Increased ventricular fibrosis in a setting of reduced repolarization reserve promotes early afterdepolarizations and triggered activity that initiate ventricular tachycardia and fibrillation.
Ventricular fibrosis plays a critical role in initiating VT/VF by facilitating early afterdepolarizations, highlighting a potential synergistic role for antifibrotic and repolarization-enhancing therapies.
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.
Morita et al. (Thu,) conducted a review in Ventricular tachyarrhythmias. Increased ventricular fibrosis in a setting of reduced repolarization reserve promotes early afterdepolarizations and triggered activity that initiate ventricular tachycardia and fibrillation.