Abstract
Sleep-disordered breathing (SDB) is a common comorbidity of heart failure (HF), which disrupts sleep. Indeed, patients with heart failure (HF) generally have quantitatively and qualitatively disturbed sleep. Central sleep apnea (CSA) is a unique feature of SDB in HF patients. CSA is likely a consequence, rather than a cause of HF, and results in further deterioration in cardiovascular function, consequently increasing morbidity and mortality. However, effects of treatment for CSA remain to be elucidated. This review article will highlight pathogenesis and pathophysiology of CSA and its management in patients with HF.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Arzt M, Young T, Finn L, Skatrud JB, Ryan CM, Newton GE, et al. Sleepiness and sleep in patients with both systolic heart failure and obstructive sleep apnea. Arch Intern Med. 2006;166:1716–22.
Kasai T, Floras JS, Bradley TD. Sleep apnea and cardiovascular disease: a bidirectional relationship. Circulation. 2012;126:1495–510.
Mentz RJ, Kelly JP, von Lueder TG, Voors AA, Lam CS, Cowie MR, et al. Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol. 2014;64:2281–93.
Yumino D, Bradley TD. Central sleep apnea and Cheyne-Stokes respiration. Proc Am Thorac Soc. 2008;5:226–36.
Yumino D, Wang H, Floras JS, Newton GE, Mak S, Ruttanaumpawan P, et al. Prevalence and physiological predictors of sleep apnea in patients with heart failure and systolic dysfunction. J Card Fail. 2009;15:279–85.
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230–5.
Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A. Effects of age on sleep apnea in men: I. Prevalence and severity. Am J Respir Crit Care Med. 1998;157:144–8.
Kasai T. Sleep apnea and heart failure. J Cardiol. 2012;60:78–85.
Berry RB, Brooks R, Gamaldo C, Harding SM, Lloyd RM, Quan SF, et al. AASM scoring manual updates for 2017 (version 2.4). J Clin Sleep Med. 2017;13:665–6.
Hanly P, Zuberi N, Gray R. Pathogenesis of Cheyne-Stokes respiration in patients with congestive heart failure. Relationship to arterial PCO2. Chest. 1993;104:1079–84.
Solin P, Bergin P, Richardson M, Kaye DM, Walters EH, Naughton MT. Influence of pulmonary capillary wedge pressure on central apnea in heart failure. Circulation. 1999;99:1574–9.
Solin P, Roebuck T, Johns DP, Walters EH, Naughton MT. Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure. Am J Respir Crit Care Med. 2000;162:2194–200.
Yamada K, Asanoi H, Ueno H, Joho S, Takagawa J, Kameyama T, et al. Role of central sympathoexcitation in enhanced hypercapnic chemosensitivity in patients with heart failure. Am Heart J. 2004;148:964–70.
Sun SY, Wang W, Zucker IH, Schultz HD. Enhanced peripheral chemoreflex function in conscious rabbits with pacing-induced heart failure. J Appl Physiol (1985). 1999;86:1264–72.
Hall MJ, Xie A, Rutherford R, Ando S, Floras JS, Bradley TD. Cycle length of periodic breathing in patients with and without heart failure. Am J Respir Crit Care Med. 1996;154:376–81.
Kasai T, Arcand J, Allard JP, Mak S, Azevedo ER, Newton GE, et al. Relationship between sodium intake and sleep apnea in patients with heart failure. J Am Coll Cardiol. 2011;58:1970–4.
Yumino D, Redolfi S, Ruttanaumpawan P, Su MC, Smith S, Newton GE, et al. Nocturnal rostral fluid shift: a unifying concept for the pathogenesis of obstructive and central sleep apnea in men with heart failure. Circulation. 2010;121:1598–605.
Kasai T, Motwani SS, Yumino D, Gabriel JM, Montemurro LT, Amirthalingam V, et al. Contrasting effects of lower body positive pressure on upper airways resistance and partial pressure of carbon dioxide in men with heart failure and obstructive or central sleep apnea. J Am Coll Cardiol. 2013;61:1157–66.
Kasai T. Fluid retention and rostral fluid shift in sleep-disordered breathing. Curr Hypertens Rev. 2016;12:32–42.
Xie A, Skatrud JB, Khayat R, Dempsey JA, Morgan B, Russell D. Cerebrovascular response to carbon dioxide in patients with congestive heart failure. Am J Respir Crit Care Med. 2005;172:371–8.
