Reviews. Introduction. Methods. with SDB and heart failure, and a meta-analysis of these published data was done.

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1 Reviews The Effects of Continuous Positive Airways Pressure Therapy on Cardiovascular End Points in Patients With Sleep-Disordered Breathing and Heart Failure: A Meta-Analysis of Randomized Controlled Trials Address for correspondence: Saurabh Aggarwal, Chicago Medical School/James A. Lovell Federal Health Center 31 Green Bay Road North Chicago, IL drsaurabhaggarwal@gmail.com Saurabh Aggarwal, ; Rashid Nadeem, ; Rohit S. Loomba, ; Mahwish Nida, MBBS; Dorice Vieira, MPH Chicago Medical School/James A Lovell Federal Health Center (Aggarwal, Nadeem), North Chicago, Illinois; Children s Hospital of Wisconsin/Medical College of Wisconsin Affiliated Hospitals (Loomba), Wauwatosa, Wisconsin; SUNY Downstate Health Center (Nida), Brooklyn, New York; New York University (Vieira), New York, New York In patients with sleep-disordered breathing and heart failure, continuous positive airway pressure has been found to be associated with an improvement in cardiovascular end points. We conducted a systematic review of the current literature and a meta-analysis to pool data from 15 published randomized controlled trials. End points analyzed were left ventricular ejection fraction, diastolic blood pressure, systolic blood pressure, heart rate, and mortality. A fixed effects model was used for end points demonstrating homogeneity among included studies, whereas a random effects model was used for end points demonstrating heterogeneity among included studies. A significant improvement in left ventricular ejection fraction was noted with continuous positive airway pressure (mean difference, 5.5%; 95% confidence interval [CI]: 3.7 to.3), diastolic blood pressure (mean difference, 1.7; 95% CI: 3.9 to.5), and heart rate (mean difference, 5.9; 95% CI: 1.1 to 1.7). No significant changes in mortality (odds ratio,.3; 95% CI:. to 1.) and systolic blood pressure were noted (mean difference,.35; 95% CI: 1.11 to.1). The analysis also revealed the need for additional studies to clarify the associations noted and the presence of publication bias with small studies with a paucity of small studies with negative results. In this meta-analysis, treatment with continuous positive airways pressure was associated with improvements in ejection fraction, diastolic blood pressure, and heart rate in patients with sleep-disordered breathing and congestive heart failure. Introduction Approximately 5.7 million patients suffer from heart failure in the United States. The incidence approaches 1 per 1 population after 5 years of age. Sleep-disordered breathing (SDB) entails both obstructive sleep apnea (OSA) and central sleep apnea (CSA). OSA is a disease seen frequently in patients with heart failure, and although it has not been established as a cause of heart failure, there are data suggestive of increased mortality in heart failure patients with OSA. 1, Continuous positive airway pressure (CPAP) therapy has been shown to be effective in reducing mortality in heart failure patients with OSA. 3, This is in contrast to the fact that CPAP therapy was not associated with improved survival in patients with CSA and heart failure in some studies. 5 Multiple studies have evaluated the effect of CPAP therapy on cardiovascular end points in patients The authors have no funding, financial relationships, or conflicts of interest to disclose. Received: April 15, 13 Accepted with revision: July 7, 13 with SDB and heart failure, and a meta-analysis of these published data was done. Methods A systematic review of the medical literature was conducted to identify studies to be included in the analysis. The search was done utilizing PubMed, Ovid, and the Cochrane Library using the time duration of January 1, 19 to December 31, 11. Searches were carried out using the following terms individually to ensure that the largest number of potentially relevant studies would be retrieved: continuous positive airway pressure, heart failure, sleep apnea, and sleep disordered breathing. Combinations of these terms were then used in searches to assist in study selection. Articles were initially screened by title and abstract. Studies were deemed appropriate for further analysis if the following criteria were met: the article was in English; compared groups of patients in which all patients had both SDB and heart failure; consisted of a group of patients who received CPAP therapy and Clin.Cardiol.37,1,57 5(1) 57 DOI:1.1/clc.1 13 Wiley Periodicals, Inc.

