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. 2022 Oct 24;10(10):CD012889.
doi: 10.1002/14651858.CD012889.pub2.

Non-invasive positive pressure ventilation for central sleep apnoea in adults

Ana Carolina Pereira Nunes Pinto  1   2   3 , Aline Rocha  4 , Daniela V Pachito  5 , Luciano F Drager  6   7   8 , Geraldo Lorenzi-Filho  9
Affiliations

Non-invasive positive pressure ventilation for central sleep apnoea in adults

Ana Carolina Pereira Nunes Pinto et al. Cochrane Database Syst Rev. .

Abstract

Background: Central sleep apnoea (CSA) is characterised by abnormal patterns of ventilation during sleep due to a dysfunctional drive to breathe. Consequently, people with CSA may present poor sleep quality, sleep fragmentation, inattention, fatigue, daytime sleepiness, and reduced quality of life.

Objectives: To assess the effectiveness and safety of non-invasive positive pressure ventilation (NIPV) for the treatment of adults with CSA.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Scopus on 6 September 2021. We applied no restrictions on language of publication. We also searched clinical trials registries for ongoing and unpublished studies, and scanned the reference lists of included studies to identify additional studies.

Selection criteria: We included randomised controlled trials (RCTs) reported in full text, those published as abstract only, and unpublished data.

Data collection and analysis: Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias of the included studies using the Cochrane risk of bias tool version 1.0, and the certainty of the evidence using the GRADE approach. In the case of disagreement, a third review author was consulted.

Main results: We included 15 RCTs with a total of 1936 participants, ranging from 10 to 1325 participants. All studies had important methodological limitations. We assessed most studies (11 studies) as at high risk of bias for at least one domain, and all studies as at unclear risk of bias for at least two domains. The trials included participants aged > 18 years old, of which 70% to 100% were men, who were followed from one week to 60 months. The included studies assessed the effects of different modes of NIPV and CSA. Most participants had CSA associated with chronic heart failure. Because CSA encompasses a variety of causes and underlying clinical conditions, data were carefully analysed, and different conditions and populations were not pooled. The findings for the primary outcomes for the seven evaluated comparisons are presented below. Continuous positive airway pressure (CPAP) plus best supportive care versus best supportive care in CSA associated with chronic heart failure In the short term, CPAP plus best supportive care may reduce central apnoea hypopnoea index (AHI) (mean difference (MD) -14.60, 95% confidence interval (CI) -20.11 to -9.09; 1 study; 205 participants). However, CPAP plus best supportive care may result in little to no difference in cardiovascular mortality compared to best supportive care alone. The evidence for the effect of CPAP plus best supportive care on all-cause mortality is very uncertain. No adverse effects were observed with CPAP, and the results for adverse events in the best supportive care group were not reported. Adaptive servo ventilation (ASV) versus CPAP in CSA associated with chronic heart failure The evidence is very uncertain about the effect of ASV versus CPAP on quality of life evaluated in both the short and medium term. Data on adverse events were not reported, and it is not clear whether data were sought but not found. ASV versus bilevel ventilation in CSA associated with chronic heart failure In the short term, ASV may result in little to no difference in central AHI. No adverse events were detected with ASV, and the results for adverse events in the bilevel ventilation group were not reported. ASV plus best supportive care versus best supportive care in CSA associated with chronic heart failure In the medium term, ASV plus best supportive care may reduce AHI compared to best supportive care alone (MD -20.30, 95% CI -28.75 to -11.85; 1 study; 30 participants). In the long term, ASV plus best supportive care likely increases cardiovascular mortality compared to best supportive care (risk ratio (RR) 1.25, 95% CI 1.04, 1.49; 1 study; 1325 participants). The evidence suggests that ASV plus best supportive care may result in little to no difference in quality of life in the short, medium, and long term, and in all-cause mortality in the medium and long term. Data on adverse events were evaluated but not reported. ASV plus best supportive care versus best supportive care in CSA with acute heart failure with preserved ejection fraction Only adverse events were reported for this comparison, and no adverse events were recorded in either group. ASV versus CPAP maintenance in CPAP-induced CSA In the short term, ASV may slightly reduce central AHI (MD -4.10, 95% CI -6.67 to -1.53; 1 study; 60 participants), but may result in little to no difference in quality of life. Data on adverse events were not reported, and it is not clear whether data were sought but not found. ASV versus bilevel ventilation in CPAP-induced CSA In the short term, ASV may slightly reduce central AHI (MD -8.70, 95% CI -11.42 to -5.98; 1 study; 30 participants) compared to bilevel ventilation. Data on adverse events were not reported, and it is not clear whether data were sought but not found.

