Early autonomic and repolarization abnormalities contribute to lethal arrhythmias in chronic ischemic heart failure: Characteristics of a novel heart failure model in dogs with postmyocardial infarction left ventricular dysfunction

Abstract

OBJECTIVESUsing a model of arrhythmias associated with ischemic left ventricular (LV) dysfunction, this study investigated autonomic and electrophysiologic mechanisms associated with sudden cardiac death (SCD) in chronic heart failure (HF).BACKGROUNDLeft ventricular dysfunction from ischemic heart disease is associated with many instances of SCD. Electrophysiologic and autonomic derangements occur in HF, but their contribution to SCD risk is poorly understood.METHODSSudden death risk was assessed in 15 dogs with a healed anterior myocardial infarction (MI) during submaximal exercise and brief acute circumflex ischemia. Left ventricular dysfunction was then induced by repetitive circumflex microembolization until LV ejection fraction reached 35%. Before embolization, six dogs were susceptible to SCD, and nine were resistant.RESULTSBaroreflex sensitivity was lower in susceptible dogs (10 ms/mm Hg ± 4 ms/mm Hg vs. 20 ms/mm Hg ± 11 ms/mm Hg, p = 0.04). QT intervals from susceptible dogs were longer after MI (246 ms ± 26 ms susceptible vs. 231 ms ± 20 ms resistant, p < 0.001) and prolonged within eight weeks after LV dysfunction was established (from 246 ms ± 26 ms to 274 ms ± 56 ms, +11%, p < 0.01). Heart rate in susceptible dogs increased during transient ischemia (+20%) and with progressive LV dysfunction (102 beats/min ± 28 beats/min baseline to 154 beats/min ± 7 beats/min LV dysfunction, p = 0.003). All susceptible dogs had spontaneous sustained ventricular tachycardia culminating in SCD. In contrast, QT intervals in resistant dogs prolonged after 24 ± 6 weeks (from 231 ms ± 20 ms to 238 ms ± 15 ms, p < 0.05), and heart rates were unchanged. Only one resistant dog died suddenly with LV dysfunction.CONCLUSIONSDepressed vagal and elevated sympathetic control of heart rate coupled with abnormal repolarization are associated with high SCD risk when post-MI LV dysfunction develops.