarditis-percarditis overlap, aiming to increase the aware-ness of the spectrum of disease, and to allow timely diagnosis and better management.IMPS ranges from isolated myocarditis to isolated pericar-ditis through mixed forms with possible reciprocal involvement, such as mypericarditis and perimocarditis. Both terms are commonly used in the medical literature, and defined in the 2015 ESC Guidelines for the diagnosis and management of pericardial diseases(see Section 8).

The rationale for the introduction of IMPS is that myocarditis and pericarditis have similar aetologies and are anatomical contiguous structures with possible secondary involvement.

The field has experienced rapid growth, with position statements proposed by different cardiac societies. 6-10 In the past, several consen-sus statements were provided, usually defining a proven myocardial based on endomyocardial biopsy(EMB). Endomyocardial biopsy is able to detect the histological type, can identify some specific aetiolo-gies, and can help to differentiate from non-inflammatory cardiomyop-athies(CMPs).10 But nowadays multimodality imaging has become a cornerstone for the diagnosis of myocardial and pericardial inflamma-tion and cardiovascular magnetic resonance(CMR) plays a crucial role, as reported in other ESC guidelines ${}^{11-13}$ (Figure 2).

The aim of these guidelines is to provide evidence-based guidance for clinical management of IMPS, to guide clinicians of all subspecialties from a clinical point of view, and to ensure qualified shared decision-making with patients(see Section 13 and Supplementary data online,Section 8).

2.1. What is new

Guidelines on pericarditis have been published twice before, ${}^{1,15}$ while myocarditis will be covered for the first time in a guideline. The TF be-lieves that combined guidelines with the recognition of the spectrum of disease are a step in a new direction, enabling a paradigm shift towards therapy based on the combined input from experts in inflammatory diseases of the myocardium and pericardium, with the support of a multidisciplinary team. In order to improve the awareness of the spec-trum of disease, a new category,‘inflammatory myopericardial syn-drome(IMPS)', will be introduced as an umbrella term to increase the understanding of the potential myocarditis-pericarditis overlap.

![Esc Guidelines\n永brella: IMPS- The spectrum of the inflammatory mypericardial syndrome\nMyopericarditis/Perimyocarditis\nPericarditis\nMyocarditis\nClinical classification\nAcute\nSubacute\nChronic\nRecurrent\nRemission with/without residuals\n<1 month\n>3months\nCommon aetologies\nInfectious\nNon-infectious\nViruses\nBacteria\nParasites\nAutoinflammatory Autoimmune\nGenetic conditions\nDrugs\nCancer-related\nClinical presentation\nOligosymptomatic\nChest pain\nArrhythmias\n(Acute)Heart failure\nAborted SCD\nSCD\nInitial IMPS assessment\nClinical history/ symptoms\nPhysical exam\nVital signs\nECG\nLab values\nEchocardiography\nRule out obstructive coronary artery disease- according to clinical likelihood/probability\nLow\nModerate\nHigh\nCoronary computed tomography\nCoronary angiography\nRisk profile and risk - adjusted assessment\nLow risk\nIntermediate risk\nHigh risk\nCardiovascular magnetic resonance\nInvasive procedures(EMB)\nFunction\nMyocardial involvement\nPericardial involvement\nHistopathology\nFurther assessment(if warranted)\nSearch for aetiology\nMultimodality imaging\nElectroanatomical mapping\nFinal diagnosis\nMyopericarditis/Perimyocarditis\nMyocarditis\nESC\nTherapy-dependent on final diagnosis\nand risk/complications\n](2/aj0YEe4oUhYkBdfpda0fYP/figurea04b7b045ba04f13a2a8b3d274453eea_0_0.png) 10

ESC Guidelines

![Definite\nPossible\nUnlike/rejected\nEMB-\nor CMR-proven\nEMB and CMR\nwith uncertain results\nClinical\n2025\nCMR + clinical\n2021/2023\n2013\nProven\nConfirmed\nSuspected\n](2/aj0YEe4oUhYkBdfpda0fYP/figure2127179e45c34ffc80ef949dd12d6684_0_2.png) Figure 2 Paradigm change in the clinical diagnosis of myocarditis. CMR, cardiovascular magnetic resonance; EMB, endomyocardial biopsy. Both EMB and CMR can provide a definitive clinical diagnosis but with different indications. Details are given in Section 5.2013 Reference: Caforio et al. ${}^{10}$ 2021 and 2023 References: Keren et al., Law et al.6.14

It is introduced as an entering diagnostic term to lead to a tailored work-up and individualized therapy. Patient-oriented case management is pro-posed in different settings such as diagnosis and therapy, as well as return to work and play avoiding strict time definitions, since the remission path-way differs from patient to patient. In addition, a novelty in the field of IMPS is the improved knowledge on its possible genetic background and its link to specific inherited CMPs. Furthermore, a paradigm shift will be introduced in its diagnostic management. This is reflecting the new capabilities of multimodality imaging, especially CMR, as it has chan-ged clinical workflow during recent years. A similar change was intro-duced in the American College of Cardiology(ACC) consensus statement in 2024.9 Endomyocardial biopsy has its place and is needed if specific decisions are warranted.

In comparison with the last ESC Guidelines for the diagnosis and management of pericardial diseases, ${}^{1}$ the current understanding

of the pathogenesis of pericarditis has greatly improved with new evi-dence on the importance of the interplay between inflammation and autoinflammatory mechanisms, the role of genetic background, and immune responses in patients with multiple recurrences. The identi-fication of a positive family history, a poor response to colchicine, and a clinical presentation with an inflammatory or non-inflammatory phenotype are useful tools to guide the selection of patients for gen-etic testing and specific pharmacological options. A new class of drugs targeting interleukin-1(IL-1), the so-called anti-IL-1 agents, has be-come available and is used in recurrent cases with a poor response to other conventional therapies. Nevertheless, we need to further im-prove our understanding of the pathogenesis of non-inflammatory dis-ease forms.

Moreover, diagnostic capabilities have increased, thanks to the role of multimodality imaging, allowing improved diagnostic accuracy and

ESC Guidelines

individualized duration of therapies according to clinical and imaging findings.

The TF recommends establishing a multidisciplinary IMPS team to ensure optimal patient care in complicated cases.

We firmly believe that recognizing IMPS will enhance the under-standing of these inflammatory conditions and hope it will inspire fur-ther research to advance personalized diagnostic and therapeutic approaches.

3. Epidemiology, classification,stages, diagnostic criteria and aetiology

3.1. Epidemiology

Population-based studies of the incidence or prevalence of IMPS are limited, and most epidemiological studies assess disease burden and sequelae in selected patient groups, such as those admitted to hos-pital. However, such studies might underestimate the true disease burden.For example, the rate of patients diagnosed with acute myo-carditis(AM) increases from 5% to 13% with the use of CMR among patients with angina-like symptoms and increased high-sensitivity troponin T(hs-TnT).16 A different registry reported an incidence of 6.3-8.6 per 100 000 inhabitants, mostly in young men.17 The cur-rent global burden of cardiovascular disease data reports a preva-lence of 4.2-8.7 per 100 000 in the age range between 35 and 39 years.18 Men and younger patients are more likely to be diag-nosed, although this could reflect the diagnostic bias towards these patient groups.19

In children<2 years of age, the sex distribution is balanced; in ado-lescents there is a male prevalence(about two-thirds of cases),20,21 which is also maintained in adult patients, suggesting the importance of hormonal factors.

The incidence of acute pericarditis(AP) is estimated to be about 3-32 cases per 100000 person-years.22,23 Similar to myocardits, men and younger individuals are more likely to be diagnosed. Recurrence occurs in about 20%-30% of patients within 18 months after a first episode of AP.24 The recurrence rate increases up to 50% after the first recur-rence.25 Pericarditis is diagnosed in 0.2% of all cardiovascular in-hospital admissions and is responsible for 5% of emergency room admissions for chest pain.23 In the observational Epidemiologie de la Douleur Thoracique(EPIDOULTHO) study,3% of patients received a final diag-nosis of IMPS.26

3.2. Classification and stages

The field of IMPS gained increasing awareness and interest during the coronavirus disease 2019(COVID-19) pandemic.27 Research in the field of all forms of IMPS has a long history, and several terminologies exist. This is also reflected in the definition of stages. We are proposing a terminology from a clinical point of view with the intention of guiding the appropriate management of patients(Table 3). In addition, time frames for the stages(acute, subacute, and chronic) are suggested to be used for myocarditis and pericarditis. However, it is not always pos-sible from a clinical point of view to identify the disease onset, for in-stance in subacute cases.1

IMPS is characterized by different stages(see Figure 3). The course of the disease differs among patients. A patient may recover completely without any residuals, but others may develop complications, in some

Table 3

|Terminology|Definition| |---|---| |IMPS|Umbrella term for inflammatory myocardial and pericardial syndromes| |Myopericarditis|Predominant pericarditisa| |Perimyocarditis|Predominant myocarditisb| |Acute myocarditis|Duration of symptoms ≤4 weeks Fulminant if: · Acute onset28 and haemodynamically unstable patients requiring inotropes or mechanical circulatory support| |Complicated myocarditis|AM and≥1 of the following:28| |Complicated myocarditis|● LVEF<50% on echocardiogram| |● Sustained ventricular arrhythmias|| |● Sustained ventricular arrhythmias|● Advanced heart block| |● Heart failure|| |● Cardiogenic shock|| |Duration of symptoms≤4 weeks|| |Duration of symptoms>4 weeks to ≤3 months|| |Subacute/incessant|Duration of symptoms>4 weeks to ≤3 months| |Chronic myocarditis/|Duration of symptoms>3 months| |pericarditis|Chronic myocarditis in association with cardiac| |cardiomyopathy|dysfunction and ventricular remodelling with clinical phenotype of hypokinetic, either dilated or non-dilated cardiomyopathy with/without arrhythmogenic substrate| |Recurrent myocarditis/ pericarditis|New symptoms or disease activity after clinical remission| |Recurrent myocarditis/ pericarditis|Regression/absence of symptoms, normalization of ECG, biomarkers, imaging abnormalities(echocardiography and CMR)| |Remission with residuals|Regression/absence of symptoms, persistence| |Remission with residuals|of abnormalities on ECG, biomarkers and/or imaging(functional and/or structural abnormalities in echocardiography or CMR)|

AM,acute myocarditis; CK-MB, creatine kinase muscle-brain type; CMR, cardiovascular resonance; ECG, electrocardiogram; IMPS, inflammatory myperocardial syndrome; LVEF, left ventricular ejection fraction.

4 Patients with definite criteria for pericarditis and elevated biomarkers of myocardial injury(high-sensitivity troponin I or T, CK-MB fraction) without newly developed regional or global impairment of left ventricular function in echocardiography or CMR.

bPatients with definite criteria for pericarditis and elevated biomarkers of myocardial injury(high-sensitivity troponin I or T, CK-MB fraction) with newly developed regional or global impairment of left ventricular function in echocardiography or CMR.Cnlessant/ongoing pericarditis: the term incessant pericarditis describes patients with persistent symptoms without a symptom-free interval of>4 weeks despite full-dose guideline-directed medical therapy(including corticosteroids), or those relapsing early during the tapering.

persistent symptoms without a symptom-free interval of>4 weeks despite full-dose guideline-directed medical therapy(including corticosteroids), or those relapsing early during the tapering.

cases leading to death. Patients may not experience every stage.Complete remission can occur at every timepoint. However, a deep understanding of the respective stages is essential for appropriate therapeutic guidance.

ESC Guidelines

![Acute stage <1 month\nSubacute stage\nChronic stage >3 months\nAcute stage\n<1 month\n1-3 months\nCardiotropic\nand\nvasculotropic\ninmate immune\nirnate immune\nviruses\nresponse\nAdaptive\n(vg. viral)\nimmune response\nIndirect damage\nViral persistence with chronic\ninflammation and/or fibrosis or recovery\nvuses\nirnase response\nNoxa: any agent\ncapable of injuring\nthe myopericardium\nGenetic\nsusceptibility\nOR\nRemission with\nDilated\nConstrictive\nviopropine and/or\ncardiomyopathy\npericarditis\nwithout residuals\nintermission with\nImbalance of pro-and\nanti-inflammatory cytokines\nNon-infectious\n(e.g.autoimmune\nAutoreactive T-cells\ntoxins etc.)\nAutantibodies\nInfectious agent\nCellular infiltration\nY(Anti-viral) antibodies\nMyo-and/or pericardial injury\nESC\n](2/aj0YEe4oUhYkBdfpda0fYP/figure8e187bb9b1bc470399b3370b24520727_0_2.png) Figure 3 Stages of inflammatory myopericardial syndrome. AHA, anti-heart antibodies; AIDA, anti-intercalated disc antibodies.

3.3. Diagnostic criteria

After the original proposed diagnostic criteria from the consensus paper in 2013, 10 multimodality imaging, in particular CMR, has made a clinical,non-invasive diagnosis of myocarditis feasible. In accordance with the paradigm change(Figure 2), the TF proposes new diagnostic criteria and a new classification, following the system introduced in the 2023 ESC Guidelines for the management of endocarditis(Table 4).29 This clinically driven approach is based on a clinical presentation, with additional support-ive findings, and positive CMR or EMB for myocarditis. Histopathological criteria and updated CMR Lake Louise criteria(LLC)30 are given in Table 5 and Figure 4, respectively. Similarly, diagnosis of pericarditis can be made with a clinical presentation, and more than one additional criterio.1ion. Cardiovascular magnetic resonance can also provide the non-invasive confirmation of the presence of pericarditis beyond clinical criteria.

3.3.1. Diagnostic criteria for myocarditis

Myocarditis can be clinically diagnosed as definite/possible with an appropriate clinical presentation and additional criterion, including

CMR-proven or EMB-proven result(see details in Table 4). The add-itional criteria include common parameters in basic work-up, such as an electrocardiogram(ECG), which may show unspecific changes, in-cluding the whole spectrum of presentations from mimicking a myocar-dial infarction with ST elevation in non-coronary distribution, as well as rhythm abnormalities, or findings in echocardiography(see Section 5.5).Laboratory analysis of serum biomarkers usually shows elevation of markers of myocardial lesion, such as hs-TnT or high-sensitivity tropo-nin I(hs-TnL). Biomarkers of heart failure(HF)(such as N-terminal pro-hormone of brain natriuretic peptide, NT-proBNP) are also needed to identify the severity of the disease, and suggest myocardial involvement.Depending on the individual case and risk(see Section 4), definitive diagnosis of myocarditis can be based on CMR(Figure 4) or EMB(Table 5).For EMB analysis quantitative immunohistochemistry criteria for inflammatory cells in lymphocytic myocarditis(LM) are under devel-opment. Asymptomatic cases may exist, e.g. vaccine- or drug-related cases, such as immune checkpoint inhibitor(ICI)-induced myocarditis,and are often underdiagnosed.

ESC Guidelines

Table 4 Diagnostic criteria and classification for inflammatory myopericardial syndrome

|IMPS|IMPS|IMPS|IMPS| |---|---|---|---| |If diagnostic criteria for myocarditis and/or pericarditis are fulfilled ${}^{8}$|||| |Definite|Myocarditis|Pericarditis|| |Definite|Clinical presentation ${}^{b}$ and CMR- or EMB-proven|Clinical presentation ${}^{b}$ with>1 additional criterion|| |Possible|Clinical presentation ${}^{b}$ with at least 1 additional criterion CMR- or EMB-uncertain or not available|Clinical presentation ${}^{b}$ with 1 additional criterion|| |Unlikely/rejected|Only clinical presentation ${}^{b}$ without additional criteria|Only clinical presentation ${}^{b}$ without additional criteria|| |Additional criteria beyond clinical presentations ${}^{b}$|||| |Myocarditis Pericarditis|||| |Clinical ${}^{b}$|Non-specific findings|Pericardial rubs|| |ECG ${}^{c}$|ST-T changes|PR depression,widespread ST-segment elevation|| |Biomarkers|Troponin elevation|C-reactive protein elevation|| |Imaging ${}^{d}$|Abnormal strain, wall motion,reduced EF Myocardial oedema and/or LGE(CMR findings)|New or worsening pericardial effusion Pericardial oedema and/or LGE(CMR findings)||

CMR,cardiovascular magnetic resonance;ECG,electrocardiogram;EF,ejection fraction;EMB,endomyocardial biopsy;IMPS, inflammatory myopericardial syndrome;LGE,late gadolinium enhancement; LLC, Lake Louise criteria.

Clinical presentations include chest pain or infarct-like symptoms, arrhythmias, heart failure, aborted sudden cardiac death.

Cardiovascular magnetic resonance:proven=2 out of 2 updated LLC fulfilled(Figure 4); uncertain= only 1 out of 2 updated LLC fulfilled; rejected= negative CMR.

EMB categories: proven, uncertain, rejected(according to pathologist consensus).

$^{a}$ One condition may be leading(see Section 8).

5See detailed description of clinical presentation in Section 4, rarely asymptomatic cases may be detected (e.g. drug-related with a distinct history, such as immune checkpoint inhibitors).If ECG changes always consider/exclude myocarditis.

5See detailed description of clinical presentation in Section 4, rarely asymptomatic cases may be detected (e.g. drug-related with a distinct history, such as immune checkpoint inhibitors).

Table 5 Histopathological criteria for myocarditis

|Term|Predominant inflammatory cells|Myocyte necrosis|Infections PCR positive(viruses, etc.)| |---|---|---|---| |Active lymphocytic myocarditis|CD3+ T lymphocytes >7/mm2, CD68+ macrophages|yes|yes/no| |Persistent lymphocytic myocarditis|CD3+ T lymphocytes >7/mm2, CD68+ macrophages|yes|yes/no| |Resolved lymphocytic myocarditis|-|no|yes/no| |Eosinophilic myocarditis (acute stage)|Eosinophils, CD3+ T lymphocytes, CD68+ macrophages|yes|yes/no| |Giant-cell myocarditis (acute stage)|Eosinophils, CD68+ giant cells, CD3+ T lymphocytes, CD68+ macrophages|yes|no| |Sarccoidosis|CD68+ giant cells, granuloma, CD3+ T lymphocytes, CD68+ macrophages|yes/no|no|

PCR,polymerase chain reaction.

Non-ischaemic myocardial inflammation can be diagnosed by CMR according to the updated LLC30(see Figure 4). This is based on at least one T2-based criterion plus ideally one T1-based criterion. Having both a positive T2-based criterion and a T1-based criterion will increase spe-cificity for diagnosing AM, but a diagnosis of possible myocarditis can

still be made by having only one(i.e. T2-based or T1-based) criterion in an appropriate clinical scenario, although with less specificity.Supportive criteria include pericardial abnormalities(which, however,suggest concomitant pericarditis), and global or regional left ventricular(LV) systolic dysfunction on cine imaging.

PCR,polymerase chain reaction.

ESC Guidelines

![Criterion\nMethods\nMethods\nT2-weighted imaging or T2 mapping\nNative T1 mapping/ post-contrast T1 mapping(ECV)/ T1-weighted imaging\nLate gadolinium n enhancement\nLate T1-twoeded imaging\nFocles\nMethod, if diffuse fibrosis\nNative T1 mapping/ mapping (ECV)/ T1-weighted imaging\nL2\n\nDescription of focal increases\nRegional or global in increase T2 or global of new of caing T2-twoighted T2-weighted\n●High signal intensity of the pericardium in T1-mapping or regional in T2-mapping or T2-weighted imaging\n●High signal intensity of the pericardium in T1-mapping\n●High signal intensity of the pericardium in T1-mapping\n\nNormal to braid ECD 2 out of 2 updated LLC main criteria fulfilled\nFunctional and wall motion abnormalities\nNatural T1 mapping/ post-contrast T1 mapping(ECV)/ T1-weighted imaging\nLate Hadolinium nenhancement\nHeaodynamic compromise\nB2\nHarmonic couldi frosis brosis\nB3\n\nFunctional and wall motion abnormalities\nNatural T1 mapping/ function eEF) and volume parameters\n●Resiﬁcation,pattern, extent, and location of LGE（positive if areas with high Sl in a nonchaemic lGE（position pattern）•Thrombi（if present）•Total LGE/LV mass（%）（no routine）\n·Presence，composition，and extent of pericardium en T1-mapping of pericardial fEFE，RVEF) and volume parameters\n●Haemodynamic (EF) and volume\n●Cardiac function (e.g. LVEF,RVEF) and volume\n●Hemodynamic in fusion\n](2/aj0YEe4oUhYkBdfpda0fYP/figure63ae0ec25dba48aca0a5396774acbbf1_0_2.png) Figure 4 Diagnostic criteria by cardiovascular magnetic resonance based on the updated Lake Louise criteria. CMR, cardiovascular magnetic reson-ance;ECV,extracellular volume;LGE,late gadolinium enhancement;LLC,Lake Louise criteria;LV,left ventricle;LVEF,left ventricular ejection fraction;RVEF, right ventricular ejection fraction; SI, signal intensity ratio.30 Presence of pericardial effusion suggests concomitant pericarditis.

ESC Guidelines

Histopathological Dallas criteria,31 in addition to immunohistological staining to detect CD3+ T cells and CD68+ macrophages, are required to identify specific histological subtypes of myocarditis and to differen-tiate from phenocopies[e.g. arrhythmogenic right ventricular cardio-myopathy(ARVC)].32,33 New quantitative criteria are presently required, since the ESC criteria of≥14 leucocytes/mm2 including≥7 CD3+ T cells/mm2 have been questioned by cardiopathologists.10 In addition, molecular analysis of EMB and blood[including assessment of viral deoxyribonucleic acid(DNA) or ribonucleic acid(RNA) in per-ipheral leucocytes and in plasma] using quantitative polymerase chain reaction(PCR) is necessary to identify the aieopathogenesis of myo-carditis and allow targeted therapies(antiviral or immunosuppressive)-immunomodulatory), if clinically useful.10,32,34 Examples are given in Section 5.9.1.

3.3.2. Diagnostic criteria for pericarditis

Pericarditis is an inflammatory pericardial syndrome with or without pericardial effusion(PEff). The definite clinical diagnosis can be made with a clinical presentation and more than one additional criterion(Table 4). The main presenting symptom is usually chest pain(85%-90% of cases), which is typically sharp and pleuritic, improves by sitting up and leaning forward, and is exacerbated by inspiration,lying down, and declution, due to increased attrition between in-flamed pericardial layers. Dyspnoea can be reported by the elderly,or right HF signs and symptoms in the case of pericarditis with con-striction. Arrhythmic presentations are rare and are usually asso-ciated with atrial fibrillation(AF). Additional criteria include a pericardial friction rub(≤33% of cases), which is a superficial scratchy or squeaking sound, caused by friction between the two inflamed pericardial layers. Electrocardiogram changes have been historically reported as a typical hallmark of AP; however, the pericardium is electrically silent, so ECG changes imply concomitant inflammation of the myocardium, warranting investigation for concurrent myocar-ditis.35 On imaging, new or worsening PEff(up to 60% of cases),which is generally mild, might be detected. As pericarditis classically manifests with an inflammatory syndrome, elevated laboratory mar-kers of inflammation, such as C-reactive protein(79%-90%),36 erythrocyte sedimentation rate(ESR), and neutrophilic leucocyt-osis,37,38 can provide additional supportive criteria. The inflamed pericardium is neovascularized and contrast-enhanced on computed tomography(CT) and CMR. Cardiovascular magnetic resonance is superior for tissue characterization and can reveal pericardial oe-dema and/or pericardial late gadolinium enhancement(LGE), provid-ing additional imaging criteria for the diagnosis.

3.4. Aetiology of myocarditis and pericarditis

Myocardial and pericardial diseases share mostly similar aetologies(see Supplementary data online, Table S1). The aetiology of IMPS can be ei-ther infectious or non-infectious. These can trigger IMPS in a genetically predisposed individual by inflammatory/autoimmune mechanisms.However, the prevalence of each aetiology and the impact of the causa-tive agent on the clinical course, prognosis, and therapeutic approach may differ between the two entities. ${}^{1,10}$

3.4.1. Aetiology of myocarditis

The most common infectious aetiology is presumed to be viral. 10,39,40 Enteroviruses, adenoviruses, parvovirus B19(B19V) and some

herpesviruses[Epstein-Barr virus(EBV), human herpesvirus 6(HHV-6)],as well as influenza and coronaviruses, are the most common viruses associated with myocarditis(Supplementary data online, Table S1).Non-cytotoxic viruses trigger myocarditis indirectly by activating the im-mune system.41,42 Bacterial infection with Borrelia species[Lyme carditis(LC)] and parasitic infections, such as Trypanosoma cruzi[Chagas disease(CD)], are additional important aetologies in specific regions of the globe.

However, several non-infectious aetologies should be recognized,including systemic diseases, autoimmune(or likely autoimmune) disor-ders[systemic lupus erythematosus(SLE), systemic sclerosis(SSc),rheumatoid arthritis(RA), eosinophilic granulomatosis with polyangii-tis(EGPA), hypereosinophilic syndrome(HES)], immune-mediated forms[such as LM, giant-cell myocarditis(GCM), eosinophilic myocar-ditis(EM), and cardiac sarcoidosis(CS)], inflammatory bowel disor-ders, drugs and toxic reactions(including ICI-associated myocarditis,see Section 9.6.1.1) and chest radiation, as well as genetic conditions such as inherited CMP(see Section 5.3);10,39 see Supplementary data online, Table S1.10

3.4.2. Aetiology of pericarditis

The aetiology largely depends on the epidemiological background,patient population, and clinical setting.1,10 Idiopathic or viral peri-carditis is the most frequent aetiology in developed countries,ranging from 50% in patient settings to>80% in outpatient settings.43-48 Tuberculosis(TB) is responsible for about 70% of all cases, especially in human immunodeficiency(HIV)-infected pa-tients, in regions where the disease is endemic. An increasing num-ber of cases are related to interventional procedures and surgery[post-cardiac injury syndrome(PCIS)] due to the increased number of procedures performed and the ageing population.49 Other com-mon causes include systemic inflammatory/autoimmune diseases and cancer(especially lung and breast cancer or lymphomas and leukaemia)(see Supplementary data online, Table S1).1

About 5%-15% of patients with recurrence have genetic mutations,sometimes related to a monogenic autoinflammatory disease, mainly fa-milial Mediterranean fever(FMF) and tumour necrosis factor receptor-associated periodic syndrome(TRAPS).50,51 A genetic predisposition and an autoinflammatory/immune-mediated pathogenesis are also sus-pected in patients with multiple recurrences. For additional information see Supplementary data online, Tables S2 and S3.50-52

4. Clinical presentation of inflammatory myopericardial syndrome

The term IMPS includes a spectrum of inflammatory diseases from isolated myocarditis to isolated pericarditis through a combination of both. IMPS should be used as an umbrella term during the initial diagnostic work-up until the final diagnosis is made. One of the ma-jor challenges for the diagnosis of IMPS is recognition itself, there-fore the TF highlighted red flags(Table 6). These symptoms and signs should suggest IMPS. The red flags for IMPS are mainly clinical signs, accompanied by serological and/or imaging biomarkers, and are not equivalent to the risk. Red flags for IMPS are warning signs,aiming to raise the awareness of the disease. If there is a suspicion of IMPS, staging based on the risk assessment should be performed(Table 7).

ESC Guidelines

Table 6 Red flags for the clinical diagnosis of myocarditis and pericarditis

|Myocarditis|Pericarditis| |---|---| |Recent or concomitant flu-like syndrome or gastroenteritis|Recent or concomitant flu-like syndrome or gastroenteritis| |Infarct-like chest pain|Pleuritic/infarct-like chest pain| |Palpitations|Right HF symptoms and signs of constriction| |HF symptoms|Fever| |ECG changes|Pericardial rubs| |Ventricular arrhythmias(isolated, complex) Syncope|C-reactive protein elevation| |Haemodynamic instability|Pericardial effusion| |Elevated markers of myocardial lesion(hs-Tn, CK-MB elevation)|Pleural effusion| |Elevated markers of HF(NT-proBNP)|Polyserositis| |Abnormal wall motion, increased wall thickness and/or impaired systolic function|CMR imaging with pericardial oedema and/or LGE| |on imaging|| |CMR imaging with myocardial oedema and/or LGE||

CK-MB, creatinine kinase muscle-brain type; CMR, cardiovascular magnetic resonance; ECG, electrocardiogram; HF, heart failure; hs-Tn; high-sensitivity troponin; LGE, late gadolinium enhancement; NT-proBNP, N-terminal prohormone of brain natriuretic peptide.

*See Section 5.1.

Table 7 Clinical risk stratification to guide work-up in inflammatory myopericial syndrome

|Risk|High risk|Intermediate risk|Low risk| |---|---|---|---| |Myocarditis|● Acute HF/cardiogenic shock ● Dyspnoea NYHA III-IV refractory to medical therapy ● Cardiac arrest/syncopea ● Ventricular fibrillation/sustained ventricular tachycardia ● High-level AV blocka|● New/progressive dyspnoea ● Non-sustained ventricular arrhythmias ● Persistent release or relapsing troponin|Stable symptoms or oligosymptomatic| ||Imaging criteria:||| ||● Newly reduced LVEF(<40%)° ● Extensive LGE on CMR° ● Preserved LVEF(≥50%) and/LGE≥2 segments on CMR|Imaging criteria:|Imaging criteria:| |Pericarditis|● Signs and symptoms of cardiac tamponade ● Fever(≥38°C) ● Effusive-constrictive pericarditis ● Failure of NSAID therapy ● Incissant pericarditis|● Signs and symptoms of right HF|● Response to adequate therapy within 1-2 weeks| ||● Fast and/or LGE≥2 segments on CMR||| ||Imaging criteria:||Imaging criteria:| ||● Large PEff(>20 mm end-diastole) ● Cardiac tamponade ● Extensive pericardial LGE on CMR|● Moderate-large PEff (10-20 mm end-diastole) ● Constrictive pericardial LGE on CMR|● Absence or mild PEff ● Absence of pericardial LGE on CMR|

AV, atrioventricular; CMR, cardiovascular magnetic resonance; HF, heart failure; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; NSAID, non-steroidal anti-inflammatory drug; NYHA, New York Heart Association classification; PEff, pericardial effusion; WMA, wall motion abnormalities.

These criteria do not lead directly towards endomyocardial biopsy; in these scenarios it is a case-by-case decision depending on the suspected underlying cause

A fast and reliable diagnosis is crucial for proper management. The ini-tial step involves triaging patients by assessing their risk factors and ruling out acute coronary syndrome(ACS), whenever indicated by the pa-tient's characteristics and clinical presentation. In addition, myocarditis

warrants consideration whether the first contact was inpatient or outpatient. ${}^{53,54}$ This approach is based on the different national healthcare systems, given that a patient may be first seen in an out-patient or inpatient setting(Figures 5-7).

ESC Guidelines

![Patient with symptoms and signsa of myocarditis presenting to the emergency room $\downarrow$ T r thanesthoracic echocardiography, chest X-ray, laboratory assessmentb (Class I)\nTreat CAD\nY\nObstructive CADc\nAdmit to ward/ICU (Class I)\nN\nHigh-risk clinical featuresd\nCardiovascular magnetic resonancee (Class I)\nPossible\nDiagnosis\nRejected/unlikely\nDefinitive\nFurther work-up\nLow risk\nEffective risk classificationd\nIntermediate risk\nStay on ward and discharge when possible (Class I)\nEstablish HF/AA therapy and/or treatment of specific aetiology\nImprovement\nCardiovascular magnetic resonance\nIf not done before)\nStay on ward and discharge when possible (Class I)\nEstablish HF/AA therapy and/or treatment of specific aetiology\nImprovement\nMultidisciplinary IMPS team discussion\nDiscussion\nIMPS team discussion\nDiscussion\nMultidisciplinary IMPS team discussion\n](2/aj0YEe4oUhYkBdfpda0fYP/figureccf560247f79488994f76a0a43e1a098_0_2.png) Figure 5 Diagnostic algorithm and triage for inpatient myocarditis. AA, anti-arrhythmic therapy; CAD, coronary artery disease; CRP, C-reactive pro-tein; ECG, electrocardiogram; HF, heart failure; ICU, intensive care unit; IMPS, inflammatory myopericardial syndrome; N, no; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; Y, yes. aSee Table 6. bLaboratory testing including troponin, NT-proBNP, C-reactive protein, differential blood count. Invasive coronary angiography or computed tomography angiography depending on clinical likelihood/probability. dSee Table 7. cConsider domyocardial biopsy. f Consider cardiovascular magnetic resonance. 8See Table 9.

ESC Guidelines

![Patient with symptoms and signsa of myocarditis presenting to the outpatient clinic\n\nFirst-line assessment with history, physical examination, ECG, transthoracic echocardiography, laboratory assessmentb (Class I)\nElevated troponinin (Y) Refer to hospital\nN\nSee inpatient algorithmc\nL\nTreat CAD\nObstructive CADd\nCardiovascular magnetic resonance${}^{e}$ (Class I)\nPossible\n\nDiagnosis\nRejected/unlikely\n$\downarrow$ \nFurther risk\nDefinitive\nFurther work-up\nLow risk\nOutpatient treatment\nOutpatient follow-up\nSmall\n\nSee inpatient algorithm\nClass I\nNegative\nOffinitive\nGlass\nOutpatient treatment\nOutpatient follow-up\nSee inpatient algorithm\nESC\n](2/aj0YEe4oUhYkBdfpda0fYP/figurec8035fd0e33440d2a84e1eb08f25ae35_0_2.png) Figure 6 Diagnostic algorithm and triage for outpatient myocarditis. CAD, coronary artery disease; CRP, C-reactive protein; ECG, electrocardio-gram; N, no; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; Y, yes. aSee Table 6. bLaboratory testing including troponin,NT-proBNP, C-reactive protein, differential blood count. cSee Figure 5. dInvasive coronary angiography or computed tomography angiography depend-ing on clinical likelihood/probability. cDepending on clinical situation (heart failure, arrhythmias) admit to ward. cSee Table 9. *See Table 7.

ESC Guidelines

![Patient with symptoms and signs of pericarditis\n$\downarrow$\nFirst-line assessment with history, physical examination,ECG,transthoracic echocardiography,X-ray,routine blood test including CRP and troponin(Class I)\nHigh-risk featuresb\nOutpatient follow-up\nResponse to therapy after 1-2 week\nK Risk evaluationb\nLow risk\nIntermediate risk\nHigh risk\n\nA\nAdmission,or aetiology search\nand anti-inflammatory therapy\nESG\n](2/aj0YEe4oUhYkBdfpda0fYP/figured441ded2e8fb48f599f5d940a91cb167_0_2.png) Figure 7 Diagnostic algorithm and triage for pericarditis. CRP,C-reactive protein; ECG, electrocardiogram; N,no;Y,yes.a^{see}Table 6. b^{f}f a patient has one or more prognostic predictors, as reported in Table 7, a high-risk patient must be admitted to hospital, and an aetiology search should be per-formed. Patients without high-risk features can be managed as outpatients without an aetiology search and admission if there is a good response to empirical anti-inflammatory therapy.

4.1. General symptoms and signs

The most common symptom of myocarditis and pericarditis is chest pain(sometimes with infarct-like features, especially for myocarditis,or pleuritic with respiratory changes, especially for pericarditis).Other common presentations include dyspnoea(myocarditis with HF presentation, but it is also the most common symptom in the elderly with pericarditis) and/or arrhythmias of different degrees(mainly ven-tricular for myocardits and supraventricular and AF for pericarditis)and, less frequently, syncope. Flow charts are provided for each type to guide the diagnostic pathway(see Section 4.3).

<BeginOfPara>Some patients may present with persistent symptoms without re-mission and are labelled as patients with incessant/ongoing IMPS.

4.2. Clinical stages of myocarditis

4.2.1. Acute myocarditis

<BeginOfPara>Acute onset is defined as symptoms and signs lasting≤4 weeks. ${}^{28}$ In myo-carditis, this entails AM and the subtype fulminant myocarditis (FM).

The presentation of AM can vary from very mild symptoms to a life-threatening condition. ${ }^{10}$ The typical symptoms and signs at presentation include chest pain in >80% of cases, and dyspnoea in 20%-50%, while fatigue, palpitations, and syncope are less common and are reported in about 5%. 28,32,55 In the majority of cases (80%),symptoms are preceded by prodromes, such as fever(60%), gastro-intestinal complaints (30%), or respiratory symptoms (25%).28,556 Other extracardic symptoms, depending on the underlying disease,can be present. Electrocardiogram is normal in a minority of patients(about 15%); most frequently, ST-segment elevation is present(57.5%), but other ST/T-segment changes can be found (23.5%), as well as conduction blocks (10%). 28,55

In most patients with acute presentation, cardiac enzymes[troponin T/I and creatinine kinase muscle-brain type(CK-MB)] are elevated.28,55 Echocardiography is important for clinical evaluation as it might reveal signs of myocarditis, including increased wall thickness and echogenicity due to myocardial oedema.P.Eff is seen in up to 25% of patients, reflect-ing concomitant pericarditis or related to haemodynamic factors. ${}^{28,55}$

ESC Guidelines

4.2.2. Fulminant myocarditis

Fulminant myocarditis(occurring in 3%-9%) is characterized by cardio-genic shock at presentation for which haemodynamic support is needed. ${}^{28}$ Isolated right ventricle(RV) dysfunction is uncommon; how-ever, biventricular failure occurs frequently in FM. Sustained ventricular arrhythmias(VA) may also occur in these patients(46.9%) and some present with sudden cardiac death(SCD)(25.8%). ${}^{28,56,57}$

In the majority of children with FM(usually<2 years of age), LV dys-function with dilation is present at initial presentation, 40 while there is usually no LV dilatation in the early phase for adults. Concurrent viral infections can be common in these children.

4.2.3. Subacute myocarditis

The subacute stage refers to cases with symptoms lasting>1 month but $\leq 3$ months.The symptoms are unspecific, and patients might either have a remission without residuals or might progress to chronic myo-carditis or inflammatory CMP(see Section 10).

4.2.4. Chronic myocarditis

Chronic myocarditis is myocarditis persisting beyond 3 months. ${}^{39}$ Chronic myocarditis might reflect an intermediate stage possibly lead-ing to inflammatory CMP, characterized by cardiac remodelling and some degree of ventricular dysfunction. ${}^{10,39}$

Milder forms may appear as hypokinetic non-dilated forms of CMP.39 Moreover, an arrhythmogenic substrate, due to fibrosis, should be con-

Symptoms may be unremarkable in chronic myocarditis.10,39 Dyspnoea and palitations might be the leading symptoms.10,39 Biomarkers of myocardial injury are usually within normal limits. ${}^{59}$ Notably, elevated C-reactive protein, hs-TnT, and impaired global lon-gitudinal strain(GLS) have been associated with EMB-proven

<EndOfPara>myocardial inflammation in patients with non-ischaemic HF. ${}^{60}$ New quantitative CMR techniques have improved the diagnostic yield in pa-tients with chronic myocarditis. ${}^{61}$

4.3. Clinical presentations of myocarditis

Myocarditis is characterized by the heterogeneity of clinical manifesta-tions(Figure 8); therefore, the diagnosis requires a high level of suspi-cion. The main patterns of clinical presentation are infarct-like chest pain(most frequent symptom), arrhythmias, and HF. Severity may range from asymptomatic/oligosymptomatic to severe life-threatening scenarios, such as severe HF or VA(potentially leading to SCD). A clin-ical classification based on presentation as high-risk or non-high-risk myocarditis(see Table 7) has been shown to meaningfully predict out-comes in large cohorts.28,62,63 Moreover, myocarditis, especially when recurrent, may represent the'hot phase' of some CMPs[e.g. desmopla-kin(DSP)-related ARVC].64 Details are given in Section 4.3.5.

4.3.1. Chest pain presentation

Chest pain is the most common form of clinical presentation(about 75%of unselected cases) in adolescents and adults.28 It is commonly associated with an increase in necrosis biomarkers, such as troponin, often with ECG alterations(especially ST-segment elevation), which may mimic ACS, des-pite the absence of significant obstructive coronary artery disease(CAD).These cases are often labeled as infarct-like.65 Patients with this presen-tation usually report a recent or concomitant viral infection, such as a re-spiratory tract infection or gastroenteritis, which often precedes myocarditis by several days to weeks(2-4 weeks). Usually, the presence of troponin release in the context of IMPS is not a negative prognostic marker, when associated with preserved biventricular function.4,66 Patients presenting with chest pain and normal left ventricular ejection fraction(LVEF) without wall motion abnormalities(WMA), no VA,and complete resolution of ECG abnormalities in the short term can

![Spectrum of myocarditis presentations and outcomes\nImage size correlates with frequency\nOligosymptomatic\nChest pain\nArrhythmias\n(Acute)\nHeart failure\nAborted\nSCD\nSCD\nRemission without or with residuals\n(presence of reduced function and or LGE)\nDilated\ncardiomyopathy\nDeath\nESC\n](2/aj0YEe4oUhYkBdfpda0fYP/figurec1bc40cfef6c4bab9d2e1ee3b14518f3_0_16.png) Figure 8 Spectrum of myocarditis presentations and outcomes.LGE, late gadolinium enhancement;SCD,sudden cardiac death.Image size correlates with presentation frequency(e.g.chest pain being the most common). Uncomplicated cases of myocarditis(about 75% of unselected cases) usually have spontaneous remission.28 In acute myocarditis diagnosed by endomyocardial biopsy, up to 50% of patients have spontaneous recovery, but up to 25%may have a persistent stable cardiac dysfunction, while 10%-25% have a progressive ventricular dysfunction, which could lead to end-stage dilated car-diomyopathy, heart transplantation, or death.

ESC Guidelines

be considered as having a low-risk presentation with an excellent long-term prognosis.4,28,62,66,67 There are possible exceptions to this general rule in a few cases with EM and GCM. Myocardial scarring as detected by CMR can be present in cases with preserved LVEF.3,68-70 Focal scarring

<EndOfPara>of any cause was shown to be relevant for outcome, and small scars (e.g.<2 segments) after >6 months seemed to be more benign.<2 months) seemed to be more benign.<2 months) seemed to be more benign<2

![Patient with acute chest pain\nClinical history and vital signs, 12-lead ECG, laboratory testinga, transthoracic echocardiography (Class I)\nClinical likelihood/probability of obstructive coronary artery disease\nHigh\nModerate\nLow\nInvasive coronary orangiography\nCT angiography (Class I)\nRed flags for IMPS\n Further aetiological work-up\nCoronary artery disease\nN\n Diagnostic criteria\nsuggestive of myocarditis\nRisk stratification^4\nGo to pericarditis algorithm e\nIf CAD not the sole explanation for the symptoms\nMechars resonance artery disease\nClnical exclusion\n (Class I)\n Further magnetic resonance9\nRed flags for IMPS\n Diagnostic criteria\nN\n Diagnostic activity suggestive of pericarditis\nRisk stratification^4\n Go to pericarditis algorithm e\n](2/aj0YEe4oUhYkBdfpda0fYP/figure6a34919be02f4206bd14555ee3d5105f_0_4.png) Figure 9 Diagnostic algorithm for acute chest pain presentation. ACS, acute coronary syndrome; CAD, coronary artery disease; CRP, C-reactive protein; CT, computed tomography; ECG, electrocardiogram; GL, guideline; IMPS, inflammatory myocardial syndrome; N, no; NT-proBNP,N-terminal prohormone of brain natriuretic peptide; Y, yes.4Laboratory testing including troponin, NT-proBNP, C-reactive protein, differential blood count. bSee Table 6. `Reference: Byrne et al. .72 dSee Table 7. `See Figure 7. `Consider cardiovascular magnetic resonance. `Consider endomyocardial biopsy on a case-by-case basis. `Depending on the underlying cause and clinical need. `See Sections 5, 8, 9, 10`.

ESC Guidelines

4.3.2. Heart failure presentation

Patients with myocarditis presenting with acute HF, in particular when associated with left ventricular dysfunction(LVEF≤40%), should be considered as a high-risk group, and their prognosis largely depends on the short-term response to therapy.28,62 Clinical presentation may range from unexplained impaired ventricular function(with or without dilated LV), new onset or worsening HF(usually over 2 weeks to 3 months), to rapidly progressive refractory HF and car-diogenic shock. Fulminant myocarditis presenting with HF has a higher rate of cardiac death and heart transplantation(HT) both in the short and long term, compared with patients with LV dysfunction without FM(see Section 4.2.2).56,73,74 In these scenarios, GCM and EM are in-dependently associated with increased mortality.56,75 An algorithm for the proposed workflow is shown in Figure 10. As a central scheme,the workflow follows the CHAMPIT approach, provided in the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.12 One should be aware that arrhythmias can be a pres-entation of myocarditis, as well as an‘alternative cause’ of HF outside the suspicion of myocarditis.

4.3.3. Presentation with arrhythmias

Patients with AM with new, recurrent, or unexplained arrhythmias may have a wide spectrum of symptoms, ranging from palpitations to syncope or life-threatening arrhythmias causing aborted SCD.10,76 Supaventricular arrhythmias, especially AF,63,77 are more common in the presence of concomitant pericarditis and PeFF, while atrioventricular blocks(AVBs) or sustained VA are gener-ally, but not exclusively, associated with LV dysfunction and HF.Patients with advanced AVB or sustained VA should be considered as high risk, even in the absence of LV dysfunction. Ventricular fibril-lation(VF)/cardiac arrest occurs in about 2.5% of myocarditis-related hospitalizations.78 Patients with sustained VA during AM have a high risk of recurrence.79

Patients with GCM(see Section 9.3) or CS(see Section 9.4) are at a high risk of VA, with a prevalence of>25%.80-82

Scar-related VA can occur at any time during follow-up, even after inflammation resolution. However, polymorphic irregular VA are more common during the active inflammatory phase, whereas mono-morphic and regular VA are associated with healed myocarditis with re-siduals.83 Consistently, catheter ablation of ventricular tachycardia(VT)is more effective when performed in the post-inflammatory stage of the disease rather than during AM.84

AVB is a common feature of myocarditis related to non-viral infec-tions(i.e. CD, LC, diphtheria),85 and can also be an initial presentation of CS. In patients with arrhythmic presentation, genetic testing for CMP[ARVC/dilated CMP(DCM)/non-dilated left ventricular CMP(NDLCV)] should be considered(see Section 5.3).

An algorithm for the proposed workflow is shown in Figure 11.

4.3.4. Sudden cardiac death

One of the causes of SCD in young adults is myocardial inflamma-tion associated with fatal arrhythmias. Sudden cardiac death attributed to myocarditis among autopsied patients ranged from 1.1% to 12%, ${}^{87,88}$ and males show higher incidence rates of SCD than fe-males, with an incidence rate ratio of 2.2.88 Most individuals are asymptomatic before SCD; however, between 18% and 48% of

patients present with symptoms, including viral illness/malaise, syn-cope, nausea/abdominal pain, chest pain, and palpitations.87,88 Only 5% show cardiac symptoms in conjunction with an infective pro-cess.87 These data highlight the need to suspect a diagnosis of myo-carditis early enough. Late gadolinium enhancement in the mid-wall layer of the anteroseptal myocardial segments has been associated with higher rates of mortality and major VA, including SCD,3,89,90 even in the presence of preserved LVEF. Septal involvement in myo-carditis can be associated with a worse prognosis in the presence of a specific genetic background, such as pathogenic desmosomal gene variants(see Section 5.3).91,92 Further studies are necessary to con-firm these data.

4.3.5. Presentation of myocarditis with a potential genetic background

A complex interaction between genetic background and inflammation might be responsible for the heterogeneity of the clinical presentation of myocarditis. An inflammatory stimulus of the heart might unveil an increased genetic susceptibility to develop overt LV dysfunction or ar-rhythmogenic phenotypes. In this setting it is important to consider additional features, such as a family history of myocarditis/pericarditis,CMP, or SCD. Autosomal dominant gene defects may be associated with myocarditis.93-95 Certain autosomal recessive defects in genes en-coding various components of the cardiac structure can predispose young individuals to myocarditis. 95,96

Different studies reported that patients with myocarditis and evi-dence of pathogenic/likely pathogenic(P/LP) desmosomal gene var-iants(mostly with DSP variations) have a higher incidence of adverse cardiovascular events, especially myocarditis recurrence and VA,than patients without.91,94 Episodes of acute chest pain with troponin elevation and normal coronary arteries may occur in about 15% of patients with DSP mutations and are associated with LV LGE in about 90% of cases.97 Specific genetic P/LP variants may increase the sus-ceptibility to superimposed myocarditis in ARVC, which may be the first clinical presentation in the natural history of the disease.The presence of so-called‘hot phases’(chest pain episodes accom-panied by ECG changes and troponin release) represents a possible clinical presentation of ARVC, which often occurs in paediatric and young patients, as well as carriers of DSP genetic variants.99-101 Currently, the role of‘hot phases' in disease progression, as well as in arrhythmic risk stratification, remains to be clarified. For more de-tails see Section 5.3.

4.4. Clinical stages of pericarditis

4.4.1. Acute pericarditis

Acute pericarditis is an inflammatory pericardial syndrome with or without Peff with an onset of≤4 weeks. The clinical diagnosis is usually character-ized by pleuritic and/or positional chest pain(>80% of cases). Dyspnoea is more common in the elderly.45,102 Physical examination may be character-ized by pericardial friction rubs in up to one-third of cases, which could dis-appear with the presence of Peff. Pericardial effusion has been reported in up to 60% of cases, and it is usually mild. ECG changes, especially PR depression as an early sign and widespread ST-segment elevations,have been reported in up to 60% of cases, especially in young patients.This is suggestive of concomitant myocardial involvement, at least of mild degree.

ESC Guidelines

![Patient with signs and symptoms of acute heart failure\nAdmission to ICU\nCardiogenic shock and/or respiratory failure\nY\nT\nClinical history and vital signs, 12-lead ECG, laboratory testinga, transthoracic echocardiography\n(Class I)\nSimultaneously use CHAMPIT approach and whether congestion/apparent HF\nacute Coronary syndrome Hypertensive emergency Arrhythmia Mechanical Pulmonary embolism Infections Tamponade\nFurther work-up\nRisk stratificationc\nAcute Coronary syndrome Hypertensive emergency Arrhythmia Mechanical Embulism Infections\nTamponade\nSimultaneously use CHAMPIT approach and whether congestion/apparent HF\nFurther new further work-up\nN\nY\nC\nCongestion/apparent HF\nN\nCongestion/apparent HF\nN\nY\nAdutey myocardial discharge\nEndomyocardial biopsy (Class I)\nNormal findings\nN\nSuggested fulminant myocarditis\n2\nHigh risk\n4\nCardiovascular magnetic resonance (Class I)\nCardiovascular resonance (Class I)\nBefore discharge\nEndomomyocardial discharge\n(Class I)\nNormal findings\nNo further work-up\nAetiological work-up\nY\nFurther work-up\nKearthe aetiological drug-up required\nFurther work-up\nN\nNo further work-up\nV3\nESC\nESC\n](2/aj0YEe4oUhYkBdfpda0fYP/figurefa260d3b30a04997a30ab4d2eebb80a5_0_2.png) Figure 10 Diagnostic algorithm for acute heart failure presentation. CRP, C-reactive protein; ECG, electrocardiogram; HF, heart failure; ICU, inten-sive care unit; N, no; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; Y, yes. J.a Laboratory testing including troponin, NT-proBNP,C-reactive protein, differential blood count. bSee Table 6. cSee Table 7. dConsider cardiovascular magnetic resonance. In stabilized heart failure patients,endomyocardial biopsy may be performed on a case-by-case basis. DDepending on the underlying cause and clinical need. 8See Sections 5, 8, 9, 10.

ESC Guidelines

![Patient with new, recurrent or unexplained arrhythmias(any type)\nIdentify arrhythmia\nCardioversion/defibrillation/transcutaneous pacing/ALS (Class I)\n(Class I)\nObstructive CADa\nN\nEvaluationb,transthoracic echocardiography\n(Class I)\nZ\n $\gamma$ \nK\nN\nD\n(Class I)\nTreat CAD\nRed flags for myocardial involvement\nRisk stratification\nHigh risk\nNon-high risk\nCardiovascular magnetic resonance\n(Class I)\nBore\nBore\nEndommyocardial biopsy\n(Class I)\nDischarge\nNormal findings\nSuggestive of non-cardiac causes or cardiomyopathies\nDefinite myocarditis\nNo further work-up\nAetiological work-up\nN\nSpecific aetiology\nType of initial arrhythmia at presentation\nN\nSee specific sections\nConduction blocks\nVentricular arrhythmia\nActive myocarditis(based on initial CMR/EMB)\nRisk stratification\n$\downarrow $\nup +\nH high risk\nBore /CR\nEndommyocardial biopsy\nI\nclass I)\nCatheter ablation\nIClass I)\nFurther aetological work-up\nAorelization\n$\downarrow $\nup +\nH Horel\nBorel\nSputingb of non-cardiac causes or cardiomyopathies\nCatheter ablation\nI Class I)\nICD indications\n(Class I)\nLca1Ia\nIorelsonicidis\n(Class I)(Class Ilb)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure31a9732c5f1843428c4c804954d08de6_0_2.png) Figure 11 Diagnostic algorithm for arrhythmia presentation. ALS, advanced life support; CAD, coronary artery disease; CMR, cardiovascular mag-netic resonance; CRP, C-reactive protein; ECG, electrocardiogram; EMB, endomycardial biopsy; ICD, implantable cardioverter-defibrillator; N,no;NT-proBNP, N-terminal prohormone of brain natriuretic peptide; PM, pacemaker; Y. yes. Invasive coronary angiography or computed tomography angiography depending on clinical likelihood/probability. bLaboratory testing including troponin, NT-proBNP, C-reactive protein, differential blood count."See Table 6. dSee Table 7. cConsider cardiovascular magnetic resonance. fConsider endomyocardial biopsy on a case-by-case basis. 8See Section 6.5 for wearable cardioverter-defibrillator. hSee Sections 5, 8, 9, 10. Isee Section 6.5 and Reference Gliokson et al. ${}^{86}$ Isee Section 6.5,Recommendation Table 14 and Reference Zejepenfeld et al. ${}^{58}$

ESC Guidelines

An inflammatory syndrome is usually present with fever of $>38^{\circ} C$ (70\%), ${}^{37}$ elevated markers of inflammation(C-reactive protein)(80%-90%), ${}^{36,37}$ ESR, neutrophil leucocytosis, ${}^{37,38}$ and pericardial and/or pleur-al effusion(approximately 50%), often with lung atectasis, leading to a possible diagnosis of pleuro-pneumonia, ${}^{37,103}$ and less commonly, peri-toneal involvement(13%). ${}^{38}$ This presentation is labelled'inflammatory phenotype' of AP.

Cardiac enzymes are usually normal, but troponin may be elev-vated in 20%-30% of cases, due to concomitant myocarditis(mypericarditis).

4.4.2. Subacute pericarditis

Subacute pericarditis refers to cases with persistent symptoms lasting>1 month and<3 months. This condition may directly progress to constructive pericarditis(CP) within a few months and requires timely optimal medical therapy and close follow-up to prevent chronic evolution.104

4.4.3. Chronic pericarditis

Chronic pericarditis refers to cases lasting>3 months. In pericarditis,management of the patient during the acute phase is of paramount im-portance,not only for symptom relief but, most importantly, for prog-nostic purposes. Hospitalization of patients with AP and high-risk features allows the prompt identification and treatment of potentially life-threatening complications, such as cardiac tamparonade(CTP).105 Moreover, appropriate screening for specific aetiology is the basis for tailored therapy. Progression of AP to subacute or chronic disease is sometimes unpredictable. Omission of colchicine administration and the use of high doses of corticosteroids with fast taper are risk fac-tors for recurrences or a chronic course of the disease.24,106-109 Recently, scores that predict the individual risk of complicated pericar-ditis and chronicity have been proposed for the identification of sub-jects who require intensive therapy in terms of medication dose and length, as well as close follow-up.43,44,110 They require further validation in prospective, multicentre studies.

In chronic forms, symptoms are similar to previous attack(s),but often milder.1 In unclear cases or in difficult-to-treat patients,CMR may be performed to assess the degree of inflammation and individualize medical therapy, especially before drug tapering or discontinuation. ${}^{111,112}$

Paradoxically,although chronic pericarditis significantly impairs qual-ity of life, the rate of progression to CP is negligible(<1%) and is lower than the risk imposed by a single episode of AP, unless a specific aeti-ology is identified.105,113,114

4.5. Clinical presentations of pericarditis

Pericarditis is characterized by a wide spectrum of clinical presentations.The main presenting symptom of pericarditis is positional chest pain,which is reported in most affected individuals. Typical pericardial pain is sharp and is worse when coughing and taking a deep breath(pleurtic).Left trapezius ridge pain is a classic symptom of pericardial irritation and is transmitted through the phrenic nerve. Other less common symptoms include shortness of breath, fever, fatigue, and arrhythmia(e.g. AF).Pericardial effusion often accompanies pericarditis(>50% of cases).Other presentations include right HF-like symptoms[elevated jugular venous pressure(JVP), peripheral ascites, ascites] when constriction is present. Hypotension is a sign of CTP(which presents with Beck's triad: hypotension, jugular venous distension, and muffled heart sounds).It is crucial to differentiate pericarditis from other diseases, such as ACS,

congestive HF, pneumonia with pleuritis, pulmonary embolism, chronic obstructive pulmonary disease, and vasculitis.

4.5.1. Dry pericarditis

Dry pericarditis(40%-50% of cases),also referred to as'pericarditis sic-ca',is a form of pericarditis that is characterized by inflammation of the pericardium without the presence of PEff. It can begin insidiously or abruptly. It is usually not associated with a specific cause or a worse prognosis.

4.5.2. Effusive pericarditis

Effusive pericarditis(50%-60% of cases) is characterized by the con-rent presence of effusion.115 A moderate to large PEff is more com-monly associated with a non-idiopathic aetiology.

4.5.3. Effusive-constrictive pericarditis

Effusive-constrictive pericarditis(ECP) is characterized by the con-current presence of PEff, along with thickening and constriction of the pericardium that restricts the normal filling of the heart.116 Effusive-constrictive pericarditis occurs when constrictive physi-ology is uncovered following the drainage of a PEff with tamponade.The exact haemodynamic definition involves the right atrial pressure(RAP) failing to fall by≥50% or to a level of<10 mmHg despite intra-pericardial pressure being lowered to near 0 mmHg with removal of pericardial fluid via pericardiocentesis.110,116,117 Current multimodal-ity imaging allows a clinical diagnosis of ECP without cardiac catheterization.

4.5.4. Pericarditis with cardiac tamponade

The two most serious complications of pericarditis are CTP and CP.Pericarditis with CTP is a life-threatening condition where inflammation of the pericardium leads to the accumulation of compressive pericardial fluid(Table 8).110,115 Symptoms may include chest discomfort, fatigue,and dyspnoea. Clinical signs include hypotension, tachycardia, raised JVP, pulsus paradoxus, muffled heart sounds, electrical alternans with decreased ECG voltage, and an enlarged cardiac silhouette on chest X-ray. The magnitude of clinical and haemodynamic abnormalities de-pends on the amount of pericardial fluid and rate of accumulation,the distensibility of the pericardium, and the compliance and filling pres-sures of the cardiac chambers118(Figure 12).

Table 8 Causes of cardiac tamponade

|Common causes(in order of relative frequency):|| |---|---| |(1)|Neoplasm/malignancy| |(2)|latrogenic/trauma| |(3)|Pericarditis| |(4)|Tuberculosis(most common in developing countries)| |Less common causes(in order of relative frequency):|| |(1)|Collagen vascular diseases(systemic lupus erythematosus,rheumatoid| |arthritis, scleroderma)|| |(2)|Pericardial injury syndrome| |(3)|Acute myocardial infarction| |(4)|Aortic dissection| |(5)|Uraemia| |(6)|Bacterial infection| |(7)|Pneumopericardum|

ESC Guidelines

![Patient with definite diagnosis of cardiac tamponade\n↓\nHigh-risk features（with cumulative score ≥6)\nPostpone pericardiocentesis Empiric anti-inflammatory therapy\n](2/aj0YEe4oUhYkBdfpda0fYP/figureb6b6953d91e943c39f0cb4e14a1c4f76_0_2.png) Pericardiocentesis with drainage

Improvement

Outpatient follow-up

Pericardial window

|Criteria for triage for patients with pericardial effusion at risk for progression to cardiac tamponade||||| |---|---|---|---|---| |Aetiology|Clinical presentation|Imaging||| |Malignant disease|2|Dyspnoea/tachypnoea|1|| |Tuberculosis|2|Orthopnoea|3|| |Recent radiotherapy|1|Hypotension(CBP<95 mmHg)|0.5|| |Recent viral infection|1|Progressive sinus tachycardia|1|| |Recurrent Peff|1|Oliguria|1|| |Chronic terminal renal failure|1|Pulsus paradoxus(>10 mmHg)|2|| |Immunosuppression|1|Pericardial chest pain|0.5|| |Dysthyroidism|-1|Pericardial friction rub|0.5|| |Systemic autoimmune disease|-1|Rapid worsening of symptoms|2|| |||Slow disease evolution|-1|| ||||Mitral/tricuspid respiratory flow variations|| ||||Swinging heart||

![](921,1123,967,1165) ESC

Figure 12 Management of cardiac tamponade. CBP, central blood pressure; ECG, electrocardiogram; IVC, inferior vena cava; N, no; PEff, pericardial effusion; Y, yes. Criteria are listed for the evaluation of patients by immediate or delayed pericardicontesis based on expert consensus. Immediate pericardioesis should be considered if there are>6 points from at least two categories.

4.5.5. Constrictive pericarditis

Pericardial constriction is a chronic condition characterized by a thick-ened, fibrotic, and often calcified pericardium that leads to impaired dia-stolic filling of the heart. It should be named CP when associated with pericarditis. Constrictive pericarditis is a consequence of chronic peri-cardial inflammation and is characterized by scarring, fibrosis, and loss of elasticity of the pericardium. The main symptoms are dyspnoea,

oedema, orthopnoea, and fatigue. The classic clinical picture is usually characterized by isolated right HF with normal or nearly normal natri-uretic peptide levels. Venous congestion, hepatomegaly, pleural effu-sions, and ascites may occur.110,115,119 Constrictive pericarditis should be treated empirically with anti-inflammatory therapy. Cases after fail-ure of medical therapy and pericardial constriction without pericarditis should be referred for pericardietomy without delay(Figure 13).

ESC Guidelines

![Patient with symptoms and signs of constrictiona\n $\downarrow$ \nFirst-line assessment with history, physical examination,ECG, transthoracic echocardiography, laboratory assessment,CT(calcifications) and CMR(inflammation)(Class I)\nDefinite diagnosis of constriction\nAdmission and cardiac catheterization\nConcomitant pericarditis\nPericardiectomy (Class I)\nY\nX\nY\n](2/aj0YEe4oUhYkBdfpda0fYP/figure044183b69e084dd78c51bfe22b6e922b_0_2.png) Figure 13 Management of constriction. CMR, cardiovascular magnetic resonance; CT, computed tomography; ECG, electrocardiogram; N, no; Y, yes.Empirical anti-inflammatory therapy is warranted only for those with evidence of pericarditis(by clinical criteria, biomarkers, and/or imaging). Low risk:clinical remission after therapy/normalization of imaging findings. Intermediate risk improved symptoms without complete remission/partial regression.High risk: persistent symptoms/persistent imaging signs of constriction. ${}^{a}$ See Table 6. ${}^{b}$ See Table 7.

4.5.6. Transient constrictive pericarditis

Transient constriction is CP with ongoing inflammation that can be re-versed following anti-inflammatory treatment or that heals spontaneously.

It develops with pericarditis with or without PEff(about 10% of cases) and resolves with anti-inflammatory therapy in>50%of cases.120,121 A trial of 3-6 months of anti-inflammatory therapy is re-commended in patients with newly diagnosed CP before referral for

<EndOfPara>pericardiectomy.122,123 Biomarkers(e.g.elevated C-reactive protein)and multimodality imaging, including CMR, are mandatory to detect pericardial inflammation.

4.5.6.1. Constrictive pathophysiology

It is important to distinguish constrictive pathophysiology from actual HF symptoms. ${}^{115,120,121,124}$ There may be features of septal bounce,

ESC Guidelines

respiratory phase-dependent shift of the ventricular septum, and Doppler features of constriction without HF symptoms(see Supplementary data online, Section 2.4 and Figure S1).

4.5.7. Pericarditis with polyserositis

Pericarditis with polyserositis is characterized by inflammation of the pericardium and concurrent inflammation of other serumes membranes lining major body cavities, such as the pleura and peritoneum.

4.5.8. Inflammatory vs non-inflammatory pericarditis

In the context of pericarditis, the terms'inflammatory' and'non-inflammatory' phenotype refer to two distinct clinical presentations based on the underlying pathophysiological mechanisms.

4.5.8.1. Inflammatory phenotype of pericarditis

The inflammatory phenotype is characterized by inflammation of the pericardium with evidence of systemic inflammation. This phenotype is often associated with fever, and/or elevated systemic inflammatory markers(e.g. C-reactive protein), PEff, and/or pleural effusion. These forms typically respond well to targeted anti-inflammatory therapies,including colchicine and anti-IL-1 agents. 37,127

4.5.8.2. Non-inflammatory phenotype of pericarditis

The non-inflammatory phenotype refers to the manifestation of pericar-ditis without C-reactive protein elevation or low elevation of markers of systemic inflammation(eg.high-sensitivity C-reactive protein).127 This oc-curs in 10%-20% of patients with pericarditis.36 The pathogenesis of peri-cardits with normal C-reactive protein is unknown and these cases are often difficult to treat. C-reactive protein is a sensitive albeit unspecific bio-marker of inflammation mainly driven by IL-6. Moreover, in autoimmune diseases characterized by the type I interferon(IFN) gene signature,C-reactive protein appears to be an unreliable marker of inflammation.52

5. Diagnosis and diagnostic work-up

The diagnostic work-up in patients with suspected IMPS should be tai-lored based on the severity of clinical presentation, response to medical therapy,and individual risk(Table 7).It includes medical history,clinical physical exam, biomarkers(myocardial injury, systemic inflammation,and HF),ECG,and multimodality imaging. Endomyocardial biopsy has its place in dedicated clinical scenarios. For IMPS, routine viral seroyology is not recommended,1 except for HIV and hepatitis C virus(HCV), as well as for suspected bacterial infections(such as Borrelia spp., rickett-sial, and T. cruz infections). Echocardiography is the basic imaging meth-od, followed by other techniques. Cardiovascular magnetic resonance is an advanced imaging test of increasing importance for detection of myocardial as well as pericardial injury. ${}^{115,128}$ Most important is a patient-tailored approach, usually driven by the dominant symptoms.Flow charts(Figures 5-7 and 9-13) illustrate the proposed workflow in different clinical scenarios. If a patient presents with clinical symp-toms suggestive of IMPS(Table 6), basic and advanced diagnostic assess-ments are recommended(see Table 9).

