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Background— Investigation of disease pathogenesis confined to protein-coding regions of the genome may be incomplete because many noncoding variants are associated with disease. We aimed to identify novel predictive markers for the course of enterovirus (CVB3) cardiomyopathy by screening for noncoding elements influencing the grossly different antiviral capacity of individual patients. Methods and Results— Transcriptome mapping of CVB3 cardiomyopathy patients revealed distinctive cardiac microRNA (miR) patterns associated with spontaneous virus clearance and recovery (CVB3-ELIM) versus virus persistence and progressive clinical deterioration (CVB3-PERS). Profiling of protein-coding genes and 754 miRs in endomyocardial biopsies of test cohorts was performed at their initial presentation, and those spontaneously eliminating the virus were compared with those with virus persistence on follow-up. miR profiling revealed highly significant differences in cardiac levels of 16 miRs, but not of protein-coding genes. Evaluation of this primary distinctive miR pattern in validation cohorts, and multivariate receiver operating characteristic curve analysis, confirmed this pattern as highly predictive for disease course (area under the curve, 0.897±0.071; 95% confidence interval, 0.758–1.000). Eight miRs were strongly induced in CVB3-PERS (miRs 135b, 155, 190, 422a, 489, 590, 601, 1290), but undetectable in CVB3-ELIM or controls. They are predicted to target multiple immune response genes, and 2 of these were confirmed by antisense-mediated ablation of miRs 135b, 190, and 422a in the monocytic THP-1 cell line. Conclusions— An immediate clinical application of the data is cardiac miR profiling to assess the risk of virus persistence and progressive clinical deterioration in CVB3 cardiomyopathy. Patients at risk are eligible for immediate antiviral therapy to minimize irreversible cardiac damage.

The clinical phenotype of human dilated cardiomyopathy (DCM) encompasses a broad spectrum of etiologically distinct disorders. We obtained the cardiac expression profile of a DCM subtype (DCMi-B19) characterized by cardiac inflammation and parvovirus B19 (B19) persistence, to identify possible new therapeutic targets in humans. By microarray analysis and TaqMan PCR endomyocardial biopsies from DCMi-P19 patients (n=8) were compared to controls w/o cardiac disease. In DCMi-B19 an expression profile with dysbalance between several gene regulatory networks was observed. Tab. 1/2 classify deregulated genes in a group closely correlated (p Table 1: EF-Independent Gene Deregulation Table 2: EF-Correlated Gene Deregulation

Introduction: Inflammation and/or viral infection are both relevant for extracellular matrix remodeling. Therefore the effects of myocardial inflammation on ECM remodeling are analyzed in this study. # Methods and results: Endomyocardial biopsies were obtained from 20 patients with established DCM (2.11±0.44 CD3 cells/mm 2 ) and 29 DCMi patients (18.91±6.41 CD3 cells/mm 2 ) comparable in age (51.45±3.15 vs. 48.48±2.39 years), LVEDD (72.7±2.2 vs. 69.76±1.06mm) and EF (26±2.99 vs. 25.86±2.0%). Total collagen content was quantified by picosiriusredstaining while the MMP2, MMP3 and TIMP1 expression was evaluated by immunohistochemistry. The MMP1, MMP3 and TIMP1 and ICTP expression in the serum was quantified by Elisa. and levels of IL6 and IL8 were measured by BioPlexAssays. Furthermore various cytokines and proteases were evaluated by real-time-PCR. In DCMi patients both CD3-lymphocyte infiltration (8.95fold, pP P P P P Conclusion: Myocardial inflammation in patients with DCMi leads to an imbalance in the MMP/TIMP-system, which attributes to the development of myocardial fibrosis.

Introduction: The biopsy based analyse, with histological, immunohistological and molecular biological analysis of myocardial tissues, represents the only possible tool to investigate the basement of inflammatory cardiomyopathy. Since development of this disease assume involvement of extracellular matrix remodelling, the analyze of this process were aimed in this article. Methods and results: Endomyocardial biopsies from patient with inflammatory cardiomyopathy (n=170) were analysed by RT-PCR, Furthermore, histological, immunohistological and biochemical methods (ELISA) were used to estimate the matrix proteins amount in myocardial tissues (n=36). All results were obtained by comparison of patient groups regarding to left ventricular ejection fraction (LVEF), EF>60 versus EF60 group. The escalating number of active CD3 cells correlated positively with BNP (ρ=0.624, p Conclusion: Myocardial inflammation lead to an imbalance in the MMP/TIMP system with development of myocardial fibrosis with significant correlation to LV-dysfunction. Extracellular matrix remodeling with an imbalance in the MMP/TIMP system plays an important role in the development of left ventricular dysfunction in inflammatory heart disease

A previously healthy 39-year-old man was admitted to our department with biventricular cardiac decompensation (New York Heart Association class IV) and acute onset of angina pectoris after a flulike disease 1 week earlier. The ECG on admission displayed ST elevations in II, III, and aVF. Troponin T on admission was increased (2.20 mg/L, normal value