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.

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.

BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Advances in myocarditis management in the light of the latest research and recent guidelines of the European Society of Cardiology.

Myocarditis remains an unknown disease with varying clinical manifestations, often leading to heart failure. The latest 2021 and 2022 guidelines of the European Society of Cardiology (ESC) are the first official European documents updating knowledge on the diagnosis and treatment of myocarditis since the 2013 ESC expert consensus statement. These guidelines and new studies allow standardization and improvements to the management of myocarditis. In this review, we discuss the most important aspects of myocarditis diagnosis, therapies and follow-up based on current knowledge.

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.

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.

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.

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.

[ANMCO Position paper: Cardiovascular disease in women - prevention, diagnosis, treatment and organization of care]. / Position paper ANMCO: Malattie cardiovascolari nella donna ­ prevenzione, diagnosi, terapia e organizzazione delle cure.

Cardiovascular diseases are still the main cause of death among women despite the improvements in treatment and prognosis achieved in the last 30 years of research. The determinant factors and causes have not been completely identified but the role of "gender" is now recognized. It is well known that women tend to develop cardiovascular disease at an older age than men, and have a high probability of manifesting atypical symptoms not often recognized. Other factors may also co-exist in women, which may favor the onset of specific cardiac diseases such as those with a sex-specific etiology (differential effects of estrogens, pregnancy pathologies, etc.) and those with a different gender expression of specific and prevalent risk factors, inflammatory and autoimmune diseases and cancer. Whether the gender differences observed in cardiovascular outcomes are influenced by real biological differences remains a matter of debate.This ANMCO position paper aims at providing the state of the research on this topic, with particular attention to the diagnostic aspects and to care organization.

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.

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.

Myocarditis in systemic immune-mediated diseases: Prevalence, characteristics and prognosis. A systematic review.

Many systemic immune-mediated diseases (SIDs) may involve the heart and present as myocarditis with different histopathological pictures, i.e. lymphocytic, eosinophilic, granulomatous, and clinical features, ranging from a completely asymptomatic patient to life-threatening cardiogenic shock or arrhythmias. Myocarditis can be part of some SIDs, such as sarcoidosis, systemic lupus erythematosus, systemic sclerosis, antiphospholipid syndrome, dermato-polymyositis, eosinophilic granulomatosis with polyangiitis and other vasculitis syndromes, but also of some organ-based immune-mediated diseases with systemic expression, such as chronic inflammatory bowel diseases. The aim of this review is to describe the prevalence, main clinical characteristics and prognosis of myocarditis associated with SIDs.

Myocardial Inflammation and Sudden Death in the Inherited Cardiomyopathies.

The best studied of the inherited cardiomyopathies-hypertrophic (HCM), dilated (DCM) and arrhythmogenic (ACM)-present overlapping clinical phenotypes with varying, often unrecognized, risk of sudden death. Risk assessment is informed by patient sex and by the specific disease-causing variant. HCM and arrhythmogenic right ventricular cardiomyopathy (ARVC) remain important causes of sudden death. A phenotype mimicking DCM in patients with inherited ACM is associated with premature sudden death in families with overlapping DCM and ACM phenotypes. The role of inflammation as a determinant of disease development and progression and sudden death is poorly understood but potentially important. Sudden death registries report myocarditis as the cause in 5% to 13%; examination of 30 hearts from victims of ARVC sudden death found focal myocarditis in areas of myocyte necrosis in 20 (67%). The link to specific disease-causing variants remains to be explored, including genetic determinants of the immune response. Clinical and experimental studies support immune- and autoimmune-mediated disease in DCM and ACM. Immunosuppression in biopsy-proven noninfectious myocarditis and inflammatory DCM is a treatment option. Recognition of ACM requires greater focus on distinguishing ACM from DCM. The potential to recognize disease before adverse events and to characterize patients who may benefit from immunosuppression or device therapy highlights the importance of more comprehensive genetic and immunologic characterization of patients with myocarditis and in those with a family history or clinical presentation of an inherited cardiomyopathy. This review will examine from a predominantly clinical perspective the potential importance of myocardial inflammation as a determinant of sudden death in inherited HCM, DCM, and ACM.

Clinically Suspected and Biopsy-Proven Myocarditis Temporally Associated with SARS-CoV-2 Infection.

We review current data on clinically suspected [European Society of Cardiology (ESC) 2013 criteria] and biopsy-proven [ESC and World Health Organization (WHO) criteria] myocarditis that is temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. ESC/WHO etiological diagnosis of viral myocarditis is based on histological and immunohistological evidence of nonischemic myocyte necrosis and monolymphocytic infiltration, i.e., myocarditis, plus the identification of a specific cardiotropic virus by molecular techniques, in particular polymerase chain reaction (PCR)/in-situ hybridization, on endomyocardial biopsy (EMB)/autopsy tissue. There is not yet definitive EMB/autopsy proof that SARS-CoV-2 causes direct cardiomyocyte damage in association with histological myocarditis. Clinical epidemiology data suggest that myocarditis is uncommon for both SARS-CoV-2-positive and -negative PCR cases. We hypothesize that the rare virus-negative biopsy-proven cases may represent new-onset immune-mediated or latent pre-existing autoimmune forms,triggered or fostered by the hyperinflammatory state of severe COVID-19. We recommend the application of the ESC/WHO definitions and diagnostic criteria in future reports to avoid low-quality scientific information leading to an inaccurate estimate of myocarditis incidence based on misdiagnosis.

