Diseases

Pepperell et al performed the only randomized sham-controlled double-blind study of ASV in HFrEF with CSA/HCSB, but the investigation examined outcomes over a limited time period. The authors examined sleep quality, indices of CHF severity, and daytime performance in 30 patients with CHF (New York Heart Association [NYHA] class II-IV, left ventricular ejection fraction [LVEF], 33%-36%) randomized to receive 1 month of either therapeutic or subtherapeutic ASV.

In an intention-to-treat analysis, patients treated with an MV-targeted ASV device demonstrated a significant decrease in mean AHI from 25 to 5/h, improved Oxford sleep resistance test results, and decreased plasma brain natriuretic peptide (BNP) and urinary metnorepinephine levels compared with those receiving sham ASV. However, LVEF and subjective daytime sleepiness did not change significantly. Adherence to ASV use was lower in the sham group, with four patients not using the device at home at all.

The surprising disparity between objective and subjective measures of sleepiness may be explained by previous reports that patients with heart failure and sleep apnea frequently do not complain of subjective daytime sleepiness. In three early studies of SRBD52-54 in patients with heart failure, the prevalence of subjective sleepiness was similar between those with and those without sleep apnea, despite some patients having severe SRBD. This lack of subjective daytime sleepiness is mysterious because patients with heart failure objectively studied for sleepiness with either the Multiple Sleep Latency Test or the Osler test18 demonstrate significant degrees of hypersomnia.

Furthermore, a significant inverse linear correlation exists between AHI and mean sleep latency on the Multiple Sleep Latency Test, and with treatment of sleep apnea, objective sleepiness improves without a change in subjective daytime sleepiness. The lack of subjective daytime sleepiness in patients with CHF and SRBD may account for the under diagnosis of sleep apnea in these individuals and poor CPAP compliance, even when the disorder is properly diagnosed and treated. The aforementioned studies focused on patients with predominantly CSA/HCSB. However, because of the frequency of coexisting OSA and CSA/HCSB, identi- fying viable treatment options in these more complex patients is very important. An 8-week prospective observational study in 10 consecutive male patients with coexisting OSA and CSA/HCSB and with and without heart failure found that flow-targeted ASV with manual titration of EPAP achieved suppression of all types of SRBDs and improved sleep architecture and frequency of arousals regardless of whether the patients had coexisting cardiovascular disease.5 The more novel combination of MV-targeted ASV with automatically titrating EPAP was tested in a similar population during a short-term pilot study.

Sixteen patients with an AHI comprising , 80% obstructive events were included. The device normalized AHI and effectively suppressed both central and obstructive events; arousals were significantly reduced as well. In a randomized prospective study comparing CPAP with ASV by Randerath et al,47 26 of 36 patients with heart failure and coexisting OSA and CSA demonstrated acceptable adherence to ASV at 12 months and exhibited a substantial improvement in both types of SRBDs, BNP level, and sleepiness and attention on a self-administered questionnaire. Patients randomized to CPAP exhibited a similar dropout rate but experienced lesser degrees of SRBD control and higher BNP levels at 12 months. In addition to the study by Randerath et al,47 several long-term observational studies of ASV devices in patients with HFrEF and sleep apnea had significant rates of PAP device nonadherence. This may not only reflect a behavior of nonadherence to other medical therapies as well but also may be characteristic of patient resistance to PAP.

In a study of Japanese patients with an average age of 72 years and LVEF of 41%, Takama and Kurabayashi reported significantly improved 1-year survival in those who successfully adhered to MV-targeted ASV using default settings and no titration. Patients using ASV for . 4 h/night were compared with patients who were not considered adherent. All patients had severe sleep apnea comprising both obstructive and central sleep-disordered breathing. However, 42% of the patients were on a b-blocker in the adherent group compared with 29% in the nonadherent group, a potential confounder. In a second study, Jilek et al reported significantly improved survival in 91 patients who used flow-targeted ASV compared with 85 untreated patients. The patients had severe sleep apnea, predominantly central sleep-disordered breathing, with a mean AHI of about 44/h. More than 85% of these patients were taking b-blocker medication consistent with current standards of care. The adjusted hazard ratio was 0.3 in favor of ASV.