Recommendation Table 1- Recommendations for clinical evaluation of myocarditis and pericarditis(see Evidence Table 1)

|Recommendations|Classa|Levelb| |---|---|---| |Complete clinical evaluation, including history, physical examination, chest X-ray, biomarkers,ECG, and echocardiography is recommended in all patients with a suspicion of myocarditis and/or pericarditis for the initial diagnostic assessment.|1|C| |CMR is recommended in patients with the clinical suspicion of myocarditis(using updated LL criteria)30 and/or pericarditis for the non-invasive diagnosis of inflammatory reaction.110,115,129|1|B| |Hospital admission is recommended for patients with high-risk pericarditis for monitoring and treatment.|1|B| |Hospital admission is recommended for patients treatment.105,130|1|C| |Hospital admission is recommended for patients with moderate- to high-risk myocarditis for monitoring and treatment.|1|C| |EMB° is recommended in patients with high-risk and/or haemodynamic instability, and/or in patients with intermediate-risk myocarditis|1|C| |not responding to conventional therapy in order to detect a specific histologic subtype and to assess the presence of viral genome for treatment.34,63,73,131||| |Invasive coronary angiography or coronary CT, depending on clinical likelihood, is recommended in patients with IMPS if an acute coronary syndrome is suspected to rule out obstructive coronary artery disease.|1|C| |Hospital admission should be considered for patients with low-risk myocarditis for monitoring and treatment.|11a|C| |Pericardial or epicardial biopsy may be considered in relapsing pericardial effusion as part of the diagnostic work-up when the diagnosis cannot be reached with multimodality imaging and laboratory examinations.|11b|C| |Routine serology is not recommended in patients with myocarditis and/or pericarditis for the evaluation of viral aetiology except for hepatitis C,HIV, and Lyme disease.|Ⅲ|C| |CMR, cardiovascular magnetic resonance; CT, computed tomography; ECG, electrocardiogram; EMB, endomyocardial biopsy; HIV, human immunodeficiency virus; hs-Tnl, high-sensitivity troponin l; hs-TnT, high-sensitivity troponin T; IMPS inflammatory myopericardy syndrome; LL, Lake Louise; NT-proBNP, N-terminal prohormone of brain natriuretic peptide. ${}^{a}$ Class of recommendation.||| |${}^{b}$ Level of evidence.||| |‘Including hs-TnT or hs-TnT, C-reactive protein, NT-proBNP.||| |${}^{a}$ Scee Table 7.|||

CMR, cardiovascular magnetic resonance; CT, computed tomography; ECG,electrocardiogram; EMB, endomyocardial biopsy; HIV, human immunodeficiency virus;hs-Tnl, high-sensitivity troponin l; hs-TnT, high-sensitivity troponin T; IMPS inflammatory myopericardy syndrome; LL, Lake Louise; NT-proBNP, N-terminal prohormone of brain natriuretic peptide.

aClass of recommendation.

bLevel of evidence.

‘Including hs-TnT or hs-TnT, C-reactive protein, NT-proBNP.

dSee Table 7.

eContemporary evaluation of EMB should be based on histology,immunohistology,and molecular pathology for detection of viral infections in myocardial and blood samples(see also Table 11).

ESC Guidelines

Table 9 Basic and advanced level assessment

Basic assessment:

History: potential causes and triggers(viral infection of upper respiratory or gastrointestinal tract, toxins, drug use, medications), recurrent symptoms,family history of IMPS/cardiomyopathy/SCD, and systemic inflammatory/autoimmune diseases

Physical examination: assess clinical stability, symptoms(chest pain, HF symptoms,palitations, syncope),malise, general weakness and fatigue,pericardial friction rub, clinical symptoms/signs of CTP

ECG:PR-segment depression,ST/T-wave changes,AVB,and ventricular arrhythmias

Chest X-ray

Basic laboratory data:

Markers of myocardial lesion(e.g. hs-TnT/Tnl)

Markers of systemic inflammation (e.g.C-reactive protein,ESR,WBC count)

Markers of heart failure(e.g.NT-proBNP)

Complete blood count(including eosinophilic count)

Renal function and electrolytes(e.g. sodium, potassium, creatinine)

Thyroid function(e.g.TSH)

Hepatic function and additional testing(e.g.lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase)

Echocardiography including strain imaging

Advanced assessment usually after admission:

Coronary anatomy evaluation(if needed for differential diagnosis by invasive coronary angiography or coronary CT depending on the clinical likelihood of ACS)

CMR to assess signs of myocardial and pericardial inflammation and/or fibrosis

Arrhythmia screening depending on risk stratification(e.g. Holter-ECG)

Additional laboratory parameters guided by clinical suspicion(e.g. if therapeutic consequences are expected)

Dedicated genetic testing if indicated

CT to assess concomitant pleuropulmonary diseases

Specific myocarditis: EMB in high-risk cases and in intermediate-risk cases on a case-by-case decision to detect specific histology and some aetiologies if needed

Specific pericarditis: diagnostic pericardiocentesis when indicateda

ACS,acute coronary syndrome;AVB,atrioventricular block;CMR,cardiovascular magnetic resonance;CT,computed tomography;CTP,cardiac tamponade;ECG,electrocardiogram;EMB,endomyocardial biopsy;ESR,erythrocyte sedimentation rate; HF, heart failure;hs-TnT/Tnl, high-sensitivity troponin T/l; IMPS, inflammatory myocardial syndrome;NT-proBNP,N-terminal prohomore of brain natriuretic peptide; SCD, sudden cardiac death;TSH,thyroid-stimulating hormone;WBC, white blood cell

*See Recommendation Table 12

5.1. Electrocardiogram

Dynamic changes in the ST segment are classic hallmarks of pericar-ditis and myocarditis. The most typical pattern includes widespread ST-segment elevation, reported in 20%-60% of cases(see Supplementary data online, Table S4). In pericarditis, ECG changes suggest concomitant myocardial involvement, and are indicative of

inflammation of the subepicardium.35 These changes are more com-mon in the initial phase and may be more frequent in younger pa-tients. ST-segment depression and T-wave inversion may also be present, albeit less frequently than in patients with acute myocardial ischaemia,132 and may be related to the extent of myocardial damage.133,134 Diffuse depression of the PR segment is a classic early finding in AP.

A decrease in the amplitude of QRS complexes on ECG can be observed in cases of AP and/or AM, especially with large effusions or extensive myocardial injury. Electrical alternans of the QRS complexes has been reported, attributed to fluctuation of the heart within a large effusion(swinging heart). Lengthening of the QT interval might oc-cur in AM.

Atrial fibrillation can occur in AP, especially in predisposed patients,in whom pericardial inflammation may be a trigger for supraventricular arrhythmias." In contrast, VA are more common in myocarditis.

AVBs and intraventricular conduction defects, particularly right bun-dle branch blocks, are not uncommon(see Section 4.3.3, and Supplementary data online, Table S4) and may be associated with more severe presentations.135-137

Electrodiogram changes are highly dynamic and may evolve over a span of hours or days, with temporal progression varying significantly among patients.Typically,ST changes resolve; however, it is important to note that a normal ECG at presentation does not exclude the pos-sibility of IMPS.

5.2. Biomarkers

5.2.1. Biomarkers in clinical routine

Recommended biomarkers in IMPS include:

● Markers of inflammation(e.g. C-reactive protein): C-reactive protein is often increased in patients with pericarditis(up to 80%)and AM(up to 80%), and contributes to the diagnosis.28,36,138 Negative results, however, do not exclude the diagnosis. In pericar-ditis, C-reactive protein is a marker of disease activity that could be used to guide the duration of anti-inflammatory therapy.D-dimers are currently being investigated for their diagnostic and prognostic relevance.36,139,140

● Markers of myocardial lesions(e.g.troponin): Troponin is ele-vated in myocardial involvement, usually indicating cardiomyocyte necrosis. Assessment of baseline troponin is crucial to diagnose the severity of myocarditis. It is typically increased in infarct-like myocarditis.

● Markers of HF(BNP or NT-proBNP): Assessment of baseline level is recommended among patients with suspected myocarditis. This measurement can be repeated at discharge and during follow-up in an outpatient setting to assess the risk of clinical events.NT-proBNP can be used in patients with myocarditis as a predictive marker of HF among patients with normal or impaired LVEF.12

5.2.2. Biomarkers beyond clinical routine

Different biomarkers may help to identify a specific aetiology and to guide risk stratification. Most of them are not part of clinical routine,

ESC Guidelines

but could help based on a strong clinical suspicion,73 e.g.miR721 was shown to have a discriminatory capacity.

In specific circumstances,tumour necrosis factor alpha(TNF-α),IL-1β,IL-6, and IL-17A may be of value. Similarly, in some cases, evaluation of cardio-specific antibodies may be helpful, according to the local labora-tory availability. These include organ-specific anti-heart autoantbodies and anti-intercalated disc autoantibodies, as well as non-organ-specific serum autoantibodies.10 These autoantibodies, especially if found at high titres, may have a negative prognostic value.

Furthermore, a specific serum biomarker, i.e. the soluble form of the IL-1 receptor-like 1(IL-1RL1), also known as ST2, was associated with a higher risk of severe HF among male myocarditis patients.143 Other biomarkers have been studied in myocarditis, including procollagen type III, gelsolin, soluble VCAM-1, galectin-3, serum alarmin S100A8/S100A9, immunoglobulin free light chain, and heparin-binding protein,for both diagnostic and prognostic purposes. However, these biomar-kers were evaluated among limited small cohorts and are clinically not routinely used.144,145

5.3. Genetics

Genetic testing is relatively new in the field of IMPS. There is a potential overlap with CMPs. Myocarditis and pericarditis will be discussed separately.

There has been increasing evidence that gene variants coding for struc-tural proteins, particularly desmosomal and sarcomeric proteins, may overlap with acute and recurrent myocarditis and affect disease sever-ity.94,95 Furthermore, it has been shown that there is an overlap of gene variants predisposing to myocardial inflammation and inherited CMP(ARVC and NDLVC).13 In particular, myocardial inflammation may be de-tected in patients with inherited CMP using serum and imaging biomar-kers.13 There is evidence that these patients are at higher risk for complicated myocarditis(Section 4.3.5).13,91,93,94 In a meta-analysis, the pooled prevalence of P/LP variants was 4.2% for uncomplicated myocar-ditis, whereas for complicated myocarditis the pooled prevalence was 22%and 45% in adults and children, respectively.95 Pathogenic/likely pathogenic variants in desmosomal genes were more common in uncomplicated myocarids(64%), while variants in sarcomeric genes were more preva-lent in complicated myocarditis(58% in adults and 71% in children).95

A case series demonstrated a high proportion of definite or prob-able pathogenic variants in patients with myocarditis with RV in-volvement or sustained VA.146 Furthermore, DSP variants have been reported in familial recurrent myocarditis.147 Another demonstrated overlap of gene variants in myocarditis and inherited CMP.96

Identifying such gene variants has several clinical implications:

(1) While in myocarditis there is a recommendation to defer on im-plantable cardiover-defibrillator(ICD) placement during the acute phase of the disease, the threshold for ICD placement is low-er in ARVC in cases of primary prevention.58

(2) Gene variants predisposing to myocarditis have relevant implica-tions for patients. ${}^{147,148}$ Details are given in the 2023 ESC Guidelines for the management of cardiomyopathies. ${}^{13}$

(3) Cascade clinical and genetic screening for relatives and familial gen-etic counselling should be offered.93,149

As scientific knowledge about gene variants and their potential pathophysiological role has been continuously increasing over re-cent years, comprehensive screening includes desmosomal and sar-comeric genes and some DCM-associated genes.64,91,96,146,150 For details, see 2023 ESC Guidelines for the management of cardiomy-opathies.13 Nevertheless, it is not clear whether the inflammatory process acts as a trigger or is fully part of the pathophysiological pro-cess in inherited CMP.151

Pathogenic/likely pathogenic variants have been identified in patients with recurrent pericarditis(RP), especially young patients, with a family history, multiple recurrences, inflammatory phenotype, and refractory or dependent on medical treatments. Recurrent pericarditis has been associated with genetic variants for monogenic autoinflammatory dis-eases(e.g.FMF,TRAPS), but also with genes related to the inflamma-tory response(Figure 14).50,51,152,153

A recent study performed whole-exome sequencing in 108 patients with RP. Overall, about 15% of patients had variants in genes related to the inflammatory response, while up to 30% of patients carried variants in different cardiac genes, worthy of a deeper investigation.51 These data suggest a genetic disposition in at least a subset of patients(positive family history of pericarditis or periodic fever, poor response to colchicine, multiple recurrences with inflammatory phenotype), and counselling may be offered.51,152 In these clinical scenarios, prolonged therapy with specific biological agents(e.g. anti-IL-1 agents) should be considered.

Recommendations Table 2- Recommendations for genetic testing(see Evidence Table 2)

|Recommendations|Classa|Levelb| |---|---|---| |It is recommended to obtain family history including pedigrees in cases of recurrent IMPS to provide clues to the underlying aetiology, determine inheritance pattern, and identify relatives at risk.||C| |Genetic testing should be considered in patients with definite myocarditis/percarditis in cases of: ${}^{50,51,64,94,150}$||| |● family history of IMPS, inherited or suspected cardiomyopathy||| |●severe ventricular arrhythmia||| |● significant left/right LGE(e.g. ring-like pattern or|lla|B| |septal LGE) or persistent LVEF systolic dysfunction||| |● recurrent myocarditis or persistent troponin||| |elevation||| |● recurrent pericarditis with an inflammatory||| |phenotype,refractory to conventional treatment||| |with the aim to detect an underlying genetic cause.|||

IMPS, inflammatory myopericidal syndrome; IL, interleukin; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction.

Class of recommendation.

See Section 4.

dEspecially poor response to colchicine and anti-IL-1 agents.

ESC Guidelines

![Acute IMPS\nAcute IMPS\nPatient 1\nsingle episode)\nPatient 2\nPatient 3\n(multiple recurrences\n2\nGenetic background\nInfection\nAutoinflammatory/ autoimmune\n[one recurrence]\nGenetic background\nAutoinflammatory/ autoimmune\n[5]\nESC\n](2/aj0YEe4oUhYkBdfpda0fYP/figureab0d9112aabf4e798a7f94e3be1fe6d2_0_2.png) Figure 14 The different courses of inflammatory myopericardial syndrome and the interplay between genetic background inflammation and auto-immunity beyond the initial infectious trigger. IMPS, inflammatory myopericardial syndrome.

5.4. Multimodality imaging

The non-invasive diagnosis of IMPS relies on advanced cardiovascular im-aging. An overview of the capabilities of different imaging modalities for the identification of pathophysiological components is provided in Supplementary data online, Table S5. Echocardiography is usually the first-step imaging modality and provides functional and morphological in-formation. Cardiovascular magnetic resonance can better differentiate myocardial tissue and shows myocardial and pericardial inflammation,as well as different patterns of fibrosis. Fluorodeoxyglucose positron emission tomography(FDG-PET) is useful to detect disease activity, es-pecially for CS(see Section 5.8). Computed tomography allows detection of calcification of the pericardium and its extent, as well as exclusion of CAD.The application of non-invasive imaging should guide therapeutic decision-making(see Section 4).

5.5. Echocardiography

Transthoracic echocardiography(TTE) is usually the initial imaging mo-dality of choice for individuals with suspected IMPS, given its ability to identify myocardial and pericardial abnormalities, as well as concomi-tant valvular disease. ${}^{115,124}$

5.5.1. Echocardiography in myocarditis

Patients with a suspicion of myocarditis should usually undergo standard TTE including speckle tracking or tissue Doppler imaging(TDI) at pres-entation.Transthoracic echocardiography helps monitor changes in car-diac chamber size, ventricular function, wall thickness, and PEff. In myocarditis, global ventricular dysfunction, diastolic dysfunction with preserved ejection fraction(EF), and regional WMA may occur. 154,155

Tissue Doppler imaging or strain imaging can be used in the setting of myocardits and may indicate myocardial injury. 156,157 Recent studies have shown that global longitudinal and circumferential strain(GLS and GCS) and strain rate were decreased in patients with AM, even with preserved EF.156 Strain may provide important prognostic infor-mation in AM.157 Regional GLS can be associated with scarring on CMR and can predict VA and outcomes in patients with AM.157 Abnormal RV strain 158 and left atrial(LA) strain 159 have been detected in AM with preserved EF.

5.5.2. Echocardiography in pericarditis

Tranthoracic echocardiography can detect the presence of PEff and assess its haemodynamic importance, as well as constrictive patho-physiology(Supplementary data online, Figure S1 and Table S6).

Table 10 Classification of pericardial effusion

|Onset|Acute(≤4 weeks)| |---|---| |Onset|Subacute(>4 weeks to ≤3 months)| |Chronic(>3 months)|| |Sizea|Mild: <10mm| |Sizea|Moderate: 10-20 mm| |Distribution|Large: >20 mm| |Composition|Circumferential/loculated| |*Maximal end-diastolic diameter||

${}^{*}$ Maximal end-diastolic diameter.

ESC Guidelines

Acute pericarditis patients may have a normal-appearing TTE(40%-50% of cases in first episodes); however, the presence of new or wor-sening Peff is a diagnostic criterion for pericarditis.24,115,160 The size of Peff is assessed by the end-diastolic distance of the echo-free space be-tween the epicardium and parietal pericardium(Table 10). ${}^{115,128}$ It is re-commended that images should include the extent and location of each effusion measurement, as this allows follow-up studies. Transthoracic echocardiography enables the recognition of CTP and the presence of constriction. ${}^{115}$

5.6. Cardiovascular magnetic resonance

Cardiovascular magnetic resonance is the accepted gold standard for the quantification of biventricular function and detection of WMA.Cardiovascular magnetic resonance has the advantage of tissue differ-entiation, non-invasively detecting myocardial and pericardial inflamma-tion, as well as fibrosis.30 The diagnostic targets in non-ischaemic myocardial inflammation include myocardial oedema, hyperaemia and capillary leak, and necrosis/fibrosis(see Supplementary data online,Figure S2).161-164 The diagnostic accuracy of CMR is higher if performed early in the time course of disease(best within the first 2 weeks).Myocardial oedema and changes due to inflammation lead to increased tissue water content that can be detected as increased signal intensities on T2-weighted imaging and/or T2 mapping: increased tissue free-water content will also lead to an increased signal in T1 mapping and extracellular volume(ECV) quantification. Myocyte necrosis and fibro-sis can result in non-ischaemic(e.g. mid-wall, subepicardial, patchy) pat-terns of LGE, which do not typically follow a coronary artery distribution. The identification of myocardial with chest pain presenta-tion is less challenging than in HF and arrhythmic scenarios. The up-dated LLC, which include parametric mapping methods(T1/T2/ECV),should be applied for diagnosis, as the combined approach increases the diagnostic accuracy(see Figure 4). ${}^{30}$ It is important to note that im-aging evidence of myocardial inflammation does not provide the under-lying history(see Supplementary data online, Figure S2).

In the case of pericarditis, CMR detects thickening, oedema, and LGE of the pericardium.110,129,165 It is important to note that pericardial LGE may imply ongoing inflammation and neovascularization rather than simple scarring(see Supplementary data online, Figure S2).Cardiovascular magnetic resonance is helpful for an objective assess-ment of the degree of inflammatory involvement of the pericardium,either for first diagnoses or follow-up(for details see Figure 7 and Table 9).

Given its physical properties, CMR is affected by ferromagnetic ob-jects, such as valvular prosthesis and implants, resulting in artefacts.The same holds true for active MR-conditional devices, such as pace-makers, ICDs, and cardiac resynchronization therapy(CRT) pace-makers/defibrillators(P/Ds), but dedicated techniques are now available to achieve better diagnostic image quality in many cases.166 Cardiovascular magnetic resonance could also be used in patients with non-conditional devices with a clear clinical indication if other im-aging modalities are not helpful. In all cases, programming of the im-planted device before and after the scan is warranted, as well as patient monitoring.

Even in intubated patients, CMR scans are feasible in order to detect inflammation. ${}^{167}$ If breath-hold capacities are reduced or the patient is uncooperative, fast imaging techniques and/or motion-corrected im-aging have to be applied. ${}^{168}$

Recommendation Table 3-Recommendations for the use of cardiovascular magnetic resonance imaging(see Evidence Table 3)

|Recommendations|Classa|Levelb| |---|---|---| |Myocarditis||| |CMR is recommended in patients with suspected myocardial diagnosis and to determine the cause of acute myocardial injury, including assessment of oedema, ischaemia, and necrosis/fibrosis/scarring. 115,164,169-183||B| |CMR is recommended for follow-up at least within the first 6 months in patients with myocarditis to identify a healed or ongoing process, for risk stratification and personalized therapy, and to enable a return to exercise.10,62,184-186||C| |Pericarditis||| |CMR is recommended in patients with suspected pericarditis when a diagnosis cannot be made using clinical criteria to assess evidence of pericardial thickening, oedema,LGE, and to assess the persistence of disease during follow-up in selected cases.110,129,165,187-194||B|

CMR, cardiovascular magnetic resonance; LGE, late gadolinium enhancement.

aClass of recommendation.

bLevel of evidence.

5.7. Computed tomography

Computed tomography is an established tool for excluding CAD de-pending on the risk score and can be used in the diagnostic work-up according to current ESC guidelines.65,72,195

Contrast-enhanced CT may be very useful to make an aetiological diagnosis in patients presenting with large PEff including tamponade.196 Computed tomography is important before pericardietomy for con-striction to evaluate the anatomy and extent of calcifications as a higher burden of pericardial calcification has been associated with a better post-surgical outcome.197 Furthermore, anatomical abnormalities,such as pectus excavatum, can be identified.198 Meanwhile,CT in com-bination with FDG-PET plays a crucial role in the detection of CS(Section 9.4).

Recommendation Table 4- Recommendations for computed tomography(see Evidence Table 4)

|Recommendations|Classa|Levelb| |---|---|---| |CT is recommended to evaluate pericardial thickness, calcifications, masses, and loculated pericardial effusions, as well as concomitant pleuropulmonary diseases and chest abnormalities.|$\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$|C|

CT, computed tomography. Remaining recommendations for CT can be found in Recommendation Table 1.

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

bLevel of evidence.

<FIGTEXT=></FIGTEXT>

ESC Guidelines

5.8. Nuclear medicine

Fluorodeoxyglucose uptake reflects metabolically active inflammatory cells in AM.201

Fluorodeoxyglucose positron emission tomography can be consid-ered as an alternative in patients when CMR is unsuitable because of an irregular heartbeat or device-related artefacts. ${}^{202}$ Simultaneous/hybrid cardiac PET-CT/CMR imaging complement each other in the assess-ment of myocarditis compared with either approach alone.201,203 Fluorodeoxyglucose positron emission tomography is also a powerful tool to detect and assess the extent of extracardiac involvement in sar-coidosis(see Section 9.4).

Appropriate fasting before FDG-PET is a must to obtain reliable re-sults.204 Typical preparation protocols include a high-fat and low-carbohydrate diet for 12-24 h followed by complete fasting other than water for the 6-12-h period prior to FDG injection.

The role of nuclear imaging in pericarditis is less well established. The use of FDG-PET/CT in pericarditis is generally complementary and is most often implemented in cases where CMR cannot be used. 205

Recommendation Table 5-Recommendations for nu-clear medicine(see Evidence Table 5)

|Recommendations|Classa|Levelb| |---|---|---| |Carb-free 18F-FDG-PET or 18F-FDG-PET/CT should be considered for the diagnostic work-up in patients with suspected myocarditis and/or pericarditis in whom echocardiography and CMR are inconclusive for the clinical diagnosis.201,206|lla|C|

CMR, cardiovascular magnetic resonance; CT, computed tomography; 18F-FDG-PET,[18F]-fluorodeoxyglucose positron emission tomography.

Class of recommendation.

bLevel of evidence.

5.9. Endomyocardial and pericardial biopsy

5.9. Endomyocardial biopsy

Endomyocardial biopsy enables the identification of the underlying histological subtype of cardiac inflammation. However, non-invasive imaging methods have significantly improved, allowing the diag-nosis of myocardial by CMR. Therefore, the role of EMB in clinical practice has changed. Endomyocardial biopsy remains important for high-risk patients and in some intermediate cases when the knowledge of the histological subtype and the identification of a possible viral eti-ology are important for targeted therapies(Figure 15).

Endomyocardial biopsy has potential complications(e.g. cardiac per-oration/tamponade, thromboembolism, valvular trauma, severe arrhyth-mias, and death). 9,210 Rates depend on the setting and centre experience and range between 0.6% and 5%, 63,211 and increase up to 26% in FM cases on mechanical circulatory support(MCS). ${}^{212}$ Children may have higher complication rates depending on age, the experience of the cen-tre, and the site of the biopsy(LV or RV). ${}^{63,213}$ On this basis, the clinical use of EMB should be tailored according to the risk-benefit ratio.

Histological and immunohstological investigations, as well as viral gen-ome analysis, allow the identification of viral or immune-mediated LM,EM-GM, and sarcoidosis.33,214,215 Moreover,EMB allows the identification of the inflammatory stages in association with the degree of myocardial ne-crosis and fibrosis. Endomyocardial biopsy is useful in the differential diag-nosis of infiltrative/storage diseases(amyloidosis, haemochromatosis,

glycogenosis), different CMPs, and genetic heart diseases 33,216 if non-invasive imaging is inconclusive. This approach is consistent with other international position statements.9,210 Endomyocardial biopsy can be use-hul in cases of chronic CMP that is progressive or unresponsive to stand-ard therapy. When FM, CM or EM are suspected, early EMB is required to start immunosuppressive therapy rapidly and improve outcomes.57 In GCM, EMB has high sensitivity(80%-93%) and a positive predictive value(71%), especially if performed within 2-4 weeks from symptom onset.217 In CS, EMB may have a low sensitivity(20%-30%) due to the focal nature of inflammatory lesions, but can be improved by guiding the EMB using CMR or electro-anatomic mapping(EAM). 218-222

Historically, diagnosis by EMB was based on the histological Dallas cri-teria in HE-stained heart tissue sections revealing myocytolysis and inter-stitial immune cells.223 However, since there is high interobserver variability, immunohistochemical detection of lymphocytes(CD3) and macrophages(CD68) can definitely increase sensitivity for the diagnosis of myocarditis.10,224-226 A recent meta-analysis indicates that the use of immunohistochemistry can increase the detection rate of inflammation in EMB specimens to~51%.227 A value of≥14 leucocytes/mm2 with T lymphocytes of≥7 cells/mm2 has been considered as the cut-off for the diagnosis of myocarditis.10 In acute LM, the number of T lymphocytes is generally higher(>25 cells/mm2).228 Additionally, the expression of MHIC class II molecules in antigen-presenting macrophages and dotheno-lial cells is routinely observed in EMB with myocarditis.33 Endomyocardial biopsy also enables the detection of viruses, such as enteroviruses,B19V,228 and herpesvices, e.g.EBV and HHV-6, using quantitative real-time(RT)-PCR and in situ hybridization. It is likely that advances in mo-lecular diagnostic techniques, such as next-generation sequencing, will help to identify potential new pathogens. Positive PCR results obtained on EMB have to be accompanied by a parallel investigation of blood sam-ples collected at the time of the EMB to exclude acute systemic virus in-fection. In cases of acute cardiac and systemic virus infection,immunosuppressive therapy must be avoided.

The most common site of EMB is the RV septum, but occasionally LV or biventricular EMB may be needed. The decision of the EMB site should be based on the clinical indication, findings of pre-procedural imaging, and operator expertise.229 A study of 755 patients with suspected myocardi-tis and non-ischaemic CMP(including infiltrative and storage disorders)indicated that biventricar EMB can increase diagnostic accuracy com-pared with selective LV or RV EMB.211 Sampling error is the major limi-tation of the diagnostic accuracy of EMB. The minimal number of required EMB samples for each technique is reported in Table 11.33

It should be emphasized that PCR in EMB tissue and in situ hybridiza-tion can be used for identification of the viral agent, because viral ser-ology concurs with the results of PCR in a minority of patients(~4%) with myocarditis.230 With PCR, the rate of viral sequences de-tected in EMB specimens is up to 67%, although the rate varies widely among studies.63,228,231 The PCR tests for the detection of infectious agents must be performed in laboratories that are accredited and cer-tified for the identification of viruses, bacteria, and parasites. The evalu-ation of these PCR results must be done in the context of histological/munohistological findings by pathologists with expertise in cardiovas-cular diseases.

The timely communication of biopsy results is crucial for optimal therapeutic guidance.

Targeted biopsies of an inflamed heart diagnosed using histology, immu-hoistochemistry, and molecular virology could be correlated with mod-ern technologies, such as genomics, epigenomics, proteomics, and metabolomics to improve the diagnosis and therapy. Recommendations for EMB can be found in Recommendation Table 1.

ESC Guidelines

Recommendation Table 6- Recommendations for endomyocardial biopsy(see Evidence Table 6)

Recommendations

EMB is recommended in patients with high-risk myocardits d, and/or haemodynamic instability, and/or in patients with intermediate-risk myocarditis not responding to conventional therapy in order to detect a specific histologic subtype and to assess the presence of viral genome for treatment. ${}^{34,63,73,131}$

EMB, endomyocardial biopsy.

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

$b$ Level of evidence.

${}^{c}$ Contemporary evaluation of EMB should be based on histology, immunohistology, and molecular pathology for detection of viral infections in myocardial and blood samples(see also Table 11).

dSee Table 7.

![Acute lymphocytic myocarditis\nChronic lymphocytic myocarditis\nEosinophilic myocarditis\nG\nH\nE\nC\nG\nH\nI\nL\nC\n$O_{C}$\nEsc\n$O_{C}$\nG\n$O_{C}$\n100μm\nLiymphocytic\nG\nH\nCD68\n100μm\nG\n](2/aj0YEe4oUhYkBdfpda0fYP/figure30dbd3c6c53a4d73a34dff3efc3b097a_0_10.png) Figure 15 Histopathological findings in myocarditis. HE, haematoxylin eosin.(A-C) Endomyocardial biopsy for acute lymphocytic myocarditis reveals cardiomyocyte necrosis(A,HE stain) and severe focal infiltration of CD3+ T cells(B) and CD68+ macrophages(C), as detected by immunohistochem-istry.(D-F) In chronic lymphocytic myocarditis, no cardiomyocyte injury is observed, but there is focal replacement fibrosis(D, HE) in the presence of CD3+ T cells(E) and CD68+ macrophages(F).(G-l) In acute eosinophilic myocarditis, necrosis of cardiomyocytes is associated with numerous eosino-philic granocytes(G, Giemsa stain), some CD3+ T cells(H), and numerous CD68* macrophages(l).(J-L) Areas with severe cardiomyocyte necrosis in the presence of extensive focal and diffuse infiltration of eosinophilic granocytes(J, Giemsa stain), CD3+ T cells(K), and CD68+ macrophages and CD68+ giant cells(L) are typical of giant-cell myocarditis.(M-O) Cardiac sarcoidosis is histologically characterized by the presence of granulomas, usu-ally in the absence of cardiomyocyte necrosis(M, Giemsa stain), but with focal infiltration of CD3+ T cells(N) and numerous CD68* macrophages and CD68+ giant cells(O).

ESC Guidelines

Table 11 Parameters for reporting by endomyocardial biopsy

|Criteria|Parameters for reporting| |---|---| |Histology(paraffin-embedded EMB,at least 3 EMB)|Presence and extent of cardiomyocyte necrosis, inflammation, fibrosis| |Immunohstology (paraffin-embedded EMB, at least 3 myocardial samples)|Presence, extent, localization, and typing of immune cells in the myocardium: CD3+ T lymphocytes, CD68+ macrophages (≥14 leucocytes/mm2 with T lymphocytes≥7 cells/mm),10 HLA-DR expression in immune cells and endothelial cells| |Molecular pathology [infections: RNAlater, snap-frozen tissue(1-2 EMB), paraffin-embedded EMB]|Presence, typing, and quantification of DNA/RNA from infectious agents by q(RT)-PCR Viruses: mainly enteroviruses, parvovirus B19, human herpesvirus 6, Epstein-Barr virus; Borrelia spp., Trypanosoma cruza q(RT)-PCR for detection of systemic infections| |Molecular pathology(genetics: RNAlater, frozen tissue, paraffin-embedded EMB, blood)|NGS for detection of pathogenic variants in cardiac genes, traditionally associated with cardiomyopathies (especially desmosomal and sarcomeric/ cytoskeletal genes)|

DNA, deoxyribonucleic acid; EMB, endomyocardial biopsy; HLA-DR, human leucocyte antigen-DR isotype; NGS, next-generation sequencing; q(RT)-PCR, quantitative(real-time) polymerase chain reaction; RNA, ribonucleic acid.

${}^{a}$ See Supplementary data online, Table S1.

5.9.2. Pericardial biopsy

In clinical practice, pericardial biopsy is rarely indicated in complicated cases not responding to conventional anti-inflammatory therapy and with a high suspicion of a specific actiology(e.g. primary pericardial tu-mours and metastases), which cannot be determined by non-invasive diagnostic methods. Pericardial biopsy can be performed by pericardio-scopy(an endoscopic study of the pericardium that is available in a lim-ited number of tertiary referral centres). It is more commonly performed with a thoracoscopic or surgical approach, usually during a pericardial drainage or a pericardial window. 1,232

5.10. Role of autopsy

In autopsy studies of SCD, myocarditis has been described as a com-mon finding, with incidences of myocarditis in children and adults ran-ging from 0.3% to 14.8%.87,88,233-235 In the majority of these studies, the incidence of myocarditis in SCD was higher in people aged under 35 years.236,237 A nationwide unselected cohort of 14 294 deaths in Denmark suggested that 6% of all autopsied SCD was caused by myo-carditis. Males have a significantly higher incidence.88 In the UK, be-tween 1994 and 2022, myocarditis was reported as a rare cause of SCD in non-hospitalized individuals(1.1%) in 7702 consecutive cases

<EndOfPara>of SCD. Here, the most common reported form was LM(56%), which corresponds well with data obtained from EMBs of patients with sus-pected myocarditis.10,63,87,238

In the guidelines for the histopathological diagnosis of myocarditis,‘fulminant’ or‘multifocal’ myocarditis can be generally considered as a reliable or acceptable cause of death, especially when inflammation is the only substantial histopathological finding. This approach is endorsed by the Association of European Cardiovascular Pathology.239

In addition to LM, other types of cardiac inflammation are observed in autopsies. In 558 of 49 612(1.1%) forensic autopsies, myocarditis was detected by histology. In a Finnish study consisting of 351 patients with CS,14% experienced fatal and aborted SCD as a presenting mani-festation. In 64%, undiagnosed granulomas in the heart were the cause of fatalities.240 The likelihood that a case of unexplained SCD is caused by an underlying inherited disorder has led to the emerging role of gen-etic testing of DNA obtained at autopsy(also called molecular autopsy or post-mortem genetic testing).239 Therefore, pathologists play an im-portant role in the identification of families at risk by reporting whether it is recommended to refer first-degree family members for clinical screening and/or to perform additional post-mortem genetic testing to identify the underlying cause of cardiac inflammation.241,242 Legal and ethical issues related to genetic testing in deceased subjects who did not give their consent are not universally regulated by law.

Recommendation Table 7- Recommendations for autopsy(see Evidence Table 7)

|Recommendations|Classa|Levelb| |---|---|---| |Comprehensive autopsy is recommended in all patients<50 years of age with SCD to evaluate the presence of acute myocardialitis as a cause and to detect potential underlying inherited cardiac diseases. 87,243-246c|$\begin{array}{l}\\ \\ \\ \\ \\ \end{array}$|$\begin{array}{l}$ B| |Retaining samples suitable for DNA extraction and consulting a cardiac pathologist is recommended in cases of SCD, when an inherited cause is suspected, or the cause of death remains unexplained.243,247c|$\begin{array}{l}\\ \\ \\ \\ \end{array}$|B|

DNA, deoxyribonucleic acid;SCD,sudden cardiac death.

a Class of recommendation.

bLevel of evidence.

cIn line with the 2022 ESC Generallines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. ${}^{58}$

5.11. Role of cardiac catheterization and coronary angiography

Given the overlap of symptoms(especially chest pain), as well as the elevation of biomarkers(such as troponin in the case of myocardial in-volvement and NT-proBNP) and ECG changes, ACS is the main differ-ential diagnosis for IMPS. Depending on the initial clinical assessment,ACS should be ruled out according to current guidelines(Figure 9).The recommended methods are coronary CT or invasive coronary angiography depending on likelihood of obstructive CAD.72,248 Coronary angiography is preferable in patients with a high likelihood of ACS. It should be noted that CAD may coexist with myocarditis in particular scenarios, including EM and ICI-induced myocarditis.249-251

Cardiac catheterization is also indicated to monitor and guide HF therapy, as well as the early need for more advanced support(HT or MCS in the case of refractory haemodynamic deterioration. ${}^{12}$

ESC Guidelines

For pericarditis, specific indications for cardiac catheterization in-clude the differential diagnosis between restrictive CMP(RCM) or CP,252 when this differentiation cannot be done by multimodality im-aging(see Supplementary data online, Section 2.6).

5.12. Electro-anatomical mapping

The diagnostic yield of traditional fluoroscopy-guided EMB in patients with suspected myocarditis may decrease with segmental or patchy myocardial involvement, as seen in CS. Electro-anatomical mapping,using bipolar and unipolar voltage mapping, allows the identification of low-voltage areas, which reflects abnormal myocardial tissue(scar-ring, inflammation), and therefore guides EMB.218-222 Unipolar EAM-guided EMB demonstrated a higher diagnostic yield than bipolar EAM(83% compared with 63%), consistent with the epicardial substrate. 84,218,221

A meta-analysis of 148 patients showed a higher diagnostic perform-ance of EAM-guided EMB in CS compared with other forms of myocar-ditis. The sensitivity of any abnormal electrogram for a positive EMB was high(92%) but was associated with moderate specificity(58%).221

Electro-anatomical mapping has demonstrated good sensitivity and specificity compared with CMR for the detection of pathological areas of the myocardium.218 The value of EAM to guide biopsy may be lower in AM as low-voltage areas correlate well with LGE, but not with oe-dema.253 There may also be discordance between low-voltage areas and LGE on CMR. However, the combination of unipolar/bipolar EAM with CMR findings increased the diagnosis yield of EMB,218 especially in CS.220 The EAM pattern may also help to differentiate between differen-tial diagnoses, especially between CS and ARVC,254 as CS often involves the basal septum and exhibits a higher bipolar/unipolar low-voltage area ratio.The reported complication rate of EAM-guided EMB is<5%.218,221

Programmed ventricular stimulation(PVS) has not been evaluated in the acute setting and should not be performed in the acute phase. It could be useful for arrhythmia stratification in selected patients with non-active myocarditis, with LGE and risk factors for ventricular arryth-mias(Section 6.5). ${}^{255}$

Recommendation Table 8- Recommendations for electro-anatomical mapping(see Evidence Table 8)

|Recommendations|Classa|Levelb| |---|---|---| |Electro-anatomical mapping should be considered in cases of suspected myocarditis(especially cardiac|la|C| |sarcoidosis) to guide endomyocardial biopsy.|la|C|

aClass of recommendation.

bLevel of evidence.

6. Therapy

The aim of medical therapy for IMPS is to relieve symptoms and to pre-vent complications, especially recurrences and mortality in complicated cases. Medical therapy targets include:(i) infectious agents;(ii) inflam-mation;(iii) immune-mediated processes;(iv) HF and ventricular dysfunction(in cases of myocarditis);(v) arrhythmias; and(vi)

constriction(in cases of pericarditis). Treatments are individualized ac-cording to the specific case and the presumed or diagnosed pathogen-esis, and specific therapeutic concepts will be discussed in the section covering specific causes. There may be differences depending on whether an isolated or a combined form is present. The current evi-dence is more focused on the isolated cases. For combined conditions,the leading one(myoperidcarditis or perimyocarditis) should guide the therapeutic decision-making and subsequent follow-up.

6.1. Non-pharmacological therapy for inflammatory myopericardial syndrome

An important non-pharmacological concept is the restriction of physical activity beyond sedentary activities until symptom resolution and clinical remission with normalization of inflammatory markers. This temporary limitation of physical activities should be individualized according to each patient, and the response to therapy until clinical remission. According to clinical presentation, at least 1 month is needed to reach clinical re-mission, but it can last longer. Depending on the stage and risk of the IMPS, physical activity should be tailored, and temporary restriction of physical activity is necessary in the acute phase of the disease(see Section 7). Previous consensus statements and guidelines1 have tried to provide a fixed time interval. This TF suggests personalizing the treat-ment until clinical remission based on a multiparametric assessment,which was also supported by the 2024 ACC expert consensus paper.Clinical remission is defined as full regression of symptoms, as well as normalization of laboratory results(e.g.C-reactive protein, troponin le-vels) and investigations(ECG,evidence of PEff,CMR evidence of active inflammation)(Table 3). Additional testing(e.g. exercise testing and Holter monitoring) is recommended for patients with myocarditis for the detection of clinical remission. After a prolonged rest period, a grad-ual,montored return to work and physical activity may be helpful, if ne-cessary, guided by a qualified rehabilitation. Currently, evidence-based data are missing on this topic, and the decision must be individualized.

6.2. Pharmacological therapy

6.2.1. Pharmacological therapy for myocarditis

6.2.1.1. General principles

This section will focus on general aspects and non-aetiology-directed therapy. It should be recognized that evidence is very limited in this field and this document will provide guidance for clinical practice.

Medical therapy of myocarditis is based on clinical presentation, case se-verity, and aetiology. It includes general supportive, non-aetiology-directed therapy(e.g.HF therapy),1259 anti-arrhythmic therapy, and specific ther-apy(aetiology-directed therapy).Corticosteroids are considered for autoimmunity-associated cases to suppress the immune system,as first-line therapy in most cases. Severe cases are considered for MCS and HT.

Uncomplicated cases of myocarditis usually present with chest pain and can be empirically treated with aspirin or non-steroidal anti-inflammatory drugs(NSAlDs) for the control of chest pain, if needed.This is supported by a small study showing no harm for patients treated with anti-inflammatory drugs. ${}^{262}$ Concomitant use of colchicine is safe in patients with hypercarditis, preventing recurrences. ${}^{263}$ In clinical practice,β-blockers are often used in patients with myocarditis. In a small study,β-blockers were associated with better outcomes, defined as freedom from cardiac death or HT. ${}^{264}$

ESC Guidelines

Several viruses can cause myocarditis and are mentioned in Section 3.4. The specific therapies for viral etologies can be found in Section 9.5 for influenza-, severe acute respiratory syndrome corona-virus 2(SARS-CoV-2), and HIV-associated myocarditis. For specific

aetologies, refer to the subsections on LM(Section 9.1), EM(Section 9.2), GCM(Section 9.3), CS(Section 9.4), LC(Section 9.5.2),CD(Section 9.5.3), and ICl-associated myocarditis(Section 9.6.1.1).Specific medical therapies are summarized in Table 12.

Table 12 Therapy for specific forms of myocarditis

|Lymphocytic myocarditis (virus-negative)| |---| |1st line therapy| |2nd line therapy| |2nd line therapy| |3rd line therapy| |Eosinophilic myocarditis| |1st line therapy| |2nd line therapy| |3rd line therapy| |Giant-cell myocarditis| |1st line therapy| |1st line therapy| |2nd line therapy| |3rd line therapy| |Cardiac sarcoidosis| |1st line therapy| |2nd line therapy| |1st line therapy| |Cardiac sarcoidosis| |1st line therapy| |2nd line therapy| |2nd line therapy| |1st line therapy| |Lyme carditis| |1st line therapy| |2nd line therapy| |2nd line therapy| |2nd line therapy| |2nd line therapy| |2nd line therapy| |2nd line therapy| |Lyme carditis| |1st line therapy| |2nd line therapy| |2nd line therapy| |2nd line therapy| |2nd line therapy| |Chagas disease| |1st line therapy| |2nd line therapy| |2nd line therapy| |2nd line therapy| |3rd line therapy| |Chagas disease| |1st line therapy| |2nd line therapy| |2nd line therapy| |3rd line therapy|

ESC Guidelines

|ICI-induced myocarditis|| |---|---| |1st line therapy|Withdraw ICI, reassess Non-severe: methyl/prednisolone 500-1000 mg/day x 3 days, then taper with oral prednisone Severe: i.v. methyl/prednisolone 7-14 mg/kg/day x 3 days, then 1 mg/kg/day| |2nd line therapy|If no response in 24-48 h: myophercenoflate mofefetl, ATG& abatacept', alemutuzumab| |3rd line therapy|Infixlipm' or adalimumkab', rituximab|

ATG,anti-thymocyte globules; b.i.d., twice daily; CTLA-4, cytotoxic T-lymphocyte antigen 4; EM, eosinophilic myocarditis; ICl, immune checkpoint inhibitor; IgG, immunoglobulin; IL,interleukin; i.v., intravenous/IGV, intravenous immunoglobulins; p.o., by mouth; s.c., subcutaneous; i.i.d., three times daily; TNF-a, tumour necrosis factor alpha.

${}^{a}$ Azathioprin(minusuppressant purine analog: 1-2 mg/kg per day.p.(typically 100-150 mg daily, in 1-2 divided doses.main target:lymphocytes).

cMyophenolate ofmetolim(immunosuppressant that inhibits inosine monophosphate dehydrogenase, main target: lymphocytes): 500-1000 mg p.o. b.i.d.(total 1-2 g/day).

°Cyclosporine(calcineurin inhibitor that prevents IL-2 transcription in activated T-cells):~3-5 mg/kg/day p.o.(divided b.i.d.) adjusted to target trough levels~150-250 ng/mL

${}^{4}$ Methotrexate(animutabolymate 3) inhibits dihydrolrolate reductase and other folate-dependent steps, reducing proliferation of active lymphocytes): 15-20 mg/week p.o. or s.c.(low-dose weekly, with folic acid supplementation).

*IVIG(immunomodulatory therapy providing pooled lgG antibodies)= standard dose off-label 2 g/kg total dose, typically administered over 1 to 2 days; alternative dosing: 0.4 g/kg/day for 5 consecutive days(less commonly used in myocarditis but sometimes used in autoimmune settings).

Plasmapheres(therapeutic plasma exchange that filters out and removes circulating autoantibodies, immune complexes, and inflammatory mediators) 3-5 sessions in 5-10 days.

&Antithymocyte Globulin(ATG; polyclonal anti-Tlymphocyte antibody that causes profound T-cell depletion):~1 mg/kg i.v.,often given daily for 3-5 days.

Cyclophosphamide(cytotoxic alkylating agent that crosslinks DNA in rapidly dividing cells, main target: lymphocytes): 600 mg/m2.v.bolus on days 1,15,and 30(pulse therapy).

'Rituximab(monoclonal antibody against CD20 on B cells):375 mg/m2 iv. weekly x4 doses(1 month).

lnfixlimab(monoclonal antibody against TNF-a):5 mg/kg iv. at 0,2,6, then every-8 weeks(maintenance).

kAladimab(anti-TNF-a fully human monoclonal antibody) 40 mg SC every week(or every 2 weeks, per clinical response).

Abatacept(CTLA-4 lg fusion protein that binds CD80/86 on antigen-presenting cells, blocking the CD28 co-stimulatory signal required for full T-cell activation): 500 mg.i.every.2 weeks x 5 doses(approximately 10 weeks).

aAltimuzumab (monoclonal antibody against CD25 of lymphocytes): 30 mg i.v. once(alternative: 15 mg i.v. daily for 2 days).

Main mechanisms of action:

T-cell suppression(e.g., corticosteroids, cyclosporine, abatacept)

B-cell depletion (rituximab)

Cytokine inhibition(TNF-a blockers like infliximad, adalumimab)

DNA synthesis inhibition(azathioprine, mycophenolate, methotrexate)

● Immunoglobulin replacement/imentodulation(IVIG)

● Plasma filtration(plasmaphesis)

6.2.1.2. Fulminant myocarditis

Fulminant myocarditis is a rare and severe presentation of myocarditis and a cause of cardiogenic shock, and should be treated accordingly with anotropic or vasopressor support or, if needed, MCS(see Section 6.3).265 It is crucial to be aware of the condition and, when needed, to refer patients to tertiary referral centres that can institute temporary MCS and perform early EMB. Early EMB has been independ-ently associated with a lower rate of death or HT/left ventricular assist device(LVAD) at 1 year.57 The timely communication of biopsy results is crucial. Specific subtypes of FM(e.g. biopsy-proven non-infectious forms) may respond to immunosuppressive therapy in addition to guideline-directed medical care.12,34 An ongoing trial is evaluating cor-ticosteroids for FM(ClinicalTrials.gov Identifier: NCT05150704).

6.2.1.3. Acute myocarditis

Acute myocarditis has a high rate of spontaneous recovery, especially in uncomplicated cases. In cases of AM diagnosed by EMB, up to 50% of patients have spontaneous recovery and up to 25% may have a persist-ent stable cardiac dysfunction. Only 10%-25% have a progressive ven-tricular dysfunction, which could lead to end-stage DCM, HT, or death.9 Treatment of AM depends on severity and clinical presentation.Risk stratification of these patients is mandatory to assess the required level of care.

The acute phase of viral myocarditis(e.g. induced by cytolytic enter-oviruses) is characterized by intense virus replication and myocyte ne-crosis and usually lasts for only a few days. ${}^{266}$ Thus, early antiviral therapy directed against an identified virus is a potential therapeutic

avenue to stop the development of viral myocarditis. The evidence on clinical application of antiviral agents is limited, and antiviral treat-ments should be agreed upon with an infectious disease expert as part of the IMPS.

Patients with AM show significant activation of the NLR family pyrin domain containing 3(NLRP3) inflammasome in the heart, thus it is a potential therapeutic target in the acute phase of myocarditis.267 Activation of NLRP3 functions as a rapid inducer of an inflammatory re-sponse through the production of IL-1β and IL-18. Theoretically, prom-ising agents are anti-IL-1 agents(anakinra, rilonacept, canakinumab) and colchicine,267 although human data on the effect of such agents in myo-carditis are still limited.

In humans, the first evidence has been reported using anakinra, an IL-1 receptor antagonist(L-1RA) that improved heart function in se-lected cases of AM refractory to standard treatment. However, in the ARAMIS trial, anainracta failed to demonstrate a benefit in patients with suspected AM without a specific aetiology(NCT03018834).268 The primary endpoint was the number of days alive free from any com-plication due to AM. The study had potential limitations related to the limited sample size, the inclusion of a low-risk population, and the short follow-up, but it proved that anakinra was safe in this setting.

Regarding modulation of the immune response, further randomized studies are needed to assess treatment with intravenous immunogloblu-lins(IVIG) in AM for adults, 269 since case series and retrospective ana-lyses suggest a benefit in terms of transplant-free survival. Intravenous immunoglobulins are commonly prescribed in paediatric patients.269 In general, treatment of AM with corticosteroids is controversial, with the exception of ICI-induced myocarditis270 and EM.271

ESC Guidelines

The efficacy of combined immunosuppression(prednisone with ei-ther cyclosporine or azathioprine), compared with placebo, was as-sessed in a single randomized controlled trial (RCT) in patients with biopsy-proven AM of unspecified aetiology, since infectious causes were not excluded by PCR.272 The trial was designed to determine whether immunosuppressive therapy improved LV function in patients with AM. There was no significant difference in survival between the two groups ( $P=0.96$ ). The study had several limitations, such as small sample size and incomplete analysis of EMB based only on histopath-ology. However, in specific histopathological forms of AM, such as GCM, immunosuppressive drugs are recommended (see Sections 9.2 and 9.3).

6.2.1.4. Subacute and chronic myocarditis

Chronic myocarditis may represent an intermediate stage between subacute myocarditis and inflammatory CMP. During chronic myo-carditis, HF may develop, and guideline-directed medical therapy(GDMT) for HF is the cornerstone in the treatment of chronic myo-carditis. ${}^{12,259}$ Antiviral therapy has little benefit in the subacute and chronic stages of myocarditis, ${}^{273}$ and the effects of immunomodula-tory drugs on chronic myocarditis of unspecified aetiology are still controversial.

Recommendation Table 9- Recommendations for medical therapy in myocarditis(see Evidence Table 9)

|Recommendations|Classa|Levelb| |---|---|---| |Management of symptoms||| |NSAIDs(together with proton pump inhibition)||| |should be considered in patients with associated symptoms of pericarditis to reduce symptoms.|lla|C| |Colchicine should be considered in patients with myopericarditis to reduce recurrences.|lla|B| |Management of heart failure||| |Adherence to the ESC HF guidelines is recommended in cases of myocarditis with LV systolic dysfunction and/or HF to reduce symptoms and to improve LV function.|1|C| |HF therapy should be considered in patients with myocarditis and LV systolic dysfunction for at least 6 months upon complete LV functional recovery to stabilize LV function.|lla|C| |Management of arrhythmias||| |β-Blockers, with a continuation for at least 6 months, should be considered in patients with acute myocarditis, especially those with troponin elevation, to control symptoms and prevent arrhythmias.|lla|C| |Anti-arrhythmic treatment should be considered in post-myocarditis patients with recurrent, symptomatic VT to reduce arrhythmic burden. 58|lla|C| |Immunosuppressive therapy||| |Corticosteroids should be considered in patients with fulminant, non-infectious forms of myocarditis to stabilize the patients.|lla|C|

|Corticosteroids may be considered in patients with acute myocarditis with impaired LVEF if refractory to standard HF therapy to stabilize patients.|lb|C| |---|---|---| |Routine use of immunosuppressive therapy is not recommended in acute myocarditis with preserved|III|C| |LV function because no outcome benefit has been shown.|||

ESC,European Society of Cardiology;HF,heart failure;LV,left ventricle;LVEF,left ventricular ejection fraction; NSAID, non-steroidal anti-inflammatory drug;VT,ventricular tachycardia.

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

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

6.2.2. Pharmacological therapy for pericarditis

6.2.1. General principles

The aims of medical therapy for pericarditis are to provide:(i) symp-tomatic care(mainly control of pericarditis chest pain);(ii) clinical re-mission; and(iii) prevention of complications, especially recurrences and constriction.

Exercise restriction limits the heart rate and may be useful to reduce pericardial friction, which can be improved using drugs that reduce it(e.g.β-blockers or iabradine for those who cannot receive or tolerateβ-blockers) for patients with a resting heart rate of>75 b.p.m., and symptoms despite empirical anti-inflammatory therapy. ${}^{274}$

6.2.2.1.1. Acute pericarditis(first episode). The mainstay of medical therapy is empirical anti-inflammatory therapy using aspirin or NSAIDs at full anti-inflammatory doses with appropriate time intervals of ad-ministration(usually every 8 h) plus colchicine to reduce the risk of re-currences.24,25,108,275-278 Gastrooprotection with a proton pump inhibitor is recommended using NSAIDs.279

When aspirin and NSAIDs are contraindicated, or for specific indica-tions, corticosteroids should be considered at low to moderate doses plus colchicine(see Tables 13 and 14).

In cases of incomplete response to aspirin/NSAIDs and colchicine,corticosteroids may be added at low to moderate doses as triple ther-apy.1 In cases of recurrence, every effort should be made not to in-crease the dose or to reinstate corticosteroids.

The use of colchicine on top of empirical anti-inflammatory therapy is supported by most of the published evidence, with the single excep-tion of a small open-label trial that was probably underpowered to test the study hypothesis for patients with AP.281 Specific dosing and duration of therapy are summarized in Table 13. Monitoring of serum C-Reactive protein and CMR imaging is recommended to assess clinical remission, guide the treatment length, and evaluate the re-sponse to therapy in more complicated and difficult-to-treat cases.In uncomplicated cases, clinical follow-up with/without echocardiog-raphy is sufficient.

6.2.2.2. Incessant and recurrent pericarditis

In patients with incessant pericarditis is advanced is always colcine in association with aspirin/NSAID or low to moderate doses of corticosteroids. For more difficult cases, chest pain can be controlled by a combination of aspirin or an NSAID plus corticosteroids at low to moderate doses and colchicine(triple therapy). The i.v. route should be considered to ensure a clinical re-sponse or to control symptoms in more difficult or resistant cases.

ESC Guidelines

Table 13 Specific initial dosing and duration of therapy for acute and recurrent pericarditis

|Therapy|Dosing|Durationa|Taperinga| |---|---|---|---| |Aspirinb|750-1000 mg 3 times daily|1-2 weeks|Decrease by 250 mg every 1-2 weeks| |lbuprofenb|600-800 mg 3 times daily|1-2 weeks|Decrease by 200 mg every 1-2 weeks| |Indomethacin|25-50 mg 3 times daily|1-2 weeks|Decrease by 25 mg every 1-2 weeks| |Colchicineb|0.5 mg once daily(<70 kg or severe renal impairment) or 0.5 mg twice daily|3-6 months|Not required| |Prednisone|0.2-0.5 mg/kg/day|2-4 weeks|Several months| |Treatment for recurrences only:|||| |Azathioprine|Starting with 1 mg/kg/day then gradually increased to 2-3 mg/kg/day|Several months|Several months| |IVIG|400-500 mg/kg i.v. daily for 5 days|5 days|Not required| |Anakinra|1-2 mg/kg/day up to 100 mg/day in adults|At least 6 months/|Needed(at least 3-6 months)/| |Rilonacepc|320 mg once daily followed by 160 mg weekly|>12 months|unknown|

IVG,intravenous immunoglobulins; NSAID, non-steroidal anti-inflammatory drug

Treatment for recurrences only

*Therapy duration as initial dosing for all treatments the attack dose is maintained until symptom resolution and normalization of inflammatory markers(e.g.C-reactive protein) and other investigations(electrocardiogram) then tapering is recommended. It should be tailored to the single patient according to disease severity and patient response. Tapering is especially important for corticosteroids where tapering is particularly slow, especially below 15 mg/day, the common threshold for recurrences(see Table 14). Monitoring is essentially based on the assessment of blood count, creatinine, creatine kinase, transaminases, C-reactive protein, echocardiography. Anakinra should be tapered after clinical remission. Different schemes are adopted: e.g. reducing one dose per week every month; every other day for all dose for at least 3 months then half-dose every other day for at least 3 months.

Aspirin and ibuprofen are common first-level treatments for the first episode of pericarditis(acute pericarditis) associated with colchicine for at least 3 months. Aspirin is the preferred choice for patients with ischaemic heart disease. Indomethacin is usually considered for incessant/recurrent cases. In incessant/recurrent cases, colchicine is maintained for at least 6 months. Aspirin/NSAID full dose is recommended for patients with normal or mildly reduced renal function. For those with moderate to severe renal impairment, dose adjustment or use of corticosteroids is recommended.

‘Rioncept is registered in the USA but is not currently available in Europe. Anakrina, due to its short half-life, may be the preferable choice in patients at increased risk of infections.

Table 14 Tapering of corticosteroids

|Prednisone|Starting dose 0.20-0.50 mg/ kg/day|Tapering| |---|---|---| |Prednisone daily dose|>50 mg|10 mg/day every 1-2 weeks| ||50-25 mg|5-10 mg/day every 1-2 weeks| ||25-15 mg|2.5 mg/day every 2-4 weeks| ||<15 mg|1.25-2.5 mg/day every 2-6 weeks|

aAvoid higher doses except for special cases, and only for a few days, with rapid tapering to 25 mg/dispenred 25 mg is equivalent to methylprednisone 20 mg.

Every decrease in prednisose dose should be done only if the patient is asymptomatic and C-reactive protein is normal, particularly for doses of<25 mg/day.

Calcium intake(supplement plus oral intake) of 1200-1500 mg/day and vitamin D supplementation of 800-1000 IU/day should be offered to all patients receiving glucocorticoids. Moreover, bisphosphonates are recommended to prevent bone loss in all men aged≥50 years and postmenopausal women in whom long-term treatment with glucocorticoids is initiated at a dose of≥5.0-7.5 mg/day of prednisone or equivalent. ${}^{280}$

Patients who develop a recurrence during corticosteroid tapering should continue colchicine and receive an NSAID on top of this treat-ment instead of increasing the dose of corticosteroids. Which medica-tion should be tapered first(corticosteroids or NSAID) depends on the specific clinical scenario(age, kidney function, haemorrhagic risk, and use of oral anticagulants).

For patients with corticosteroid dependence, colchicine resistance,and evidence of elevated C-reactive protein(baseline or subsequent episode), clinical trials and an international registry supported the use of an anti-IL-1 agent(anakin r or riloncept).108,275,282-284 An

advantage of these agents is the rapid onset of action and the possibility of rapid withdrawal of corticosteroids.285 There is evidence of efficacy with anti-IL-1 agent(anakrina or rilonacept) monotherapy.

However, concomituent use of colchicine could be helpful to reduce re-currences and prolong recurrence-free survival, providing a sequential block of the pro-inflammatory pathway leading to the generation of IL-1.28 Chcolicine should be maintained and withdrawn as the last drug only after stable remission. Moreover, colchicine has the safest car-diovascular profile and is now proposed to prevent major adverse cardiac events(MACE) in patients with atherosclerotic cardiovascular dis-eases.248 In patients obtaining stable remission with a chronic low dose of corticosteroids(e.g. prednisone≤5 mg or equivalent) plus colchicine,the decision of switching to IL-1 blocker treatment should be tailored to the patient on an individualized basis, taking into account several para-meters(such as tolerability, age and sex issues, patient preference).The use of anti-IL-1 agents may be associated with a moderate increase in the overall risk of mild to moderate infections. Safety data on anti-IL-1 agents are reassuring when considering new malignancy risk, whereas their safe administration in patients with known active malignancies has not been well investigated to date.

There is limited evidence for other drugs for pericarditis.Azathiornhe has been empirically used in patients with recurrences and a lack of response to first- and second-level options such as as-pirin/NSAID, colchicine, and corticosteroids.287 However, this drug seems more appropriate as a steroid-sparing agent, and has limited ef-ficacy for those with acute pain. Intravenous immunoglobulins have also been tested in patients with refractory RP after failure of first and second options, as well as anti-IL-1 agents. These drugs may be efficacious either for infectious or non-infectious aetologies, since they are able to clear infectious agents and modulate the immune response.288 Both corticosteroids and immunoglobulins have been

ESC Guidelines

![Patient with acute pericarditis\n $\downarrow$\nExercise-restriction and first level therapy\nASA or NSAID (usually ibuprofen or indomethacin) plus colchicine (Class I)\nResponse to medical therapy\nY\nTapering of ASA/NSAID and colchicineb for 3-6 months to reduce recurrence risk\nN\nIncessant/recurrent\nLow to moderate doses of corticosteroids plus colchicine or triple medical therapy with corticosteroids, NSAID and colchicinec(Class II)\nResponse to medical therapy\nY\nTapering of corticosteroids and colchicineb for at least 6 months to reduce recurrence risk\nN\nIncessant/recurrent\nAnticent/recurrent\nAnti-IL-1 agents(Anakinra or Rilonacept) (Class I)d\nESC\n](2/aj0YEe4oUhYkBdfpda0fYP/figure339cd81158ff49d7ae2e8d32248f8320_0_2.png) Figure 16 Proposed algorithm of medical therapy for pericarditis in adults(not including interventional therapies and pericardiectomy). ASA, acetyl salicylic acid; IL-1,interleukin-1; CRP,C-reactive protein; CMR,cardiovascular magnetic resonance; LOE, level of evidence; N, no; NSAID, non-steroidal anti-inflammatory drug; Y,yes.°ASA is the first option if patients are already on antiplate therapy with ASA. Ibuprofen is usually preferred as the first NSAID. Try more than one agent to evaluate response. Gastropture with a proton pump inhibitor is always recommended with use of aspirin/NSAID. bColchicine is recommended to prevent recurrence. Consider at least 3 months for the first episode of pericarditis and at least 6 months for incessant/recurrent cases. Colchicine to be withdrawn as last drug only after stable remission. Tapering is recommended to reduce the persistence/recurrence of symptoms. Tapering is slower for corticosteroids. Colchicine tapering is usually not performed due to the duration of>3-6 months of therapy. Suggested schemes of tapering are reported in Table 12. For response to therapy we considered clinical remission.°Low to moderate dose of corticosteroids(e.g. prednisone 0.2-0.5 mg/kg/day or equivalent doses of an alternative corticosteroid). dClass I LOE A, Class II LOE C re-gardless of C-reactive protein levels if CMR evidence of pericardial inflammation.

proposed for a non-inflammatory presentation(so-called non-inflammatory phenotype). ${}^{288,289}$

More recently, hydroxychloroquine has shown a steroid-sparing ef-fect and increased flare-free survival in RP in patients with colchicine re-sistance and corticosteroid dependence.290 Treatment duration with aspirin/NSAIDs and steroids should be extended in an individualized

manner, and the tapering process should be slower than for a first epi-sode of AP. ${}^{1}$

The dosing and duration of most common drugs used for pericarditis is summarized in Table 13, while the proposed algorithm of medical therapy for pericarditis(not including interventional therapies and peri-cardiatry) is illustrated in Figure 16.

ESC Guidelines

Recommendation Table 10- Recommendations for medical therapy in pericarditis(see Evidence Table 10)

|Recommendations|Classa|Levelb| |---|---|---| |Colchicine is recommended as first-line therapy in patients with pericarditis as an adjunct to aspirin/NSAID or corticosteroid therapy to reduce subsequent recurrences. ${}^{24,25,108,275-278}$|I|A| |Anti-IL-1 agents(akinnra or riloncept) are recommended for patients with recurrent pericarditis after failure of first-line therapies and corticosteroids and elevation of C-reactive protein levels to reduce recurrences and allow corticosteroid withdrawal. ${}^{108,275,282-284}$|I|A| |High-dose aspirin or NSAIDs with proton pump inhibitors are recommended as first-line therapy in patients with pericarditis to control symptoms and reduce recurrences. ${}^{291,292}$|I|B| |Aβ-blocker should be considered in symptomatic patients, despite full anti-inflammatory therapy, and heart rate at rest>75 b.p.m.in order to improve symptom control. ${}^{274}$|IIa|C| |Anti-IL-1 agents(akinnra or riloncept) should be considered in cases of incessant/recurrent pericarditis with evidence of pericardial inflammation on CMR after failure, contraindications, and intolerance to first-line therapies and corticosteroids regardless of C-reactive protein levels to reduce recurrences and allow corticosteroid withdrawal.|IIa|C| |Low- to medium-dose° corticosteroids should be considered for patients with pericarditis only in cases of contraindication/failure of aspirin/NSAIDs and colchicine, or when there is a specific indication to control symptoms and reduce recurrences.|IIa|C| |Hydroxychloroquine may be considered in patients with recurrent pericarditis refractory to standard therapy(including corticosteroids and anti-IL-1 agents) to prolong recurrence-free survival. 290|IIb|B| |Corticosteroids are not recommended as the first option for patients with pericarditis therapy without a specific indication.|III|C|

b.p.m.,be peaks in minute; CMR, cardiovascular magnetic resonance; IL,interleukin; NSAID,non-steroidal anti-inflammatory drug.

Class of recommendation.

bLevel of evidence.

<See Table 13.

${}^{d}$ For example, systemic inflammatory disease on maintenance therapy with corticosteroids,post-pericardiotomy syndromes, post-vaccine pericarditis, severe renal failure,concomitant therapies interacting with NSAIDs such as oral anticoagulant.

6.3. Interventional techniques including circulatory support

6.3.1. Myocarditis

6.3.1.1. Short-term mechanical circulatory support

Myocarditis patients who present with rapid deterioration in haemo-dynamic status and rapidly progressive myocardial dysfunction are

amongst those who respond best to temporary MCS. ${}^{293}$ Among tem-porary MCS, veno-arterial extracorporeal membrane oxygenation(VA-ECMO) represents the most frequently applied or recommended approach,ranging from 75% to 85% of AM cases.75,294-296 Despite the high risk and markedly compromised state of patients undergoing VA-ECMO support for FM, the prognosis is rather favourable, with a high rate of myocardial recovery and patient survival. Several national and international multicentre studies showed in-hospital survival ran-ging from 61% to 72%,297-300 but no freedom from HT in patients with giant-cell FM.294 Temporary MCS should be performed early and in a timely manner in patients with FM with refractory cardiogenic shock because of the high likelihood of recovery.

