Heart failure duration progressively modulates the arrhythmia substrate through structural and electrical remodeling

Abstract

Listen

Translate article

AimsVentricular arrhythmias are a common cause of death in patients with heart failure (HF). Structural and electrical abnormalities in the heart provide a substrate for such arrhythmias. Canine tachypacing-induced HF models of 4–6weeks duration are often used to study pathophysiology and therapies for HF. We hypothesized that a chronic canine model of HF would result in greater electrical and structural remodeling than a short term model, leading to a more arrhythmogenic substrate. Main methodsHF was induced by ventricular tachypacing for one (short-term) or four (chronic) months to study remodeling. Key findingsLeft ventricular contractility was progressively reduced, while ventricular hypertrophy and interstitial fibrosis were evident at 4month but not 1month of HF. Left ventricular myocyte action potentials were prolonged after 4 (p<0.05) but not 1month of HF. Repolarization instability and early afterdepolarizations were evident only after 4months of HF (p<0.05), coinciding with a prolonged QTc interval (p<0.05). The transient outward potassium current was reduced in both HF groups (p<0.05). The outward component of the inward rectifier potassium current was reduced only in the 4month HF group (p<0.05). The delayed rectifier potassium currents were reduced in 4 (p<0.05) but not 1month of HF. Reactive oxygen species were increased at both 1 and 4months of HF (p<0.05). SignificanceReduced Ito, outward IK1, IKs, and IKr in HF contribute to EAD formation. Chronic, but not short term canine HF, results in the altered electrophysiology and repolarization instability characteristic of end-stage human HF.