Introduction Central sleep apnoea (CSA), including Cheyne–Stokes respiration, is known to be a marker of poor prognosis in severe heart failure (HF), but its association with mortality in mild HF has not been reported.
Aim To describe the association between CSA and mortality over a 6-year period in patients with mild HF.
Methods and Results Between October 2002 and 2003, 59 men (aged 61 ± 10 years, with left ventricular ejection fraction (LVEF) of 31 ± 10%) were recruited into a study investigating the prevalence of sleep disordered breathing (SDB) in men with mild symptoms of congestive HF (NYHA II) on optimal medical therapy (98% on ACE inhibitors or angiotensin II receptor blockers, 78% on beta-blockers, 87% on loop diuretics and 49% on spironolactone). The presence of SDB was determined by nocturnal polysomnography, and defined as apnoea–hypopnoea index (AHI) greater than 15 per hour of sleep. The prevalence of SDB was found to be 56% (with a median central apnoea index of 6.3; interquartile range (IQR) 3–13/h). The type of SDB was further divided into obstructive sleep apnoea (OSA) and CSA when more than 50% of apnoea–hypopnoeas were obstructive or central in origin, respectively. 10 (17%) patients had OSA, 23 (39%) patients had CSA and 26 (44%) had no significant SDB. The 10 patients with OSA were referred for treatment with positive pressure support, as were three patients with CSA who complained of daytime hypersomnolence. All CSA and no-SDB patients were followed up (n = 49) to November 2008 giving a median follow-up of 65 months (IQR 60–67), with 10 deaths in the CSA group and four in the no-SDB group. Patients with CSA at baseline were older (67 ± 9 vs 58 ± 13 years; p<0.01), had steeper minute ventilation/carbon dioxide production slopes (33 (28–42) vs 28 (27–30); p<0.01) higher levels of brain natriuretic peptide (31 (10–73) vs 7 (3–15) pmol/l; p<0.01) and endothelin-1 (1.7 (1.2–2.5) vs 1.0 (0.9–1.7) pmol/l; p<0.01) than patients with no-SDB. There were no differences between the two groups for LVEF (30 ± 10 vs 31 ± 10%, p = 0.5), or percentage predicted maximum oxygen consumption (74 (51–80) vs 68 (61–74)%; p = 0.6). Patients with CSA had a substantially higher mortality than the no-SDB group (hazard ratio (HR) 4.3, 95% CI 1.2 to 15.8; p = 0.02), with a 39% mortality at 5 years compared with 11%. After adjustment for age and factors associated with mortality (brain natriuretic peptide, endothelin-1, steeper minute ventilation/carbon dioxide production slope) patients with SDB still had a significantly worse prognosis than those with no-SDB, with a 6% increase in mortality for each unit increase in the central apnoea index (HR 1.06, 95% CI 1.03 to 1.10; p = 0.02; see fig).
Conclusion CSA, even in patients with mild, well-treated, HF identifies a group with a much increased risk of death. This risk appears to persist to at least 6 years of follow-up, and is independent of other factors associated with prognosis. Randomised trials are needed to determine whether the treatment of such breathing disorders with non-invasive ventilation improves prognosis.
Funding British Heart Foundation.