6.1.3.1. Intra-oortic balloon pump

As mentioned, EMB should be performed as soon as possible, even in the presence of temporary MCS,212,295 and specific immunosuppres-sive therapy should be considered at least as an initial option, while de-termining the myocardial response.295 An intra-aortic balloon pump(IABP) should be considered in cardiogenic shock as first-line MCS with prompt escalation to more powerful MCS if haemodynamic and end-organ perfusion improvement is not observed within a short time(1 h maximum).295

Recommendation Table 11- Recommendations for interventional techniques including circulatory support in myocarditis(see Evidence Table 11)

|Recommendations|Classa|Levelb| |---|---|---| |A timely and dedicated Shock Team discussion is recommended in patients with myocarditis in the presence of haemodynamic compromise, to decide on the need for escalation to MCS and to determine a long-term management plan.|I|C| |Temporary MCS' should be considered in patients with myocarditis and cardiogenic shock or acute decompensation in chronic myocarditis to stabilize the patients.|lla|C|

IABP, intra-aortic balloon pump; MCS, mechanical circulatory support; PLVAD,percutaneous left ventricular asist device; VA-ECMO, veno-arterial extracorporeal membrane oxygenation.

aClass of recommendation.

bLevel of evidence.

${}^{i}$ ABP,PLVAD,VA-ECMO.

6.3.2. Pericarditis

Pericardium-related interventional procedures are increasingly applied and require specific expertise. 1,301 The use of percutaneous interven-tional techniques for pericarditis is not limited to perform percutan-eous drainage, but also to obtain fluid samples for cytology and other pathological examinations(see Supplementary data online, Table S7).Moreover, interventional techniques are used to provide alternative treatment, such as balloon pericardiotomy or, less commonly,intraper-icardial drug administration(e.g. corticosteroids or chemotherapy).

6.3.2.1. Pericardiocentesis and pericardial drainage

Percutaneous pericarditis esstis guided by echocardiography or fluor-oscopy is indicated for CTP and symptomatic moderate to large PEfs

ESC Guidelines

not responding to medical therapy, or when a search for aetiological agents is needed(e.g. suspicion of cancer, bacterial infection).Whenever possible, pericardiocentesis should not drain a large amount of pericardial fluid(usually<500 mL) to prevent pericardim decom-pression syndrome. Complete drainage of the PEff can be achieved,leaving a drain to be removed when the daily drainage is<30 mL.Surgical drainage is required when percutaneous pericardiocentesis is not feasible or purulent effusion is present, to allow complete drainage of the effusion and prevent its organization. Clinical triage has been pro-posed to indicate urgent management.118 An overall score of>6 indi-cates the need for urgent pericardiocentesis, whereas a lower score suggests delaying the intervention(see Figure 12).

Imaging is an essential component for guiding percutaneous peri-cardiocentesis. Under echocardiography,CT, or fluoroscopic guidance,a needle(usually 16-20 gauge) should be introduced into the sub-xyphoid space, although an apical or left-lateral approach might be used. The catheter should usually remain in situ for a few days, also based on the type and efficacy of concomitant systemic and/or topic pharmacological treatment.

6.3.2.2. Percutaneous balloon pericardiotomy

Percutaneous balloon pericardiotomy represents a percutaneous alter-native to the endoscopic or surgical pleuro-pericardial window, which al-lows relapsing pericardial fluid to be absorbed through the ample pleural serosa, especially as pallative and temporary relief.1 It should not be used as a first- or second-line intervention, but rather reserved for very rare cases, such as recurrent neoplastic Peff and CTP, as well as for absolute contraindications for surgery or in the case of a very poor quality of life in terminal patients(see Supplementary data online, Table S8).1

6.3.2.3. Intrapericardial drug administration

Percutaneous access to the pericardium is done using an intrapericardial catheter following pericardial drainage. It may be used to deliver drugs targeting different conditions. Anti-inflammatory agents have been deliv-ered with some efficacy. Intrapericardial crystalminorone,300 mg/m2 of body surface, can be used for autoreactive or recurrent Peffs that do not respond to other conventional therapies, and to avoid or limit systemic side effects of oral corticosteroids. Chemotherapeutics have also been delivered, such as cisplatin and thiotepa(usually for lung and breast cancer, respectively), with demonstrated reduction of Peff re-lapse.302-304 Currently, due to improved chemotherapy, the systemic route is favoured, and therapeutic planning should involve a multidiscip-linary team with cardiologists and oncologists.

Sclerosing agents, such as tal, to enhance pericardium-epicardium adherence and to reduce relapsing Peff, should not be used, because of reduced efficacy compared with a pericardial window or pericar-dietomy, and the risk of inducing constriction. 305,306

6.3.2.4. Pericardioscopy

This procedure is sometimes considered as part of the diagnostic work-up, allowing pericardial biopsy. Pericardial access is also increasingly used for mapping and ablation of the epicardial substrates of VA,with an improved success rate and avoidance of a surgical procedure.

6.3.2.5. Pericardial fluid analysis, pericardial and epicardial biopsy Percutaneous pericardial access may be used also to provide fluid samples for pathological and pathogen examinations(bacterial or viral aetiology),and/or to perform pericardial as well as epicardial biopsies, particularly in cancer screening(see Supplementary data online, Table S7).

6.3.2.6. Circulatory support

Mechanical circulatory support has been shown to be applied in up to 12% of pericardiectomy patients with pre-procedural RV dilatation/dysfunction,307-309 and is sometimes considered peri-operatively.307-309 The association of pre-procedural RV dilatation/dysfunction and re-duced LV function also represent risk factors for a peri-procedural risk of early mortality, calling for timely and prophylactic MCS.

Recommendation Table 12- Recommendations for interventional techniques in pericarditis(see Evidence Table 12)

|Recommendations|Classa|Levelb| |---|---|---| |Pericardiectonesis(echocardiography-,CT-,or fluoroscopy-guided) is recommended for cardiac tamponade, or suspected bacterial or neoplastic pericarditis, or symptomatic moderate to large pericardial effusion despite medical therapy.|1|C| |Surgical pericardial drainage is recommended in patients with pericardial effusion when percutaneous pericardiacites is not feasible or with purulent pericardial effusion to allow complete drainage and to prevent constriction.|1|C| |Surgical pericro-pericardial window is recommended in patients with relapsing pericardial effusion despite medical therapy.|1|C|

CT, computed tomography. ${}^{2}$ Class of recommendation.bLevel of evidence.

6.4. Surgical therapy

6.4.1. Myocarditis

The surgical treatment of myocarditis mainly accounts for HT, when there is no myocardial recovery. In addition to infective or autoimmune aetiol-gies, radiation-induced myopericarditis(usually secondary to haemato-logical cancer) may contribute to the indications for such an intervention. Limited series of HTs due to radiation-induced myocarditis have been described with satisfactory results. Secondary malignancy, lung and kidney failure are negative prognostic factors for post-operative mor-bidity and mortality.310 A durable ventricular assist device(VAD) or a total artificial heart are other alternatives for advanced cardiac support.295

6.4.2. Pericarditis

6.4.2.1. Surgical pericardiacentesis

Surgical pericardiocentesis is rarely performed for urgent/emergency conditions, but for large PEff requiring expeditious drainage, not achiev-able with percutaneous-based drainage(e.g. for purulent PEff or clot aspiration).

6.4.2.2. Pericardiotomy/pericardial window

These surgical procedures are carried out to create a connection, namely a pleuro-pericardial window, usually between the lateral or left posterior pericardium and the left pleura. The indication is relapsing Peff with haemodynamic compromise despite conservative treatment or percutan-eous drainage. The pleuro-pericardial window is meant to promote drain-age from the pericardium to the left pleural space.1 Such a window may be created by a small thoracotomy or endoscopically. In selected cases, a pericardial window can also be created in the peritoneal cavity.

ESC Guidelines

6.4.2.3. Pericardiectomy

Pericardiectomy is the mainstay treatment for chronic constriction or CP not responding to anti-inflammatory therapy.311 Complete pericar-dietomy is recommended for the management of CP, as it offers su-perior long-term outcomes and significantly reduces the risk of recurrences compared with partial anterior or anterophrenic pericar-dietomy, which may leave residual constrictive tissue and contribute to persistent or recurrent symptoms. Due to the relative rarity of the condition, and the complexity of patients, pericardiectomy should be performed at high-volume centres that have the required expertise.

Early pericardiectomy within 6 months after the onset of symptoms is associated with the lowest operative mortality.312,313 The occurrence of refractory RP and/or pericardial fluid formation, despite optimal medical and interventional therapy, is also considered a possible indication for surgical pericardiectomy. In the absence of a surgical plane for proper de-corification, a pragmatic approach, named the waffle procedure, can be considered. This technique utilizes longitudinal and horizontal incisions to allow some relief of constriction. However, it usually offers only tem-porary improvement, with a high rate of recurrent constriction.314,315 Extracorporeal circulation may be required in difficult operative condi-tions, such as extensive calcifications with a high risk of marked bleeding during pericardiectomy. Previous 2015 ESC guidelines recommended re-section'of as much as possible' of the pericardium with avoidance of car-diopulmonary bypass(CBP), using this only in circumstances of difficult control of bleeding.1 Cardiopulmonary bypass can play an important role in enabling safe and complete pericardiectomy, particularly in se-lected complex or high-risk cases.

Pericardiectomy is commonly performed without CPB. However,CPB may be necessary in specific clinical scenarios. These include dense adhesions between the pericardium and the myocardium,particularly involving the posterior surface of the heart. CPB is also indicated in cases of haemodynamic instability during dissection.This is especially relevant when heart lifting is required to access the diaphragmatic or posterior pericardium. Additional indications include calcific constrictive pericarditis with myocardial involve-ment, challenging anatomical conditions, or the need for concomi-tant cardiac procedures, such as valve surgery or coronary artery bypass grafting.

Possible benefits of CPB include providing a bloodless field and im-proved visibility for complete pericardial resection, especially posterior-ly, avoiding myocardial injury by decompressing the heart during dissection, maintaining haemodynamic stability, particularly in patients with borderline cardiac output or tamponade physiology. However,the full heparinization required to perform CPB may, in some cases,favour bleeding generated by pericardial resection. Therefore, the indication for the use of CPB must always be taken into consideration intra-operatively and according to the anatomical as well as haemo-dynamic conditions encountered during the surgical procedure. It is,however, self-explanatory that a radical pericardietomy, including also the posterior site of the pericardium, would be usually possible and advisable with the application of CPB. However, diaphragmatic pericardial resection may often be performed without CPB use, taking care to perform resection in a stepwise manner, without prolonging heart lifting and avoiding marked haemodynamic compromise.

Heart transplantation is very rarely indicated in patients with CP.However, it may be considered as a last-resort option in highly selected,exceptional cases. This applies when pericardietomy is not feasible or cannot be completed due to extensive pericardial calcification with myo-cardial involvement, prior surgeries, radiation therapy, or infections that have caused severe adhesions and scarring. Surgical inaccessibility of

critical regions, such as the posterior pericardium, may also preclude complete resection. In some patients, persistent heart failure symptoms and progressive functional deterioration may occur despite maximal medical therapy and attempted pericardietomy. In these cases, heart transplantation might be considered.

It is also an option when coexistent myocardial disease or a mixed con-strictive-restrictive physiology is present, where pericardial resection would not be expected to improve symptoms or haemodynamic function.

In CP,tricuspid regurgitation(TR) is a common finding due to chron-ic elevated right-sided pressures, annular dilation secondary to long-standing volume overload and atrial enlargement, tethering of leaflets due to pericardial constraint. When TR is present in patients undergo-ing pericardietomy, leaving the valve unrepaired can lead to persistent right HF symptoms(e. oedema, ascites, fatigue), poorer functional re-covery post-operatively, and higher long-term mortality, as shown in retrospective observational studies. During pericardietomy, the tri-cuspid valve is accessible, and repair(usually annuloplasty) can be safely performed with minimal added risk-especially when CP surgery is done under CPB. Thus, repair is recommended when TR is more than mild, and anatomy is suitable, and the patient is already undergoing pericardietomy(i.e. no added surgery is required beyond access).Supporting evidence is limited. While RCTs are lacking, the recommen-dation is based on retrospective findings showing improved symptom relief and outcomes with combined surgery, and surgical principles in valve disease management but also the practicality and safety of valve repair when the chest is already open.

Contraindications for pericardietomy may include severe hepatic dysfunction with cirrhosis and ascites, uncontrolled infection or sepsis,and other life-limiting diseases. In some situations, advanced therapy,such as HT, might be the only solution due to unreasonable cardiac decor-tication, because of extensive calcifications or a high risk of cardiac and major vascular injury during pericardiectomy(for predictors of out-comes after pericardiectomy see also Supplementary data online,Table S8 and Section 3.2).

Recommendation Table 13- Recommendations for surgical therapy(see Evidence Table 13)

|Recommendations|Classa|Levelb| |---|---|---| |Surgical pericardietomy is recommended in patients with chronic pericardietic constriction or persistent constractive pericarditis despite medical therapy to improve symptoms and survival.312,313|1|C| |Tricuspid valve repair is recommended in patients with pericardial constriction and severe tricuspid valve regurgitation to improve symptoms and survival.|1|C|

aClass of recommendation.

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

6.5. Management of arrhythmias and prevention of sudden cardiac death in myocarditis

Patients with myocarditis are known to be vulnerable to life-threatening arrhythmias, and careful observation and management of patients ac-cording to the risk stratification is needed. In the 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the pre-vention of sudden cardiac death, significant attention was paid to active

ESC Guidelines

and chronic myocarditis. ${}^{58}$ In addition to these guidelines, our aim is to provide a special focus on several selected scenarios.

6.5.1. Role of active devices(wearable and implanted devices) in acute myocarditis

In AM,AVB may be reversible, and temporary pacing is often necessary in cases of haemodynamic compromise as a bridge to recovery.317 In this setting, temporary transavenous external pacing with an active lead can be used for patients who require prolonged temporary pacing.86,318-320 In the absence of recovery within a clinically reasonable period, defini-tive cardiac pacing is usually necessary in patients with persistent high-degree AV. In patients with LV dysfunction needing frequent ventricular pacing. CRT or conduction system pacing may be helpful.86,321 Permanent pacemaker placement can be considered in patients with AM for persisting high-degree AVB despite medical therapy.

Sustained VA in the context of AM is a rare phenomenon, ${}^{79}$ yet it poses a substantial risk of recurrence, persisting even after resolution of the acute phase. Studies indicate a high recurrence rate ranging from 28% to 60%, which appears higher in patients with monomorphic VT, chronically active myocarditis, antroseptal LGE, and reduced LVEF.71,79,89,222,322-325 In myocarditis, polymorphic and irregular VA are more common during the active inflammatory phase, whereas monomorphic and regular VA are associated with healed myocarditis and scars.79,83,325 An arrhythmic presentation may raise suspicion of an underlying inherited CMP.95 GCM is associated with a high risk of life-threatening VA and ICD implantation can be considered.326 The use of a wearable cardioverder-defibrillator(WCD) is feasible in selected pa-tients with AM at higher risk of VA, when waiting for recovery or with a temporary contraindication for ICD.327-330 The resolution of inflam-mation does not necessarily indicate the absence of risk, because myo-cardial fibrosia may constitute an arrhythmogenic substrate,predisposing a patient to VA long after the acute episode. On this basis,arrhythmia risk stratification should be performed in patients with per-sistent LGE after the acute phase.325 In patients with prior myocarditis,sustained or non-sustained VT during an exercise test performed 6 months after the acute episode was found to be more common among those with an arrhythmic presentation, and was associated with subse-quent adverse events, including malignant VA.331 Late gadolinium en-hancement was also identified as a significant predictor of adverse events, including malignant arrhythmias, irrespective of LVEF, especially in an anteroseptal location.332-334 Implantable loop recorders can be use-ful for early detection of VA in selected patients. 98 Details regarding oral anticoagulation can be found in the 2019 ESC Guidelines for the manage-ment of patients with supraventricular tachyocardia, the 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death, and the 2024 ESC Guidelines for the management of atrial fibrillation.58,260,261

Recommendation Table 14- Recommendations for management of arrhythmias and prevention of sudden cardiac death in myocarditis(see Evidence Table 14)

|Recommendations|Classa|Levelb| |---|---|---| |Pacing in myocarditis||| |Temporary transvenous external pacing should be||| |considered in patients with acute myocarditis and high-degree conduction disorders as a bridge to|IIa|C| |recovery.86,317,335|||

|WCD in myocarditis|WCD in myocarditis| |---|---| |A WCD should be considered for 3-6 months in patients with sustained ventricular arrhythmia during the acute phase of myocarditis as a bridge to|IIa| |323,325,327-330|| |Ablation in myocarditis|| |Catheter ablation, performed in specialized centres, should be considered in post-myocarditis patients with recurrent symptomatic SMVT or ICD shocks in whom AAD are ineffective, not tolerated, or not desired.58|IIa| |ICD in myocarditis|| |Secondary prevention|| |ICD implantation is recommended in patients with non-active° myocarditis and haemodynamically not-tolerated sustained VT to prevent|1| |SCD.78,79,322,336|| |ICD implantation should be considered in patients with non-active° myocarditis and haemodynamically tolerated sustained VT to prevent SCD.78,79,322,336|IIa| |ICD implantation may be considered in patients with acute myocarditis and sustained VA(VT/VF) in the acute phase to prevent SCD.71,79,89,222,323-325|IIb| |ICD implantation may be considered in patients with myocarditis after the acute phase(3-6 months) and persistent risk factors for VAD to prevent|IIb| |SCD.93,323,324,336||

AAD, anti-arrhythmic drugs; CMR, cardiovascular magnetic resonance; ICD, implantable cardioverter-defibrillator; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; NSVT, non-sustained ventricular tachycardia; PVS, programmed ventricular stimulation; SCD, sudden cardiac death; SMVT, sustained monomorphic ventricular tachycardia; VA, ventricular arrhythmias; VF, ventricular fibrillation; VT,variant tachycardia; WCD, wearable cardioverter-defibrillator.

bLevel of evidence.

${}^{c}$ Non-active based on CMR evidence of activity(T2), see Figure 4.dNST,extensive LGE,unexplained syncope,positive PVS,reduced LVEF<50%.

7. Prognosis

The current literature focuses on the single condition, but one could expect that a patient with concomitant involvement of the myocardium and pericardium will have a worse prognosis. However, current pub-lished evidence suggests that patients with uncomplicated pericarditis and myopericarditis have a good overall prognosis, despite combined involvement of the pericardium and myocardium.4,337 The TF expects that the introduction of the term IMPS will increase awareness and will lead to dedicated studies in this regard.

7.1. Complications and outcomes for myocarditis

One of the main prognostic factors is the initial clinical presentation of myocarditis(Figure 8). Low-risk myocarditis(about 75% of unselected cases) usually has a chest pain presentation with preserved biventricular function, and an overall benign short- and long-term prognosis.28 Acute complicated myocarditis with arrhythmic presentation, and especially HF presentation, has a worse prognosis.56 There is conflicting evidence

ESC Guidelines

on the role of sex in the prognosis of IMPS.73 Women seem to have a more favourable prognosis than men in myocarditis. 338 Young age and a previous myocarditis were independent relapse predictors. Fulminant onset, lower LVEF at presentation, distinct autoimmune features,espe-cially in women, and high-titre organ-specific anti-heart autoantibodies and antinuclear autoantibodies were independent predictors of death and HT.73 Genetic predisposition may also increase the risk(see Section 5.3).

The aetiology also plays a relevant role, e.g. EM, GCM and CS are associated with a worse prognosis(Sections 9.2-9.4). Outcomes are worse in patients with FM, in the case of late diagnosis and delayed interventions.57 Factors associated with increased mortality or HT are GCM, QRS duration of>120 ms on initial ECG, or the need for temporary MCS other than IABP.56 Biventricular dysfunction has been described as the main predictor of death or HT in myocarditis.63,66,73

Multimodality imaging contributes to the assessment of prognosis.For example, myocarditis patients with normal CMR have a good prognosis.339 Late gadolinium enhancement on CMR at initial presen-tation is an important prognostic finding.340 In a multicentre study with AM and preserved EF, the presence of anteroseptal LGE in the mid-wall layer was the best independent predictor of the com-bined endpoint of cardiac death, appropriate ICD interventions, re-suscitated cardiac arrest, and hospitalization for HF[odds ratio(OR) 2.73;95% confidence interval(CI) 1.2-9;5=.P=.01]. At a median follow-up of 4.3 years, 7.7% of these patients reached the combined endpoint.3 Anterosoftal LGE was the best independent predictor of SCD[hazard ratio(HR) 4.59; 95% CI 1.38-15.24; P=.01].Myocardial fibrosis was present in 95% of patients with SCD, com-pared with 41% in patients without SCD.341 Additionally, major ar-rhythmic onset(sustained VT or VF), presence of fibrosis at EMB,and induction of major VA on PVS all predicted major arrhythmic events. 63,73,255

In another study, including patients with AM and life-threatening arrhythmias, positive LGE in two or more myocardial segments and absence of edema on initial CMR were associated with an in-creased risk for recurrent major arrhythmic events, including SCD[HR 4.51(95% CI 2.39-8.53) and HR 2.59(95% CI 1.40-4.79),respectively]. ${}^{71}$

Large studies are needed in the future to develop a risk stratification with a high negative predictive value for SCD and the need for ICD im-plantation. Variables for risk stratification for the progression to DCM are given in Supplementary data online, Table S9.

7.1. Sequela and mortality in myocarditis

The main long-term complications are evolution to DCM with sub-sequent HF and(recurrence of) VA, including SCD.76 LVEF recov-ery after myocarditis can be complete or partial. Recovery rates vary from 50% to 94% depending on the initial presentation. ${}^{74}$ These patients usually have a gradual deterioration of LVEF and subsequent dilation and might remain unrecognized and asymp-tomatic until development of overt HF. Myocarditis can cause about 10% of DCM.66 Patients with B19V AM present most often with an infarct-like syndrome, and may have a favourable long-term prognosis,342 but there is evidence describing cases with severe fatal outcomes.228 In contrast, patients with HHV-6 myocarditis(and especially those with B19V and HHV-6 co-infection) usually

present with acute HF symptoms, and frequently progress to chronic HF.342

Arrhythmias during myocarditis range from mild conduction ab-normalities to life-threatening VT or VF, requiring medication and/or device therapy(refer to Section 6.5). The risk of VA is independent of LVEF.83,343

Myocarditis may have a significant mortality. Initial complicated presentation and histological subtype predict the risk. Outcomes are worse in patients with FM, with a reported mortality at 60 days of 24%.56.73 Mortality also depends on the underlying cause of FM.In a study of GCM survivors beyond 1 year, the combined rate of death, HT, VAD implantation, or GCM recurrence was 47% at 5 years.344 Reported in-hospital mortality and long-term outcomes after an episode of AM vary.345 In a multicentre registry of patients with AM, complicated AM occurred in 27%, including 9% cases of FM.In-hospital mortality was 8.5%, compared with 0% in uncom-plicated cases. Heart transplantation or LVAD was required in 3% and 4% of patients, respectively. Heart transplantation or death occurred in 18% of complicated cases after 5 years. Recurrences or VA occurred in approximately 3%-9% of cases over a period of 19-90 months.28 In the recently reported contemporary ESC multicentre myocarditis registry of 581 patients with myocarditis,27.7% of patients died, 1.7% received a HT, 0.7% underwent VAD implantation, and 3.9% underwent ICD implantation at 1-year follow-up.62,63,73

7.1.2. Follow-up

Patients with low-risk myocarditis with chest pain presentation can be discharged when cardiac enzymes tend towards normalization. Time to recovery in AM varies from a few days to a few months. Relapses occur in about 10% of cases, with a 1-year recurrence rate of around 5%.10,73,346

Follow-up is recommended in all patients with myocarditis, with clinical assessment, ECG, Holter-ECG registration, exercise test(if no signs of ongoing inflammation),chocardiography,and CMR within at least 6 months after the index hospitalization(see Table 15). ${}^{10,62}$ The prognosis is determined by baseline and 6-month LV function, re-gardless of the initial clinical presentation. ${}^{62,63,73}$ Cardiovascular mag-netic resonance should be performed at least within the first 6 months in patients with definite myocarditis to guide the timepoint for return to work, based on the individual case.

It is generally accepted to wait 3-6 months after an acute episode of myocarditis to evaluate the need for an ICD. In some patients at high risk for VA(see Section 6.5.1),71 a WCD should be considered during follow-up as a bridge to recovery.58 Subsequently, after 3-6 months of follow-up, the decision on whether or not to implant a definitive ICD is based on the individual patient, with increasing in-dication based on risk factors including genetic predisposition(see Section 5.3, Section 6.5.1; see Figure 17). In patients presenting with symptomatic VA, or heart block in GCM or CS, early consideration of an ICD is warranted. 58 Recommendations concerning arrhythmias and SCD in specific forms of myocarditis are discussed in Section 6.5.58 in uncomplicated cases, a follow-up at 6, 12, and 24 months is suffi-cient, while it should be prolonged and be lifelong in complicated cases or with residuals.

See Supplementary data online, Section 8 for patient communication advice.

ESC Guidelines

Recommendation Table 15- Recommendations for risk stratification, complications, and outcomes of in-flammatory myopericardial syndrome(see Evidence Table 15)

|Recommendations|Classa|Levelb| |---|---|---| |Follow-up with clinical assessment, biomarkersc,||| |ECG,exercise test,Holter-ECG monitoring,||| |echocardiography,and CMR at least within 6 months||| |after the index hospitalization is recommended in all||| |patients with myocarditis to identify a potential||| |progression or new risk factors.|62|| |Long-term follow-up is recommended for patients||| |progression or new complications.28,74||| |Long-term follow-up is recommended for patients with incessant or recurrent pericarditis to identify a||| |potential progression and new complications.|1|C|

CMR, cardiovascular magnetic resonance; ECG, electrocardiogram.

Class of recommendation.

bLevel of evidence.

${}^{c}$ At least troponin.

dSee definition of complicated myocarditis in Table 3.

7.2. Complications and outcomes for pericarditis

Risk stratification of patients with pericarditis must be performed at the initial presentation at the emergency department or in an ambulatory setting. Admission is recommended in high-risk cases.105,130 Non-high-risk cases can be managed as outpatients with a close follow-up within 1 to 2 weeks(Figure 7). ECG changes(mainly widespread ST-segment elevation) and troponin elevation were usually not negative

prognostic markers in this setting with an infarct-like presentation and$$\text{ preserved biventricular function.}^{4,35}$$

In the real world, approximately 25% of patients diagnosed with AP present with at least one predictor of poor prognosis and require hos-pitalization.130 The in-hospital mortality rate for AP is around 1% on average, but can be higher in older patients and those with severe co-infections.23

According to the clinical presentation, additional diagnostic work-up should be performed only for a specific clinical suspicion, the presence of high-risk features, or a lack/incomplete response to empirical anti-inflammatory therapy(Table 16).

The usual course of AP is characterized by clinical remission after medical therapy within 4-6 weeks. The most common and problematic complication of pericarditis is RP, which affects 20%-30% of patients not treated with colchicine. About 10% of patients may present with continued symptoms without clinical re-mission. Such cases have been labelled as‘incessant’, and may dir-ectly progress to constriction in few months, 104 while this complication is extremely rare in idiopathic RP.114,347 A course with multiple recurrences is possible, but not usual in simple pre-sumed viral pericarditis, and should prompt a search for an under-lying cause(Figure 14).

Cardiac tamponade is relatively rare in AP, as well as CP(<1% of cases). The risk for complications is related to the aetiology. For in-stance, the risk of CP is low after presumed viral/idiopathic pericarditis intermediate for immune-mediated aetiology, as well as PCIS and neo-plastic pericarditis(2%-5%), and high for bacterial pericarditis(20%-30%), especially if purulent.347

At least three scores ${}^{43,44,348}$ have been proposed recently to iden-tly patients at increased risk of developing complicated pericarditis and chronicity, requiring close follow-up(see Supplementary data online, Tables S2 and S3). However, these scores have not been va-lidated or replicated in additional larger studies, and remain investigational.

Table 15 Follow-up in inflammatory myopericardial syndrome after discharge

|||Within 1 month|Within 3-6 months|12 months|>1 year and long-term FUa| |---|---|---|---|---|---| |Clinical evaluation and ECG|Myocarditis|X|X|X|X| ||Pericarditis|X|X|X|X| |Biomarkers(Tnl,C-reactive protein)|Myocarditis|X|X|(X)|(X)| ||Pericarditis|X|X|(X)|(X)| |Rhythm (stress and/or Holter-ECG)|Myocarditis|-|X|(X)|(X)| ||Pericarditis|-|-|-|-| |Imaging myocarditis|TTE|X|X|X°|X°| ||CMR|X|X|X°|X°| |Imaging pericarditis|TTE|X|X|X°|X| ||CMR|(X)^{b}|(X)^{b}|(X)^{d}|(X)^{d}|

CMR, cardiovascular magnetic resonance; ECG, electrocardiogram; FU, follow-up; IMPS, inflammatory myocardial syndrome; Tnl, troponin l; TTE, transthoracic echocardiography.All follow-ups should be adapted to the clinical situation and severity. In round brackets, optional testing according to clinical presentation[(X), case-by-case decision].

$^{a}$ In complicated cases or if abnormal at 1 month, imaging should be repeated between 3 and 6 months.

$${}^{a}\text{if abnormal at} 6\text{ months, imaging should be repeated within the next} 6\text{ months and/or in the next} 12\text{ months}.$$

${}^{4}$ Follow-up proposed for uncomplicated cases of acute pericarditis. Long-term follow-up, tailored to the single patient, is recommended for high-risk cases.

ESC Guidelines

![WCD as bridge to recovery\nICD\nAbnormal LV\nAdditional risk factorsa\n3 to 6 months follow-up\nAcute\nmyocarditis\nArrhythmic presentation\nRecovery\nMedical therapy\nESC\n](2/aj0YEe4oUhYkBdfpda0fYP/figure3c1ffababd15482591449e085271417e_0_2.png) Figure 17 Follow-up and risk stratification after acute myocarditis with arrhythmic presentation. ICD, implantable cardioverter-defibrillator; LGE,late gadolinium enhancement; LV, left ventricle; LVEF, left ventricular ejection fraction; NSVT, non-sustained ventricular tachycardia; PVS, programmed ventricular stimulation; WCD, wearable cardioverter-defibrillator. Rarely for a high risk, cardioverter-defibrillator implantation may be considered be-fore discharge(see text for detailed discussion). aAdditional risk factors(at least 1, increasing risk and indication with>1 or more): NSVT, extensive LGE, unexplained syncope, positive PVS, reduced LVEF of<50%327-329

Table 16 Indicators of non-viral aetologies and complications(high-risk features or red flags in acute pericarditis)

Major

Fever>38℃(HR 3.56)

Subacute onset(HR 3.97)

Large pericardial effusion(>20 mm on echocardiography)(HR 2.15)

Cardiac tamponade(HR 2.15)

Lack of response to aspirin or NSAID after at least 1 week of therapy(HR 2.50)

Minor

Pericarditis associated with myocarditis

Immunodepression

Trauma

Oral anticoagulant therapy

HR,hazard ratio;NSAID,non-steroidal anti-inflammatory drug,Major features have been validated in multivariable analysis in a prospective cohort study of patients with acute pericarditis. ${}^{105}$

8. Inflammatory myopericardial syndrome overlapping types:myopericarditis and perimycarditis

IMPS includes a spectrum of inflammatory diseases from isolated myo-carditis to isolated pericarditis through a combination of both. IMPS should be used as an umbrella term, also covering overlapping forms of myocarditis and pericarditis.1 The diagnosis of predominant pericar-ditis with myocardial involvement, or'myopericarditis', can be clinically established if patients with definite criteria for AP show elevated bio-markers of myocardial injury, without newly developed focal or diffuse impairment of LV function on TTE or CMR.The term mypericarditis indicates a primarily pericarditic syndrome with minor myocardial in-volvement, which describes the majority of combined pericarditis and myocarditis cases encountered in clinical practice. On the other hand, evidence of new-onset focal or diffuse reduction of LV function in patients with elevated myocardial biomarkers, and clinical criteria for AP, suggests predominant myocarditis with pericardial involvement,

ESC Guidelines

termed'perimycarditis'. The clinical management and outcomes of mixed forms follow the predominant involvement. At present, patients with mypericarditis can be treated as patients with pericarditis, while patients with perimycarditis should be managed as patients with pure myocarditis. The knowledge in the field is rapidly evolving and ongoing trials and evidence will provide more updated guidance for clinical management.

A common scenario with overlapping forms of myocarditis and peri-carditis is represented by systemic immune disorders, which can affect either the myocardium or pericardium, or both.

Several systemic inflammatory and autoimmune diseases may present with myocardium, peridits, mixed forms, or Peff without pericarditis.Main conditions include RA,SLE,Sjogren's syndrome,SSc,polymyositis and dermatomyositis, and vasculitis(e.g. particularly EGPA).

8.1. Inflammatory myopericardial syndrome in systemic disorders

Inflammatory hyperocardial syndrome may complicate several types of systemic diseases, generally immune-mediated, 349,350 either with myocardial(mycarditis) or pericardial involvement(pericarditis and or PEff). Symptoms and signs that may raise the suspicion of a rheum-atic autoimmune disease are family history, history of low-grade fever,joint symptoms, dry eyes and mouth, headache, lymphadenopathy,Raynaud phenomenon, skin rash, oral and genital aphthae, deep or superficial vein thrombosis, recurrent foetal losses, lymphopenia, and chronic increase of CK and other inflammatory markers. Targeted therapy should be applied, if a specific diagnosis is reached during the diagnostic work-up.

8.1.1. Rheumatoid arthritis

Pericarditis can be seen as part of the inflammatory activity in RA, and is often present concurrently with pleuritis. It is the most common cardiac manifestation, affecting up to 50% of patients, as detected on post-mortem examination. Myocarditis may also be present, and generally re-solves if the disease is controlled.351 Anakina, already registered for the treatment of RA, can be used also for related pericardial involvement.

8.1.2. Systemic lupus erythematosus

Pericarditis is the most common cardiac manifestation of SLE, reported in approximately 25% of patients, and it is included in the American Rheumatism Association/American College of Rheumatology(ARA/ACR) classification criteria.352 Myocardial involvement in SLE affects about 5% of patients.353,354,355 Symptoms of IMPS are often non-specific, including elevated troponin, alterations on the ECG, LVEF ab-normalities, and Peff. These manifestations are usually associated with typical symptoms of SLE, including fever, arthritis, nephritis, and skin rashes.356,357 The diagnosis can be supported by specific laboratory markers, as well as multimodality imaging, to guide the therapy.358,359 Endomyocardial biopsy could be rarely considered in selected cases. Cardiac tamponade occurs in less than 2% of cases, and CP is extremely rare. Cardiomyopathy is uncommon clinically, but autopsy studies found myocardial involvement in 40%-50% of patients.

8.1.3. Antiphospholipid syndrome

Antiphospholipid syndrome is associated with the presence of anti-cardiolipin and/or anti-β2-glycprotein antibodies, and/or lupus anticoagulant, and may be the cause of myocardial dysfunction through various mechanisms. While myocarditis can manifest in this syndrome,

mediated by autoimmune mechanism, myocardial damage can be also caused by microthrombotic phenomena. ${}^{360,361}$

8.1.4. Sjogren's syndrome

In Sjogren's syndrome, the most common clinical manifestation of cardiac damage is pericarditis, which has been reported in less than one-third of cases. Myocarditis and myocardial fibrosis are also possible,362 and may occur associated with rhythm disturbances. Specific antibodies(anti-Ro/SSA) could also be identified in unexplained heart blocks.

8.1.5. Systemic sclerosis

Inflammatory mypericardial syndrome is frequent in SSc, 364 often clin-ically occult and, when symptomatic, the prognosis is poor. It may be related to ventricular dysfunction and/or structural damage of the microvascular bed, leading to repeated focal ischaemic injuries and irre-versible myocardial fibrosis. It can be also due to a primary systemic myositic disease.349,365 Damage usually follows two pathways.366 The first one is linked to the production of collagen by activated fibroblasts at the myopericardial level, especially at the subepicardial level, with consequent fibrosis, valve stenosis, coronary spams, and ischaemic events.The second pathway is caused by renal and pulmonary involve-ment, with severe cardiac consequences.367,368 Further research is needed to improve the understanding of IMPS in SSc.364

8.1.6. Polymyositis and dermatomyositis

The myocardium can be affected in inflammatory myopathies, such as polymyositis and dermatomyositis.369 with consequent myocardial hypertrophy, ischaemia, cardiac enlargement, and systolic and diastolic ventricular dysfunction.370 Cardiac involvement in inflammatory myop-athies is clinically occult in most patients, but may be suspected by multi-modality imaging 371,372 and is related to poor outcome.370,372 Myocarditis occurs in up to 30% of autopsied patients, with or without concomitant coronary or vessel vasculitis. Pericarditis is rarely reported in these patients.

8.1.7. Vasculitis

Myocardial involvement is prognostically relevant in vasculitis, particu-larly EGPA.In EGPA, about 15%-60% of patients present with cardiac disease350 including Peff, conduction disturbances, and motion abnor-malities, as well as ACS, often due to coronary spasm, and EM(see Section 9.2). While cardiac involvement in EGPA often occurs early, it can be late in the course of the disease, and mainly affects anti-neutrophil cytoplasmic antibody(ANCA)-negative patients with high eosinophil counts. Myocardial and pericardial involvement is also pos-sible in other vasculitis, especially in Kawasaki's disease, where myocar-ditis is a common cardiovascular complication(see Supplementary data online, Figure S3).373

Cooperation with specialists is important in all these systemic condi-tions to reach the correct diagnosis and to plan appropriate treatment.The diagnosis of EGPA may be particularly challenging.

8.2. Inflammatory myopericardial syndrome in COVID-19 disease

The COVID-19 pandemic raised the awareness of IMPS, as in many pa-tients the myocardium as well as the pericardium were affected. It is not proven whether the SARS-CoV-2 virus can directly damage cardiomyo-cytes or pericardioytes, as it was suggested in cultivated human cardi-omyocytes.374 Autopsy studies could only detect small amounts of virus

ESC Guidelines

in the myocardium and pericardium. ${}^{375-379}$ The true estimate of COVID-19-associated IMPS is variable depending on CMR/EMB-derived diagnosis ranging from 0.1-4.5/1000 cases ${}^{380,381}$ up to 2%-8% of cases in symptomatic patients.32 Symptoms as well as diag-nostic work-up are similar to those described for general IMPS(see Sections 4 and 5).

The predominant management of symptomatic complicated SARS-CoV-2-related IMPS is antiviral treatment for SARS-CoV-2 virus together with supportive therapy. Several immunosuppressive therapy,such as anti-IL-1(aninra and caninakum) and anti-IL-6(cotilizu-mab and sarilumab), have demonstrated promising results in critically ill patients hospitalized for COVID-19.383-385 In less severe cases, the key elements for treatments are those recommended for IMPS. More de-tails can be found in Supplementary data online, Section 5.1.2.

9. Specific types of myocarditis

9.1. Lymphocytic myocarditis

The diagnosis of LM is based on pathological criteria and reflects an in-flammatory disease that may be caused by viruses, but also by other in-fectious agents, including bacteria(such as Borrelia spp.) and protozoa(such as T. cruz).10 Furthermore, contemporary single-centre and multi-centre cohort studies suggest that LM is more commonly non-infectious or immune-mediated/autoimmune. 63,73 It is important to note that the aatiopathogenesis and outcome of viral LM varies considerably, based on the different infections. Cytolytic viruses, such as enterovirus(e.g.coaxkeachievines and echoviruses), destroy cardiomyocytes and induce severe infiltration by macrophages and lymphocytes.386 In contrast to en-teroviruses, vasculotrophic B19V, which infects cardiac endothelial cells,but not cardiomyocytes, can also induce severe LM, especially in young children.228,387 High viral copy numbers(>500 viral DNA copies/μg of cardiac DNA) were found to be associated with cardiac inflammation and/or systemic infection.228,388 Low B19V DNA copy numbers in car-diac tissue rather reflect virus persistence, and are usually not related to cardiac inflammation. Lymphotropic viruses of the Herpesirovidae family[HHV-6,EBV, human cytomegalovirus(CMV)], as well as HCV, influenza viruses, and SARS-CoV-2 may indirectly trigger myocarditis by activating the immune system.389 Regarding the aetiology and pathogenesis of myo-carditis,microRNAs(miRNAs) may be promising diagnostic markers,as well as prognostic and therapeutic targets in myocarditis.141,390 However, the precise role of miRNAs in myocarditis remains to be de-termined.391 In addition to infectious agents, organ-specific autoimmune-ity to heart autoantigens,66 different systemic immune-mediated diseases, toxic substances, and drugs, including Icls, are known to induce different forms of acute and chronic LM.66 Immune-mediated mycardi-ts may occur with exclusive cardiac involvement or in the context of sys-temic immune-mediated diseases, such as SLE,SSc, and others.349,392 Interestingly, genetic host susceptibilities have also been linked to cardiac dysfunction following myocarditis. 91,150

9.1.1. Presentation

Since LM can be induced by various causes, there is no universal, specific clinical presentation. Instead, it must be considered in the context of the different diseases, in line with the stages of myocarditis.

9.1.2. Diagnosis and therapy

The diagnostic pathways were described above and vary depending on the cause. The diagnostic and therapeutic approach has to follow the clinical situation and the stages as described in Section 4(see Table 12).

9.2. Eosinophilic myocarditis

Eosinophilic myocarditis is a rare form of myocarditis, characterized by eosinophilic infiltration of the myocardium. Underlying disorders that should be evaluated during the work-up of EM include: hypersensitivity and allergic reactions.271 immune-mediated disorders, in particular EGPA; undefined complex HES or its myeloproliferative variant; para-sitic infections; and cancer.349 A meta-analysis of single cases or small case series reported a rate of in-hospital death of up to 22%, and a sig-nificantly increased occurrence of the hypersensitivity form, up to 36%.271

9.2.1. Presentation

The clinical presentation of EM can be variable, ranging from oligosymp-tomatic to acute FM, or chronic RCM(Loeffler CMP or endomyocar-ditis). ${}^{271}$ Nevertheless, prior study demonstrates that EM often has a fulminant presentation with abrupt impairment of LVEF, a high risk of malignant arrhythmias, and a high risk of thromboembolic complica-tions, related to the formation of ventricular thrombi. ${}^{271}$ Although EM is often accompanied by peripheral eosinophilia, it should be noted that this finding is absent in up to 25% of patients with EM, and may con-tribute to the undidegosis of EM.

9.2.2. Diagnosis

The diagnosis of EM can be established by either the EMB-proven pres-ence of eosinophilic infiltration of the myocardium, or the presence of CMR-proven myocarditis with pathognomonic findings associated with peripheral eosinophilia(Supplementary data online, Figure S3).Furthermore, general clinical signs related to EGPA or HES disorders should be evaluated, such as an increased number of eosinophilic cells,history of asthma and sinusitis, and characteristic skin lesions. Left ven-tricular function may be preserved, and DCM can occur, but often the phenotype of RCM is present. On echocardiography, a typical finding is Loeffler endocarditis. In the diagnostic work-up, systemic screening for the above-mentioned etologies should be carried out systematically.

9.2.3. Therapy

The first-line therapy for EM is the administration of i.v. corticosteroids,but caution should be exercised if EM is caused by an infectious agent.The optimal dose and duration of corticosteroids are unclear, but it is proposed to administer a daily i.v. bolus of corticosteroids followed by dosage tapering in severe forms, while oral steroid administration(see Table 12) can be considered in patients with mild LV dysfunction.39,271 The identification of an EM-associated condition is crucial to administer specific treatments, such as cyclophosphamide or IL-5 inhibitors in EGPA-related EM,34 imatinib in the myeloproliferative variant of platelet-derived growth factor receptor alpha(PDGFRA)-associated HES, or abandolez in Toxocara canis infection. In hypersensitivity/aller-gic EM, first-line therapy is to withdraw the potential cause of eosinophilia.

Since endocavary thrombi were reported in 12% of EM cases, the use of anticoagulation during the acute phase could be considered for the prevention of endocavary thrombi. ${}^{271}$

9.3. Giant-cell myocarditis

Giant-cell myocarditis is a very rare, but often rapidly progressive dis-ease with a poor prognosis, with an~85% rate of death or HT at 3 years.56,82 The incidence of GCM was reported to range from 0.007% to 0.051% in autopsy studies; however, this number might

ESC Guidelines

underestimate the true disease burden. 393,394 Giant-cell myocarditis generally affects young and middle-aged adults without a sex predom-inance. In a large multicentre registry of GCM cases, patients were aged from 16 to 69 years at the time of diagnosis.82

Giant-cell myocarditis is recognized as a non-infectious myosin-induced autoimmune form, as experimental models suggest,395 and an association with autoimmune disorders has been reported in~20% of cases.82

9.3.1. Presentation

Early symptoms of GCM might not differ from other types of myocar-ditis and vary widely at the time of presentation. In an international registry of 63 GCM patients, HF was the presenting symptom in 75%of cases.82 The initial manifestations might be progressive haemo-dynamic deterioration or cardiogenic shock, intractable arrhythmias,and SCD.The condition often progresses rapidly to death, often within days to months. A systematic analysis including 51 patients with GCM showed that the cumulative incidence of SCD(fatal or aborted) was 22% at 1 year and 26% at 5 years after presentation, and the composite incidence of SCD or VT was 41% at 1 year and 55% at 5 years.326 Other early GCM manifestations include bradyarhythrmias and cardiac conduction abnormalities, including complete AVB. In a study from Finland, 25% of individuals<55 years of age with clinically idiopathic heart block had GCM or CS on heart biopsy.396 The presence of AM complicated by treatment-resistant HF or cardiogenic shock, VA, and AVB should increase the clinical suspicion of GCM.

9.3.2. Diagnosis

Endomocardial biopsy remains the gold-standard diagnostic modality for GCM and can identify these patients at an early stage. 397,398 Patients diagnosed with GCM through EMB had a shorter symptom-onset-to-diagnosis time and milder heart damage than those diagnosed during HT.398

The presence of multinucleated giant cells in the absence of well-organized granulomatous lesions in the myocardial biopsy specimen is the hallmark of GCM. The giant cells are typically located in the inter-stitum or around blood vessels and are characterized by their large size,mutinucleation, and cytoplasmic granules.

Giant-cell myocarditis is characterized by myocardial destruction mediated by a large number of T cells, macrophages, multinucleated giant cells, and eosinophils in EMB.39 Generally, the histological diagno-sis of GCM is guided by myocyte necrosis, diffuse infiltration of inflam-matory cells,and interstitial fibrosis.399,400 The severity of necrosis and fibrosis in EMB predicts the outcome.401 It is important to understand that one set of non-diagnostic EMB samples does not exclude GCM.The sensitivity of the first biopsy is 68% and increases to 93% when the biopsy is performed up to three times. Thus-repeated EMB should be considered when there is a high clinical suspicion of GCM.217 In a single-centre case series of GCM,LGE on CGM was present in 96%of cases, and its distribution correlated with the histology.401 Prompt EMB in the setting of suspected GCM can affect the choice of MCS,leading to an early listing for HT and consideration of cyclosporine-based immunosuppression.402 Administration of i.v. steroids prior to EMB may reduce the diagnostic yield of EMB. There should be an agree-ment in specialized centres to prioritize the evaluation of EMB, and to provide the results at least within 3 days, optimally within 8 h.

9.3.3. Therapy

As soon as GCM is suspected, immunosuppressive therapy should be in-itated promptly to avoid disease progression and delay HT. It is crucial

that the therapy should be initiated based on a strong clinical suspicion.Historically, the survival of patients with GCM without immunosuppres-sion was about 3 months from symptom onset to death or HT. Many studies have shown that immunosuppression is useful for the treatment of GCM. Immunosuppressive therapy typically involves two or three drugs, including corticosteroids, and at least one, and usually two add-itional immunosuppressive agents(see Table 12). In GCM patients, im-munosuppression with corticosteroid monotherapy is not associated with a prolongation of transplant-free survival. ${}^{82}$

Patients with GCM should receive the same guideline-based treat-ment for HF and arrhythmias as patients with heart disease from other causes.12,58

Cyclosporine is the most commonly used immunosuppressant. In multiple retrospective and prospective studies, concomitant use of cyclosporine was associated with improved prognosis. Combining im-munosuppressive therapy with corticosteroids and cyclosporine,azathioprOR, or both improved transplant-free survival on average to 12 months, while patients treated with corticosteroids alone survived on average 4 months.82 A cases series of GCM reported that 1-year transplant-free survival was 73% in patients who received corticoster-oids and cyclosporine with or without muuronab-CD3, with a re-ported decrease of the degree of necrosis, cellular inflammation, and giant cells after 4 weeks of treatment.403 A systematic review of 27 studies with 43 biopsy-proven GCM cases requiring MCS showed that the administration of immunosuppressive therapy prior to MCS implantation was associated with significantly better survival than treat-ment with MCS alone.Immunosuppression may reduce the severity of HF in these patients by preventing further autoimmune destruction of the myocardium.404

Cessation or reduction of immunosuppression is associated with GCM recurrence as long as 8 years after diagnosis.344,403

In a single-centre study, the risk of life-threatening VA in GCM pa-tients exceeded 50% at 5 years after admission. Permanent ICD effect-ly terminated life-threatening ventricular tachyarrhythmias, and no GCM patient with the device suffered from a SCD.326

Transplantation could be considered for GCM patients who fail to respond to GDMT and immunosuppression. A recent systematic re-view and meta-analysis of 499 patients with CS and 69 with GCM who underwent HT found that 1- and 5-year survival rates in GCM pa-tients were similar to those in transplant recipients with other HF aetologies.

Recommendation Table 16- Recommendations for giant-cell myocarditis(see Evidence Table 16)

|Recommendations|Classa|Levelb| |---|---|---| |EMB is recommended in patients with suspected GCM due to unexplained new-onset HF of up to 2 weeks associated with a normal or dilated left ventricle and new ventricular arrhythmias, second-or third-degree AVB, or failure to respond to usual care within 1 to 2 weeks to initiate specific treatment.402|I|C| |Combined immunosuppressive therapy is recommended in patients with a diagnosed GCM.217|I|C|

AVB, atrioventricular block;EMB, endomyocardial biopsy; GCM, giant-cell myocarditis; HF, heart failure.

aClass of recommendation.

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

<FIGTEXT=></FIGTEXT>

ESC Guidelines

9.4. Myocarditis in sarcoidosis

Cardiac sarcoidosis is a form of inflammatory heart disease, coexisting with systemic sarcoidosis in 5%-10% of cases,406 or rarely, in isolation.The aetiology of sarcoidosis is not well understood, but may involve an autoimmune response after certain trigger(s) and genetic predisposition,which leads to the formation of non-caseating granulomas in multiple or-gans, typically in the lungs.407 On histopathology, the granula consists of CD68+ macrophages, CD68+ giant cells, CD3+ T lymphocytes, and CD20+ B lymphocytes. It is characterized by inflammation, oedema,lymphocytic infiltration, and replacement fibrosis.408 Cardiac sarcoidosis is often subclinical, with an estimated cardiac involvement in around 25%of cases on autopsy series in patients with sarcoidosis.409,410

9.4.1. Presentation

Manifestations of CS may range from cardiac inflammation, conduction system disease, frequent ectopy, tachyrarrhythmia, and HF, to SCD.407 Cardiac sarcoidosis may mimic different cardiac phenotypes, including ARVC, 254,411-413 DCM, and hypertrophic CMP(HCM), but may also occur in patients with normal cardiac function.414 Symptoms are non-specific, and often related to arrhythmias, especially AVBs and VTs.The challenge is to identify patients at risk, since SCD due to malignant ar-rhythmias is common.415,416

9.4.2. Diagnosis

The diagnostic algorithm of CS is different in patients with or without known extracardic sarcoidosis. Pathognomonic findings in non-invasive imaging are sufficient for the diagnosis of CS in cases with known systemic sarcoidosis.117 In contrast, the diagnostic pathway in primary CS is more challenging, but typical multimodality imaging pat-terns are usually sufficient. Cardiac sarcoidosis can manifest as abnor-malities on ECG,echocardiography,CMR,PET,EMB,and cardiac and inflammatory blood biomarkers(see Section 5.4). Electrocardiogram or cardiac rhythm monitoring may demonstrate conduction system ab-normalities(such as AVB or bundle-branch block) and arrhythmias, in-cluding VT.418 Echocardiography may reveal regional WMA in a non-coronary distribution, septal thinning, and ventricular aneurysms.Endomyocardial biopsy may be helpful in selected patients, but negative results do not rule out CS due to potential sampling errors. ${}^{419}$ Endomyocardial biopsy guided by imaging or EAM may improve the diagnostic yield(see Section 5.12).

Multimodality advanced cardiac imaging, such as CMR and FDG-PET,plays an increasing role in the management of suspected CS. Overall,compared with FDG-PET, CMR has higher sensitivity of 89%-95% vs 84%,respectively, but similar specificity of 78%-85% vs 82%,respectively, for the diagnosis of CS.408,420-428

On CMR,CS has a wide range of potential findings, and is often con-sidered the‘great mimicker’ of various cardiac conditions, but the inter-ventricular septum is often involved ${}^{408}$ and the‘hook sign ${}^{+429}$ is recognized to be associated with a high probability of CS. For more de-tails, see Supplementary data online, Figure S3. A heavy burden of LGE is associated with a poorer prognosis and predisposes to VA, HF, and death in CS, and may guide clinical decision-making 430-436 Aside from LGE, the identification of ongoing myocardial inflammation is possible.30,437-441

Fluorodeoxyglucose-positron emission tomography also allows detec-tion of cardiac inflammation in CS.426 It requires careful patient prepar-ation to suppress physiological 18F-FDG uptake. The classical finding is focal 18F-FDG uptake in the basal septum, with a concordant perfusion defect. Perfusion defects in the active stage of CS may be due to micro-vascular obstruction by inflammatory oedemia, necrosis, or both, and are

not necessarily located in the same region as the 18F-FDG uptake. 427 Hybrid PET-CMR may enable better detection of cardiac inflammation in a more comprehensive manner, 440,442,443 but its availability is limited.Both CMR and PET may be used for imaging-guided EMB.

The intensity and extent of FDG uptake on PET is of prognostic rele-vance.43-449 In a meta-analysis of 37 studies of patients with CS, LGE on CMR and FDG uptake on PET were both predictive of MACE(all-cause death, cardiac death and aborted SCD, VA, and HF hospitalization).

Fluorodeoxyglucose positron emission tomography has proved to be useful in predicting and monitoring the anti-inflammatory therapy response in sarcoidosis,204,450 however, the optimal timing for repeat-ing PET studies for the assessment of treatment response is not well established.

In addition to clinical assessment, imaging modalities should be used for the short- and long-term management of patients with CS.

9.4.3. Therapy

The treatment of CS is currently not standardized, and is based on patient-tailored assessment, often with multidisciplinary input.451 Treatment is targeted at controlling cardiac inflammation, myocardial scarring and dysfunction.13,431-436 First-line therapy includes corticos-teroids(see Table 12).

Since resolution of conduction abnormalities with anti-inflammatory treatment remains unpredictable, definitive cardiac pacing is usually needed.AVB and the need for cardiac pacing are associated with a high-er risk of sustained VA, which reached 31% at 5 years in the Finnish registry.416,452,453 Thus, it appears reasonable to propose an ICD with pacing ability rather than a pacemaker in CS patients with pacing indications. The risk of VA during follow-UP is high in observational studies, in patients with low LVEF.416,452,454,455 presence of LGE on CMR,434,456-459 and positive PVS.456,460-464 There is a lack of data on the relationship between scarring extent and arrhythmia risk.Positon emission tomography-computed tomography may also help to stratify patients.465

Heart transplantation could be considered in a subgroup of patients with CS, similarly to GCM.405

Recommendation Table 17- Recommendations for myocarditis in sarcoidosis(see Evidence Table 17)

|Diagnosis|Classa|Levelb| |---|---|---| |Diagnosis||| |CMR, using tissue characterization techniques, is recommended in patients with suspected CS to assess cardiac inflammation and myocardial involvement.408,421-425|$1$|B| |${}^{18}$ F-FDG-PET is recommended for the diagnostic work-up, including detection of inflammation, as well as for follow-up and assessment of therapeutic response in patients with C.426-428|$1$|B| |Therapy||| |ICD implantation is recommended in patients with CS and sustained ventricular arrhythmia(VT/VF) or aborted CA to prevent SCD. ${}^{58,396,416,454,455,466}$|$1$|B| |CDI implantation is recommended in patients with CDI implantation is recommended in patients with CS and LVEF≤35% to prevent SCD.|$1$|C|

Continued

<FIGTEXT=></FIGTEXT>

ESC Guidelines

ICD implantation should be considered in patients with CS and LVEF>35% after resolution of the active phase with significant LGE, a history of arrhythmias,unexplained syncope, inducible sustained VA at PVS,or with persistent high-degree AVB to prevent SCD.416,434,452,453,456-464.467

AVB,atrioventricular block;CA, cardiac arrest; CMR, cardiovascular magnetic resonance;CS, cardiac sarcoidosis; 18F-FDG-PET, $[{}^{18}~F]$ -fluorodeoxyglucose positron emission tomography; ICD, implantable cardioverter-defibrillator; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; PVS, programmed ventricular stimulation; SCD, sudden cardiac death; VA, ventricular arrhythmias; VF, ventricular fibrillation; VT, ventricular tachycardia.

Class of recommendation.

bLevel of evidence.

9.5. Specific infectious myocarditis(Viruses, Lyme, Chagas)

9.5.1. Viruses

A large variety of infectious agents(Supplementary data online, Table S1)can cause myocardial inflammation, but viruses are considered the most common cause among infectious forms of myocarditis. Data on the true prevalence of viral myocarditis are difficult to determine, since EMB is performed only in a subgroup of high-risk patients and in complicated cases. Moreover, a positive viral serological test does not imply myocar-dial infection and is not routinely recommended. Exceptions are HIV and HCV and for specific infections such as Lyme disease. ${}^{10}$ The epidemi-ology of viral myocarditis has changed during the past three decades;while enteroviruses and adenoviruses have been considered the most common causes of viral myocarditis, 468 vasculotropic viruses such as B19V,63,66,468 and lymphotropic viruses such as HHV-6 are increasingly found in EMB samples. ${}^{342,469}$ The prognostic relevance of persistent B19V infection with low viral copy numbers remains controversial be-cause its presence in myocardial tissue may not have direct pathogenetic significance, ${}^{470,471}$ in contrast to A19B19V infection. ${}^{228}$

9.5.1.1. Presentation

Symptoms vary according to the underlying cause and severity of dis-ease. However, it generally follows the presentation of acute and chronic stages, as presented in Section 4.

9.5.1.2. Diagnosis

The diagnostic approach should follow the description outlined in Section 4(Figures 5 and 6). The presence of more than 500 copies/μg of DNA in EMB is considered as the threshold for virus-related myocar-dial inflammation, and usually guides therapeutic choices(e.g. starting immunosuppression). Viral PCR analysis in EMB samples is performed to better characterize the pathological substrate causing myocarditis.If immunosuppression is needed, viral presence has to be ruled out by EMB.10 Contemporary PCR analysis for viral presence in EMB speci-mens and blood samples is utilized to rule out possible tissue contamination.10,469

9.5.1.3. Therapy

Data are insufficient to support antiviral therapy for AM, as well as treat-ment with IVIG for presumed viral myocarditis.42 Anti-herpesvirus drugs in patients with CMV or HHV-6 infection can be considered, al-though their efficacy has not been directly studied in patients with

myocarditis.10 Treatment with type I IFN in patients with enterovirus 273,473-475 Antiviral therapies have to be prescribed and managed in collaboration with an infectious diseases expert with shared decision-making in the IMS team.1,472

9.5.1.3.1. Influenza viruses. Supportive management is the backbone of severe influenza treatment. Myocardial involvement is rare, but should be considered in patients of any age with chest pain, tachycardia, and haemodynamic instability within 2-4 weeks from symptom onset.The effect of antiviral therapy on myocarditis is not clear, although osel-tamivir is utilized in both inpatient and outpatient settings. Peramiriv and zanamvir are used only for hospitalized patients.There are individ-ual case reports of successful treatment with neuraminidase inhibi-tors.476-479 Peramiriv has often been used in combination with either osetamvir480,481 or zanamvir482

9.5.1.3.2. Human immunodeficiency virus. The pathogenesis of HIV-associated myocarditis involves direct viral infection, co-infection with other viruses or bacteria, cytokine activity, side effects of highly active antiretroviral therapy(HAART),immune system dysregulation,and/or ischaemia. If HIV-associated myocarditis is diagnosed, therapy for HIV infection has to be started or continued. Highly active anti-retroviral therapy has been reported to significantly decrease the in-cidence of cardiac involvement, especially pericarditis, arrhythmias,and DCM compared with patients treated with nucleoside reverse transcriptase inhibitors in a retrospective study of 1042 patients. 483

9.5.2. Lyme carditis

Lyme carditis may be an early manifestation of Lyme borreliosis, a tick-borne disease, caused by Borrelia spp., which is one of the most com-mon vector-borne diseases in the northern hemisphere.

9.5.2.1. Presentation

In cases of early disseminated infection, AM with possible associated pericarditis may occur, but LC is typically characterized by varying de-grees of AVB, with third-degree AVB in approximately 25% of cases.Chronic LC often shows manifested persistent symptoms and signs,such as fatigue, cognitive dysfunction, headaches, sleep disturbance,neuropsychiatric and musculoskeletal symptoms, electrical conduction delays, and DCM.

9.5.2.2. Diagnosis

The suspicious index in LC score has been proposed to evaluate the like-lhood of high-degree AVB to be caused by LC. It allows categorization of patients into low-, intermediate- and high-risk categories.485 Continuous ECG monitoring is required for patients presenting with syncope or with a PR interval of>300 ms, since this is a high-risk marker of progression to complete AVB.484 Serological tests are recommended for patients presenting with high-degree AVB and suspected LC.

9.5.2.3. Therapy

Atrioventricular block is often transient and typically resolves within 1-2 weeks of antibiotic treatment, therefore permanent pacemaker placement is not warranted for AVB associated with LC before starting therapy. Intravenous therapy with ceftriaxone is the recommended first-line treatment for patients with LC and AV disturbances,486 fol-lowed by oral antibiotics(doxycycline, amoxicillin, or fefuroxime) for

ESC Guidelines

at least 14 days and up to 21 days(total antibiotic course), depending on the severity of clinical presentation and response to treatment.The prognosis for early-treated disseminated LC is favourable,with complete recovery occurring in most patients treated with antibiotics.484,487

Although LC may resolve spontaneously, antibiotic therapy shortens the disease duration and prevents further complications.

9.5.3. Chagas disease

Chagas disease(CD) is a systemic disorder caused by the protozoan parasite T. cruzi, which is transmitted through a hematophagous tria-tomine insect vector in endemic areas, such as Latin America, and can be transmitted transplacentally, by infected blood, or even orally through ingestion of contaminated food and drinks. Current migration has made CD a global disease, and congenital transmission has become relevant in non-endemic areas, including Europe.

9.5.3.1. Presentation

Acutely infected individuals remain asymptomatic or show mild and non-specific symptoms. Intense direct tissue parasitism may result in AM in less than 5% of cases. Chagas disease may evolve into CMP in 20%-30% of cases. Common findings in patients with Chagas CMP in-clude brady- or tachyarrhythmias, dilated ventricles with regional(mainly inferior, inferolateral, or apical) or global systolic dysfunction,and thromboembolism.

9.5.3.2. Diagnosis

Diagnosis of CD requires a high clinical suspicion. Polymerase chain reaction testing is the most sensitive test in acute infection while,for diagnosing chronic CD, the combination of two serological tests with antigens that detect different antibodies against T. cruzi is prefer-able. Multimodality imaging is able to support the diagnosis, as often apical aneurysms with and without thrombi can be detected by CMR.488

9.5.3.3. Therapy

Eradication of the parasite is a target in early phases, and anti-parasitic treatment should be provided as soon as possible, following detection of an acute infection. In the BENEFIT(Benznidazole Evaluation for Interrupting Trypanosomiasis) trial, 2854 patients with Chagas CMP were randomized to either benzridazole or placebo for 80 days.Benznidazole significantly reduced serum parasite detection, but there was no significant reduction in clinical cardiac deterioration at 5 years.489 Therefore, anti-trypanosomal treatment should not be rou-tinely used in adult patients with chronic CMP, but it can be considered in early and mild forms ${}^{490,491}$ (see Table 12). Patients with Chagas CMP should be treated according to HF guidelines. Chagas disease is asso-ciated with high morbidity and mortality, with an annual rate of cardio-vascular death of 6%.492 In this population, the benefit of ICD in primary and secondary prevention is controversial, since observational studies did not demonstrate a mortality benefit compared with amidorone. ${}^{493}$ However, a systematic review and meta-analysis showed that, in pa-tients with previous VT, appropriate ICD interventions and electric storms were frequent, occurring at a rate of 25% and 9% per year, re-spectively, with an overall mortality of 9% per year. ${}^{494}$ A case-based de-cision is warranted.

9.6. Drug- or vaccine-induced myocarditis 9.6.1. Drug-induced myocarditis

9.6.1. Immune checkpoint inhibitor-induced myocarditis

Immune checkpoint inhibitors have revolutionized cancer treatment and are approved in multiple cancer types. These agents are monoclo-nal antibodies blocking specific molecules that inhibit the immune response-CTLA-4(cytotoxic T-lymphocyte antigen 4), PD-1(pro-grammed cell death protein 1) and its ligand PD-L1(programmed death ligand 1), and LAG-3(lymphocyte activation gene 3)-strongly enhancing T-cell responses against cancer. By activating the immune system,ICls may induce immune-related adverse events, which can af-fect any organ. Myocarditis is one of the most feared complica-tions,495-497 although rare, as it affects approximately 1% of treated patients, within the first weeks following the initiation of therapy.495 Since a growing number of patients are eligible for ICI treatment,the absolute number of cases is increasing. One of the largest case ser-ies, including 122 patients with ICI-associated myocarditis, recorded early onset after treatment initiation(median 30 days), and up to 50% mortality.496 A systematic analysis of the World Health Organization(WHO) pharmacovigilance database confirmed a high mortality rate up to 33%.498

The main risk factor for ICI-induced AM is combination therapy with two types of ICl, such as an anti-CTLA-4, e.g. ipilimumab, combined with an anti-PD-1, e.g. nivolumab.499

This complication affects mostly men 495 and older patients(median age 65 years) with more comorbidities. 28,495 Furthermore, if ICls are combined with other cancer therapies, their toxicity aggravates.

9.6.1.1. Presentation. Immune checkpoint inhibitor-induced myo-carditis is especially arrhythmogenic, including a risk of conduction disorders, and HF with reduced EF occurs in about half of patients.Myocarditis is frequently associated with peripheral myositis, which,when associated with respiratory failure, can negatively affect survival.