Authors' conclusions: CPAP plus best supportive care may reduce central AHI in people with CSA associated with chronic heart failure compared to best supportive care alone. Although ASV plus best supportive care may reduce AHI in people with CSA associated with chronic heart failure, it likely increases cardiovascular mortality in these individuals. In people with CPAP-induced CSA, ASV may slightly reduce central AHI compared to bilevel ventilation and to CPAP. In the absence of data showing a favourable impact on meaningful patient-centred outcomes and defining clinically important differences in outcomes in CSA patients, these findings need to be interpreted with caution. Considering the level of certainty of the available evidence and the heterogeneity of participants with CSA, we could draw no definitive conclusions, and further high-quality trials focusing on patient-centred outcomes, such as quality of life, quality of sleep, and longer-term survival, are needed to determine whether one mode of NIPV is better than another or than best supportive care for any particular CSA patient group.

PubMed Disclaimer

Conflict of interest statement

ACPNP: none known.

AR: none known.

DVP: ResMed Brasil ‐ consultancy activities for economic studies related to continuous positive airway pressure therapy.

LFD: ResMed Foundation ‐ scientific consultant for real world data.

GLF: Biologix ‐ ownership of stocks of a startup of a simple device for sleep apnoea diagnosis.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: CPAP plus best supportive care versus best supportive care (or inactive control) in CSA associated with chronic heart failure, Outcome 1: AHI ‐ short term
1.2
1.2. Analysis
Comparison 1: CPAP plus best supportive care versus best supportive care (or inactive control) in CSA associated with chronic heart failure, Outcome 2: All‐cause mortality ‐ long term
2.1
2.1. Analysis
Comparison 2: ASV versus CPAP in CSA associated with chronic heart failure, Outcome 1: AHI ‐ short term
3.1
3.1. Analysis
Comparison 3: ASV plus best supportive care versus best supportive care alone (or inactive control) in CSA associated with chronic heart failure, Outcome 1: Quality of life ‐ short term
3.2
3.2. Analysis
Comparison 3: ASV plus best supportive care versus best supportive care alone (or inactive control) in CSA associated with chronic heart failure, Outcome 2: All‐cause mortality ‐ long term
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Teschler 2001 {published data only}
    1. Teschler H, Dohring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. American Journal of Respiratory and Critical Care Medicine 2001;164 C(4):614-9. [DOI: 10.1164/ajrccm.164.4.9908114] - DOI - PubMed

