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Heinzpeter Schultheiss - One of the best experts on this subject based on the ideXlab platform.
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betaferon in chronic Viral Cardiomyopathy bicc trial effects of interferon β treatment in patients with chronic Viral Cardiomyopathy
Clinical Research in Cardiology, 2016Co-Authors: Heinzpeter Schultheiss, Matthias Pauschinger, Cornelia Piper, Olaf Sowade, F Waagstein, Joachim Friedrich Kapp, Karl Wegscheider, Georg Groetzbach, Felicitas Escher, Eloisa ArbustiniAbstract:Chronic Viral infections of the heart are considered one antecedent event leading to progressive dysfunction of the myocardium, often with an impaired prognosis due to a virus- or immune-mediated myocardial injury. Symptomatic treatment does not influence the Viral cause of heart failure, and the effect of antiViral treatment has not been determined, yet. In this phase II study 143 patients with symptoms of heart failure and biopsy-based confirmation of the enterovirus (EV), adenovirus, and/or parvovirus B19 genomes in their myocardial tissue were randomly assigned to double-blind treatment, and received either placebo (n = 48) or 4 × 106 (n = 49) and 8 × 106 IU (n = 46) interferon beta-1b (IFN-β-1b) for 24 weeks, in addition to standard heart failure treatment. Patients with active myocarditis or other specific causes of heart failure were excluded. Compared to placebo, virus elimination and/or virus load reduction was higher in the IFN-β-1b groups (odds ratio 2.33, p = 0.048), similarly in both interferon groups and both strata. IFN-β-1b treatment was associated with favourable effects on NYHA functional class (p = 0.013 at follow-up week 12), improvement in quality of life (Minnesota Heart Failure score; p = 0.032 at follow-up week 24) and patient global assessment (follow-up week 12 to follow-up week 24; p = 0.039). The frequency of adverse cardiac events was not higher in the IFN-β-1b groups compared to the placebo group. Immunomodulatory IFN-β-1b treatment is a well-tolerated and safe treatment option, leading to effective virus clearance or reduction of the virus load in patients with chronic Viral Cardiomyopathy. Favourable clinical effects assess quality of life, NYHA functional class, and patient global assessment. ClinicalTrials.gov identifier: NCT001185250
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the toll like receptor 4 ligands s100a8 and s100a9 are crucial factors in Viral Cardiomyopathy
Journal of the American College of Cardiology, 2013Co-Authors: Peter Moritz Becher, Heinzpeter Schultheiss, Diana Lindner, Kostantinos Savvatis, Irene Muller, Matthias Frohlich, Thomas J Vogl, Johannes Roth, Carsten TschopeAbstract:Various Toll-like receptors (TLRs) are a part of the innate immune system and involved in cardiac immune response after Viral infection. Potential endogenous ligands of TLRs and their function in Viral myocarditis still remain unclear. In the present study we investigated the role of the alarmins
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antiViral interferon β treatment in patients with chronic Viral Cardiomyopathy
2010Co-Authors: Heinzpeter Schultheiss, Michel Noutsias, Uwe KuhlAbstract:The etiology of “idiopathic” dilated Cardiomyopathy (DCM) is due to persistence of viruses in ca. 60% of the patients presenting with DCM. This can be concluded from the high rate of detectable Viral genomes in endomyocardial biopsy (EMB) samples in such patients. The pivotal role of interferons (IFN) as a natural defense system against viruses is well documented by experimental data. In an open-label pilot trial, 22 patients with EMB-proven persistence of Viral genomes [enterovirus (EV), 15 patients; adenovirus (ADV), 7 patients] were treated with recombinant IFN-β1a. In parallel to the Viral elimination proven after 6-month antiViral treatment, left ventricular ejection fraction (LVEF) improved, end-diastolic diameters declined significantly, and an amelioration of heart failure symptoms was evident. In patients with immunohistologically proven intramyocardial inflammation a substantial decrease of infiltrates and cell adhesion molecule expression was noted after IFN treatment. There were no severe side effects. Based on the favorable results of this pilot study, the randomized European-wide multicenter BICC trial (Betaferon®: Interferon-β in Patients With Chronic Viral Cardiomyopathy) for IFN-β1b treatment of patients with EMB-proven persistence of EV, ADV and parvovirus B19 (B19V) was conducted.
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differential aspects of endothelial function of the coronary microcirculation considering myocardial virus persistence endothelial activation and myocardial leukocyte infiltrates
Circulation, 2005Co-Authors: Katja B Vallbracht, Peter L Schwimmbeck, Uwe Kuhl, Ursula Rauch, Bettina Seeberg, Heinzpeter SchultheissAbstract:Background— Viral Cardiomyopathy resulting from myocardial virus persistence can be associated with inflammatory immune responses that involve the myocardium and coronary blood vessels. The aim of this study was to investigate the differential impact of myocardial virus persistence and inflammation on endothelial function of the coronary microcirculation. Methods and Results— In 71 patients with nonischemic Cardiomyopathy, myocardial biopsies were examined for virus persistence (by polymerase chain reaction) and inflammation (by immunohistology). Endothelial function of the coronary microcirculation was examined during heart catheterization by measuring diameter (by quantitative coronary angiography) and velocity changes (by intracoronary Doppler) of the left anterior descending artery in response to acetylcholine. Coronary blood flow (CBF) was calculated. Endothelium-independent vasoreactivity to adenosine was assessed. Mean age of the patients (37 men, 34 women) was 43±13 years; mean ejection fraction w...
Mingdong Zhou - One of the best experts on this subject based on the ideXlab platform.