9.6.1.1.2. Diagnosis. When suspected, rapid diagnostic triage is needed.495-497 Early diagnosis is extremely important, usually including la-boratory tests and multimodality imaging(Section 5). The detection of a coexisting CAD in older patients should not refrain from further work-up for myocarditis(Table 4). In inconclusive cases an EMB can be necessary.For more details, see the 2022 ESC cardio-oncology guidelines. ${}^{501}$

9.6.1.1.3. Therapy. After diagnosis, immediate discontinuation of ICl and early(within the first 24 h) initiation of corticosteroids is war-ranted. Up to 50% of patients will be refractory to corticosteroids. In this situation, second-line immunosuppression treatments are neces-sary(see Table 12).502 In a prospective registry, the combination of rux-olitinib and high doses of abatacept, and screening for concurrent respiratory muscle failure, was associated with improved survival.502 Long-term cardiovascular effects of ICls become more and more rele-vant since a growing number of cancer patients are exposed to this therapy.503,504 Rechallenge with an ICl has to be considered following a multidisciplinary team discussion, based on factors such as the severity of the myocarditis, cancer prognosis, oncology treatment options, and patient preference.504,505 Details are given in the 2022 ESC guidelines for cardio-oncology.501

ESC Guidelines

Recommendation Table 18- Recommendations for immune checkpoint inhibitor-associated myocarditis(see Evidence Table 18)

|Recommendations|Classa|Levelb| |---|---|---| |Diagnostic triage within 24 h is recommended in patients with suspected myocarditis induced by ICI to initiate treatment rapidly.|1|C| |Immediate disruption of ICI and administration of high-dosage corticosteroids are recommended in patients with ICI-associated myocarditis in order to stop the inflammatory reaction and stabilize the patient.504|1|C| |Second-line immunosuppression treatment should be considered in patients with steroid-refractory ICI-associated myocarditis.501,504|1a|C| |Second-line immunosuppression treatment may be considered in patients with fulminant/severe ICI-associated myocarditis.501,504|11b|C|

ICI, immune checkpoint inhibitor.

aClass of recommendation.

bLevel of evidence.

“See Figure 5.

9.6.1.2. Other drugs associated with myocarditis

Many drugs have been associated with myocarditis(see Supplementary data online, Table S10), especially clozapine.506 The reported incidence of clozapine-associated myocarditis ranges from 0.1% to 5%.507,508 Drug-induced myocarditis may be associated with drug reaction with eo-sinophilia and systemic symptoms(DRESS) syndrome.509 Treatment is based on discontinuation of the drug and use of corticosteroids.

9.6.2. Vaccine-induced myocarditis

In 2002 the‘Brighton collaboration’ was established with the aim to pro-vide standards for the definition of adverse events after vaccination.510

In a clinical context, different vaccines, apart from the SARS-CoV-2 vaccine, have been associated with myocarditis. The main association is with smallpox vaccine, 511 with data deriving mainly from the US mili-tary population.

A systematic review reported cardiac events including IMPS after in-fluenza vaccination, pneumocammoc vaccine, and tetanus toxoid.51

Few data reported myocarditis after receiving different vaccines(e.g.meningococcus, hepatitis A and B, diphtheria, poliovirus)(see Supplementary data online, Table S11).513-518

A recent multicentre study reported good mid-term outcomes after COVID-19 vaccine-associated myocarditis without death or need for HT.519 More detailed information can be found in Supplementary data online, Section 5.1.2.

9.7. Pregnancy-associated myocarditis

Peripartum CMP(PPCM) is sometimes associated with myocardial in-flammation, more common particularly in patients presenting with ar-rhythmias.520 Pregnancy-associated myocarditis(PaM) is a rare condition, and its incidence and prognosis varies regionally. 521-523 Nutritional deficiencies, viral myocarditis, and autoimmune processes have been postulated as triggers. Recent data support the role of

neurohormonal changes of late pregnancy and delivery, as well as the role of genetic predisposition. 524

9.7.1. Presentation

There is no clear distinction between the phenotype of PaM and PPCM. Women develop symptoms of HF during late pregnancy or after deliv-ery, with the majority being diagnosed after delivery, typically in the first month post-partum. A minority of patients may present with pulmon-ary oedema, cardiogenic shock, severe arrhythmias,525 cardio pulmonary arrest, thromboembolic complications, and brain injury.

9.7.2. Diagnosis

There are no specific studies for PaM, therefore the guidance for PPCM should be followed. Transthoracic echocardiography should be per-formed in any suspected case. In PPCM, LVEF is typically<45%.526 Careful examination should be undertaken to clearly view the LV apex to detect intracardiac thrombi. Brain natriuretic peptide/n-terminal prohormone of brain natriuretic peptide are usually mark-edly elevated.527-529

Cardiovascular magnetic resonance imaging is an advanced imaging modality if echocardiogram is inadequate, but gadolinium-based contrast agents should be avoided during pregnancy.530-532 Cardiovascular mag-netic resonance is crucial to differentiate underlying causes.533 The detec-tion of active inflammation can be performed without application of contrast media in CMR(Figure 4).

Peripartum CMP has been associated with a higher rate of recovery than other forms of HF with reduced EF,534 and remission frequently occurs within the first 3 to 6 months.535 Delayed recovery can also oc-cur after 2 years.536,537

9.7.3. Therapy

There are no dedicated studies for PaM, so advice is based on published literature for PPCM.

Treatment of HF is essential, with modifications to ensure foetal safety during pregnancy.521,538-540

Low-molecular-weight heparins do not cross the placenta, and are preferred during pregnancy if the thromboembolic risk is high.541 Direct oral anticoagulants are less well studied in pregnancy, and should be avoided. Anticoagulation should be continued until recovery of LV function.

Bromopriation has been shown to improve LVEF at 6 months, but the results are contradictory.521,542-545

Following delivery, most HF medications are compatible with breast-feeding, Many patients may also relapse. Treatment withdrawal and in-complete recovery of LV function are risk factors for recurrences.546,547

Lifelong treatment has not been proven to be necessary.Pre-conception counselling should include discussion of the potential risks of recurrent myocardial dysfunction, even after recovery.

Multidisciplinary teams are warranted for patient management.

10. Inflammatory cardiomyopathy

Inflammatory CMP is defined by chronic myocarditis in association with cardiac dysfunction and ventricular remodelling, with a clinical hypoki-netic phenotype, either dilated or non-dilated, with or without arrhyth-mogenic substrate. It can also manifest as the evolution of a prior myocardits, whether treated or untreated. Inflammatory CMP is in-volved in the pathogenesis of DCM. It includes immune-mediated/auto-immune forms and infectious subtypes. ${}^{12,550}$ A genetic predisposition is

ESC Guidelines

also important for the pathogenesis of inflammatory CMP.9 However,the rates, risk factors, and other characteristics of cases progressing from AM to chronic myocarditis or inflammatory CMP remain unknown.

10.1. Presentation

Patients with inflammatory CMP may present with new-onset/acute,subacute, or chronic HF. Although myocarditis resolves in>50% of cases, even spontaneously, approximately 25% of cases may present with persistent ventricular dysfunction, and more severe cases may progress to DCM.10

10.2. Diagnosis

A variety of clinical assessment, ECG, multimodality imaging, and, if needed, EMB can be used to reach a diagnosis. Persistent or chronic myocardial inflammation should be suspected in cases with non-ischaemic ventricular dysfunction associated with low QRS voltages,and persistent mild elevation of hs-TnT/Tnl. The absence of significant remodelling may be observed in the early phase of the disease. This sus-picion can be confirmed by multimodality imaging(echocardiography and CMR) and EMB, especially in the presence of myocardial oedema observed at CMR. Inflammatory CMP may be familial in rare cases. In these patients, genetic testing should be discussed.

10.3. Therapy

Guideline HF treatment is recommended in patients with inflammatory CMP.12,259 Medical therapy should be tailored to the underlying cause in case of systemic disorders, especially in autoimmune diseases. Only one RCT showed an improvement of cardiac function with immuno-suppressive treatment in patients with virus-negative inflammatory CMP.551 Other non-randomized studies, often derived from single-centre and/or retrospective studies,34,131,551-555 suggest the efficacy of immunosuppression on top of optimized HF therapy, and support its safety. In patients with different immune-mediated myocarditis and HF, immunosuppressive therapy was safe.34,131,552-555 Therefore,the treatment should be based on histological/immunohistological and viral PCR examination of the biopsy specimens.

In untreated cases, progression to DCM and transplantation or death are observed.10,39

Recommendation Table 19- Recommendations for inflammatory cardiomyopathy(see Evidence Table 19)

|Recommendations|Classa|Levelb| |---|---|---| |Guideline-directed heart failure treatments are recommended in patients with inflammatory cardiomyopathy to improve and/or stabilize left ventricular function.|I|C| |Specific medical therapy for the potentially underlying systemic disease is recommended in inflammatory cardiomyopathy.|I|C| |Immunosuppressive therapy, guided by endomyocardial biopsy, should be considered in virus-negative inflammatory cardiomyopathy to suppress the autoimmune response. 34,131,551-555|lla|B|

Class of recommendation.

11. Specific types of pericarditis

11.1. Tubculporis pericarditis

In high-income countries, TB pericarditis accounts for up to 4% of pericar-dial disease, but it is increasing due to immigration. On the other hand,TB is the cause of clinically significant Peff in approximately 90% of HIV-infected and 50%-70% of non-HIV-infected individuals living in devel-oping countries with a high prevalence of TB.556 It should be emphasized that most of the information on TB pericarditis comes from endemic areas in low-income countries and immunosuppressed patients.Notably, the disease can occur at any age, and men are affected more fre-quently than women.48 Tuberculous pericarditis has an overall mortality rate of 17%-40% at 6 months after diagnosis.557

11.1.1. Presentation

Clinical presentations of TB pericardial involvement include AP(most commonly with Peff), ECP, and CP, with these manifestations repre-senting consecutive stages of a unique process rather than independent conditions.558,559 Specifically, the evolution of TB pericarditis encom-passes four stages(Figure 18). The first stage or dry stage of AP is with-out effusion, the second stage with Peff (this is the form most commonly encountered in clinical practice) in up to 80% of cases, the third stage with progressive absorption of effusion, and the fourth stage with pericardial constriction. In the effusive phase, pericardiocentesis usually yields bloody feedback of effusion, and effusive-constrictive physiology may emerge after pericardial drainage. At this stage, lymphocytic exud-ate is mainly observed.560 The duration of each stage varies and de-pends on individual factors(e.g.HIV status), and early treatment may prevent progression.

11.1.2. Diagnosis

The diagnosis of TB pericarditis is challenging and in 15%-20% of cases the diagnosis may be missed.561 A'definite' diagnosis of TB is based on the presence of tubercle bacilli in the pericardial fluid or on a histologic-al sample of the pericardium, by culture or by PCR(Xpert MTB/RIF and RIF ultra) testing. A'probable' diagnosis is made when there is proof of TB elsewhere in a patient with unexplained pericarditis, a lymphocytic pericardial exudate with elevated unstimulated IFN-y(ulFN-y), adeno-sinease inaseby lysozyme levels, and/or an appropriate response to antuberculosis therapy in endemic areas. 558 In a meta-analysis, the sensitivity and specificity of adenosine deaminase, which is probably the most widely use biomarker, were 90% and 86%, respectively,for the diagnosis of TB pericarditis.562 Xpert MTB/RIF is highly specific(100%); however, it has a sensitivity of 64%, which increases to 78%when pericardial biopsy samples are employed.563,564 Pericardial fluid culture shows low sensitivity(53%-75%) and it is also time-consuming,needing more than 3 weeks to yield results. Interferon gamma offers su-perior accuracy for the diagnosis of microbiologically confirmed TB peri-cardits compared with the adenosine deaminase(ADA) assay and the Xpert MTB/RIF test.563 In a meta-analysis, values of ulFN-y in the pericar-dial fluid from studies using thresholds of 14-200 pg/mL showed very high sensitivity(97%) and specificity(99%) for the diagnosis of TB peri-carditis, with a positive likelihood ratio of 187 and a negative likelihood ratio of 0.03.565 On the other hand, the tuberculin skin test and IFN-y release assays are of limited value, especially in areas with a high burden of TB, since they cannot discriminate between previous exposure to Mycobacterium and active disease. ${}^{566}$ A detailed approach is outlined in Supplementary data online, Table S12.

ESC Guidelines

![Stage of tuberculous pericarditis\nStage I\nStage III\nStages of tuberculous pericarditis\nDry pericarditis\nEffusive-constrictive\nPericarditis\nStage IV\nStage II\nStage IV\nExtensive-constrictive\npericarditis\npericarditis constriction\nESC\n](2/aj0YEe4oUhYkBdfpda0fYP/figurea3b4666b58704860bc65f198a3bf6837_0_2.png) Figure 18 Stages of tuberculous pericarditis.

11.1.3. Therapy

Medical treatment consists of a regimen including rifampicin, isoniazid,pyrazinamide, and ethambutol for at least 2 months, followed by isoni-azid and rifampicin for an additional 4 months, which is effective in treating extrapulmonary TB.1,567 Treatment for≥9 months gives no better results and has the disadvantages of increased cost and poor compliance.567

However, it should be emphasized that, excluding isoniazid,poor drug penetration into the pericardial space is a matter of concern,also considering the emerging evidence of intraperacial bacillary load and mortality.568

With the prompt use of antubercular medications, steroids(oral or intrapericardial), and the widespread use of pericardial drainage with or without intrapericardial fibrinolysis, the currently reported rates of CP are between 5% and 25%. 569 Moreover, contemporary treatment has accounted for a 20% reduction in all-cause mortal-ity.567,569-572

Pericardial drainage by any means(pericordiosis or pericardial window) is recommended as an essential part of the work-up in pa-tients with suspected TB pericarditis, both for diagnostic and thera-peutic purposes.

Constriction generally develops in up to 50% of patients with-in 6 months of presentation prior to the introduction of effect-ive TB therapy.1 Appropriate antibiotic therapy is essential to prevent this progression.570 In addition, two interventions may reduce the incidence of constriction:(i) intrapericardial urokinase; and(ii) high-dose adjunctive prenisolone for 6 weeks.569,573

However, the coexistence of TB and HIV infection requires spe-cial attention. Prednisolone was associated with an increased risk of HIV-associated malignancies.569 On this basis, it may be reasonable to use adjunctive corticosteroids in patients with TB pericarditis without HIV infection and to avoid them in HIV-infected individuals. ${}^{569}$

Recommendation Table 20- Recommendations for tuberculous pericarditis(see Evidence Table 20)

|Recommendations|Classa|Levelb|| |---|---|---|---| |Diagnosis and treatment of tuberculous pericarditis|||| |Diagnostic pericardicitesis is recommended in all patients with suspected tuberculous pericarditis when diagnosis is not confirmed by non-invasive tests to identify the aetiological agent in pericardial fluid.|1|C|| |Empirical antuberculosis|||| |recommended in patients living in endemic areas with exudative pericardial effusion after excluding other causes to treat the most likely cause.567,570|1|C|| |Standard antuberculosis|multidrug treatment for 6 months is recommended in patients with tuberculous pericarditis for the prevention of pericardial constriction.570|1|C| |Pericardicey is recommended in patients with tuberculous pericarditis if the condition is not improving or is deteriorating after 4-8 weeks of antituberculosis therapy to change the course of disease.|1|C|| |Adjunctive steroid therapy is essential to prevent this progression. In addition, two interventions may reduce the incidence of constriction:(i) intrapericardial urokinase; and(ii) high-dose adjunctive prenisolone for 6 weeks. ${}^{569,573}$|In non-endemic areas a pericardial biopsy may be considered in patients with>3 weeks of illness without aetologic diagnosis. Empirical antituberculosis treatment is not recommended in patients living in non-endemic areas.|lla $\qquad$ C||

HIV, human immunodeficiency virus; TB, tuberculosis.

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

bLevel of evidence.

ESC Guidelines

11.2. Pericardial involvement in neoplastic disease

11.2.1. Presentation

Neoplastic pericardial involvement is occasionally manifested by peri-carditis or, more commonly, an isolated PEff(usually moderate to large, or CTP) with or without evident masses on imaging. It is usually related to metastatic lymphatic involvement(especially for lung can-cer) or haematogenous spread(especially for breast cancer). In add-tion, lymphomas, leukaemias, and melanoma may affect the pericardium, as may cancer of contiguous organs(e.g. oesophageal cancer).574,575 Primary neoplastic disease. For pericardium is the most common form, and it may pre-sent as ECP or CP in advanced cases. On this basis, the term'neoplas-tic pericarditis' is often used incorrectly instead of‘neoplastic pericardial effusion'.

11.2.2. Diagnosis

The definitive diagnosis is based on the confirmation of malignant in-filtration within the pericardial fluid by cytology(pericardiocentesis)or pericardial biopsy. A probable diagnosis may be achieved by the detection of tumour markers in the pericardial fluid(e.g. CEA,CYFRA 21-1,NSE,CA-19-9,CA-72-4,SCC,GATA3,and VEGF),al-though none of these tumour markers has been proven to be accur-ate enough for distinguishing malignant from benign effusions.576,577 Evidence of malignant disease elsewhere and concomitant pericardi-tis or PEff is also suggestive, although in almost two-thirds of patients with documented malignancy, pericardial involvement is caused by non-malignant diseases,15 e.g. radiation,578,579 chemotherapy,580 or infections. Cytological analyses of pericardial fluid are mandatory for the confirmation of malignant pericardial disease.581 Analyses of pericardial fluid and less commonly pericardial or epicardial biop-sies are essential for the confirmation of malignant pericardial disease.

11.2.3. Therapy

The management of these patients requires a multidisciplinary ap-proach involving oncologists, cardiologists, and radiotherapists, as well as other specific subspecialty experts according to the type of cancer.

General principles of treatment include systemic antineoplastic treatment as baseline therapy. Local antineoplastic treatment is based on tailored intrapericardial therapy according to the type of tumour(e.g. cisplatin is efficacious in lung cancer, thotopic in breast cancer),582 and intrapericardial instillation of cytostatic/sclerosing agents to pre-vent recurrences. Maligner Peffs show a high recurrence rate(>50%). Extended pericardial drainage can be necessary in patients with suspected or definite neoplastic PEFF to prevent effusion recur-rence and provide a route for intrapericardial therapy. Additional inter-ventions for recurrent effusions may include pericardiotomy,pericardial window, and percutaneous balloon pericardiotomy. All techniques are palliative and aimed at improving the quality of life of pa-tients with a poor short-term outcome.

Radiation therapy is very effective in controlling malignant PEff in pa-tients with radiosensitive tumours, such as lymphomas and leukemias.

In clinical practice, management is often palliative at late stages with advanced disease, and it is aimed only at the relief of symptoms rather than treatment of the underlying disease, considering the prognosis,and the overall quality of life of the patient.

Recommendation Table 21- Recommendations for neoplastic pericardial involvement(see Evidence Table 21)

|Recommendations|Classa|Levelb| |---|---|---| |Pericardiocentesis is recommended for patients with cardiac tamponade to receive symptoms and establish the diagnosis of malignant pericardial effusion.576,583|1|C| |Extended pericardial drainage(3-6 days) is recommended in patients with suspected or definite pericardial effusion to prevent effusion|1|B| |Cytological analysis of pericardial fluid is recommended in patients with neoplastic pericarditis for the confirmation of malignant pericardial disease.581|1|C| |Systemic antineoplastic treatment is recommended in confirmed cases of neoplastic aetiology to treat the primary and secondary metastatic neoplastic involvement.582|1|C| |Pericardiocentesis should be considered in patients with moderate to large pericardial effusion to establish the diagnosis of malignant pericardial effusion when the diagnosis cannot be reached by multimodality imaging.584|1a|C| |Pericardial or epicardial biopsy may be considered in patients with suspected malignant pericardial disease.584|11b|C| |Intraperarial therapy, in agreement with the oncologist, may be considered in cases refractory to systemic antineoplastic treatment.|11b|C|

aClass of recommendation.

bLevel of evidence.

11.3. Post-cardiac injury syndrome

The term PCIS is an umbrella term indicating a group of inflamma-tory pericardial syndes, including late post-acute myocardial infarction(post-AMI) pericarditis(or Dressler syndrome), post-pericardiotomy syndrome(PPS), and post-traumatic pericarditis with or without bleeding. Currently several post-traumatic cases are iatrogenic and related to cardiovascular interventions. ${}^{585,586}$

Nowadays, Dressler syndrome appears in<1% of cases, mainly in larger infarctions and/or late reperfusion, typically 1-2 weeks after AMI.587 Notably, patients with a post-AMI Peff of>10 mm at end-diastole should be investigated for a possible subacute heart rupture.588,589

In contrast, cases developing after cardiac device implantation or ar-rhythmia ablation(e.g. pericarditis appears in~10% of cases after AF ablation) are becoming increasingly common due to the growing number of invasive procedures.586,587,590,591

Such syndromes are presumed to have an autoimmune pathogenesis triggered by pericardial bleeding and/or pleura incision. 47,592 An immune-mediated pathogenesis is supported by a latent period,

ESC Guidelines

generally a few weeks, until the appearance of the first manifestations,the positive response to anti-inflammatory drugs, and the possibility of recurrences.

11.3.1. Diagnosis

According to proposed diagnostic criteria, the diagnosis of PCIS may be reached in the presence of at least two of the following five criteria:(i)fever without alternative causes;(ii) pericardial or pericardial chest pain;(iii) pericardial or pleural rubs;(iv) evidence of PEff; and/or(v) pleural effusion with elevated C-reactive protein.593-595

The rationale for proposing specific criteria is that these syndromes may have concomitant pleuro-pericardial involvement and possible pul-monary infiltrates, and are not simply pericarditis.595 Moreover, it is sometimes difficult to differentiate PISC from the simple mechanical consequences of surgery(such as early pericardial or pleural effusion).The demonstration of inflammatory activity(e.g.C-reactive protein ele-vation) is essential to establish the diagnosis. Multimodality imaging can be helpful for the diagnosis of complicated cases(e.g. loculated effu-sions, evidence of inflammation).

11.3.2. Therapy

The same therapeutic scheme adopted for AP, essentially based on em-pirical anti-inflammatory therapy, is effective for all forms of PCIS, and may improve remission rates and reduce the risk of recurrences. In early post-AMI pericarditis, a 5-7-day course of aspirin seems the most reasonable option, in association with colchicine.587

Different treatment strategies(namely aspirin, methylprednisolone,dexamethasone, and colchicine) have been adopted for the primary prevention of PPS, and the effects of such treatments have been ad-dressed in a meta-analysis that showed that only colchicine was asso-ciated with a decreased risk of PPS(OR 0.38), sometimes, however,with an increased risk of gastrointestinal side effects. ${}^{593,594,596-500}$ Preventive administration of colchicine can be given after cardiac sur-gery using weight-adjusted doses(i.e. 0.5 mg once for patients≤70 kg and 0.5 mg twice daily for patients>70 kg) and without a load-ing dose for the prevention of PPS and continued for 1 month. ${}^{596}$

In this guideline document, the LOE for colchicine recommendation for the prevention of PPS is based on analysis of the available evidence from more than one RCT, systematic reviews and the consensus opin-ion of the TF members.

Neither NSAIDs nor colchicine have to be administered for post-operative effusions in the absence of systemic inflammation. ${}^{601,602}$ Early post-operative PEfs are relatively common after cardiac surgery,and usually disappear spontaneously in 7-10 days.1 Asymptomatic small Pefs do not require treatment; however, moderate to large effusions(observed in one-third of cases) can progress to CTP at a rate of 10% within 1 month after surgery and need pericardial decompres-sion.603 Treatment of these asymptomatic effusions by NSAIDs has been shown to be ineffective[e.g. diclofenac in the Post-Operative Pericardial EFOPE) trial], and may be associated with an in-creased risk of side effects.601

The prognosis of PPS is generally good.600 In the largest published series on PPS patients after cardiac surgery, complication rates were low:<4% for recurrences;<2% for CTP; and no cases of constriction,although hospital stay may be prolonged in these patients.592 Moreover, the development of CP has been reported in~3% of cases.347 Both early post-AMI pericarditis and Dressler syndrome are markers of larger infarct size, but without independent prognostic significance.587

Recommendation Table 22- Recommendations for post-cardiac injury syndrome(see Evidence Table 22)

|Recommendations|Classa|Levelb| |---|---|---| |Anti-inflammatory therapy is recommended in patients with PCIs to hasten symptom remission and reduce recurrences.292,600|1|B| |IL-1 antagonists are recommended in patients with refractory PCIs to prevent recurrences and progression to constriction.604|1|B| |High-dose aspirin is recommended as the first-choice anti-inflammatory therapy for post-myocardial infarction pericarditis and in patients being already on antiplatelet therapy.|1|C| |Colchicine, started 48 to 72 h before cardiac surgery, should be considered for 1 month in patients after cardiac surgery for the prevention of PCIS if there are no contraindications and if it is tolerated.594,596|1a|A| |Careful follow-up should be considered in patients with PCIs to exclude possible evolution towards constrictive pericardits. ${}^{347}$|1la|C| |with PCIs to exclude possible evolution towards constrictive pericardits. ${}^{347}$|||

IL,interleukin;PCIS, post-cardiac injury syndrome.

aClass of recommendation.

bLevel of evidence.

11.4. Pericarditis and autoinflammatory diseases Compared with the previous guidelines, it has become evident that some inflammatory forms of RP share similarities with genetic autoinflamma-tory diseases characterized by periodic fevers, e.g.FMF and TRAPS.50,51

These are genetic disorders characterized by mutations of genes in-volved in the regulation of the inflammatory response, without involve-ment of specific T cells or autoantibodies. These disorders are usually detected in the pediatric population, although some patients ex-perience disease onset during adulthood. The most common monogenic autoinflammatory syndromes include FMF, in which serositis episodes last only 1-3 days, and TRAPS, in which fever and symptoms last for weeks.605 Mutations associated with these disorders have been reported in up to 10% of patients with multiple recurrences, especially with a positive family history, and a poor response to colchicine.152 Recently, rare deleterious MEFV variants were observed more frequently in idiopathic RP than in ancestry-matched controls(allele frequency 9/200 vs 2932/129 200,P=0.040).50 These conditions are characterized by the exaggerated pro-duction of IL-1 by the inflammasome. Familial occurrence of pericarditis has been reported among the relatives of idiopathic RP patients, ranging from 4%50 to 10%.113 These data suggest a genetic predisposition in at least a subset of patients; counselling may be warranted in these cases.

11.5. Purulent pericarditis

Purulent pericarditis, namely the most serious manifestation of bacter-ial pericarditis, is characterized by the macro- or microscopic presence of purulent Peff. It is an exceedingly rare form of pericarditis in the Western world, accounting for<1% of AP cases. ${}^{606}$ It has a high mor-tality in untreated cases while, in optimally treated patients, the re-ported survival rate is approximately 15%-40%. ${}^{606}$

In developed countries, the most common organisms isolated in purulent pericarditis include staphylococci and streptococci, while

ESC Guidelines

the predominant associated lesions are empyema(50%) or pneumonia(33%).In immunosuppressed patients or following thoracic surgery,the most frequently encountered bacterial/fungal agents are Staphylococcus aureus(30%) and fungi(20%), while anaerobic bacteria, originating from the oropharynx, have also been reported.607,608

It should be stressed that in the modern era of atrogenic and HIV-associated immunosuppression, more unusual organisms may ac-count for pericardial infection.1,607

11.5.1. Presentation

Purulent pericarditis has generally manifested as a serious febrile disease,and the underlying sepsis may predominate, including septic shock.606-608 Constrictive pericarditis complicates 20%-30% of cases.347

11.5.2. Diagnosis

Suspicion of purulent pericarditis is an indication for pericardial drainage independently from the haemodynamic status. Surgical pericardial drain-age is recommended to allow complete removal of the fluid and prevent its organization and progression to constriction. Low pericardial-to-serum glucose ratio(mean 0.3) and elevated pericardial fluid white cell count with a high proportion of neutrophils(mean cell count 2.8/mL, 92% neu-trophils) differentiate purulent from tuberculous(glucose ratio 0.7, mean cell count 1.7/mL, 50% neutrophils) and neoplastic pericarditis(glucose ratio 0.8, mean cell count 3.3/mL, 55% neutrophils).

Fluid must be sent for bacterial, fungal, and tuberculous studies along with blood and tissue samples, as guided by the clinical presentation. ${}^{1}$

11.5.3. Therapy

Intravenous antimicrobial therapy should be started empirically until microbiological results are available. Afterwards, pathogen-directed anti-biotic therapy is warranted based on antibiotic susceptibility. ${}^{1}$ The dur-ation of antibiotic therapy should be individualized until fever and clinical signs resolve, with the minimum period of administration being 3 weeks.

Purulent effusions are often heavily located and likely to rapidly re-accumulate.Subiphoid pericardiotomy and rinsing of the pericardial cav-ity should be considered.1 This allows more complete drainage of the effusion, since loculations can be manually used. Intrapericardial fibrinoly-sis is a possible treatment for cases of loculated effusions to achieve ad-equate drainage. ${}^{609}$ Fibrinolysis has been shown to prevent complications in approximately 86% of cases without fatal complications. ${}^{573,609,610}$ In the unfortunate case that percutaneous measures fail to control infec-tion, and worsening HF occurs along with constrictive physiology fea-tures, referral to surgical pericardiotomy is advised. ${}^{610}$

Recommendation Table 23- Recommendations for purulent pericarditis(see Evidence Table 23)

|Recommendations|Classa|Levelb| |---|---|---| |Urgent pericardiocentesis and/or a surgical window||| |is recommended in patients with suspicion of|1|C| |purulent pericarditis to establish a diagnosis.|606|| |Intrapericardial fibrinolysis should be considered in||| |patients with purulent pericarditis to allow complete||| |drainage of purulent fluid and to prevent||| |constriction. 573,610|||

Class of recommendation.

bLevel of evidence.

11.6. Incessant and recurrent pericarditis

The TF proposes to adopt the term‘incessant’ for cases of persistent symptoms without clear remission, and thus also to include cases of symptom persistence/recurrence during drug tapering. Recognition of these cases is of paramount importance, since they can directly progress to CP within a few months. ${}^{104}$ Recurrent pericarditis is defined as a re-lapse after a documented first episode of AP, a symptom-free interval,complete discontinuation of anti-inflammatory therapy, and evidence of subsequent recurrence of pericarditis. Recurrence usually occurs with in 18 months from the index episode, and is the most common and problematic complication of AP, ranging from 15% to 30% of cases after a first episode of pericarditis. It may increase to 50% after a first recur-rence in patients with inadequate treatment of the first episode(e.g.too fast tapering, not treated with colchicine, treated with corticoster-oids).25,611 In developed countries, the aetiology of recurrences is poorly known, and most cases are labelled as idiopathic. Historically, most cases were probably related to an autoinflammatory/autoimmune pathogen-esis. This is based on the inflammatory/non-inflammatory phenotype,the latency at the acute attack(several weeks after the index episode),the presence of autoantibodies, and the response to anti-inflammatory/immunosuppressive treatments. ${}^{52,283,284,287}$

11.7. Inflammatory and non-inflammatory pericardial effusion

The normal pericardial contains 10-50 mL of pericardial fluid, a plasma ultrafiltrate that acts as a lubricant between the pericardial layers. Any pathological process that causes pericardial inflammation in-creases the amount of fluid, causing PEff(exudate). Alternative mechan-isms causing PEff include decreased reabsorption following increased systemic venous pressure, as observed in congestive HF or pulmonary hypertension(transudate) or alternatively, decreased lymphatic drain-age. ${}^{612}$ The regimen of pressures in the epicardium and pericardial cav-ity is shown in Supplementary data online, Figure S4.

11.7.1. Classification and aetiology

The reported incidence and prevalence of PEff in developed countries is estimated at 3% and 6%-9%, respectively, based on echocardiographic laboratory records.613 Pemicardial effusion was detected in 14% of sub-jects in a prospective registry of consecutive patients who underwent chest CT.198

The classification of PEff is shown in Table 10. Echocardiography pro-vides semiquantitative assessment of the effusion size, which is useful for estimating the risk of having a non-idiopathic aetiology and complications(see Supplementary data online, Figure S5).105 In the past three decades,six major surveys have been published on the characteristics of moderate to large PEff(see Supplementary data online, Table S13).556,614-618 According to these series, many cases remain idiopathic in developed countries(up to 50%), while additional aetologies include cancer(10%-32%), infections(15%-30%), iatrogenic causes(15%-20%), and connective tissue diseases(5%-15%), whereas TB is the dominant cause in developing countries(>60%), where TB is endemic.

11.7.2. Presentation

A significant proportion of patients with Peff are asymptomatic, and Peff is an incidental during routine examination. The clinical presentation of Peff varies according to the speed of accumulation of fluid(see Supplementary data online, Figure S4). Classic symptoms include exertional dyspnoea progressing to orthopnoea, chest pain, and feeling of fullness.

ESC Guidelines

Additional symptoms due to the compression of adjacent structures in-clude nausea(diaphragm), dysphagia(oesophagus), hoarseness(recur-rent laryngeal nerve), and hiccups(phrenic nerve). ${}^{118,619}$

11.7.3. Diagnosis

Physical examination may be normal in patients without haemodynamic compromise.Echocardiography is the primary diagnostic tool for diagnosis, sizing,assessment of haemodynamic effects, and follow-up

(see Supplementary data online, Figure S5). ${}^{115,124}$ Advanced imaging(CT and CMR) provides valuable information concerning local inflam-mation,masses,associated chest abnormalities(e.g.pectus excavatum),loculated effusions, and systemic diseases.196,198,620 Pericardial effusion is often associated with known or unknown medical conditions(e.g.hypothyroidism) in up to 60% of cases, especially if moderate/large.A practical routine evaluation for the triage of PEff is presented in Figure 19. ${}^{1}$

![Pericardial effusion\n㈩\nFirst-line assessment with history,physical examination,ECG,chest X-ray transthoracic echocardiography, laboratory assessment\nthe cardiomyist is the primary diagnostic tool for eystern,speciformer is the annular diagnostic for the triage of PNeff is presented in\nThe treat as pericarditis\nTreat as pericarditis\nConcomitant pericarditis\n\nAssociated systemic disease\nLarge(>20mm) and chronic(>3 months) effusion\n\\㈩\nSymptomatic\n㈩\nOupatient follow-up\nPericardiocentesis with drainage\n㈩\nEmpiric anti-inflammatory therapy\n㈩\nOutpatient follow-up\nC\nTreat the systemic condition\n㈩\nAssociated systemic disease\n㈩\nLarge(>20mm) and chronic(>3 months) effusion\n㈩\nOupatient follow-up\nC\nFromout to study follow-up\nC\n](2/aj0YEe4oUhYkBdfpda0fYP/figurefe77f8bd413648168b64aabab7fbee58_0_6.png) 62

ESC Guidelines

Patients presenting with Peff without inflammatory marker elevation has an increased risk of a neoplastic aetiology(likelihood ratio 2.9).615 In chronic effusions with no definite aetiology, and without inflamma-tory markers, empirical anti-inflammatory treatment is futile.1,621 In worsening large effusions without evidence of systemic inflammation,the exclusion of cancer with advanced imaging(mainly CT) is war-ranted.196 C-reactive protein should be measured before pericardio-centesis, since it can increase after the procedure.622 Notably, the classical Light criteria used for the classification of pleural effusions should not be applied to Peff due to the high rate of misclassification of fluids as exudates, since pericardial fluid is rich in mesothelial cells,proteins, albumin, and lactate dehydrogenase(LDH). 623,624

11.7.4. Therapy

The treatment of Peff is shown in Figure 19. Therapy of Peff should be targeted at the aetiology, as much as possible. In the absence of pericar-dial inflammation(namely in the absence of C-reactive protein elevation and evidence of pericardial inflammation by an imaging technique) anti-inflammatory treatment is not recommended. According to recent data, the usefulness of pericardial drainage in asymptomatic or oligo-symptomatic, large, chronic, idiopathic effusions without evidence of pericarditis has been revised.49,621 Conservative treatment improves outcomes, the risk of CTP being only 2.2%/year without reported deaths. ${}^{625}$ In addition, survival after recurrence or complications is significantly better in patients treated conservatively without interven-tions. Nevertheless, if during follow-up the Peff becomes symptomatic and haemodynamic impairment is observed by echocardiography,drainage is warranted.

11.7.5. Prognosis and follow-up

The prognosis of PEFF is essentially related to its etiology.626 Moderate to large effusions are more common for specific etiologies.105,615 In general, PEff should be considered as a marker of the severity of the underlying disease.584 Small, idiopathic, asymptomatic Peff have an overall good prognosis with a very low risk of complications, although not all studies concur.613 Those individuals should be reassured about the benign nature of the condition, and should not restrict their physical activity if C-reactive protein is normal.1 The follow-up of Peff is mainly based on the evaluation of symptoms, using focused echocardiography to assess size changes, and haemodynamic issues, as well as C-reactive protein. Asymptomatic patients with mild idiopathic effusions do not generally require specific monitoring. In asymptomatic patients with at least moderate effusions, a reasonable follow-up is every 6 months,ideally in specialized centres. The latter patients should be instructed to seek medical advice in case of symptom appearance, such as dyspnoae or fatigue, and/or chest pain suggesting pericarditis.

11.8. Cardiac tamponade

Cardiac tamponade is a pericardial syndrome occurring when Peff im-pairs diastolic filling of the heart until cardiac output is reduced. The size of the effusion as well as its distribution may vary. Since the pericar-dium is relatively stiff, if pericardial fluid collects quickly, such as in haemo-pericardium, the limit of pericardial stretching is reached quickly with volumes of 200-300 mL.In contrast, slowly accumulating Peff may reach 1 to 2 L before the development of CTP(Supplementary data online,Figure S4). This pathophysiology explains that CTP is a last-drop phenom-enon. Thus, a small increase of pericardial volume may precipitate the

syndrome, and the aspiration of small amounts of pericardial fluid with pericardioestis may greatly improve the clinical condition. ${}^{118}$

Pericardial effusions are usually circumferential, but after trauma or cardiac surgery, they may be loculated and even be responsible for lo-calized compression and the development of CTP.

11.8.1. Presentation

Beck identified a triad of signs, consisting of hypotension, increased JVP,and quiet heart sounds as presenting symptoms.118,619

This triad was classically identified in'surgical tamponade' with acute CTP due to intraperarial haemorrhage because of trauma, or myo-cardial/aortic rupture. Beck's triad may be lacking in patients with'med-ical tamponade' with slowly accumulating pericardial fluid. Acute CTP is usually associated with tachycardia and low blood pressure(<90 mmHg) that is only slightly reduced in subacute, chronic tampon-ade.118,619 On physical examination, classical signs include neck vein dis-tention with elevated JVP, pulsus paradoxus, and diminished heart sounds. Pulsus paradoxus is defined as an inspiratory reduction of the systolic blood pressure by at least 10 mmHg. 118,619 Pulsus paradoxus is due to exaggerated ventricular interdependence occurring in CTP,when the overall volume of ventricles becomes unable to expand,and any change in the volume on one side of the heart causes opposite changes on the other side. On ECG, the patient usually shows tachycar-dia, low QRS voltages, and electrical alternans due to the damping effect of pericardial fluid and swinging heart. 118,619

11.8.2. Aetiology and diagnosis

Cardiac tamponade shares the same causes of Peff. In clinical practice,the most common aetiolages include cancer, TB, purulent infections,trauma, itrogenic complications of cardiovascular interventions(e.g.ablation of arrhythmias, device implantation, PCIS), acute aortic disease,systemic inflammatory diseases, and renal failure. ${}^{118}$ In the setting of AP with a viral or idiopathic aetiology, CTP is rare(1%-2% of cases) and is more common with pericarditis associated with a non-idiopathic aeti-ology(20%).347 The diagnosis of CTP is a clinical diagnosis based on the combination of a suggestive history, symptoms, signs, and imaging confirmation by echocardiography(Table 17). ${}^{118}$

Table 17 Echocardiographic signs of cardiac tamponade

|Echocardiographic feature|Sensitivity|Specificity| |---|---|---| |Large pericardial effusion with swinging|n.a.|n.a.| |heart||| |Diastolic collapse of the RA|50%-100%|33%-100%| |Duration of diastolic collapse of the RA as a ratio of the cardiac cycle length>0.34|>90%|100%| |Diastolic collapse of the RV|48%-100%|72%-100%| |Respiratory changes of the mitral E velocity>25%-30%, tricuspid E velocity|n.a.|n.a.| |>40%-60%||| |Inferior vena cava plethora(dilatation >20 mm and <50% reduction of diameter with respiratory phases), as well as hepatic vein dilatation|97%|40%| |$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|||

n.a.,not available;RA,right atrium,RV,right ventricle.

ESC Guidelines

The diagnosis of CTP identifies high-risk patients with an increased risk of complications during follow-up and a high probability of a non-viral aetiology. The patients should be admitted for therapy and monitoring.1,105

The definitive therapy is pericardioesis, which should be per-formed urgently according to the clinical presentation.

11.8.3. Therapy

The treatment for CTP is drainage of the pericardial fluid, preferably by needle pericardiocentesis with the use of echocardiographic or fluoro-scopic guidance, and should be performed without delay in unstable pa-tients. Alternatively, drainage is performed by a surgical approach,especially in situations such as purulent pericarditis, or urgent situations with bleeding into the pericardium.

Pericardiocentesis should be performed by experienced operators trained/certified in acute cardiovascular care and carries a variable risk of complications from 4% to 10%, depending on type of monitor-ing operator's skill, and setting(emergent vs urgent vs elective). The most common complications include arrhythmias, coronary artery or cardiac chamber puncture, haemorthax, pneumothorax, pneumoper-icardium, and hepatic injury.1 Mechanical ventilation with positive air-way pressure should be avoided in CTP. In addition, diuretic therapy should be avoided, and temporary fluid administration can be helpful to stabilize the patient while waiting for urgent pericardiocentesis.

11.8.4. Outcomes and prognosis

The prognosis of CTP is essentially related to its aetiology. Cardiac tam-ponade in patients with cancer and metastatic involvement of the peri-cardium has a bad short-term prognosis, since this is a sign of advanced disease.In contrast, patients with CTP and a final diagnosis of idiopathic pericarditis generally have a good long-term prognosis.1.105

11.9. Pericardial constriction and constrictive pericarditis(calcified and non-calcified)

11.9.1. Introduction

Pericardial constriction is a chronic condition usually characterized by a thickened, fibrotic, and often calcified pericardium that leads to im-paired diastolic filling of the heart. Constrictive pericarditis is

constriction associated with pericarditis.114,119,347 There is a high risk of progression in bacterial pericarditis(20%-30%), especially purulent pericarditis, intermediate risk in immune-mediated pericarditis and neoplastic pericarditis 2(%-5%), and a low risk in viral and idio-pathic pericarditis(<1%).347 Cases of CP after pericardietomy have been reported, especially after partial pericardietomy.627-630 In devel-oped countries, the most common reported causes are: viral or idio-pathic(42%-49%); post-cardiac surgery(11%-37%); post-radiation therapy, mostly for breast cancer or Hodgkin's disease(9%-31%); con-nective tissue disorders(3%-7%); post-infectious causes(purulent peri-carditis or TB in 3%-6%); and miscellaneous causes(<10%). TB is a major cause of CP in developing countries. 630,631

11.9.2. Presentation

The classical clinical presentation comprises signs and symptoms of right HF with preserved biventricular function without previous or con-comitant myocardial disease. Subacute/chronic inflammatory pericardi-tis can evolve into CP, and the duration of progression from initial pericardial inflammation and the onset of constriction is variable.347 Systolic dysfunction due to myocardial fibrosis or atrophy can aggravate the haemodynamic impairment in more advanced cases.

In up to 20% of cases, constriction might be present with normal pericardial thickness, while advanced and classic cases demonstrate prominent pericardial thickening and calcifications.119

11.9.3. Diagnosis

The diagnosis is made by multimodality imaging methods, such as echo-cardiography,CT,and CMR(Figure 13). Cardiac catheterization should be considered only if non-invasive multimodality imaging methods are inconclusive.115,124,632,6338 The Mayo Clinic has proposed specific diag-nostic criteria, based on echocardiography to diagnose CP, that have been confirmed by other centres. They include the presence of septal bounce or ventricular septal shift with either medial e' of>8 cm/s or hepatic vein expiratory diastolic reversal ratio of>0.78(sensitivity 87%, specificity 91%; specificity may increase to 97% if all criteria are present with a corresponding decrease of sensitivity to 64%). In add-ition, respirophasic variation E-wave mitral inflow of>25%/tricuspid in-flow of>40% can be recorded in these patients 632,634(see Supplementary data online, Figures S1, S5, and Table S14). The main re-ported constrictive syndromes are shown in Table 18.

Table 18 Definitions and therapy of main constructive pericardial syndromes

|Syndrome|Definition|Therapy| |---|---|---| |Transient constriction (d.d. permanent constrictive pericarditis, restrictive CMP)|Reversible pattern of constriction following spontaneous recovery or anti-inflammatory therapy|A 3-6 month course of empirical anti-inflammatory medical therapy| |Effusive-constrictive pericarditis (d.d. cardiac tamponade, constrictive pericarditis)|Failure of the right atrial pressure to fall by 50% or to a level <10 mmHg after pericardiocentesis May be diagnosed also by non-invasive imaging|Pericardiocentesis followed by medical therapy Surgery for persistent cases| |Chronic constriction (d.d. transient constriction, restrictive CMP)|Persistent constriction after 3-6 months|Radical pericardiectomy, medical therapy for advanced cases or high risk of surgery or mixed forms with myocardial involvement|

CMP,cardiomyopathy;d.d.,differential diagnosis.

ESC Guidelines

11.9.4. Therapy

Medical therapy is considered for specific aetologies, such as TB,to prevent progression to constriction.558 Antituberculosis drugs may significantly reduce the risk of constriction from>80%to<10%.569 Anti-inflammatory therapy may help to resolve tran-sient constriction in 10%-20% of cases of AP. ${}^{121,122}$ In such cases,to identify patients with potentially reversible forms of constric-tion, pericarditis should be excluded by testing markers of inflam-mation(e.g. C-reactive protein) or looking for imaging evidence of pericardial inflammation(e.g. pericardial oedema and/or LGE on CMR).

In advanced cases, medical therapy is supportive of controlling symp-toms of congestion, but surgery should never be delayed to improve outcomes.

Pericardectomy is the standard therapy for symptomatic chronic constriction without inflammation or not responding to anti-inflammatory therapy(see Section 6.4.2). For milder disease or more advanced disease, or for those with radiation-induced disease, reduced EF, or advanced renal disease, caution is necessary. Radical pericardict-omy rather than anterior phrenic-to-phrenic pericardictomy is war-ranted for the best outcomes.311,635-637

In general, pericardietomy has been seen as a high-risk surgery with operative mortality of 6%-10%. However, recent studies show better results for early surgery in high-volume centres. The risk is related to the aetologies and other comorbidities. Idiopathic causes have the low-est risk of<1.5%.638-640

Recommendation Table 24- Recommendations for constrictive pericarditis(see Evidence Table 24)

|Recommendations|Classa|Levelb| |---|---|---| |Diagnosis||| |Multimodality imaging is recommended in all patients with suspected constrictive pericarditis to make the diagnosis and assess pericardial thickening, calcifications, and active inflammation. ${}^{632}$|I|C| |Cardiac catheterization for haemodynamic assessment should be considered in patients with suspected constrictive pericarditis when multimodality imaging is inconclusive. ${}^{633}$|lla|C| |Therapy||| |Anti-inflammatory therapy is recommended in haemodynamically stable patients with a transient or new diagnosis of constriction with concomitant evidence of pericardial inflammation to prevent progression to constriction and avoid pericardictomy. ${}^{122,123}$||| |Pericardiectomy is recommended in patients with permanent constriction if there is no active inflammation or anti-inflammatory treatment is not successful after 3-6 months.||C|

CMR, cardiovascular magnetic resonance.

aClass of recommendation.

bLevel of evidence.

${}^{c}$ i. C-reactive protein elevation or pericardial enhancement on CMR.

11.10. Effusive-constrictive pericarditis

11.10.1. Introduction

In ECP, pericardial fluid is present, and the scarred pericardium puts pericardial fluid under increased pressure, constricts the cardiac vo-lumes, and leads to signs of CTP.116,117 Classically it is defined haemo-dynamically as failure of the RAP to fall by 50% or to a level below 10 mmHg after pericardiocentesis.117 Modern multimodality imaging allows a non-invasive diagnosis without cardiac catheterization.

11.10.2. Aetiology

Limited data have been published on ECP, and it appears to be a com-mon condition in developing countries. ${}^{117}$ Idiopathic cases are most commonly found in developed countries, while TB appears to be the most common cause in developing countries. The other reported causes are neoplasia, radiation, chemotherapy, infections(mainly TB and purulent type), and post-surgical pericardial disease. ${}^{641}$

11.10.3. Presentation

Clinical features of either CP or CTP, or sometimes both, are typically present in patients with ECP. In patients who appear to have uncompli-cated CTP,the diagnosis usually becomes evident during pericardiocen-tesi.117 Tricuspid regurgitation or right HF may cause persistently elevated RAP after efficient pericardiocentesis.

11.10.4. Diagnosis

To diagnose ECP, non-invasive imaging may be valuable.641 Thickening of the epicardial-pericardial layer is responsible for the constrictive compo-nent. After pericardiotensis for CTP, careful detection of constriction on Doppler findings can be reported.124 Without haemodynamic mon-itoring, ECP can also be suspected on echocardiography and CMR(see Supplementary data online, Table S14). Cardiovascular magnetic reson-ance may provide helpful information, especially in differentiating con-striction from RCM(Table S14). An accurate evaluation of ventricular interdependence and septal bounce can be made by assessing ventricular coupling with echocardiography and/or real-time cine CMR.115 Echo-Doppler findings indicating effusive constriction may be detected prior to pericardiocentesis. ${}^{116,124}$ Currently, the diagnosis can be made using multimodality imaging without cardiac catheterization.

11.10.5. Treatment

Effusive constriction can often resolve spontaneously or be treated with anti-inflammatory therapies in the case of evidence of transient constric-tion. ${}^{641}$ In resistant cases, visceral pericardiectomy must be performed,since the epicardial layer is responsible for constricting the heart.The visceral component of pericardietomy requires sharp dissection of many small frag-ments until ventricular motion is improved. Only pericardial centres with ex-perience and competency should perform pericardietomy for CP.

12. Age- and sex-related aspects in inflammatory myopericardial syndrome

12.1. Sex distribution

Acute myocarditis is more prevalent in males(75%-84%).

On the contrary, the male-to-female ratio is similar in fulminant cases(46% females). ${}^{56,75,643}$ Sex differences in pericarditis are less evident,

ESC Guidelines

with some studies showing a mild prevalence in males of 59% in A.P 37 Males aged 16-65 years are at higher risk of pericarditis(relative risk 2.02) than females. On the other hand, the probability of pericarditis recurrence is higher in females(HR 1.67), probably due to the higher frequency of specific causes(e.g. autoimmune diseases). ${}^{105}$

12.2. Paediatric patients

12.2.1. Myocarditis

The annual incidence of myocarditis during childhood is between 1 and 2 cases per 100 000 children. 21,644,645 In children<6 years of age, the sex distribution was balanced, 50% each, 20 but boys had a significantly higher incidence at ages 6 to 15 years.21

The proposed diagnostic approach in adults applies also for children,including CMR(e.g.in the MYKKE registry).646

There are conflicting data regarding the complication rates of EMB in children, with some studies reporting similar incidence of complications as in adults, both around 5%, mainly from RV sampling. 40,63 Particular care should be taken in children aged 1<1 year and in the case of LV bi-opsies with reported complication rates up to 30%. ${}^{213}$

In particular, very young children are predisposed to severe myocar-ditis. Critically ill children admitted to the intensive care unit(ICU)mostly survived, if receiving high-resource therapies, including MCS.647 In a prospective multicentre registry it was shown that in acute HF and FM, MCS including VAD improved survival. ${}^{648}$ Similar results have also been reported from Japan.

In infants, enteroviruses, such as Coxsackievirus, were found more commonly than in adults.649 A presumed viral etiology was identified in 11%-50%, 40,63 with a death or HT rate of 2%, similar to adults.21 In biopsy-proven myocarditis, the HT rate rises to 7%, and the mortality rate increases to 4%-6%.40

Therapy for myocarditis in children is not well defined. In a meta-analysis evaluating corticosteroids, no mortality reduction was observed, but a significant improvement in LVEF was reached with the use of steroids of other studies.650-652 In a meta-analysis evaluating IVIG,628 treatment was not associated with better survival. This was also supported by a prospective trial653 and a multicentre cohort study.654 On the contrary, another meta-analysis 655 in FM concluded that IVIG therapy(usually 1-2 g/kg over 24-48 h) significantly reduced in-hospital mortality and improved LVEF.

Genetic evaluation might help in the future in differentiating subsets of children and tailoring therapies.93

12.2.2. Pericarditis

In children aged 12 years or less, the incidence of AP was 2.8/100 000 in a population study from 2009 to 2021.64 The diagnostic criteria(see Table 4),etalogies, and risk of recurrences(see Tables S2 and S3) are similar to those reported in adults(see Supplementary data online,Table S1).Most paediatric cases of pericardits are related to PPS, particu-larly after atrial septal defect closure. Compared with adults, children more commonly have an inflammatory phenotype.65 Non-steroidal anti-inflammatory drugs remain the mainstay of therapy at high dosages(see Supplementary data online, Table S15). Most paediatricors avoid aspirin.Ccholichine halved recurrences in children, similarly as for adults. ${}^{665,667}$ The use of corticosteroids should be restricted even more than in adults,given that their side effects(including striae rubrae and growth impair-ment) are particularly deleterious in growing children. Anti-interleukin-1 agents have been used for the first time in children with autoinflammatory diseases and then adopted for RP in them, representing a new therapeutic option, especially if they are corticosteroid-dependent. However, it is

often difficult to withdraw these drugs when clinical remission is achieved;for instance, in one study only 15% of children were able to stop anti-IL-1 agents after a mean follow-up of 2.6 years. ${}^{658}$ Few paediatric patients were enrolled in RCTs testing anakinra and riloncept.

12.3. Pregnancy, lactation, and reproductive issues

There is very limited published evidence on this topic. There are only case reports for myocarditis, 659-663 and one case series describing pregnant women with RP.664 Pregnancy-associated myocarditis is de-scribed in Section 9.7. Pericardial effusion is the most common manifest-ation of pericardial diseases during pregnancy. Effusions during pregnancy are typically benign, mild or moderate, and well tolerated,with spontaneous resolution after delivery, and no specific treatment is required in such cases. However, PEff may be associated with pre-eclampsia.665 Acute pericarditis is the second most common condition.Pre-conception consulting is essential in women of childbearing with pre-RP or previous myocarditis. In such cases, pregnancy should be planned in a phase of disease remission, and therapy should be re-viewed. Pre-conception assessment should include multidisciplinary evaluation. Echocardiography is the preferred imaging method, while X-ray,CT scan, and CMR can be used in selected cases.

In patients with IMPS, vaginal delivery is not excluded in uncompli-cated cases, while Caesarean section may be required in the presence of haemodynamic instability.666 Appropriate follow-up with a multidis-ciplinary team with experience in the field is recommended throughout pregnancy to ensure good maternal and foetal outcomes.

High-dose aspirin or NSAIDs, such as ibuprofen and indomethacin can be used up to the 20th week of gestation. Corticosterolds at the minimal effective dose can be given in patients with active pericarditis throughout pregnancy along with NSAIDs and in selected cases colchi-cine. Azathioprine and IVIG are compatible with pregnancy and breeding. All these medications, apart from high-dose aspirin, may be used during lactation. Colchicine is compatible with pregnancy and breast-breastfeeding, and it can be continued throughout pregnancy to pre-vent recurrences. 664,667-669 The use of IL-1 blockers during pregnancy is controversial. Available literature data seem encouraging; however,the relevant studies are cant and retrospective. Despite the limited evi-dence, anakina may be continued through conception, pregnancy, and lactation in women with rheumatic and musculoskeletal diseases who are not able to use alternative therapies.668-670 More details regarding drug dosages can be found in Supplementary data online, Table S16.

There are no specific limitations for men with pericarditis who are planning to have children because they can safely continue therapy.667,668

Recommendations Table 25- Recommendations for pregnancy, lactation, and reproductive issues(see Evidence Table 25)

Recommendations Classa Levelb Pre-conception counselling is recommended in women with recurrent pericarditis or myocarditis to assess disease activity and to review therapy.NSAIDs should be considered in pregnant patients with pericardits until the 20th week to treat an incessant/recurrent course.664

Continued

ESC Guidelines

Anti-inflammatory therapies should be considered in patients with pericarditis during lactation to treat and prevent pericarditis with timing adjusted to reduce drug exposure of the breastfed infant.During pregnancy and breastfeeding, corticosteroids at the minimal effective dose(preferably up to 20 mg prednisone daily) should be considered in patients with active pericarditis, despite NSAID(if feasible),to prevent an incessant/recurrent course.Colchicine may be considered in pregnant patients with pericarditis, especially in patients already receiving this drug to prevent recurrences.Anakinra may be considered through pregnancy and lactation in pregnant patients with recurrent pericarditis who are not able to use alternative therapies to prevent an incessant/recurrent course.

NSAID, non-steroidal anti-inflammatory drug.Blevel of evidence.

12.4. The elderly

Myocarditis is more prevalent in young people, with a median age be-tween 20 and 40 years. ${}^{28,55,63,73}$ In a Swedish study, 64% patients were younger than 50 years of age. In this study, HF/DCM and deaths occurred more commonly in patients aged>50 years.17 Myocarditis is probably more commonly related to drugs in the elderly, e.g.IClS28,495 and clozapine. Age-and sex-based differences have been evaluated in two studies with AP, and one study with RP.45,102,671 In these studies,elderly patients less often had chest pain,fever,ST elevation,and PR de-pression.They had lower C-reactive protein values but dyspnoea,AF,and Peff were more common. Moreover, they received glucocorticoids more commonly, and had a lower risk of recurrences compared with younger patients. In the elderly, therapy compliance may be problem-atic, because of cognitive impairment and comorbidities, but the stron-gest predictor of non-adherence is the number of medications. ${}^{672}$ Non-steroidal anti-inflammatory drugs should be used cautiously; dos-ing should be adapted(e.g. colchicine dose should be halved in some cases), and attention should be paid to evaluate renal impairment and drug interactions.

12.5. Physical activity in inflammatory myopericardial syndrome

Patients with active IMPS are advised to restrict physical activity. It has been proposed that exercise can aggravate myocardial and pericardial inflammation through several mechanisms, including a tachycardia-mediated process. The importance of controlling heart rate is con-firmed by observational studies, in which the empirical use ofβ-blockers to control heart rate in patients with pericarditis improved symptom control.274 Previous recommendations have made distinc-tions between athletes and non-athletes, providing arbitrary times for abstention from 3 to 6 months. This TF recommends an individualized approach, based on remission times. A complete clinical remiash should be considered in athletes/non-athletes with normalization of symptoms, biomarkers, and imaging.

During the acute stage of myocarditis, patients are advised to rest completely, since exercise has been associated with arrhythmias and

SCD. To ensure resolution of the disease, recovery should be moni-tored,including clinical assessment,rhythm control,laboratory analysis,and multimodality imaging(see Table 15). A personalized prescription of exercise should be performed, based on the patient(athletes, non-atletes), and type of exercise.

12.5.1. Mental health effect of restricting exercise

Exercise restriction can affect patient mental health, especially in chil-dren and young adults. It can lead to frustration, sadness, and depres-sion in patients. Freedom to exercise should be approached with shared decision-making, taking into account the risk vs benefit ratio in the single case.

Recommendation Table 26- Recommendations for physical activity and myocarditis/pericarditis(see Evidence Table 26)

|Recommendation|Classa|Levelb| |---|---|---| |Restriction of physical exercise until remission, for at least 1 month, is recommended in athletes and non-athletes after IMPS using an individualized approach to accelerate recovery.||C|

IMPS, inflammatory hyperocardial syndrome.

aClass of recommendation.

bLevel of evidence.

12.6. Multidisciplinary teams for the management of inflammatory and pyromericardial syndrome

It is recommended to have a multidisciplinary team for high-risk cases with IMPS. The team should be composed of a clinical cardiologist, a CMR imaging specialist with expertise in IMPS, a pathologist with ex-pertise in cardiovascular diseases, and additionally, depending on the case, a rheumatologist(or clinical immunologist), an infectious disease specialist, a geneticist(or a cardiologist with expertise in genetics),interventional cardiologists(including electrophysiologists), and a car-diac intensive care specialist. A cardiac surgeon might be involved sub-sequently when interventional or surgical decisions are anticipated.More details are given in Figure 20. It is of paramount importance that physicians develop competence and skills in IMPS to allow timely diagnosis and therapy for patients, since mixed forms are common in clinical practice. Patient involvement is important, particularly when the evidence is scarce to foster shared decision-making. ${}^{375,673,674}$

Recommendation Table 27- Recommendations for multidisciplinary teams in myopericardial syndromes(see Evidence Table 27)

|Recommendations|Classa|Levelb| |---|---|---| |A multidisciplinary team discussion at a referral centre is recommended in patients with high-risk/ complicated IMPS to provide a patient-tailored approach. ${}^{375,673}$||C|

IMPS, inflammatory myoperic cardinal syndrome.

aClass of recommendation.

bLevel of evidence.

<FIGTEXT=>©ESC 2025</FIGTEXT>

![](2/aj0YEe4oUhYkBdfpda0fYP/figure7ca075981c6d494b90300bf4ece26617_0_0.png) 68

ESC Guidelines

14.4. Teamwork, competencies, and advances in imaging techniques

Building a contemporary multidisciplinary team requires knowledge of recent advancements in imaging techniques, as well as evidence-based strategies for drug,interventional, and surgical therapies.63,674-676 The conventional organization of academic or practice departments of-ten operates in isolation, hindering the requirements of diseases that demand the insights and skills of a diverse expert panel. These centres should endorse a comprehensive team setup that encourages regular,ongoing communication among all members.The role of physician-led vs nurse-led tertiary centres should be explored further674,675 in view of the increasing number and complexity of these patients, and the util-ity of monitoring inflammatory markers and serial monitoring of cardiac imaging, even in an outpatient setting.

15. Key messages

The recognition of the whole spectrum of IMPS is increasing within the medical community. This is based on a deeper understanding leading to a more systematic evaluation, as well as more data being generated by prospective trials. Although these entities have been explored for some time, the COVID-19 pandemic was the main trigger to increase the awareness on the spectrum of disease. Advanced multimodality imaging technologies, including CMR, allow a patient-tailored diagnostic and therapeutic approach. A major diagnostic paradigm change is the cap-ability of reaching a clinical diagnosis of certainty by non-invasive multi-modality imaging(CMR for myocarditis), while EMB remains important in selected intermediate- and high-risk cases, if a targeted specific ther-apy, based on specific histotypes or aetologies, is needed.

15.1. Aetiology

Inflammatory myopericardial syndrome is a spectrum of inflammatory diseases with some common aetiology, either infectious or non-infectious, that can affect either the myocardium(myocarditis) or peri-cardium(pericarditis) in isolated forms, or combined(myopericarditis)and perimycocarditis).

15.2. Clinical presentation and diagnosis

In a large percentage of cases, myocarditis and pericarditis have a chest pain presentation, and generally preserved biventricular function with good outcomes. For myocarditis, complicated forms include those pre-senting with severe HF and arrhythmias. Nevertheless, uncomplicated presentations may also develop life-threatening complications, albeit less commonly, and therefore also may need fast management.For pericarditis, complicated cases include those with an incessant or recurrent course. Many cases with persistent symptoms may show constrictive physiology, which can be reversible after appropriate med-ical therapy. The diagnosis of non-high-risk cases is based on clinical evaluation, including ECG and biomarkers, with non-invasive confirm-ation of the clinical suspicion by evidence of inflammatory involvement using multimodality imaging(mainly echocardiography and CMR).Endomyocardial biopsy is recommended for intermediate- and high-risk cases on a case-by-case decision, only when results are expected to change management.

15.3. Therapy

The treatment of uncomplicated IMPS is empirical, aiming at the control of symptoms and prevention of complications. Anti-inflammatory

drugs and colchicine are useful to control chest pain, while additional therapies should be guideline-directed for specific complicated courses.If a specific aetiology is identified, treatment should be targeted at the specific cause. In all cases of IMPS, restriction of physical activity is re-commended in the acute phase, while return to work and physical ac-tivity should be individualed according to clinical remission times.

15.4. Prognosis and outcomes

The prognosis of IMPS varies. Most patients presenting with chest pain have a favourable outcome, although recurrences, especially for peri-carditis, may severely affect the quality of life of patients and require long-term follow-up. For complicated cases of myocarditis with HF and arrhythmias, a tworal and individualized approach is warranted.Such patients require long-term follow-up, usually lifetime monitoring.

15.5. Multidisciplinary team

Management of patients with IMPS should usually be guided by a multi-disciplinary team, which should be tailored to the specific patient.This team should be composed of different clinicians, all with expertise in cardiovascular diseases(e.g. imaging experts, a pathologist, a rheuma-tologist, an infectious disease specialist, a geneticist, interventional car-diologists, intensive care specialists, and surgeons). It is of paramount importance that physicians develop competence and skills either in myocarditis or pericarditis to allow timely diagnosis and therapy for pa-tients, because mixed forms are common in clinical practice.

16. Gaps in evidence

The field of IMPS has significant knowledge gaps across all aspects, from pathogenesis to therapy. However, growing awareness has led to nu-merous ongoing studies. Advances in multimodality imaging have en-abled a more comprehensive and non-invasive understanding of disease progression, opening the way to patient-tailored approaches.Despite these advancements, large-scale prospective multicentre trials with predefined outcome measures are lacking. These uncertainties are especially pronounced in chronic conditions, as well as in specific pa-tient groups, such as children, women of childbearing age, during preg-nancy, lactating women, and in the elderly.

A further challenge is the handling of the return to work and physical activity as there is a need for a patient-specific approach, taking into consideration the individual risk. Lessons learned from other diseases should lead to less restrictive guidance in comparison with previous advice.

16.1. Myocarditis

Knowledge about myocarditis has evolved during recent years, as the different mechanisms are better understood. Several causes, such as viral and toxic ones, including chemotherapy, as well as systemic disor-ders, have been investigated, and targeted therapeutic approaches were proposed. However, further research into specific therapy is needed based on advanced diagnostic approaches.

Nevertheless, a specific challenge for myocarditis is related to the low frequency of complications and the high rate of spontaneous remis-sion. On this basis, clinical trials on medical therapy for myocarditis might be currently underpowered to assess the clinical benefit of a spe-cific treatment with small sample sizes. In addition, many antiviral ther-apies are off-label for myocarditis and controlled trials are missing.

ESC Guidelines

Currently, quantitative immunohistochemistry criteria for the diag-nosis of LM are under discussion among cardio-pathologists to present more definite criteria for EMB.

Furthermore, a better understanding of the pathogenic and prognos-tic role of viral loads is needed(e.g. active/causative vs latent/innocent bystanders in cardiac viral infections).

Moreover, the role of genetic predisposition in recurrent myocardi-tis is not thoroughly clarified. Research into the role of genetic predisposition is evolving to change the classification of disease and may influence therapeutic pathways in the future. An increase of 'overlap-ping' conditions, especially DCM and ARVC, can be expected and may change our understanding of the disease in the future.

That means, more research is warranted on the prognosis and SCD risk stratification.

16.2. Pericarditis

There are significant knowledge gaps in individualized treatment and pathogenesis of various types of pericarditis, as well as the understand-ing of the interaction among genetic background, inflammation, and autoimmune mechanisms. Better knowledge of the pathogenesis of re-currences may also help to develop more targeted and individualized therapies.

The genetic background requires further evaluation in complicated,recurrent cases and could be helpful to elucidate the mechanisms lead-ing to incessant/recurrent forms. New therapeutic options should also be considered and evaluated in clinical trials to explore new drugs for more complicated, incessant, or recurrent cases to develop a more in-dividualized and efficacious approach for the treatment of pericarditis.

A significant management issue is the treatment of patients not re-sponding to colchicine and anti-IL-1 agents, as well as the causes of drug dependence to maintain stable clinical remission, such as for cor-ticosteroids and anti-IL-1 agents.

Additional research is also warranted to understand the prognostic significance of persistent LGE of the pericardium.

There are limited data to support the best timing of return to work and physical activity, and further research is needed on this topic with appropriate clinical trials or observational studies.

