Editor's Note: Commentary based on Galetke W, Ghassemi BM, Priegnitz C, et al. Anticyclic modulated ventilation versus continuous positive airway pressure in patients with coexisting obstructive sleep apnea and cheyne–stokes respiration: a randomized crossover trial. Sleep Med 2014;15:874-9.

Background

Sleep-disordered breathing is of common occurrence in a host of cardiac conditions including hypertension, ischemic heart disease, and systolic heart failure. A variety of ventilator modes and protocols have been used with mixed results to treat obstructive sleep apnea (OSA) and Cheyne-Stokes respiration (CSR), although these disorders often overlap and coexist. The authors chose to use a new mode of positive airway ventilation to treat patients with coexistent OSA and CSR.

Methods

Thirty-nine cardiac patients with an apnea-hypoapnea index (AHI) of >15 were enrolled from the sleep laboratory of a single center. After baseline polysomnography, patients were randomized (operator and patient blinded) to be treated with fixed continuous positive airway pressures (CPAP) versus anticyclic modulated ventilation (ACMV). The ACMV combined an adaptive servo-ventilation mode and an automatic positive airway pressure algorithm. Patients received treatment for four weeks with the initial mode, followed by repeat polysomnography and a washout phase of one week. The patients then crossed over to the other treatment mode and were observed for another four weeks prior to the final evaluation. Primary outcome was total number of respiratory events (obstructive and central). Secondary endpoints included treatment adherence, sleep quality, and change in ejection fraction.

Results

Mean age of participants was 65.5±9.7 years with hypertension being the most common cardiac condition and the majority of the patients were in New York Heart Class I and II. At baseline, total AHI was 48.4 ± 18.7. Both the treatment modes significantly reduced the total AHI; however, ACMV led to a greater reduction in total AHI in comparison to fixed CPAP mode. There was significant reduction in obstructive and central respiratory events with either modes but to greater magnitude with the ACMV mode. CPAP reduced the total AHI to <10 per hour in half of the patients whereas ACMV reduced it <10 per hour in all but two patients. The treatment did not show any difference in total sleep time, but there was significant decrease in light sleep and an increase in REM sleep with both the modes. Cardiac function improved with both the modes but the ejection fraction was significantly increased with ACMV mode. Treatment adherence was >6 hours per night with both the modes and did not differ significantly. Eighty-two percent of the patients preferred the ACMV mode over the CPAP at the end of the study, for long-term home treatment.

Conclusion

This small, single-center, randomized, crossover study reveals significant improvement in the respiratory events with both the treatment modes but superior results with the ACMV mode, in patients with coexistent obstructive sleep apnea and Cheyne–Stokes respiration.

Commentary/Perspective

The association of sleep-disordered breathing with heart failure has been well established by a number of observational studies. Among other mechanisms, sleep-disordered breathing has been known to perpetuate hypoxia, augment the sympathetic drive leading to a higher burden of arrhythmias and, in some studies, confer adverse prognosis. Many of these patients present with sleep-disordered breathing of mixed etiology, with OSA as a result of upper airway tissue edema and CSA related to heightened chemosensitivity and circulatory delay. It has been convincingly demonstrated that CPAP is effective in the treatment of OSA, but its utility in CSR is not as well established; in fact, CPAP may exacerbate CSR. Emerging evidence has shown adaptive servo-ventilation to effectively suppress CSR in the short term. The authors tested a new mode of ventilation that combines adaptive servo-ventilation and an automatic positive airway pressure algorithm and compared it to the fixed CPAP mode. The ACMV mode provides varying tidal volumes between periods of apneas and hyperventilation; thus, decreasing CSR and the automatic PAP helps relieve the pressure at the end of expiration, thus mitigating the obstructive component. Both treatment strategies improved the obstructive as well as central events and led to reduction in AHI, with superior results in the ACMV mode. The relative improvement in left ventricular function with ACMV mode should be interpreted with caution as it is on the borderline and falls within the margin of error. The objective measures of quality of sleep were indifferent between the groups; subjective sleepiness was better with the fixed CPAP, yet the preference of patients towards the ACMV mode should be further explored with future studies. This study included less sick patients, and, hence, the generalizability of the results towards sicker population is not feasible. This study serves as a successful pilot study and as a platform to a larger, longer, and well-randomized, prospective study to better understand the role of sophisticated PAP technology on outcomes in patients with sleep-disordered breathing and heart failure.

References

1. Bradley TD, Logan AG, Kimoff RJ, et al. for the CANPAP Investigators. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005;353:2025-33.
2. Randerath W, Galetke W, Kenter M, et al. Combined adaptive servo-ventilation and automatic positive airway pressure (anticyclic modulated ventilation) in co-existing obstructive and central sleep apnea syndrome and periodic breathing. Sleep Med 2009;10:898-903.

Keywords: Apnea, Sleep Apnea, Obstructive, Sleep Apnea Syndromes, Algorithms, Arrhythmias, Cardiac, Cheyne-Stokes Respiration, Continuous Positive Airway Pressure, Cross-Over Studies, Edema, Heart Failure, Heart Failure, Systolic, Hypertension, Hyperventilation, Myocardial Ischemia, Polysomnography, Prospective Studies, Respiration, Sleep Stages, Sleep, REM, Tidal Volume, Ventricular Function, Left

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