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neuregulin 1 erbb activation improves cardiac function and survival in models of ischemic dilated and Viral Cardiomyopathy
Journal of the American College of Cardiology, 2006Co-Authors: Xifu Liu, Jianjie Chang, Ping Chen, Jing Jin, Denghong Chen, Donna Lai, Robert M Graham, Mingdong ZhouAbstract:Objectives We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2aisoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Background Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced Cardiomyopathy. Methods rhNRG-1 was administered IV to animal models of ischemic, dilated, and Viral Cardiomyopathy, and cardiac function and survival were evaluated. Results Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and Viral Cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. Conclusions These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.
Xifu Liu - One of the best experts on this subject based on the ideXlab platform.
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neuregulin 1 erbb activation improves cardiac function and survival in models of ischemic dilated and Viral Cardiomyopathy
Journal of the American College of Cardiology, 2006Co-Authors: Xifu Liu, Jianjie Chang, Ping Chen, Jing Jin, Denghong Chen, Donna Lai, Robert M Graham, Mingdong ZhouAbstract:Objectives We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2aisoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Background Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced Cardiomyopathy. Methods rhNRG-1 was administered IV to animal models of ischemic, dilated, and Viral Cardiomyopathy, and cardiac function and survival were evaluated. Results Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and Viral Cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. Conclusions These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.
Carsten Tschope - One of the best experts on this subject based on the ideXlab platform.
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the toll like receptor 4 ligands s100a8 and s100a9 are crucial factors in Viral Cardiomyopathy
Journal of the American College of Cardiology, 2013Co-Authors: Peter Moritz Becher, Heinzpeter Schultheiss, Diana Lindner, Kostantinos Savvatis, Irene Muller, Matthias Frohlich, Thomas J Vogl, Johannes Roth, Carsten TschopeAbstract:Various Toll-like receptors (TLRs) are a part of the innate immune system and involved in cardiac immune response after Viral infection. Potential endogenous ligands of TLRs and their function in Viral myocarditis still remain unclear. In the present study we investigated the role of the alarmins
Uwe Kuhl - One of the best experts on this subject based on the ideXlab platform.
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antiViral interferon β treatment in patients with chronic Viral Cardiomyopathy
2010Co-Authors: Heinzpeter Schultheiss, Michel Noutsias, Uwe KuhlAbstract:The etiology of “idiopathic” dilated Cardiomyopathy (DCM) is due to persistence of viruses in ca. 60% of the patients presenting with DCM. This can be concluded from the high rate of detectable Viral genomes in endomyocardial biopsy (EMB) samples in such patients. The pivotal role of interferons (IFN) as a natural defense system against viruses is well documented by experimental data. In an open-label pilot trial, 22 patients with EMB-proven persistence of Viral genomes [enterovirus (EV), 15 patients; adenovirus (ADV), 7 patients] were treated with recombinant IFN-β1a. In parallel to the Viral elimination proven after 6-month antiViral treatment, left ventricular ejection fraction (LVEF) improved, end-diastolic diameters declined significantly, and an amelioration of heart failure symptoms was evident. In patients with immunohistologically proven intramyocardial inflammation a substantial decrease of infiltrates and cell adhesion molecule expression was noted after IFN treatment. There were no severe side effects. Based on the favorable results of this pilot study, the randomized European-wide multicenter BICC trial (Betaferon®: Interferon-β in Patients With Chronic Viral Cardiomyopathy) for IFN-β1b treatment of patients with EMB-proven persistence of EV, ADV and parvovirus B19 (B19V) was conducted.
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new therapeutics targets in chronic Viral Cardiomyopathy
Ernst Schering Research Foundation workshop, 2006Co-Authors: W Poller, Uwe Kuhl, Henry Fechner, Matthias Pauschinger, H P SchultheissAbstract:Dilated Cardiomyopathy (DCM) is a prevalent heart muscle disease characterized by impaired contractility and dilation of the ventricles. Recent clinical research suggests that cardiotropic viruses are important environmental pathogenic factors in human DCM, which may therefore be considered as a chronic Viral Cardiomyopathy. All virus-positive DCM patients thus come into the focus of virological research and should be considered for antiViral strategies. Interferon-β therapy has been shown to mediate virus elimination in patients with adenovirus or coxsackievirus persistence.We discuss here several possible new molecular targets for patients infected with cardiotropic viruses in (1) the cellular virus uptake system, (2) virus-induced cellular signaling pathways, and (3) interactions between virus-encoded proteins with important cellular target proteins. The potential of these approaches in the setting of a chronic Viral infection is significantly different from that in an acute Viral infection. Specific problems encountered in a chronic situation and possible solutions are discussed.
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differential aspects of endothelial function of the coronary microcirculation considering myocardial virus persistence endothelial activation and myocardial leukocyte infiltrates
Circulation, 2005Co-Authors: Katja B Vallbracht, Peter L Schwimmbeck, Uwe Kuhl, Ursula Rauch, Bettina Seeberg, Heinzpeter SchultheissAbstract:Background— Viral Cardiomyopathy resulting from myocardial virus persistence can be associated with inflammatory immune responses that involve the myocardium and coronary blood vessels. The aim of this study was to investigate the differential impact of myocardial virus persistence and inflammation on endothelial function of the coronary microcirculation. Methods and Results— In 71 patients with nonischemic Cardiomyopathy, myocardial biopsies were examined for virus persistence (by polymerase chain reaction) and inflammation (by immunohistology). Endothelial function of the coronary microcirculation was examined during heart catheterization by measuring diameter (by quantitative coronary angiography) and velocity changes (by intracoronary Doppler) of the left anterior descending artery in response to acetylcholine. Coronary blood flow (CBF) was calculated. Endothelium-independent vasoreactivity to adenosine was assessed. Mean age of the patients (37 men, 34 women) was 43±13 years; mean ejection fraction w...
