Central Sleep Apnea in Congestive Heart Failure: Prevalence, Mechanisms, Impact, and Therapeutic Options

ABSTRACT

Heart failure due to left ventricular systolic dysfunction is a prevalent syndrome and associated with morbidity, mortality, and huge economic cost. According to reports from several laboratories, a large number of patients with heart failure have central sleep apnea. Central sleep apnea causes arousals and sleep disruption, alters blood gases, and increases sympathetic activity. The pathophysiological consequences of central sleep apnea could adversely affect left ventricular structure and functions and worsen prognosis of heart failure.

Several treatment options, including use of nocturnal supplemental oxygen, positive airway pressure devices, and theophylline have been systematically studied and have been shown to improve central sleep apnea. Long-term studies, however, are necessary to determine the impact of therapy on natural history of left ventricular systolic dysfunction.

KEYWORDS

Central sleep apnea - oxygen - CPAP - theophylline

REFERENCES

• 1 Javaheri S. Sleep-related breathing disorders in heart failure. In: Mann DL Heart Failure, A Companion to Braunwald's Heart Disease. Philadelphia; WB Saunders 2004: 471-487
• 2 Ward M. Periodic respiration: a short historcal note.  Ann R Coll Surg Engl. 1973;  52 330-334
• 3 Allen E, Turk J L, Murley R. The Case Books of John Hunter FRS. New York; Parthenon 1993: 29-30
• 4 Cheyne J. A case of apoplexy, in which the fleshy part of the heart was converted into fat.  Dublin Hospital Reports and Communications. 1818;  2 216-223
• 5 Stokes W. Observations on some cases of permanently slow pulse.  Dublin Quarterly Journal of Medical Sciences. 1846;  2 73-85
• 6 American Heart Association .Heart and stroke statistical update-2004. Dallas; American Heart Association 2003
• 7 Javaheri S, Parker T J, Wexler L et al.. Occult sleep-disordered breathing in stable congestive heart failure.  Ann Intern Med. 1995;  122 487-492 , Erratum. Ann Intern Med 1995;123:77
• 8 Hanly P J, Millar T W, Steljes D G et al.. Respiration and abnormal sleep in patients with congestive heart failure.  Chest. 1989;  96 480-488
• 9 Javaheri S, Parker T J, Liming J D et al.. Sleep apnea in 81 ambulatory male patients with stable heart failure: types and their prevalences, consequences, and presentations.  Circulation. 1998;  97 2154-2159
• 10 Tremel F, Pépin J-L, Veale D et al.. High prevalence and persistence of sleep apnoea in patients referred for acute left ventricular failure and medically treated over 2 months.  Eur Heart J. 1999;  20 1201-1209
• 11 Solin P, Bergin P, Richardson M et al.. Influence of pulmonary capillary wedge pressure on central apnea in heart failure.  Circulation. 1999;  99 1574-1579
• 12 Sin D D, Fitzgerald F, Parker J D et al.. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure.  Am J Respir Crit Care Med. 1999;  160 1101-1106
• 13 Yasuma F, Nomura H, Hayashi H et al.. Breathing abnormalities during sleep in patients with chronic heart failure.  Circ J. 1989;  53 1506-1510
• 14 Lofaso F, Verschueren P, Rande JL D et al.. Prevalence of sleep-disordered breathing in patients on a heart transplant waiting list.  Chest. 1994;  106 1689-1694
• 15 Fries R, Bauer D, Heisel A et al.. Clinical significance of sleep-related breathing disorders in patients with implantable cardioverter defbrillators.  Pacing Clin Electrophysiol. 1999;  22 223-227
