In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.

Myocarditis is an inflammatory disease of the heart frequently resulting from viral infections and/or post-viral immune-mediated responses. It is one of the important causes of dilated cardiomyopathy worldwide. The diagnosis is presumed on clinical presentation and noninvasive diagnostic methods such as cardiovascular magnetic resonance imaging. Endomyocardial biopsy remains the gold standard for in vivo diagnosis of myocarditis. The therapeutic and prognostic benefits of endomyocardial biopsy results have recently been demonstrated in several clinical trials. Although remarkable advances in diagnosis, understanding of pathophysiological mechanisms, and treatment of acute myocarditis were gained during the last years, no standard treatment strategies could be defined as yet, apart from standard heart failure therapy and physical rest. In severe cases, mechanical support or heart transplantation may become necessary. There is some evidence that immunosuppressive and immunomodulating therapy are effective for chronic, virus-negative inflammatory cardiomyopathy. Further investigations by controlled, randomized studies are needed to definitively determine their role in the treatment of myocarditis.

Background-Endomyocardial biopsy (EMB) represents the gold standard for diagnosing myocarditis and nonischemic cardiomyopathies. This study focuses on the risk of complications and the respective diagnostic performance of left ventricular (LV), right ventricular (RV), or biventricular EMB in patients with suspected myocarditis and/or cardiomyopathy of unknown origin. Methods and Results-In this 2-center study, 755 patients with clinically suspected myocarditis (nϭ481) and/or cardiomyopathy of nonischemic origin including those with infiltrative or connective tissue disease (nϭ274) underwent either selective LV-EMB (nϭ265; 35.1%), selective RV-EMB (nϭ133; 17.6%), or biventricular EMB (nϭ357; 47.3%) after coronary angiography and exclusion of significant coronary artery disease. Cardiovascular magnetic resonance, including late gadolinium enhancement, imaging was performed in 540 patients (71.5%). The major complication rate for LV-EMB was 0.64% and for RV-EMB, 0.82%. Considering postprocedural pericardial effusion that occurred after biventricular EMB, the minor complication rate for LV-EMB varied between 0.64% to 2.89% and for RV-EMB, between 2.24% and 5.10%. Diagnostic EMB results were achieved significantly more often in those patients who underwent biventricular EMBs (79.3%) compared to those who underwent either selective LV-EMB or selective RV-EMB (67.3%; PϽ0.001). In patients with biventricular EMB, myocarditis was diagnosed in LV-EMB samples in 18.7% and in RV-EMB samples in 7.9% (Pϭ0.002) , and it was diagnosed in both ventricles in 73.4%. There were no differences in the number of positive LV-EMB, RV-EMB, or LV-and RV-EMB findings when related to the site of cardiovascular magnetic resonance-based late gadolinium enhancement. Conclusions-Both

In patients with biopsy-proven cardiac amyloidosis, late gadolinium enhancement frequently occurs in a peculiar pattern. On the basis of the gold standard, EMB, noninvasive CMRI can be used to diagnose or rule out cardiac amyloidosis with good sensitivity and excellent specificity in a clinical routine setting.

Cardiovascular magnetic resonance imaging and EMB have good diagnostic performances as single techniques in patients with TnI-positive acute chest pain in the absence of CAD. The combined application of CMR and EMB yields a considerable diagnostic synergy by overcoming some limitations of CMR and EMB as individually applied techniques.

Coronary vasospasm is one of the main reasons for atypical chest pain in patients with clinical signs of myocarditis and biopsy-proven PVB19 myocarditis in the absence of significant CAD.

Systemic forms of amyloidosis affecting the heart are mostly light-chain (AL) and transthyretin (ATTR) amyloidoses. The latter is caused by deposition of misfolded transthyretin, either in wild-type (ATTRwt) or mutant (ATTRv) conformation. For diagnostics, specific serum biomarkers and modern non-invasive imaging techniques, such as cardiovascular magnetic resonance imaging (CMR) and scintigraphic methods, are available today. These imaging techniques do not only complement conventional echocardiography, but also allow for accurate assessment of the extent of cardiac involvement, in addition to diagnosing cardiac amyloidosis. Endomyocardial biopsy still plays a major role in the histopathological diagnosis and subtyping of cardiac amyloidosis. The main objective of the diagnostic algorithm outlined in this position statement is to detect cardiac amyloidosis as reliably and early as possible, to accurately determine its extent, and to reliably identify the underlying subtype of amyloidosis, thereby enabling subsequent targeted treatment.

We could demonstrate in humans that USPIO-based contrast agents enable a more detailed characterization of myocardial infarct pathology mainly by detecting infiltrating macrophages. Considering the multi-functionality of USPIO-based particles and their superior safety profile compared with gadolinium-based compounds, these observations open up new vistas for the clinical application of USPIO.