Nocturnal ventricular repolarization lability predicts cardiovascular mortality in the Sleep Heart Health Study

Abstract

Background-The objective of this study was to quantify repolarization lability and its association with sex, sleep stage and cardiovascular mortality. Methods-We analyzed polysomnographic recordings of 2,263 participants enrolled in the Sleep heart health study (SHHS-2). Beat-to-beat QT interval variability (QTV) was quantified for consecutive epochs of 5 minutes according to the dominant sleep stage (AWAKE, NREM2, NREM3, REM). To explore the effect of sleep stage and apnea-hypopnea index (AHI) on QT interval parameters we employed a general linear mixed model and mixed ANOVA. Cox proportional hazards model was used for cardiovascular disease (CVD) death prediction. Results-Gender-related differences in T wave amplitude (p < 0.001) result in artificial QTV differences. Hence, we corrected QTV parameters by T wave amplitude for further analysis. Sleep stages showed a significant effect (p < 0.001) on QTV. QTV was decreased in deep sleep compared to wakefulness, is higher in REM than in NREM, and shows a distinct relation to AHI in all sleep stages. T wave amplitude corrected QT interval variability index (cQTVi) in REM sleep was predictive of CVD death (Hazard ratio: 2.067, 95% confidence interval: 1.105 - 3.867; p < 0.05) in a proportional hazards model. Conclusions-We demonstrate a significant impact of sleep stages on ventricular repolarization variability. Gender differences in QTV are due to differences in T wave amplitude, which should be corrected for. Independent characteristics of QTV measures to sleep stages and AHI show different behaviors of HRV and QTV expressed in cQTVi. cQTVi during REM sleep predicts CVD death.