17. Sex differences

There is limited published evidence on this topic. Inflammatory myo-pericardial syndrome seems to affect males more than females from a young age. Myocarditis complicated by VA is more common in males,while in females, a relatively higher proportion of cases presents with complicated forms compared with males, and systemic autoimmune disorders are more commonly diagnosed. This was addressed in the relevant sections. The diagnostic approaches are similar, but care should be taken when applying normal values, especially in imaging.Medication should be adapted in women of childbearing age, pregnancy,and during lactation(more details are specified in specific sections).

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

Table 19 lists all Class I and Class III recommendations from the text alongside their level of evidence.

Table 19‘What to do’ and‘What not to do’

|Recommendations|Recommendations|Classa|Levelb| |---|---|---|---| |Recommendations for clinical evaluation of myocarditis and pericarditis|||| |Complete clinical evaluation, including history, physical examination, chest X-ray, biomarkers,ECG,and echocardiography is recommended in all patients with a suspicion of myocarditis and/or pericarditis for the initial diagnostic assessment.|1|C|| |CMR is recommended in patients with the clinical suspicion of myocarditis(using updated LL criteria) and/or pericarditis for the non-invasive diagnosis of inflammatory reaction.|1|B|| |Hospital admission is recommended for patients with high-risk pericarditis for monitoring and treatment.|1|B|| |Hospital admission is recommended for patients with moderate- to high-risk myocarditis for monitoring and treatment.|1|C|| |EMB is recommended in patients with high-risk myocarditis and/or haemodynamic instability, and/or in patients with intermediate-risk myocarditis not responding to conventional therapy in order to detect a specific histologic subtype and to assess the presence of viral genome for treatment.|1|C|| |Invasive coronary angiography or coronary CT, depending on clinical likelihood, is recommended in patients with IMPS if an acute coronary syndrome is suspected to rule out obstructive coronary artery disease.|1|C|| |Routine serology is not recommended in patients with myocarditis and/or pericarditis for the evaluation of viral aetiology except for hepatitis C,HIV and Lyme disease.|III|C|| |Recommendations for genetic testing|||| |It is recommended to obtain family history including pedigrees in cases of recurrent IMPS to provide clues to the underlying aetiology, determine inheritance pattern, and identify relatives at risk.|I|C|| |Recommendations for the use of cardiovascular magnetic resonance imaging|||| |Myocarditis|Myocarditis|Myocarditis|Myocarditis| |CMR is recommended in patients with suspected myocarditis to reach a clinical diagnosis and to determine the cause of acute myocardial injury, including assessment of oedema, ischaemia, and necrosis/fibrosis/scarring.|I|B||

Continued

<FIGTEXT=></FIGTEXT>

ESC Guidelines

CMR is recommended for follow-up at least within the first 6 months in patients with myocarditis to identify a healed or ongoing process,for risk stratification and personalized therapy, and to enable a return to exercise.

Pericarditis

CMR is recommended in patients with suspected pericarditis when a diagnosis cannot be made using clinical criteria to assess evidence of pericardial thickening, oedema,LGE,and to assess the persistence of disease during follow-up in selected cases.

Recommendations for computed tomography

CT is recommended to evaluate pericardial thickness, calcifications, masses, and loculated pericardial effusions, as well as concomitant pleuropulmonary diseases and chest abnormalities.

Recommendations for endomyocardial biopsy

EMB is recommended in patients with high-risk myocarditis, and/or haemodynamic instability, and/or in patients with intermediate-risk myocarditis not responding to conventional therapy in order to detect a specific histologic subtype and to assess the presence of viral genome for treatment.

Recommendations for autopsy

Comprehensive autopsy is recommended in all patients <50 years of age with SCD to evaluate the presence of acute myocarditis as a cause

Retaining samples suitable for DNA extraction and consulting a cardiac pathologist is recommended in cases of SCD, when an inherited cause is suspected, or the cause of death remains unexplained.

Recommendations for medical therapy in myocarditis

Management of heart failure

Adherence to the ESC HF guidelines is recommended in cases of myocarditis with LV systolic dysfunction and/or HF to reduce symptoms and to improve LV function.

Immunosuppressive therapy

Routine use of immunosuppressive therapy is not recommended in acute myocarditis with preserved LV function because no outcome benefit has been shown.

Recommendations for medical therapy in pericarditis

Colchicine is recommended as first-line therapy in patients with pericarditis as an adjunct to aspirin/NSAID or corticosteroid therapy to reduce subsequent recurrences.

Anti-IL-1 agents (anakinra or lriocapent) are recommended for patients with recurrent pericarditis after failure of first-line therapies and corticosteroids, and elevation of C-reactive protein levels to reduce recurrences and allow corticosteroid withdrawal.

High-dose aspirin or NSAIDs with proton pump inhibitors are recommended as first-line therapy in patients with pericarditis to control symptoms and reduce recurrences.

Corticosteroids are not recommended as the first option for patients with pericarditis therapy without a specific indication.

Recommendations for interventional techniques, including circulatory support in myocarditis

A timely and dedicated Shock Team discussion is recommended in patients with myocarditis in the presence of haemodynamic compromise, to decide on the need for escalation to MCS and to determine a long-term management plan.

Recommendations for interventional techniques in pericarditis

Pericendocistesis(echocardiography CT-, or fluoroscopy-guided) is recommended for cardiac tamponade, or suspected bacterial or neoplastic pericarditis, or symptomatic moderate to large pericardial effusion despite medical therapy.

Surgical pericardial drainage is recommended in patients with pericardial effusion when percutaneous pericardiocentesis is not feasible or with purulent pericardial effusion to allow complete drainage and to prevent constriction.

Surgical pleuro-pericardial window is recommended in patients with relapsing pericardial effusion despite medical therapy.

Recommendations for surgical therapy

Surgical pericardietomy is recommended in patients with chronic pericardial constriction or persistent constrictive pericarditis despite medical therapy to improve symptoms and survival.

Tricuspid valve repair is recommended in patients with pericardial constriction and severe tricuspid valve regurgitation to improve symptoms and survival.

Recommendations for management of arrhythmias and prevention of sudden cardiac death in myocarditis

ICD in myocarditis-secondary prevention

ICD implantation is recommended in patients with non-active myocarditis and haemodynamically not-tolerated sustained VT to prevent SCD.

Continued

<FIGTEXT=></FIGTEXT>

ESC Guidelines

Recommendations for risk stratification, complications, and outcomes of inflammatory myopericardial syndrome

Follow-up with clinical assessment, biomarkers, ECG, exercise test, Holter-ECG monitoring, echocardiography, and CMR at least within 6 months after the index hospitalization is recommended in all patients with myocardits to identify a potential progression or new risk factors.

Long-term follow-up is recommended for patients with complicated myocarditis to identify a potential progression or new complications.

Long-term follow-up is recommended for patients with incessant or recurrent pericarditis to identify a potential progression and new complications.

Recommendations for giant-cell myocarditis

EMB is recommended in patients with suspected GCM due to unexplained new-onset HF of up to 2 weeks associated with a normal or dilated left ventricle and new ventricular arrhythmias, second- or third-degree AVB, or failure to respond to usual care within 1 to 2 weeks to initiate specific treatment.

Combined immunosuppressive therapy is recommended in patients with a diagnosed GCM.

<EndOfPara> C

Recommendations for myocarditis in sarcoidosis

Diagnosis

CMR, using tissue characterization techniques, is recommended in patients with suspected CS to assess cardiac inflammation and myocardial involvement.

1 B

${}^{18}$ F-FDG-PET is recommended for the diagnostic work-up, including detection of inflammation, as well as for follow-up and assessment of therapeutic response in patients with CS.

Therapy

ICD implantation is recommended in patients with CS and sustained ventricular arrhythmia (VT/VF) or aborted CA to prevent SCD.CI implantation is recommended in patients with CS and LVEF ≤35% to prevent SCD.

1 B

Recommendations for immune checkpoint inhibitor-associated myocarditis

Diagnostic triage within 24 h is recommended in patients with suspected myocarditis induced by ICI to initiate treatment rapidly.Immediate disruption of ICI and administration of high-dosage corticosteroids are recommended in patients with ICI-associated myocarditis in order to stop the inflammatory reaction and stabilize the patient.

<EndOfPara> I C P C

Recommendations for inflammatory cardiomyopathy

Guideline-directed HF treatments are recommended in patients with inflammatory cardiomyopathy to improve and/or stabilize left ventricular function.

1 C

Specific medical therapy for the potentially underlying systemic disease is recommended in inflammatory cardiomyopathy.

Recommendations for tuberculosis pericarditis

Diagnosis and treatment of tuberculosis pericarditis and effusion

Diagnostic pericardiocentesis is recommended in all patients with suspected tuberculosis pericarditis when diagnosis is not confirmed by non-invasive tests to identify the aetiological agent in pericardial fluid.

Empirical antituberculosis chemotherapy is recommended in patients living in endemic areas with exudative pericardial effusion after excluding other causes to treat the most likely cause.

Standard antituberculosis multidrug treatment for 6 months is recommended in patients with tuberculosis pericarditis for the prevention of pericardial constriction.

Pericardiectomy is recommended in patients with tuberculosis pericarditis if the condition is not improving or is deteriorating after 4-8 weeks of antituberculosis therapy to change the course of disease.

Recommendations for neoplastic pericardial involvement

Pericardiocentesis is recommended for patients with cardiac tamponade to relieve symptoms and establish the diagnosis of malignant pericardial effusion.

Extended pericardial drainage (3-6 days) is recommended in patients with suspected or definite neoplastic pericardial effusion to prevent effusion recurrence.

Cytological analysis of pericardial fluid is recommended in patients with neoplastic pericarditis for the confirmation of malignant disease.

Systemic antineoplastic treatment is recommended in confirmed cases of neoplastic aetiology to treat the primary and secondary metastatic neoplastic involvement.

Continued

ESC Guidelines

Recommendations for post-cardiac injury syndrome

Anti-inflammatory therapy is recommended in patients with PCIS to hasten symptom remission and reduce recurrences.IL-1 antagonists are recommended in patients with refractory PCIS to prevent recurrences and progression to constriction.

High-dose aspirin is recommended as the first-choice anti-inflammatory therapy for post-myocardial infarction pericarditis and in patients already on antiplatelet therapy.

Recommendations for purulent pericarditis

Urgent pericordentesis and/or a surgical window is recommended in patients with suspicion of purulent pericarditis to establish a diagnosis.

Recommendations for constrictive pericarditis

Multimodality imaging is recommended in all patients with suspected constrictive pericarditis to make the diagnosis and assess pericardial thickening, calcifications, and active inflammation.

Therapy

Anti-inflammatory therapy is recommended in haemodynamically stable patients with a transient or new diagnosis of constriction with concomitant evidence of pericardial inflammation to prevent progression to constriction and avoid pericardietomy.Pericardiectomy is recommended in patients with permanent constriction if there is no active inflammation or anti-inflammatory treatment is not successful after 3-6 months.

Recommendations for pregnancy, lactation, and reproductive issues

Pre-conception counselling is recommended in women with recurrent pericarditis or myocarditis to assess disease activity and to review therapy.

Recommendations for physical activity and myocarditis/perocarditis

Restriction of physical exercise until remission, for at least 1 month, is recommended in athletes and non-athletes after IMPS using an individualized approach to accelerate recovery.

Recommendations for multidisciplinary teams in mypericardial syndromes

A multidisciplinary team discussion at a referral centre is recommended in patients with high-risk/complicated IMPS to provide a patient-tailored approach.

AVB, atrioventricular block;CA, cardiac arrest;CMR, cardiovascular magnetic resonance;CS,cardic sarcadosis;CT,computed tomography;DNA,deoxyribonucleic acid;ECG,electrocardiogram;EMB,endomyocardial biopsy;ESC,European Society of Cardiology; ${}^{18} F$ -FDG-PET, ${}^{18} F$ -Fluorodeoxyglucose positron emission tomography; GCM, giant-cell myocarditis; HF, heart failure; HIV, human immunodeficiency virus; ICD, implantable cardioverter-defibrillator; ICI, immune mechanical circulatory support; INSAD, non-steroidal mycoradic syndrome; LGE, late gadolinium enhancement; LV, left ventricle; LVEF, left ventricular ejection fraction; MCS, mechanical circulatory support; NSAID, non-steroidal anti-inflammatory drug; PCIS, post-cardiac injury syndrome; SCD; sudden cardiac death; VF, ventricular fibrillation; VT, ventricular tachycardia.

Level of evidence.

19. Evidence tables

Evidence tables are available at the European Heart Journal online.

20. Data availability statement

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

21. Author information

Author/Task Force Member Affiliations: Valentino Collini,Cardiology, Cardiothoracic Department, Santa Maria della Misericordia University Hospital, Urdine, Italy; Jan Grschel, Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, ECRC Experimental and Clinical Research Center, Berlin, Germany, and DZHK(German Centre for Cardiovascular Research), partner site Berlin, Berlin,Germany, and Deutsches Herzzentrum der Charite, Klinik fur

Kardiologie, Angiologie und Intensivmedizin, Berlin, Germany;Yehuda Adler, Sackler Medical School, Tel Aviv University, Tel Aviv,Israel; Antonio Brucato, Department of biomedical and clin-ical sciences, University of Milano, Fatebenefratelli Hospital, Milano,Italy;Vanessa Christian(United Kingdom), ESC Patient Forum,Sophia Antipolis, France; Vanessa M. Ferreira, Oxford Centre for Clinical Magnetic Resonance Research(OCMR), University of Oxford, Oxford, United Kingdom; Estelle Gandjbakhch,Cardiology Department, Sorbonne Université, APHP, Hopital Pitie Salpetriere, Paris, France, Pitié Salpetriere, Paris, France, and Referral Center for Inherited Cardiac Diseases, APHP, Hopital Pitié Salpetriere, Paris,France,and Inserm 1166,IHU ICAN, Paris, France; Bettina Heidecker,Deutsches Herzzentrum der Charité, Universitatsmedizin Berlin,Berlin, Germany, and Berlin Institute of Health(BIH), Charité,Universitatsmedizin Berlin, Berlin, Germany, and DZHK(German Centre for Cardiovascular Research), partner site Berlin, Berlin,Germany; Mathieu Kernelsone, Sorbonne Université, Paris,France,and ACTION Group, Paris, France, and UMRS 1166 Inserm, Paris,France, and Institute of Cardiology, Hopital Pitié-Salpétriere,

ESC Guidelines

Assistance Publique-Hópitaux de Paris(AP-HP), Paris, France; Allan L. Klein, Center for the diagnosis of pericardial disease, department of cardiovascular medicine, heart, vascular and thoracic institute,Cleveland clinic, Cleveland, Ohio, United States of America; Karin Klingel, Institute for Pathology and Neuropathology, University Hospital Tuebingen, Tuebingen, Germany; George Lazaros,Cardiology, School of medicine, Hippokration General Hospital,National and Kapodistrian University of Athens, Athens, Greece;Roberto Lorusso, Cardio-Thoracic Surgery, Maastricht University Medical Centre, Maastricht, Netherlands, and Cardiovascular Research Institute Maastricht, Maastricht, Netherlands; Elena G. Nesukay,Department of non-coronary heart diseases, rheumatology and therapy,National scientific center"The M.D. Strazheskoite institute of cardiology,clinical and regenerative medicine', Kiev, Ukraine; Kazem Rahimi,Nuffield department of women's and reproductive health, University of Oxford, Oxford, United Kingdom; Arsen D. Ristic, Department of Cardiology, University Clinical Center of Serbia, Belgrade, Serbia,and Faculty of Medicine, Belgrade University, Belgrade, Serbia;Marcin Rucinski(Poland), ESC Patient Forum, Sophia Antipola, France; Leyla Elif Sade, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America, and Department of Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA,United States of America; Hannahchaubroeck Intensive Care Unit, Ghent University Hospital, Ghent, Belgium; Anne Grete Semb, Department of research and innovation, REMEDY centre,Diakonhjemmet Hospital, Oslo, Norway; Gianfranco Sinagra,Center for Diagnosis and Treatment of Cardiomyopathies,Cardiothoracovascular Department, Azianda Sanitarum Universitaria Giuliano-Insatina(ASUGI), University of Trieste,triangle, Italy; Jens Jakob Thune, Department of cardinalology, Copenhagen University Hospital-Bispejberg and Frederikbergs, Copenhagen, Denmark, and Department of clinical medicine, University of Copenhagen,Copenhagen,Denmark.

22. Appendix

ESC Scientific Document Group

Includes Document Reviewers and ESC National Cardiac Societies.

Document Reviewers: Elena Elo(CPG Review Co-ordinator)(Spain), Cristina Basso(CPG Review Co-ordinator)(Italy), Mariana Adamo(Italy), Suleman Aktaa(United Kingdom),Enrico Ammirati(Italy), Lisa Anderson(United Kingdom), Eloisa Arbustini(Italy), Emanuele Bobbio(Sweden), Giuseppe Borani(Italy),Margarita Brida(Croatia), Robert A. Byrne(Lalido), Alida L.P.Caforio(Italy), Gh.-Andrei Dan(Romania), Fernando Dominguez(Spain), Suznean Fredericks(Canada), Geeta Gulati(Norway), Borja Ibanez(Spain), Stefan James(Sweden), Alexander Kharlamov(Netherlands), Sabine Klaassen(Germany), Jolaya Klun(Netherlands), Konstantinos C. Koskinas(Switzerland), Petr Kuchynka(Czech Republic), Vijay Kunadian(United Kingdom), Lif Landmesser(Germany), Gregory Y.H. Lip(United Kingdom),Bernhard Maisch(Germany), Federica Marille-Berg(United Kingdom), Pilar Martin(Spain), John William McEvoy(Ireland),Borislav Mihaylova(Yind Kingdom), Richard Mindham(United Kingdom), Inge Moelgaard(Denmark), Saidi A. Mohiddin(United Kingdom), Jens Cosedis Nielsen(Nemden), Agnes A. Pasquet(Belgium), Giovanni Perretto(Italy), KaliPIi Pilichou(Italy), Nicolas Pirou(France), Eva Prescott(Denmark), Amina Rakisheva(Kazakhstan), Bianca Rocca(lta), Xavier Rossello(Spain), Anna

Sannino(Germany), Franziska Seidel(Germany), Felix C. Tanner(Switzerland), Witoldy Zbyszek Tomkowski(Poland), Ilonca Vaartjes(Netherlands), Sophie Van Linthout(Germany), Christiaan Vrints(Belgium), Romuald Wojnicz(Poland), Katja Zeppenfeld(Netherlands)

ESC National Cardiac Societies actively involved in the review process of the ESC Guidelines for the management of myocarditis and pericardits:

Albania: Albanian Society of Cardiology, Albana Doko Banushi;Albania: Algerian Society of Cardiology, Mohammed Chettibi;Armenia: Armenian Cardologists Association, Hamayak S. Sisakian;Azerbaijan: Azerbaijan Society of Cardiology, Ogtay Musayev;Belgium: Belgian Society of Cardiology, Bernard P. Paelinck; Bosnia and Herzegovina: Association of Cardiologists of Bosnia and Herzegovina, Alden Begc; Bulgaria: Bulgarian Society of Cardiology,Yayvo Laskakov, Cratio: Croatian Cardiac Society, Bosko Skoric;Cyprus: Cyprus Society of Cardiology, Marios Ioannides; Czechia: Czech Society of Cardiology, Tomas Palecek; Denmark: Danish Society of Cardiology, Kasper Rossing; Egypt: Egyptian Society of Cardiology, Haytham Soliman Ghareeb; Estonia: Estonian Society of Cardiology, Uni Hint: Finland: Finnish Cardiac Society, Markku Kupari: France: French Society of Cardiology, Emmanuelle Berthelot; Georgia: Georgian Society of Cardiology, Vaja Agladze;Germany: German Cardiac Society, Brenda Gerull; Greece:Helenic Society of Cardiology, Alexandroskai Kasakogias; Hungary:Hungarian Society of Cardiology, Hajnalka Vago; Iceland: Icelandic Society of Cardiology, Inga Jóna Inglimarsdottir; Ireland: Irish Cardiac Society, Emer Joyce; Israel: Israel Heart Society, Sorel Goland; Italy: Italian Federation of Cardiology, Enrico Fabris;Kazakhstan: Association of Cardiologists of Kazakhstan;�Razakhstan: Fahrat Amanzholovich Mukarov; Kosovo(Republic of): Kosovo(Republic of):Kyrgyz Society of Cardiology, Ginta Kamzola; Lebanon: Lebanon Society of Cardiology, Naji J. Abrached; Libya: Libyan Cardiac Society, Aiman M. Smer; Lithuania: Lithuanian Society of Cardiology, Vaida Mizariene; Luxembourg: Luxembourg Society of Cardiology,Maztals: Maltese Cardiac Society, Tiziana Felice;Moldova(Republic of): Moldavian Society of Cardiology,Eleonora Boris Viramatam; Morocco; Morocco; Romania;Cardiology, Aida Soufani; Netherlands: Netherlands Society of Cardiology, Geertruida Petronella Bijvoet; North Macedonia: National Society of Cardiology of North Macedonia, Irena Mitevska;Norway: Norwegian Society of Cardiology, Haavard Ravnestad;Poland: Polish Cardiac Society, Karol Kaminski; Portugal:Portuguese Society of Cardiology, Nunno Cardiology, Nuino Cardim; Romania:Romanian Society of Cardiology, Oliviana Geavlete; San Marino: San Marino Society of Cardiology, Emilio Troiani; Serbia: Cardiology Society of Serbia, Marija Zdravkovic; Slovakia: Slovak Society of Cardiology, Marcela Dankova; Slovenia: Slovenia: Slovenian Society of Cardiology, Andreja Cerne Cerke; Spain: Spanish Society of Cardiology, Fernando Dominguez; Sweden: Swedish Society of Cardiology, Gabriel Arefalk; Switzerland: Swiss Society of Cardiology, Philip Haaf; Syrian Arab Republic; Syrian Cardiovascular Association, Mohammed Yassin Marhej;Turkiy: Turkish Society of Cardiology, Baris Kiliclasan; Ukraine:Ukrainian Association of Cardiology, Sergii Cherniuk; United Kingdom of Great Britain and Northern Ireland: British Cardiovascular Society, Saidi A. Mohiddin, Uzbekistan: Association of Cardiologists of Uzbekistan, Amayak Kevorkov

$$\text{ ESC Guidelines}$$

ESC Clinical Practice Guidelines(CPG) Committee: Ulf Landmeser(Cairperson(Pomez), Stefan James Co.(CoChairerson)(Sweden), Marianna Adamo(Italy), Suleman Aktaa(United Kingdom),Folkert W. Asbergsler(Netherlands), Colin Baentig(Jrental Kingdom),Michael A. Borger(Germany), Giuseppe Boriani(Italy), Margarita Brida(Croatia), Robert A. Byrne(Alyne), Ireland(Bersealik, Kingdom), Bettina Heidecker(Germany), Anja Henennuth(Germany), Borja bilanez(Spain), Peter Jini(United Kingdom), Gregory H.Y-Lip(United Kingdom), John William McEvoy(Ireland), Borrisal Mavhialya(United Kingdom), Inge Moelgeard(Dermark), Linalec.Unbeck(United Kingdom),Eva Prescott(Denmark), Bianca Rocca(Italy), Xavier Rossello(Spain),Anna Sannino(Germany), Felix C. Tanner (Switzerland), Wottek Wojakowski(Poland), Katja Zeppenfeld (Netherlands)

Contributor either withrew or was engaged in only a part of the re-view process: Gerhard Poelzl(Austria)

23. References

1. Adler Y,Charron P,Imozio M,Badano L,Barón-Esquivias G,Bogaert J,et al.2015 ESC Guidelines for the diagnosis and management of pericardial diseases: the task force for the diagnosis and management of pericardial diseases of the European Society of Cardiology(ESC) Endors: by the European Association for Cardio-Thoracic Surgery(EACTS). Eur Heart J 2015;36:2921-64.https://doi.org/10.1093/eurheartj/ehv318

2. Adamopoulos S,Miliopoulos D,Karavidas A,Nikolaou M,Lazaros G,Gkouziaota A,et al. Hellenic Registry on Myocardium. Syndroméns on beffeld of Hellenic Heart Failure Association: the HERMES-HF registry. ESC Heart Fail 2020:7:3676-84.https://doi.org/10.1002/ehf.12894

3. Aquaro GD,Perfoyt M.,Camstra G,M.,Monti L.,Delottlegregles A,M.,Core et al. Cardiac MR was late gadolinium enhancement in acute myocarditis with preserved systolic function: ITAMY study.J Am Coll Cardiol 2017;70:1977-87.https://doi.org/10.1016/j.jacc.2017.08.044

4. Imazio M, Brucato A, Barbieri A, Ferroni F, Maestroni S, Lagheq B, et al. Good prog-nosis for pericardits with and without myocardial involvement: results from a multi-center, prospective cohort study. Circulation 2013;128:42-9. https://doi.org/10.1161/C81C/C811119001131531

5. Punntmu V,Caron,LW Wetsi,Fahm A,Ramendt C,Hoffmann J,et al.Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from cor-onavirus disease 2019(COVID-19).JAMA Cardiol 2020;5-1265-73.https://doi.org/10.1097/amocardio.2020.3557

6. Keren A, Asleh, R. BariE Y, Birey N, Gal et R, Galad M. Definition and diagnosis of acute myo-carditis: a position statement of the Israel Heart Society. Isr Med Assoc J 2023:25:519-24.

7. Montera MW, Marcondes-Bragra FG, Simoes V/Moura LAZ, Fernandes F, Mangine S et al. Brazil Society of Cardiology guideline on myocarditis-2022. Arq Bros Cardiol 2022;119:143-211.https://doi.org/10.36600abc.202020412

8. Nagai T, Inomata T, Kohno T, Sato T, Tada A, Kubo T, et al. JCS 2023 guideline on the diagnosis and treatment of myocarditis. Circ 2023;87:674-754. https://doi.org/10.1253/circj.CJ-22-0696

9. Writing Committee; Drazner MH,Bozkurt B, CooperLT,Agarwal NR,Basso C,et al.2024 ACC expert consensus decision pathway on strategies and criteria for the dag-nosis and management of myocarditis: a report of the American College of Cardiology Solution Set Oversight Committee./Am Coll Cardiol 2025:85:391-431.https://doi.org/10.1016/j.acc.2024.10:080

10. Caforio ALP, Pankuett S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al.Current state of knowledge on aetology, diagnosis, management, and therapy of myo-carditis a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013;34:2636-48, 2648a-48d.https://doi.org/10.1093/eur�yie/210

11. Pelliccia A, Sharma S, Gati S, Back M, Börson M, Caselli S, et al. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021;2021:14:27-196.https://doi.org/10.1099/eurheah605

12.McDonagh TA,Traet M,Adamo M, Gardner RS,Baumbach A,Bohm M,et al.2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599-726. https://doi.org/10.1093/ourearhi/ehab368

13. Arbelo E, Protonotarios A, Gimnoiro JR, Arbustini E, Barriales-Villa R, Basso C, et al.2023 ESC Guidelines for the management of cardiomyastitis. Eur Heart J 2023;44:3503-626.https://doi.org/10.1093/eurheart/ehad194

14. Law YM,Lal AK,Chen S,Chiková,C.Dooper,LeT al,Deshpande S,and Ie diagnosis and management of myocarditis in children: a scientific statement from the American

Heart Association. Circulation 2021;144:e123-35. https://doi.org/10.1161/CIR.000000000001001

15. Maisch B, Seferovic PM, Ristric AD, Erbel R, Rienmüller R, Adler Y, et al. Guidelines on the diagnosis and management of pericardial diseases executive summary: the task force on the diagnosis and management of pericardial diseases of the European Society of Cardiology. Eur Heart J 2004;25:587-610. https://doi.org/10.1016/j.ejh.2004.02.002

16. Patriki D, Gresser E, Manka R,Emmert MY, Lüscher TF, Heidecker B. Approximation of the incidence of myocarditis by systematic screening with cardiac magnetic reson-ance imaging.JACC Heart Fof 2018;6:573-9.https://doi.org/10.1016/j.jchf.2018.03.002

17.Fu M,Kontogeorgos S,Thunstrom E,Zverkova Sandstrom T, Kroon C,Bollano E,et al.Trends in myocarditis incidence, complications and mortality in Sweden from 2000 to 2014. Sci Rep 2022;12:18:3011.https://doi.org/10.1038/s41598-022-05951-z

18. Roth GA, Mensah GA,12ohnson CO, Addolorato G, Ammirati E, Baddour LM, et al.Global burden of vascular diseases and risk factors, 1990-2019: update from the GBD 2019 study.J Am. Coll Cardiol 2020;76:2982-3021.https://doi.org/10.1016/j.zacc.2020.11.010

19. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national in-cidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;386:743-800.https://doi.org/10.1016/S0140-6736(15)60692-4

20.Messrohghi DR,Pickard T,Fischer M,Openg-Rhein B,Papakostas K,Bocker D,et al.Toward evidence-based diagnosis of myocarditis in children and adolescents: rationale,design, and first baseline data of MYKKE, a multicenter registry and study platform.Am Heart Journal 2017;187:133-44.https://doi.org/10.1016/j.ahj.2017.02.027

21.Arola A,Pikkarainen E, Sipila JO, Pykari J, Rautava P,Kyto V. Occurrence and features of childhood myocarditis: a nationwide study in Finland. J Am Heart Assoc 2017;6:e00536.https://doi.org/10.1016/j.AHA.116.005306

22.Imazio M,Cecchi E,Denichielis B,Chinaglia A,Lerna S,Demarie D,et al Myocardiumic versus viral or idiopathic pericarditis. Heart 2008;94:498-501.https://doi.org/10.1136/hrt.2006.104067

23.Kyto V,Sipila J,Rautavata L,Cerimichal profile and influences on outcomes in patients hos-pitalized for acute pericarditis. Circulation 2014;130:1601-6.https://doi.org/10.1161/CIRCULATIONAHA.114.010376

24.Imao M, Brucato A,Cemin B, Cemin S, Maggiolini S, Beqaraj F, et al. A randomized trial of colforine at acute pericarditis. N Engl J Med 2013;369:1522-8. https://doi.org/10.1056/ENM.Ja1208536

25.Insigma M, Bell R, Brucato A,Cernin R, Ferrua S, Beqaraj F, et al. Efficacy and safety of colchricate for treatment of multiple recurrences of pericarditis(CORP-2): a multicen-tre, double-blind, placebo-controlled, randomized trial. Lancet 2014;383:2232-7.https://doi.org/10.1016/S01410-6736(13)62709-9.

26. Charpentier B, Saunee B, Joly LM, Khoury A, Duchateau F-X, Briot R, et al.Management of chest pain in the French emergency healthcare system: the prospect-ive observational EPIDULOTHO study.Eur JEmerg Med 2018;25:404-10.https://doi.org/10.1097/ME0000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000

27. Sexon Teltagr, Kun Mino, Al-Ammouri I, Sorganvran F, Guggilla RK, Khuri-Bulos N,et al.Myocarditis and periditsis: case definition and guidelines for data collection,ana-lys, and presentation of immunization safety data. Vaccine 2022:40:1499-511.https://doi.org/10.1016/j.vaccine.2021.11.074

21. Ametrati C, Ciipani M, Mono C, Raineri C, Pini M, Sonroi P, Cini D. Clinical presentaity and outcome in a contemporary cohort of patients with acute myocarditis-Toramic Lontorby Regs�line. Circulation 2018;138:1088-99. https://doi.org/10.1161/CIRCULATIONAHA.118.035319

29.Delgado V,Amyone Maran N, de Waha S,Bonaros N, Brida M, Burri H,et al. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J 2023;44:3494-4042.https://doi.org/10.1093/eurheart/ehad193

30. Ferreira of WM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechltem U, et al.Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations.J Am Call Cardiol 2018;72:3158-76. https://doi.org/10.1016/j.jacc.2018.09.072

31.Aretz HT.Hyocardia: The Dallas criteria. Hum Pathol 1987;18:619-24.https://doi.org/10.1016/50046-81717(87)80363-5

32. Tschope C, Ammiri E, Bozkurt B, Caforio ALP, Cooper LT, Felix SB, et al.Pyocardius and Inflammatory: current evidence and future direc-tions. Net Rev Cardiol 2021;18:169-93. https://doi.org/10.1038/s41569-020-00435-x

3. Leone O, Veinot P, Angelini A, Baandrup UT, Basso C, Berry G, et al. 2011 Consensus statement on endocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology. Cardiovasc Pathology 2012:21:245-74. https://doi.org/10.1016/j.carpatho.2011.10.001

34.Calorio LP, Giangardi AS, Bartittusio A, Marcolongo D, Vicenzetto C, Tarantini G,et al. Long-term efficacy and safety of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis: a propensity-weighted study. Eur J Heart Fail 2024;26:1175-85.https://doi.org/10.1002/ejhf.3220

ESC Guidelines

35. Imazio M,Squarotti GB,Andreis A, Agosti A, Millesimo M,Frea S,et al. Diagnostic and prognostic role of the electrocardiogram in patients with pericardits. Heen 2022:1081474-8.https://doi.org/10.1136/heartjnl-2021-320443

36.Imazo M, Brucato A, Maestrois,C. Dumietne A, Nattel G, et al. Prevalence of C-reactive protein elevation and time course of normalization in acute pericarditis:implications for the diagnosis, therapy, and prognosis of pericarditis. Circulation 2011;123:1092-7. https://doi.org/10.1161/CIRCULATIONNAHA-110.986372

37. Pisacra AM, Mascolo R, Nivoriu M, Dominioni CC, Gatiab C, Trotta L, et al. Acute pericardits with peripulmonary involvement, fewer and elevated C-reactive protein:a systemic autoinflammatory disease? A cohort study. Eur J Intern Med 2023;113:45-8.https://doi.org/10.1016/j.eijm.2023.03.034

38.Tombetti E.Barcin F, Bezi Bezer,S. Mascolo R,Pallini G,et al.Relasing pericardits:peripheral blood neutrophil, lymphopenia and high neutrophil-to-lymphocyte ratio herald acute attacks, high-grade inflammation, multisusol involvement, and predict multiple recurrences. Int Rheum Dis 2023;2637-33.473.https://doi.org/10.1111/1756-185X.14523

39.Amirmati E,Firgeri M,Andler ED,Basso C,Birneu BD,Brambatti M,et al.Management of acute myocarditis and chronic inflammatory cardiomyopathy: an ex-pert consensus document. Circ Heart Fail 2020;13:e007405.https://doi.org/10.1161/8748/1120070475

40. Seidel F, Ogen-Rhein B, Rentzsch A, Boehne M, Wannemanner B, Boecker D, et al.Clinical characteristics and outcome of biopsy-proven myocarditis in children-results of the German prospective multicentre registry MYKKE. Int J Cordiol.2022:357:95-104.https://doi.org/10.1016/j.jcard.2022.03.026

41.Kuhl U,Pauschinger M,Noutsias S,Beierse B,Bock T,Lassner D,et al.High preva-lence of genomes and multiple viral infections in the myocardium of adults with'diopathic' left ventricular dysfunction. Circulation 2005;111:887-93. https://doi.org/10.10161.CIR.0000155616,07901.35

42. Ukimura A, Satomi H, Ooi Y, Kanzaki Y, Myocarditis associated with influenza A H1N1pdm2009. Influenza Res Treat 2012:2012:351979. https://doi.org/10.1155/2012/351979

43. Lazarou E, Lazaros G, Antonopoulos AS, Imazio M, Vasileiou P, Karavidas A, et al. A risk score for pericarditis recurrence Eur. Clin Jin Inver 2011:193602.100350.

44.Imazio A,Andreis A, Lubian M, Lazaros G, Lazarou E, Brucato A, et al. The Torino Pericardis Score: a new-risk stratification tool to predict complicated pericardits.Intern Emerg Med 2021;16:1921-6.https://doi.org/10.1007/s11739-021-02803-y

45.Lazaros G,Antonopoulos AS,Lazarou E,Vachopoulos C,Vogiatzi G,Vassilopoulos D,et al.Eto and Age- and sex-based differences in patients with acute pericarditis. Eur J Linst 2011;10:1111/1/111/13392

V6eechá,El Haigcu J2,Del Bell MS,Bonova Aura, Mauro AG,Wohford G,et al.Clinical presentation and outcomes of acute pericarditis in a large urban hospital in the United States of America. Chest 2020:158:2556-67. https://doi.org/10.1016/j.chinard.200207.039

47. Gourief, Levy-P, Yazasita, J.P., Zandotti C, Cortelli, P, Lepid et al. Etology of peri-carditis in a prospective cohort of 1162 cases. Am J Med 2015;128:7841.e-8. https://dol.org/10.1016/j.amjmed 2015.01.040

48. Mayosi BM,Wiyonsce G,NTskehe M, Volminka J,Gumeed F, Maartens G,et al.Clinical characteristics and initial management of tuberculosis percolation in the HIV era: The investigation of the Management of Pericarditis in Africa (IMPI Africa) registry.BMC Infect Dis 2006;6:2.https://doi.org/10.1186/1471-2334-6-2.

Clinical characteristics and initial management of pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry.BMC Infect Dis 2006;6:2.https://doi.org/10.1186/1471-2334-6-2.

49.Conte E,Tamannsi S, Bizi E, Mastroni S, Cumetti D, Novembre 10/1003d. Postcard injury syndrome and pericardial effusion recurrence after pericardial-fusion drainage in chronic idiopathic pericardial effusion. Eur J Intern Med 2024;123:123-7.https://doi.org/10.1016/j.ejm.2024.01.024

50. Peet CJ,Rowzenio D,Omynimci,E Papadopoulou C,Mapalo BBR,Wood MR,et al.Pericarditis and autoinflammation: a clinical and genetic analysis of patients to national compaction pericarditricis and monogenic autoinflammatory diseases at a national referral center. J Am Heart Assoc 2021;11:02e0431.https://doi.org/10.1161/JAHA.121029431

51. Amioz M,Faltraef,F.Zucco J,Mic,Carraro M,Gava AM,et al.Genetic variants in pa-tients with recurrent pericarditis. J Cardiovasc Med(Hagerstown) 2024;25:799-804.https://doi.org/10.1459/00000000000006169

52.Caforio ALP, Brucato A, Doria A, Brambilla G, Angelini A, Ghirardello A, et al.Fair-heart and anti-interated disk outbautologies: evidence: BHL; Aefio et J. Hermitian 3021;23:228.88

53. Basso C. Myocarditis, N. Ed 2022:387:1488-500. https://doi.org/10.1056/EJNEMA2114478

54. Ammirati, Moseleji JJ. Diagnosis and treatment of acute myocarditis: a review. JAMA 2023:329:1098-113.https://doi.org/10.1016/j.2023.3371

55. Younis A,Matetzky S,Mulla W,Masala A,Efal,Y.Chernordomik,F.et al.Epidemiology characteristics and outcome of patients with clinically diagnosed acute myocarditis. An J Med 2020;2033:492-9.https://doi.org/10.1016/j.amjmed.2019.1015.

56.Ammirati E,Veronese B,Gambramti M,Merlo M,Cipriani M,Potena L,et al.Fulminant versus acute nonulfurminic myocarditis in patients with left ventricular systolic dysfunc-tion.J Am Coll Cardiol 2019;74:299-311.https://doi.org/10.1016/j.jacc.2019.04.063

57. Huang,F.Amirni et E,Ponaiah M,Montero S,Raimbault V,Abrams D,Edal.Fulminant myocardium myocarditis by early biopsy and outcomes. Eur Heart J 2023;44:5110-24.https://doi.org/10.1093/eurheart/ehad707

58.Zeperpened K, Tlett-Hansen J, de Riva M, Winkel BG, Behr E, Blom NA, et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: developed by the task force for the manage-ment of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology(ESC) Endorsed by the Association for European Pediatric and Congenital Cardiology(AEC). Eur Heart J 2022;43:3997-4126.https://doi.org/10.1093/eurheart/ehac262

59. Berg J, Kottwitz J, Baltensberger N, Kissel CK, Lovinovic M, Mehra T, et al. Cardiac magnetic resonance imaging in myocarditis reveals persistent disease activity despite normalization of cardiac enzymes and inflammatory parameters at 3-month follow-up.Circ Heart Fail 2017;10:e004262.https://doi.org/10.1161/CIRCHEARTFAILURE.117.004262.https://doi.org/10.1161/CIRCHEARTFAILURE.117.004262.https://doi.org/10.1161/CIRCHEARTFAILURE.117.004262.https://doi.org/10.1161/CIRCHEARTFAILURE.117.004262.https://doi.org/10.1161/CIRCHEARTFAILURE.117.004262.https://doi.org/10.1161/CIRCHEARTFAILURE.117.004262.https://doi.org/10.1161/CIRCHEARTFAILURE.117.004262.https://doi.org/10.1161/CIRCHEART![](461,155,478,171)2021;97-299

6. Schwouchow-Thonke S, Gobel S, Erich T, Schmitt VH,Fueting F, Klank C, et al.Increased C reactive protein, cardiac troponin I and GLS are associated with myocar-dial inflammation in patients with non-schemic heart failure. Sci Rep 2021;11:3008.https://doi.org/10.1038/s41598-021-82592-8

61. Krumm P, Bendel JM, Klingel K, Müller KAL, Kübler J, Grani C, et al. Using multipara-metric cardiac magnetic resonance to phenotype and differentiate biopsy-proven 5047.https://doi.org/10.3390/jcm11175047

62. Anzini M, Merlo M, Sabinardi G, Barbati G, Finocchiaro G, Pinamonti B, et al.Long-term evolution and prognostic stratification of biopsy-proven active myocarditis.Circulation 2013;128:2384-94.https://doi.org/10.1161/CIRCULATIONAHA.113.003092

6.Cafioro ALP,Kaki JP,Gimeno JR,Elliott PM,Larcheo C,Tavazzi L,et al.Endomyocardial biopsy:safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. Eur Heart 2024;45:2548-69.https://doi.org/10.1093/eurheart/heae169

6. Lopez-Ayala JM.Pastor-Qurante F, Gonzalez-Carrillo J, Lopez-Cuenca D,Sanchez-Zunjo,Milj,Oilva-Sandoval MJ,et al.Genetics of myocarditis in arrhythmogenic right ventricular dysplasia. Heart Rhythm 2015;12:766-73. https://doi.org/10.1016/j.hrth.2015.01.001

65.Cellet-J,Pieh,Theléhe,BBartheémy,O.Bauersachs,JBhattDL,et al.2020 ESC Guidelines for the baseline of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021;42:1289-367. https://doi.org/10.1093/eurheart/heema575

66.Calario AL,PAl.Calabresri F,Angelini A,Tona F,Vinci A,Bottaro S,et al.A prospective study of biopsys-proven myocarditis: prognostic relevance of clinical and aetropioghe-netic features at diagnosis. Eur Heart J 2007;28:1326-33. https://doi.org/10.1093/eurpheno/j676

67. Buiti A, Merlo M, Pinamonti B, De Biasio M, Bussani R, Sinagra G. Clinical presenta-nion and long-term follow-up of perimycoritsditis. J Cardiovasc Med(Hagerstown) 2013;14:235-41.https://doi.org/10.2459/JCM.0b013e328315d6a

65.Abde-Aty,Boy P,Zagrosek A,Wassmuth R,Kumar A,Messroghli D,et al.Diagnostic performance of cardiovascular magnetic resonance in patients with sus-pected acute myocardium: comparison of different approaches. J Am Coll Cardiol 2005;45:1815-22.https://doi.org/10.1016/j.jacc.2004.11.069

69. Zagroschi A, Abdel AY, Boye P, Wasshm R, Messroghli D, Utz W, et al. Cardiac magnetic resonance mirrors reversible and irreversible myocardial injury in myocar-ditis.JACC Cardiovascular Imaging 2009;2:131-8. https://doi.org/10.1016/j.jcm.2008.09.014

70.Groeschel J, Broyhooy O, Blaszczyk E, Trauzeddel RF, Viezzer D, Saad H, et al. Different impacts on the heart after COVID-19 infection and vaccination: insights from cardio-vascular magnetic resonance. Front Cardiovasc Med 2022:9:916922. https://doi.org/10.389f/cfm.2022.916922

71. Gentile P.Meroi,M Perito E,Gammirati E,Sala S,Della Bella P,et al.Post-discharge arrhythmic risk stratification of patients with acute myocarditis and life-threatening ventricular tachyrrhythmias. Eur J Heart Fail 2021;23:2045-54. https://doi.org/10.1002/jehj2288

722. Byrne R, Rossello X, Foughlan JJ, Barbato E, Berry C, Chiefo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur J Heart 2023;44:3720-826.https://doi.org/10.1093/eurheart/ehad191

73. Bartiusslia A, Schaviao A,Basso C,Giordani AS,Cheng C-Y,Pontara E,et al. Predictors of relapse, death or heart transplantation in myocarditis before the introduction of im-munosuppression: negative prognostic impact of female gender, fulminant onset, low-e rjection and serum autoantibodies. Eur J Heart Fail 2022;24:2033-44.https://doi.org/10.1002/ehjf.202496

ESC Guidelines

74. Ammirati E,Cipriani M,Lilloui M,Sormani P,Varrenti M,Raineri C,et al. Survivalved al ventricular function changes in Fimulari versus nonfimular acute myocarditis.Circulation 2017;136:529-45.https://doi.org/10.1161/CIRCULATIONAHA.117.026386

75. Kondo T.; Ochumura, T. Shbataa Imiura, T. Dohi Kawa H, et al. Differences in prognosis and cardiac function according to required cutaneous mechanical circu-latory support and histological findings in patients with fulminantive myocardits: insights from the CHANGE PLMP 29 study.J Am Heart Assoc 2021:e23719.html.1016/11/AHA 121.023719

76. Peretto,G.Sala,S.Rizzo S,De Luca G,Campochari C,Sarteris Oll,S.et al.Rhythmias in myocardia: state of the heart. Heart Rhythm 2019;16:793-801.https://doi.org/10.1016/j.rthm.2018.11.024

77.Imzio M,Lazrosi G,Picardi E,Vasileou P,Orlando F,Carraro M et al.Incidence and prognostic significance of new onset atrial fibrillation/flutter in acute pericarditis. Heart 2015;101:1463-7.https://doi.org/10.1136/heartijin-2014-307398

78. Shah Z, Mohammed V, Muddandas, V Anarini MW, Masomoui R, Gupta K. National trends, gender, management, and outcomes of patients hospitalized for myocarditis.Am J Cardiol 2019;124:131-6.https://doi.org/10.1016/j.amjcard.2019.03.036

9. Rosier L.Zougha A,Barré V.A,Marins P,Robutem P,Marino E,et al.Hrghof 1803 of sustained ventricular arrhythmia recurrence after acute myocarditis. J Clin Med 2020;9:848.https://doi.org/10.3390/jcm9030848

80. Birnie DH,Sauer WH,Bongun,Fooper JM,Curvin Da Daveron CS,et al.HRS ex-pert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rythm 2014;11:305-23. https://doi.org/10.1016/j.thrmd.2014.03/0442

8. Bobbio E,Hijalmarson C,Bjorkenstam M,Polte CL, Old Forsun O, Lstrom U,et al.Diagnosis,management,and outcome of cardiac sarcoidosis and giant cell myocarditis: a Swedish single center experience. BMC Cardiovasc Disordi 2022:22:19. https://doi.org/10.1186/s12872-022-02639-0

82 Cooper LT,Berry GJ,Shabetai R.Idiopatic-gian cell myocarditis-natural history and treatment. N Engl J Med 1997;336:1860-66. https://doi.org/10.1056/NEJ1997062636203

83. Peretto G,Sala,S Rizzo S, Palmisano A, Esposito A, De Cobelli F,et al. Ventricular ar-rhythmias in myocarditis: characterization and relationships with myocardial inflamma-son, J Am Coll Cardiol 2020;754-10-57. https://doi.org/10.1016/j.jacc.2020.01.036

84. Peretta G,Sala,SASo,Brenzo S,Palmisano A,Esposito A,De Cobelli F,et al. Ventricular ar-ratencym in myocarditis: characterization and relationships with myocardial inflamma-

85. van der Linde MR. Lyme carditis: clinical characteristics of 105 cases. Scand J Infect Dis Suppl 1991;77:81-4.https://doi.org/10.1019/j.199123suppl 77:01

86. Glikson M,Nielsen J.C.,Kronborg MB,Michowitz Y.,Auricchio A,Barbash IM,et al.2021 ESC guidelines on cardiac pacing and cardiac resynchronization therapy of the Task Force on cardiac pacing and cardiac resynchronization therapy of the European Heart Rhythm Association(EHRA). Eur Heart J 2021;42:3427-5001;https://doi.org/10.1093/earhein/abh364

87. Bhatia RT, Finocchioar G, Westaby J, Chatrath N, Behr E, Papadakis M, et al.Myocarditis and sudden cardiac death in the community-clatal and pathological in-sights from a national registry in the United Kingdom. Circ Arrhythm Electrophysio 2023;16:e01219.https://doi.org/10.1161/CIRCEP.123.012129

88. Lyng,TH.Neels T.S.,Gregors Winkel, B.Ttén-Harsen J. Budden cardiac death caused by myocarditis in persons aged 1-19 years: a nationwide study of 1429 deaths in Denmark. Forens Sci Res 2019:4:247-56. http://doi.org/10.1080/2096.179019:19519532

89. Peretto,G,Mazzone P,Hagopino G,Maziroa T,Satsinitsak G,Rizzo S,et al. Continuous elec-trical monitoring in patients with arrhythmic myocardits: insights from a referral cen-ter.J Clin Med 2021;10:5142;10:1390/1.3390/cm10215142.

90. Bartiausio,Cheng Y.,Creimi,G.Alovello,H.,Lernozoni,Giordani AAS,et al. CMR predictors of favorable outcome in myocarditis: a single-center experience. J Clin Med 2024;13:1229.https://doi.org/10.3390/jcm13051229

91.Ammirati,Roinardi,Frimiou N,S.Rardoiri F,Ihlimohidin,SMAzmann A,et al.Acute myocardis at associated with desmosal gene variants.JACC Heart Fol 2021:714-27.https://doi.org/10.1016/j.jchf.2022.06.013

92.Kontorovich AR,Tang Y, Patel N, Georgievski Z, Shadrina M, Williams N, et al.Burden of cardiomyatic genetic variation in lethal pediatricarycos. Circ Genom Precis Med 2021;14:e003426. https://doi.org/10.1161/CIRCGENB.121.003246

9.Szei of H. Fhtogrewe M,A.Weak-Rogar,M.Oen-Rin, Bertsen B.J.,Hertst C.et al. Pathofogenic variants associated with dilated cardiomyopathy predict outcome in pediatric myocardis. Circ Genom Precis Med 2021;14:e003425.https://doi.org/10.1016/CIRCGEN 12003250

40. Lta Oas, HABezroek MR, Theotokins P, Wassai R, Sallar B, Halliday BP, et al. Genetic architecture of acute myocarditis and the overlap in inherited myocardity. Circ Circulation 2021;14:1162-334;https://doi.org/10.1016/CIRCULATIONAHA.121:058457

95. Monda E,Bakalakos A,Cannie D,O'Mahony C.Syrrias K,PjKas et al,Prevalence of pathogenic variants in cardiomyopathy-associated genes in acute myocardis: a

systematic review and meta-analysis. JACC Heart Fail 2024;12:1101-11. https://doi.org/10.1016/j.jch.2024.02.012

96. Belkaya S, Kontorovich AR, Byun M, Mulero-Navarro S, Bajolle F, Cobat A, et al.Autosimal recessive resalbyity presenting as acute myocarditis. J Am Coll 2012,479:1653-65.https://doi.org/10.1016/j.jacc.2017.01.043

97. Smith ED, Lakadwazn NK, Paotoutsidakis N, Aubert G, Mazzanti A, McCanta AC, et al.Desmpliak cardiomyopathy, a fibrotic and inflammatory form of cardiomyopathy distinct from typical dilated or arrhythmogenic right ventricular cardiomyopathy.Circulation 2020;141:1872-84. https://doi.org/10.1161/CIRCULATIONAHA.119.044939

98. Peretto G,De Luca G,Villatore A,Di Resta C,Sala S, Palmisano A,et al. Multimodal detection and targeting of biopsy-proven myocardial inflammation in genetic cardio-phyapries: a pilot report. JACC Basic Transl Sci 2023;8:755-65. https://doi.org/10.1016/j.jabts.2023.02.018

99. Barriani R.Cipani R,Arozino R,S.Cleighin R,Bueno Marinas M,Giorgi B,et al.‘Hot phase'inderical presentation in arrhythmogenic cardiomyopathy. Europace 2021;23:907-17.https://doi.org/10.1093/europace/euaa343

1013Rarii Riger to J,Ciprani A, Bueno Marinas M, Celeghin R, Basso C, et al.Myocardia-like episodes of patients with arrhythmogenic cardiomyopathy: a system-atic review on the so-called hot-phase of the disease. Biomolecules 2022;12:1324.https://doi.org/10.3390/bm1091234

101. Bassetto G, Merlo M, Dal Ferro M, Setti M, Paldino A, Collesi C, et al. Apoptosis, a use-ful marker in the management of hot-phase cardiomyopathy? Eur J Heart Fail 2024;26:590-7. https://doi.org/10.100102/ejhf.3173

102. Collini V,Siega Vignut L, Angriman F, Braidotti G, De Biasio M, Imazio M. Age-stratified patterns in clinical presentation, treatment and outcomes in acute pericardits: a retro-spective cohort study. Heart 2024;110:1139-44. https://doi.org/10.1136/heartjnl-202424:32421

103. Lazaros G.,Antonopoulos AS,Imzio M,Solomou E, Lazarou E,Vassilopoulos D,et al.Clinical significance of pleural effusions and association with outcome in patients hos-pitalized with a first episode of acute pericarditis. Intern Emerg Med 2019;14:745-51.https://doi.org/10.1007189-019-02041-3

104. Imazio M, Pivetta E, Andreis A, Serra C, Carbone F, Masoero M, et al. Incessant peri-carditis as a risk factor for complicated pericarditis and hospital admission. Circulation 101;143:401-2-https://doi.org/10.1161/CIRCULATIONAHA.120.051156

105. Imazio C, Celech D, Memielis B, Lerna S, Demarie D, Ghisio A, et al. Indicators of poor prognosis of acute pericarditis. Circulation 2007;115:2739-44. https://doi.org/10.1161/CIRCULATIONAHA.120.051156

106.Imazio M, Crubato C,Auichi met D, Brambilla G, Demichelis B, Ferro S, et al.Corticosteroids for recurrent pericarditis: high versus low doses: a nonrandomized ob-servation. Circulation 2008;18:667-71.https://doi.org/10.1016/CIRCULATIONAHA.107.761064

107.Lazaros G. Antonopoulos AS, VLachopoulos C, Oikonomou E, Karavidas A,Chrysohocou C, et al. Predictors of switching from nonsteroidal anti-inflammatory drugs to corticosteroids in patients with acute pericarditis and impact on clinical out-come.Hellenic J Cardiol 2019;60:357-63. https://doi.org/10.1016/j.hjc.2018.04.001

10. Melendo-Viu M, Marchan-Loupe A, Guarch CJ-L,Roubin SR, Abu-Assi E, Meneses RT,et al. A systematic review and meta-analysis of randomized controlled trials evaluating pharmacologic therapies for acute and recurrent pericarditis. Trends Cardiovasc Med 2023:3319-26.https://doi.org/10.1016/j.tcm.2022.02.001

109. Tomr G,Koren-Morag N.S.,Spodick DH, Brucato A, Guindo J, Bayes-de-Luna A,et al.Pretreatment with corticoidens attenuates the efficacy of colchicine in preventing recurrent pericardits: a multi-centre all-case analysis. Eur Heart J 2005;26:723-27.https://doi.org/10.1093/earhieh197

110.Klein AL,Wang KM,Chercet A,Deblatt A,Asch B,Adery,C,Ater al.Pericard dis-esses intemal position statement on new concepts and advances in multimodal-ity activity imaging.JACC Cardiovasc Imaging 2024;17:937-88.https://doi.org/10.1016/j.jc.2024.04.010

111. Chabrando JG, Bonaventura A, Vecchié A, Wohlford GF, Mauro AG, Jordan JH,et al.Comagement of acute and recurrent pericarditis: JACC state-of-the-art review.J Am Coll Cardiol 2020;75:76-92. https://doi.org/10.1016/j.jacc.2019.11.021

121. Creper C.Tang Mu, Karwa A, Alraies MC, Benatti R, Schuster A, et al. Quantitative assessment of pericardial delayed hyperenhancement predicts clinical improvement in burden of cardioperic studies treated with anti-inflammatory therapy. Circ Cardiovascular 2015;8:e003125. https://doi.org/10.1016/CIRCIMAGING.114.003125

13.Bruato C, Brambella G, Moore A, Alberti A, Munforti C, Ghirardello A, et al.Long-term outcomes in difficult-to-treat patients with recurrent pericarditis. Am J Cardiol 2006:98:267-71.https://doi.org/10.1016/j.amjcard.2006.01.086

114. Imazo M. Brucato A. Adler Y, Brambilla G, Gromce E, Cgehi et al. Prognosis of idio paratic recurrent pericarditia as determined from previously published reports. Am J Cardiol 2007;100:1026-8. https://doi.org/10.1016/j.amjcard.2007.04.047

115. Kien Al, Babla S, Aager DA, Appleton CP, Asher C, Hoit B, et al. American Society of Chocardiography clinical recommendations for multimodality cardiovascular im-aging of patients with pericardial disease: endorsed by the Society for Cardiovascular Magnetic Resonance and Society of Cardiovascular Computed

ESC Guidelines

Tomography.J Am Soc Echocardiogr 2013;26:965-1012.e15.https://doi.org/10.1016/j.choe.2013.06.023

116. Miranda WR, Newman DB, Sinak JL, Espinosa RE, Anavekar NS, Goel K, et al. Pre-and post-pericocentisens echo-Doppler features of effusive-constrictive pericardits compared with cardiac tamponade and constructive pericardits. Eur Heart J Cardiovasc Imaging 2019;20:298-306.https://doi.org/10.1093/ehjci:yjey081

117. Sagrsa-Saledu J. Angel J. Sinzhe A. Parmaney-Mirada G. Soler-Soler J.Effusive-constrictive pericarditis. N Engl J Med 2004:350:469-75. https://doi.org/10.1056/NEMoa035630

188 Ristic AD,Imazo A, Admer Y.,Adastasiastos A,Budano IP,Brucato A.L.,Trstra strat-egy for urgent management of cardiac tamperinga: a position statement of the European Society of Cardology Working Group on Myocardial and Perdemic Diseases. Eur Heart J 2014;35:2279-84. https://doi.org/10.1093/eurheart/ehu217

119. Talira DR, Edwards WD, Danielson GK, Schaff HV, Tajik AJ, Tazelaar HD, et al.Constrictive pericardits in 26 patients with histologically normal pericardich thickness.Circulation 2003;108:1852-7.https://doi.org/10.1161/011.CIR.000087606.18453FD

120.Sagrista-Sauleda, J. Permaney-Miralida G, Candell-Riera J, Angel J, Soler-Rios. Transient cardiac constriction an unrecognized pattern of evolution in elusive acute idiopatic arciditis. Am J Cardiol 1987:59:961-6. https://doi.org/10.1016/0002-9149(87)91134-9

121. Haley J,Haj T,Audieon G,Schakr H.Fivugl,Shu Ok,Sh. Transient constructive pericardits: causes and natural history. J Am Coll Cardiol 2004;43:271-75. https://doi.org/10.1016/j.jac.2003.08.032

1230 S. Akyo A, Ayache A, Kumar A, Cremer PC, Griffin B, Popovic ZB, et al. Improvement in left ventricular mechanics following medical treatment of constructive pericardits. He 2021:107828-35. https://doi.org/10.1163/haerji-2020-317304

123. Feng D, Glockner J, Kim K, Martinez M, Syed IS, Araosz P, et al. Cardiac magnetic res-onance imaging pericardial late gadolinium enhancement and elevated inflammatory markers can predict the reversibility of constructive pericardits after antinflammatory medical therapy: a pilot study. Circulation 2011;124:1830-7.https://doi.org/10.1061/1161/CIRCULATIONAHA.111.026070

124. Cosys B, Plein S, Nishoyanopoulas S, Smethio E, Achachen S, Androa M, et al.European Association of Cardiovascular Imaging(EACVI) position paper: multimodal-ty imaging in percolated circularity. DeEar J) Heart Cordova 2005;16:12-31.https://doi.org/10.1093/ehjciu/jeju128

125. Lopalco G,Venerito V, Brucato A,Emmi G,Giacomelli R,Cauli A,et al.Anakinaref-fectiveness in refractory polyseroids: an Italian multicenter study. Joint Bone Spine Mediterranean ferter. Rheumatol Reatural Online 2011 Jjsbunin 2021.1059269152969-015-0057-1

126.Kilic A, Varkal MA, Durmus MS,Yudiz I,Yildrlin ZNY,Turunc G,et al.Relationship between clinical findings and genetic mutations in patients with familial Mediterranean Ferneral. Federat Rheumatol Online 2011 J5:159.https://doi.org/10.1186/s12969-015-0057-1

127.Kumar,S.Hubber,S.Revalen,AGR,Acrewer,APCIM,to Amines et al.Involves in imaging and targeted therapies for recurrent periciditis: a review. JAMA Cardiol 2022;7975-85. https://doi.org/10.1001/jamarcard.2022.2584

128. Habib G, Ricucciare-Clucci C, Caforio ALP, Cardim N, Carron,Cosys B, et al.Multimodality imaging in restrictive cardiomyopathies: an EACV1 expert consensus document in collaboration with the"Working group on myocardial and pericardial dis-eases' of the European Society of Cardiology Endorsing by The Indian Academy of Echocardiography. Eur Heart J Cardiovasc imaging 2017;18:1090-121.https://doi.org/10.1019/ehjici:xyo134

129. Imazio, P Evetta, P aliocial Restre S, Sormani P, Petrodri Q, Pquarta G, et al.Usefulness of cardiac Jntacardry resonance for recurrent periciditis. Am J.12020;125:146-51.https://doi.org/10.1016/j.jamard.2019.09.026

130. Imao,Midembelis B,Parrini I,Guiggia,C Mecchi E,Chasnoy G,et al.Day-hospital treatment of acute pericardits: a management program for outpatient therapy. J Am Coll Cardiol 2004;43:1042-46.https://doi.org/10.1016/j.jacc.2003.09.055

131. Chimeri C, Russo MA, Frustaci A. Immunosuppressive therapy in virus-negative in-flammatory cardiomyopathy: 20-year follow-up of the TIMC trial. Eur. JHT 2022;43,4363-73.https://doi.org/10.1093/euriehj/ehac348

132. Rao K,De Silva K,Sood A,Denniss AR,Hsu C.J.-Predicting patients with troponin posi-tive chest pain and unobstructed coronary arteries with electrocardiogram, troponin kinetics and GRACE score. Heart Lung Circ 2022;31:1219-27.https://doi.org/10.1016/j.jhcc.2022.05

133. De Lazzari M,Zorzi A,Baritussio A,Siliano GMilgiore F,Suorano A,et al. Relationship between T-wave inversion and transmural myocardial edema as evidenced by cardiac magnetic resonance in patients with clinically suspected acute myocarditis clinical and prognostic implications. J Electrocardiol 2016;49:587-95. https://doi.org/10.1016/j.jaelectrocard.2016.04.002

134. Nuclorta G. Miorl D,Di Charlo A. Piccol G, Aricoil, P. Appitato M. El: alfr-like acute myocardis: relation between electrocardiographic findings and myocardial damage as assessed by cardiac magnetic resonance imaging. Clin Cardiol 2013;36:146:52. https://doi.org/10.1002/ck22088

135.Wang Z,Wang Y,Lin H,Wang S,Cai X,Gao D.Early characteristics of fulminant myo-carditis vs non-fulminant myocardial: a meta-analysis. Medicine(Baltimore) 2019:98 e14697.https://doi.org/10.1097/M000000000014697

136. Ukena C, Mahfoud F, Kindermann I, Kandolf R, Kindermann M, Bohm M. Prognostic electrocardiographic, parameters in patients with suspected myocarditis. Eur J Heart Fail 2011;13:398-405.https://doi.org/10.1093/eurjhf/hq229

137. Jannaram S, Fuisz A, Lindsay J.The spectrum of electrocardiographic manifestations of acute myocarditis: an expanded understanding.J Electrocardiol 2014;47:941-7. https://doi.org/10.1016/j.jlectrocardi.2014.07.018

138. Bartusiou A, Cheng C-Y, Lorenzoni G, Basso C, Rizzo S, De Gaspari M, et al.A machine-learning model for the prognostic role of C-reactive protein in myocarditis.J Clin Med 2022;11:7068.https://doi.org/10.3390/jcm11237068

13. Lazaros G, Vachakis PK, Theofilis P, Dasoula F, Imazio M, Lazarou E,et al. D-dimer as a diagnostic and prognostic plasma biomarker in patients with a first episode of acute pericardits.Eur J Intern Med 2023;19:2133-9.https://doi.org/10.1016/j.ejim.2023.06.017

140. Mauro A,Bizzi E,Wu Ma,Mascolo R,Chirico C,Conte E,et al.D-dimer and procal-ctionin in patients with recurrent pericardits: a prospective study. Intern Emerg Med 2024;19:2139-3.https://doi.org/10.1007/s11739-024-03712-6

11. Blanco-Domingue R, Sánchez-Diaz R, de la Fuente H, Jiménez-Borrequero LJ,Matesanz-Marin A, Relaho M, et al. A novel circulating microRNA for the detection of acute myocarditis. N Engl J Med 2021;384:2014-27.https://doi.org/10.1056/NEMoa2003608

12.Calorio ALP,De Luca,G.Barnitssou A,Seguso M,Gallo N,Bison E,et al.Serum organ-specific anti-heart and anti-intercalated disk autoantibodies as new autoimmune markers of cardiac involvement in systemic sclerosis: frequency, clinical and prognostic correlates.Diagnostics(Basel) 2021:1125.https://doi.org/10.3390/diagnostics11112165

13. Coronal JO, Bruno KA, Blauwet LA, Schtope C, Cunningham MW, Pankuweit S,et al.Elevated sera S72 is associated with heart failure in men≤50 years old with myo-carditis.J Am J Heart Asso 2019;8:00e80968.https://doi.org/10.1016/JAHA.118.008968

144. Muller I, Vogl T, Kuhl U, Kurlanich A, Banks A, Trippel T, et al. Serum alarmin S100A8/1009A levels and its potential role as biomarker in myocardial is. Chest Heart Fail.2020;7:1442-51.https://doi.org/10.1002/ehf2.12760

145. Muller I, VoglT, Pappritz K, Mitetava K, Sawatis K, Rohde D, et al. Pathogenic role of the damage-associated molecular patterns S100A8 and S100A9 in Coxosckievirus B3-induced myocarditis. Circ Heart Fail 2017;10:004125. https://doi.org/10.1161/CircHEARTFALLURE 117.004125

146. Ader F,Surget E,Charr P,Redheuil A,Zouaghi A,Maltret A,et al.Inherited cardio-myopheties revealed by clinically suspected myocarditis: highlights from genetic testing,Circ Genol Prec Med 2020;13:e002744. https://doi.org/10.1161/CIRCGEN.119.002744

147.Poller W, Haas J, Klingel Kühnich Kühnich J, Gast M, Kaya Z, et al. Familial recurrent myo-carditis triggered by exercise in patients with a truncating variant of the desmoplakin gene.J Am Heart Asso 20,9:e151289. https://doi.org/10.1161/AHA.119.015289

148. Ollitrault P, AlKhour Y M, Troadec Y, Calcagno Y, Champ-Rigot L, Ferchaud V, et al.Recurrent acute myocarditis: an under-recognized clinical entity associated with the later diagnosis of a genetic arrhythmogenic cardiomyopathy. Front Cardiovasc Med 2022:9.98883.https://doi.org/10.3389/fcvm.2022.998883.