Bradley TD. Crossing the threshold: implications for central sleep apnea. Am J Respir Crit Care Med. 2002;165:1203–4.
Milionis HJ, Alexandrides GE, Liberopoulos EN, Bairaktari ET, Goudevenos J, Elisaf MS. Hypomagnesemia and concurrent acid-base and electrolyte abnormalities in patients with congestive heart failure. Eur J Heart Fail. 2002;4:167–73.
Suda SKT, Matsumoto H, Shiroshita N, Kato M, Kawana F, Yatsu S, et al. Prevalence and clinical correlates of sleep-disordered breathing in patients hospitalized with acute decompensated heart failure. Can J Cardiol. 2018;34:784–90.
Alex CG, Onal E, Lopata M. Upper airway occlusion during sleep in patients with Cheyne-Stokes respiration. Am Rev Respir Dis. 1986;133:42–5.
Badr MS, Toiber F, Skatrud JB, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl Physiol (1985). 1995;78:1806–15.
Patrick GB, Strohl KP, Rubin SB, Altose MD. Upper airway and diaphragm muscle responses to chemical stimulation and loading. J Appl Physiol Respir Environ Exerc Physiol. 1982;53:1133–7.
Taranto Montemurro L, Kasai T. The upper airway in sleep-disordered breathing: UA in SDB. Minerva Med. 2014;105:25–40.
Naughton MT, Benard DC, Liu PP, Rutherford R, Rankin F, Bradley TD. Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep apnea. Am J Respir Crit Care Med. 1995;152:473–9.
Spaak J, Egri ZJ, Kubo T, Yu E, Ando S, Kaneko Y, et al. Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea. Hypertension. 2005;46:1327–32.
Leung RS, Diep TM, Bowman ME, Lorenzi-Filho G, Bradley TD. Provocation of ventricular ectopy by Cheyne-Stokes respiration in patients with heart failure. Sleep. 2004;27:1337–43.
Mann DL. Inflammatory mediators and the failing heart: past, present, and the foreseeable future. Circ Res. 2002;91:988–98.
Rauchhaus M, Doehner W, Francis DP, Davos C, Kemp M, Liebenthal C, et al. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation. 2000;102:3060–7.
Schmalgemeier H, Bitter T, Fischbach T, Horstkotte D, Oldenburg O. C-reactive protein is elevated in heart failure patients with central sleep apnea and Cheyne-Stokes respiration. Respiration. 2014;87:113–20.
Sano K, Watanabe E, Hayano J, Mieno Y, Sobue Y, Yamamoto M, et al. Central sleep apnoea and inflammation are independently associated with arrhythmia in patients with heart failure. Eur J Heart Fail. 2013;15:1003–10.
Khayat R, Jarjoura D, Porter K, Sow A, Wannemacher J, Dohar R, et al. Sleep disordered breathing and post-discharge mortality in patients with acute heart failure. Eur Heart J. 2015;36:1463–9.
Khayat R, Abraham W, Patt B, Brinkman V, Wannemacher J, Porter K, et al. Central sleep apnea is a predictor of cardiac readmission in hospitalized patients with systolic heart failure. J Card Fail. 2012;18:534–40.
Tamura A, Kawano Y, Kadota J. Carvedilol reduces the severity of central sleep apnea in chronic heart failure. Circ J. 2009;73:295–8.
Baylor P, Tayloe D, Owen D, Sanders C. Cardiac failure presenting as sleep apnea. Elimination of apnea following medical management of cardiac failure. Chest. 1988;94:1298–300.
Weng CL, Chen Q, Ma YL, He QY. A meta-analysis of the effects of atrial overdrive pacing on sleep apnea syndrome. Pacing Clin Electrophysiol. 2009;32:1434–43.
Lamba J, Simpson CS, Redfearn DP, Michael KA, Fitzpatrick M, Baranchuk A. Cardiac resynchronization therapy for the treatment of sleep apnoea: a meta-analysis. Europace. 2011;13:1174–9.
Yamamoto U, Mohri M, Shimada K, Origuchi H, Miyata K, Ito K, et al. Six-month aerobic exercise training ameliorates central sleep apnea in patients with chronic heart failure. J Card Fail. 2007;13:825–9.
