Correspondence
Central Sleep Apnea and Heart Failure
N Engl J Med 2000; 342:293-294January 27, 2000
- Article
To the Editor:
The article by Javaheri (Sept. 23 issue)1 expands our understanding of the key role of enhanced central chemoreflex sensitivity, including increased ventilatory responsiveness to hyperoxic hypercapnia while awake, in the pathophysiology of central sleep apnea in patients with congestive heart failure. However, it remains to be determined whether this abnormality is a predisposing factor for, or a consequence of, the development of congestive heart failure.
We reported our observation of increased ventilatory responses in patients with heart failure and central sleep apnea in 1993,2 and we subsequently reported that patients with obstructive apnea and heart failure had normal ventilatory responses to hypercapnia.3 In addition, a recent study by Narkiewicz et al.4 demonstrated increased ventilatory and blood-pressure responses to hypercapnia in patients with congestive heart failure who are not known to have sleep-disordered breathing.
Central sleep apnea is believed to occur as a consequence of the development of congestive heart failure.5 Among normal subjects there is a very wide range of ventilatory responsiveness to hypercapnia. Although we agree that it is plausible that the onset of congestive heart failure may increase responses to pathologically high levels, to our knowledge the occurrence of respiratory control abnormalities before the development of cardiac failure has not been documented.
5 ReferencesIan Wilcox, M.B., Ph.D.
Stephen G. McNamara, M.B., Ph.D.
Colin E. Sullivan, M.B., Ph.D.
Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia1
Javaheri S . A mechanism of central sleep apnea in patients with heart failure. N Engl J Med 1999;341:949-954
Full Text | Web of Science | Medline2
Wilcox I ,Grunstein RR ,Collins FL ,Berthon-Jones M ,Kelly DT ,Sullivan CE . The role of central chemosensitivity in central apnea of heart failure. Sleep 1993;16:Suppl:S37-S38
Web of Science | Medline3
Wilcox I ,McNamara SG ,Dodd MJ ,Sullivan CE . Ventilatory control in patients with sleep apnoea and left ventricular dysfunction: comparison of obstructive and central sleep apnoea. Eur Respir J 1998;11:7-13
CrossRef | Web of Science | Medline4
Narkiewicz K ,Pesek CA ,van de Borne PJ ,Kato M ,Somers VK . Enhanced sympathetic and ventilatory responses to central chemoreflex activation in heart failure. Circulation 1999;100:262-267
Web of Science | Medline5
Wilcox I ,McNamara SG ,Wessendorf T ,Willson GN ,Piper AJ ,Sullivan CE . Prognosis and sleep disordered breathing in heart failure. Thorax 1998;53:Suppl 3:S33-S36
CrossRef | Web of Science | Medline
To the Editor:
Javaheri reports that among patients with congestive heart failure, those who have central sleep apnea have a higher ventilatory response to carbon dioxide than do those who do not have central sleep apnea. Although we do not dispute his findings, we are concerned about his interpretation of the data. The author concludes that enhanced sensitivity of the central chemoreceptors plays a critical part in the genesis of central sleep apnea in patients with congestive heart failure. However, this statement is inconsistent with data from another of his papers, in which he and colleagues demonstrated that theophylline diminished the occurrence of central sleep apnea in patients with congestive heart failure.1 If enhanced chemoreceptor sensitivity is responsible for the genesis of central sleep apnea, exposure to theophylline should exacerbate this disorder in patients with congestive heart failure, not improve it as reported,1 because theophylline is a known respiratory stimulant that increases minute ventilation and the ventilatory response to hypercapnia.2
A recent study by Solin et al. suggests an alternative explanation.3 Solin et al. found that pulmonary-capillary wedge pressure was associated with the severity and frequency of central sleep apnea and that lowering it through treatment resulted in a significant improvement in the severity of the apnea. Since pulmonary-capillary wedge pressure indirectly reflects the severity of left ventricular dysfunction, the heightened ventilatory response to hypercapnia among patients with central sleep apnea may reflect increased ventilatory stimulation through vagal reflexes as a result of pulmonary edema.4 Indeed, in the present study, patients with congestive heart failure and central sleep apnea had a lower left ventricular ejection fraction and lower systolic blood pressure than those without central sleep apnea, differences that suggest that the patients with central sleep apnea also had worse cardiac function. An analysis with control for the severity of pulmonary congestion would therefore have provided a more compelling argument in favor of augmented central drive as the main culprit in central sleep apnea in patients with congestive heart failure.
4 ReferencesDon D. Sin, M.D.
Godfrey C. Man, M.D.
Richard L. Jones, Ph.D.
University of Alberta, Edmonton, AB T6G 2B7, Canada1
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;335:562-567
Full Text | Web of Science | Medline2
Javaheri S ,Guerra L . Lung function, hypoxic and hypercapnic ventilatory responses, and respiratory muscle strength in normal subjects taking oral theophylline. Thorax 1990;45:743-747
CrossRef | Web of Science | Medline3
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;99:1574-1579
Web of Science | Medline4
Cherniack NS . Apnea and periodic breathing during sleep. N Engl J Med 1999;341:985-987
Full Text | Web of Science | Medline
Author/Editor Response
Dr. Javaheri replies:
To the Editor: In a preliminary study,1 Wilcox and colleagues found that in eight patients with heart failure and central sleep apnea, the ventilatory responses to carbon dioxide were greater than published values for normal subjects. Without a well-matched control group, it is not possible to determine whether the increase in carbon dioxide sensitivity resulted from heart failure or from central sleep apnea. Meanwhile, other investigators measured the ventilatory response to carbon dioxide in patients with heart failure, as compared with that in normal subjects; one investigation found a significant difference,2 whereas the other found no significant difference.3
In a detailed study, Wilcox and colleagues assessed the ventilatory response to carbon dioxide in patients with heart failure who had central sleep apnea and those who had obstructive sleep apnea.4 My interpretation of that study, as noted in my article, is that the enhanced sensitivity in heart failure was specific to central but not obstructive sleep apnea.