References to studies awaiting assessment

Alter 2013 {published data only}
    1. Alter P, Wagner J, Apelt S, Rupp H, Heitmann J. Influences of continuous positive airway pressure (CPAP) ventilation on cardiac function and left ventricular wall stress in dilative heart failure as assessed by cardiac magnetic resonance imaging. Somnologie 2013;17:75.
Arzt 2013 {published data only}
    1. Artz M, Series F, Lewis K, Escourrou P, Obermeier R, Keh IV, et al. Effects of auto-servo ventilation on cardiovascular function in patients with congestive heart failure and sleep-disordered breathing - a multicenter randomised controlled trial. European Respiratory Journal 2011;38:1743.
    1. Arzt M, Schroll S, Series F, Lewis K, Benjamin A, Escourrou P, et al. Auto-servoventilation in heart failure with sleep apnoea: a randomised controlled trial. European Respiratory Journal 2013;42:1244-54. [DOI: 10.1183/09031936.00083312] - DOI - PubMed
    1. Arzt M, Series F, Lewis K, Benjamin A, Escourrou P, Luigart R, et al. Treatment of central and obstructive sleep apnea in stable heart failure patients with auto-servo ventilation reduces sleep fragmentation - a randomized controlled trial. European Respiratory Journal 2012;40(C Suppl 56):588s [3289].
    1. Birner C, Series F, Lewis K, Benjamin A, Escourrou P, Luigart R, et al. Treatment with auto-servo ventilation of patients with sleep-disordered breathing, stable systolic heart failure and concomitant diastolic dysfunction - a randomized controlled pilot study. European Respiratory Journal 2012;40:3467.
    1. Birner C, Series F, Lewis K, Benjamin A, Wunderlich S, Escourrou P, et al. Effects of auto-servo ventilation on patients with sleep-disordered breathing, stable systolic heart failure and concomitant diastolic dysfunction: subanalysis of a randomized controlled trial. Respiration 2014;87(1):54-62. [DOI: 10.1159/000351797] - DOI - PubMed
CAT‐HF 2016 {published data only}
    1. Daubert MA, Whellan DJ, Woehrle H, Tasissa G, Anstrom KJ, Lindenfeld J, et al. Treatment of sleep-disordered breathing in heart failure impacts cardiac remodeling: insights from the CATHF Trial. American Heart Journal 2018;201:40-8. [DOI: 10.1016/j.ahj.2018.03.026] - DOI - PubMed
    1. Fiuzat M, Oldenberg O, Whellan DJ, Woehrle H, Punjabi NM, Anstrom KJ, et al. Lessons learned from a clinical trial: design, rationale, and insights from The Cardiovascular Improvements with Minute Ventilation-targeted Adaptive Sero-Ventilation (ASV) Therapy in Heart Failure (CAT-HF) Study. Contemporary Clinical Trials 2016;47:158-64. [DOI: 10.1016/j.cct.2016.01.001] - DOI - PubMed
    1. O'connor C, Whellan D, Fiuzat M, Benjafield A, Woehrle H, Punjabi N, et al. Adaptive servo-ventilation in heart failure: results of a randomized, controlled clinical trial. European Journal of Heart Failure 2016;18:318. [DOI: 10.1002/ejhf.539] - DOI
    1. O'Connor CM, Whellan DJ, Fiuzat M, Punjabi NM, Tasissa G, Anstrom KJ, et al. Cardiovascular outcomes with minute ventilation-targeted adaptive servo-ventilation therapy in heart failure: the CAT-HF trial. Journal of the American College of Cardiology 2017;69(12):1577-87. [DOI: 10.1016/j.jacc.2017.01.041] - DOI - PubMed
    1. Piccini JP, Pokorney SD, Anstrom KJ, Oldenburg O, Punjabi NM, Fiuzat M, et al. Adaptive servo-ventilation reduces atrial fibrillation burden in patients with heart failure and sleep apnea. Heart Rhythm 2019;16:91-7. [DOI: 10.1016/j.hrthm.2018.07.027] - DOI - PubMed
De Michelis 2008 {published data only}
    1. De Michelis C, Prest G, Perretta E, Riva L, Zoccali P. Congestive heart failure and Cheyne-Stokes periodic respiration breathing: new modalities of positive airways pressure ventilation alternative to CPAP. Rassegna di Patologia dell'Apparato Respiratorio 2008;23(1):17-25.
Egea 2004 {published and unpublished data}
    1. Egea C, Aizpuru F, Pinto J, Ayuela J, Ballester E, Zamarron C, et al. Cardiac function after CPAP therapy in chronic heart failure and sleep apnea. A multicenter study. In: American Thoracic Society International Conference; 2007 May 18-23; San Francisco. [A296]
    1. Egea C, Pinto J, Ayuela J, Ballester E, Zamarron C, Sojo A, et al. Eficacy of the treatment with CPAP in patients with chronic heart failure and sleep apnoea. European Respiratory Journal 2004;24 C(Suppl 48):564s.
    1. Egea CJ, Aizpuru F, Pinto JA, Ayuela JM, Ballester E, Zamarron C, et al. Cardiac function after CPAP therapy in patients with chronic heart failure and sleep apnea: a multicenter study. Sleep Medicine 2008;9 C(6):660-6. [DOI: 10.1016/j.sleep.2007.06.018] - DOI - PubMed
Goldberg 2007 {published data only}
    1. Goldberg LR, Horstkotte D, Shakar SF, Lowes BD, Walker JM, Cloward TV, et al. Long term results of a randomized multicenter trial comparing adaptive servo ventilation positive airway pressure to nasal oxygen in heart failure patients with central sleep apnea. Journal of the American College of Cardiology 2007;49(9):94A-5A.
Miyata 2012 {published data only}
