Sudden cardiac death in dogs with remodeled hearts is associated with larger beat?to?beat variability of repolarization

Abstract

Increased proarrhythmia in dogs with chronic AV block (AVB) has been explained by ventricular remodeling causing a decrease in repolarization reserve. Beat-to-beat variability of repolarization (BVR) has been suggested to reflect repolarization reserve, in which high variability represents diminished reserve and larger propensity for repolarization-dependent ventricular arrhythmia. A subset of chronic AVB dogs (10%) suffers sudden cardiac death (SCD). With the assumption that repolarization defects constitute a potentially lethal proarrhythmic substrate, we hypothesized that BVR in SCD dogs are larger than in matched control chronic AVB dogs. From a population of 200 chronic AVB dogs, initially two groups were chosen retrospectively: 8 dogs that died suddenly (SCD) and 8 control dogs. Control dogs had a longer lifespan after AVB (10 to 18 weeks) than SCD dogs (5 to 10 weeks). All dogs had undergone electrophysiological testing under anesthesia where ECG, left and right ventricular endocardial monophasic action potentials (MAP) were recorded. BVR was assessed from 30 consecutive beats, illustrated by Poincare plots and was the only parameter discriminating between SCD and control group. All other electrophysiological parameters (RR, QT and MAP durations) were comparable for the two groups. Extending the number of animals and groups confirmed a larger BVR in the SCD group (SCD: 5.1 +/- 2.7; n = 11 versus control: 2.5 +/- 0.4 ms; n = 61; P < 0.05) and showed reverse-use dependence of BVR. In comparison, dogs with acute AVB had low variability (1.3 +/- 0.3 ms; n = 9; P < 0.05 versus chronic AVB). Cardiac electrical remodeling after AVB is associated with an increase in beat-to-beat variability of repolarization. Chronic AVB dogs displaying further elevated variability of repolarization are prone to arrhythmia-related SCD.