Long-term efficacy and safety of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis: A propensity-weighted study.

AIMS: Standardized immunosuppressive therapy (IS) had been previously investigated in biopsy-proven (BP) lymphocytic myocarditis with heart failure (HF). This study evaluated efficacy and safety of tailored IS in BP immune-mediated myocarditis, irrespective of histology and clinical presentation. METHODS AND RESULTS: Consecutive BP myocarditis patients treated with long-term tailored IS on top of optimal medical therapy (OMT), were compared with OMT non-IS controls using propensity-score weighting. The primary outcome was a composite of death or heart transplant, the secondary outcome was a composite of biventricular function, New York Heart Association (NYHA) class variation, and relapse. IS was managed by a multidisciplinary Cardioimmunology Team, involved a safety checklist and active patients' education. Ninety-one IS patients were compared with 267 non-IS patients. IS patients more frequently had systemic immune-mediated diseases (35% vs. 9.7%), lower baseline echocardiographic left ventricular ejection fraction (35% vs. 43%), lower right ventricular fractional area change (34% vs. 41%) and higher frequency of active lymphocytic, eosinophilic and giant cell myocarditis (71% vs. 58%, 12% vs. 1.1%, and 6.6% vs. 1.5%, respectively). At 5-year follow up, no difference was observed in the primary outcome (survival rate 93% in IS vs. 87% in non-IS), but IS patients had a higher relapse rate. Thus, IS patients, with a lower biventricular function and a higher risk profile at baseline, presented similar biventricular function and NYHA class to non-IS patients at follow-up. Minor adverse drug reactions occurred in 13% of patients, all resolved with therapy switch. CONCLUSIONS: Prolonged tailored IS is effective and safe in BP immune-mediated myocarditis irrespective of histology and clinical presentation.

CMR Predictors of Favorable Outcome in Myocarditis: A Single-Center Experience.

Background: Cardiovascular magnetic resonance (CMR) has emerged as the most accurate, non-invasive method to support the diagnosis of clinically suspected myocarditis and as a risk-stratification tool in patients with cardiomyopathies. We aim to assess the diagnostic and prognostic role of CMR at diagnosis in patients with myocarditis. Methods: We enrolled consecutive single-center patients with 2013 ESC consensus-based endomyocardial biopsy (EMB)-proven or clinically suspected myocarditis undergoing CMR at diagnosis. The pre-specified outcome was defined as NYHA class > I and echocardiographic left ventricular ejection fraction (LVEF) < 50% at follow-up. Results: We included 207 patients (74% male, median age 36 years; 25% EMB-proven). CMR showed the highest sensitivity in myocarditis with infarct-like presentation. Patients with EMB-proven myocarditis were more likely to have diffuse LGE and right ventricular LGE (p < 0.001), which was also more common among patients with arrhythmic presentation (p = 0.001). The outcome was met in 17 patients at any follow-up time point, more commonly in those with larger biventricular volumes (p < 0.001), CMR-based diagnosis of dilated cardiomyopathy (p < 0.001), and ischemic LGE (p = 0.005). Higher biventricular systolic function (p < 0.001) and greater LGE extent (p = 0.033) at diagnosis had a protective effect. Conclusions: In our single-center cohort of rigorously defined myocarditis patients, higher biventricular systolic function and greater LGE extent on CMR at diagnosis identified patients with better functional class and higher left ventricular ejection fraction at follow-up. Conversely, larger biventricular volumes, CMR-based DCM features, and the presence of an ischemic LGE pattern at diagnosis were predictors of worse functional class and LV systolic dysfunction at follow-up. Larger prospective studies are warranted to extend our findings to multi-center cohorts.

Uneventful COVID-19 Infection and Vaccination in a Cohort of Patients with Prior Myocarditis.