Pirouhi N,Marteau L,Kyndt F,Serfaty JM,Toquet C,Le Gloan L,et al.Familial screening in case of acute myocarditis reveals inherited arrhythmogenic left ventricular cardio-myopathies. ESC Heart Fai 2010;7:520-33.https://doi.org/10.1002/efh2.12686

150. Arico J,Merlo M,Delcardo G,Cannata A,Gentile P,De Angelis G,et al.Lymphocytic myocarditis: a genetically predisposed disease? J Am Coll Cardiol 2020;75:3098-100.https://doi.org/10.1016/j.jacc.2020.04.048

15. Verdonschot AJ, Heymans SRB. Dilated cardiomyopathy: second hits knock-down the heart. Eur Heart J 2024:45:500-1. https://doi.org/10.1093/eurheart/ehad778

132.Cantani L, Luenchiem O, Brucato A, Barone L, Cumet d, Lactoniop, F. et al. Clues to detect tumor necrosis factor receptor-associated periodic syndrome(TRAPS) among patients with idiopathic recurrent acute pericarditis: results of a multicentre study. Clin Res Cardiol 2012;101:525-31.https://doi.org/10.1007/s00392-012-0422-8

135. Brucato A,Shinar B, Yrambia G, Robbiolo L, Ferrioli G, Patrosno MC, et al. idiopathic recurrent acute pericardits: familial Mediterranean fever mutations and disease evolu-tion in a large cohort of Caucasian patients. Lupus 2005;14:670-4.https://doi.org/10.1196/09123035u2197a

154. Felker G, Bohrano P, Hubutans GM, Kasper EK, Baughman KL, et al. Ochecardiographic findings in fulminant and acute myocarditis. J Am Coll Cardiol 2000;36:227-32.https://doi.org/10.1016/s0735-1097(00)0690-2

15. Pinamonti B,Alberti E,Cigolatto A,Dreas L,Salvi A,Silvestri F,et al.Echocardiographic findings in myocarditis. Am J Cardiol 1988:62:285-91. https://doi.org/10.1016/0002-919(94)88/226-32

115. Uppc Sh, Alah, Weigen Jic, Nuelsen J, Ko, HH Parness, LA et. Two-dimensional speckle-tracking-based segmental peak systolic longitudinal strain identifies regional myocardial involvement in patients with myocarditis and normal global left ventricular systolic function. Cardiol 2015;36:950-9.https://doi.org/10.1007/s00246-015-1105

157.Sperlongano S,D7Amato A,Taglamonte E, Russo V, Desiderio A, Ilardi F, et al. Acute myocardis: prognostic role of speckle tracking echocardiography and comparison with cardiac magnetic resonance features. Heart Vessels 2022:37:121-31. https://doi.org/10.1007/s30080-021-01893-0

$$\text{ ESC Guidelines}$$

158. Ben-Joya D, Kaplan A, Baruch G, Rothschild G, Rothschild E, Beer G, Banai S, et al. The prevalence of abnormal right ventricular speckle in strain in the setting of acute myocardits and pre-served left ventricle function. Int J Cardiovasc Imaging 2023;39:1231-8. https://doi.org/10.1007/s10554-0238-0289-7

159.Miendl C, Paulus M, Poschenrieder F, Hamer OW,Zeman FA, Maier LS, et al. Left atrial strain parameters derived by echocardiography are impaired in patients with acute myocarditis and preserved systolic left ventricular function. Int J Cardicovskii Imaging 2023:39:1157-65.https://doi.org/10.1007/s10554-0238-027-9

16. Imazio M, Bobbio M, Cecchi E, Demarie D, Demichels B, Pomar F, et al. Colchicine in addition to conventional therapy for acute pericardits: results of the Colchicine for acute Pericardits(COPE) trial. Circulation 2005;112:2012-6. https://doi.org/10.1161/CIRCULATIONAHA5.1054.27389

161. Lles LM,Ellims,Ah Lewellyn H,Hare JL,Kaye DM,McLean L,et al.Histological val-ation of cardiac magnetic resonance analysis of regional and diffuse interstitial myocardial lterial. Eur. Heart J. Cardioev imaging 2015;16:14-22. https://doi.org/10.1093/efjehie102/

162. Miller CA, Naish JH, Bishop C, Putouts G, Clark D, Zhao S, et al. Comprehensive val-ation of cardiovascular magnetic resonance techniques for the assessment of myo-cardial extracellular volume. Circ Cardiovasc imaging 2013;6:373-83. https://doi.org/10.161/CRCMAGING.112,000192

16. Voigt A,Elgeti T, Durmus T, Idiz ME, Butler M, et al. Cardiac magnetic res-onance imaging in dilated cardiomyopathy in adults-towards identification of myocardial inflammation. Eur. Rediol 2011;21925-35. https://doi.org/10.1007/s003030-0101-985-2

164. Lurz P,Luecke C,Eitel,Fohrenbach,F Frank,C Grothoff M,et al.Comprehensive car-dac magnetic resonance imaging in patients with suspected myocarditis: the MyoRacer-Trial. J Am Coll Cardiol 2016;67:1800-11. https://doi.org/10.1016/j.jacc.2016.02.013.

165.Zurick AO,Bolen Ma,Kwon,Dan TL,Copovic ZB,Razjeswaran J,et al. Pericardial delayed hyperenhancement with CMR imaging in patients with constrictive pericarditis undergoing surgical pericardomyectomy: a series with histopathological correlation.JACC Cardiovascular Imaging 2011;4:1180-91.1905://doi.org/10.1016/j.jc.2011.108

166 Kramer CM, Barkhausen J, Buccarelli-Ducci, Carm, Flul Kim, Raj Nel E.Standard cardiovascular magnetic resonance imaging(CMR) protocols.2020 up-date. J Cardiovascular M Reson 2020;22:17.https://doi.org/10.1186/s12968-020-00607-1

167. Muenberg F, Blazszycz E, Wllik Z, Wickez S, Brederau J, Schub-Menger J.Characterization of critically ill patients with sephostic and sepsis-associated cardiomyopathy using cardiovascular MRI. ESC Heart Fafal 2022147-56. https://doi.org/10.1002/1ehf23913

168.Groschel J.,Ammann C,Zange L.,Viezer D.,Forman C,Schmidt M,et al.,Fast acquisi-tion of and right ventricular function parameters applying cardiovascular magnetic resonance in clinical routine-validation of a 2-shot compressed sensing cine se-quence. Scardvios Jc2026:56:266-75. https://doi.org/10.1080/141743.2021.2099010

169. Mileva N, Paolislo P, Gallinoro E, Fabricatore D, Munhoz D, Bergasmasi L, et al.Diagnostic and prognostic role of cardiac magnetic resonance in MINOCA: systematic review and meta-analysis.JACC Cardiovasc Imaging 2023;16:376-89.https://doi.org/10.1016/j.jcmm.2022.12.029

170. Machanahal Balakrishna Ariha, M. Thara A. Waters R, Ganevanan A, Vuganula d et al. Diagnostic value of cardiac magnetic resonance imaging and intraconary optical coherence tomography in patients with a working diagnosis of myocardial infarction with non-obstructive coronary arteries-a systematic review and meta-analysis.Curr Probl Cardiol 2023;48:101126.https://doi.org/10.1016/j.cpcardiol.2022.101126

171. Hauserat A. Smilowicz NR, R. B. Redel-Tac, R. Qui G. Qian, Y. et al. Myocarditis in relation to angiographic findings in patients with provisional of MINOCA.JACC Cardiovascular Imaging 2020;13:1906-13.https://doi.org/10.1016/j.jcsc.2020.0237

17.Tornall P, Gerba E, Behagel A, Chopard R, Collote S., Largoditaet al. E, et al.Myocarditis or true'trueion for cardiac magnetic resonance in patients with a clinical diagnosis of myocardial infarction without obstructive coronary disease: a meta-analysis of individual patient data. Atherosclerosis 2015;241:87-91.https://doi.org/10.1016/j.atherosclerosis.2015.04.816

17.Bohnen S, Radunski, UK L, Gund Kall, Rohinger S, Channingen B, B et al.Performance of T1 and T2 mapping cardiovascular magnetic resonance to detect ac-tive myocarbidics in patients with recent-onset heart failure. Circ Cardiovasc Imaging 2015;8:e030073;https://doi.org/10.1161/CIRIMCAGMING.114.003073

174. Khanna S, Asmarakera AT, Li C, Bhat A, Chen HHL, Gan GCH, et al. The utility of cardiac magnetic resonance imaging in the diagnosis of adult patients with acute myo-carditis: a systematic review and meta-analysis. Int J Cardiol 2022;363:225-39. https://doi.org/10.1016/j.ijcard.2022.06.047

17.Jia Z.,Wang Li,Ja,Y.Ju,Zhao H.Huo,Let al. Detection of acute myocarditis using T1 and T2 mapping cardiovascular magnetic resonance: a systematic review and meta-analysis.J Appl Clin Med Phys 2021;22:239-48.https://doi.org/10.1002/acm2.13365

176. Blissett S, Chocron Y, Kovacina B, Afilano J. Diagnostic and prognostic value of cardiac magnetic resonance in acute myocarditis: a systematic review and meta-analysis. Int J Cardiovasc Imaging 2019;35:2221-9.https://doi.org/10.1007/s10554-019-01674-x

177. Pan J A, Lee Y, Salmo, M A29. Diagnostic performance of extracellular volume, native T1,T and T2 mapping versus Lake Louise criteria by cardiac magnetic resonance for detec-tion of acute myocardia: meta-analysis. Circ Cardiovasc Imaging 2018;11:e007598 https://doi.org/10.1161/CIRCIMAGING.118.007598

17. Wei S,Fu J,Chen L,Yu S. Performance of cardiac magnetic resonance imaging for diag-nosis of myocarditis compared with endomyocardial biopsy: a meta-analysis. Med Sci Mont 2017:23:3687-96. https://doi.org/10.12659/msm.902155

179. Greenwood JP, Maredne N, Younger JF, Brown JM, Nixon J, Everett CC, et al.Cardiovascular magnetic resonance and single-photon emission computed tomog-raphy for diagnosis of coronary heart disease(CE-MARC): a prospective trial.Lanctet 2012:379:453-60.https://doi.org/10.1016/S0140-6736(11)61335-4

180.Greenwood JP,Riley DP,Berry C,McCann GP,Plein S, Bucciarelli-Ducci C,et al.Effect of care guided by cardiovascular magnetic resonance, myocardial perfusion scin-tigraphy, or Nice guidelines on subsequent unnecessary angiography rates: the CE-MARC 2 randomized clinical trial. JAMA 2016;316:1051-60.https://doi.org/10.1001/jama.2016.12680

18.Nagel E,Greenwood JP,Mecann GP,Bettencourt N,Shah AM,Hussain ST,et al.Magnetic resonance perfusion or fractional flow reserve in coronary disease. N Engl J/M 2019;380:2418-28.https://doi.org/10.1056/NEJm01716734

182.Arai AE, Schult-Menger J. Berman D, Mahrholdt H, Han Y, Bandettini WP, et al.Gadobutrol-enhanced cardiac magnetic resonance imaging for detection of coronary artery disease. J Am Coll Cardiol 2020;76:1536-47.https://doi.org/10.1016/j.jacc.2020.07.060

13. Kwong RY,Ge Y,Stel K, Shanghai S, Abdulah S, Fujikura K,et al.Cardiac magnetic resonance stress perfusion imaging for evaluation of patients with chest pain.J Am Cell Cardiol 2019:74:1741-55.https://doi.org/10.1016/j.jacc.2019.07.074

18.Bohm P,Scharaghar,Jeyer M,T Data from a nationwide registry on sports-related sud-den cardiac deaths in Germany. Eur J Prev Cardiol 2016;23:649-56.https://doi.org/10.1177/204781539087

18. Pelliccia A, Solberg EE, Epiee, Papadakis M, Adami PE, Biffi A, Caselli S, et al.Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies, myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology(EAPC).Eur Heart J(2019) 10:19-33.https://doi.org/10.1093/eurheart/ehy730

16. Maron BJ, Udelson JE, Bonov RO, Nishimura RA, Ackerman MJ, Estes NAM,et al.Eligibility and disqualification recommendations for competitive athletes with cardiovascu-lar abnormalities: Task Force 3: hypertrophic cardiomyopathy, arrhythmogenic right en-$$\text{tricardial cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific}$$statement from the American Heart Association and American College of Cardiology.

187. Sechtem U,Tcholakoff D,Higgins CB. MRI of the normal pericardium. AJR Am J Regenoenko 1968;147:239-44.https://doi.org/10.2214/aj.147.2239

18. Stark DD, Higgins CB, Lanzer P, Lipton MJ, Schiller N, Crooks LE, et al. Magnetic resonance imaging of the pericardium: normal and pathologic findings. Radiology 1984;150:46-74. https://doi.org/10.1148/radiology.150.26691103

19.Tscholakoff S, Dectem US, Degeer G, Schmidt H, Higgins CB. Evaluation of pleural and pericardial effusions by magnetic resonance imaging. Eur J Radiol 1987;7:169-74.

19. Power JA, Thompson DV, Rayaroao G, Doyle M, Biederman RWW. Cardiac magnetic resonance radiofrequency tissue tagging for diagnosis of constrictive pericardits: a proof of concept study. J Thoracocaric Voscarsurg 2016;151:1348-55. https://doi.org/10.1016/j.jtcs.2015.12.035

191. Gastl Mokskol J, Polkacini M, Gotschy A, von Spiczak Brzezinski J, Alkadhi H, et al.Parametric mapping CMR for the measurement of inflammatory reactions of the peri-cardium. Open Heart 2022;9001919.https://doi.org/10.116/openhrt-2021-001919

12. Conte E,Agalab, Coutari L, Gushtasq S, Cia AD,Bonomi A,et al.Cardiac MRI after first episode of acute pericarditis: a pilot study for better identification of high risk pa-tients. Int J Cardiol 2022:354-7.https://doi.org/10.1016/j.jicard.2022.03.007

193. Young PM, Glockner JF, Williamon EE, Morris MF, Araoaz P, Julsrud PR, et al. MR im-ing findings in 76 consecutive surgically proven cases of pericardial disease with CT and pathologic correlation. ln J Cardiovasc Imaging 2012;28:1099-109.https://doi.org/10.1007/s10554-011-991-06

194 Taylor AM, Dryakowski S, Verbeken K, Bogaart J, Detection of pericardial inflam-mation with late-enhancement cardiac magnetic resonance imaging: initial results. Eur Redol 2006;16:569-74.https://doi.org/10.1007/s00330-005-0025-0

15 Knutti,Jwins W,Saraste A,Capodano D,Barbato E,Funk-Brentano C,et al.2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur. Heart J 2003;4014:47-77.https://doi.org/10.1093/eurinethz/4259

1966Mligi S,De Carlini CC,Ferrari LA,Colombo Clago,Mieles E,et al.The role of early contrast-enhanced heat computed tomography in the atiological diagnosis of patients presenting with cardiac tamponade or large pericidial effusion. Eur Heart J Cardiovasc Imaging 2016;17:421-8.https://doi.org/10.1016/902/ehjci/jev225

19. Lee Y-H, Kim Kim, Kim Ek, Park S-J, Lee S-C, Park SW, et al. Pattern of pericardial cal-cification determines mid-term postoperative outcomes after pericardectomy in

ESC Guidelines

chronic constructive pericarditis. Int J Cardiol 2023;387:131133. https://doi.org/10.1016/j.jicard.2023.131133

198. Conte E,Agalbato C, Lauri G, Mushtaq S, Carollo C, Bonomi A, et al. Prevalence and prognosis of pericardial effusion in patients affected by pectus excitavastum: a case-control study. Int J Cardiol 2021:344:179-83. https://doi.org/10.1016/j.icj.2021.10.005

199. Bogart,Jeyms,M.Budaymarkins,Simevea.Purmeis B.Calcified constructively peri-cardus: prevalence, distribution patterns, and relationship to the myocardium. JACC Cardiovasc Imaging 2016;9:1013-4.https://doi.org/10.1016/j.cmc.2015.08.011

20.Azu A. Morosin A. Antonopoulos AS, Capocos, M. Resonard A.�Uohmadin R.Cardac decompression by pericardidectomy for constructive pericarditis: multimodality imaging to identify patients at risk for prolonged intrinsic support(Cvardosc imaging 2011;29:361-72.https://doi.org/10.4250/cjvi.c2020.0223

201. Peretto G, Busnardo E, Ferro P, Palmisano A, Vignale D, Esposito A, et al. Clinical ap-plications of FDG-PET scan in arrhythmic myocardits. JCC Cardiovasc Imaging 2023.15:1771-80.https://doi.org/10.1016/j.jcmg.2022.0229

2022. Palmisano A, Vignale D, Peretto G, Busnardo E, Calcagano C, Campocaro C, et al.Hydrable FDG-PET or MRG-PEDC/TCT to detect disease activity in patients with per-sisting arrhythmias after myocarditis. ICC Cardioscovim Imaging 2021;14:288-92. https://doloro/10.1016/j.jcmg.2020.03.009

33. Hanneman K,Kadoch M,Guo HH,Jamalai M,Qanou,A Lagarla A,et al.inlattience with simultaneous 18F-FDG PET/MRI in the evaluation of cardiac sarcoidosis and myocarditis.Cin Nud Med 2017;42:38-34.https://doi.org/10.1016/j.cmp.2015.48.1007.

2042Choreaitheave P, Beanlands RS, Chen W, Dorbala S, Miller RJ, Murthy VL, et al.Joint SNMIMl-ASNC expert consensus document on the role of 18F-FDG PET/CT in cardiac carcardol detection and therapy monitoring. J Nud Med 2017;58:1341-53.https://doi.org/10.2976/junment.117.196287

205. Salomaki SP,Hohenthal U,Kemmpainen P,Jiril L,Saraste A. Visualization of pericar-ditis by fluorodeoxyglucose PET. Eur Heart J. Cardioscavage Imaging 2014;15:291.https://doi.org/10.1093/ehjci/jet179

206. Nena F.,Klitch J. Teggeh, P. Peopel T, Handue, P. Geogbe J. et al. Fessibility of FDG-PET in myocarditis comparison: to CMR using integrated PET/MRI. Jl Nuod Cardiol 2018;25:785-94.https://doi.org/10.1007/s12350-016-0616-y

207.Basso C,Cabrelas F,Angelini A,Cartura E,Tinere G. Classification and histological,Immunohistochemical, and molecular diagnosis of inflammatory myocardial disease.Hear Fail Rev 2013;18:673-81.https://doi.org/10.1007/s10741-012-9355-6

208. Murphy L, McGucin M, Glibin G, Kehogc A, M Goehn B, Fabre A, et al. The role of endomyocardial biopsy in suspected myocarditis in the contemporary era: a 10-year National Tranplant Centre experience. Cordovics Pathol 2021:54:107366. https://doi.org/10.1016/j.carpatho.2021.107366

209. Lu ZA, Aubry MC,Fallon JT,Fishnei MC,Giordano C,Klingel K,et al.Myocarditis and endocardial biopsy: achieving consensus diagnosis on 100 cases. Cardiovasc Pathol 2023:62704 PM.https://doi.org/10.1016/j.carpatho.2022.107492

210. Seferovic T.,Tsutsui H, McNamara M, Stromic AD, Abasso C,Bozkurt,B et al. Heart Failure Society position statement on endoyocardial biopsy. Eur J Heart Fail 2021;2385-71.https://doi.org/10.1002/efh.2190.

211.Yilmaz A, Kindermann 1, Kindermann M, Mahafou F, Ulesere A, Athanasias A, et al.Comparative evaluation of left and right ventricular endomyocardial biopsy: differ-ences in complication rate and diagnostic performance. Circulation 2010;122/900-9,https://doi.org/10.1161/CIRCULATIONAHA.109.924167

212 van der Boon R, den Dekker W, Meuwese W, Celusso R, von der Junen J,Constantnesacu, AC et al. of safety of endomyocardial biopsy in new-onse acute heart failure requiring veno-arterial extranorepacial membrane oxygen. Circ Heart Fail 2021;14:e008387.https://doi.org/10.1161/CIRCHEARTFAILURE.A01.1008387

13. Mueller GC. Michel-Behne-Ikne, Kirsch W. Hasa NA, Abdul-Khalil Hq, Gitter et al.Feasibility, safety and diagnostic impact of endocardial angiopshies for the diagnosis of myocardial disease in children and adolescents. cUrenetrolment 2018:148.995-195.https://doi.org/10.4244/EJ-E-18-00128

24. De Gasparl M, Larsen BT, d'Amgi K, Kreuzk K, Sasso C, McHaich K, et al. Diagnosing myocarditis in endomyocardial biopsies: survey of current practice. Cardiovasc Path 2023;64:107494.https://doi.org/10.1016/j.carpatho.2022.107494

215. Gartshen Y., Tamargo M, Fleischer S, Kapoor T, Li J, Asaskan A, et al.Endomocardial biopsies in the diagnosis of myocardial biopsies in the diagnosis of myocardial biopsies in the diagnosis of myocardial biopsies in the diagnosis of myocardial biopsies in the diagnosis of myocardial biopsies.

216. Heymans S. Lakwdani NK, Tschke, Clique Kingel, Kinedl. Cardidomyopathy causes, me-chanisms, and current and future treatments approaches. Lancet 2023;402:998-1011.https://doi.org/10.1016/S0140-6736(23)01241-2

217. Kandin R. Lehtonen, L. Shenkenik, R. Kaisen-Solokowski A. Lommi J. Kupari M.Diagnosis, treatment, and outcome of giant-cell myocarditis in the era of combined immunosuppression. Circ Heart Fail 2013:6-15:22. https://doi.org/10.1161/CIRCHEARTFAULURE 112,969261

218. Casella M, Dello Russo B, Bergonti M, Catto V, Cesome, Linnara V, et al. Diagnostic yield of electroneatomic voltage mapping guiding endocardial biopsies. Circulation 2020;142:1249-60.https://doi.org/10.1161/CIRCULATIONAHA.12046900

219. Casella $M, P$ ziggiamlo F, Dello Russo A, Carbucicchio C, Al-Mohani G, Russo E, et al.Feasibility of combined unipolar and bipolar voltage maps to improve sensitivity of en-domyocardial biopsy. Circ Arrhythm Electrophysiol 2015;8:625-32. https://doi.org/10.1161/CRCPB114.002216

220. Ezzedine FM,Kapa S,Rosenbaum A, Blauwet L, Deshmukh AJ, AbouEzzedine OF,et al. Electrogram-guided endomyocardial biopsy yield in patients with suspected car-diac sarcoidosis and relation to outcomes.J Cardiovasc Electrophysiol 2021;32:2486-95.https://doi.org/10.1111/jcc.15191

221. Vaidya VR,Abudan AA,Vasudevan K,Shantha G,Cooper LT,Kapa S,et al.The efficacy and safety of electroatomic mapping-guided endocardial biopsy: a systematic review.J Interc Card Electrophysiol 2018;53:63-71.https://doi.org/10.1007/s10840-018-0410-7

22. Pelagonio G, Pincroache G, Narducci ML, Pieroni M, Perna F, Bencardino G, et al. long-term arrhythmic risk assessment in biopsy-proven myocarditis. JACC Clin Electrophysio 2020:574-82. https://doi.org/10.1016/j.ijacep.2019.12.010

22. Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio J, et al.Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol 1987;1987:13-14.

2244.Schintl SJ,Canoi PS,Schoen F.Jt. Quantitation of lymphocytes in endomyocardial biop-sies. Use and limitations of antibodies to leukocyte common antigen. Hum Pathol 1987;18,796-800.https://doi.org/10.1016/s/0046-8177(87)80053-9

225.Linder J, Cassling RS, Rogler WC, Wilson JE, Markin RS, Sears TD, et al.Immunohistochemical characterization of lymphocytes in uninflamed ventricular myo-cardium. Implications of myocarditis. Arch Pathol Med 1985;109:917-20.

226. Ohta-Ogo K,Sugano Y,Cogata S,Nakayama T,Komori T,Eguchi K,et al.Myocardial T-tymphocytes as a prognostic risk-stratifying marker of dilated cardiomyopathy-re-sults of the multicenter territory to investigate inflammatory cell infiltration in dilated cardiomyopathy in tissues of endomocardial biopsy(indICATE study). Circ J 2022;86:101-191. https://doi.org/10.1253/circ.JC-21-0529

22. Katzmann JL, Schlattmann P, Rigopoulos AG, Noutiase B, Bigalke B, Pauschinger M,et al. Meta-analysis on the Immunohstological detection of inflammatory cardiomyop-ity in endodyial cardiomyosis. Heart Fail Rev 2020;25:277-94. https://doi.org/10.1007/s10741-019-09835-9

288. Pellet L M. Montino S. Sauter M, Manuylova T, Vogel U, Klingel K. Lymphocytic myocarditis in children with parvolarus B19 infection: pathological and molecular insights.Biomedicines 2024;12:1909.https://doi.org/10.3390/biomedicines 12081909

29. Stermaier T,Fohenbach F,Frenbach F,Kangelin K,Kandolf R,Boudriot E,Sandri M,et al.Biventricular endomyocardial biopsy in patients with suspected myocarditis: feasibility,complication rate and additional diagnostic value. Int J Cardiol 2017;230:364-70.https://doi.org/10.1016/j.carpatho.2022.10766

20. Mahfoud F, Gartner B, Kentermann M, Ukena C, Gadomski K, Klingel K, et al. Virus serology in patients with suspected myocarditis: utility or futility? Eur Heart J 2011;32:897-903. https://doi.org/10.1093/eurheart/ehq493

231. Heidecker B,Williams SH,Jain K,Oleynik A,Patrikidi D,Kottwitz J,et al.Virme sequen-cing in patients with myocarditis: Circ Heart Fail 2020;13:e007103.https://doi.org/10.1161/CIRCHEARTFAILURE.120.007103

232. Maisch B, Rupth R, Rustic A, Pankuweit S. Pericardoscopy and epi- and pericardial bi-opsy-9 new window to the heart improving etiological diagnoses and permitting tar-geted intraperiodal therapy. Heart Fail Rev 2013;18:317-28.https://doi.org/10.1007/s10741-013-9828-

33. Ding Zing, Yang M, Wang Y, Wu S, Qiu X, Liu Q. Retrospective analysis of 769 cases of sudden sudden cardiac death from 2006 to 2015: a forensic experience in China. Forensic Sci Med Pathol 2017;13:336-41.https://doi.org/10.1007/s12024-017-9888-z

234. Vassalini M, Verkezetti A, Restori M, De Ferrari F. An autopsy study of sudden cardiac death in persons aged 4-10 years in Brcia(lty).J Cardiovasc Med(Hagerstown) 2016;17:446-53.https://doi.org/10.1016/j.McC.2000000000000023

253.Wu Yi,Au,Bardese ASA, Zhang, L Wu, Yu Y, Kin et al.The forensic pathological ana-lysis of sport-related sudden cardiac death in Southern China. Forensic Sci Res 2020;57-45. https://doi.org/10.1080/20961790.2017.1319785

236. Wang H,Yao Q,Zhu,S Zhang G,Wang Z,Li Z,et al.The autopsy study of 553 cases of sudden cardiac death in Chinese adults. Heart Vessels 2014;29:486-95.https://doi.org/10.1007/03830-013-0388-0

237. Doolan A, Langlois N, Sersamarian C. Causes of sudden cardiac death in young Australians. Australians. Med J Aust 2004;180:11-20. https://doi.org/10.5694/j.1326-5377.2004.

238. Harris KM, Mackey-Bojacki S, Bennett M, Nwaudo D, Duncanson E, Maron BJ. Sudden unexpected death due to myocarditis in young people, including athletes. Am J Cardiol 2021;143:131-4.https://doi.org/10.1016/j.amjcard.2020.12.028

29. Basso C,Aguilara,Banner J,Cohleh S,d'Amati G,de Gouvea RH,et al.Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology. Virchows Arch 2017,471:691-705.https://doi.org/10.1007/s00428-017-2221-0

240. Extremal K, Letononen J, Nordenswan H-K, Mayranpa, Ml, Raisanen-Sokolowski A,Kandrolin R, et al. Sweden in cardiac sarcoidosis: an analysis of nationwide clinical and cause-of-death registries. Eur Heart J 2019;40:3121-8. https://doi.org/10.1093/eurheart/ehz428

ESC Guidelines

241. Ackerman MJ,Priori SG,Willems S, Berul C, Brugada R, Calkins H, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies. This document was developed as a partnership between the Heart Rhythm Society(HRS) and the European Heart Rhythm Association(EHR).

242.Wilhelm M,Bolliger SA,Bartsch,C,Fokstuen S,Grani C,Martos V,et al.Sudden cardiac death in forensic medicine-Swiss recommendations for a multidisciplinary approach.Swiss Med Klyw 2015;145:w14129.https://doi.org/10.4414/swm.2015.14129

24. De norona Boh,SV er, Papadakis M, Ohta-Ogo K, Banya W, Wells J, et al. The im-portance of specialist cardiac histopathological examination in the investigation of young sudden cardiac deaths. Europace 2014;16:899-907. https://doi.org/10.1093/eporce/3293

244. De Gasparini,Fedelu,Ya,SamicaTan,Eilukou,Pilchou K,Corrado D,et al.Rate and cause of sudden cardiac death in the young during the COVID-19 pandemic and vaccination.Circulation 2023;148:2069-71.https://doi.org/10.1161/CIRCULATIONAHA.123.066270

245. Du Long R,Fronczek,J Niesen HWM, van der Wal A, de Boer H.The histopathologic al-10 spectrum of myocardial inflammation in relation to circumstance of death: a retro-spective cohort study in clinical and forensic autopsies. Forensic Sci Res 2022:7:238-46.https://doi.org/10.1080/20961790.2021.1989793

246. Li Zhang,Yurke A,Bue A Zue Zh,Tower F. Do et al. Demographic, clinical and pathological features of sudden deaths due to myocorids: results from a state-wide population-based autopsy study. Forensic Sci 2017;2721:81-6160116(forsjcont.2016.12.037

247. Gulino SP, Burns K, Gunther WM, MacLeod H. Lim improving forensic pathologic investi-gation of sudden death in the young tools, guidance, and methods of cardiovascular dissection from the sudden death in the young years registry. Acadoncis Forensic Path 2018;8:347-91.https://doi.org/10.1177/1925362118782077

248. Trives C,AndroEtir,Fokikas,Kocrossé,Liano Erylsh,Erylsh,Erylsh,et al.2024 ESC guidelines for the management of chronic coronary syndromes. Eur Heart J 2024;45:3415-537.https://doi.org/10.1093/eurheart/ehae177

249.Wnowatz Jkeu Gedyel, P Palaska N, Lehmann L, Ederry S, Zhu H. et al. Coronary artery disease and revascularization associated with immune checkpointer myocardis: report from an international registry(Eu; Palaska N, Lehmann L, Ederry S, Zhu H. et al. Coronary artery disease and revascularization associated with immune checkpointer myocardis: report from an international registry(Eu; Palaska N, Lehmann L, Ederry S, Zhu H. et al. Coronary

250.Drobni ZD, Alvi R,Taron J,Zafar A,Murphy SP,RamarbTK,et al.Association be-tween immune checkpoint inhibitors with cardiovascular events and atherosclerotic pro-que.Circulation 2020;142:2299-311.https://doi.org/10.1016/1016/CIRCULATIONAHAA120.049891

251.Zoller,BJ,J.Sundquist J,Sundquist K.Rokis of coronary heart disease in patients with a director signide follow-up study from Sweden. Eur J Cancer 2012;48:121-8.https://doi.org/10.1016/j.jceja.2011.09.015

252.Jain CC,Miranda WR,E1 Sabbagh A,Nishimura RA.A simplified method for the dag-sion of constrictive pericarditis in the cardiac catheterization laboratory.JAM Cardiol 2022:7-1004.https://doi.org/10.1016/j.camprado.2012:2478

25. Casella, M.,Gasperetti A.,Compagnucci P.,Narducci ML,Pelagonio,Gatto C,Catto V,et al.Different phases of disease in lymphocytes myocarditis: clinical and electrophysiological characteristics, JCCl Clin Electrophysiol 2023;914-26; https://doi.org/10.1016/j.acep-2022.10.004

254. Hoogendoorn JC, Samko M, Venlet J, Siontis KC, Kumar S, Singh R, et al.Electromanolical voltage mapping to distinguish right-sided cardiac: sarcosoditis from arrhythmic right ventricular cardiomyopathy. JACC Clin Electrophysio 2020;6:696-707.https://doi.org/10.1016/j.jaceq.2020.02008.

25. Peretto,Ga S,Sal Bso C, Della Bella P. Programmed ventricular stimulation in pa-tients with active vs previous arrhythmic myocardial. J. Cardiovasc Electrophysi 2020:34:697-701.https://doi.org/10.1111/jpe.14374

256. Haanschten D, Admiyan A, P.J'tt NARA, J. Elpera FL, Yan A. Value of 3D mapping-guided endodynamic cardiomy biopsy. Cardiac Oscin's view of an value of electro-atomic mapping-guided endomyocardial biopies. Eur J Clin Invest2021;51:e13497.https://doi.org/10.1111/eci:13497

257. Muser D,Santangeli P,Liang,JJ,Castro SA,Magnani S,Hayashi T,et al.Characterization of the electroatomic substrate in cardiac sacardoidosis: correlation with imaging find-ings of scar and inflammation. JACC Clin Electrophysiol 2018:49:2913.https://doi.org/10.1016/j.jacep.2017.09.175

258. Liang J, Hebl VB, DeSimone CV, Madhavan M, Nanda S, Kapa S, et al. Spectrologica un-ance: a method to increase the precision and diagnostic yield of endomyocardial biopsy for suspected cardiac sacardoids and myocarditis. AccI Heart Fall 2014;2:4667-43.https://doi.org/10.1016/j.chf.2014.03.015

259.McDonagh TA,Metra M,Adamo M,Gardner RS,Baumbach A,Bohm M,et al.2023 Focused study of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2023;44:3627-39.https://doi.org/10.1093/eurieh/11954

260.Van Gelder, McRan M.,Burking CV,Aesado-Aroroyo,R Caso,Crinsy HGM,et al.2024 ESC Guidelines for the management of atrial fibrillation developed in collabor-ation with the European Association for Cardio-Thoracic Surgery(EACTS). Eur Heart J 2024:45:314-414.https://doi.org/10.1093/earheil/hae

261. Brugada J, Katritis DG, Arberlo E, Arribas F, Bax JJ, Blomstrom-Lundqvist C, et al. 2019 ESC guidelines for the management of patients with supraventricular tachycardia. The Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology(ESC). Eur Heart J 2020;41:65-720. https://doi.org/10.1093/erfourhe/eh2467

262. Berg J., Lovirovino M., Baltensperger N, Kissel CK, Kottwitz J, Manka R, et al.Non-storylal anti-inflammatory drug use in acute myopericarditis: 12-month clinical follow-up. Open Heart 2019;6:e000990.https://doi.org/10.1136/openhr-2018-000990

26. Collini V,De Martino M,Andreis A,De Biasio M,Gaspard F,Paneva E,et al.Efficacy and safety of calcine for the treatment of myopericardits. Heart 2024;110:735-9.https://doi.org/10.1136/heartn-2023-323484

264. Kindernam L, Kindernmann M, Kandolf R, Klingel K, Bultmann B, Müller T, et al.Predictors of outcome in patients with suspected myocarditis. Circulation 2008;118:639-48.https://doi.org/10.1161/CIRCULATIONAHA.108.769489

265.Chonior C, Parisio, J. Mediasa A, Thiele H, Desch S, Bauersch s, et al. Epidemiology,pathophysiology and contemporary management of cardiogenic shock-a position statement from the Heart Failure Association of the European Society of Cardiology.Eur J Heartol F 2020;22:1315-41.https://doi.org/10.1002/ehf.1922

26. Heymans S, Van Linthout S., Kraus SM, Cooper L, NTusi NAB. Clinical characteristics and mechanisms of acute myocarditis. Circ Res 2024;135:397-411.https://doi.org/10.1001/CRCRESHA124.324674

267.Pappritz K,Lin,Shelfe-Aghy,M.Fechner H,Kuhl U,Alogna A,et al.Colchicine prevents disease progression in viral myocytes via modulating the NLRP3 inflammasome in the cardioscale axis. ESC Heart Fail 2022:9-925-41.https://doi.org/10.1002/ehf2.13845

268. Kernis M,Cohen F,Comber A,Amoura Z,Pare C,Brugier D,et al.Rationale and de sign of the ARAMIS trial: arakina minira versus placebo, a double blind randomized con-trialized for the treatment of acute myocarditis. Arch Cardiovasc Dis 2023;116:460-6.https://doi.org/10.1016/j.acvd.2023.07.004

26. Li Y,Yu,Yu,Ten,S.Lao Y,Du J.Corticosteroids and intravenous immunoglobulin in pediatric myocarditis: a meta-analysis. Front Pediatr 2019;7:342. https://doi.org/10.1183/ped.2019.00342

270.Chen HS,Wang W,Wu S,Niu JP.Corticosteroids for viral myocarditis. Cochrane Database Syst 2013:2013:CD004471. https://doi.org/10.1002/14651858.CD004471 pub3

271. Brambatti M, Matmasini V, Adler ED, Klingel K, Camici PG, Ammirati E. Eosinophilic myocarditis: characteristics, treatment, and outcomes. J Am Coll Cardiol 2017;70:2363-75.https://doi.org/10.1016/j.jacc.2017.09.023

27. Mason JW,O'Connell JB,Helowitz A,Rose NR,McManus BM,Billingham ME,et al.A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med 1995;333:265-75.https://doi.org/10.1016/j.jacc.2017.09.023

273. Schultheis H-P,Perin,C.Sowhaw O,Waagstein F,Kapp J-F,Wegscheider K,et al.Betferonin in chronic viral cardiomyopathy(BICC) trial: effects of interferon-βat-tion in patients with chronic viral cardiomyopathy. Clin Res Cardiol 2016;105:763-73.https://doi.org/10.1016/j.s00392-016-0986-9

274.Imazo An Andres A,Agosti A,Piroli F,Avondo S,Casula M,et al. Usefulness of beta-blockers to control symptoms in patients with pericarditis. Am J Cardiol 2021;146:115-9.https://doi.org/10.1016/j.amjcard.2021.01.032

725. Avondo S, Andreis A, Casula M, Biondi-Zoccai G, Imzio M. Pharmacologic treatment of acute and recurrent pericarditis: a systematic review and meta-analysis of controlled clinical trials. Pomneneu Med 2021;63:314-23.https://doi.org/10.2376/S0031-0808.214263-4

26. Lutschinger LL, Rigopoulos AG, Schlippmann P, Matiakis M, Sedding D, Schulze PC,et al. Meta-analysis for the value of colchicine for the therapy of pericarditis and postperioratory syndrome chemistry. BMC Cardiovasc Disord 2019;19:207.https://doi.org/10.1186/s12872-1919-1190-4

27.LiY-LQ,Guo L,Lue Y,J.Zhao,LJ Zhang H-F.Colchine in addition to con-ventional therapy for pericarditis recurrence: an update meta-analysis. Herz 2016;41:630-8.https://doi.org/10.1007/s00059-016-4410-z

728.Papageorgoni N, Bourisas N, Lazaros G, Imzio M, Tousoulis D. Colchicine for pre-vention and treatment of cardiac diseases: a meta-analysis. Cardiovasc Ther 2017;35:10-18. https://doi.org/10.1111/1755-592.122226

297ally,SBerson,Embers Jr.,Spazar,E.Reith,Cavies K,Halls H,et al.Effects of gastropro-tectant drugs for the prevention and treatment of peptic ulcer disease and its compli-cations: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol 2018;3:231-41.https://doi.org/10.1016/S2468-1253(18)30037-2

280.Humphrey MR, Russell L, Danila Ml, Fink HA, Guyatt G, Cannon M, et al. 2022 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatol 2023;75:2088-102. https://doi.org/10.1002/art.42464

21. Sabbola A,Roca Lueq L, Mercarcé J, Alguersuari J, Francisco Pascual J, Garcia-Dorado D,et al. Colchicine administered in the first episode of acute idiopathic pericarditis: a ran-domized multicenter open-label study. Rev Esp Cardiol(Engl Ed) 2019;72:709-16.https://doi.org/10.1016/j.repc.2018.11.016

282. Imazio M, Andrei P, Roinsli F, Lazaros G, Gattorno M, Lewinter M, et al.Interanti-leminok 1 agents for the treatment of recurrent pericardits: a systematic

ESC Guidelines

review and meta-analysis. Heart 2021;107:1240-5. https://doi.org/10.1136/heartjnl-2020-318869

28. Klein AL, Imazio M, Cremer P, Brucato A, Abbate A, Fang F, et al. Phase 3 trial of interleukin-1-rap trionacein on recurrent pericards. En Nj Eng Jol 2023:3831-41.https://doi.org/10.1056/NEJMoa2027892

284. Brucato A,Imazio M,Gattorno M, Lazaros G, Maestroni S,Carraro M,et al. Effect of arakina on recurrent pericardits among patients with colicine resistance and con-ticosteroid dependence: the AIRTRIP randomized clinical trial. JAMA 2016;316:1906-12.https://doi.org/10.1001/jama.2016.15826

28. Brucato A. Wheeler A. Lisa S. Abbate A, Creater PC, Zou L. et al. Transition to ri-lonacepton therapy from oral therapies in patients with recurrent pericardits.Hent 2023;109:297-304.https://doi.org/10.1136/heartn-2022-321328

28. Collini V, Andreis A, De Biasio M, De Martino M, Isola M, Croatto N, et al. Efficacy of colchicine in addition to anakina in patients with recurrent pericardits. Open Heart 2024:411:00599;https://doi.org/10.1163/openhi-Rpt-2023-002599

287.Vianello F,Cinetetin,F.Cavarro M,Battisti A,Castelli M,Imbergano S,et al.Azathioprine in isolated recurrent pericardits: a single instance. Int. J Cardiol 2011;147:477-8.https://doi.org/10.1016/j.jcard.2011.01.027

88. Imazio M, Lazar G., Picardi E, Viseouli P, Carrao M, Tousoulou D, etisou D., Intravenous human immunoglobulins for recratory recurrent pericardits: a systematic review of all published cases.J Cardiacvod of(Hagenesen) 2016;17:263-9.https://doi.org/10.2459/CM000000000000260

289. Marcolong R.,Gusor,Russo L.,Raveden F.,Novente F.,Agostini,F. Omminusuppressive ther-apvents recurrent pericarditis. J Am Coll Cardiol 1995;26:1276-9. https://doi.org/10.1016/0739-1097(95)00302-9

290. Lazarros G. Antonopoulos AS, Antaronu K, Scendros P, Ris K, Hadyansynis E, et al.Hydroxychloroquine for colchicine-resistant glucocorticoid-dependent idiopidate current-icarditis a pilot observational prospective study. Int J Cardiol 2020:311:77-82.https://doi.org/10.1016/j.icard2020.0369

21. Motlorite M. Biondi-Zocai J. Gimao I, Castagno D, Reganti M, Cabbate A et al.International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences. Ann Heart J 2010:1666-70.https://doi.org/10.1016/j.ahj.2010.06.015

292.Horneffer PJ, Miller RH, Pearson R, Tyraek PM, Reitz FA, Gardner T. The effective treatment of postpericardiomy syndrome after cardiac operations. A randomized placebo-controlled trial.J Thorac Cardiovasc Surg 1990;100:292-6.https://doi.org/10.1016/5002-5223(19)35571-0

29.Attn U, Ulloye BV, MacArthur JVW, Goldstone AB, Farman AS, Hesinger W, et al.Rapid onset of fulminant myocardium portsderts and favourable prognosis and the ability to bridge mechanical circulatory support to recovery. Eur J. Cardiothor Surg 2013;43:379-82.https://doi.org/10.1093/ejcets/Esz242

294.Montero S,Aissou N,Tadié J-M,Bizouna P,Resscher V,Persichin R,et al.Fulminant giant-ell myocarditis on mechanical circulatory support management and outcomes of a French multicentre cohort. Int J Cardiol 2018;253:105-12.https://doi.org/10.1016/j.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.2017.

1959. Bernhardt AM, Cosdelar and Waldes AG, Jultig, Givert Zern, M. Task Force 1; et al.The International Society for Heart and Lung Transplantation/Heart Failure Society of America and Metrica. Clinical Circulatory Support. J Heart Lung Transplant 2023:42:64.https://doi.org/10.1016/j.heal/10.1028.1028

296.Lorusso R,Shekar K,MacenL,G,Smitman P,Mellogera V,Nysen B,et al.EOster interim guidelines for venocarteral extracoreal membrane oxygenation in adult cardiac pa-tients.AA/00/21:67:824-44.https://doi.org/10.1097/MAT.MAT.00000000001510

297.Lorusso R, Centofanti P, Gelsomino S, Barlii F, Di Mauro M, Orlando P, et al.Venoasteracorteporal membrane oxygenation for acute fulminotic myocarditis in adult patients: a 5-year multi-institutional experience. Ann Thorol Surg 2016;1919-96.25. http://doi.org/10.1016/10.1016/3axioral.2015.08.014

298. Mirel M, Luyt C-E, Legrpe P, Trouillet J-L- Lerg,Pieav et al. Outcomes, long-term quality of life, and psychologic assessment of fulminantic myocardits patients res-cued by mechanical circulatory support. Cat Care Med 2019;39:1029-35.https://doi.org/10.1097/CCM.0103e131820ead45

29. Diddle JW, Almodovar MC, Rajagopal SK, Rycus PT, Thiaragarian RR. Extracorporeal membrane oxygen for the support of adults with acute myocarditis. Care Cut Med 2015;43:1016-25.https://doi.org/10.1097/CCM.000000000000920

300.Nunez JI, Grand EU, Weyes-Rast, Cabe S, Quintero, P. Motivwa S, et al.Outcomes with peripheral venoateral extracorporeal membrane oxygenation for suspected acute myocarditis: 10-year experience from the extracorporeal life support organization regurg. Care. He Int 2023;16:010152.2011CIRCHEARTFAILURE122.010152

301. Strobbe A, Ardenssens T, Bennett, Dubois C, Desmet W, McCutcheon K, et al.Estology and long-term outcome of patients undergoing pericentericities. J Am Heart Assoc 2017;6:e007598.https://doi.org/10.1016/j.AHA/117.007598

2020.Maisch B, Ristic AD,Pankuweit S, Neubauer A, Moll R. Neoplastic perionic effusion.Efficacy and safety of intraperatinal treatment with equilibration. Eur. Heart 200223-1625-31.https://doi.org/10.1053/ehu2002.3328

303. Martini A. Copila C. CMol Cardure D, Civell M. Lamantia, G. Colleoni M, et al.Long-term results of intraperiodic chemotherapeutic treatment of malignant

pericardial effusions with thiotepa. Chest 2004;126:1412-6. https://doi.org/10.1378/chest.15.4121

304. Colleoni M, Martinelli G, Beretta F, Marone C, Gallino A, Fontana M, et al. Intracavitary chemotherapy with thiopea in malignant pericardial effusions: an active and well-tolerated regimen. J Clin Oncol 1998;16:2371-6. https://doi.org/10.1200/JCO.1998.16:2371-6. https://doi.org/10.1200/JCO.1998.

305. Kunohit K,T.Haraura T.,Shibata T.Imai M,Nishiwaki Y,Nishiwaki Y.,Nishiwaki et al.A randomised trial of intraperable perionic canxyin for malignant pericadhesion with lung cancer(CJ(COG9811). Br J Cancer 2009;100:464-9. https://doi.org/10.1038/sj.bjc.6604866

306. Shepherd A.F.,Morgan C,Eanswos K,Ginsberg J,Fatt,D.Murphy K.Medical manage-ment of malignant pericardial effusion by tetracycline sclerosis. Am J Cardiol 1987;60:1161-4.https://doi.org/10.1016/0002-9149(87)90411-5

307. Beckmann E, Ismail I, Cebotari S, Busse A, Martens A, Shrestha M, et al. Right-sided heart failure and extracorporal life support in patients undergoing pericardiectomy for constrictive pericarditis: a risk factor analysis for adverse outcome. Thorac Cardiovascular Surg 2017;65:720-70.https://doi.org/10.1055/s-0036-1593817

08.Busch C,Penov K,Amorim A,Garbade J,Davierwala P,Schuler GC,et al.Risk factors for mortality after pericarditomy for chronic constructive pericarditis in a large single-centro cohort. Eur J Cardiothorac Surg 2015:48:e110-6. https://doi.org/10.1093/ects/ev322.

90. Zundran R, Ylski B, Berezowski M, Polycarpou A, Born F, Guenther S, et al.Preemptive extracorporal life support for surgical treatment of severe constrive pericarditis. Ann Thorac Surg.2019;108:1376-81.https://doi.org/10.1016/j.athoracsur.

310.Saxena,P.Joyce LD,Daly R.C.,Kushwaha SS,Schinger JR A,Rosedahl J,et al.Cardiac trans-plantation for radiation-induced cardiomyopathy: the Mayo Clinic experience. Ann Thorac Surg 2014;98:2115-21.https://doi.org/10.1016/j.athorocrasur.2014.06.056

11. Al-Kaz-Mink, Klein, Al-LK, Crestanello JA, Cremer PC, Tong MZ, et al. Pericardial diseases and best practices for pericardiotomy: JACC state-of-the-art review. J Am Coll Cardiol 2024;84:561-80. https://doi.org/10.1016/j.jacc.2024.05.048

31.Vairinstern N.Chen C,Mazine A,Bouchard D,Hebert Y,Carrer M,et al. Pericardiotc Incretor for pericarditis: 20 years of experience at the Montreal Heart Institute.Ann Thorac Surg 2015;1007-107-13.https://doi.org/10.1016/j.athorassur.2015.02.054

313. Lee, Lee, Joo, JSP, Park, YK, Kim, Jung, JC, et al. Impact of pericardial calcification on early postoperative outcomes after pericardiac: a retrospective observational study.J Cardiothoros Surg 2014;29:449.https://doi.org/10.1186/s13019-024-02842-4

31. Yamamoto Nano.Tokara K,Neie M,Toriis S,Inoue N,Miyaji K.For what type of constructive pericarditis is the waffle procedure effective? Asian Cardiovasc Thorac Ann 2011;19:115-8 https://doi.org/10.1177/0218492311399496

31. Matsuura K,Mogi Katahara Y. Off-pump waffle procedure using an ultrasonic scalar del perforicis. Aion for pericarditis. Eur J Cardiothor Surg 2015;47:e220-2.https://doi.org/10.1093/jects/ezn54

13. Calderon-Rojas RD,Greason KL,King KS,Luis sa,Oh JK,Stulak JM,et al. Outcomes of tricuspid valve operation at the time of pericardiectomy for constructive pericarditis.Anar Thorac Surg 2021;111:125:2-7.https://doi.org/10.1016/j.athorascur.2020.06.106

317. Li T-T,Cheng Jlincal an analysis of temporary pacemaker implantation in 13 children.Transl Pediatr 2022;11:174-82.https://doi.org/10.1016/j.thorasur.2020.06.106

38. Suarez K,BanchS.JE a Rev of temporary permanent pacemakers and a comparison with conventional temporary pacemakers. J Innov Card Rhythm Manog 2019;10:3652-61,https://doi.org/10.1016/2021.1905050

319. Braun M, RUWalfor T, Bock M, Kappert U, Boscheri A, Schnabel A, et al. Percutaneous lead implantation connected to an external device in stimulation-dependent patients with systemic infection--a prospective and controlled study. Pacing Clin Electrophysiol 2006;29:875-9. https://doi.org/10.1011/j.1540-8159.2006.00454.x

320.Zei P,Cockart E,Steepman LM. Modified temporary cardiac pacing using transavenous active fixation leads and external re-sterilized pulse generators.J Am Coll Cardiol 2006;47:1487-9.https://doi.org/10.1016/j.jacc.2006.01.006

31.Chung RK,Nattton,Kau,Lau C,P,Forno ARJD,A-Khatib SM,Arora V,et al.2023 HRS/APHS/LHARHS LAG标识ine cardiaketic pacing for the avoidance and mitiga-tion of heart failure. Heart Rhythm 2023;20:e17-91.https://doi.org/10.1016/j.hrthm.2023.10:1538

32. Casella M, Bergoni M, Narducci ML, Persampieri S, Gasperetti A, Conte E, et al. Prior myocarditis and ventricular arrhythmias: the importance of scar pattern. Heart Rhythm 2021:18:589-96. https://doi.org/10.1016/j.hrthm.2020.12.016

32.Rav-Acha M,Shah K, Hasing T, Gumuser E, Tovia-Brode O, Shauer A, et al. Incidence and predictors for recurrence of ventricular arrhythmia presenting during acute myo-cardiac: its multivariate study. JACC Clin Electrophysiol 2024;10:1161-74.https://doi.org/10.1016/j.jacep.2024.02.027

324 Sako B, Patschun D,Nordbeck P, Seidmayer L, Andresen H, Jansch M, et al. Secondary prevention of potentially life-threatening arrhythmia using implantable cardioviter than biopsics in patients with biopsy-proven viral myocarditis and preserved ejection activation of pathways of intrarperic blood invaryl myocarditis and preserved ejection

325. Peretto,G.Sala,S.Carturare,E,Rizzo S,Villatore A,De Luca G.La et al.Clinical profiling and outcomes of viral myocarditis manifesting with ventricular arrhythmias. Eur Heart J Open 2023;3:020:132.https://doi.org/10.1093/ehjopen/oead132

$$\text{ ESC Guidelines}$$

326. Ekstrom K, Lehtonen J, Kandolin R, Raisanen-Sokolowski A, SalmenkiK, Kupari M.Incidence, risk factors, and outcome of life-threatening ventricular arrhythmias in giant cell myocarditis. Circ Arrhythm Electrophysi 2016;9:e004559. https://doi.org/10.1161/CRCIP.116.004559

327. Scholl V,Wielander D,Kelch F,Stroux A,Aftasanio T,Pschcoe C,et al.Benefit of a wearable cardiover defibrator for detection and therapy of arrhythmias in pa-tients with myocarditis. Esc. Heart FCol 2021:8:248-37. https://doi.org/10.1026/ehf 213353

328. Blaschke F, Lacour P, Parngu L, Parnyas A, Hohendner F, Walter T, et al. Wearable cardiover-defibrertor- friend or foe in suspected myocarditis? Esc Heart Fo21;2038-91:1506. https://doi.org/10.1002/ehf213430

329.Wabng NIC,Harmitng R. Quim,M 55,Phueckie C,Rottaskstf,F.Smkymiewic J.et al.Experience with the wearable cardiover-defibrator in patients at high risk for sudden cardiac death. Circulation 2016;134:635-43. https://doi.org/10.1161/CIRCULATIONAHA-115.019124

330. El-Battrawy I,Koepsel K,Tenbrink D,Kovacs B,Dreher TC,Blockhaus C.,et al. Use of the wearable cardioverter-defibrator among patients with myocarditis and reduced ejection fraction or ventricular tachyrimass data; from a multicenter registry J Am Heart Assoc 2023;12:e030615.https://doi.org/10.1161/JAHA.113.0230615

31. Perto G,Gullets S,Stavich M,Camparochi C,Rigavale D,Du G.Cu et al. Exercise stress test late after arrhythmic versus nonrhythmic presentation of myocarditis.J Pers Med 2022;12:1702.https://doi.org/10.3390/jpm1210702

322.Fang,Wang,JIU,WU,Xu,Yan W.K,Zeng R,et al.The prognostic value of late gado-linium enhancement in myocarditis and clinically suspected myocarditis: systematic re-view and meta-analysis. Eur Radiol 2020;30:2616-26. https://doi.org/10.1007/s00330-019:06643-5

333. Georgiopoulos G,Figlizzi S,Sanguineti F,Aquaro GD,Diella G,Stamatelopoulos K et al. Prosthicogni impact of late galaxies. Imaging 2000 and Jcarvital magnetic resonance in myocarditis. Circ. Cardiovasc imaging 2021;14:e011492. https://doi.org/10.1016/CRCIMAGING.120.011492

334. Schumm J, Greluich S, Wagner A, Grun S, Pong B, Kentem K, and Cardiovascular mag-netic resonance risk stratification in patients with clinically suspected myocarditis.J Cardiovascular Magon Reson 2014;16:14.https://doi.org/10.1186/1532-429X-16-14

35.Salmanama,DiJieVanuva,Pilamente P,Coccari A.Gonzalez de Moros,B.Resyes G.et al.COVID-19:fulminant myocarditis's successfully treated with temporary mechanical is circulatory support. JACC Cardiovascular Imaging 2020;13:2457-9.https://doi.org/10.1016/j.cmp.2020.05.003

336. Pavlicek V,Kindermann I, Wintrich J, Mahfoud F, Klingel K, Bohm M, et al. Ventricular arrhythmias and myocardial inflammation: long-term follow-up of patients with sus-pected myocarditis. Int J Cardiol 2019;274:132-7.https://doi.org/10.1016/j.jicard.2018.07.142

37.Imposio M, Brucato A, Spodick D, Ader Y., Prognis of myopic adbitards as deter-mined from previously published reports. J Cardiosu c(Medos (Hagerstow) 2014;15:835-9. https://doi.org/10.2459/CJ.000000000000082

338.Cranchini M.Poracciang A,Baggio C,Gognoe G,Maone D,Batfrar et al,Gex differences in natural history of cardiovascular magnetic resonance- and biopsy-proven lympho-cytic myocarditis. Esc Heart fail 2022:9:4010-9. https://doi.org/10.1002/efh.214.1021

339 Grun S, Schumm J, Greulsh, Wagner S, Wagner A, Schneider B, Druber O, et al. Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery.A.J Am Cardiol 2012:90:164-15.https://doi.org/10.1016/j.jcard.2012.07:1007

340.Amirati E,Varrenti M,Sormani P,Bernasconi D,Moro C,Grosu A,et al.Long-term prognostic performance of cardiac magnetic resonance imaging markers versus com-plicated clinical presentation after an acute myocarditis. Int J Cardiol 2024;417:132567.https://doi.org/10.1016/j.iclr.2024.132567

341.Greulich S,Seitz A,Muller K,Grun S,Ong P,Bebadi N,et al.Predictor of mortality in patients with biopsy-proven viral myocarditis: 10-year outcome data. Am JAm Assume 2020,2020:01351:https://doi.org/10.11611/AHA.119A.11901533

34. Mahrhold H, Wagner A, Deluigi CC, Kispert E, Hager S, Meinhardt G, et al.Presentation, patterns of myocardial damage, and clinical course of viral myocarditis.Circulation 2006;114:1581:90.http://doi.org/10.1161/CIRCULATIONAHA.105.606509

34. Narducci ML, Pelongario G, La Rosa G, Inzani F, d'Amati G, Novelli V, et al. Role of extensive diagnostic workup in young athletes and nontheishes with complex ventricu-lar arrhythmias. Heart Rhythm 2020;17:230-7.https://doi.org/10.1016/j.hrmm.2019.08.022

344.Maleszewski J. Orellana VM, Hodge DOo, Kuhl U, Schulze HIFs, HOP. Cooper LT.Long-term risk of recurrence, morbidity and mortality in giant cell myocarditis. Am J Cardiol 2015;115:1733-8. https://doi.org/10.1016/j.amardic.2015.03.023

345.Kim J.-M. Jung-Ho, Kim H.,Bae Y. Lee, SY.Jon, DS.10-year survival outcome after 19-clinically suspected acute myocarditis in adults: a nationwide study in the pre-COVID-19 era. Ro 5.023:188281796; http://doi.org/10.1016/j.amardic.20187296

346. KyTo V, Sipila J, Rautava P. Rate and patient features associated with recurrence of acute myocardits. Eur J Intem 2014;25:946-50.https://doi.org/10.1016/j.eijm.2014.11.001

347. Imazio 400 M Kruca A, Macato Aaoni S, Cumetti D, Belli R, Trinchero R, et al. Risk of con-strictive pericardits after acute pericardits. Circulation 2011;124:1270-5. https://doi.org/10.1161/CIRCULATIONAHA.111.018580

38Yiyasprak A.Kurman AK,Agrawal A,Furquan MM,Verma BR,Syed AB,et al.Predicting long-term clinical outcomes of patients with recurrent pericarditis. J Am Coll Cardiol 2024:84:1193-204.https://doi.org/10.1016/j.jacc.2024.05.072

394.Calorof A ALp, A Raly F, Agostini C, Allanore Y, Anastasakis A, Arad M, et al. Diagnosis and management of myocardial involvement in systemic immune-mediated diseases: a position statement of the European Society of Cardiology Working Group on Myocardial and Perarcidal Disease. Eur Heart J 2017;38:2649-62. https://doi.org/10.1093/eur�ht/exh21

350 Cheng C-Y,Barbitrary A,Giordani AS,Iliceto S,Marcolongo R,Caforio ALP.Myocarditis in systemic immune-mediated diseases: prevalence, characteristics and prognosis. A systematic review. Autoimmunn Rev 2022;21:103037. https://doi.org/10.1016/j.autresv.2022;103037

15. Marveni G., Bratis K.,Sfendrour A., Papadopoulou E., Kolovou G. Myopericarditis as the first sign of rheumatoid arthritis relapse, evaluated by cardiac magnetic reson-ance. Infomm Alery Drug Targets 2013;12:206-11. https://doi.org/10.2174/187152811131203008

352.Aringer M,Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, et al.2019 European League Agasht Rheumatism/American College of Rheumatology clas-sification criteria for systemic lupus erythematosus. Arthritis Rheumatol 2019;71:1400-12.https://doi.org/10.1002/art-40930

353. Jia E,Geng H, Liu Q, Xiao Y,Zhang Y, Xie J, et al. Cardiac manifestations of Han Chinese patients with systemic lupus erythematosus: a retrospective study. Ir J Med So 2019;198:801-601,https://doi.org/10.1007/s11845-018-193-7

34. WanTani,Jeltselos,G.Kladman,Du.SJ,Urowitzwus,LBupus myocarditis: a single center experience and a comparative analysis of observational cohort studies. Lupus 2018:27:1296-302.https://doi.org/10.1177/0961203318770018

35. Thomas G., Cohen Tabu F, Chiche L, Haroche J, Hie M, Hervier B, et al. Lupus myo-carditis: initial presentation and longterm outcomes in a multicentric series of 29 pa-tients.The Ruhurant 2017:44:32.https://doi.org/10.3899/rheum.160493

356. Mathian A, Mouries-Martin S, Dorgham K, Devilliers H, Yssel H, Garrido Castillo L et al. Ustrassensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse. Ann Rheum Dis 2019;78:1669-76. https://doi.org/10.116/1016/j.cmp.2020.05.003

357. Mathian A,Mouries-Martin S,Dorgham K,Devilliers H, Barnabei L, Ben Salahel E, et al.Monitoring disease activity in systemic lupus erythematosus with single-molecule array digital enzyme-linked immunosorbent assay quantification of serum interferon-a.Arthritis Rheumatol 2019;71756-65.https://doi.org/10.1002/art of 40792

358. Du To R.,HBerst PG,Abserman C, Pecoraro AJ, Claassen D, Cyster HP,et al.Outcome of clinical and subclinical myocardial injury in systemic lupus erythematom-sui a prospective cohort study. Lupus 2021:30:256-68. https://doi.org/10.1177/912033-2079600

359.Hinarqin F,Boote F,Losele S,Marmer M,Mayr M,Carr-White G,et al.Native T1 and T2 mapping by CMR in lupus yocarditis: disease recognition and response to treatment.Int J Cardiol 2016:22:717-26.https://doi.org/10.1016/j.icard.2016.07.182

36. Sacric K,Brihaye B,Hyufir,Fersubet B,Nerrano C-M,et al.Asymptomatic myocardial ischemic disease in antiphospholidium: a controlled cardiac mag-netic resonance imaging study. Arthritis Rheum 2010;62:2093-100. https://doi.org/10.10027.27488

36. Pineton de Chramun M.,Cherne P,Feng A, Leud May, Jamma M, et Jamem M, et al.In-hospital mortality-assisted factors in patients with thrombotic antiphospholipid syndrome requiring ICU, lussoel admission. Chest 2020;157:1158-66. https://doi.org/10.1016/j.chestu.2019.11.01910

26. Yong. WC, Sangnekaro A, Upala S. Association between primary Sjogren's syndrome,arter stiffness, and subclinity atherosclerosis: a systematic review and meta-analysis Clin Clin Rheumatol 2019;38:447-55.https://doi.org/10.1007/s10067-018-4265-1

36. Lazzenini PE, Murphy Ginupalli VK, Srivastava U, Bertolozzi I, Bacarelli MR, Verrengia D,et al.Tro-Ri-SSO/LVOSDOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSOSO

364. Bruni C, Buch MH, Furst De, Luca G, Djokovic A, Dumitru RB, et al. Primary sys-temic sclerosis where movement a systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition.J. Scleroderma Reli Disord 2022:7:24-32.https://doi.org/10.1177/23971983211053246

365. Krumm P. Mueller KRA, Klinger K, Ruter M, Horger MS, Zitzelsberger T, et al.Cardiovascular magnetic resonance patterns of biopsy proven cardiac involvement in systemic sclerosis. J Cardavoclasma. Magn Reson 2016;18:70. https://doi.org/10.1186/s12686.016-0289-3

366. De Luca,Camparochci,A De Santis M,Sartorelli S, Peretta G,Sala S,et al.Systemic sclerosis myocarditis has unique clinical, histological and prognostic features: a com-parative histological analysis. Rheumatology(Oxford) 2020:59:2523-33. https://doi.org/10.1091/10.1007/heurakz658

367.Feri C,Valenti Z, Goefzzi, Bestbastiani M, Micheliass C, La Montagna G, et al. Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian

ESC Guidelines

patients. Medicine(Baltimore) 2002:81:139-53. https://doi.org/10.1097/00005792-2002030-00000-00000

368. Bruni C, Buch MH, Djokovic A, De Luca, Dumca, D. Rumtru RB, Glio, et al. Consensus on the assessment of systemic sclerosis-associated primary heart involvement. World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis,and follow-up assessment. J Sercloderma Relon Disord 2023;8:169-82. https://doi.org/10.1177/2379197831163143163.