• 16 Staniforth A D, Kinnear W JM, Starling R et al.. Nocturnal desaturation in patients with stable heart failure.  Heart. 1998;  79 394-399
• 17 Lanfranchi P A, Braghiroli A, Bosimini E et al.. Prognostic value of nocturnal Cheyne-Stokes respiration in chronic heart failure.  Circulation. 1999;  99 1435-1440
• 18 Guilleminault C, Hill J H, Simmons S B, Powell N, Riley R, Stoohs R. Passive constriction of the upper airway during central apneas: fiberoptic and EMG investigations.  Respir Physiol. 1997;  108 11-22
• 19 Badr M S, Toiber F, Skatrud J B, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea.  J Appl Physiol. 1995;  78 1806-1815
• 20 Dowdell W T, Javaheri S, McGinnis W. Cheyne-Stokes respiration presenting as sleep apnea syndrome: clinical and polysomnographic features.  Am Rev Respir Dis. 1990;  141 871-879
• 21 Cherniack N S. Respiratory dysrhythmias during sleep.  N Engl J Med. 1981;  305 325-330
• 22 Khoo MC K, Kronauer R E, Strohl K P et al.. Factors inducing periodic breathing in humans: a general model.  J Appl Physiol. 1982;  53 644-659
• 23 Cherniack N S, Longobardo G S. Cheyne-Stokes breathing: an instability in physiologic control.  N Engl J Med. 1973;  288 952-957
• 24 Carley D W, Shannon D C. A minimal mathematical model of human periodic breathing.  J Appl Physiol. 1988;  65 1400-1409
• 25 Khoo MC K, Gottschalk A, Pack A I. Sleep-induced periodic breathing and apnea: a theoretical study.  J Appl Physiol. 1991;  70 2014-2024
• 26 Khoo MC K. Theorectical models of periodic breathing in sleep apnea. In: Bradley TD, Floras JS Implications in Cardiovascular and Cerebrovascular Disease New York; Marcel Dekker 2000 146: 335-384
• 27 Guyton A C, Crowell J W, Moore J W. Basic oscillating mechanisms of Cheyne-Stokes breathing.  Am J Physiol. 1956;  187 395-398
• 28 Younes M. The physiologic basis of central apnea and periodic breathing.  Curr Opin Pulm Med. 1989;  10 265-326
• 29 Millar T W, Hanly P J, Hunt B et al.. The entrainment of low frequency breathing periodicity.  Chest. 1990;  98 1143-1148
• 30 Hall M J, Xie A, Rutherford R et al.. Cycle length of periodic breathing in patients with and without heart failure.  Am J Respir Crit Care Med. 1996;  154 376-381
• 31 Javaheri S. A mechanism of central sleep apnea in patients with heart failure.  N Engl J Med. 1999;  341 949-954
• 32 Dempsey J A, Skatrud J B. Fundamental effects of sleep state on breathing.  Curr Opin Pulm Med. 1988;  9 267-304
• 33 Skatrud J B, Dempsey J A. Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation.  J Appl Physiol. 1983;  55 813-822
• 34 Dempsey J A, Skatrud J B. A sleep-induced apneic threshold and its consequences.  Am Rev Respir Dis. 1986;  133 1163-1170
• 35 Nakayama H, Smith C A, Rodman J R et al.. Effect of ventilatory drive on CO₂ sensitivity below eupnea during sleep.  Am J Respir Crit Care Med. 2002;  165 1251-1258
• 36 Xie A, Skatrud J B, Puleo D S et al.. Apnea-hypopnea threshold for CO₂ in patients with congestive heart failure.  Am J Respir Crit Care Med. 2002;  165 1245-1250
• 37 Tkacova R, Hall M L, Luie P P et al.. Left ventricular volume in patients with heart failure and Cheyne-Stokes respiration during sleep.  Am J Respir Crit Care Med. 1997;  156 1549-1555
• 38 Hanly P, Zuberi N, Gray R. Pathogenesis of Cheyne-Stokes respiration in patients with congestive heart failure: relationship to arterial PCO₂ .  Chest. 1993;  104 1079-1084
• 39 Naughton M, Bernard D, Tam A et al.. Role of hyperventilation in the pathogenesis of central sleep apneas in patients with congestive heart failure.  Am Rev Respir Dis. 1993;  148 330-338