Ueno LM, Drager LF, Rodrigues AC, Rondon MU, Braga AM, Mathias W Jr, et al. Effects of exercise training in patients with chronic heart failure and sleep apnea. Sleep. 2009;32:637–47.
Akkanti B, Castriotta RJ, Sayana P, Nunez E, Rajapreyar I, Kumar S, et al. Ventricular assist devices and sleep-disordered breathing. Sleep Med Rev. 2017;35:51–61.
Braver HM, Brandes WC, Kubiet MA, Limacher MC, Mills RM Jr, Block AJ. Effect of cardiac transplantation on Cheyne-Stokes respiration occurring during sleep. Am J Cardiol. 1995;76:632–4.
Mansfield DR, Solin P, Roebuck T, Bergin P, Kaye DM, Naughton MT. The effect of successful heart transplant treatment of heart failure on central sleep apnea. Chest. 2003;124:1675–81.
Javaheri S, Parker TJ, Wexler L, Liming JD, Lindower P, Roselle GA. Effect of theophylline on sleep-disordered breathing in heart failure. N Engl J Med. 1996;335:562–7.
Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med. 2006;173:234–7.
Javaheri S, Sands SA, Edwards BA. Acetazolamide attenuates Hunter-Cheyne-Stokes breathing but augments the hypercapnic ventilatory response in patients with heart failure. Ann Am Thorac Soc. 2014;11:80–6.
Khayat RN, Xie A, Patel AK, Kaminski A, Skatrud JB. Cardiorespiratory effects of added dead space in patients with heart failure and central sleep apnea. Chest. 2003;123:1551–60.
Andreas S, Weidel K, Hagenah G, Heindl S. Treatment of Cheyne-Stokes respiration with nasal oxygen and carbon dioxide. Eur Respir J. 1998;12:414–9.
Giannoni A, Baruah R, Willson K, Mebrate Y, Mayet J, Emdin M, et al. Real-time dynamic carbon dioxide administration: a novel treatment strategy for stabilization of periodic breathing with potential application to central sleep apnea. J Am Coll Cardiol. 2010;56:1832–7.
Guilleminault C, Clerk A, Labanowski M, Simmons J, Stoohs R. Cardiac failure and benzodiazepines. Sleep. 1993;16:524–8.
Sasayama S, Izumi T, Seino Y, Ueshima K, Asanoi H, Group C-HS. Effects of nocturnal oxygen therapy on outcome measures in patients with chronic heart failure and Cheyne-Stokes respiration. Circ J. 2006;70:1–7.
Shigemitsu M, Nishio K, Kusuyama T, Itoh S, Konno N, Katagiri T. Nocturnal oxygen therapy prevents progress of congestive heart failure with central sleep apnea. Int J Cardiol. 2007;115:354–60.
Staniforth AD, Kinnear WJ, Starling R, Hetmanski DJ, Cowley AJ. Effect of oxygen on sleep quality, cognitive function and sympathetic activity in patients with chronic heart failure and Cheyne-Stokes respiration. Eur Heart J. 1998;19:922–8.
Andreas S, Clemens C, Sandholzer H, Figulla HR, Kreuzer H. Improvement of exercise capacity with treatment of Cheyne-Stokes respiration in patients with congestive heart failure. J Am Coll Cardiol. 1996;27:1486–90.
Momomura S. Treatment of Cheyne-Stokes respiration-central sleep apnea in patients with heart failure. J Cardiol. 2012;59:110–6.
Krachman SL, D'Alonzo GE, Berger TJ, Eisen HJ. Comparison of oxygen therapy with nasal continuous positive airway pressure on Cheyne-Stokes respiration during sleep in congestive heart failure. Chest. 1999;116:1550–7.
Campbell AJ, Ferrier K, Neill AM. Effect of oxygen versus adaptive pressure support servo-ventilation in patients with central sleep apnoea-Cheyne Stokes respiration and congestive heart failure. Intern Med J. 2012;42:1130–6.
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:e000366.
Abraham WT, Jagielski D, Oldenburg O, Augostini R, Krueger S, Kolodziej A, et al. Phrenic nerve stimulation for the treatment of central sleep apnea. JACC Heart Fail. 2015;3:360–9.
Ponikowski P, Javaheri S, Michalkiewicz D, Bart BA, Czarnecka D, Jastrzebski M, et al. Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea in heart failure. Eur Heart J. 2012;33:889–94.
