Exploiting rate-related hysteresis in repolarization alternans to improve risk stratification for ventricular tachycardia

OBJECTIVES We sought to study the effect of heart rate acceleration and deceleration on the ability of repolarization alternans (RPA) to stratify ventricular tachycardia (VT) risk. BACKGROUND Heart rate fluctuations alter arrhythmic propensity, yet it is unclear whether fluctuations, as well as absolute rate, dynamically increase VT risk. We hypothesized that repolarization heterogeneity reflected by RPA would exhibit hysteresis during rising and falling heart rate, which may reflect arrhythmic propensity. METHODS The RPA magnitude (absolute voltage of alternation [Valt] and T-wave alternans ratio [TWAR]) and temporal distribution were determined from the electrocardiogram (ECG) in 60 patients during paced heart rate acceleration from 100 to 150 beats/min, then deceleration to 100 beats/min at electrophysiologic study (EPS). The Valt and TWAR thresholds were varied prospectively to generate receiver-operating characteristics (ROC) for the prediction of inducible VT at EPS. RESULTS Thirty-six patients were induced into VT and 24 were not. Hysteresis of RPA was seen. The Valt reached steady-state within 60 beats of each rate transition and was higher in deceleration than in acceleration at matched heart rates. In induced patients, Valt rose then fell with heart rate. In noninduced patients, Valt was insensitive to acceleration, but rose on initial deceleration. The RPA distributed later within repolarization in induced patients but, on deceleration, moved earlier in both groups. By ROC analysis, Valt = 2.6 μV in late repolarization at 120 beats/min provided optimal sensitivity and specificity for VT in acceleration (87.5% and 88.7%, respectively) versus deceleration (80% and 62.5%, respectively; p = 0.004, chi-square test). CONCLUSIONS 1) Physiologic fluctuations in heart rate may affect the clinical utility of RPA for VT risk stratification; and 2) repolarization dispersion measured by RPA is more exaggerated during deceleration than acceleration at matched heart rates (rate hysteresis).