• 40 Javaheri S, Corbett W S. Association of low PaCO₂ with central sleep apnea and ventricular arrhythmias in ambulatory patients with stable heart failure.  Ann Intern Med. 1998;  128 204-207
• 41 Javaheri S. Central sleep apnea and heart failure.  Circulation. 2000;  342 293-294
• 42 Zhou X S, Shahabuddin S, Zahn B R et al.. Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep.  J Appl Physiol. 2000;  89 192-199
• 43 Britten M B, Zeiher A M, Schächinger V. Clinical importance of coronary endothelial vasodilator dysfunction and therapeutic options.  J Intern Med. 1999;  245 315-327
• 44 Biegelsen E S, Loscalzo J. Endothelial function and atherosclerosis.  Coron Artery Dis. 1999;  10 241-256
• 45 Yu A Y, Shimoda L A, Iyer N V et al.. Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α.  J Clin Invest. 1999;  103 691-696
• 46 Koong A C, Chen E Y, Giaccia A J. Hypoxia causes the activation of nuclear factor kB through the phosphorylation of IkBα on tyrosine residues.  Cancer Res. 1994;  54 1425-1430
• 47 Kanagy N L, Walker B R, Nelin L D. Role of endothelin in intermittent hypoxia-induced hypertention.  Hypertension. 2001;  37 511-515
• 48 Adhikary G, Kline D, Yuan G et al.. Gene regulation during intermittent hypoxia: evidence for the involvement of reactive oxygen species.  Adv Exp Med Biol. 2001;  499 297-302
• 49 Ichikawa H, Flores S, Kvietys P R et al.. Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells.  Circ Res. 1997;  81 922-931
• 50 Samarasinghe D A, Tapner M, Farrell G C. Role of oxidative stress in hypoxia-reoxygenation injury to cultured rat hepatic sinusoidal endothelial cells.  Hepatology. 2000;  31 1600-1605
• 51 Willam C, Schindler R, Frei U et al.. Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells.  Am J Physiol. 1999;  276 H2044-H2052
• 52 Prabhakar N R. Physiological and genomic consequences of intermittent hypoxia. Invited review: oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms.  J Appl Physiol. 2001;  90 1986-1994
• 53 Prabhakar N R. Sleep apneas: an oxidative stress?.  Am J Respir Crit Care Med. 2002;  165 859-860
• 54 Gozal D, Daniel J M, Dohanich G P. Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in rat.  J Neurosci. 2001;  21 2442-2450
• 55 Row B W, Liu R, Xu W, Kheirandish L, Gozal D. Intermittent hypoxemia is associated with oxidative stress and spatial learning deficits in the rat.  Am J Respir Crit Care Med. 2003;  167 1548-1553
• 56 Van de Borne P, Oren R, Abouassaly C et al.. Effect of Cheyne-Stokes respiration on muscle sympathetic nerve activity in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.  Am J Cardiol. 1998;  81 432-436
• 57 Shimizu T, Takahashi Y, Kogawa S et al.. Muscle sympathetic nerve activity during central, mixed and obstructive apnea: are there any differences?.  Psychiatry Clin Neurosci. 1997;  51 397-403
• 58 Naughton M T, Benard D C, Liu P P et al.. Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep apnea.  Am J Respir Crit Care Med. 1995;  152 473-479
• 59 Mansfield D, Kaye D M, LaRoacca H B, Bolin P, Esler M D, Naughton M T. Raised sympathetic nerve activity in heart failure and central sleep apnea is due to heart failure severity.  Circulation. 2003;  107 1396-1400
• 60 Findley L J, Zwillich C W, Ancoli-Israel S et al.. Cheyne-Stokes breathing during sleep in patients with left ventricular heart failure.  South Med J. 1985;  78 11-15