Jagielski D, Ponikowski P, Augostini R, Kolodziej A, Khayat R, Abraham WT. Transvenous stimulation of the phrenic nerve for the treatment of central sleep apnoea: 12 months’ experience with the remede® System. Eur J Heart Fail. 2016;18:1386–93.
Fox H, Bitter T, Horstkotte D, Oldenburg O, Gutleben KJ. Long-term experience with first-generation implantable neurostimulation device in central sleep apnea treatment. Pacing Clin Electrophysiol. 2017;40:498–503.
Kato T, Suda S, Kasai T. Positive airway pressure therapy for heart failure. World J Cardiol. 2014;6:1175–91.
Arzt M, Bradley TD. Treatment of sleep apnea in heart failure. Am J Respir Crit Care Med. 2006;173:1300–8.
Javaheri S. Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure. Circulation. 2000;101:392–7.
Dohi T, Kasai T, Narui K, Ishiwata S, Ohno M, Yamaguchi T, et al. Bi-level positive airway pressure ventilation for treating heart failure with central sleep apnea that is unresponsive to continuous positive airway pressure. Circ J. 2008;72:1100–5.
Arzt M, Floras JS, Logan AG, Kimoff RJ, Series F, Morrison D, et al. Suppression of central sleep apnea by continuous positive airway pressure and transplant-free survival in heart failure: a post hoc analysis of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure Trial (CANPAP). Circulation. 2007;115:3173–80.
Davies RJ, Harrington KJ, Ormerod OJ, Stradling JR. Nasal continuous positive airway pressure in chronic heart failure with sleep-disordered breathing. Am Rev Respir Dis. 1993;147:630–4.
Bradley TD, Holloway RM, McLaughlin PR, Ross BL, Walters J, Liu PP. Cardiac output response to continuous positive airway pressure in congestive heart failure. Am Rev Respir Dis. 1992;145:377–82.
Mehta S, Liu PP, Fitzgerald FS, Allidina YK, Douglas Bradley T. Effects of continuous positive airway pressure on cardiac volumes in patients with ischemic and dilated cardiomyopathy. Am J Respir Crit Care Med. 2000;161:128–34.
Kiely JL, Deegan P, Buckley A, Shiels P, Maurer B, McNicholas WT. Efficacy of nasal continuous positive airway pressure therapy in chronic heart failure: importance of underlying cardiac rhythm. Thorax. 1998;53:957–62.
Kato T, Kasai T, Yatsu S, Murata A, Matsumoto H, Suda S, et al. Acute effects of positive airway pressure on functional mitral regurgitation in patients with systolic heart failure. Front Physiol. 2017;8:921.
Naughton MT, Benard DC, Rutherford R, Bradley TD. Effect of continuous positive airway pressure on central sleep apnea and nocturnal PCO2 in heart failure. Am J Respir Crit Care Med. 1994;150:1598–604.
Naughton MT, Liu PP, Bernard DC, Goldstein RS, Bradley TD. Treatment of congestive heart failure and Cheyne-Stokes respiration during sleep by continuous positive airway pressure. Am J Respir Crit Care Med. 1995;151:92–7.
Granton JT, Naughton MT, Benard DC, Liu PP, Goldstein RS, Bradley TD. CPAP improves inspiratory muscle strength in patients with heart failure and central sleep apnea. Am J Respir Crit Care Med. 1996;153:277–82.
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. J Am Coll Cardiol. 1997;30:739–45.
Sin DD, Logan AG, Fitzgerald FS, Liu PP, Bradley TD. Effects of continuous positive airway pressure on cardiovascular outcomes in heart failure patients with and without Cheyne-Stokes respiration. Circulation. 2000;102:61–6.
Bradley TD, Logan AG, Kimoff RJ, Series F, Morrison D, Ferguson K, et al. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med. 2005;353:2025–33.
Teschler H, Dohring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med. 2001;164:614–9.
Javaheri S, Goetting MG, Khayat R, Wylie PE, Goodwin JL, Parthasarathy S. The performance of two automatic servo-ventilation devices in the treatment of central sleep apnea. Sleep. 2011;34:1693–8.
Pepperell JC, Maskell NA, Jones DR, Langford-Wiley BA, Crosthwaite N, Stradling JR, et al. A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure. Am J Respir Crit Care Med. 2003;168:1109–14.