Sin and colleagues made one error in their statements. They misquoted the results of my study of theophylline5 by stating that theophylline increases the ventilatory response to carbon dioxide. This is incorrect. In that study, 10 normal subjects were given therapeutic doses of theophylline orally for four days. The values for the slopes of the ventilatory response to carbon dioxide before, during, and after discontinuation of theophylline therapy did not differ significantly. Another study with oral theophylline has produced similar results.6 I propose that the therapeutic effects of theophylline in central sleep apnea may be mediated by adenosine antagonism.
I am afraid that the alternative explanation proposed by Sin et al. to explain our findings also is probably not germane to my data. They cite a study by Solin et al. that showed that in patients with heart failure and central sleep apnea, pulmonary-capillary wedge pressure inversely correlated with the partial pressure of carbon dioxide, emphasizing the relation of a high wedge pressure and pulmonary congestion to hyperventilation. The study groups in my investigation were well matched, with similar mean values for minute ventilation, respiratory rate, tidal volume, and partial pressure of arterial carbon dioxide. Furthermore, the percentages of patients with crackles and leg edema were lower in the group of patients with heart failure who had central sleep apnea than in the group of patients who did not. For all these reasons, I do not think that the difference in ventilatory responses in my patients was due to differences in wedge pressure.
6 ReferencesShahrokh Javaheri, M.D.
Veterans Affairs Medical Center, Cincinnati, OH 452201
Wilcox I ,Grunstein RR ,Collins FL ,Berthon-Jones M ,Kelly DT ,Sullivan CE . The role of central chemosensitivity in central apnea of heart failure. Sleep 1993;16:Suppl:S37-S38
Web of Science | Medline2
Chua TP ,Clark AL ,Amadi AA ,Coats AJ . Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol 1996;27:650-657
CrossRef | Web of Science | Medline3
Andreas S ,von Breska B ,Kopp E ,Figulla HR ,Kreuzer H . Periodic respiration in patients with heart failure. Clin Investig 1993;71:281-285
CrossRef | Medline4
Wilcox I ,McNamara SG ,Dodd MJ ,Sullivan CE . Ventilatory control in patients with sleep apnoea and left ventricular dysfunction: comparison of obstructive and central sleep apnea. Eur Respir J 1998;11:7-13
CrossRef | Web of Science | Medline5
Javaheri S ,Guerra L . Lung function, hypoxic and hypercapnic ventilatory responses, and respiratory muscle strength in normal subjects taking oral theophylline. Thorax 1990;45:743-747
CrossRef | Web of Science | Medline6
Swaminathan S ,Paton JY ,Ward SL ,Sargent CW ,Keens TG . Theophylline does not increase ventilatory responses to hypercapnia or hypoxia. Am Rev Respir Dis 1992;146:1398-1401
Web of Science | Medline
- Citing Articles (8)
Citing Articles
1
Richard S. T. Leung, Vikram R. Comondore, Clodagh M. Ryan, Daniel Stevens. (2011) Mechanisms of sleep-disordered breathing: causes and consequences. Pflügers Archiv - European Journal of Physiology
CrossRef2
Safwan Badr. (2009) Central sleep apnea in patients with congestive heart failure. Heart Failure Reviews 14:3, 135-141
CrossRef3
Farouk Mookadam, Andrew D. Calvin, Virend K. Somers. (2008) Prevalence and management of central sleep apnea in heart failure patients. Current Heart Failure Reports 5:4, 233-237
CrossRef4
Biju Paul, Majo Joseph, Carmine G. De Pasquale. (2008) Domiciliary Oxygen Therapy Improves Sub-Maximal Exercise Capacity and Quality of Life in Chronic Heart Failure. Heart, Lung and Circulation 17:3, 220-223
CrossRef5
STEPHANE GARRIGUE, PHILIPPE BORDIER, S. SERGE BAROLD, JACQUES CLEMENTY. (2004) Sleep Apnea:. A New Indication for Cardiac Pacing?. Pacing and Clinical Electrophysiology 27:2, 204-211
CrossRef6
S Garrigue, P Bordier, J Clémenty. (2003) Apnées du sommeil et stimulation cardiaque : mécanismes d’action et perspectives. Annales de Cardiologie et d'Angéiologie 52:4, 239-245
CrossRef7
(2002) Atrial Pacing in Sleep Apnea Syndrome. New England Journal of Medicine 347:6, 445-446
Full Text8
Garrigue, Stephane, Bordier, Philippe, Jaïs, Pierre, Shah, Dipen C., Hocini, Meleze, Raherison, Chantal, Tunon De Lara, Manuel, Haïssaguerre, Michel, Clementy, Jacques, . (2002) Benefit of Atrial Pacing in Sleep Apnea Syndrome. New England Journal of Medicine 346:6, 404-412
Full Text