Myocarditis has in rare cases been associated with COVID-19 infection and has emerged as a possible rare side effect of vaccination with anti-COVID-19 messenger RNA vaccines. However, little is known about possible COVID-19 infection- and/or vaccination-related myocarditis relapse in patients with previous clinically suspected or biopsy-proven myocarditis. Myocarditis may relapse, particularly in females with immune-mediated/autoimmune features and a predisposing immunogenetic background. We aimed to assess the prevalence of myocarditis relapse during the COVID-19 outbreak and following COVID-19 vaccination in a cohort of patients with prior myocarditis. We included in the analysis myocarditis patients on active follow-up, for whom COVID-19 infection and vaccination statuses were known, and collected data on clinical, laboratory and echocardiographic findings, and myocarditis relapse. We enrolled 409 patients, of whom 114 (28%) reported COVID-19 infection and 347 (85%) completed the vaccination scheme. Only one patient, having COVID-19 infection before the vaccination campaign started, was admitted to hospital because of pneumonia; the remaining patients had an uneventful COVID-19 infection course, with only mild symptoms. No myocarditis relapse was recorded following COVID-19 infection or vaccination. Moreover, the frequency of new myocarditis cases following the COVID-19 outbreak was not different compared to the three-year period preceding the COVID-19 era. In conclusion, in our cohort of patients with prior myocarditis, both COVID-19 infection and vaccination were uneventful.

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.

Introduction: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. Methods: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Results: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. Conclusion: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

Fulminant Myocarditis: When One Size Does Not Fit All - A Critical Review of the Literature.

Fulminant myocarditis, rather than being a distinct form of myocarditis, is instead a peculiar clinical presentation of the disease. The definition of fulminant myocarditis has varied greatly in the last 20 years, leading to conflicting reports on prognosis and treatment strategies, mainly because of varied inclusion criteria in different studies. The main conclusion of this review is that fulminant myocarditis may be due to different histotypes and aetiologies that can be diagnosed only by endomyocardial biopsy and managed by aetiology-directed treatment. This life-threatening presentation requires rapid, targeted management both in the short term (mechanical circulatory support, inotropic and antiarrhythmic treatment and endomyocardial biopsy) and in the long term (including prolonged follow-up). Fulminant presentation has also recently been identified as a risk factor for worsened prognosis, even long after the resolution of the acute phase of myocarditis.

Transient pericardial constriction: A not so rare entity.

Constrictive pericarditis is a rare, potentially treatable, cause of heart failure with preserved ejection fraction that is characterized by insidious onset, challenging diagnosis and dismal prognosis, even following complete surgical pericardiectomy, particularly in advanced disease stages. In recent years it has been proposed that transient pericardial constriction may occur, with an even rarer frequency, during early phases of acute pericarditis and may resolve following specific treatment without progressing to the chronic, irreversible form. We recently observed two cases of well-documented transient pericardial constriction. In the present work we describe these two cases and provide a review on this rare condition, that, if unrecognized and left untreated, may lead to irreversible constrictive pericarditis.

Immunosuppressive Therapy of Biopsy-Proven, Virus-Negative, Autoimmune/Immune-Mediated Myocarditis-Focus on Azathioprine: A Review of Existing Evidence and Future Perspectives.

The use of immunosuppressive therapy (IT) in biopsy-proven, autoimmune/immune-mediated (AI), virus-negative myocarditis has become the standard of care. In particular, according to recent guidelines, azathioprine (AZA), in association with steroids, is a cornerstone of first-line therapy regimens. IT may have a crucial impact on the natural history of AI myocarditis, preventing its progression to end-stage heart failure, cardiovascular death, or heart transplantation, provided that strict appropriateness and safety criteria are observed. In particular, AZA treatment for AI virus-negative myocarditis requires the consideration of some crucial aspects regarding its pharmacokinetics and pharmacodynamics, as well as a high index of suspicion to detect its overt and/or subclinical side effects. Importantly, besides a tight teamwork with a clinical immunologist/immuno-rheumatologist, before starting IT, it is also necessary to carry out a careful "safety check-list" in order to rule out possible contraindications to IT and minimize patient's risk. The aim of this review is to describe the pharmacological properties of AZA, as well as to discuss practical aspects of its clinical use, in the light of existing evidence, with particular regard to the new field of cardioimmunology.

