Increased intraventricular pressures are as harmful as the electrophysiological substrate of heart failure in favoring sustained reentry in the swine heart

Abstract

Background: Heart failure (HF) electrophysiological remodeling (HF-ER) often includes the effect of chronically increased intraventricular pressures (IVPs) and promotes ventricular tachycardia/ventricular fibrillation (VT/VF). In addition, acutely increased IVPs have been associated with a higher rate of VT/VF episodes in chronic HF.

Objective: We hypothesized that increased IVPs and/or an ionic-imbalanced (acidified), catecholamine-rich (adrenergic) milieu (AA milieu) may contribute as much as HF-ER to the substrate for reentry in HF. We used a porcine model of tachycardiomyopathy and evaluated the individual/combined contributions of (1) increased IVPs, (2) HF-ER, and (3) an AA milieu.

Methods: HF-ER was induced in 7 pigs by rapid pacing. Seven pigs were used as controls. Hearts were isolated and Langendorff perfused. Programmed ventricular stimulation was conducted under low or increased IVP and normal/AA milieu (4 combinations). Epicardial optical mapping was used to quantify conduction velocity (CV), action potential duration (APD), and dispersion of repolarization (DoR).

Results: HF-ER decreased CV (-34%; P = .002) and increased APD (11%; P = .024) and DoR (21%; P = .007). Increased IVP amplified DoR (36%; P < .001) and decreased CV (-17%; P = .001) and APD (-8%; P < .001). The AA milieu consistently modified only APD (-9%; P < .001) and led to amplified inter-/intra-subject heterogeneity. Increased IVP similarly raised the odds of inducing sustained VT/VF as the presence of HF-ER (>6-fold).

Conclusion: By magnifying DoR, decreasing CV, and shortening APD, increased IVP was as harmful as HF-ER in favoring the substrate for sustained reentry in this model. The AA milieu contributed to a much lesser extent. Thus, a stricter control of IVP might be postulated as a useful add-on antiarrhythmic strategy in HF.

Keywords: Arrhythmias; Heart failure; Optical mapping; Reentry; Remodeling; Stretch.