Evaluation of Autonomic Function in Patients with Sickle Cell Disease in Relation to Nighttime Hypoxemia

Sickle cell disease (SCD) is a genetic condition resulting from a homozygous hemoglobin S mutation of the beta globin gene. HbS polymerizes in the deoxygenated state, causing the red cell membrane to become rigid and obstruct blood flow. Ischemia results leading to early organ damage, impaired quality of life and short life expectancy. Patients with SCD die from many causes including infection, splenic sequestration, stroke, and pulmonary emboli, however; a number of deaths in this population are acute and unexplained. The increased risk of sudden death is hypothesized to be associated with autonomic dysfunction. Heart rate variability (HRV) is a measurement of autonomic function and predictor of risk of sudden death. Measures of HRV can be compared to other factors associated with autonomic dysfunction. Individuals with obstructive sleep apnea have increased sympathetic tone. We hypothesized that SCD subjects that experienced nighttime hypoxemia will have autonomic dysfunction.

Subjects were fitted with an ambulatory electrocardiogram device (Acitheart, CamNTech, Inc) and monitored for 24 hours. High frequency power (HFP), a measure of cardiac parasympathetic tone, and low:high ratio (LHR), a measure of sympathovagal balance, were calculated from the HRV by the product software. During sleep, baseline oxyhemoglobin saturation (SpO₂) and number of desaturations below 88% was monitored using an ambulatory pulse oximeter (WristOX, Respironics, Inc). Bivariate analysis of the median HFP and LHR values over a 24 hour period were compared to baseline SpO₂and number of desaturation events. Sex, age and hematologic values including hemoglobin, CRP and lactate dehydrogenase values were also considered.

30 SCD subjects (mean age= 26.1 years+10.96, 36% male) were evaluated. Baseline nighttime SpO2 was 95.5+2.8% with 1 subject with a baseline SpO2 < 90%. Baseline SpO₂ did not correlate with HF with R² = 0.03 but did correlate with LHR with R² = 0.46. There was a mean number of desaturation events of 16.6+38.3 with 4 subjects greater than 25 desaturation events. The number of desaturation events did not correlate with HF with R² = 0.027 but did correlate with LHR with R²= 0.63. Stepwise multivariate analysis was performed including the baseline SpO2, number of desaturation events, sex, age and hematologic parameters showed that the number of desaturation events was the best predictor of LHR.

SCD subjects that experienced nighttime hypoxemia and increased number of desaturation events during sleep have higher LHR ratios consistent with increased sympathovagal tone.

Coates:Novartis: Speakers Bureau; Apopharma: Consultancy. Wood:Ferrokin Biosciences: Consultancy; Shire: Consultancy; Apotex: Consultancy, Honoraria; Novartis: Honoraria, Research Funding.