Acute clinical presentation of nonischemic cardiomyopathies: early detection by cardiovascular magnetic resonance.

Nonischemic cardiomyopathies include a wide range of dilated, hypertrophic and arrhythmogenic heart muscle disorders, not explained by coronary artery disease, hypertension, valvular or congenital heart disease. Advances in medical treatments and the availability of implantable cardioverter defibrillators to prevent sudden cardiac death have allowed a substantial increase in the survival of affected individuals, thus making early diagnosis and tailored treatment mandatory. The characterization of cardiomyopathies has received a great boost from the recent advances in cardiovascular magnetic resonance (CMR) imaging, which, to date, represents the gold standard for noninvasive assessment of cardiac morphology, function and myocardial tissue changes. An acute clinical presentation has been reported in a nonnegligible proportion of patients with nonischemic cardiomyopathies, usually complaining of acute chest pain, worsening dyspnoea or palpitations; 'hot phases' of cardiomyopathies are characterized by a dynamic rise in high-sensitivity troponin, myocardial oedema on CMR, arrhythmic instability, and by an increased long-term risk of adverse remodelling, progression of myocardial fibrosis, heart failure and malignant ventricular arrhythmias. Prompt recognition of 'hot phases' of nonischemic cardiomyopathies is of utmost importance to start an early, individualized treatment in these high-risk patients. On the one hand, CMR represents the gold standard imaging technique to detect early and typical signs of ongoing myocardial remodelling in patients presenting with a 'hot phase' nonischemic cardiomyopathy, including myocardial oedema, perfusion abnormalities and pathological mapping values. On the other hand, CMR allows the differential diagnosis of other acute heart conditions, such as acute coronary syndromes, takotsubo syndrome, myocarditis, pericarditis and sarcoidosis. This review provides a deep overview of standard and novel CMR techniques to detect 'hot phases' of cardiomyopathies, as well as their clinical and prognostic utility.

Sex differences in patients with acute coronary syndromes and non-obstructive coronary arteries: Presentation and outcome.

BACKGROUND: A substantial number of patients present with a suspected ACS and non-obstructive coronary arteries; sex differences in these patients are not well understood. This study aims to evaluate the impact of sex on clinical presentation and outcome in patients with suspected acute coronary syndrome (ACS) and non-obstructive coronary arteries with a final diagnosis confirmed by cardiovascular magnetic resonance imaging (CMR). METHODS: Consecutive patients with ACS and non-obstructive coronary arteries (n = 719) with an unclear cause from a single tertiary centre who were referred for CMR were included. The primary endpoint was all-cause mortality. RESULTS: CMR was performed at a median time of 30 days after presentation and identified a diagnosis in 74% of patients. All-cause mortality was 9.5% over a median follow up of 4.9 years, with no significant difference between sexes (8.8% versus 10.1%; p = 0.456). Men were more likely to have non-ischaemic aetiology on CMR than women (55% v 41%, p < 0.001), but were equally likely to have an ischaemic cause (25% v 27%, p = 0.462). Age group (HR 1.58, p < 0.001) and LV ejection fraction (HR 0.98, p = 0.023) were independent predictors of mortality. CONCLUSIONS: There is no difference in all-cause mortality between sexes in patients presenting with suspected ACS and non-obstructive coronary arteries.

Multi-modality imaging to guide the implantation of cardiac electronic devices in heart failure: is the sum greater than the individual components?

