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.

Our data show that activating autoantibodies against human beta-adrenergic receptors exist in approximately 25% of patients with dilated cardiomyopathy. Counteraction of such autoantibodies might contribute to the beneficial effects of beta-adrenergic receptor blockade in chronic heart failure.

Today, dilated cardiomyopathy (DCM) represents the main cause of severe heart failure and disability in younger adults and thus is a challenge for public health. About 30% of DCM cases are genetic in origin; however, the large majority of cases are sporadic, and a viral or immune pathogenesis is suspected. Following the established postulates for pathogenesis of autoimmune diseases, here we provide direct evidence that an autoimmune attack directed against the cardiac β 1 -adrenergic receptor may play a causal role in DCM. First, we immunized inbred rats against the second extracellular β 1 -receptor loop (β 1 -EC II ; 100% sequence identity between human and rat) every month. All these rats developed first, receptorstimulating anti-β 1 -EC II Ab's and then, after 9 months, progressive severe left ventricular dilatation and dysfunction. Second, we transferred sera from anti-β 1 -EC II -positive and Ab-negative animals every month to healthy rats of the same strain. Strikingly, all anti-β 1 -EC II -transferred rats also developed a similar cardiomyopathic phenotype within a similar time frame, underlining the pathogenic potential of these receptor Ab's. As a consequence, β 1 -adrenergic receptor-targeted autoimmune DCM should now be categorized with other known receptor Ab-mediated autoimmune diseases, such as Graves disease or myasthenia gravis. Although carried out in an experimental animal model, our findings should further encourage the development of therapeutic strategies that combat harmful anti-β 1 -EC II in receptor Ab-positive DCM patients.Nonstandard abbreviations used: β1-adrenergic receptor (β1-AR); β1-AR second extracellular receptor loop (β1-ECII); body weight (BW); cAMP-dependent protein kinase (PKA); cardiac output (CO); dilated cardiomyopathy (DCM); glutathione-Stransferase (GST); human embryonal kidney (HEK); immunofluorescence microscopy (IFM); 125 I-labeled cyanopindolol ([ 125 I]-CYP); isobutylmethylxanthine (IBMX); left ventricular (LV); LV end-diastolic diameter (LVED); LV end-diastolic pressure (LVEDP); LV area (LVA); LV cavity area (LVCA); LV wall area (LVWA); peak change in LV pressure per time (interval) (dp/dtmax); velocity-time integral (VTI).

Background— Trials investigating efficacy of disease management programs (DMP) in heart failure reported contradictory results. Features rendering specific interventions successful are often ill defined. We evaluated the mode of action and effects of a nurse-coordinated DMP (HeartNetCare-HF, HNC). Methods and Results— Patients hospitalized for systolic heart failure were randomly assigned to HNC or usual care (UC). Besides telephone-based monitoring and education, HNC addressed individual problems raised by patients, pursued networking of health care providers and provided training for caregivers. End points were time to death or rehospitalization (combined primary), heart failure symptoms, and quality of life (SF-36). Of 1007 consecutive patients, 715 were randomly assigned (HNC: n=352; UC: n=363; age, 69±12 years; 29% female; 40% New York Heart Association class III-IV). Within 180 days, 130 HNC and 137 UC patients reached the primary end point (hazard ratio, 1.02; 95% confidence interval, 0.81–1.30; P =0.89), since more HNC patients were readmitted. Overall, 32 HNC and 52 UC patients died (1 UC patient and 4 HNC patients after dropout); thus, uncensored hazard ratio was 0.62 (0.40–0.96; P =0.03). HNC patients improved more regarding New York Heart Association class ( P =0.05), physical functioning ( P =0.03), and physical health component ( P =0.03). Except for HNC, health care utilization was comparable between groups. However, HNC patients requested counseling for noncardiac problems even more frequently than for cardiovascular or heart-failure–related issues. Conclusions— The primary end point of this study was neutral. However, mortality risk and surrogates of well-being improved significantly. Quantitative assessment of patient requirements suggested that besides (tele)monitoring individualized care considering also noncardiac problems should be integrated in efforts to achieve more sustainable improvement in heart failure outcomes. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN23325295.

Today, dilated cardiomyopathy (DCM) represents the main cause of severe heart failure and disability in younger adults and thus is a challenge for public health. About 30% of DCM cases are genetic in origin; however, the large majority of cases are sporadic, and a viral or immune pathogenesis is suspected. Following the established postulates for pathogenesis of autoimmune diseases, here we provide direct evidence that an autoimmune attack directed against the cardiac β 1 -adrenergic receptor may play a causal role in DCM. First, we immunized inbred rats against the second extracellular β 1 -receptor loop (β 1 -EC II ; 100% sequence identity between human and rat) every month. All these rats developed first, receptorstimulating anti-β 1 -EC II Ab's and then, after 9 months, progressive severe left ventricular dilatation and dysfunction. Second, we transferred sera from anti-β 1 -EC II -positive and Ab-negative animals every month to healthy rats of the same strain. Strikingly, all anti-β 1 -EC II -transferred rats also developed a similar cardiomyopathic phenotype within a similar time frame, underlining the pathogenic potential of these receptor Ab's. As a consequence, β 1 -adrenergic receptor-targeted autoimmune DCM should now be categorized with other known receptor Ab-mediated autoimmune diseases, such as Graves disease or myasthenia gravis. Although carried out in an experimental animal model, our findings should further encourage the development of therapeutic strategies that combat harmful anti-β 1 -EC II in receptor Ab-positive DCM patients.Nonstandard abbreviations used: β1-adrenergic receptor (β1-AR); β1-AR second extracellular receptor loop (β1-ECII); body weight (BW); cAMP-dependent protein kinase (PKA); cardiac output (CO); dilated cardiomyopathy (DCM); glutathione-Stransferase (GST); human embryonal kidney (HEK); immunofluorescence microscopy (IFM); 125 I-labeled cyanopindolol ([ 125 I]-CYP); isobutylmethylxanthine (IBMX); left ventricular (LV); LV end-diastolic diameter (LVED); LV end-diastolic pressure (LVEDP); LV area (LVA); LV cavity area (LVCA); LV wall area (LVWA); peak change in LV pressure per time (interval) (dp/dtmax); velocity-time integral (VTI).