Heterogeneous regional endocardial repolarization is associated with increased risk for ischemia-dependent...

Repolarization Heterogeneity and Sudden Death Risk.

The aim of this study was to investigate whether the characteristics of endocardial ventricular repolarization are associated with differential risk for sudden death. Prolonged surface QT interval is associated with increased arrhythmic risk after myocardial infarction (MI), but the underlying mechanism of QT prolongation and its relation to lethal arrhythmias are unclear.

Ventricular fibrillation (VF) risk was assessed in 12 dogs 1 month after anterior MI during an exercise test coupled with brief circumflex coronary occlusion. Susceptible dogs (n = 5) developed VF during the brief ischemic episode, whereas resistant dogs did not (n = 7). Surface QT interval was measured at rest. Endocardial electroanatomic catheter maps of left ventricular repolarization were obtained in four unique regions identified by echocardiography and compared between groups. Compared to resistant dogs, susceptible dogs were characterized by prolonged surface QT intervals (240 +/- 10 msec vs 222 +/- 7 msec, P = 0.04). In addition, they had lower baroreflex sensitivity (9.7 +/- 1.5 msec/mmHg vs 28 +/- 9.8 msec/mmHg, P < 0.01) and a tachycardic response to acute ischemia suggesting higher propensity for stronger sympathetic reflexes. Surface QT interval prolongation in susceptible dogs was due to a marked heterogeneity of endocardial left ventricular repolarization (239 +/- 42 msec, basal anterior wall vs 197 +/- 35, lateral wall; P < 0.001). Resistant animals had no regional differences in endocardial repolarization.

Sympathetic activation following MI not only produces adverse structural remodeling but also contributes to adverse electrophysiologic remodeling resulting in heterogeneous ventricular repolarization and in a myocardial substrate conducive to lethal reentrant arrhythmias.