Heart failure is a clinical syndrome with an increasing prevalence and incidence worldwide that impacts patients' quality of life, morbidity, and mortality. Implantable cardioverter-defibrillator and cardiac resynchronization therapy are pillars of managing patients with HF and reduced left ventricular ejection fraction. Despite the advances in cardiac imaging, the assessment of patients needing cardiac implantable electronic devices relies essentially on the measure of left ventricular ejection fraction. However, multi-modality imaging can provide important information concerning the aetiology of heart failure, the extent and localization of myocardial scar, and the pathophysiological mechanisms of left ventricular conduction delay. This paper aims to highlight the main novelties and progress in the field of multi-modality imaging to identify patients who will benefit from cardiac resynchronization therapy and/or implantable cardioverter-defibrillator. We also want to underscore the boundaries that prevent the application of imaging-derived parameters to patients who will benefit from cardiac implantable electronic devices and orient the choice of the device. Finally, we aim at providing some reflections for future research in this field.

Clinical application of CMR in cardiomyopathies: evolving concepts and techniques : A position paper of myocardial and pericardial diseases and cardiac magnetic resonance working groups of Italian society of cardiology.

Cardiac magnetic resonance (CMR) has become an essential tool for the evaluation of patients affected or at risk of developing cardiomyopathies (CMPs). In fact, CMR not only provides precise data on cardiac volumes, wall thickness, mass and systolic function but it also a non-invasive characterization of myocardial tissue, thus helping the early diagnosis and the precise phenotyping of the different CMPs, which is essential for early and individualized treatment of patients. Furthermore, several CMR characteristics, such as the presence of extensive LGE or abnormal mapping values, are emerging as prognostic markers, therefore helping to define patients' risk. Lastly new experimental CMR techniques are under investigation and might contribute to widen our knowledge in the field of CMPs. In this perspective, CMR appears an essential tool to be systematically applied in the diagnostic and prognostic work-up of CMPs in clinical practice. This review provides a deep overview of clinical applicability of standard and emerging CMR techniques in the management of CMPs.

A Machine-Learning Model for the Prognostic Role of C-Reactive Protein in Myocarditis.

Aims: The role of inflammation markers in myocarditis is unclear. We assessed the diagnostic and prognostic correlates of C-reactive protein (CRP) at diagnosis in patients with myocarditis. Methods and results: We retrospectively enrolled patients with clinically suspected (CS) or biopsy-proven (BP) myocarditis, with available CRP at diagnosis. Clinical, laboratory and imaging data were collected at diagnosis and at follow-up visits. To evaluate predictors of death/heart transplant (Htx), a machine-learning approach based on random forest for survival data was employed. We included 409 patients (74% males, aged 37 ± 15, median follow-up 2.9 years). Abnormal CRP was reported in 288 patients, mainly with CS myocarditis (p < 0.001), recent viral infection, shorter symptoms duration (p = 0.001), chest pain (p < 0.001), better functional class at diagnosis (p = 0.018) and higher troponin I values (p < 0.001). Death/Htx was reported in 13 patients, of whom 10 had BP myocarditis (overall 10-year survival 94%). Survival rates did not differ according to CRP levels (p = 0.23). The strongest survival predictor was LVEF, followed by anti-nuclear auto-antibodies (ANA) and BP status. Conclusions: Raised CRP at diagnosis identifies patients with CS myocarditis and less severe clinical features, but does not contribute to predicting survival. Main death/Htx predictors are reduced LVEF, BP diagnosis and positive ANA.

Prospective multiparametric CMR characterization and MicroRNA profiling of anthracycline cardiotoxicity: A pilot translational study.