Philippe C, Stoica-Herman M, Drouot X, Raffestin B, Escourrou P, Hittinger L, et al. Compliance with and effectiveness of adaptive servoventilation versus continuous positive airway pressure in the treatment of Cheyne-Stokes respiration in heart failure over a six month period. Heart. 2006;92:337–42.
Fietze I, Blau A, Glos M, Theres H, Baumann G, Penzel T. Bi-level positive pressure ventilation and adaptive servo ventilation in patients with heart failure and Cheyne-Stokes respiration. Sleep Med. 2008;9:652–9.
Kasai T, Kasagi S, Maeno K, Dohi T, Kawana F, Kato M, et al. Adaptive servo-ventilation in cardiac function and neurohormonal status in patients with heart failure and central sleep apnea nonresponsive to continuous positive airway pressure. JACC Heart Fail. 2013;1:58–63.
Cowie MR, Woehrle H, Wegscheider K, Angermann C, d'Ortho MP, Erdmann E, et al. Adaptive servo-ventilation for central sleep apnea in systolic heart failure. N Engl J Med. 2015;373:1095–105.
Kasai T, Usui Y, Yoshioka T, Yanagisawa N, Takata Y, Narui K, et al. Effect of flow-triggered adaptive servo-ventilation compared with continuous positive airway pressure in patients with chronic heart failure with coexisting obstructive sleep apnea and Cheyne-Stokes respiration. Circ Heart Fail. 2010;3:140–8.
Randerath WJ, Nothofer G, Priegnitz C, Anduleit N, Treml M, Kehl V, et al. Long-term auto servo-ventilation or constant positive pressure in heart failure and co-existing central with obstructive sleep apnea. Chest. 2012;142:440–7.
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;87:54–62.
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 left ventricular ejection fraction and sleep-disordered breathing. Eur J Heart Fail. 2013;15:543–50.
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. J Am Coll Cardiol. 2017;69:1577–87.
Cowie MR, Woehrle H, Wegscheider K, Angermann C, d'Ortho MP, Erdmann E, et al. Rationale and design of the SERVE-HF study: treatment of sleep-disordered breathing with predominant central sleep apnoea with adaptive servo-ventilation in patients with chronic heart failure. Eur J Heart Fail. 2013;15:937–43.
Eulenburg C, Wegscheider K, Woehrle H, Angermann C, d'Ortho MP, Erdmann E, et al. Mechanisms underlying increased mortality risk in patients with heart failure and reduced ejection fraction randomly assigned to adaptive servoventilation in the SERVE-HF study: results of a secondary multistate modelling analysis. Lancet Respir Med. 2016;4:873–81.
Woehrle H, Cowie MR, Eulenburg C, Suling A, Angermann C, d'Ortho MP, et al. Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis. Eur Respir J. 2017;50:1601692.
Naughton MT. Cheyne-Stokes respiration: friend or foe? Thorax. 2012;67:357–60.
Perger E, Inami T, Lyons OD, Alshaer H, Smith S, Floras JS, et al. Distinct patterns of hyperpnea during Cheyne-Stokes respiration: implication for cardiac function in patients with heart failure. J Clin Sleep Med. 2017;13:1235–41.
Cowie MR, Woehrle H, Wegscheider K, Vettorazzi E, Lezius S, Koenig W, et al. Adaptive servo-ventilation for central sleep apnoea in systolic heart failure: results of the major substudy of SERVE-HF. Eur J Heart Fail. 2018;20:536–44.
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. Eur J Heart Fail. 2017;19:579–87.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Takatoshi Kasai reports no relevant conflicts of interest. Takatoshi Kasai reports financial interests in Philips-Respironics, Fukuda Denshi, and ResMed outside the submitted work.
Hiroki Matsumoto reports no relevant conflicts of interest. Hiroki Matsumoto reports financial interests in Philips-Respironics, Fukuda Denshi, and ResMed outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
This article is part of the Topical Collection on Heart Disease and Sleep Disturbances
Rights and permissions
About this article
Cite this article
Matsumoto, H., Kasai, T. Central Sleep Apnea in Heart Failure: Pathogenesis and Management. Curr Sleep Medicine Rep 4, 210–220 (2018). https://doi.org/10.1007/s40675-018-0125-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40675-018-0125-4