369.Fairley JL,Wicks I,Peters S,Day J. Defining cardiac involvement in idiopathic invarium-tory myopathies: a systematic review. Rheumatology(Oxford) 2021;61:103-20. https://doi.org/10.1097/heumatology/keab873

370. Danko K,Ponyi A,Constant T,Borgulya G,Szegedi G. Long-term survival of patients with idiopathic inflammatory polymates according to clinical features: a longitudinal study of 162 cases. Medicine(Baltimore) 2004;83:35-42. https://doi.org/10.1097/001701.md0001097555.69154.1e

371. Allanova Y, Vigraux O, Armaud, L. Puckud Y, Phax S, Duboc D, et al. Effects of corti-costeroids and immunosuppressors on idiopathic inflammatory myopathy modelated myocarditis evaluated by magnetic resonance imaging. Ann Rheum Dis 2006;65-249.52:https://doi.org/10.1163/2025.308679

372.Zhang L,Wang G,Mal,Lu Z.Nacardic involvement in adult polymosis or myotiso: a systematic review. Clin Cardiol 2012;35:686-91.https://doi.org/10.1002/ccl.20206

373.Groh M,Mascioclo G,Kirchner E,Kristen A,Pellegrini C,Nvarous S,et al. Heart trans-plantation in patients with exophyls granulomatics with polyangitis(Churg-Sustrass syndrome). J Heart Lung Transplant 2014;33:842-50. https://doi.org/10.1016/j.healun.2014.02.023

374.Bokova W.,Dagner JUG,Hurum Skulimakia,MASn al,Salesem U,Hansen,A et al.SARS-CoV-2 and infectes and outputs toxic effects in human cardiomyocytes.Cardiovasc Res 2020;116:2207-15.https://doi.org/10.1093/cvr/cav26a7

375. Pereto G., Willato R. Azzo S. Espito A, De Luca G. Palmasno A. et al. The spec-trum of COVID-19-associated myocarditis: a patient-tailored multidisciplinary ap-proach.J Clin Med 2021;10:1974.https://doi.org/10.3390/jcm10091974

376. Wecklt LC,Turia A Beterer,S.Krahan Brado A.Jell H. Zelmulac: J et al. Myocardial inflammation and dysfunction in COVID-19-associated myocardial injury. Circ Cardiovasc Imaging:2001;14:02220.https://doi.org/10.1161/CIRICIMAGING-120.011713

37. Basso C, Leone O, Rizzo S, De Gasparini M, van der Wal A, Aubry M-C, et al.Pathological features of COVID-19-associated myocardial injury: a multicentre carlo-vascular pathology. Eur Heart J 2020/41:3827-35. https://doi.org/10.1093/eurheart/ehaa664

378. HalushaMK, PerHavo Westeire H. PSycardias is rare in COVID-19 autospinaries-cular findings across 277 postmortem encaminations. Cardiovasc Vol.2021:50:107300.https://doi.org/10.1016/j.carpatho.2020.107300

379. Lindner, D.Fitzel A, Brimen A, Hlscheva S, Geler, G. Messner K, et al.Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases.JAMA Cardiol 2020;5:1281-5:https://doi.org/10.1001/jagarc.2020.3551

380.Aquaro GD, Licordari R, Doriagre E, Lanni,O. Dellegrotagle S, Restivo L, et al. Incidence of acute myocarditis and pericardits during the coronavirus disease 2019 pandemic:comparison with the prependemic period.J.Cardoviscus Med(Mohesstow) 2022:234-57.https://doi.org/10.2459/CJ.MCM.00000000001330

381. Boehmer TK,Kompaniysel,Lavery A H,Shu J,Ko JY,Yusuf H,et al.Association be-tween COVID-19 and myocarditis using hospital-based administrative data-United States, March 2020-January 2021. MMW MORr Malt Wky Rep 2021:70:1228-3.https://doi.org/10.15855/mmm-wmr.7035e5

382. Daniels CJ, April S. Greensheil F, Rothesenol. GLH, Zheng F. Termin, M. et al.Prevalence of clinical and subclinical myocarditis in competitive athletes with recent SARS-CoV-2 infection: results from the big ten COD-19 cardiac registry.JAM Cardiol 2021;6:1078-87.https://doi.org/10.1001/jamacardio.2021.2065

38. Cavalli G, De Luca G, Campocardi O, Cella-Droter-R, Epi A, Canetti D, et al.Interleukin-1 blockable with high-dose analinsina in patients with COVID-19, acute resistivity syndrome stress, and hyperinflation: an a retrospective short study.Lancet Reumotol 2020;2:e325-31.https://doi.org/10.1016/S2665-9913(20130)272-2

38. REMAP-CAP investigators; Gordon AC,Moncey PR,Ai-Beh-Rawan KM, Nichol AD,et al. Interleukin-1 receptor antagonists in critically in patients with Covid-19. N Engl J Med 2021:384:1491-502.https://doi.org/10.1056/NEJMo2100433

385 Gupta,W,Wayesk SS,Lan,Mathes KS,Lamethes M.Lelst al. Association between early treatment with tocizumab and mortality among critically ill patients with COVID-19.JAmminted in Mettiscol and LNAem int Med 2021;18:141:51-11.https://doi.org/10.1001/jamainterned.2020.6252

386. Klingel K, Hohenadl C, Canu A, Albrecht M, Seemmann M, Mall G, et al. Ongoing enterovirus-induced myocardits is associated with persistent heart muscle infection:quantitative analysis of virus replication, tissue damage, and inflammation. Proc Natl Acad Sci U S A 1992:89:314-8. https://doi.org/10.1073/pnas.89.131.34

387. Schowengert Ko, N.J. Denfeld SW, Faiger Kui,Rj. Bowne NE. Rosenthal G, et al.Association of parvivus B19 genome in children with myocardial and cardioid-graft rejection: diagnosis using the polymerase chain reaction. Circulation 1997;96:3549-54.https://doi.org/10.1161/01c.976.10.3549

388. Bock C-T, Klingel K, Kando R, F. Human parvovirus B19-associated myocarditis. N EngJ/ Med 2010;362:148-9. https://doi.org/10.1056/NEJMc0911362

389. Huang C-H,Vallejo JG,Kolillas G,Mann DL.Role of the innate immune system in acute viral myocardisas. Basic Res Cardiol 2009;104:228-37.https://doi.org/10.1007/s00395-008-0765-5

390. Costen MF, Papageorgiou A, Verhesen W, Carai P, Lindow M, Obad S, et al.MicroRNA profiling identifies microRNA-155 as an adverse mediator of cardiac injury and dysfunction during acute viral myocarditis. Circ Res 2012;111:415-25. https://doi.org/10.1161/CIRCRESAH.A112.267443

3019.Goldberg L,Trosh-Wagner T,Vardi A,Abbas H, Pillar N,Shomron N,et al.Circulating microRNAs: a potential biomarker for cardiac damage, inflammatory response, and left ventricular function recovery in pediatric viral myocarditis. J Cardiovasc Trans Res 2018;11:319-28. https://doi.org/10.1007/s12265-018-9814-0

39. Mueller KAL, Mueller I, Eppler D, Zuern CS, Seizer P, Kramer U, et al. Clinical and histopathological features of patients with systemic sclerosis undergoing endomyocar-dial biopsy. PSo One 2015;10:e0126707. https://doi.org/10.1371/journal.pone.20126707

39. Walafuk O, Szaka R, Twenty year autopsy statistics of myocarditis incidence in Japan.JnJc Circ 1986:50:1288-93.https://doi.org/10.1025/jcj.50.1288

39. Vaideavesar P, Cooper LT. Giant cell myocarditis: clinical and pathological features in an Indian population. Cardiovasc Pathol 2013;22:70-4. https://doi.org/10.1016/j.carpathin.2012.06.003

35.Caloro AL,Angelini A, Bankl M, Shani A, Kivity S, Goddard G,et al. Passive transfer of affinity-purified anti-heart autoiontibodies(AHA) from sera of patients with myocardi-tis induces experimental myocarditis in mice.Int J Cardiol 2015;179:166-77.https://doi.org/10.1016/j.colar.2014.10.165

39.Kandolin R, Lehtonen J.,Cupari M. Cardiac sarcoidosis and giant cell myocarditis as causes of arterirom block in young and middle-aged adults. Circ Arrhythm Electrophysiol 2011;4:303-9.https://doi.org/10.1161/CIRCEP.110.959254

39.Bozkurt B,Colin M,Cook J,Cooper LT,Deswal A,Fonarrow GC,et al.Current diag-nostant and treatment strategies for specific dilated cardiomyopathies: a scientific state-ment from the American Heart Association. Circulation 2016;134:e579-e646.https://doi.org/10.1161/CIRICIPMAGING.12000000000455

398. Lu,SZeng,Shen,Lu,Wu,Yao.Lincyan identification and characteristic analysis of giant cell myocardis in 12012 and Front. Cardiovasc Med 2021;8:649094.https://doi.org/10.1038/fcm.2021:649094

39.Okura Y,Yocar,Where JM,Kodama M,Berry G,Tazelaar HD,et al.Aclinical and histopathologic comparisons of cardiac sarcoidosis and idiopathic giant cell myocarditis.J Am Cell Cardiol 2003;41322-9.https://doi.org/10.1016/s7397-1097(02)02715-8

402. Berthelot-Rie, O. C-Moriog R, K.,Moron K, Bernier, T. Trahan S, Couture C, Dubois M, et al.When should we consider the diagnosis of giant cell myocarditis? Revisiting‘classic’cardiographic and clinical features of this rare pathology. Exp Clin Transplant et al.106:565-8.https://doi.org/10.6002/ect.2013.0218

401. Ekstrom K, Lehtonen J, Kandolin R, Raisanen-Sokolowski A, Salmenkvi K, Kupari M.Long-term outcome and its predictors in giant cell myocarditis. Eur J Heart Fail 2016;18:1452-8.https://doi.org/10.1002/ejhf.606

402. Cooper LT,Baughman KL,Feldman AM,Frustaci A,Jessup M,Kuhl U,et al.The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific state-ment from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endors by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol 2007:5019-141.31.https://doi.org/10.1016/j.jacc.2007.09.008

403. Cooper LT,Hare MJ,Tazelaaral HD,Edwards WD,Starling RC, Deng MC,et al.Usefulness of immunosuppression for giant cell myocarditis. Am J Cardiol 2008;102:1353-9. https://doi.org/10.1016/j.amjcard.2008.07.041

404 Patel SUN, Patm Ea, Wood CT, O'Malley T, Haynes EJ, Entwistle JWC, et al.Outcomes of mechanical circulatory support for giant cell myocarditis: a systematic review, J Clin Med 2020:93905. https://doi.org/10.3390/cm9123905

405. Bobbio E,Bjorkenstam M,Nwaru Bl,Gialiauria F,Hessman E,Bergh N,et al.Short- and long-term outcomes after heart transplantation in cardiac sarcoidosis and giant-cell myocarditis: a systematic review and meta-analysis. Clin Res Cardiol 2022;111:125.40.https://doi.org/10.1007/s00392-021-01920-0

406. Baughman RP,Trein Peier S, Judson Ma, Rossman MD, Yeager H, Bresnitz EA, et al.Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001;164:1885-9.https://doi.org/10.1164/ajrcm.164.10.2104046

407. Lehtenon J, Ustaliov V, Payhonen P, Mayranpa M, Kupari M. Cardiac sarcoidosis:phenotypes, diagnosis, treatment, and prognosis. Eur Heart J 2023;44:1495-510.https://doi.org/10.1093/heart/ehad067

408. Okasha O, Kamcrzakr F, Chen K-HA, Farazhan-Efar, A Shenoy C. Myocardial involve-ment in patients with histologically diagnosed cardiac sarcoidosis; a systematic review and meta-analysis of gross pathological images from autopsy or cardiac transplantation cases.J Am Heart Assoc 2019;8:e011253. https://doi.org/10.1161/JAHA.118.011253

409. Iwai K,Tachiman,Tahara T,Matsui Y,Yitaki M,Kawabata Y. Pathological stud-ies on sarcoidosis atypos. Epidemiological features of 320 cases in Japan. Acta Pathol Junne 1993;437-32.https://doi.org/10.1111/j.1440-1827.1993.tb01148.x

ESC Guidelines

410. Perry A. Vuit F. Causes of death in patients with sarcoidosis. A morphologic study of 38 autopsies with clinicopathologic correlations. Arch Pathol Lab Med 1995;119-167-72.

411. Philips B. Mavishan S, James CA. Tei Ruef J.MMUR, Murray B. Tichnell C. C, et al.Arrrthymogenic right ventricular dysplasia/cardiomyopathy and cardiac sarcoidosis:distinguishing features when the diagnosis is unclear. Circ Arrthmodrophysiol.2014:730-6.https://doi.org/10.1016/CR1CPER-133.00992

412. Gasperreti A, Rossi VA, Chiodini A, Casella M, Costa S, Akdis D, et al. Differentiating hereditary arrhymogenic right ventricular cardiomyopathy from cardiac sarcoidosis fulfilling 4010 ALKary force criteria. Heart Rythm 2021;18:231-8. https://doi.org/10.1016/j.hrthm.2020.09.015

413. Corrado D, Perozallo Mra M Zori, Zais A. Beftaga G. Ciplari A, Lazzard MD, et al.Diagnosis of arrhythmogenic cardiomyopathy. The Padca Int. J Card 2020;319:106-14.https://doi.org/10.1016/j.jlccard.2020.06.005

4114. Bayman In, Hopco VLB, Sheepar M, Cardiac sarcoidosis and sudden death. The heart may look normal or mimic other cardiomyopathy. Virchows Arch 2011;458:671-8.https://doi.org/10.1007/s00428-010-1003-8

415.Athwalt P.Sch,Chibra S.lamma R,Imfa l,Margimol FC,Mamakirzak,F.et al.Cardiovascular magnetic resonance imaging phenotypes and long-term outcomes in patients with suspected cardiac sarcoidosis. JAMA Cardiol 2022;107:56-66. https://doi.org/10.1001/jamcardo.2022.2981

416. Azoulay L-D,Wintraub X,Harcoje J.,Amoura Z,Cohen Aubart F.Factors associated with implantable cardioverfert defillators appropriate therapy in cardiac sarcoidosis a meta-analysis. Sarcoidosis Vasc Diffuse Lung Dis 2020;37:17-23. https://doi.org/10.3611/svdv371.8271

417. Sharma R.,Kouranova V, Cooper,LT,Mura R.,Mafaic A,Heederlet,B. The of

18.Sanle JC,Michaelis Man Fubng BL,Estes NAM,Evaluation and management of heart rhythm distances due to cardiac sarcoidosis. Heart Lung Circ 2014:23:1100-9.https://doi.org/10.1016/j.hlc.2014.07.065

419. Ardehali H, Howard DL, Hariri A, Qasim A, Hrema B, Muughan KL, et al. A positive endomyocardial biopsy result for sarcoidosis at associated poor prognosis in patients with unsteady unplandication moi. Am. Heart 1900;254:459-63. https://doi.org/10.1016/j.2024.10.006

420.Kouranos V, Tzelepis G, Rapti A, Mrogenvi S, Aglegi K, Douskou M, et al.Complementary role of CMR to conventional screening in the diagnosis and prognosis of cardiac sarcoidosis.JACC Cardiovascular Imaging 2017;10:14737-47.https://doi.org/10.1016/j.cmg.2016.11.019

421.Ahadudah,M Paulad,Belkhi H,Adathwah M,Marsouh L,Ku Kouskou M,et al.dacic magnetic resonance imaging and fluorodeoxyglucose positron emission tomog-raphy in the assessment of cardiac sarcoidosis: meta-analysis and systematic review.J Nucl Cardiol 2023:30:1574-876.https://doi.org/10.1007/12550-0213-02198.

422. Ori,Tanimoto,T Ota,S Takagah,Ti,Hanaka R,Fujiwara,Jet al.Diagnostic accuracy of cardiac magnetic resonance imaging for cardiac sarcoidosis in complete heart block pa-tients implanted with magnetic resonance-conditional pacemaker.J Cardiol 2020;76:191-7. https://doi.org/10.1016/j.jc.2020.02.014

23. Staron Kum, Gangara M, Core T. Peierger J. Clema D, McGuire M, Torillo P, et al.The utility of cardiac magnetic resonance imaging in the diagnosis of cardiac sarcoidosis.Herst Lung Circ 2017;26:1911-9.https://doi.org/10.1016/j.hcl.2017.02.021

42. Patel MR,Cawley PEJ Hnerf,Tjlem K.Maroudi WA,ouard L,et al. Detection of myocardial damage in patients with sarcoidosis. Circulation 2009;120:1969-77.https://doi.org/10.1016/C116CIRCULATIONAHA.109.851352

425.Zhang,Ji Y,Yu,Q.Xu,B.Wang H. Cardiac magnetic resonance imaging for diagnosis of cardiac sarcoidosis: a meta-analysis. Can Respir J 2018;2018:7457369.https://doi.org/10.1155/2018/7457369

426. Youssef G,Leung E,Ymlosina I,Nery P,Williams K,Wenberg G,et al.The use of 18f-FDG PET in the diagnosis of cardiac sarcoidosis: a systematic review and metaana-ysis including the Ontario experience J Med 2015;2341:8-8. https://doi.org/10.2967/unid.1110.09662

427.Dweck MR,Abgral R,Trivieris MG,Robson PM,Karakatsan Nisani,VM et al.,Hybrid magnetic resonance imaging and positron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography with postron emission tomography

428. Okumura W, Iwasaki T, Toyama T, Iso T, Araul M, Oriuchi N, et al. Usefosting of flax-18F-FDG PET in identification of cardiac sarcoidosis. J Nucl Med 2004;45:1989-98.https://doi.org/10.1016/j.jcmg.2017.04.01332

429.Vita T,Okada DR, Veillet-Chowdhury M, Bravo PE, Mullins E, Hulten E, et al.Complementary value of cardiac magnetic resonance imaging and positron emission tomography-computed tomography in the assessment of cardiac sarcoidosis.Circus Cardiovasc Imaging 2018;11:e007030. https://doi.org/10.1016/CIRIMAGING.117.007030

430.Aopton-Coles-Lou K.Sosu,Sre Kosce,Dier Kosse,Fobet Clon,Bich et al.,of aligh mass(>18>g) of late gadolinium enhancement on CMR imaging is associated with ma-jor cardiac events on long-term outcome in patients with biopsy-proven extracarculic sarcoidosis.In J Cardiol 2016,222:950-9.https://doi.org/10.1016/j.icl.2016.2017.233

431. Greulich S, Deluig C,Glock S,Wahl A,Zurn C,Kramer U,et al.CMR imaging pre-dits deaths and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging 2013;6:501-11.https://doi.org/10.1016/j.jcmg.2012.10.021

Nardal, LZfelder V, Tovskobonin, Y. Tavoldin, Y. Fadoolinun enhancement identi-fied with cardiac magnetic resonance imaging in sarcoidosis patients is associated with long-term ventricular arrhythmia and sudden cardiac death. Eur Heart J Cardiovasc imaging 2015;16:634-41.https://doi.org/10.1093/ehjciju/294

433. Muragh G,Laffin L.,Beshai J,F. Maffessanti F,Bonham CA,Patel AV,et al.Prognosis of myocardial damage in sarcoidosis patients with preserved left ventricular ejection frac-tion: risk stratification using cardiovascular magnetic resonance. Circ Cardiovasc Imaging 2016;9:e003738.https://doi.org/10.1161/CIRCIMAGING.115.003738

434.Clemano GC, Shaw PW, Bahlardino PC, Gonzalez JA, Kramer CM, Patel AR, et al.Prognostic value of myocardial scarring on CMR in patients with cardiac sarcoidosis.JACG Cardiovasc Imaging 2017;10:411-20.https://doi.org/10.1016/j.jcmg.2016.05.009

35. Smedema-J-P van Geours RJ J.Ector J, Heidbuchel H, Ainslie G, Crins JHGM. Right ven-tricular involvement and the extent of left ventricular enhancement with magnetic res-onance predict adverse outcome in pulmonary sarcoidosis. ESC Heart Fail 2018;57-171;https://doi.org/10.1002/ehf2.12201

436. Velang PS,Chen K,Har,A.Kazmiczak F,Okasha O, von Wald L, Roukoz H,et al.Right ventricular abnormalities on cardiovascular magnetic resonance imaging in patients with sarcoidosis.JACC Cardicovasc Imaging 2020;13:1395-405.https://doi.org/10.1016/j.ccm.2019.12.011

437. Greuich S, Kitterer D, Latus J, Aguor E, Steubing H, Kaesemann P, et al.Comprehensive cardiovascular magnetic resonance assessment in patients with sar-coidosis and preserved left ventricular ejection fraction. Circ Cardiovasc Imaging 2016;9:005022. https://doi.org/10.1161/CIRCIMAGING.116.005022

438.Puntun VOI,Inc-Hinar J,Roote F,Larr-White G,Nagel E,T1 and T2 mapping in recognition of early cardiac involvement in systemic sarcoidosis. Radiology 2017;285;63-72.https://doi.org/10.1148/radiol.2017167232

439. Crouer ed, Ruden E.,Julian MW, Raman SV. Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis. J Investig Med 2016;64:1148.50.https://doi.org/10.1148/j.201716-000144

440.Greulich S,Gatidis S,Grani C,Blankstein R,Glatthaar A, Mezger K,et al.Hybrid cardiac magnetic resonance fluorodeoxyglucose positron emission tomography to differenti-ative at active from chronic cardiac sarcoidosis. JACC Cardiovasc Imaging 2022;15:445-56.https://doi.org/10.1016/j.jcmg.2021.08.018

Crouser, Openo C, Tran T, He X, Raman SV. Improved detection of cardiac sarcoid-osis using magnetic resonance with myocardial T2 mapping. Am J Respir Cite Care Med 2014;189:109-12.https://doi.org/10.1164/rccm.201309-1668LE

42. Cheung,E.Ahmad,S,Ahten M,Chan R,Iwanochko RM,Balter M,et al.Combined sim-utaneous FDG-FET-MRI with T1 and T2 mapping as an imaging biomarker for the diagnosis and prognosis of suspected cardiac sarcoidosis. Eur J Hybrid Imaging 2021;§24.https://doi.org/10.1186/s41824-021-00119-w

443. Wicks EC, Menzes LJ, Barnes A, Mohidin SA, Sekhri N, Porter JC, et al. Diagnostic accuracy and prognostic value of simultaneous hybrid 18F-fluorodeoxyglucose posi-tron emission tomography/magnetic resonance imaging in cardiac sarcoidosis. Eur Heart J Cardivocos Imaging 2018;19:757-67.https://doi.org/10.1093/ehjci/jex340

44A. Atken M, Davidson M, Chan, Vuresa Fno, Vasque L, HuO Y, R et al.Prognostic value of cardiac MRI and FDG PET in cardiac sarcoidosis: a systematic re-view and meta-analysis. Radiology 2023:307:e222483. https://doi.org/10.1148/radiol.222483

445.McArdle BA,Birne DH,Klein R,De Kemp RA,Leung R,Enaud J,et al.Is et al. Is there an association between clinical presentation and the location and extent of myocardial involvement of cardiac sarcoidosis as assessed by 18F-fluorodeoxyglucose positron emission tomography? Circicardiac Imaging 2013;6:617-26. https://doi.org/10.1161/CIRCIPAGING.112.000289

46. Muser D,Sontangeli,P,Castanglo S,Changlo J,Enriquez A,Werner TJ,Tet al.Prognostic role of serial quantitative evaluation of 18F-fluorodeoxyglucose uptake by PET/CT in pa-tients with cardiac sarcoidosis presenting with ventricular tachycardia. Eur J Nucl Med Mol Imaging 2018:45:1394-404.https://doi.org/10.1007/s00259-018-4001-8

447. Ahmed Al, Abeabe AT,Han Y,Alnabeli T,Agrawal T,Kassi M,et al.The prognostic role of cardiac positron emission tomography imaging in patients with sarcoidosis: a sys-tematic review.J NuCardiol 2021:28:1545-52.https://doi.org/10.1007/s12350-021-0681-z

48. Flores RJ,Flahey Harri, Zin Bokhari S. The prognostic value of quantitating and local-izing F-18 FDG uptake in cardiac sarcoidosis. J Nucl Cardiol 2020;27:2003-10.https://doi.org/10.1007/s12350-018-01504-y

49. Sperry RW, Tamarappook, Oldan JD, Javed O, Culver DA, Brunken R, et al.Prognostic impact of extent, severity, and heterogeneity of abnormalities on 18F-FEDG PET scans for suspected cardiac sarcoidosis. JACC Cardiovascular Imaging 2018;11:336-45. https://doi.org/10.1016/j.jmc.2017.04.020

45. Obsoone MT, Hulten,AH, Singh A, Waller Ah, Bittencourt MS, Stewart GC, et al.Reduction in F14=Fluoroodeoxyglucose uptake on serial cardiac positron emission tom-ography is associated with improved left ventricular ejection fraction in patients with cardiac sarcoidosis. J Nucl Cardiol 2014;21:166-74. https://doi.org/10.1007/s12350-018-9828-6

ESC Guidelines

41. Birnie, Bands RNS, Bryon P,Aaron SD, CLuver Da, KEMP RA, et al. Cardiac sarcoidosis-multi-center randomized controlled trial(CHAS CM-SRC). Acte 1. Cardiac 2020;220:246-52.https://doi.org/10.1016/j.ajd.2019.10.003

452. Nordersan-HH,Lebonen J.,Eriston K,Mandironen Simo,P. Maymyraan P.Lae et al.Orcsout of Cardic sarcoidosis presenting with high-grade atrioventricular block. Circ Arrhythm Electrophysiol 2018;11:e006145.https://doi.org/10.1161/CIRCEP.117.006145

453. Halawa A, Jain R, Turagam MK, Kusumoto FM, Woldu HG, Gautam S. Outcome of implantable cardioverdefibrator in cardiator cardicosids: a systematic review and meta-analysis. J Interc Card Electrophysiol 20020:58:233-42. https://doi.org/10.1007/s10840-020-00705-1

454. Schuler ZJ,Pyzele C,Mawford T,Beng Fis,Benzh F,Patel A,et al.Forplandic electrolyte for derivatorial therapy in patients with cardiac sarcoidosis. J Cardiovasc Electrophysiol 2012;23:925-9.https://doi.org/10.1111/j.1540-8167.2012.02350x

455. Betensky BP,Tchabrum CM,Zado ES,Goldberg LR,Marchinsky FC,Carf,et al.Long-term follow-up of patients with cardiac sarcoidosis and implantable cardiover-defibrillators. Heart Rhythm 2012;9:884-91.https://doi.org/10.1016/j.rk.

456.Franke KB,Marshall H,Kennewell P,Pham H,D-Tully PJ,Rattanakit T,et al.Risk and predictors of sudden death in cardiac sarcoidosis a systematic review and meta-analysis. Int J Cardiol 2021;328:130-40.https://doi.org/10.1016/j.jicard.2020.11.044

457. Mathissen H.Baker ALm,Balt,C.Akid,Fim van Es.HW.Veltkamp M.et al.Predictors of appropriate implantable cardiac defibrator therapy in cardiac sarcoidosis|Cardiovasc Electrophysiol 2022:33:1272-80.https://doi.org/10.1111/jce.15484

458. Crawford T. Mueller G. Saram S, Prastumourch H.,Canen H. Gu. et al. Magnetic resonance imaging for identifying patients with cardiac sarcoidosis and preserved or mildly reduced left ventricular function at risk of ventricular arrhythmia.Crr Arrhythm Electrophysiol 2014;7:1109-15.https://doi.org/10.1161/CIRCEP.113.000156

459. Shafea P., Fukuda K, Wakayama Y, Nakano M, Kondo H, Masebe Y, et al. Delayed enhancement on cardiac magnetic resonance imaging is a poor prognostic factor in pa-tients with cardiac sarcoidosis.J Cardiol 2012;60:448-53.https://doi.org/10.1016/j.jcc.2012.08.002

460. Metaa,Dorni,GNoldh Sch,Bulin,Swinevsky,PJ etterin A.Primary preven-tion of sudden death in silent cardiac sarcoidosis: role of programmed ventricur-lar stimulation. Circ Arrhythm Electrophysiol 2011;4:43-8. https://doi.org/10.1161/CIPRC-11098522

461. Okada DR, Smith J, Derakhansh A, Gowani Z, Zimmerman SL, Misra S, et al.Electrophysiology study for risk stratification in patients with cardiac sarcoidosis and abnormal cardiac imaging. Int J Cardiol Heart Vasc 2019;23:100342.https://doi.org/10.1016/j.jcha.2019.03.002

462.Ahaduk,M. Paudueli B, Liu K, Awhath M, McGudic M. The role of electrophysiology study in risk stratification of cardiac sarcoidosis: meta-analyses and systemic review.Int J Cardiol 2022:349-55-61.https://doi.org/10.1016/j.jcard.2021.11.061

46.Zpi M.Paim, Tsou W, Schuller J, Alonie RG, Varoyos PD, Tomins C, et al.Electrophysiologic testing for diagnostic evaluation and risk stratification in patients with suspected cardiac sarcoidosis with preserved left and right ventricular systolic function. J Cardiovasc Electrophysiol 2019:30:1939-48. https://doi.org/10.111/jce 14058

464.Tandon P, Mosels H, Mettusta M,Audimow K,Hillm M,Morgenthau AS. Utility of electrophysiologic testing for sudden death risk stratification in cardiac sarcoidosis pa-tients with mildly impaired left ventricular function. Respir Med 2022;191:106712.https://doi.org/10.1016/2021.5021:106712

465. Blankstein R, Osborne M, Naya M, Waller A, Kim CK, Murthy VL, et al. Cardiac posi-tion emission tomography enhances prognostic assessments of patients with ps-tected cardiac sarcoidosis.J Am Coll Card 2012;43:36:39-36.https://doi.org/10.1016/j.jacc.2013.09.022

466. Kron J.Saver W.,Schulber B, Gogan F, Warrouti S, Saras T. et al. Efficacy and safety of implantable cardiac defibrators for treatment of ventricular arrhythmias in patients with cardiac sarcoidosis. Europace 2013;15:347-54.https://doi.org/10.1093/europe/aceu-ue316

467. Stevenson A,Bray JH,Tregigo L,Abmmad,Sharma A,Ng,A et al.Prognostic value of late gadolinium enhancement detected on cardiac magnetic resonance in cardiac sar-coidosis.JACC Cardiovascular Imaging 2013:345-57.https://doi.org/10.1016/j.cmm.2022.10.018

468. Veronese G,Ammirati B,Brambati M, MeriCori, Pianiang P, Potena L, et al. Viral gen-ome search in myocardium of patients with fulminant myocarditis. Eur J Heart Fail 2020;22:1277-80.https://doi.org/10.1002/1002/ehjfr1378

469.Sagra G.,Porra C.,Purgentic A.,Proteri,Tabos F.,Bussaran R.,Viral presence-guided immunomodulation in lymphocytic cardiocarditis: an update. Eur J Heart Fail 2021:2311-6.https://doi.org/10.1002/ejf.1969

470.Moinsa 2,Saczhaga S,Meroi M,Buastin A,Annei M,Dress et al. In:ofidic dilated cardiomyopathy and persistent viral infection: lack of association in a controlled study using a quantitative assay. Heart Lung Circ 2012;21:287-93.https://doi.org/10.1016/j.lhc.2012.07.01

471. Stewart GC, Lopez-Molina R, Gottumukkala RVSKR, Rosner GF, Anello MS, Hecht JL,et al. Myocardial paravovirus B91 persistence: lack of association with clinicopathologic phenotype in adults with heart failure. Circ Heart Fail 2011;4:71-8.https://doi.org/10.1161/CIRCERHTAFTALURE 110.958249

47. Robinson J, Hartling L, Vandermeer B, Sebastianski M, Klassen TP. Intravenous im-munoglobulin for preserved viral myocarditis in children and adults. Cochrane Database Syr. Rev.2002&8CD004370.https://doi.org/10.1002/14651858.CD004370.pub4

473. Kuhl U, Paussinger M, Schwimmbbeck PL, Seeberg B, Lober C, Noutsias M, et al.Interferon- B 09:1007-2020.10/1007/10/1007 function in patients with myocardial persistence of viral genomes and left ventricular dys-function. Circulation 2003;10:7793-8. https://doi.org/10.1161/01.CIR.0000072766.617501.51

474. Kuhl U, Lassner D, von Schlippenbach J, Poller W, Schultheiss H-P. Interferon-beta im proves survival in enterovirus-associated cardiomyopathy.J Am Coll Cardiol 2012;60:1295-6.https://doi.org/10.1016/j.jacc.2012.06.026

47. Schultheiss H- B.Pc K-Pc T, Aleshevche G, Baumeier C, Poller W, Escher F.Interferon-β suppresses transcriptionally active vorvirus B19 infection in viral car-riophyoma: a subgraph analysis of the BICC-trial. Viruses 2022;14:444.https://doi.org/10.3390v/14020444

47.Cobas M,AAblo,L.Santos M,Baccini-Jauregui C,Pham S.Successful management of fulminant influenza A Subtype H1N1 myocarditis. BMJ Case Rep 2010;2010:bcB20201763.https://doi.org/10.1136/bcr.02.2010.2763

477.Bak SH,Jeong HS,Kim J,Soon YOK,Sohn JW,Jim MJ.A case of influenza associated fulminant myocarditis successfully treated with intravenous peramivir. Infect Chemother 2015;47727-7-1.https://doi.org/10.3947/20015.47.4.272

478. Jhans-F,P.Ben-Ben-Namouda N,Kirsch M,Roumy A,Liaudet L. Intravenous zamamivir for influenza myocarditis and external malabsorption. Crit 2018:22:332.https://doi.org/10.1186/195404-018-2263-y

497.Mzlltelli,G.Farolano,F.Retriani A,Barreica GS,Quirino A,Giancotti A,et al. Severe myocarditis due to influenza A(H1N1)pdm09 viral infection in a young woman suc-cessfully treated with intravenous zamamir: a case report. Clin Case Rep 2019;7:2336-40.https://doi.org/10.1002/corr.3.2499

480. Yoshimu N,Nomara T,Tto,Nishida Y,Wada Y,Sohmiya K,et al.Repetitive ful-minant influenza myocarditis requiring the use of circulatory assist devices.Intern Med 2015;43:109-14.https://doi.org/10.1161/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/j.hor.1016/

48. Khouzam RNan, Parisauz C,Hafiz AM,Chawla S,Schwartz R.Fulminant myocarditis as-scribed with Intel NHTI in influenza A. Hafiz Lurg 2011;40:566-8.https://doi.org/10.1016/j.hrtling.2011.0014

421 to N.Sato M.,Momo N.,Aoyagi Y,Endo K.,Chishiki M.,et al.Influenza A H1N1 p09d-associated myocardial transizes vanimatter therapy. Pediatr Int 2015;57:1172-4.https://doi.org/10.1111/pep-127121

43.Puglesiee A. Harndard S.,Ascarabelli T,Raddino R,Rotre D.Impact of highly active antretroviral therapy in HIV-positive patients with cardiac involvement.J Infect 2000;40:2824.https://doi.org/10.1053/jinf:2000.0672

48. Stee AC,Batsford WP,Weinberg M,Alexander J,Berger HJ,Wolfson S,et al.Lyme carditis: cardiac abnormalities of Lyme disease. Ann Intern Med 1980;93:8-16.https://doi.org/10.7326/0003-4819-93-1

48. Besantin, G Wan, D Yeung, Clakely B, Transcombe, P. Suarez-Fuster L, et al. Suspicious index in Lyme cysts: systematic review and proposed new risk score. Clin Cardiol 2018;4161:1611-6.https://doi.org/10.1002/cld.23102

48. Lantos PM, Rumbaugh J, Bockenstedt LK, Falck-Ytter YT, Aguero-Rosenfeld ME,Auuwaerter PG,et al. Clinica Practice Guidelines by the Infectious Diseases Society of America(IDSA), American Academy of Neurology(AAN), and American College of Rheumatology(ACR): 2020 guidelines for the prevention, diagnosis, and treatment of Lyme disease. Arthritis Res of Hoboken(Bohoken) 2021;73:1-9.https://doi.org/10.1126/2402495

487. Costello JM,Alexander ME,Greco KM,Perez-Atayde AR, Laussen PC.Lyme carditis in children: presentation, predictive factors, and clinical course. Pediatrics 2009;123:e85-41.https://doi.org/10.1542/peds.2008-3058

88.Nunes MCP, Baden,PAP, Marin-Neto JA, Edvardsen T, Fernandez-Golfin C,Buccarelli-Ducco C, et al. Multimodality imaging evaluation of Chagas disease: an ex-pert consensus of Brazilian Cardiovascular Imaging Department(DIC) and the European Association of Cardiovascular Imaging(EACVI). Eur Heart J Cardiovasc Imaging 2018;19:459-60. https://doi.org/10.1093/ehjci/jex154

489. Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A, Rosas F, et al.Randomized trial of benzridazole for chronic chagas' cardiomyopathy. N Engl J Med 2018:495-306.https://doi.org/10.1056/NEJMoa.1507574

490. Perez-Molina JA, Perez-Ayala A, Moreno S, Fernández-Gonzalez MC, Zamora J,Lopez-Velez R. Use of benzhenzadole to treat chronic Chagas' disease: a systematic re-view with a meta-analysis, J Antimicrob Chemother 2009;64:1139-47.https://doi.org/10.1093/cdp/dk357

491.Viotri,Vilagano C,Lococco B,Bertocchi G,Petti M,Alvarez MG,et al.Long-term car-diac outcomes of treating chronic Chagas disease with benzridazole versus no treat-ment a nonrandomized trial. Ann Intern Med 2006;144:724-34.https://doi.org/10.1162/0006015140-149-110-200605160-00006

ESC Guidelines

492. Chadawa S, Rassi A, Samara O, Monzon A, Gudapati D, Vargas Barahona L, et al.Mortality risk in chronic Chagrass cardiomyopathy, a systematic review and meta-analysis. ESC Heart Fail 2021:8:5466-81.https://doi.org/10.1002/ehf.213648

493. Carmo AAL,ous La Sousa IR,Bojores E,Raocho E,Raocho ALP,et al.Implantable cardiover-defibrator in Chasing 2013 as heart disease: a systematic review and meta-analysis of observational studies. Int J Cardiol 2018;267:88-93. https://doi.org/10.1016/j.ijcard.2018.05.091

49. Russi FM, Minohara L, Rassi A, Correia LCL, Marin-Neto JA, Rassi A, et al. Systematic review and meta-analysis of clinical outcome after implantable cardioverter-defibrillator therapy in patients with Chagas heart disease. JACC Clin Electrophysi 2019;5:1213-23.https://doi.org/10.1016/j.jacep.2019.07.003

49.Mahmodi S5. Fradig, Mc Cohen, N. Rohma, N. Reynolds L,et al.Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 2018;71:1755-64.https://doi.org/10.1016/j.jacc.2018.02.037

49. Salem's Li-For Mnoucha Hmi, M. Lebrun-Vignables, Bastane, Léarite, L. Aefol.2010 Cardiovascular toxicities associated with immune checkpoint inhibitors: an observa-tional, retrospective, pharmacovigilance study. Lancet Oncol 2018;19:1579-89,https://doi.org/10.1016/s16704-20540(18)3098-96.

49. Suzuki Y, Kaneko H, Tamura Y, Okada F, Ajujiu K, Michata N, et al. Cardiovascular events after the intonation of immune checkpoint inhibitors. Herley 2023;9:16373.https://doi.org/10.1016/j.helyon.2023.e16733.

49. Nguyen LS, Cooper LT, Kreneris M, Funck-Brentano C, Silavin J, Brechot N, et al.Systematic analysis of drug-associated myocardits reported in the World Health Organization pharmacovilance database. Nat Commun 2022;13:25.https://doi.org/10.1038/s41467-021-27631-8

499. Liu,Cheng X,N.Ri,Zheng B,Huang,Yang,Jlardoticity of immune checkpoint inhibitors: a frequency network meta-analysis. Front Immunol 2022;13:1006860.https://doi.org/10.3389/fimmu.2022.1006860

500.Pradhan R,Nautalya A,Singh S. Diagnosis of immune checkpoint inhibitor-associated myocarditis: a systematic review. Int J Cardiol 2019;296:113-21.https://doi.org/10.1016/j.ijaccard 2019.07.025

501.Lyon R,Leopz-Fernandez T,Couch LS,Astegiano R,Aznar MC,Bergler-Klein J,Eal.2022 ESC Guidelines on cardi-onology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology(ESTRO) and the International Cardio-onology Society(IC-OS).Eur Heart J 2022;43:4229-361.https://doi.org/10.1093/erheur/ehac244

502. Salem J.E. Bretager M. Abbar B., Leonard-Louis S. Eherley R. S5500, A et al.Bextabatic/ruxutibin and screening for concomitant respiratory muscle failure to miti-gte fatality of immune-checkpoint inhibitor myocarditis. Cancer Disov 2021:1100-15.https://doi.org/10.1158/2159-8290.CD-22-1180

503. L'Orphenir J-M, Dollallie C, Akroun J, Alexandre J, Dompartin A. Cardiovascular im-munotocytic associated with immune checkpoint inhibitors in metastatic melanoma.Cans(Besal) 2023;15:2170.https://doi.org/10.1039/cansers15072170

504. Tocchetti CGF, Farmakis D, Koop Y, Andres M, QSCH, LS formiana L, et al.Cardiovascular toxicoties of immune therapies for cancer--scient statement of the Heart Failure Association(HFA) of the ESC and the ESC Council of Cardio-Encology. Eur J Heart Fail 2024:26:2055-76.https://doi.org/10.1002/elfh.3340

505. Dolladille C,Erderys S, Massier, Cautela J.,Thuny F, Cohen AA,et al. Immune check-point inhibitor rechallenge after immune-related adverse events in patients with can-cer.JAMA Ocola:20006:865-71.https://doi.org/10.1001jamaoncol.2020.0726

506.Chapham E,Reutins L.J,Mrandt L,Sundstrom J,Robden R.The association be-tween exposure to clozapine,olazupine, and zequtine and the outcomes per impoine-cardites and heart failure a population-based cohort study. Psychiatry Res 2023:236:115336.https://doi.org/10.1016/j.psychres.2023.113536

507.Sandarsh S,Bishnoi RJ,Shashank RB,Miller BJ,Freedenreich Oc,McEvoy JP. Monitoring for myocardits during treatment initiation by scapins Acta Psychiard Scom 2021;144:194-200.https://doi.org/10.1016/j.acpsr.1923.11363

508.Sukind D,Sehui,Cross,JChua,Y.TY's Mines,N.Chen D.et al. Systematic review and meta-analysis of rules of aclosez-conjugate myocardial and cardiomyopathy. Aust N 29J Psychiatry 2020:54:467-81.https://doi.org/10.1111/acps.198760

509. Sereophan-aminan C, Assanarkhomano N,Nilino Jrope-Tongextracorporal mem-brane oxygenation support in a patient with drug reaction with eosinophila and sys-temic symptoms syndrome-associated fulminant myocardia-tis: a case report and literature heart. Reutet 2014:1211-7. https://doi.org/10.11927.2020.14.112

510 Bonhoefer J, Kohl K, Chen R, Duclos P, Heijbel H, Heininger U, et al. The Brighton Collaboration addressing the need for standardized case definitions of adverse events following immunization(AEF). Vaccine 2002;21:298-302. https://doi.org/10.1016/s0264-410x(02)00449-8

511.Engler RJM,Montgomery JR.Osponer CE,Nelson RC.Lilcs RC.Lanica MA et al.Myocarditis and paricarditis recovery following small proxopyine 2002:6-2016:com parative observational cohort study in the military health system.PLoS 2023:18:e0283988.https://doi.org/10.1371/poumalone.0289388

51. Parmar K, Subramaniamy S, Del Rio-Pertuz G, Sethi P, Argueta-Sosa E. Cardiac adverse after vaccination-a systematic review. Vocines(Bas) 2022;10:700.https://doi.org/10.3390/vcines10050700

513. Thanjan MT, Ramasamy W P, Lai WW, Lytrivir ID. Acute myopercarditis after multiple vaccinations in an adolescent: case report and review of the literature. Pediatrics 2007;119:1400-3.https://doi.org/10.1542/peds.2006-2605

514. Diber E,Karagzte R,Yanol T,ORzer S,Alehan D,Oto A,et al. Acute myocarditis as-sociated with tetusin vaccination. Mayo Clin Proc 2003;78:1431-3.https://doi.org/10.4065/78.11.1431-a

515. Boccaara B, Benzaiem S, Yatemoyi, C. Ozer S, Alehan D, Oto A, et al. Acute myocarditis as-sociated with tetanus vaccination. Mayo Clin Proc 2003;78:1431-3. https://doi.org/10.4065/78.11.1431-a

516. Barton M, Finkles Y. Azyankowis MA, Ito S, Ho T, Ford-Jones LE, et al. Eosinophilic myocarditis temporally associated with conjugate meningococcal C and hepatitis B vaccines in children. Pediatr Is 2008;27:831-5. https://doi.org/10.1097/INF.Ob013e31816ff7b

517. Lu,Zhang X,Xu H,Li Z.Inspiration to mRNA-based COVID-19 vaccination: serious adverse case reports with hepatitis B vaccine in real-world. Front Pediatr 2022;10:888686.https://doi.org/10.3389/fped.2022.888686

518. Nagano N,Yano T,Fujita Y,Koyama M,Hasegawa R,Nakata J,et al.Hemodynamic collapse after influenza vaccination: a vaccine-induced fulminant myocarditis? Can J Cardiol 2020;36:1545.e-7.https://doi.org/10.1016/j.cca.2020.05.005

519. Jan SS,Anderson SA,Steele JM,JM,Wilson HC,Muniz JC,Soslow JH,et al.Cardiac man-ifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination(MACIV)multicenter study.EclinicalMedicine 2024;76:102809.https://doi.org/10.1016/j.eclnn.

520. Peretto G,Micagio E,Cicote G,Maia M,Luzzi M,Cariello M,et al.The'arrhythmic'presentation of peripartum cardiomyopathy: case series and critical review of the lit-erature. Front Cardiac Vosed 2024;11:1362692. https://doi.org/10.3389/fcmv.2024.136292

521.Hovemolden,EJ,Engel ME,Muller E,Hohlfeld A,Bohm M,Sliwa K,et al.Global perspec-tive on the management and outcomes of peripartum cardiomyopathy: a systematic review and meta-analysis. Acta Psychol J Heart Fail 2022;24:1719-36. https://doi.org/10.1002/8023.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.2022.

522.Gunderson EP,Croen LA,Chiang V,Yoshida CK,Walton D,Go AS.Epidemiology of peripartum cardiomyopathy: predictors, and outcomes. Obstet Gynecol 2011;118:583-91.https://doi.org/10.1097/AOG.0b013e3182296ede

523.Karaye KM, Ishaq NA,Saidi H,Baralabe SA,Talle MA, Isa MS,et al. Incidence, clinical characteristics, and risk factors of peripartum cardiomyopathy in Nigeria: results from the PEACE Registry. ESC Health Fail 2020:7:235-43.https://doi.org/10.1002/efh2.12562

524. Goi R.L.,JiBrandmao,L.Relevine LD,Ris V,McAfee Q,et al.Genetic and phenotypic landscape of peripartum cardiomyopathy. Circulation 2021;143:1852-62. https://doi.org/10.1161/CIRCULATIONNAHA-120.025395

52.Malkelli-Hethi-Reddy S,Ainkantoey,E.Trehanen,Sharma,Sasrioulis,Ajadeesh K,et al.Burdenen of thyrin apparatus in peritumar cardiomyopathy: analysis of 9841 hospitaliza-tions. Int J Cardiol 2017:235.114-7.https://doi.org/10.1016/j.ijcard.2017.02.084

526. Sila, Kilhi-Kellerin D, Petrolein MC, Mebazaa A, Pieske B, Buchmann E, et al. Current state of knowledge on aetology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy.Eur J Heart Fail 2010;12:767-78.https://doi.org/10.1093/eurifh/fhqx120

57.Tanous,Du S,Clu,Sson J,Greutmann M,Wald RM,Parker JD,et al.B-type natriuretic peptide in pregnant women with heart disease. J Am Coll Cardiol 2010;56:1247-53.https://doi.org/10.1016/j.jacc.2010.02.076

528.Ebrandin FD,Z.,Zafar,S.Panthang V,Cyril Kurupr AR,Raju A,Luthra G,et al. Utility of N-terminal(NT)-brain nucleotide peptide(proBNP) in the diagnosis and prognosis of pregnancy associated vascular conditions: a systematic review. Cureus 2022;14:e32848.https://doi.org/10.759/cureus.32848

529. Li W, Li H, Long, Clinical characteristics and long-term predictors of persistent left ventricular systolic dysfunction. Eur in peripartum cardiomyopathy. Can J Cardiol 2016;3282-86.https://doi.org/10.1016/j.cjca.2015.07.733

530. Arora NP,Mahanin,Mahamad T,Kottam A,Afonso LC,Danrad R,et al.Cardiac magnetic resonance imaging in peripartum cardiomyopathy. Am J Med Sci 2014;347:112-7.https://doi.org/10.1091/0.0b013e31828155e3

51. Ordosar KG, Baldarass A, Bucciarelli-Ducci C, Carr J, Fernandes JL, Ferreira VM,Cardiova: Cardovagous resonance in women with cardiovascular disease: pos-ition statement from the Society for Cardiovascular Magnetic Resonance(SCMR). J Cordova: Magc Reson 2021:23:52. https://doi.org/10.1186/s12968-021-0074-06

522. Ray JJG,Vermeulen MJh,Braha,Aontmaan WJ,Rap AL Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA 2016;316:952-61.https://doi.org/10.1001/jama.2016.12126

33. Schelber EB,Ekoulay U,Comper LT,Givert MM,Alexis JD,Briller J,et al.Myocardial damage detected late late columnen enhancement cardiac magnetic resonance is un common in peripartum cardiomyopathy. J Am Heart Assoc 2017;6:e005472. https://doi.org/10.1161/AHA.117.005472

54.Coper LT,Pretton MJ,Alexis JD, Pauly DF, Torre-Amione G, Wittstein IS, et al.Myocardial recovery in peripartum cardiomyopathy: prospective comparison with

ESC Guidelines

recent onset cardiomyopathy in men and periparontomen w.J Card Fail 2012;18:28-33.https://doi.org/10.1016/j.cardfail.2011.09.009

535. McNamara DM,Elayam U,Alharethi R,Damp J,Hsich E,Wedg al. et al. Clinical out-comes for perpartum cardiomyopathy in North America: results of the IPAC study(investigations of pregnancy-associated cardiomyopathy). J Am Coll Cardiol 2015;66-905-14.https://doi.org/10.1016/j.jaccard.2015.06.1309

536. Bteker M, Ozley K, Cic, Cel, Oldan G, Ev al. Predictor's of early and de-layed recovery in peripartum cardiomyopathy: a prospective study of 52 patients.J Matem Fetal Neonatal Med 2020;33:390-7. https://doi.org/10.1080/14767058.2018.1494166

537. Fett JD, Christie LG, Carraway RD, Murphy JG. Five-year prospective study of the in-cidence and prognosis of peripartum cardiomyopathy at a single institution. Mayo Clin Proc.2005;80:162-60.https://doi.org/10.4065/80.12/1602.

538. Moulig P, Pfeffer TJ, Rike-Hoch M, Schlothauer S, Koenig T, Schwab J,et al. Long-term follow-up in perpartum cardiomyopathy patients with contemporary treatment: low mortality, high cardiac recovery, but significant cardiovascular co-morbidities. Eur J Heart Fail 2019;21:1534-42.https://doi.org/10.1002/efjh.1624.

539. Sliwa, A. Kobani F, Bard J. Osman A. Zuhlike L, Lachmann A. et al. Reducing late ma-ternal death due to cardiovascular disease- a pragmatic pilot study. Int J Cardiol 2018;272:70-6.https://doi.org/10.1016/j.ijcard.2018.07.140

540. Buaversels Jr,Aigman H.;Filker-Kleiner V.Detell,COSre,Cisto-Liero-Mg,et al. Current management of patients with severe acute peripartum cardiomyopathy:practical guidance from the Heart Failure Association of the European Soocty of Cardiology Study Group on peripartum cardiomyopathy. Eur J Heart Fail 2016;109-105.https://doi.org/10.1002/efh.586

541.Fu,K.Zhang H.,Chen H.N.,Yu Xiao J.,Zhang X.J.,et al.Risk factors for intracardac thrombus in peripartum cardiomyopathy: a retrospective study in China. ESC Heart Fail 2023:10:148-58.https://doi.org/10.1002/efh.142158

542.Hiff-Kinerle-Dhakhina,Ribenter,D.Guelten-Sicaus,JWhanje,Frak et al.Bromorogine for the treatment of peripartum cardiomyopathy: a multicentre rando-molyed study.Eur Heart J 2017;38:2671-9.https://doi.org/10.1093/eurieftah;ehx355

544. Sliwa K,Blauwet,T.Lzraevaku Z.,Hiblerboua,S.M.,Berechoua J.-P. Becker et al. Evaluation of bromocritine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept plot study. Circuit 2010:1216-743.https://doi.org/10.1016/1161/CIRCULATIONAHA.109.901496

544. Kumar A,Ravi S,Rivakumar RK,Chidamaram V,Jella Maigh,M Sina,Shu et al. Prolactin inhibition in peramartion cardiomyopathy: systematic review and meta-analysis. Curr Probol Cardiol 2023:481461.https://doi.org/10.1016/j.jpccardiol.2022.101461

545. Trongrotansak A,Kitipubil V, Mahabir S, Ibrahim S, Crointy RG, Hernandez R, Hernandez GA,et al.Effects of bromocirinopetine in perpartum cardiomyopathy: a systematic review and meta-analysis. Heart Fail Rev 2022;27:533-43. https://doi.org/10.1007/s107471-021-10185-8

546. Halliday BP, Wastell R, Lala Khalique Z, Greson J, Newomes S, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilar c-domiomyopathy(IETH), an if-abel plot, model randomt. Luron 2019;393:61-73.https://doi.org/10.1016/S0140-67637(18)32844-X

547. Codsi E,Rose CH,Blawuety LA. Subsequent pregnancy outcomes in patients with peri-partum cardiomyopathy. Obstet Gynecol 2018;13:327-7. https://doi.org/10.1097/A0G00000000002439

548. Meng M-L, Arendt KW, Banayan JM, Bradley EA, Avta H, Eamed, AB et al.Anesthetic care of the pregnant patient with cardiovascular disease is a scientific statement from the American Heart Association. Circulation 2023;147:e657-73. https://doi.org/10.1061/C1RIC.000000000001121

549. De Backer J.,Haugura K. 2025 ESC Guidelines for the management of cardiovascular disease and pregnancy. Eur Heart J. 2011;32:3147-97. https://doi.org/10.1093/eurberth/28478-18

550. Richardson P, McKenna W, Bristow M, Maichas, B Mauter, O'Connell, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology, Task Force on the definition and classification of cardiomyopathies.Circulation 1996;93:841-2.https://doi.org/10.1016/1.0161/cir.93.541

551. Frustaci A, Russo Ma, Chimenti C. Randomized study on the efficacy of immunosup-pressive therapy in patients with virus-negative inflammatory cardiomyopathy: TIMIC study. Eur. Heart J 2009;30:1995-2002. https://doi.org/10.1093/eurheart/ehp-249

552. Escher F,Kuhl U Lasser D,Peller W, Westernann D,Peske B, Lour al-tempong-out come of patients with virus-negative chronic myocarditis or inflammatory cardiomyopathy after immunosuppressive therapy. Clin. Res Cardiol 2016;1016:1011-201.https://doi.org/10.1007/s00392-016-1011-z

55.Merken J,Hazebroek M, Van Paassen P, Verdonschot J, Van Perdensot, Kl and Aonon, J. J. Immunosuppressive therapy improves both short- and long-term prognosis in patients with virus-negative noninflamantin cardiomyopathy. Circ Heart Fail 2018:11:e004228.https://doi.org/10.1161/CIRCHEARTFAILURE 117.004228

554. De Luc,Gampc Charoam,Cortare S.Selfer,P.P.,Berteso P.,Gala S.Salmaano et al.Efficacy and safety of myopencephonate motif in patients with virus-negative lymphotic myo-carditis: a prospective cohort study.J.Amutoinum 2020;106:10230.https://doi.org/10.1016/j.jaut.2019.102330.

555. Peretto G, Sal,Se, Dalca Gca, Marcolongo R, Campochiaro C, Sartorelli S, et al.Immunosuppressive therapy and risk stratification of patients with myocarditis pre-senting with ventricular arrhythmias. JACC Clin Electrophysiol 2020;6:1221-34.https://doi.org/10.1016/j.jaccard.2020.05.013

556. Reuter H, Burgess JL, Doubl et AF. Epidemiology of peridard effusions at a large aca-demic hospital in South Africa. Epidemiol Infect 2005;133:393-9. https://doi.org/10.1017/095268804003577

557. Mayosi BM, Wiyomse CS, Ntskehke M, Gumedze F, Volmink JA, Maartens G, et al.Mortality patients treated for tuberculosis periditis in sub-Saharan Africa. S Afr Med J 2008;98:36-40.

558. Mayosi BM, Burgess J L, Doubell AF. Tuberculous pericarditis. Circulation 2005;112:3608-16. https://doi.org/10.1161/CIRCULATIONAHA.105.543066

159. Isiguo C,Du Bruyn E,Hollett P,Ntsekhte M. Diagnosis and management of tubercu-lous pericandits: what is new? Curr Cardiol Rep 2020;22:2.https://doi.org/10.1007/s18868-1202-1254-1

560.Ntekeh M,MayiBMos.Tuberculous pericarditis with and without HIV. Heart Fail Rev 2013;18:367-73.https://doi.org/10.1007/s10741-012-9310-6

561.Noubiaj J.Agbor VN,Ndoadoumgue AL,Nkeck JR,Kangua A,Nyaga UF,et al.Epidemiology of pericardial diseases in Africa: a systematic scoping review. Heart 2019;105:180-8.https://doi.org/10.1136/hentjrl-2018-313922

562.Xie DL,Cheng R,Sheng Y,Jin J. Diagnostic accuracy of adenosine deaminase for tuber-culous pericardits: a meta-analysis. Eur Rev Med Pharmacol Sci 2015;19:4411-8.https://doi.org/10.1632/eurrev_2015_19_22_4411

563. Pandie S, Peter JG, Kerbler ZS, Meldau R, Theron G, Govender U, et al. Diagnostic accuracy of quantitative PCR(Xpert MTB/RIF) for tuberculosis pericarditis compared to adenosine deminase and unimperated interferon-y in a high burden setting a pro-spective study. BMC Med 2014;12:101.https://doi.org/10.1186/1741-7015-12-101

564. Yu G,Ye B,Chen D,Zhong F,Chen G,Yang J,et al. Comparison between the diag-nostic validations of Xpert MTR/BIR and interferon-y release assays for tuberculous peri-ics carditis using pericardite tissue. PLoS One 2017;12:e0188704.https://doi.org/10.1371/jp.pone.0188704.

556. Liu C.,Cui Y.,Ling D,C.M.,Inch L,Y-H,L-Liu X,F.et al.Diagnostic accuracy of interferon-gamma in peridium effusions for tuberculosis peridium: a meta-analysis.JorThocis D 2018:1085-640.https://doi.org/10.21037/jtd.1017.12.107

56. Cattanchi A, Smith R, Steingart KR, Metcalfe JZ, Date A, Coleman C, et al.Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis. J Acim Proximal, Defic Syndr 2011;56:230:38. https://doi.org/10.1097/QA103b013e31820b07ab

567.Wiyonsche S,Nkteh S,M�heb L,Volmink J,Majombozi D,Gumedze F,et al.Interventions for treating tuberculosis Corchine Database Syst Rev 2017;9.CD000526 https://doi.org/10.1002/14651858. CD000526.pub2

56. Pasapianoyu M, Jagubman M, Ntsekme M, Pandie S, Magazzi BT, Gumedze F, et al.Tuberculous pericardits is multibacillary and bacterial burden drives high mortality.BioMedicine 2015;2:1634-9.https://doi.org/10.1016/j.ebiom.2015.09.034

569 Mayolis BM, Ntsheke M, Bosch J, Pandie S, Nagu G, Hmedze F, et al.Mycobacterium in tubularic pericarditis. N Engl J Med 2014;371:1121-30.https://doi.org/10.1016/j.ebiom.2014.107380

570. Reuter H. Burgess LJ, Louve J, Double AF. The management of tuberculous pericar-dial diffusion: experience in 233 consecutive patients. Cardiovasj S J Afr 2007;18:20-5.

