Sleep-disordered breathing destabilizes ventricular repolarization: Cross-sectional, longitudinal, and experimental evidence

Abstract

Background: Sleep-disordered breathing (SDB) increases the risk of cardiac arrhythmias and sudden cardiac death.

Objective: This study sought to characterize the associations between SDB, intermittent hypoxemia, and the beat-to-beat QT variability index (QTVI), a measure of ventricular repolarization lability associated with cardiac arrhythmias and sudden cardiac death.

Methods: Three distinct cohorts were used: a matched sample of 122 participants with and without severe SDB for cross-sectional analysis; a matched sample of 52 participants with and without incident SDB for longitudinal analysis; and a sample of 19 healthy adults exposed to acute intermittent hypoxia and ambient air on 2 separate days. The cross-sectional and longitudinal cohorts were the Sleep Heart Health Study participants with no known comorbidities who were not taking any drugs known to affect cardiac repolarization and satisfied the inclusion criteria. Electrocardiographic measures were calculated from 1-lead electrocardiograms.

Results: Participants with severe SDB had greater QTVI than those without SDB (P = .027). Total sleep time with <90% oxygen saturation, but not the arousal frequency, was a predictor of QTVI. QTVI during sleep was predictive of all-cause mortality. With incident SDB, mean QTVI increased from -1.23 to -0.86 during 5 years (P = .017). Finally, experimental exposure of healthy adults to acute intermittent hypoxia for 4 hours progressively increased QTVI (P = .016).

Conclusion: The results show that both prevalent SDB and incident SDB are associated with ventricular repolarization instability and suggest intermittent hypoxemia as the underlying mechanism that may contribute to increased mortality in SDB.

Keywords: AHI; Apnea/hypopnea index; ECG; Heart rate variability; Hypoxemia burden; Incident sleep apnea; Intermittent hypoxemia; Template-matching algorithm.