Sex-related differences in daytime Cheyne-Stokes respiration in heart failure

Background: Cheyne-Stokes respiration (CSR) is characterized by alternating phases of central apneas (CA) and hyperventilation and may be observed in a large subset of heart failure (HF) patients. Long considered a sleep-disorder, CSR has been described also in awake patients, more markedly among men, and its 24-hour persistence held negative prognostic significance. The possible sex-related differences in the burden of daytime-CSR have never been investigated and represent the aim of this study. Methods: Consecutive patients with chronic HF and no evidence of obstructive sleep apneas underwent: cardiorespiratory ambulatory monitoring to stratify the severity of CA/CSR across the 24-hour, expressed as the apnea-hypopnea index (AHI); assessment of chemoreflex sensitivity through the rebreathing test. Results: Finally, 574 patients (115 women, 20%) were recruited. Compared to men, women showed a lower severity of CA/CSR both at nighttime and at daytime (night-AHI 7 vs 23, day-AHI 2 vs 10 events/h, pl0.05). Women had a lower chemosensitivity to hypoxia and to hypercapnia (0.30 vs. 0.41 L/min/1%SaO2; 0.61 vs 0.82 L/min/mmHg, pl0.01), that was a predictor of daytime-CA/CSR only among men. During follow-up, a lower rate of cardiac events was observed in women (9% vs 22%; log-rank=4.3, p=0.03), but such difference was no more present when using daytime-CA/CSR as a covariate (25% in both groups; log-rank=0.2, p=0.64). Conclusion: Women with HF show a lower incidence of CA/CSR compared to men, due to differences in cardiac function and chemoreflex sensitivity. The presence of daytime-CA/CSR is associated to poor prognosis in both women and men and its detection may individuate patients more at risk of cardiac death.