Investigating Electrophysiological Markers of Arrhythmogenesis in a Chronic Myocardial Infarction Ovine Model

Cardiac alternans has been associated with an increased propensity to lethal tachyarrhythmias such as ventricular tachycardia and fibrillation (VT/VF). Myocardial infarction (MI), resulting from restricted oxygen supply to the heart, is a known substrate for VT/VF. Here, we investigate the utility of cardiac alternans as a predictor of tachyarrhythmias in a chronic MI ovine model. In-vivo electrophysiological studies were performed to assess the change in microvolt T-wave alternans (TWA) with induction of acute ischemia following coronary artery occlusion. 24-hour telemetry was performed in an ambulatory animal for 6 weeks to monitor the progression of TWA with chronic MI. At 6 weeks, ex-vivo optical mapping experiments were performed to assess the spatiotemporal evolution of alternans in sham (n=5) and chronic MI hearts (n=8). Our results demonstrate that chronic MI leads to significant electrophysiological changes in the cardiac substrate. Significant increase in TWA is observed post occlusion and a steady rise in alternans is seen with progression of chronic MI. Compared to sham, chronic MI hearts show significant presence of localized action potential amplitude alternans, which spatially evolve with an increase in pacing frequency. Clinical Relevance — Our results demonstrate that localized alternans underlie arrhythmogenesis in chronic MI hearts and microvolt TWA can serve as a biomarker of disease progression during chronic MI.