Sleep-disordered breathing (SDB) is associated with an increased risk of cardiac arrhythmias, sudden cardiac death, and all-cause mortality; however, the underlying mechanisms are unclear. Here, we examine the effects of prevalent and incident SDB on ventricular repolarization lability, a risk factor for adverse cardiac events.
Polysomnographic recordings from three cohorts were used. Cross-sectional: a matched sample of 122 participants with and without severe SDB; longitudinal: a matched sample of 52 participants with and without incident SDB at 5-year follow-up; and experimental: a sample of 19 healthy adults exposed to intermittent hypoxia and ambient air on two separate days. None of the participants had prevalent myocardial infarction, coronary artery bypass surgery, heart failure, or angina, and none were on beta-blockers, calcium channel blockers, or antiarrhythmic agents. Mean heart rate, heart rate variability (SDNN), and QT variability index (QTVI), a measure of ventricular repolarization lability, were calculated from one-lead ECG recordings. All-cause mortality was analyzed using the least absolute shrinkage and selection operator (lasso) method.
Participants with severe SDB had larger QTVI (P=0.027), heart rate (P=0.028), SDNN (P=0.018), and hypoxemia burden as assessed by the total sleep time with oxygen saturation less than 90% (TST90; P<0.001) than those without SDB. TST90, but not the frequency of arousals, was an independent predictor of QTVI (P=0.017). Both heart rate and QTVI were predictive of all-cause mortality, suggesting sympathetic hyperactivity as the mechanism underlying the SDB-associated increased mortality risk. For those who developed incident SDB, QTVI increased from -1.23±0.15 to 0.86±0.14 (P=0.017) over the 5 years of follow-up. QTVI didn't change for those who didn't develop SDB. Finally, exposure to intermittent hypoxia for four hours progressively increased QTVI (P=0.016). The results show that prevalent and incident SDB are associated with increased ventricular repolarization lability, most likely mediated by SDB-induced hypoxemia.