Correspondence

Continuous Positive Airway Pressure in Patients with Heart Failure

N Engl J Med 2003; 349:93-95July 3, 2003

Article

To the Editor:

The results of the study by Kaneko and colleagues (March 27 issue)1 could have serious implications for the practice of physicians caring for patients with heart failure. The prevalence of obstructive sleep apnea in patients with heart failure has been estimated to be as low as 11 percent and as high as 37 percent.2,3 This variability raises the possibility of selection bias.3 If the prevalence of obstructive sleep apnea in patients with heart failure is as high as 37 percent, physicians should order polysomnography more frequently. If the true prevalence is at the lower end of this range, physicians will need to know how to identify patients who are likely to have obstructive sleep apnea. Since the patients enrolled in the study snored habitually without having subjective daytime sleepiness, the authors should clarify their indications for polysomnography in patients with heart failure. They should also clarify the enrollment process, including the number of patients who underwent screening, underwent polysomnography, and agreed to the initiation of continuous positive airway pressure and randomization. This information will help their findings to be generalized to clinical practice, particularly in centers with limited sleep-disorder services.

Aiman Tulaimat, M.D.
Babak Mokhlesi, M.D.
Cook County Hospital, Chicago, IL 60612
atulaimat@prodigy.net

Damien Stevens, M.D.
Rush Medical College, Chicago, IL 60612

3 References

1. 1

   Kaneko Y, Floras JS, Usui K, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med 2003;348:1233-1241
   Full Text | Web of Science | Medline

2. 2

   Javaheri S, Parker TJ, Liming JD, 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
   Web of Science | Medline

3. 3

   Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD. 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
   Web of Science | Medline

To the Editor:

Given the high prevalence of heart failure and the great cost associated with it, the identification and treatment of potential exacerbating factors are important. However, with regard to the study by Kaneko and colleagues, the following should be noted. First, the values for the apnea–hypopnea index at base line in the control and treatment groups are consistent with the presence of a moderate-to-severe degree of sleep-disordered breathing. It is unclear whether the results can be generalized to patients with milder disease. Javaheri et al.1 found the overall prevalence of obstructive sleep apnea to be 11 percent in an unselected group of patients with heart failure; therefore, the subgroup of patients likely to derive benefit from the intervention may be quite limited. Furthermore, to the extent that right ventricular wall thickness but not left ventricular mass has been shown to be increased in patients with sleep-disordered breathing,2,3 one wonders whether the hemodynamic changes seen might not have resulted from improvements in pulmonary arterial hypertension. It remains to be shown whether improving the ejection fraction in such patients would improve clinical outcomes.

Michael D. Weinstein, M.D.
Winthrop University Hospital, Mineola, NY 11501
mweinstein@winthrop.org

3 References

1. 1

   Javaheri S, Parker TJ, Liming JD, 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
   Web of Science | Medline

2. 2

   Guidry UC, Mendes LA, Evans JC, et al. Echocardiographic features of the right heart in sleep-disordered breathing: the Framingham Heart Study. Am J Respir Crit Care Med 2001;164:933-938
   Web of Science | Medline

3. 3

   Niroumand M, Kuperstein R, Sasson Z, Hanly PJ. Impact of obstructive sleep apnea on left ventricular mass and diastolic function. Am J Respir Crit Care Med 2001;163:1632-1636
   Web of Science | Medline

Author/Editor Response

Tulaimat and colleagues and Weinstein underscore the considerable implications of our findings for the management of heart failure. Clues to the presence of obstructive sleep apnea in patients with heart failure include snoring, male sex, a body-mass index above 30, and persistent systolic hypertension, but most patients do not report daytime sleepiness.1,2 The 37 percent prevalence of obstructive sleep apnea reported by Sin et al.1 arises from a retrospective analysis of 450 patients with heart failure who were referred to our heart failure clinics. We have since performed polysomnography prospectively in 150 consecutively referred patients; 44 percent and 21 percent had obstructive sleep apnea with apnea–hypopnea indexes of 10 or higher and 20 or higher, respectively. Patients in our institutions now undergo polysomnography routinely if they have symptomatic heart failure despite optimal medical therapy. Subjects for the current trial were recruited from among 138 such patients. Of the 29 (21 percent) found to have obstructive sleep apnea with an apnea–hypopnea index of 20 or higher, 24 (83 percent) volunteered for this study. We are therefore confident that our experience reflects the general prevalence of obstructive sleep apnea among patients referred to tertiary heart failure clinics.

Weinstein wonders whether our findings in patients with severe obstructive sleep apnea (mean apnea–hypopnea index, 40) can be generalized to those with milder obstructive sleep apnea. In a recent randomized trial involving patients with heart failure who had milder obstructive sleep apnea (mean apnea–hypopnea index, 25), continuous positive airway pressure increased the ejection fraction from 38 percent to 43 percent (P<0.04),3 suggesting that our results may indeed be generalizable.

The studies concerning ventricular mass that are cited by Weinstein did not report pulmonary-artery pressure or assess patients with heart failure. Long-term use of continuous positive airway pressure in patients with heart failure has been shown to reduce mitral regurgitation,4 a change that would passively decrease pulmonary-artery pressure. However, amelioration of pulmonary hypertension per se cannot explain the reductions in systemic blood pressure, heart rate, and left ventricular end-systolic dimensions and the improvements in ejection fraction documented in our patients who were treated with continuous positive airway pressure.

Weinstein makes the point that improvements in the ejection fraction do not necessarily translate into improved clinical outcomes, as we acknowledge in our Discussion section. However, one should not underestimate the challenges involved in conducting an outcomes trial in which therapy with continuous positive airway pressure would be withheld from a group of control patients with heart failure and obstructive sleep apnea for extended periods. Fortunately, the long-term application of continuous positive airway pressure to patients with heart failure and central sleep apnea has been shown to decrease the rates of hospitalization, death, and transplantation and to improve the quality of life as well as the ejection fraction.5

T. Douglas Bradley, M.D.
Toronto General Hospital–University Health Network, Toronto, ON M5G 2C4, Canada
douglas.bradley@utoronto.ca

John S. Floras, M.D., D.Phil.
Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada

Kengo Usui, M.D., Ph.D.
Toronto Rehabilitation Institute, Toronto, ON M5G 2A2, Canada

5 References

1. 1

   Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD. 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
   Web of Science | Medline

2. 2

   Sin DD, Fitzgerald F, Parker JD, et al. Relationship of systolic BP to obstructive sleep apnea in patients with congestive heart failure. Chest 2003;123:1536-1543
   CrossRef | Web of Science | Medline

3. 3

   Mansfield DR, Gollogly NC, Bergin P, et al. Cardiomyopathy, (obstructive) sleep apnea and trial of nasal positive airway pressure (CATNAP Study). Am J Respir Crit Care Med 2003;167:A835-A835 abstract.
   CrossRef | Web of Science

4. 4

   Tkacova R, Liu PP, Naughton MT, Bradley TD. Effects of continuous positive airway pressure on mitral regurgitant fraction and atrial natriuretic peptide in patients with heart failure. J Am Coll Cardiol 1997;30:739-745
   CrossRef | Web of Science | Medline

5. 5

   Bradley TD, Floras JS. Sleep apnea and congestive heart failure. II. Central sleep apnea. Circulation 2003;107:1822-1826
   CrossRef | Web of Science | Medline