Abstract 500: Progression of Chronic Ischemia-Mediated Arrhythmogenesis in a Rat Model of Heart Failure

Abstract

Background: Worldwide, the prevalence of heart failure (HF) is increasing and HF patients are living longer. Chronic ischemic HF presents with increased vulnerability to ventricular tachycardia and fibrillation. However, the mechanism of these arrhythmias differ between the acute infarction phase and the chronic, namely via myocyte membrane potential instability in the acute phase versus substrate-mediated reentry in the chronic phase. We propose our chronic heart failure (CHF) model to recapitulate the potentially progressive nature of arrhythmogenesis in the chronic phase. Methods: Adult male Sprague Dawley rats underwent permanent left coronary artery ligation and were maintained for six or ten weeks; SHAM operations were also performed. At each respective endpoint, SHAM and CHF rats underwent transthoracic echocardiography and invasive hemodynamic evaluation. Finally, a median sternotomy was performed for epicardial electrophysiology (EP) assessment. Programmed electrical stimulation was utilized to assess susceptibility to induced ventricular tachycardia (VT) and also to determine effective refractory period (ERP). Results: Six-week CHF (n=50) induction proved successful as evidenced by the decrease in left ventricular ejection fraction (LVEF) (76±3% to 35±2%, p<0.0001) and the increase in left ventricular end-diastolic pressure (LVEDP) (6±1 mmHg to 20±2 mmHg, p=0.0008) compared to SHAM (n=15). Progression to ten-week CHF (n=18) also proved successful via LVEF and LVEDP maintenance (35±2% to 38±3%, p=0.3909) (20±2 mmHg to 15±3 mmHg, p=0.1578). EP studies revealed an increase in the incidence of induced VT between SHAM and six-week CHF (0% to 60%, p<0.0001) and a prolongation of the ERP (54±4 milliseconds to 69±3 ms, p=0.0228). The incidence of induced VT and ERP did not continue to increase between six- and ten-week CHF (60% to 50%, p=0.5804), (69±3 ms to 68±3 ms, p=0.8221). Conclusion: Myocardial infarction-mediated arrhythmogenesis is known to exist in an acute and a chronic phase. Here, we examine the chronic phase of ischemic HF and show evidence to support that once the adverse remodeling-mediated substrate stabilizes, proarrhythmic deterioration ceases.