    1. Miyata M, Yoshihisa A, Suzuki S, Sugimoto K, Yamaki T, Kunii H, et al. Adaptive servo ventilation improves cardiac function and reduces re-hospitalization in chronic heart failure patients with Cheyne-Stokes respiration after cardiac resynchronization therapy. European Heart Journal 2012;33:332. [DOI: 10.1016/j.jjcc.2012.01.021] - DOI
    1. Miyata M, Yoshihisa A, Suzuki S, Yamada S, Kamioka M, Kamiyama Y, et al. Adaptive servo ventilation improves cardiac function and prognosis in chronic heart failure patients with Cheyne-Stokes respiration after cardiac resynchronization therapy. In: American Heart Association (AHA) Scientific Sessions; 2011 Nov 12-16; Orlando. 2011.
Murase 2016 {published data only}
    1. Murase K, Ono K, Akao M, Miki S, Nohara R, Mishima M, et al. The clinical effects of adaptive servo ventilation versus nocturnal oxygen therapy for sleep disordered breathing in heart failure patients: a randomized trial. American Journal of Respiratory and Critical Care Medicine 2015;191:A6109.
    1. Murase K, Ono K, Yoneda T, Iguchi M, Yokomatsu T, Mizoguchi T, et al. Adaptive servoventilation versus oxygen therapy for sleep disordered breathing in patients with heart failure: a randomised trial. Open Heart 2016;3(1):e000366. [DOI: 10.1136/openhrt-2015-000366] - DOI - PMC - PubMed
Noda 2007 {published data only}
    1. Noda A, Izawa H, Asano H, Nakata S, Hirashiki A, Murase Y, et al. Beneficial effect of bilevel positive airway pressure on left ventricular function in ambulatory patients with idiopathic dilated cardiomyopathy and central sleep apnea-hypopnea: a preliminary study. Chest 2007;131(C(6)):1694-701. [DOI: 10.1378/chest.06-2271] - DOI - PubMed
Teschler 2000 {published data only}
    1. Teschler H, Dohring J, Wessendorf TE, Wang YM, Thilmann A, Berthon Jones M. Effect of autoset CS servo-ventilation on central sleep apnea in brainstem stroke. American Journal of Respiratory and Critical Care Medicine 2000;161 C(3 Suppl):A361.
Tkacova 1997 {published data only}
    1. Tkacova R, Liu PP, Naughton MT, Bradley TD. Effect of continuous positive airway pressure on mitral regurgitant fraction and atrial natriuretic peptide in patients with heart failure. Journal of the American College of Cardiology 1997;30(3):739-45. - PubMed
Toepfer 2003 {published data only}
    1. Toepfer V, El-Sebai MA, Schulz R, Wessendorf TE, Teschler H. Six weeks adaptive servo-ventilation increases exercise capacity and reduces sympathetic activity in central sleep apnea due to heart failure [Abstract]. In: American Thoracic Society 99th International Conference; 2003 May 16-21; Seattle. 2003.
Ushijima 2014 {published data only}
    1. Ushijima R, Joho S, Akabane T, Oda Y, Inoue H. Differing effects of adaptive servoventilation and continuous positive airway pressure on muscle sympathetic nerve activity in patients with heart failure. Circulation Journal 2014;78(6):1387-95. [DOI: 10.1253/circj.cj-13-1468] - DOI - PubMed
Vogt‐Ladner 2002 {published data only}
    1. Vogt Ladner G, Schacher C, Ditterich W, Vogt M, Teschler H, Worth H. Nocturnal oxygen therapy (NOY) versus adaptive servo-ventilation (ASV) in patients with severe chronic heart failure (CHF) and Cheyne Stokes respiration (CSR). American Journal of Respiratory and Critical Care Medicine 2002;165(C Suppl 8):A247.
Yoshihisa 2009 {published data only}
    1. Yoshihisa A, Sato T, Suzuki H, Saito S, Ishibashi T, Takeishi Y. Adaptive servo ventilation restores cardiac dysfunction in heart failure patients with Cheyne-Stokes respiration. European Journal of Heart Failure 2009;8:ii75.
Yoshihisa 2013 {published data only}
    1. Yoshihisa A, Suzuki S, Takeishi Y. Impact of adaptive servo ventilation on cardiovascular function and prognosis in patients with HFpEF and sleep-disordered breathing. Journal of Cardiac Failure 2014;20(10):S140.
    1. Yoshihisa A, Suzuki S, Yamaki T, Sugimoto K, Kunii H, Nakazato K, et al. Impact of adaptive servo-ventilation on cardiovascular function and prognosis in heart failure patients with preserved leC ventricular ejection fraction and sleep disordered breathing. European Journal of Heart Failure 2013;15:543-50. [DOI: 10.1093/eurjhf/hfs197] - DOI - PubMed
Zhao 2006 {published data only}
    1. Zhao Z, Liu Z, Luo Q. The effect of positive pressure ventilation in patients with heart failure and sleep apnea. In: American Thoracic Society International Conference; 2008 May 16-21; Toronto. 2008:A480.
    1. Zhao ZH, Liu ZH, Luo Q, Xiong CM, Ni XH, Zhang J, et al. Positive pressure ventilation treatment reduces plasma levels of amino terminal-pro brain natriuretic peptide in congestive heart failure patients with sleep apnea. Circulation Journal 2006;70(5):572-4. [DOI: 10.1253/circj.70.572] - DOI - PubMed
    1. Zhao ZH, Liu ZH, Luo Q, Zhang J, Xiong CM, Ni XH, et al. The effects of noninvasive positive pressure ventilation treatment on plasma concentration of amino terminal-pro brain natriuretic peptide in congestive heart failure in patients with sleep apnea. Zhonghua nei ke za zhi [Chinese Journal of Internal Medicine] 2006;45(5):386-8. - PubMed

