In this prospective study of well-defined, severe, stable HF outpatients, on optimized therapy, we found a high prevalence of SA (AHI ≥ 5- 72.8%, AHI ≥ 15- 44.7%), independent of clinical suspicion or symptoms (ESS < 10- 66%). This emphasizes the relevance of the association between those public health problems and question the need for screening of SA in HF population.
It is in agreement with previous studies, but there is a high variability in the reported prevalence of SA in HF (40-70%) [13–18]. Possible explanations are the small number of patients involved in most studies, predominantly men, the heterogeneity of populations and the different used diagnostic criteria and methods. Our study is one of the largest in this area, using more recent sleep sensors technology and international diagnostic criteria . It reports data from a heart failure clinic, including patients with significant comorbidities. Most patients were referred to the clinic after an acute HF episode. These patients, although not representative of the general population, have some characteristics similar to Heart Failure in the general population. Epidemiological studies performed in Portugal and Spain reported a medium age of 64 and 65 years in Heart Failure patients [28, 29]. Our study included 55% of patients older than 65 years (mean age 66 years), higher than other studies previously published [13–18]. Mared et al reported a high prevalence of Cheyne-Stokes respiration in an older HF population (mean age 73 years) . However, patients were hospitalised for decompensated HF and not stable and ambulatory as in our study.
Unlike previously reported, in our HF population, SA was predominantly obstructive.
Central SA has been seen as a consequence of HF, correlated with its severity and prognosis [19–21]. However, this could not explain our results since we had a high prevalence of severe LV systolic dysfunction in the total population (56.3%), significantly associated with SA (63.9 vs 33.3, p-0.018) but not to central/mixed type. Also, in contrast to other studies [15, 16], SA was predominantly obstructive (60%). Only 9.3% of patients had pure central SA and a significant proportion had both types (30.7%).
Despite the severity of HF, patients were stable and on optimized therapy which could contributed to lower the prevalence of central SA in our study. The management of HF has evolved in last decade, with widespread use of ACE-inhibitors and beta-blockers [1–4]. The new pharmacotherapy has significantly improved prognosis of HF [3, 4], but the impact in the prevalence and type of SA has not been evaluated [16, 17, 31, 32]. Two recent studies have shown that HF patients taking beta-blocker have a lower prevalence and severity of SA [31, 32]. In contrast to some of the previous studies, our patients were receiving optimal treatment for HF (beta-blocker- 90.3%, ACE-inhibitors- 95.1%, spironolactone- 42.7%). In some of the studies that reported predominance of central SA, use of beta-blocker was lower (10 and 78%) [15, 16].
Javaheri et al studied 100 patients with severe stable HF . Prevalence of moderate to severe SA (AHI ≥ 15) was similar to our population (49.0 vs 44.7%) but central SA was the predominant type (37.0 vs 12.0%). However, only men were included and the investigation started in nineties, when current HF therapy was not widespread (beta-blocker-10%, ACE-inhibitors- 91%). More recently, Vazir et al reported similar results  in a HF population with improved treatment (beta-blocker- 78%, ACE-inhibitors- 98%, spironolactone- 49%).
Nevertheless, other studies found a high proportion of obstructive SA, in according to our results [14, 17, 18]. In a population of 53 outpatients with stable HF, prevalence of SA (AHI > 10) was 68%, predominantly obstructive (53%) . Oldenburg et al studied 700 patients and found 76% prevalence of SA (AHI ≥ 5), 36% obstructive . Schulz and colleagues studied 203 patients and reported a prevalence of 71% (AHI > 10), 43% obstructive . In the two last studies, diagnosis was based in polygraphy which can underestimate AHI. As a consequence, the prevalence and severity of SA might even be higher.
Our patients were overweight which could contribute to the predominance of obstructive SA. However, BMI was not different in patients with and without SA and median BMI was similar to studies where central SA was predominant [15, 16]. Neck circumference was significantly greater in patients with SA which could contribute to the predominance of the obstructive type. Ferrier et al studied a HF population with a larger neck (41.0 vs 37.0 cm) and found similar results . Craniofacial anthropometric characteristics were not mentioned in other studies [13, 15–18].
Characteristics that could help to identify HF patients with SA have been described: male gender for both types of SA; age > 60 years, atrial fibrillation and hypocapnia for central SA; for obstructive SA, higher BMI in men and age > 60 years in women . However, this study was retrospective, patients were recruited from a population referred for suspected SA and asymptomatic patients were excluded. In the study by Javaheri et al, NYHA class III, low LV ejection fraction, atrial fibrillation and hypocapnia were associated with central SA . Obesity and snoring were risk factors for obstructive SA. Similar results were reported by other authors [14, 16, 17].
We did not find characteristic risk factors for SA in patients with HF. Male gender, larger neck, severe systolic dysfunction, LV hypertrophy, LV and LA dilatation were significantly associated with SA. However, in multivariate analysis, only LA diameter was an independent predictor of SA. Its significance is uncertain, but LA dilatation could be an early marker of hypertension and diastolic dysfunction which have been independently associated with SA .
Patients with obstructive SA had larger neck and a trend for higher BMI, snoring and higher ESS score which is in agreement with literature . Patients with central/mixed SA were predominantly men and older. Unlike previously reported [13, 15], awake hypocapnia was not associated with central SA.
As previously described , in our population NT-proBNP levels were not different in all groups but patients with SA had more severe LV systolic dysfunction. Severe systolic dysfunction was not associated to a specific pattern of SA. Other authors found higher levels of NT-proBNP in patients with SA but no difference in LV systolic dysfunction .
In our study, sleep efficiency was unsatisfactory. This could be explained by the "first-night effect", resulting from insomnia related to a different environment. However, as sleep efficiency was not different in patients with or without SA, it didn't interfere with the results.
Patients with SA had more sleep fragmentation and nocturnal desaturation but not increased daytime sleepiness, in accordance with other studies [15–18]. This suggests that subjective daytime sleepiness measured by ESS is not useful in screening of SA in HF patients, but deleterious effects of inefficient sleep are present.
We are aware of some limitations to our study. The number of patients in each group is relatively small but, to our knowledge, it is one of the largest studies in the literature. Other studies involved a much larger number of patients but they were retrospective and in a HF population with suspected SA . Unlike in our study, diagnosis was based in polygraphy [17, 18] which is not still validated in HF population . The small number of patients with pure central SA and its association with mixed type, could limit interpretation of data.