Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and sudden cardiac death

Abstract

Many survivors of sudden cardiac death (SCD) have normal global ventricular function and severe coronary artery disease but no evidence of symptomatic ischemia or infarction before the development of lethal ventricular arrhythmias, and the trigger for ventricular tachycardia (VT)/ventricular fibrillation (VF) remains unclear. We sought to identify the role of spontaneous ischemia and temporal hemodynamic factors preceding SCD using continuous telemetry of left ventricular (LV) pressure and the ECG for periods up to 5 mo in swine (n = 37) with hibernating myocardium who experience spontaneous VT/VF in the absence of heart failure or infarction. Hemodynamics and ST deviation at the time of VT/VF were compared with survivors with hibernating myocardium as well as sham controls. All episodes of VT/VF occurred during sympathetic activation and were initiated by single premature ventricular contractions, and the VT degenerated into VF in ∼ 30 s. ECG evidence of ischemia was infrequent and no different from those that survived. Baseline hemodynamics were no different among groups, but LV end-diastolic pressure during sympathetic activation was higher at the time of SCD (37 ± 4 vs. 26 ± 4 mmHg, P < 0.05) and the ECG demonstrated QT shortening (155 ± 4 vs. 173 ± 5 ms, P < 0.05). The week before SCD, both parameters were no different from survivors. These data indicate that there are no differences in the degree of sympathetic activation or hemodynamic stress when VT/VF develops in swine with hibernating myocardium. The transiently elevated LV end-diastolic pressure and QT shortening preceding VT/VF raises the possibility that electrocardiographically silent subendocardial ischemia and/or mechanoelectrical feedback serve as a trigger for the development of SCD in chronic ischemic heart disease.

Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy

“…These factors would also tend to promote interstitial fibrosis, which would delay ventricular impulse conduction and increase the risk of reentry. They could also lead to stretch-induced arrhythmogenesis which has been observed in an animal model of sudden death from chronic ischemia without infarction 21 .…”

Prognostic Significance of Imaging Myocardial Sympathetic Innervation

“…These changes are accompanied by an increased risk of SCD from VT/VF in the absence of severely depressed global function as well as acute or chronic infarction [25–27]. Myocardial uptake of 123 I-MIBG was reduced in swine with hibernating myocardium with the greatest reduction seen in the subendocardium [8], coinciding with the region with the most severe limitation in coronary flow reserve.…”

Life-Threatening Ventricular Arrhythmias: Current Role of Imaging in Diagnosis and Risk Assessment

“…In preclinical studies, viable dysfunctional myocardial regions can exhibit partial sympathetic denervation (25), evidence of reinnervation as reflected by sympathetic nerve sprouting (25, 26) and alterations in beta adrenergic receptor density (27). The translational relevance of these findings is underscored by the fact that animal models of viable dysfunctional myocardium exhibit one of the highest rates of spontaneous SCA from VF during brief sympathetic activation in the absence of infarction(28, 29). …”