Background: Anthracycline cardiotoxicity is a significant clinical challenge. Biomarkers to improve risk stratification and identify early cardiac injury are required. Objectives: The purpose of this pilot study was to prospectively characterize anthracycline cardiotoxicity using cardiovascular magnetic resonance (CMR), echocardiography and MicroRNAs (MiRNAs), and identify baseline predictors of LVEF recovery. Methods: Twenty-four patients (age 56 range 18-75 years; 42 % female) with haematological malignancy scheduled to receive anthracycline chemotherapy (median dose 272 mg/m2 doxorubicin equivalent) were recruited and evaluated at three timepoints (baseline, completion of chemotherapy, and 6 months after completion of chemotherapy) with multiparametric 1.5 T CMR, echocardiography and circulating miRNAs sequencing. Results: Seventeen complete datasets were obtained. CMR left ventricular ejection fraction (LVEF) fell significantly between baseline and completion of chemotherapy (61 ± 3 vs 53 ± 3 %, p < 0.001), before recovering significantly at 6-month follow-up (55 ± 3 %, p = 0.018). Similar results were observed for 3D echocardiography-derived LVEF and CMR-derived longitudinal, circumferential and radial feature-tracking strain. Patients were divided into tertiles according to LVEF recovery (poor recovery, partial recovery, good recovery). CMR-derived mitral annular plane systolic excursion (MAPSE) was significantly different at baseline in patients exhibiting poor LVEF recovery (11.7 ± 1.5 mm) in comparison to partial recovery (13.7 ± 2.7 mm), and good recovery (15.7 ± 3.1 mm; p = 0.028). Furthermore, baseline miRNA-181-5p and miRNA-221-3p expression were significantly higher in this group. T2 mapping increased significantly on completion of chemotherapy compared to baseline (54.0 ± 4.6 to 57.8 ± 4.9 ms, p = 0.001), but was not predictive of LVEF recovery. No changes to LV mass, extracellular volume fraction, T1 mapping or late gadolinium enhancement were observed. Conclusions: Baseline CMR-derived MAPSE, circulating miRNA-181-5p, and miRNA-221-3p were associated with poor recovery of LVEF 6 months after completion of anthracycline chemotherapy, suggesting their potential predictive role in this context. T2 mapping increased significantly on completion of chemotherapy but was not predictive of LVEF recovery.

Society for Cardiovascular Magnetic Resonance 2021 cases of SCMR and COVID-19 case collection series.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). "Cases of SCMR" is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. The COVID-19 Case Collection highlights the impact of coronavirus disease 2019 (COVID-19) on the heart as demonstrated on CMR. Each case in series consists of the clinical presentation and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2021 Cases of SCMR and the 2020 and 2021 COVID-19 Case Collection series of nine cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar literature search engine.

Role of Cardiac Imaging Modalities in the Evaluation of COVID-19-Related Cardiomyopathy.

Cardiac involvement has been described during the course of SARS-CoV-2 disease (COVID-19), with different manifestations. Several series have reported only increased cardiac troponin without ventricular dysfunction, others the acute development of left or right ventricular dysfunction, and others myocarditis. Ventricular dysfunction can be of varying degrees and may recover completely in some cases. Generally, conventional echocardiography is used as a first approach to evaluate cardiac dysfunction in patients with COVID-19, but, in some cases, this approach may be silent and more advanced cardiac imaging techniques, such as myocardial strain imaging or cardiac magnetic resonance, are necessary to document alterations in cardiac structure or function. In this review we sought to discuss the information provided by different cardiac imaging techniques in patients with COVID-19, both in the acute phase of the disease and after discharge from hospital, and their diagnostic and prognostic role. We also aimed at verifying whether a specific form of cardiac disease due to the SARS-CoV-2 can be identified.

Predictors of relapse, death or heart transplantation in myocarditis before the introduction of immunosuppression: negative prognostic impact of female gender, fulminant onset, lower ejection fraction and serum autoantibodies.

