Increased ventricular premature contraction frequency during rem sleep in patients with coronary artery disease and obstructive sleep apnea

Abstract

Background: Patients with obstructive sleep apnea are reported to have a peak of sudden cardiac death at night, in contrast to patients without apnea whose peak is in the morning. We hypothesized that ventricular premature contraction (VPC) frequency would correlate with measures of apnea and sympathetic activity.

Methods: Electrocardiograms from a sleep study of 125 patients with coronary artery disease were evaluated. Patients were categorized by apnea-hypopnea index (AHI) into Moderate (AHI <15) or Severe (AHI>15) apnea groups. Sleep stages studied were Wake, S1, S2, S34, and rapid eye movement (REM). Parameters of a potent autonomically-based risk predictor for sudden cardiac death called heart rate turbulence were calculated.

Results: There were 74 Moderate and 51 Severe obstructive sleep apnea patients. VPC frequency was affected significantly by sleep stage (Wake, S2 and REM, F=5.8, p<.005) and by AHI (F=8.7, p<.005). In Severe apnea patients, VPC frequency was higher in REM than in Wake (p=.011). In contrast, patients with Moderate apnea had fewer VPCs and exhibited no sleep stage dependence (p=.19). Oxygen desaturation duration per apnea episode correlated positively with AHI (r(2)=.71, p<.0001), and was longer in REM than in non-REM (p<.0001). The heart rate turbulence parameter TS correlated negatively with oxygen desaturation duration in REM (r(2)=.06, p=.014).

Conclusions: Higher VPC frequency coupled with higher sympathetic activity caused by longer apnea episodes in REM sleep may be one reason for increased nocturnal death in apneic patients.

Keywords: arrhythmia; autonomic nervous system; coronary disease; sleep; sudden death.

Figure 1

Sleep time as percent of total sleep time (top panel), VPC count per sleep stage (center panel) and VPC frequency (bottom panel) for the different sleep stages for patients with No, Moderate, or Severe obstructive sleep apnea as defined by apnea-hypopnea index (AHI) value. Error bars indicate SEM. Severe sleep apnea patients spent more time in S1 sleep than patients with No or Moderate apnea. Both VPC count and frequency increased with increasing severity of apnea.

Figure 2

Histogram of sleep stage distribution of VPC frequency in patients with AHI <15 (left panel) and AHI>15 obstructive sleep apnea (right panel). In each patient, an ordered list of sleep stages was constructed from sleep stage with maximum VPC frequency to minimum VPC frequency. The ordering was tallied over all patients. The vertical axis shows number of patients. For example, the left panel shows Wake was the stage with the highest VPC frequency in 16 patients, whereas REM was the stage with the highest VPC frequency in 14 patients.

Figure 3

Correlation between oxygen desaturation duration/ apnea event and AHI. Duration of oxygen desaturation >2% (sec) from baseline per apnea event was more closely correlated with AHI and shorter in duration in non-REM sleep compared to REM sleep. Each patient is represented by one AHI value and two oxygen desaturation duration values, one for REM (filled circle) and one for non-REM (empty circle) sleep.

Figure 4

Relationship between heart rate turbulence values and oxygen desaturation duration per apnea event in REM stage sleep. Turbulence slope (TS) and turbulence onset (TO) were worse when the apnea duration was longer.