Abstract
Byline: Soroosh Solhjoo, Johns Hopkins Univ Sch of Medicine, Baltimore, MD; Naresh M Punjabi, Univ of Miami Miller Sch of Medicine, Miami, FL; Trishul Siddharthan, Univ of Miami Miller Sch of Medicine, Miami, FL; Abigail L Koch, Univ of Miami Miller Sch of Medicine, Miami, FL; Ciprian M Crainiceanu, Johns Hopkins Bloomberg Sch of Public Health, Baltimore, MD; Mark C Haigney, F. Edward HȨbert Sch of Medicine, Bethesda, MD Introduction : Obstructive sleep apnea (OSA) is highly prevalent in the general population. OSA is associated with adverse cardiovascular events, including sudden cardiac death, but the mechanism is unclear. Intermittent hypoxemia, a pathognomonic feature of OSA, could increase the propensity for abnormal ventricular repolarization. We previously found that short-term exposure of awake healthy subjects to recurrent hypoxic episodes increased their heart rate (HR) and HR variability. Hypothesis: Exposure to intermittent hypoxia increases ventricular repolarization instability in awake healthy subjects. Methods: Healthy adults (N = 19) were exposed to either intermittent hypoxia or air for 4 hours on two different days in a randomized order. Intermittent hypoxia was induced with exposure to hypoxic gas (95% N2 and 5% O2) or ambient air in an alternative fashion at a frequency of üô 25 times/hour, mimicking moderate to severe OSA. Repolarization stability was assessed using the QT variability index (QTVI), a validated predictor of cardiac arrhythmias and mortality. HR and QTVI were measured from one-lead ECG over consecutive 5-min epochs. Paired sample t-test was used to assess statistical associations. Results: Mean oxygen saturation levels were lower during exposure to intermittent hypoxia (90.86 Ø 0.19%) versus normoxia (97.37 Ø 0.20%, P < 10-13). Electrocardiographic measures at baseline were similar between the two conditions. No changes in these measures were noted during the conditions of normoxia. However, with intermittent hypoxia, mean HR and QTVI steadily increased (HR: 63.31 Ø 1.51 initial, 69.21 Ø 2.14 final, P < 0.001; QTVI: -1.85 Ø 0.04 initial, -1.64 Ø 0.07 final, P = 0.016). By the end of the 4-hour experiment, QTVI was greater in hypoxia vs. normoxia (final QTVI in hypoxia: -1.64 Ø 0.07, in normoxia: -1.86 Ø 0.06, P = 0.021). Conclusion: Four hours of intermittent hypoxia in awake normal healthy subjects progressively destabilized ventricular repolarization. Chronic exposure to recurrent periods of intermittent hypoxemia in OSA can increase ventricular repolarization and contribute to the OSA-associated adverse cardiovascular events, including sudden cardiac death.