• 61 Hanly P, Zuberi-Khkhar N. Increased mortality associated with Cheyne-Stokes respiration in patients with congestive heart failure.  Am J Respir Crit Care Med. 1996;  153 272-276
• 62 Sin D D, Logan A G, Fitzgerald F S et al.. Effects of continuous positive airway pressure on cardiovascular outcomes in heart failure patients with and without Cheyne-Stokes respiration.  Circulation. 2000;  102 61-66
• 63 Ancoli-Israel S, DuHamel E R, Stepnowsky C, Engler R, Cohen-Zion M, Marler M. The relationship between congestive heart failure, sleep apnea, and mortality in older men.  Chest. 2003;  124 1400-1405
• 64 Gorra U, Giordano A, Bosimini E et al.. Oscillatory ventilation during exercise in patients with chronic heart failure.  Chest. 2002;  121 1572-1580
• 65 Leite J J, Mansur A J, Freitas G D et al.. Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation.  J Am Coll Cardiol. 2003;  41 2175-2181
• 66 Roebuck T, Solin P, Kaye D M, Bergin P, Bailey M, Naughton M T. Increased long-term mortality in heart failure due to sleep apnoea is not yet proven.  Eur Respir J. 2004;  23 735-740
• 67 Andreas S, Hagenah G, Möller C et al.. Cheyne-Stokes respiration and prognosis in congestive heart failure.  Am J Cardiol. 1996;  78 1260-1264
• 68 Javaheri S. Treatment of central sleep apnea in heart failure.  Sleep. 2000;  23 S224-S227
• 69 Ribeiro J P, Knutzen A, Rocco M B et al.. Periodic breathing during exercise in severe heart failure: reversal with milrinone or cardiac transplantation.  Chest. 1987;  92 555-556
• 70 Braver H M, Brandes W C, Kubiet M A et al.. Effect of cardiac transplantation on Cheyne-Stokes respiration occurring during sleep.  Am J Cardiol. 1995;  76 632-634
• 71 Murdock D K, Lawless C E, Loeb H S et al.. The effect of heart transplantation on Cheyne-Stokes respiration associated with congestive heart failure.  J Heart Transplant. 1986;  5 336-337
• 72 Mansfield D R, Solin P, Roebuck T, Bergin P, Kaye D M, Naughton M T. The effect of successful heart transplant treatment of heart failure on central sleep apnea.  Chest. 2003;  124 1675-1681
• 73 Madden B P, Shenoy V, Dalrymple-Hay M et al.. Absence of bradycardic response to apnea and hypoxia in heart transplant recipients with obstructive sleep apnea.  J Heart Lung Transplant. 1997;  16 394-397
• 74 Collop N A. Cheyne-Stokes ventilation converting to obstructive sleep apnea following heart transplantation.  Chest. 1993;  104 1288-1289
• 75 Klink M E, Sethi G K, Copeland J G et al.. Obstructive sleep apnea in heart transplant patients: a report of five cases.  Chest. 1993;  104 1090-1092
• 76 Nkere U U, Hall MC S, Corris P A. Sleep apnoea/hypopnoea syndrome: a potential cause of graft failure following heart transplantation.  Eur J Cardiothorac Surg. 1998;  13 203-205
• 77 Javaheri S, Abraham W T, Brown C, Nishiyama H, Giesting R, Wagoner L E. Prevalence of obstructive sleep apnoea and periodic limb movement in 45 subjects with heart transplantation.  Eur Heart J. 2004;  25 260-266
• 78 Javaheri S. Pembrey's dream: the time has come for a long-term trial of nocturnal supplemental nasal oxygen to treat central sleep apnea in congestive heart failure.  Chest. 2003;  123 322-325
• 79 Javaheri S, Ahmed M, Parker T J et al.. Effects of nasal O₂ on sleep-related disordered breathing in ambulatory patients with stable heart failure.  Sleep. 1999;  22 1101-1106
• 80 Hanly P F, Millar T W, Steljes D G et al.. The effect of oxygen on respiration and sleep in patients with congestive heart failure.  Ann Intern Med. 1989;  111 777-782