Management of myocarditis in clinical practice.

Myocarditis is an inflammatory heart muscle disease characterized by heterogeneous clinical presentation and outcome. Clinical heterogeneity of myocarditis, ranging from acute onset chest pain with electrocardiographic changes resembling an acute coronary syndrome, to arrhythmic storm and chronic decompensated heart failure, makes diagnosis challenging. However, a correct diagnosis is fundamental to proper patients' management and should always be seeked. Although a definite diagnosis is only provided by endomyocardial biopsy, the European Society of Cardiology task force on myocardial and pericardial diseases provided specific criteria for the diagnosis of clinically suspected myocarditis, which has been facilitated by the advent of noninvasive imaging tests (i.e. cardiovascular magnetic resonance based myocardial tissue characterization). Due to the heterogeneous presentation and disease course of myocarditis, a tailored treatment would be the best strategy, but a standardized management is still not available. However, over the years, new, promising therapies, such as antiviral and immune-suppressive treatment, have come side by side to the standard pharmacological heart treatment, i.e. antiheart failure medications. In this paper we will review the basic principles of myocarditis management in clinical practice, including diagnostic work-up, conventional and disease-specific therapy and patients' follow-up.

Serum Anti-Heart and Anti-Intercalated Disk Autoantibodies: Novel Autoimmune Markers in Cardiac Sarcoidosis.

BACKGROUND: Sarcoidosis is an immune-mediated disease. Cardiac involvement, a granulomatous form of myocarditis, is under-recognized and prognostically relevant. Anti-heart autoantibodies (AHAs) and anti-intercalated disk autoantibodies (AIDAs) are autoimmune markers in nonsarcoidosis myocarditis forms. OBJECTIVE: The aim was to assess serum AHAs and AIDAs as autoimmune markers in cardiac sarcoidosis. METHODS: This is a cross-sectional study on AHA and AIDA frequency in: 29 patients (aged 46 ± 12, 20 male) with biopsy-proven extracardiac sarcoidosis and biopsy-proven or clinically suspected and confirmed by 18-fluorodeoxyglucose positron emission tomography and/or cardiovascular magnetic resonance (CMR) cardiac involvement; 30 patients (aged 44 ± 11, 12 male) with biopsy-proven extracardiac sarcoidosis without cardiac involvement (no cardiac symptoms, normal 12-lead electrocardiogram, echocardiography and CMR), and control patients with noninflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141) and normal blood donors (NBDs) (n = 270). Sarcoidosis patients were recruited in two recruiting tertiary centers in the USA and Italy. AHAs and AIDAs were detected by indirect immunofluorescence on the human myocardium and skeletal muscle. RESULTS: AHA and AIDA frequencies were higher in sarcoidosis with cardiac involvement (86%; 62%) than in sarcoidosis without cardiac involvement (0%; 0%), NICD (8%; 4%), IHF (7%; 2%) and NBD (9%; 0%) (p = 0.0001; p = 0.0001, respectively). Sensitivity and specificity for cardiac sarcoidosis were 86% and 92% for positive AHAs and 62% and 98% for positive AIDAs, respectively. AIDAs in cardiac sarcoidosis were associated with a higher number of involved organs (p = 0.04). CONCLUSIONS: Serum AHAs and AIDAs provide novel noninvasive diagnostic autoimmune markers for cardiac sarcoidosis.

A rare cause of effusive-constrictive pericarditis.

Effusive-constrictive pericarditis (ECP) is an uncommon diagnosis, frequently missed due to its heterogeneous presentation, but a potentially reversible cause of heart failure. A 62-year-old Caucasian male presented with remittent right heart failure and mild-moderate pericardial effusion. Following an initial diagnosis of idiopathic pericarditis, indomethacin was started, but the patient shortly relapsed, presenting with severe pericardial effusion and signs of cardiac tamponade, requiring pericardiocentesis. ECP was diagnosed on cardiac catheterization. Cardiac computed tomography showed non-calcified, mildly thickened and inflamed parietal pericardium. Pericardiectomy was performed with symptoms remission. On histological examination of pericardium, chronic non-necrotizing granulomatous inflammation was noted. Polymerase chain reaction assay was positive for non-tuberculous mycobacteria. This case represents a rare finding of ECP with unusual presentation due to atypical mycobacteriosis in a non-immunocompromised patient and in a non-endemic area. Pericardiectomy can be an effective option in cases unresponsive to anti-inflammatory treatment, even in the absence of significant pericardial thickening or calcification.

A Novel Circulating MicroRNA for the Detection of Acute Myocarditis.

BACKGROUND: The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. METHODS: To identify a microRNA specific for myocarditis, we performed microRNA microarray analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Th17) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. RESULTS: We confirmed that Th17 cells, which are characterized by the production of interleukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Th17 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:96, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. CONCLUSIONS: After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.).

Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases.

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.