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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2006.05.004 Byline: Stefan Stork (a), Valerie Boivin (b), Rudiger Horf (a), Lutz Hein (b), Martin J. Lohse (b), Christiane E. Angermann (a), Roland Jahns (a)(b) Abstract: The aim of this study was to estimate the independent and incremental prognostic value of the presence of stimulating autoantibodies directed against the human [beta].sub.1-adrenergic receptor (anti-[beta].sub.1-AR) in patients with chronic heart failure. Author Affiliation: (a) Department of Internal Medicine I / Center of Cardiovascular Medicine, University of Wurzburg, Wurzburg, Germany (b) Institute of Pharmacology and Toxicology, University of Wurzburg, Wurzburg, Germany Article History: Received 12 January 2006; Accepted 2 May 2006 Article Note: (footnote) Funding source: Deutsche Forschungsgemeinschaft, Grant Ja 706/2-4; Ernst und Berta Grimmke Stiftung, Dusseldorf, Germany.

Objective: Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results: Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion: This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise localization of tissue damage free of MR contrast agents., Version of Record

Background: The aim of this study was to estimate the independent and incremental prognostic value of the presence of stimulating autoantibodies directed against the human β1-adrenergic receptor (anti–β1-AR) in patients with chronic heart failure. Methods: One hundred five antibody-typed chronic heart failure patients with dilated cardiomyopathy (DCM, n = 65) or ischemic cardiomyopathy (ICM, n = 40) were prospectively followed for 10.7 ± 2.5 years. Information on all-cause and cardiovascular mortality was collected throughout the observation period. Results: Stimulating anti–β1-AR were prevalent in 26% (17/65) of patients with DCM and 13% (5/40) with ICM. All-cause mortality in antibody-positive patients was 65% in those with DCM and 80% in those with ICM, and in antibody-negative patients 44% and 49%, respectively. In univariate and multivariable Cox regression analysis (P < .05), presence of stimulating anti–β1-AR was associated with increased all-cause and cardiovascular mortality risk in DCM but not in ICM. Information on antibody status improved the prognostic capacity in models containing already extensive information on clinical profile, Holter electrocardiography, and invasive hemodynamic measurements (area under the receiver operating characteristic curve, 0.91; 95% confidence interval, 0.85-0.97; P < .05 for increase in receiver operating characteristic area). Conclusion: The presence of stimulating anti–β1-AR autoantibodies independently predicts increased all-cause and cardiovascular mortality risk in DCM conferring incremental prognostic value in addition to established risk predictors. Our data indicate a clinical relevance of stimulating anti–β1-AR in DCM and encourage further research into antibody-directed strategies as a therapeutic principle. [Copyright &y& Elsevier]