AIMS: Outcome predictors in myocarditis are not well defined; we aimed at identifying predictors of death, heart transplantation (HTx) and relapse before the introduction of immunosuppression. METHODS AND RESULTS: From 1992 to 2012, 466 consecutive patients (68% male, mean age 37 ± 17 years, single centre recruitment, median follow-up 50 months) were included, of whom 216 had clinically suspected and 250 biopsy-proven myocarditis. Serum anti-heart (AHA) and anti-intercalated disk (AIDA) autoantibodies were measured by indirect immunofluorescence. Univariable and multivariable analyses of clinical and diagnostic features at diagnosis were performed. Survival free from death or HTx at 10 years was 83% in the whole study population and was lower in biopsy-proven versus clinically suspected myocarditis (76% vs. 94%, p < 0.001). Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1-6.5), fulminant presentation (HR 13.77, 95% CI 9.7-261.73), high-titre organ-specific AHA (HR 4.2, 95% CI 1.2-14.7) and anti-nuclear antibodies (ANA) (HR 5.2, 95% CI 2.1-12.8) were independent predictors of death or HTx; higher echocardiographic left ventricular ejection fraction (LVEF) at diagnosis was protective, with a 0.93-fold risk reduction for each 1% LVEF increase (95% CI 0.89-0.96). History of myocarditis at diagnosis (HR 8.5, 95% CI 3.5-20.7) was an independent predictor of myocarditis relapse at follow-up; older age was protective (HR 0.95, 95% CI 0.91-0.99). Predictors of death, HTx and relapse did not differ in biopsy-proven versus clinically suspected myocarditis. CONCLUSIONS: Young age and a previous myocarditis were independent relapse predictors; female gender, fulminant onset, lower LVEF at presentation and high-titre organ-specific AHA and ANA were independent predictors of death and HTx, suggesting that autoimmune features predict worse prognosis.

Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition.

Introduction: Primary heart involvement in systemic sclerosis may cause morpho-functional and electrical cardiac abnormalities and is a common cause of death. The absence of a clear definition of primary heart involvement in systemic sclerosis limits our understanding and ability to focus on clinical research. We aimed to create an expert consensus definition for primary heart involvement in systemic sclerosis. Methods: A systematic literature review of cardiac involvement and manifestations in systemic sclerosis was conducted to inform an international and multi-disciplinary task force. In addition, the nominal group technique was used to derive a definition that was then subject to voting. A total of 16 clinical cases were evaluated to test face validity, feasibility, reliability and criterion validity of the newly created definition. Results: In total, 171 publications met eligibility criteria. Using the nominal group technique, experts added their opinion, provided statements to consider and ranked them to create the consensus definition, which received 100% agreement on face validity. A median 60(5-300) seconds was taken for the feasibility on a single case. Inter-rater agreement was moderate (mKappa (95% CI) = 0.56 (0.46-1.00) for the first round and 0.55 (0.44-1.00) for the second round) and intra-rater agreement was good (mKappa (95% CI) = 0.77 (0.47-1.00)). Criterion validity showed a 78 (73-84)% correctness versus gold standard. Conclusion: A preliminary primary heart involvement in systemic sclerosis consensus-based definition was created and partially validated, for use in future clinical research.

Personalized Management of Myocarditis and Inflammatory Cardiomyopathy in Clinical Practice.

Myocarditis is an inflammatory heart disease induced by infectious and non-infectious causes frequently triggering immune-mediated pathologic mechanisms leading to myocardial damage and dysfunction. In approximately half of the patients, acute myocarditis resolves spontaneously while in the remaining cases, it may evolve into serious complications including inflammatory cardiomyopathy, arrhythmias, death, or heart transplantation. Due to the large variability in clinical presentation, unpredictable course of the disease, and lack of established causative treatment, myocarditis represents a challenging diagnosis in modern cardiology. Moreover, an increase in the incidence of myocarditis and inflammatory cardiomyopathy has been observed in recent years. However, there is a growing potential of available non-invasive diagnostic methods (biomarkers, serum anti-heart autoantibodies (AHA), microRNAs, speckle tracking echocardiography, cardiac magnetic resonance T1 and T2 tissue mapping, positron emission tomography), which may refine the diagnostic workup and/or noninvasive follow-up. Personalized management should include the use of endomyocardial biopsy and AHA, which may allow the etiopathogenetic subsets of myocarditis (infectious, non-infectious, and/or immune-mediated) to be distinguished and implementation of disease-specific therapies. In this review, we summarize current knowledge on myocarditis and inflammatory cardiomyopathy, and outline some practical diagnostic, therapeutic, and follow-up algorithms to facilitate comprehensive individualized management of these patients.