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

The objective of the present study was to quantify repolarization lability and its association with sex, sleep stage, and cardiovascular mortality. 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 min according to the dominant sleep stage [wakefulness, nonrapid eye movement stage 2 (NREM2), nonrapid eye movement stage 3 (NREM3), and rapid eye movement (REM)]. To explore the effect of sleep stage and apnea-hypopnea index (AHI) on QT interval parameters, we used a general linear mixed model and mixed ANOVA. The Cox proportional hazards model was used for cardiovascular disease (CVD) death prediction. Sex-related differences in T wave amplitude ( P < 0.001) resulted 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 with wakefulness, was higher in REM than in NREM, and showed a distinct relation to AHI in all sleep stages. The T wave amplitude-corrected QTV 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. We demonstrated a significant impact of sleep stages on ventricular repolarization variability. Sex 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 showed different behaviors of heart rate variability and QTV expressed as cQTVi. cQTVi during REM sleep predicts CVD death. NEW & NOTEWORTHY We demonstrate here, for the first time, a significant impact of sleep stages on ventricular repolarization variability, quantified as QT interval variability (QTV). We showed that QTV is increased in rapid eye movement sleep, reflective of high sympathetic drive, and predicts death from cardiovascular disease. Sex-related differences in QTV are shown to be owing to differences in T wave amplitude, which should be corrected for.