• 81 Franklin K A, Eriksson P, Sahlin et al.. Reversal of central sleep apnea with oxygen.  Chest. 1997;  111 163-169
• 82 Andreas S, Clemens C, Sandholzer H et al.. Improvement of exercise capacity with treatment of Cheyne-Stokes respiration in patients with congestive heart failure.  J Am Coll Cardiol. 1996;  27 1486-1490
• 83 Andreas S, Von Zur Muhlen F, Stevens J et al.. Nocturnal oxygen and hypercapnic ventilatory response in patients with congestive heart failure.  Respir Med. 1998;  92 426-431
• 84 Andreas S, Bingeli C, Mohacsi P, Lischer T F, Noll G. Nasal oxygen and muscle sympathetic nerve activity in heart failure.  Chest. 2003;  123 366-371
• 85 Staniforth A D, Kinneart WJ M, Hetmanski D J et al.. 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;  19 922-928
• 86 Andreas S, Plock E H, Heindl S et al.. Nasal oxygen effects on arterial carbon dioxide pressure and heart rate in chronic heart failure.  Am J Cardiol. 1999;  83 795-798
• 87 Dowell A R, Heyman A, Sicker H O et al.. Effect of aminophylline on respiratory-center sensitivity in Cheyne-Stokes respiration and in pulmonary emphysema.  N Engl J Med. 1965;  273 1447-1453
• 88 Dowdell W T, Javaheri S, McGinnis W. Cheyne-Stokes respiration presenting as sleep apnea syndrome: clinical and polysomongraphic features.  Am Rev Respir Dis. 1990;  141 871-879
• 89 Javaheri S, Parker T J, Wexler L et al.. Effect of theophylline on sleep-disordered breathing in heart failure.  N Engl J Med. 1996;  335 562-567
• 90 White D P, Zwillich C S, Pickett C K, Douglas N J, Findley L J, Weil J V. Central sleep apnea improvement with acetazolamide therapy.  Arch Intern Med. 1982;  182 1816-1819
• 91 DeBacker W A, Verbraecken J, Willemen M, Wittesaele W, DeCock W, Van deHeynin P. Central apnea index decreases after prolonged treatment with Acetazolamide.  Am J Respir Crit Care Med. 1995;  151 87-91
• 92 Sutton J R, Houston C S, Mansell A L et al.. Effect of acetazolamide on hyopoxemia during sleep in high altitude.  N Engl J Med. 1979;  301 1329-1331
• 93 Javaheri S. Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure.  Circulation. 2000;  101 392-397
• 94 Naughton M T, Bernard D C, Liu P P et al.. Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep apnea.  Am J Respir Crit Care Med. 1995;  152 473-479
• 95 Naughton M T, Liu P P, Benard D C et al.. Treatment of congestive heart failure and Cheyne-Stokes respiration during sleep by continuous positive airway pressure.  Am J Respir Crit Care Med. 1995;  151 92-97
• 96 Guilleminault C, Clerk A, Labanowski M et al.. Cardiac failure and benzodiazepines.  Sleep. 1993;  16 524-528
• 97 Buckle P, Millar T, Kryger M. The effects of short-term nasal CPAP on Cheyne-Stokes respiration in congestive heart failure.  Chest. 1992;  102 31-35
• 98 Davies RJ O, Harrington K J, Omerod J M et al.. Nasal continuous positive airway pressure in chronic heart failure with sleep-disordered breathing.  Am Rev Respir Dis. 1993;  147 630-634
• 99 Keily J L, Deegan P, Buckley A et al.. Efficacy of nasal continuous positive airway pressure therapy in chronic heart failure: importance of underlying cardiac rhythm.  Thorax. 1998;  53 956-962
• 100 Teschler H, Döhring J, Wang Y M et al.. Adaptive pressure support servo-ventilation.  Am J Respir Crit Care Med. 2001;  164 614-619
• 101 Garrigue S, Bordier P, Jaïs P et al.. Benefit of atrial pacing in sleep apnea syndrome.  N Engl J Med. 2002;  346 404-412