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.

Effect of β3-adrenoceptor on cardiac fibrosis in rat cardiac fibroblast cells and its potential mechanism

“…Furthermore, collagen is the most abundant protein in animal tissues and also the major component in the interstitial extracellular matrix. Previous researches have revealed that Col-I and Col-III would be overexpressed in patients with cardiac fibrosis, and Col-I/III could be considered as the biomarkers of cardiac fibrosis [20,21]. In our present investigation, up-regulation of β3-AR increased the expressions of Col-I and Col-III.…”

Therapy for ventricular arrhythmias in structural heart disease: a multifaceted challenge

“…The fibrosis of the myocardial scar may cause arrhythmias through different mechanisms. Fibrosis can unbalance the sink-source mechanism that is responsible for eliminating early after-depolarizations induced by oxidative stress, allowing for a greater susceptibility to early after-depolarizations and resulting triggered activity (Morita et al 2014).…”

Effect of myocyte-fibroblast coupling on the onset of pathological dynamics in a model of ventricular tissue

“…Recently, there has been much interest in understanding the proarrhythmic tendencies of fibrosis, especially through its effect on afterdepolarization26. These afterpotentials can result in triggered activity causing fibrillation in both the atria27 and the ventricles2829.…”