References to ongoing studies

ChiCTR‐TRC‐12003881 {published data only}
    1. ChiCTR-TRC-12003881. Multicenter study on diagnosis of central sleep apnea complicated with heart failure by diaphragm electromyogram and efficacy of bi-level positive airway pressure ventilation. www.chictr.org.cn/hvshowproject.aspx?id=8123 (first received 1 January 2014).
NCT01128816 {published data only}
    1. Lyons OD, Floras JS, Logan AG, Beanlands R, Cantolla JD, Fitzpatrick M, et al. Design of the effect of adaptive servo-ventilation on survival and cardiovascular hospital admissions in patients with heart failure and sleep apnoea: the ADVENT-HF trial. European Journal of Heart Failure 2017;19(4):579-87. [DOI: 10.1002/ejhf.790] - DOI - PubMed
    1. NCT01128816. Effect of adaptive servo ventilation (ASV) on survival and hospital admissions in heart failure [A multi-centre, randomized study to assess the effects of adaptive servo ventilation (ASV) on survival and frequency of hospital admissions in patients with heart failure (HF) and sleep apnea (SA) - The ADVENT-HF Trial]. clinicaltrials.gov/show/NCT01128816 (first received 24 May 2010).
NCT01212705 {published data only}
    1. NCT01212705. Effect of adaptive servoventilation on cardiac function in chronic heart failure and Cheyne-Stokes respiration [Effect of adaptive servoventilation on cardiac function, exercise tolerance and quality of life in patients with chronic heart failure and Cheyne-Stokes respiration]. clinicaltrials.gov/show/NCT01212705 (first received 1 October 2010).

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Pachito 2017
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