Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.

Myocarditis is a diverse group of heart-specific immune processes classified by clinical and histopathological manifestations. Up to 40% of dilated cardiomyopathy is associated with inflammation or viral infection. Recent experimental studies revealed complex regulatory roles for several microribonucleic acids and T-cell and macrophage subtypes. Although the prevalence of myocarditis remained stable between 1990 and 2013 at about 22 per 100,000 people, overall mortality from cardiomyopathy and myocarditis has decreased since 2005. The diagnostic and prognostic value of cardiac magnetic resonance has increased with new, higher-sensitivity sequences. Positron emission tomography has emerged as a useful tool for diagnosis of cardiac sarcoidosis. The sensitivity of endomyocardial biopsy may be increased, especially in suspected sarcoidosis, by the use of electrogram guidance to target regions of abnormal signal. Investigational treatments on the basis of mechanistic advances are entering clinical trials. Revised management recommendations regarding athletic participation after acute myocarditis have heightened the importance of early diagnosis.

G iant-cell myocarditis (GCM) is known as a rare, rapidly progressive, and frequently fatal myocardial disease in young and middle-aged adults. It is attributed to a T lymphocyte-mediated inflammation of the heart muscle and associates with systemic autoimmune diseases in ≈20% of cases. 1,2The most common early manifestations are heart failure, ventricular arrhythmias, and atrioventricular block, but GCM may also disguise as an acute myocardial infarction and rarely presents as an unexpected sudden cardiac death.1-3 The diagnosis of GCM rests fully on microscopy of the heart muscle and even in experienced centers >4 in 10 cases may escape detection until autopsy or cardiac transplantation. Aside from nonspecific measures to combat its symptomatic manifestations, the treatment of GCM relies on immunosuppression. Retrospective observations from the Multicenter GCM Registry 1,4 and a small prospective study with repeat biopsies 5 suggest that cyclosporine-based combined immunosuppression may be able to reduce myocardial inflammation 5 and improve clinical outcome. 1,4,5 Yet, these data are uncontrolled and suffer from lack of details about the treatments given 1,4 and the possibility of survivor bias. 1,4,5 The key problem is that the rarity and seriousness of GCM make controlled treatment trials, let alone use of a placebo arm, virtually impossible. The only such attempt, a cooperative endeavor by 17 centers, was terminated after 6 years because of difficulties in recruiting patients.5 Therefore, carefully studied observational patient series continue to add to the knowledge about GCM. We report here our experience in 32 patients with GCM, of whom 26 received combined immunosuppression. We focus on the diagnosis of GCM and on the outcome of patients with contemporary treatment. Our key observations suggest that repeat and imaging-guided biopsies increase the detection rate of GCM and that combined immunosuppression supported by therapy for heart failure and arrhythmias may result in transplant-free survival in two thirds of patients. Clinical Perspective on p 22 Methods PatientsFrom the year 1991 through 2011, 32 patients with histologically verified GCM were seen at the Division of Cardiology, Helsinki University Central Hospital. The majority of diagnoses (29/32) were made after year 2000, that is, during the latter half of the study period. The medical records, laboratory test, imaging studies, and available biopsy material of all patients were retrospectively reviewed and © 2012 American Heart Association, Inc. Background-Giant-cell myocarditis often escapes diagnosis until autopsy or transplantation and has defied proper treatment trials for its rarity and deadly behavior. Current therapy rests on multiple-drug immunosuppression but its prognostic influence remains poorly known. We set out to analyze (1) our experience in diagnosing giant-cell myocarditis and (2) the outcome of patients on combined immunosuppression. Methods and Results-We reviewed the histories, diagnostic procedures, details of treatment, a...

Background-This study was designed to assess the epidemiology, characteristics, and outcome of cardiac sarcoidosis (CS) in Finland. Methods and Results-We identified in retrospect all adult (>18 years of age) patients diagnosed with histologically confirmed CS in Finland between 1988 and 2012. A total of 110 patients (71 women) 51±9 years of age (mean±SD) were found and followed up for outcome events to the end of 2013. The annual detection rate of CS increased >20-fold during the 25-year period, reaching 0.31 in 1×10 5 adults between 2008 and 2012. The 2012 prevalence of CS was 2.2 in 1×10 5 . Nearly two thirds of patients had clinically isolated CS. Altogether, 102 of the 110 patients received immunosuppressive therapy, and 56 received an intracardiac defibrillator. Left ventricular function was impaired (ejection fraction <50%) in 65 patients (59%) at diagnosis and showed no overall change over 12 months of steroid therapy. During follow-up (median, 6.6 years), 10 patients died of a cardiac cause, 11 patients underwent transplantation, and another 11 patients suffered an aborted sudden cardiac death. The Kaplan-Meier estimates for 1-, 5-, and 10-year transplantation-free cardiac survival were 97%, 90%, and 83%, respectively. Heart failure at presentation predicted poor outcome (log-rank P=0.0001) with a 10-year transplantation-free cardiac survival of only 53%. Conclusions-The detection rate of CS has increased markedly in Finland over the last 25 years. With current therapy, the prognosis of CS appears better than generally considered, but patients presenting with heart failure still have poor longterm outcome. (Circulation. 2015;131:624-632.