51. Strang JJ,Kakaaz HH,Gibson DG,Girling DJ,Nunn AJ,Fox W.Controlled trial of pred-nisone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei.Lancet 1987:2148-122.https://doi.org/10.1016/s0140-6736(87)91127-5

572. Strang JJ,Nun A,Junson A, Daasin B,Gong DJin,Gongling JD. Management of tuberculosis constractive pericarditis and tuberculous pericarditis effusion in Transkei:results at 10 years follow-up. QJ M 2004;97:525-35.https://doi.org/10.1093/qjm/hedc/h086

537.C.Hul B.Chen X,Y.Cu C,C-L.Shou X-L,Liu X,Yao X-W,et al. Prevention of pericar-dial constriction by transcatheter intraperiodic fibrinolysis with urokinase. Chin Med Sci[2005;20:5-10.https://doi.org/10.1016/j.chmedsci.2005.01.002

574 Maisch B,Risstic A, Parkuetwels F. Evaluation and management of pericardial effusion in patients with neoplastic dease. Procardic Javascis Dis 2010;53:157-63.https://doi.org/10.1016/j.campsid.2010.06.003

575.Inamio,M.,Demelsb B,Parrini,Favro E,Beqaraj,F,Cecchi E,et al.Relation of acute pericardial disease to massigny. Am J Cardiol 2005;9:1359:1393-4. https://doi.org/10.1016/j.amjard.2005.01.094

57. Pawlak Cieslik S, Astrumowicz M, Fijakowska A, Gatarek J, Gralec R,Blasinska-Przerwa K, et al. Diagnosis of malignant pericardits: a single centre experi-ence. Lancordol 2012/70:1147-53. https://doi.org/10.33963/v.kp.79064

57. Karatios K, Pankuweit S, Akamis B. Diagnostic value of biochemical biomarkers in ma-lignant and non-malignant pericardial effusion. Heart Fail Rev 2013;18:337-44.https://doi.org/10.1007/s107101-9237-x

578. Wang Ek,Blan MJ, Deal M, Lipner M, Zagar TM, Wang Y, et al. Cardiac toxicity after radiotherapy for stage III on-small-cell lung cancer: pooled analysis of dose-escalation trials delivering 70 to 90 Gy. J Clin Oncol 2017;35:1387-94. https://doi.org/10.1200/NOC.2016.70.0229

579 Takata N, Katoka M, Hamamoto Y,Tsuoruka S,Kanzaki H,Uwatsu K,et al.Risk fac-tors for pericardial effusion in chemorachylation for thoracic esophageal cancer-

$$\text{ ESC Guidelines}$$

comparison of four-field technique and traditional two opposed fields technique. J Rodat Res 2018;59:291-7.https://doi.org/10.1093/jrr/ror/029

580.Gevail SA, Halvorsen S, Sinnaeva R, Sambola A, Gulati G, Lancellotti P, et al.Evaluution and management of cancer patients presenting with acute cardiovascular disease: a Consensus Document of the Acute Cardiovascular Care (ACVC) associ-ation and the ESC Council of Cardio-Oncology-Part 1: acute coronary syndromes and acute pericardiac diseases. Eur. Heart J e Aute: Cardiovasc Core.2021;10:947-59.https://doi.org/10.1093/ehccu/20.058uab

581. Saab J,Hoda RS,Narula N,Hoda SA,Geraghty BE,Nasar,A.et al.Diagnostic yield of cytopathology in evaluating pericadial efficiencies: clinicopathologic analysis of 419 spe-cimens. Cancer Gytopathol 2017;125:128-37.https://doi.org/10.1002/cncy.21790

582. Numico G.,Cristofano A,Occal M.Surocia,M.Mozalsson de FEA,E. et al.Prolonged drainage and intraperical percoliaenm�ic administration for cardiampatokon second-ary to cancer-related pericardial effusion. Medicine(Baltimore) 2016;95:e3273. https://doi.org/10.1097/MHD00000000003273

58. Kim SR,Kim EOK,Cho J,Chang S,A-Park S,J.Lee S-C,S.Let al.Effect of anti-inflammatory drugs on clinical outcomes in patients with malignant pericardial effusion.J Coll Cardiol 2020;76:1551-61.https://doi.org/10.1016/j.accs.2020.08.003

58. De Filippo O,Gatti,Pretegnoz S,Inaccano M,D'Ascenzo F,Lazaros G,et al.Isi-peri-ardial effusion a negative prognostic marker? Meta-analysis of outcomes of pericardial effusion.J Cardiovascular Med(Gherostomer 2019) 20:39:45.https://doi.org/10.2459/JCM.00000000000720

58. Gatzlais K,Oranskita S,Tisbrakia L.,Zuslazos P.,Apostopoulos T,Zenovopoulos G.et al. Post-cardiac injury syndrome after permanent electronic cardiac device implantation. Incidence, presentation, management and long-term prognosis. Int J Cardiol 2014;17416-173.https://doi.org/10.1016/j.jarcard.2014.03.170

586. Nakla S, Mentas A, Rymer C, Huszen A, Wazni O, Rickard J, et al. Acute pericarditis after atrial fibrillation ablation: incidence, characteristics, and risk factors. Heart Rhythm 2022;3:248-51.https://doi.org/10.1016/j.1016/j.2022.02.008

587.Imao M,Negro A,Belli R,Beqaraj F,Rorno F,Diammaia M,Cristella and Neuromal interaction's significant influence of percutary myocardial infarction by primary percutaneous coronary intervention. Am J Cardiol 2009;103:1525-9.https://doi.org/10.1016/j.amjard.2009.01.366

88. Figures.Jaral,C. Carillov A, Corollary Intel, Solaras J. Solar and progression of peri-cardial perfusion in patients with a first myocardial infarction: relationship to age and free wall rupture. Am Heart J 2002;144:251-8. https://doi.org/10.1067/mmh.org/1.2002.12384

Figures.Jarnabis,A.Jerra,Caltadorio,Lidusen J.Lon-R,M.Carzino,A.et al.Hospital outcome of moderate to severe pericardial effusion complicating ST-elevation acute myocardial infarction. Circulation 10,1012:1920-1,992.https://doi.org/10.1161/CIRCULATIONAHA.109.934968

59. Mohanty S, Mohanty P, Kessler G, Jianao B,Chao KK, Morris T, et al. Impact of col-chine monotherapy on the risk of acute pericardits following atrial fibrillation ab-tion. JACC Clin Electrophysiol 2023;9:1051-9.1 https://doi.org/10.1016/j.jacep.2023.01.037

591. Lehtjo, Kivmien T. Gum, J. Araginai J. Rautaar P. Kkyo v. Occurrence of posper-tionicardi syndrome: association with operation type and postoperative mortality after open-heart operations. J Am Heart Assoc 2018:7:010269. https://doi.org/10.1161/AHA.118.010269

592. Imazio, Rucato, Rover Me, Garcia Aino, Cemin R. Rerrau, S et al. Contemporary features,risk factors, and prognosis of the post-pericentotomy syndrome. Am J Cardiol 2011:1088:113.7-7.https://doi.org/10.1016/j.amjcard.2011.06.025

593.Finkelstein Y,Sheshem J, Mahlab K, Abramov D, Bar-El Y,Sagie A,et al. Colchicine for the prevention of pericoporditerotomy syndrome. Herz 2002:27.791-4. https://doi.org/10.1007/s00059-0023-276-5

594.Imozio M,Trinocher R,UCroato R,_Verore Me,Gandino A,Cemin A,R.ol Chilcicine for the Prevention of the Post-per-cardiotomy syndrome(COPICS) and multicentre, ran-domized, double-blind, placebo-controlled trial. Eur J Heart 2010;31:2749-54.https://doi.org/10.1094/ourouriterheq1939

595. Imzio M, Brucato A, Ferrazzi P, Spodickd, AdH. Posterarycardiostomy syndrome.a proposal for diagnostic criteria. J Cardiovasc Med(Hogerstown) 2013;14:351-3.https://doi.org/10.102459(CJ0801013)285383807

96. Imazio M, Brucato A,Ferrazzi P, Pullara A, Adler Y, Barrosi A, et al. Colchicine for pre-vention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPS-2 randomized clinical trial. JAMA 2014;3126:1013-26. https://doi.org/10.1001/jama.2014.11026

97.51. Gill PJ, Forbes K Coe JY. The effect of short-term prophylacticity and survival closure of a trial septal defects.Pediatr Cardiol 2009;30:1061-7.https://doi.org/10.1007/s00246-009-9495-1

598.Mott Ar,FRin C.,KousnOR,Ayinge GekeM,Nid al,RG,Drescher KL,et al.The ef-fect of short-term prophylactic methyl-prednisolone on the incidence and severity of postpericardiotomy syndrome in children undergoing cardiac surgery with cardiopulmonary by Jm. Coll A Cardiol 2007;19:70017-6. https://doi.org/10.1016/j.morj2037-0399-107(01)01223-2

59. Bunge JH, Genas D, Exchoule D. Maibman J, Jacob KA, Kluin J, van Dek, et al. Dexamethasone for the prevention of pericotopidiratory syndrome. A Dexamethasone for Carduc

0317.Surgery substum. Am Heart J 2014;168:126-31.e1.https://doi.org/10.1016/j.ahj.2014.03017

600.Imazio M,Brucato A,Markel G,Cemin R,Trinchero R,Spodick DH,et al.Meta-analysis of randomized trials focusing on prevention of the postpericardiotomy syndrome.Amj Cardiol 2011;108:575-9. https://doi.org/10.1016/j.jamcard.2011.03.087

601.Meurin P,Tabet Y,Thatab G,Cristofini P,Farroki T,Fischbach M,et al.Nonsteroidal anti-inflammatory drug treatment for postoperative pericardial effusion: a multicenter randomized, double-blind trial. Ann Intern Med 2010;152:137-43. https://doi.org/10.7236/0034-4819-152-3-20102020-00004

602.Meurin P,Lelay-Kubas P,S.pereira P,Haperia P,Bavy P,Iliou MC,et al.Colchicine for post-operative pericardial effusion: a multicentre, double-blind, randomised controlled trial.Hear 2015;101711-11-6 https://doi.org/10.1136/heartjnl-2015-307827

603. Meurin P, Weber H, Renaud N, Larrazet F, Tabet JY, Demolis P, et al. Evolution of the postoperative pericardial perfusion after day 15: the problem of the late tamponade.Chest 2004:125:218-2-7. https://doi.org/10.1378/chest.125.6.2182

604. Andreis A, Imao M, Giusteco A, Adler Y, De Ferrari GM. Anakinra for constructive pericardits associated with incessant or recurrent pericarditis. Heart 2020;106:1561-5.https://doi.org/10.1136/heartjnl-2020-316898

605. Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentjevich I, et al. Classification criteria for autoinflammatory recurrent fessers. Ann Rheum Dis 2019;78:1025-32.https://doi.org/10.1136/annrheumdis-2019-215048

606. Sagrista-Sauleda, J., Barrabé J.A, Permermany-Miralda G, Soler-Soler J. Purient pericar-dits review of a 20-year experience in a general hospital. J Am Coll Cardiol 1993;22:1661-5.https://doi.org/10.1016/002-9343(79)90523-c

607.Rubin RH, MoellerRC. Clinical, microbiologic and therapeutic aspects of purulent pericardias. Am MJ 1957;59:68-78. https://doi.org/10.1016/0002-9343(75)90323-x-100817-55. https://doi.org/10.1016/0002-9343(75)90323-x

608. Brook J, Frazier H. Microblic of acute purlar pericardits. A 12-year experience in a military hospital. Arch Inten Med 1996;156:1857-60. https://doi.org/10.1001/architeu.1996.0044015011313

96.Wiyab Heu, Chao Oya, Wileyson CS,Kakia A, Awatedu AA, Ristic A, et al. A system-atic review of the efficacy of intrapericardial fibrinolysis in patients with peri-cardial effusion. Int J Cardiol 2018;250:223-8.https://doi.org/10.1016/j.ijcard.2017.10.049

610.Augustin P,Desmand M, Mordant P, Lasocki S, Maury J-M, Heming N,et al. Clinical re-view: intraperarial fibrinolysis in management of purulent pericarditis. Crit Care 2011;15:220.https://doi.org/10.1186/cc10022

611.Imazio M,Brucato A,Cemin A,Cernin R,Ferrua S,Belli R,Maestroni S,et al. Colchicine for re-current pericitisardins(CORITAC): a randomized trial. Ann Intern Med 2011;155:409-14.https://doi.org/10.1061/j.2003-0003-00039

61.Qogatzidis K,Zarogannis G,Aidonidis I,Solenov El,Molyvdas P-A,Gourgoulianis KI et al.Physiology of pericardial fluid production and drainage. Front Physiol 2015;6:62.https://doi.org/10.1399.2018/399.2015.00062

613. Mittyu,Heidenra P.A.,Heidenra P.A.,A small pericardial effusion is a marker of increased mor-tality.Am Heart J 2011;161:152-7.https://doi.org/10.1016/j.ahj.2010.10.007162.0006

614. Corey GR,Campbell PT, Van Trigt P, Kenney RT, O'Connor CM, Sheikh KH, et al.Etiology of large pericardial effusions. Am J Med 1993;95:209-13. https://doi.org/10.1016/s0002-9343(9)93/00262-n

615. Sagrista-Saaledu J.,Mercé J.,Cermany-Meriralda G.,Soler-Soler J.,Clinical clues to the causes of large pericardial effusions. Am J Med 2000;109:95-101. https://doi.org/10.1016/s0002-9343(0004)00459-9

616. Levy P-Y,Corey R, Berger P, Habib G, Bonnet J-L, Levy S, et al. Etiologic diagnosis of 204 pericardial effusions. Medicine(Baltimore) 2003;82:385-91. https://doi.org/10.10971/00.0010001574.54295.73

617. Ma W,Lu J,Zeng Y,Zeng H,Zeng Y,Ye et al.Causes of moderate to large peri-cardial effusion requiring pericardiotensis in 140 Han Chinese patients. Herz 2012;37:183-7.https://doi.org/10.1017/s00059-011-3428-5

618.Adallahar R,Atar S.Seltin and characteristics of large symptomatic pericardial effu-in a community in hospital theory. QJM 2014;107:363-8. https://doi.org/10.1093/jogh/tcd 2015/2027.105.99

6197.Ry.,CL.Minor MA, Brookhart M, Choudhry NK. Does this patient with a pericardial effusion have cardiac trapamotele? JAMA 2007;297:1810-8. https://doi.org/10.1001/jama.2977.16.1810

620. Cremer PC,Kumar A,Kontias A,Tan CD,Rodriguez ER,Imazio M,et al.Complicated pericarditis: understanding risk factors and pathophysiology to inform imaging and treatment.J Am Coll Cardiol 2016:68:2311-28. https://doi.org/10.1016/j.jacc.2016.07.785

62.Lazaros G. Antonopoulos S, Lazarou E, Vlachopoulos C, Foukarakis E, Androulakis A,et al. Long-term outcome of pericardial drainage in cases of chronic, large, hemo-dynamically insignificant, c- reactive protein negative, idiopathic pericardial effusions.Am J Cardiol 2020;126:89:93.https://doi.org/10.1016/j.amjcard.2020.03.035

62. Lazarros L,G.,Okonomouov A, Oznauridis K, Vlachopoulos C, Vogiatz G,et al. Recurrence of pericardial effusion after pericardiocentesis: does catheter-induced acute pericardial inflammation play a role? Am J Med Sci 2021;361:676-8.https://doi.org/10.1016/j.amjms.2020.10.012

ESC Guidelines

62. Buoro,S. Bottenti, E. Cerriotti F, Simon C, Cugola D, Seghezzi M, et al. What is the nor-mal composition of pericardial fluid: Heart 2021:10874-190.https://doi.org/10.1136/heartjni-2020-317966

62. Imaxio M. Biono A, Ricdo B, Dofini M, Bfinu P, Brucata E, Brucato A. Contemporary bio-chemical analysis of normal pericardial fluid. Heart 2020;106:541-4.https://doi.org/10.1136/heartjnl-2018-314574

625.Imzio M.Lazlosa,G Valiente A Carriu N3o Caragini,Moglioli S,Favet us et al:Outcomes of idiopathic chronic large pericardial effusion. Heart 2019;105:477-81.https://doi.org/10.101136/heartjnl-2018-313532

627. Frohlich GM, Keller S, Pchirdne F, Wolfum M, Orankan M, Falk et al.Che al Haymodynamically irrelevant pericardial effusion is associated with increased mortality in patients with chronic heart failure. Eur. Heart 2013;34:1414-23.https://doi.org/10.1039/eurieft/het006

627. Porta-Sanchez A, Sagrta-Sauleda J, Ferreira-Gonzalez I, Torsferan-Nadez A,Roca-Luque I, Garcia-Dorada D. Constrictive pericardiest: etologic spectrum, pat-terns of clinical presentation, prognostic factors, and long-term-up. Rev Esp Cardiol(Engl) Edl 2015;68:1092-100.https://doi.org/10.1016/j.rec.2014.12018.2018.

628.Luoh Oh,Shu K,Schaff HV,Daniowel G,Kahmeney,DW.Seward J,B.et al.Constructive pericardin is the modern era: evolving clinical spectrum and impact on outcome after pericardidomy. Circulation 1999;100:1380-6.https://doi.org/10.1161/01/cir.1001.1380

627. Bertog SC,Thamborais Skar,Pizuk,Shechenko A,Pzodun V,Houghting PL,et al.Constructive pericardiostic: etiology of cause-specific survival after pericardiict-omy.J Am Coll Cardiol 2004;4345-52.https://doi.org/10.1016/j.jacc.2003.11.048

630.Myutaba AK,Balkaran S,Cloete,R du Plessis N,Badri M,Brink J,et al.Constructive cardiarysic during pericarctomy at Groote Schur Hospital, Cape Town, South Africa: causes and perioperative outcomes in the HIV era(1990-2012).J Thoroc Cardiovasc Surg 2014;148:3058-65e.1 https://doi.org/10.1016/j.tcs.2014.07.065

61. Yang,Ji Xang,W.He R,Zhang P.Tuberculous constructive pericentricis: arformed'armardet's QM. 2024:147:69-80. https://doi.org/10.1016/j.tjcs4.2013.78

63. Welch TD, Ling LH, Reespin A, Resavean N, Wisse H, Lahr BD, et al.Echocardiographic diagnosis of constricative periodic callus: Mayo Clinic criteria. Circ Cardiovascular Imaging 2014;75:326-419.https://doi.org/10.1161/CRCIMAGNING.113.01613

633. Talre DR, Nishimura RA, Oh JK, Holmes DR. Constrictive pericarditis in the modern criteria of novel criteria for diagnosis in the cardiac catheterization laboratory. J Am Coll Cardiol 2008;51:315-9. https://doi.org/10.1016/j.jacc.2007.09.039

64. Qramuddin S, Alkharabshe SK, Sato K, Kumar A, Cremer PC, Chetrit M, et al.Differentiating constriction from restriction(from the Mayo Cell: Neurochic echocardiographic)Jermi.A) Cardiol 2019;124:932-8.https://doi.org/10.1016/j.jaccard.2019.06.002

635.Saito T.,Fukushima S, Yamasaki T., Kawamoto N., TadoroKo N., Kakuta T, et al.Pericardectomy for constructive pericardits in a single Japanese center of 20 years of ex-perience. Gen Thorac Cardiovasc Surg 2022:70:430-8. https://doi.org/10.1007/s11748-021-01718-x

636.Chai MS.Jong,Oh Ds JK,Chang S,A.P.,Sang S,Lang Sng. Long-term results of radical pericardiectomy for constructive pericarditis in Korean population. J Cardiothoroc Surg 2019:14:32.https://doi.org/10.1166/1319709-019-0845-7

637. George J,Tarnout Agnakis J, Beaty CJ, Caikin, PaAMgira AT, Conte N, Conte J. Contre 2010;Amit Conrolidis 2004;44:45-51,https://doi.org/10.1016/j.achasur 2012.0379

638.Tzani A, Dourelis A, Tzoumasi B, CaVE A, Kilcomic A, Paunbari G, Letn 成e.Li-Meta-analysis of population characteristics and outcomes of patients undergoing per-cardiatry for constructive pericarditis. Am J Cardiol 2021:10.0133

9. Ganzia Z, Prakash A, Namburi N, Johnson B, Timsina L, Lee LS. Fteen-year experience perichardicity at a tertiary referral center. J Cardiorhoc Surg 2021;16:180.https://doi.org/10.1186/s13019-021-01561-4

640.Gilmarpe Ela,Stapul,M.DyRC,Calserne JO,Loyd et al. J et al.2010 aerien-ence with isolated pericardiectomy: analysis of indications and Joc. Thorac Cardiovascular Surg 2016;152:448-58.https://doi.org/10.1016/j.jtcvs.2016.03.098

41. Ntsneke, M19, Shey Wysonge C, Commerford PJ, Mayosis BM. The prevalence out-come of fulactive constructive pericarditis: a systematic review of the literature.Cardioys J Afr 2012:23:281-5.https://doi.org/10.5830/CV/JA1-2011-072

642. The Vathreathas T, Kimson A, KLai R, Paul Jusek R, Leich S, et al. Sex and age char-acteristics in acute or chronic myocarditis, a descriptive, multicenter cohort.JACC Adv 2024;3:100857.https://doi.org/10.1016/j.jaccad.2024.100857

Kanaoka K,Oonue K,Tersaki S,Kanano T,Nakai M,Sumita Y,et al.Features and out-comes of histologically proven myocarditis with fulmanent presentation. Circulation 2022:146:1253-33.https://doi.org/10.1016/j.CircLACATIONAHA.12:1058869

644. Conte Leon, OAmmirati, I Amrazio I, Mbrucato A. Incidence of myocarditis and peri-carditis considered as separate clinical events over the years and SARS-Cv2 vac-cration in adults and children. Eur J Intern Med 2023;115:140-2 https://doi.org/10.1016/j.eijm.2023.06.002

645.Klugman D,Berger JT,Sable CA,He J,Khandelwal SG,Slonim AD.Pediatric patients hospitalized with myocarditis: a multi-institutional analysis. Pedorax Cardiol 2010:322-8.https://doi.org/10.1007/s20046-009-9589-9

646.Pitak B, Ogen-Rhein B, Schubert S, Reneker K, Wiegand B, Goecker D, et al.Cardiovascular magnetic resonance in children with suspected myocarditis current:

practice and applicability of adult protocols. Cardiol Young 2022:32:1957-65. https://doi.org/10.1017/51074951121005291

647. Peng DM, Kwiatkowski DM, Lasa JJ, Zhang W, Banerjee M, Mikesell K, et al.Contemporary care and outcomes of critically-ill children with clinically diagnosed myocarditis. Cardi J. Fail 2023;30:350-8. https://doi.org/10.1016/j.cardfail.2023.04.010

648.Schubert S, Ogen-Rhein B, Boehme N, Weigelt A, Wagner R, Müller G, et al. Severe heart failure and the need for mechanical circulatory support and heart transplantation in pediatric patients with myocarditis: results from the prospective multicenter region'MYKKE. Pediatr Transplant 2019;23:e13548. https://doi.org/10.1111/petr.13548

Matsuura H.C.,Hfai S.Jia S.,Ogawa S,Wakki K,Kaneko M.et al.Clinical features of acute and fulminant myocardits in children-2nd Nationwide Survey by Japanese Society of Pediatr Cardiology and Cardiac Surgery. Circ J 2016:80:2362-8. https://doi.org/10.1253/circj.CJ-16-0234

1520. Yao Q.Zan, SChin Zocortoid in anti-inflammatory treatment of pediatric acute myo-carditis: a systematic review and meta-analysis. It J Pediatr 2023;49:30.https://doi.org/10.1186/s13052-023-01423-w

651.Camargo PR,Snitcosky R,da Luz Pl,Mazzier R,Higuchi ML,Rati M,et al.Favorable effects of immunosuppressive therapy in children with dilated cardiomyopathy and ac-tive myocarditis. Pediatr Cardiol 1995;16:61-8.https://doi.org/10.1007/BF00796819

652. Izak ZU,Patel N,Sadullah N,Tasneem H,Thaweren H,Talpur S.Acute viral myocar-ditis role of immunosuppression: a prospective randomised study. Cardiol Young 2010;20:509-15.https://doi.org/10.1017/S1047951110000594

633. Lin M.S,Tseng Y-H.Chen M.-Y.Chem Stai M.-H.Chen M.-P.C.,et al. In-hospital and post-discharge outcomes of pediatric acute myocarditis underwent after high-dose steroid or intravenous immunoglobulin therapy. BMC Cardiovasc Disord 2019;19:10.https://doi.org/10.1186/s12872-018-0981-3

645. Butts RJ,Boyle GJ,Deshande SR,Gambetta K,Knecht KR,Prada-Ruiz CA,et al.Characteristics of clinically diagnosed pediatric myocarditis in a contemporary multi-center cohort. Pediatr Cardiol 2017;38:1175-82. https://doi.org/10.1007/s00246-017-1638-1

655. Huang,Xu X. K,Shui X. Intravenous immunoglobulin therapy for acute myocarditis in children and adults. Int Heart J 2019;60:359-65. https://doi.org/10.1015/ghi18-199

656. Imazo M.,Brucato A,Phymakers N,Breda L,Balca C,Gantar L,Calabini T,et al.Recurrent pericitants in children and adolescents: a multicentre cohort study. J Cardiovasc Med(Hogerstown) 2016;17:707-12.https://doi.org/10.2459/JCM.0000000000030003

51.Amsabri,M.Elayed Sels,Bromy AB,Aboelmag K,Ayyad M,AqeeqBF,et al.Efficacy and safety of collicine in pediatricic pericarditis: a systematic review and future direc-tions.Pedorat Cardiol 2024;https://doi.org/10.1007/s00246-02436-06-6

68 Caorsi R,Insalaco A,Bobiref,Martini G,Cattalini M,Chinali M,et al. Pediatric recurrent pericarditis: appropriateness of the standard of care and response to IL-1 blockade.J Pedorat 2023.256:18-26.eB.https://doi.org/10.1016/j.jpeds.2022.11.0348

659. Sunohara D, Motokoh S, Haagman T, Esibawa S, Okada A, Ando H, et al. Biopsy detection and clinical management of acute lymphocytic myocarditis in pregnancy.J Cardiol Cases 2019:2016-17:4. https://doi.org/10.1016/j.jccase.2019.07.010

660. Veronese G,Noni S,Cannata A,Aresta F,Olivier G,Montrasio E,et al.Fulminant lymphocarity myocardits during pregnancy treated with temporary mechanical circu-latory supports and aggressive immunosuppression. Circ Heart Fail 2022;15:e009810.https://doi.org/10.1161/CIRCHEARTFAILURE.122.009810

661. Moore CR, Bierci SM, Roseh T, Schelton TN, Martin JN. Lymphocytic myocarditis presenting as nausea, omitting, and hepatic dysfunction in the first trimester of preg-nancy. Obstet Gynecol 2006;108:815-7.https://doi.org/10.1097/01.AOG000021616.91685.52

66. Marceau A, McGinnis JM, Derakhshan F, Liu Ya, Sathanhanan G, Sosa Cazales AC,et al. Interdisciplinary approach to an unusual case of myocarditis in pregnancy. QC Open 2019;10:1-53. https://doi.org/10.1016/j.cqco.2019.02.001

63.Mova R, Brown SB, Morris DL, Figueredo VM. Anakina for myocarditis in juvenile idiopathic arthritis. Tex Heart Inst J 2013;40:623-5.

646. Brucut A, Pluymeraks N, Tombetti R, Lampello S, Maestroni S, Lucianetti M, et al.Management of idiopathic recurrent pericarditis during pregnancy. Int J Cardiol 2019;282:60-5.https://doi.org/10.1016/j.ijcard.2019.02.003

656. Putam A, Rasanen J, Airpakinen K, Vu-Poulteenho OJ, Laatikainen T, Changes in ma-ternal heart dimensions and plasma atrial natriuretic peptide levels in the early puer-perum of normal and pre-eclamptic pregnancies. Br J Obstet Gynecol 1996;10398-982.https://doi.org/10.1111/j.1471-0528.1996.tb09548.x

666: Griztaz-Rogzovk V,Ros-Hoesselink|W,Buaversachs J,Blomstrom-Lundqvist C,CifkováR,De Bonis M,et al.2018 ESC Guidelines for the management of cardiovascular dis-eases during pregnancy. Eur Heart J 2018:39:3165-241. https://doi.org/10.1093/eurheurj400y

667. Schreier K, Schreirman M, Russell MD, Dey M, Flint J, Allen A, et al. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: co-morbidity medications used in rheumatology practice. Rheumatology 2023;62:89-e104.https://doi.org/10.1093/rheumatology/keac552

668. Sammarintan, R. Bongen, R. Wiegan, K. Wiegand, B. Decker, B. et al., 2010. MB, Chakravarty EE, Chambers, C. Clowse MEB, Lockshin MD,et al.2020 American College of Rheumatology Guideline for the management

ESC Guidelines

of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol 2020;72:529-56.https://doi.org/10.1002/art.41191

669. Gotestam Skoren C, Hoeltzenbein M Tincani A,Fischer-Betz R,Elfante E,Chambers C,et al.The EULAR points to consider for use of antirheumatic drugs before preg-nancy, and during pregnancy and lactation. Ann Rheum Dis 2016;75:795-810.https://doi.org/10.1136/annrheumds-2015-208840

670.Russell MD,Dey M,Flint J,Davie P,Allen A,Crossley A,et al. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immu-nomodulatory anti-rheumatic drugs and corticosteroids. Rheumatology 2023;62:e48-e88.https://doi.org/10.1093/rheumatology/keac551

671. Bizzi E,Cavaleri F,Mascolo R,Conte E,Maggiolini S,Decarlini CC,et al.Recurrent peri-carditis in older adults: clinical and laboratory features and outcome.J Am Geriatr Soc 2024;72:3467-75.https://doi.org/10.1111/jgs.19150

672. Pasina L,Brucato AL,Falcone C,Cucchi E,Bresciani A,Sottocorno M,et al.Medication non-adherence among elderly patients newly discharged and receiving polypharmacy.Drugs Aging 2014;31:283-9.https://doi.org/10.1007/s40266-014-0163-7

673. Peretto G, De Luca G, Camporhio C, Palmisano A, Busnardo E, Sartorelli S, et al.Telemedicine in myocardialis: evolution of a mutidisciplinary'disease unit' at the time of COVID-19 pandemic. Am Heart J 2020:229:121-6. https://doi.org/10.1016/j.ahj.2020.07.015

674. Aldajani A, Berubé M, Mardigyan V. How and why to set up a pericardial disease clinic.Can J Cardiol 2023;39:1149-51. https://doi.org/10.1016/j.cja.2023.04.028

675. Mizia-Stec K, Charron P, Gemno Blanes JR, Elliott P, Kaski JP, Maggioni AP, et al.Current use of cardiac magnetic resonance in tertiary referral centres for the diagnosis of cardiomyopathy; the ESC ERP cardiomyopathy/mycarditis registry. Eur Heart J Cardiovasc Imaging 2021;22:781-9.https://doi.org/10.1093/ehjcji/jeaa329

676. Kaski JP, Norrish G, Gimo Blanes JR, Charron P, Elliott P, Tavazzi L, et al.Cardiomyopathies in children and adolescents: aetiology, management, and outcomes in the European Society of Cardiology EUROObservational Research Programme Cardiomyopathy and Myocarditis Registry. Eur Heart J 2024;45:1443-54. https://doi.org/10.1093/eurheart/ehae109

表 1
Level of evidence A	Data derived from multiple randomized clinical trials or meta-analyses.
Level of evidence B	Data derived from a single randomized clinical trial or large non-randomized studies.
Level of evidence C	Consensus of opinion of the experts and/or small studies, retrospective studies, registries.

表 2
Terminology	Definition
IMPS	Umbrella term for inflammatory myocardial and pericardial syndromes
Myopericarditis	Predominant pericarditisa
Perimyocarditis	Predominant myocarditisb
Acute myocarditis	Duration of symptoms ≤4 weeks Fulminant if: · Acute onset28 and haemodynamically unstable patients requiring inotropes or mechanical circulatory support
Complicated myocarditis	AM and≥1 of the following:28
Complicated myocarditis	● LVEF<50% on echocardiogram
● Sustained ventricular arrhythmias
● Sustained ventricular arrhythmias	● Advanced heart block
● Heart failure
● Cardiogenic shock
Duration of symptoms≤4 weeks
Duration of symptoms>4 weeks to ≤3 months
Subacute/incessant	Duration of symptoms>4 weeks to ≤3 months
Chronic myocarditis/	Duration of symptoms>3 months
pericarditis	Chronic myocarditis in association with cardiac
cardiomyopathy	dysfunction and ventricular remodelling with clinical phenotype of hypokinetic, either dilated or non-dilated cardiomyopathy with/without arrhythmogenic substrate
Recurrent myocarditis/ pericarditis	New symptoms or disease activity after clinical remission
Recurrent myocarditis/ pericarditis	Regression/absence of symptoms, normalization of ECG, biomarkers, imaging abnormalities(echocardiography and CMR)
Remission with residuals	Regression/absence of symptoms, persistence
Remission with residuals	of abnormalities on ECG, biomarkers and/or imaging(functional and/or structural abnormalities in echocardiography or CMR)

表 3
IMPS	IMPS	IMPS
If diagnostic criteria for myocarditis and/or pericarditis are fulfilled ${}^{8}$
Definite	Myocarditis	Pericarditis
Definite	Clinical presentation ${}^{b}$ and CMR- or EMB-proven	Clinical presentation ${}^{b}$ with>1 additional criterion
Possible	Clinical presentation ${}^{b}$ with at least 1 additional criterion CMR- or EMB-uncertain or not available	Clinical presentation ${}^{b}$ with 1 additional criterion
Unlikely/rejected	Only clinical presentation ${}^{b}$ without additional criteria	Only clinical presentation ${}^{b}$ without additional criteria
Additional criteria beyond clinical presentations ${}^{b}$
Myocarditis Pericarditis
Clinical ${}^{b}$	Non-specific findings	Pericardial rubs
ECG ${}^{c}$	ST-T changes	PR depression,widespread ST-segment elevation
Biomarkers	Troponin elevation	C-reactive protein elevation
Imaging ${}^{d}$	Abnormal strain, wall motion,reduced EF Myocardial oedema and/or LGE(CMR findings)	New or worsening pericardial effusion Pericardial oedema and/or LGE(CMR findings)

表 4
Term	Predominant inflammatory cells	Myocyte necrosis	Infections PCR positive(viruses, etc.)
Active lymphocytic myocarditis	CD3+ T lymphocytes >7/mm2, CD68+ macrophages	yes	yes/no
Persistent lymphocytic myocarditis	CD3+ T lymphocytes >7/mm2, CD68+ macrophages	yes	yes/no
Resolved lymphocytic myocarditis	-	no	yes/no
Eosinophilic myocarditis (acute stage)	Eosinophils, CD3+ T lymphocytes, CD68+ macrophages	yes	yes/no
Giant-cell myocarditis (acute stage)	Eosinophils, CD68+ giant cells, CD3+ T lymphocytes, CD68+ macrophages	yes	no
Sarccoidosis	CD68+ giant cells, granuloma, CD3+ T lymphocytes, CD68+ macrophages	yes/no	no

表 5
Myocarditis	Pericarditis
Recent or concomitant flu-like syndrome or gastroenteritis	Recent or concomitant flu-like syndrome or gastroenteritis
Infarct-like chest pain	Pleuritic/infarct-like chest pain
Palpitations	Right HF symptoms and signs of constriction
HF symptoms	Fever
ECG changes	Pericardial rubs
Ventricular arrhythmias(isolated, complex) Syncope	C-reactive protein elevation
Haemodynamic instability	Pericardial effusion
Elevated markers of myocardial lesion(hs-Tn, CK-MB elevation)	Pleural effusion
Elevated markers of HF(NT-proBNP)	Polyserositis
Abnormal wall motion, increased wall thickness and/or impaired systolic function	CMR imaging with pericardial oedema and/or LGE
on imaging
CMR imaging with myocardial oedema and/or LGE

表 6
Risk	High risk	Intermediate risk	Low risk
Myocarditis	● Acute HF/cardiogenic shock ● Dyspnoea NYHA III-IV refractory to medical therapy ● Cardiac arrest/syncopea ● Ventricular fibrillation/sustained ventricular tachycardia ● High-level AV blocka	● New/progressive dyspnoea ● Non-sustained ventricular arrhythmias ● Persistent release or relapsing troponin	Stable symptoms or oligosymptomatic
	Imaging criteria:
	● Newly reduced LVEF(<40%)° ● Extensive LGE on CMR° ● Preserved LVEF(≥50%) and/LGE≥2 segments on CMR	Imaging criteria:	Imaging criteria:
Pericarditis	● Signs and symptoms of cardiac tamponade ● Fever(≥38°C) ● Effusive-constrictive pericarditis ● Failure of NSAID therapy ● Incissant pericarditis	● Signs and symptoms of right HF	● Response to adequate therapy within 1-2 weeks
	● Fast and/or LGE≥2 segments on CMR
	Imaging criteria:		Imaging criteria:
	● Large PEff(>20 mm end-diastole) ● Cardiac tamponade ● Extensive pericardial LGE on CMR	● Moderate-large PEff (10-20 mm end-diastole) ● Constrictive pericardial LGE on CMR	● Absence or mild PEff ● Absence of pericardial LGE on CMR

表 7
Common causes(in order of relative frequency):
(1)	Neoplasm/malignancy
(2)	latrogenic/trauma
(3)	Pericarditis
(4)	Tuberculosis(most common in developing countries)
Less common causes(in order of relative frequency):
(1)	Collagen vascular diseases(systemic lupus erythematosus,rheumatoid
arthritis, scleroderma)
(2)	Pericardial injury syndrome
(3)	Acute myocardial infarction
(4)	Aortic dissection
(5)	Uraemia
(6)	Bacterial infection
(7)	Pneumopericardum

表 8
Criteria for triage for patients with pericardial effusion at risk for progression to cardiac tamponade
Aetiology	Clinical presentation	Imaging
Malignant disease	2	Dyspnoea/tachypnoea	1
Tuberculosis	2	Orthopnoea	3
Recent radiotherapy	1	Hypotension(CBP<95 mmHg)	0.5
Recent viral infection	1	Progressive sinus tachycardia	1
Recurrent Peff	1	Oliguria	1
Chronic terminal renal failure	1	Pulsus paradoxus(>10 mmHg)	2
Immunosuppression	1	Pericardial chest pain	0.5
Dysthyroidism	-1	Pericardial friction rub	0.5
Systemic autoimmune disease	-1	Rapid worsening of symptoms	2
		Slow disease evolution	-1
			Mitral/tricuspid respiratory flow variations
			Swinging heart

表 10
Recommendations	Classa	Levelb
Complete clinical evaluation, including history, physical examination, chest X-ray, biomarkers,ECG, and echocardiography is recommended in all patients with a suspicion of myocarditis and/or pericarditis for the initial diagnostic assessment.	1	C
CMR is recommended in patients with the clinical suspicion of myocarditis(using updated LL criteria)30 and/or pericarditis for the non-invasive diagnosis of inflammatory reaction.110,115,129	1	B
Hospital admission is recommended for patients with high-risk pericarditis for monitoring and treatment.	1	B
Hospital admission is recommended for patients treatment.105,130	1	C
Hospital admission is recommended for patients with moderate- to high-risk myocarditis for monitoring and treatment.	1	C
EMB° is recommended in patients with high-risk and/or haemodynamic instability, and/or in patients with intermediate-risk myocarditis	1	C
not responding to conventional therapy in order to detect a specific histologic subtype and to assess the presence of viral genome for treatment.34,63,73,131
Invasive coronary angiography or coronary CT, depending on clinical likelihood, is recommended in patients with IMPS if an acute coronary syndrome is suspected to rule out obstructive coronary artery disease.	1	C
Hospital admission should be considered for patients with low-risk myocarditis for monitoring and treatment.	11a	C
Pericardial or epicardial biopsy may be considered in relapsing pericardial effusion as part of the diagnostic work-up when the diagnosis cannot be reached with multimodality imaging and laboratory examinations.	11b	C
Routine serology is not recommended in patients with myocarditis and/or pericarditis for the evaluation of viral aetiology except for hepatitis C,HIV, and Lyme disease.	Ⅲ	C
CMR, cardiovascular magnetic resonance; CT, computed tomography; ECG, electrocardiogram; EMB, endomyocardial biopsy; HIV, human immunodeficiency virus; hs-Tnl, high-sensitivity troponin l; hs-TnT, high-sensitivity troponin T; IMPS inflammatory myopericardy syndrome; LL, Lake Louise; NT-proBNP, N-terminal prohormone of brain natriuretic peptide. ${}^{a}$ Class of recommendation.
${}^{b}$ Level of evidence.
‘Including hs-TnT or hs-TnT, C-reactive protein, NT-proBNP.
${}^{a}$ Scee Table 7.
It is recommended to obtain family history including pedigrees in cases of recurrent IMPS to provide clues to the underlying aetiology, determine inheritance pattern, and identify relatives at risk.		C
Genetic testing should be considered in patients with definite myocarditis/percarditis in cases of: ${}^{50,51,64,94,150}$
● family history of IMPS, inherited or suspected cardiomyopathy
●severe ventricular arrhythmia
● significant left/right LGE(e.g. ring-like pattern or	lla	B
septal LGE) or persistent LVEF systolic dysfunction
● recurrent myocarditis or persistent troponin
elevation
● recurrent pericarditis with an inflammatory
phenotype,refractory to conventional treatment
with the aim to detect an underlying genetic cause.

表 11
Onset	Acute(≤4 weeks)
Onset	Subacute(>4 weeks to ≤3 months)
Chronic(>3 months)
Sizea	Mild: <10mm
Sizea	Moderate: 10-20 mm
Distribution	Large: >20 mm
Composition	Circumferential/loculated
*Maximal end-diastolic diameter

表 12
Recommendations	Classa	Levelb
Myocarditis
CMR is recommended in patients with suspected myocardial diagnosis and to determine the cause of acute myocardial injury, including assessment of oedema, ischaemia, and necrosis/fibrosis/scarring. 115,164,169-183		B
CMR is recommended for follow-up at least within the first 6 months in patients with myocarditis to identify a healed or ongoing process, for risk stratification and personalized therapy, and to enable a return to exercise.10,62,184-186		C
Pericarditis
CMR is recommended in patients with suspected pericarditis when a diagnosis cannot be made using clinical criteria to assess evidence of pericardial thickening, oedema,LGE, and to assess the persistence of disease during follow-up in selected cases.110,129,165,187-194		B
CT is recommended to evaluate pericardial thickness, calcifications, masses, and loculated pericardial effusions, as well as concomitant pleuropulmonary diseases and chest abnormalities.	$\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$ $\mid$	C
Carb-free 18F-FDG-PET or 18F-FDG-PET/CT should be considered for the diagnostic work-up in patients with suspected myocarditis and/or pericarditis in whom echocardiography and CMR are inconclusive for the clinical diagnosis.201,206	lla	C

表 15
Criteria	Parameters for reporting
Histology(paraffin-embedded EMB,at least 3 EMB)	Presence and extent of cardiomyocyte necrosis, inflammation, fibrosis
Immunohstology (paraffin-embedded EMB, at least 3 myocardial samples)	Presence, extent, localization, and typing of immune cells in the myocardium: CD3+ T lymphocytes, CD68+ macrophages (≥14 leucocytes/mm2 with T lymphocytes≥7 cells/mm),10 HLA-DR expression in immune cells and endothelial cells
Molecular pathology [infections: RNAlater, snap-frozen tissue(1-2 EMB), paraffin-embedded EMB]	Presence, typing, and quantification of DNA/RNA from infectious agents by q(RT)-PCR Viruses: mainly enteroviruses, parvovirus B19, human herpesvirus 6, Epstein-Barr virus; Borrelia spp., Trypanosoma cruza q(RT)-PCR for detection of systemic infections
Molecular pathology(genetics: RNAlater, frozen tissue, paraffin-embedded EMB, blood)	NGS for detection of pathogenic variants in cardiac genes, traditionally associated with cardiomyopathies (especially desmosomal and sarcomeric/ cytoskeletal genes)

表 16
Recommendations	Classa	Levelb
Comprehensive autopsy is recommended in all patients<50 years of age with SCD to evaluate the presence of acute myocardialitis as a cause and to detect potential underlying inherited cardiac diseases. 87,243-246c	$\begin{array}{l}\\ \\ \\ \\ \\ \end{array}$	$\begin{array}{l}$ B
Retaining samples suitable for DNA extraction and consulting a cardiac pathologist is recommended in cases of SCD, when an inherited cause is suspected, or the cause of death remains unexplained.243,247c	$\begin{array}{l}\\ \\ \\ \\ \end{array}$	B
Electro-anatomical mapping should be considered in cases of suspected myocarditis(especially cardiac	la	C
sarcoidosis) to guide endomyocardial biopsy.	la	C

表 18
Lymphocytic myocarditis (virus-negative)
1st line therapy
2nd line therapy
2nd line therapy
3rd line therapy
Eosinophilic myocarditis
1st line therapy
2nd line therapy
3rd line therapy
Giant-cell myocarditis
1st line therapy
1st line therapy
2nd line therapy
3rd line therapy
Cardiac sarcoidosis
1st line therapy
2nd line therapy
1st line therapy
Cardiac sarcoidosis
1st line therapy
2nd line therapy
2nd line therapy
1st line therapy
Lyme carditis
1st line therapy
2nd line therapy
2nd line therapy
2nd line therapy
2nd line therapy
2nd line therapy
2nd line therapy
Lyme carditis
1st line therapy
2nd line therapy
2nd line therapy
2nd line therapy
2nd line therapy
Chagas disease
1st line therapy
2nd line therapy
2nd line therapy
2nd line therapy
3rd line therapy
Chagas disease
1st line therapy
2nd line therapy
2nd line therapy
3rd line therapy

表 19
ICI-induced myocarditis
1st line therapy	Withdraw ICI, reassess Non-severe: methyl/prednisolone 500-1000 mg/day x 3 days, then taper with oral prednisone Severe: i.v. methyl/prednisolone 7-14 mg/kg/day x 3 days, then 1 mg/kg/day
2nd line therapy	If no response in 24-48 h: myophercenoflate mofefetl, ATG& abatacept', alemutuzumab
3rd line therapy	Infixlipm' or adalimumkab', rituximab

表 20
Recommendations	Classa	Levelb
Management of symptoms
NSAIDs(together with proton pump inhibition)
should be considered in patients with associated symptoms of pericarditis to reduce symptoms.	lla	C
Colchicine should be considered in patients with myopericarditis to reduce recurrences.	lla	B
Management of heart failure
Adherence to the ESC HF guidelines is recommended in cases of myocarditis with LV systolic dysfunction and/or HF to reduce symptoms and to improve LV function.	1	C
HF therapy should be considered in patients with myocarditis and LV systolic dysfunction for at least 6 months upon complete LV functional recovery to stabilize LV function.	lla	C
Management of arrhythmias
β-Blockers, with a continuation for at least 6 months, should be considered in patients with acute myocarditis, especially those with troponin elevation, to control symptoms and prevent arrhythmias.	lla	C
Anti-arrhythmic treatment should be considered in post-myocarditis patients with recurrent, symptomatic VT to reduce arrhythmic burden. 58	lla	C
Immunosuppressive therapy
Corticosteroids should be considered in patients with fulminant, non-infectious forms of myocarditis to stabilize the patients.	lla	C

表 21
Corticosteroids may be considered in patients with acute myocarditis with impaired LVEF if refractory to standard HF therapy to stabilize patients.	lb	C
Routine use of immunosuppressive therapy is not recommended in acute myocarditis with preserved	III	C
LV function because no outcome benefit has been shown.

表 22
Therapy	Dosing	Durationa	Taperinga
Aspirinb	750-1000 mg 3 times daily	1-2 weeks	Decrease by 250 mg every 1-2 weeks
lbuprofenb	600-800 mg 3 times daily	1-2 weeks	Decrease by 200 mg every 1-2 weeks
Indomethacin	25-50 mg 3 times daily	1-2 weeks	Decrease by 25 mg every 1-2 weeks
Colchicineb	0.5 mg once daily(<70 kg or severe renal impairment) or 0.5 mg twice daily	3-6 months	Not required
Prednisone	0.2-0.5 mg/kg/day	2-4 weeks	Several months
Treatment for recurrences only:
Azathioprine	Starting with 1 mg/kg/day then gradually increased to 2-3 mg/kg/day	Several months	Several months
IVIG	400-500 mg/kg i.v. daily for 5 days	5 days	Not required
Anakinra	1-2 mg/kg/day up to 100 mg/day in adults	At least 6 months/	Needed(at least 3-6 months)/
Rilonacepc	320 mg once daily followed by 160 mg weekly	>12 months	unknown

表 23
Prednisone	Starting dose 0.20-0.50 mg/ kg/day	Tapering
Prednisone daily dose	>50 mg	10 mg/day every 1-2 weeks
	50-25 mg	5-10 mg/day every 1-2 weeks
	25-15 mg	2.5 mg/day every 2-4 weeks
	<15 mg	1.25-2.5 mg/day every 2-6 weeks

表 24
Recommendations	Classa	Levelb
Colchicine is recommended as first-line therapy in patients with pericarditis as an adjunct to aspirin/NSAID or corticosteroid therapy to reduce subsequent recurrences. ${}^{24,25,108,275-278}$	I	A
Anti-IL-1 agents(akinnra or riloncept) are recommended for patients with recurrent pericarditis after failure of first-line therapies and corticosteroids and elevation of C-reactive protein levels to reduce recurrences and allow corticosteroid withdrawal. ${}^{108,275,282-284}$	I	A
High-dose aspirin or NSAIDs with proton pump inhibitors are recommended as first-line therapy in patients with pericarditis to control symptoms and reduce recurrences. ${}^{291,292}$	I	B
Aβ-blocker should be considered in symptomatic patients, despite full anti-inflammatory therapy, and heart rate at rest>75 b.p.m.in order to improve symptom control. ${}^{274}$	IIa	C
Anti-IL-1 agents(akinnra or riloncept) should be considered in cases of incessant/recurrent pericarditis with evidence of pericardial inflammation on CMR after failure, contraindications, and intolerance to first-line therapies and corticosteroids regardless of C-reactive protein levels to reduce recurrences and allow corticosteroid withdrawal.	IIa	C
Low- to medium-dose° corticosteroids should be considered for patients with pericarditis only in cases of contraindication/failure of aspirin/NSAIDs and colchicine, or when there is a specific indication to control symptoms and reduce recurrences.	IIa	C
Hydroxychloroquine may be considered in patients with recurrent pericarditis refractory to standard therapy(including corticosteroids and anti-IL-1 agents) to prolong recurrence-free survival. 290	IIb	B
Corticosteroids are not recommended as the first option for patients with pericarditis therapy without a specific indication.	III	C
A timely and dedicated Shock Team discussion is recommended in patients with myocarditis in the presence of haemodynamic compromise, to decide on the need for escalation to MCS and to determine a long-term management plan.	I	C
Temporary MCS' should be considered in patients with myocarditis and cardiogenic shock or acute decompensation in chronic myocarditis to stabilize the patients.	lla	C
Pericardiectonesis(echocardiography-,CT-,or fluoroscopy-guided) is recommended for cardiac tamponade, or suspected bacterial or neoplastic pericarditis, or symptomatic moderate to large pericardial effusion despite medical therapy.	1	C
Surgical pericardial drainage is recommended in patients with pericardial effusion when percutaneous pericardiacites is not feasible or with purulent pericardial effusion to allow complete drainage and to prevent constriction.	1	C
Surgical pericro-pericardial window is recommended in patients with relapsing pericardial effusion despite medical therapy.	1	C
Surgical pericardietomy is recommended in patients with chronic pericardietic constriction or persistent constractive pericarditis despite medical therapy to improve symptoms and survival.312,313	1	C
Tricuspid valve repair is recommended in patients with pericardial constriction and severe tricuspid valve regurgitation to improve symptoms and survival.	1	C
Pacing in myocarditis
Temporary transvenous external pacing should be
considered in patients with acute myocarditis and high-degree conduction disorders as a bridge to	IIa	C
recovery.86,317,335

表 29
WCD in myocarditis	WCD in myocarditis
A WCD should be considered for 3-6 months in patients with sustained ventricular arrhythmia during the acute phase of myocarditis as a bridge to	IIa
323,325,327-330
Ablation in myocarditis
Catheter ablation, performed in specialized centres, should be considered in post-myocarditis patients with recurrent symptomatic SMVT or ICD shocks in whom AAD are ineffective, not tolerated, or not desired.58	IIa
ICD in myocarditis
Secondary prevention
ICD implantation is recommended in patients with non-active° myocarditis and haemodynamically not-tolerated sustained VT to prevent	1
SCD.78,79,322,336
ICD implantation should be considered in patients with non-active° myocarditis and haemodynamically tolerated sustained VT to prevent SCD.78,79,322,336	IIa
ICD implantation may be considered in patients with acute myocarditis and sustained VA(VT/VF) in the acute phase to prevent SCD.71,79,89,222,323-325	IIb
ICD implantation may be considered in patients with myocarditis after the acute phase(3-6 months) and persistent risk factors for VAD to prevent	IIb
SCD.93,323,324,336

表 30
Recommendations	Classa	Levelb
Follow-up with clinical assessment, biomarkersc,
ECG,exercise test,Holter-ECG monitoring,
echocardiography,and CMR at least within 6 months
after the index hospitalization is recommended in all
patients with myocarditis to identify a potential
progression or new risk factors.	62
Long-term follow-up is recommended for patients
progression or new complications.28,74
Long-term follow-up is recommended for patients with incessant or recurrent pericarditis to identify a
potential progression and new complications.	1	C

表 31
		Within 1 month	Within 3-6 months	12 months	>1 year and long-term FUa
Clinical evaluation and ECG	Myocarditis	X	X	X	X
	Pericarditis	X	X	X	X
Biomarkers(Tnl,C-reactive protein)	Myocarditis	X	X	(X)	(X)
	Pericarditis	X	X	(X)	(X)
Rhythm (stress and/or Holter-ECG)	Myocarditis	-	X	(X)	(X)
	Pericarditis	-	-	-	-
Imaging myocarditis	TTE	X	X	X°	X°
	CMR	X	X	X°	X°
Imaging pericarditis	TTE	X	X	X°	X
	CMR	(X)^{b}	(X)^{b}	(X)^{d}	(X)^{d}

表 32
Recommendations	Classa	Levelb
EMB is recommended in patients with suspected GCM due to unexplained new-onset HF of up to 2 weeks associated with a normal or dilated left ventricle and new ventricular arrhythmias, second-or third-degree AVB, or failure to respond to usual care within 1 to 2 weeks to initiate specific treatment.402	I	C
Combined immunosuppressive therapy is recommended in patients with a diagnosed GCM.217	I	C

表 33
Diagnosis	Classa	Levelb
Diagnosis
CMR, using tissue characterization techniques, is recommended in patients with suspected CS to assess cardiac inflammation and myocardial involvement.408,421-425	$1$	B
${}^{18}$ F-FDG-PET is recommended for the diagnostic work-up, including detection of inflammation, as well as for follow-up and assessment of therapeutic response in patients with C.426-428	$1$	B
Therapy
ICD implantation is recommended in patients with CS and sustained ventricular arrhythmia(VT/VF) or aborted CA to prevent SCD. ${}^{58,396,416,454,455,466}$	$1$	B
CDI implantation is recommended in patients with CDI implantation is recommended in patients with CS and LVEF≤35% to prevent SCD.	$1$	C

表 34
Recommendations	Classa	Levelb
Diagnostic triage within 24 h is recommended in patients with suspected myocarditis induced by ICI to initiate treatment rapidly.	1	C
Immediate disruption of ICI and administration of high-dosage corticosteroids are recommended in patients with ICI-associated myocarditis in order to stop the inflammatory reaction and stabilize the patient.504	1	C
Second-line immunosuppression treatment should be considered in patients with steroid-refractory ICI-associated myocarditis.501,504	1a	C
Second-line immunosuppression treatment may be considered in patients with fulminant/severe ICI-associated myocarditis.501,504	11b	C
Guideline-directed heart failure treatments are recommended in patients with inflammatory cardiomyopathy to improve and/or stabilize left ventricular function.	I	C
Specific medical therapy for the potentially underlying systemic disease is recommended in inflammatory cardiomyopathy.	I	C
Immunosuppressive therapy, guided by endomyocardial biopsy, should be considered in virus-negative inflammatory cardiomyopathy to suppress the autoimmune response. 34,131,551-555	lla	B

表 36
Recommendations	Classa	Levelb
Diagnosis and treatment of tuberculous pericarditis
Diagnostic pericardicitesis is recommended in all patients with suspected tuberculous pericarditis when diagnosis is not confirmed by non-invasive tests to identify the aetiological agent in pericardial fluid.	1	C
Empirical antuberculosis
recommended in patients living in endemic areas with exudative pericardial effusion after excluding other causes to treat the most likely cause.567,570	1	C
Standard antuberculosis	multidrug treatment for 6 months is recommended in patients with tuberculous pericarditis for the prevention of pericardial constriction.570	1	C
Pericardicey is recommended in patients with tuberculous pericarditis if the condition is not improving or is deteriorating after 4-8 weeks of antituberculosis therapy to change the course of disease.	1	C
Adjunctive steroid therapy is essential to prevent this progression. In addition, two interventions may reduce the incidence of constriction:(i) intrapericardial urokinase; and(ii) high-dose adjunctive prenisolone for 6 weeks. ${}^{569,573}$	In non-endemic areas a pericardial biopsy may be considered in patients with>3 weeks of illness without aetologic diagnosis. Empirical antituberculosis treatment is not recommended in patients living in non-endemic areas.	lla $\qquad$ C

表 37
Recommendations	Classa	Levelb
Pericardiocentesis is recommended for patients with cardiac tamponade to receive symptoms and establish the diagnosis of malignant pericardial effusion.576,583	1	C
Extended pericardial drainage(3-6 days) is recommended in patients with suspected or definite pericardial effusion to prevent effusion	1	B
Cytological analysis of pericardial fluid is recommended in patients with neoplastic pericarditis for the confirmation of malignant pericardial disease.581	1	C
Systemic antineoplastic treatment is recommended in confirmed cases of neoplastic aetiology to treat the primary and secondary metastatic neoplastic involvement.582	1	C
Pericardiocentesis should be considered in patients with moderate to large pericardial effusion to establish the diagnosis of malignant pericardial effusion when the diagnosis cannot be reached by multimodality imaging.584	1a	C
Pericardial or epicardial biopsy may be considered in patients with suspected malignant pericardial disease.584	11b	C
Intraperarial therapy, in agreement with the oncologist, may be considered in cases refractory to systemic antineoplastic treatment.	11b	C
Anti-inflammatory therapy is recommended in patients with PCIs to hasten symptom remission and reduce recurrences.292,600	1	B
IL-1 antagonists are recommended in patients with refractory PCIs to prevent recurrences and progression to constriction.604	1	B
High-dose aspirin is recommended as the first-choice anti-inflammatory therapy for post-myocardial infarction pericarditis and in patients being already on antiplatelet therapy.	1	C
Colchicine, started 48 to 72 h before cardiac surgery, should be considered for 1 month in patients after cardiac surgery for the prevention of PCIS if there are no contraindications and if it is tolerated.594,596	1a	A
Careful follow-up should be considered in patients with PCIs to exclude possible evolution towards constrictive pericardits. ${}^{347}$	1la	C
with PCIs to exclude possible evolution towards constrictive pericardits. ${}^{347}$
Urgent pericardiocentesis and/or a surgical window
is recommended in patients with suspicion of	1	C
purulent pericarditis to establish a diagnosis.	606
Intrapericardial fibrinolysis should be considered in
patients with purulent pericarditis to allow complete
drainage of purulent fluid and to prevent
constriction. 573,610

表 40
Echocardiographic feature	Sensitivity	Specificity
Large pericardial effusion with swinging	n.a.	n.a.
heart
Diastolic collapse of the RA	50%-100%	33%-100%
Duration of diastolic collapse of the RA as a ratio of the cardiac cycle length>0.34	>90%	100%
Diastolic collapse of the RV	48%-100%	72%-100%
Respiratory changes of the mitral E velocity>25%-30%, tricuspid E velocity	n.a.	n.a.
>40%-60%
Inferior vena cava plethora(dilatation >20 mm and <50% reduction of diameter with respiratory phases), as well as hepatic vein dilatation	97%	40%
$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$

表 41
Syndrome	Definition	Therapy
Transient constriction (d.d. permanent constrictive pericarditis, restrictive CMP)	Reversible pattern of constriction following spontaneous recovery or anti-inflammatory therapy	A 3-6 month course of empirical anti-inflammatory medical therapy
Effusive-constrictive pericarditis (d.d. cardiac tamponade, constrictive pericarditis)	Failure of the right atrial pressure to fall by 50% or to a level <10 mmHg after pericardiocentesis May be diagnosed also by non-invasive imaging	Pericardiocentesis followed by medical therapy Surgery for persistent cases
Chronic constriction (d.d. transient constriction, restrictive CMP)	Persistent constriction after 3-6 months	Radical pericardiectomy, medical therapy for advanced cases or high risk of surgery or mixed forms with myocardial involvement

表 42
Recommendations	Classa	Levelb
Diagnosis
Multimodality imaging is recommended in all patients with suspected constrictive pericarditis to make the diagnosis and assess pericardial thickening, calcifications, and active inflammation. ${}^{632}$	I	C
Cardiac catheterization for haemodynamic assessment should be considered in patients with suspected constrictive pericarditis when multimodality imaging is inconclusive. ${}^{633}$	lla	C
Therapy
Anti-inflammatory therapy is recommended in haemodynamically stable patients with a transient or new diagnosis of constriction with concomitant evidence of pericardial inflammation to prevent progression to constriction and avoid pericardictomy. ${}^{122,123}$
Pericardiectomy is recommended in patients with permanent constriction if there is no active inflammation or anti-inflammatory treatment is not successful after 3-6 months.		C

表 43
Recommendation	Classa	Levelb
Restriction of physical exercise until remission, for at least 1 month, is recommended in athletes and non-athletes after IMPS using an individualized approach to accelerate recovery.		C

表 44
Recommendations	Classa	Levelb
A multidisciplinary team discussion at a referral centre is recommended in patients with high-risk/ complicated IMPS to provide a patient-tailored approach. ${}^{375,673}$		C

表 45
Recommendations	Recommendations	Classa	Levelb
Recommendations for clinical evaluation of myocarditis and pericarditis
Complete clinical evaluation, including history, physical examination, chest X-ray, biomarkers,ECG,and echocardiography is recommended in all patients with a suspicion of myocarditis and/or pericarditis for the initial diagnostic assessment.	1	C
CMR is recommended in patients with the clinical suspicion of myocarditis(using updated LL criteria) and/or pericarditis for the non-invasive diagnosis of inflammatory reaction.	1	B
Hospital admission is recommended for patients with high-risk pericarditis for monitoring and treatment.	1	B
Hospital admission is recommended for patients with moderate- to high-risk myocarditis for monitoring and treatment.	1	C
EMB is recommended in patients with high-risk myocarditis and/or haemodynamic instability, and/or in patients with intermediate-risk myocarditis not responding to conventional therapy in order to detect a specific histologic subtype and to assess the presence of viral genome for treatment.	1	C
Invasive coronary angiography or coronary CT, depending on clinical likelihood, is recommended in patients with IMPS if an acute coronary syndrome is suspected to rule out obstructive coronary artery disease.	1	C
Routine serology is not recommended in patients with myocarditis and/or pericarditis for the evaluation of viral aetiology except for hepatitis C,HIV and Lyme disease.	III	C
Recommendations for genetic testing
It is recommended to obtain family history including pedigrees in cases of recurrent IMPS to provide clues to the underlying aetiology, determine inheritance pattern, and identify relatives at risk.	I	C
Recommendations for the use of cardiovascular magnetic resonance imaging
Myocarditis	Myocarditis	Myocarditis	Myocarditis
CMR is recommended in patients with suspected myocarditis to reach a clinical diagnosis and to determine the cause of acute myocardial injury, including assessment of oedema, ischaemia, and necrosis/fibrosis/scarring.	I	B

图示：Functions of recommendations Class I Class I Evidence and/or general agreement Is recommended or is indicated Class I Conflicting evidence and/or a divergence of opinion about the usefulness/ class II effacy of the given treatment or procedure. Class II Class Ila Weight of evidence/opinion is in favour of usefulness/efficacy. Usefulness/effacy is less well established by evidence/opinion. Class III Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases Should be recommended Ivsan

图示：Esc Guidelines 永brella: IMPS- The spectrum of the inflammatory mypericardial syndrome Myopericarditis/Perimyocarditis Pericarditis Myocarditis Clinical classification Acute Subacute Chronic Recurrent Remission with/without residuals <1 month >3months Common aetologies Infectious Non-infectious Viruses Bacteria Parasites Autoinflammatory Autoimmune Genetic conditions Drugs Cancer-related Clinical presentation Oligosymptomatic Chest pain Arrhythmias (Acute)Heart failure Aborted SCD SCD Initial IMPS assessment Clinical history/ symptoms Physical exam Vital signs ECG Lab values Echocardiography Rule out obstructive coronary artery disease- according to clinical likelihood/probability Low Moderate High Coronary computed tomography Coronary angiography Risk profile and risk - adjusted assessment Low risk Intermediate risk High risk Cardiovascular magnetic resonance Invasive procedures(EMB) Function Myocardial involvement Pericardial involvement Histopathology Further assessment(if warranted) Search for aetiology Multimodality imaging Electroanatomical mapping Final diagnosis Myopericarditis/Perimyocarditis Myocarditis ESC Therapy-dependent on final diagnosis and risk/complications

图示：Definite Possible Unlike/rejected EMB- or CMR-proven EMB and CMR with uncertain results Clinical 2025 CMR + clinical 2021/2023 2013 Proven Confirmed Suspected

图示：Acute stage <1 month Subacute stage Chronic stage >3 months Acute stage <1 month 1-3 months Cardiotropic and vasculotropic inmate immune irnate immune viruses response Adaptive (vg. viral) immune response Indirect damage Viral persistence with chronic inflammation and/or fibrosis or recovery vuses irnase response Noxa: any agent capable of injuring the myopericardium Genetic susceptibility OR Remission with Dilated Constrictive viopropine and/or cardiomyopathy pericarditis without residuals intermission with Imbalance of pro-and anti-inflammatory cytokines Non-infectious (e.g.autoimmune Autoreactive T-cells toxins etc.) Autantibodies Infectious agent Cellular infiltration Y(Anti-viral) antibodies Myo-and/or pericardial injury ESC

图示：Criterion Methods Methods T2-weighted imaging or T2 mapping Native T1 mapping/ post-contrast T1 mapping(ECV)/ T1-weighted imaging Late gadolinium n enhancement Late T1-twoeded imaging Focles Method, if diffuse fibrosis Native T1 mapping/ mapping (ECV)/ T1-weighted imaging L2 Description of focal increases Regional or global in increase T2 or global of new of caing T2-twoighted T2-weighted ●High signal intensity of the pericardium in T1-mapping or regional in T2-mapping or T2-weighted imaging ●High signal intensity of the pericardium in T1-mapping ●High signal intensity of the pericardium in T1-mapping Normal to braid ECD 2 out of 2 updated LLC main criteria fulfilled Functional and wall motion abnormalities Natural T1 mapping/ post-contrast T1 mapping(ECV)/ T1-weighted imaging Late Hadolinium nenhancement Heaodynamic compromise B2 Harmonic couldi frosis brosis B3 Functional and wall motion abnormalities Natural T1 mapping/ function eEF) and volume parameters ●Resiﬁcation,pattern, extent, and location of LGE（positive if areas with high Sl in a nonchaemic lGE（position pattern）•Thrombi（if present）•Total LGE/LV mass（%）（no routine） ·Presence，composition，and extent of pericardium en T1-mapping of pericardial fEFE，RVEF) and volume parameters ●Haemodynamic (EF) and volume ●Cardiac function (e.g. LVEF,RVEF) and volume ●Hemodynamic in fusion

图示：Patient with symptoms and signsa of myocarditis presenting to the emergency room $\downarrow$ T r thanesthoracic echocardiography, chest X-ray, laboratory assessmentb (Class I) Treat CAD Y Obstructive CADc Admit to ward/ICU (Class I) N High-risk clinical featuresd Cardiovascular magnetic resonancee (Class I) Possible Diagnosis Rejected/unlikely Definitive Further work-up Low risk Effective risk classificationd Intermediate risk Stay on ward and discharge when possible (Class I) Establish HF/AA therapy and/or treatment of specific aetiology Improvement Cardiovascular magnetic resonance If not done before) Stay on ward and discharge when possible (Class I) Establish HF/AA therapy and/or treatment of specific aetiology Improvement Multidisciplinary IMPS team discussion Discussion IMPS team discussion Discussion Multidisciplinary IMPS team discussion

图示：Patient with symptoms and signsa of myocarditis presenting to the outpatient clinic First-line assessment with history, physical examination, ECG, transthoracic echocardiography, laboratory assessmentb (Class I) Elevated troponinin (Y) Refer to hospital N See inpatient algorithmc L Treat CAD Obstructive CADd Cardiovascular magnetic resonance${}^{e}$ (Class I) Possible Diagnosis Rejected/unlikely $\downarrow$ Further risk Definitive Further work-up Low risk Outpatient treatment Outpatient follow-up Small See inpatient algorithm Class I Negative Offinitive Glass Outpatient treatment Outpatient follow-up See inpatient algorithm ESC

图示：Patient with symptoms and signs of pericarditis $\downarrow$ First-line assessment with history, physical examination,ECG,transthoracic echocardiography,X-ray,routine blood test including CRP and troponin(Class I) High-risk featuresb Outpatient follow-up Response to therapy after 1-2 week K Risk evaluationb Low risk Intermediate risk High risk A Admission,or aetiology search and anti-inflammatory therapy ESG

图示：Spectrum of myocarditis presentations and outcomes Image size correlates with frequency Oligosymptomatic Chest pain Arrhythmias (Acute) Heart failure Aborted SCD SCD Remission without or with residuals (presence of reduced function and or LGE) Dilated cardiomyopathy Death ESC

图示：Patient with acute chest pain Clinical history and vital signs, 12-lead ECG, laboratory testinga, transthoracic echocardiography (Class I) Clinical likelihood/probability of obstructive coronary artery disease High Moderate Low Invasive coronary orangiography CT angiography (Class I) Red flags for IMPS Further aetiological work-up Coronary artery disease N Diagnostic criteria suggestive of myocarditis Risk stratification^4 Go to pericarditis algorithm e If CAD not the sole explanation for the symptoms Mechars resonance artery disease Clnical exclusion (Class I) Further magnetic resonance9 Red flags for IMPS Diagnostic criteria N Diagnostic activity suggestive of pericarditis Risk stratification^4 Go to pericarditis algorithm e

图示：Patient with signs and symptoms of acute heart failure Admission to ICU Cardiogenic shock and/or respiratory failure Y T Clinical history and vital signs, 12-lead ECG, laboratory testinga, transthoracic echocardiography (Class I) Simultaneously use CHAMPIT approach and whether congestion/apparent HF acute Coronary syndrome Hypertensive emergency Arrhythmia Mechanical Pulmonary embolism Infections Tamponade Further work-up Risk stratificationc Acute Coronary syndrome Hypertensive emergency Arrhythmia Mechanical Embulism Infections Tamponade Simultaneously use CHAMPIT approach and whether congestion/apparent HF Further new further work-up N Y C Congestion/apparent HF N Congestion/apparent HF N Y Adutey myocardial discharge Endomyocardial biopsy (Class I) Normal findings N Suggested fulminant myocarditis 2 High risk 4 Cardiovascular magnetic resonance (Class I) Cardiovascular resonance (Class I) Before discharge Endomomyocardial discharge (Class I) Normal findings No further work-up Aetiological work-up Y Further work-up Kearthe aetiological drug-up required Further work-up N No further work-up V3 ESC ESC

图示：Patient with new, recurrent or unexplained arrhythmias(any type) Identify arrhythmia Cardioversion/defibrillation/transcutaneous pacing/ALS (Class I) (Class I) Obstructive CADa N Evaluationb,transthoracic echocardiography (Class I) Z $\gamma$ K N D (Class I) Treat CAD Red flags for myocardial involvement Risk stratification High risk Non-high risk Cardiovascular magnetic resonance (Class I) Bore Bore Endommyocardial biopsy (Class I) Discharge Normal findings Suggestive of non-cardiac causes or cardiomyopathies Definite myocarditis No further work-up Aetiological work-up N Specific aetiology Type of initial arrhythmia at presentation N See specific sections Conduction blocks Ventricular arrhythmia Active myocarditis(based on initial CMR/EMB) Risk stratification $\downarrow $ up + H high risk Bore /CR Endommyocardial biopsy I class I) Catheter ablation IClass I) Further aetological work-up Aorelization $\downarrow $ up + H Horel Borel Sputingb of non-cardiac causes or cardiomyopathies Catheter ablation I Class I) ICD indications (Class I) Lca1Ia Iorelsonicidis (Class I)(Class Ilb)

图示：Patient with definite diagnosis of cardiac tamponade ↓ High-risk features（with cumulative score ≥6) Postpone pericardiocentesis Empiric anti-inflammatory therapy

图示：原图识别中

图示：Patient with symptoms and signs of constrictiona $\downarrow$ First-line assessment with history, physical examination,ECG, transthoracic echocardiography, laboratory assessment,CT(calcifications) and CMR(inflammation)(Class I) Definite diagnosis of constriction Admission and cardiac catheterization Concomitant pericarditis Pericardiectomy (Class I) Y X Y

图示：Acute lymphocytic myocarditis Chronic lymphocytic myocarditis Eosinophilic myocarditis G H E C G H I L C $O_{C}$ Esc $O_{C}$ G $O_{C}$ 100μm Liymphocytic G H CD68 100μm G

图示：Patient with acute pericarditis $\downarrow$ Exercise-restriction and first level therapy ASA or NSAID (usually ibuprofen or indomethacin) plus colchicine (Class I) Response to medical therapy Y Tapering of ASA/NSAID and colchicineb for 3-6 months to reduce recurrence risk N Incessant/recurrent Low to moderate doses of corticosteroids plus colchicine or triple medical therapy with corticosteroids, NSAID and colchicinec(Class II) Response to medical therapy Y Tapering of corticosteroids and colchicineb for at least 6 months to reduce recurrence risk N Incessant/recurrent Anticent/recurrent Anti-IL-1 agents(Anakinra or Rilonacept) (Class I)d ESC

图示：WCD as bridge to recovery ICD Abnormal LV Additional risk factorsa 3 to 6 months follow-up Acute myocarditis Arrhythmic presentation Recovery Medical therapy ESC

图示：Stage of tuberculous pericarditis Stage I Stage III Stages of tuberculous pericarditis Dry pericarditis Effusive-constrictive Pericarditis Stage IV Stage II Stage IV Extensive-constrictive pericarditis pericarditis constriction ESC

图示：Pericardial effusion ㈩ First-line assessment with history,physical examination,ECG,chest X-ray transthoracic echocardiography, laboratory assessment the cardiomyist is the primary diagnostic tool for eystern,speciformer is the annular diagnostic for the triage of PNeff is presented in The treat as pericarditis Treat as pericarditis Concomitant pericarditis Associated systemic disease Large(>20mm) and chronic(>3 months) effusion \\㈩ Symptomatic ㈩ Oupatient follow-up Pericardiocentesis with drainage ㈩ Empiric anti-inflammatory therapy ㈩ Outpatient follow-up C Treat the systemic condition ㈩ Associated systemic disease ㈩ Large(>20mm) and chronic(>3 months) effusion ㈩ Oupatient follow-up C Fromout to study follow-up C

图示：原图识别中

引用 / 出处

2025 ESC指南：心肌炎和心包炎的管理. 2025.