title: Cardiac fibrosis as a determinant of ventricular tachyarrhythmias.
abstract: Animal and emerging clinical studies have demonstrated that increased ventricular fibrosis in a setting of reduced repolarization reserve promotes early afterdepolarizations (EADs) and triggered activity that can initiate ventricular tachycardia and ventricular fibrillation (VT/VF). Increased ventricular fibrosis plays a key facilitatory role in allowing oxidative and metabolic stress-induced EADs to manifest as triggered activity causing VT/VF. The lack of such an arrhythmogenic effect by the same stressors in normal non-fibrotic hearts highlights the importance of fibrosis in the initiation of VT/VF. These findings suggest that antifibrotic therapy combined with therapy designed to increase ventricular repolarization reserve may act synergistically to reduce the risk of sudden cardiac death.
authors: Division of Cardiology, Department of Medicine, Tokai University Hachioji Hospital, Tokyo, Japan.
authors: Norishige
authors: N
authors: Morita
authors: Translational Arrhythmia Research Section, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors: William J
authors: WJ
authors: Mandel
authors: Division of Cardiology, Department of Medicine, Tokai University Hachioji Hospital, Tokyo, Japan.
authors: Yoshinori
authors: Y
authors: Kobayashi
authors: Division of Cardiology, Department of Medicine, Tokai University Hachioji Hospital, Tokyo, Japan.
authors: Hrayr S
authors: HS
authors: Karagueuzian
keywords: Cardiac fibrosis; anti-fibrotic therapy; oxidative stress; repolarization reserve; ventricular fibrillation
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