2 another group of patients who received no intervention or sham therapy; documented baseline demographics; and reported the impact of CPAP on systolic blood pressure, diastolic blood pressure, heart rate, left ventricular ejection fraction (LVEF), brain natriuretic peptide levels, atrial natriuretic peptide levels, plasma norepinephrine levels, urine norepinephrine levels, hospitalizations, and all-cause mortality. Because all searches were done over 3 databases, redundant results had to be excluded. Any publication reporting even a single end point but fulfilling the inclusion and exclusion criteria was included. Full text of the articles found appropriate for further evaluation were obtained. Studies with redundant data, lack of relevant data, or unusable data were excluded, and the remainder were included in the pooled analysis. Evaluation of all articles was done by separate authors who scored each article based on the inclusion criteria. Differences in scoring between authors were then evaluated by the third author. Data were extracted from studies selected to be included by individual authors, and results were compared by the third author to ensure accuracy of data extraction. Study selection methodology is outlined in Figure 1. A pooled analysis was used to evaluate the effect of CPAP therapy on each end point individually. A mean difference and 95% confidence interval (CI) was calculated for continuous variables, whereas a common odds ratio (OR) and 95% CI was calculated for OR variables. The Mantel- Haenszel fixed effects model was used for the analysis of end points that demonstrated homogeneity across studies, whereas the random effects model was used for the analysis of end points that demonstrated heterogeneity. A P value of <.5 was considered to be statistically significant. Results of heterogeneity analysis for each end point is included in its respective forest plot. Results Search Strategy Searching PubMed, Ovid, and Cochrane Library, 353 articles were found when continuous positive airway pressure was used as the search term, 1 95 when heart failure was used as the search term, and when sleep-disordered breathing was used as the search term. When all 3 search terms were used together, 3 articles were found. After reviewing titles and abstracts of these articles, 3 were found to be appropriate for fulltext evaluation. Ultimately, 15 studies met the prespecified criteria and were included in the analysis. These include 1 randomized control trials and 3 case control studies. In all studies there was an experimental group with CPAP and the control group, which included either no intervention, or a Continuous Positive Airway Pressure 353 Heart Failure 1,95 Sleep Disordered Breathing, Continuous Positive Airway Pressure + Heart Failure + Sleep Disordered Breathing 3 Redundant studies, nonrandomized studies, studies with incompatible endpoints excluded 33 Studies with unusable results, incompatible study design excluded 15 Figure 1. Study selection methodology. 5 Clin. Cardiol. 37, 1, 57 5 (1) DOI:1.1/clc.1 13 Wiley Periodicals, Inc.

3 Table 1. Quality of evidence: number and level of evidence of peer-reviewed and published papers. Hierarchy of evidence* Level of evidence Description No. of studies 1a Systemic review (with homogeneity*) of randomized, controlled clinical trials (RCTs) 1b Individual randomized controlled clinical trial (RCT) (with narrow Confidence Interval ) 1 1c All or none case series a Systemic review (with homogeneity*) of cohort studies b Individual cohort study (including low quality RCT; e.g., <% follow-up) c Outcomes Research; Ecological studies 3a Systemic review (with homogeneity*) of case control studies 3b Individual Case Control Study 3 Case-series (and poor quality cohort and case control studies) 5 Expert opinion without explicit critical appraisal, or based on physiology, bench research or first principles Others Letters to editor, Abstract Figure. Forest plot of the effect of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) on left ventricular ejection fraction (LVEF) in patients with OSA and congestive heart failure. Abbreviations: CI, confidence interval; IV, inverse variance; SD, standard deviation. sham CPAP, or nocturnal oxygen therapy. Due to the lack of an adequate number of studies reporting brain natriuretic peptide, atrial natriuretic peptide, plasma norepinephrine, urinary norepinephrine, and hospitalizations, these end points were excluded because of the possible risk of bias. To prevent bias, we excluded studies evaluating the effect of CPAP in heart failure with preserved ejection fraction. Studies Composition and Outcomes A total of 5 end points were extracted from 1 studies: systolic blood pressure, diastolic blood pressure, heart rate, LVEF, and all-cause mortality. There were no significant differences in patient demographics between the groups included. The number of subjects in the included studies ranged from 17 to 5. The average apnea-hypopnea index (AHI) in all studies fell into the severe SDB category. Moreover, many studies included young men who were not hypertensive at baseline. Effect of CPAP on LVEF Data from 13 studies were pooled for the analysis of LVEF. Heterogeneity analysis resulted in an I value of 9% (P =.1) that demonstrated significant heterogeneity between studies. The pooled mean difference was found to be 5.5 with a 95% CI of 3.7 to.3 using the random effects model. This result significantly favored the use of CPAP therapy (Figure ). Subgroup analysis was performed by separating the studies into groups: studies with subjects predominantly with CSA or Cheyne-Stokes Respiration (CSR), or studies with subjects with >5% OSA (predominantly obstructive events). Effect of CPAP on LVEF in Predominantly CSA Group 1 (CSA + CSB) had 7 studies with pooled analysis for LVEF showing heterogeneity with an I value of 3% (P =.1). The pooled mean difference was found to be 5., with a 95% CI of 3.5 to 7. using the random effects Clin. Cardiol. 37, 1, 57 5 (1) 59 DOI:1.1/clc.1 13 Wiley Periodicals, Inc.

4 Table. Baseline characteristics of subjects from studies included in the meta-analysis Age mean(sd) Gender Male % BMI BMI AHI mean(sd) F/u mo. Bradley 5 3.(9.1) 3.5(9.) 9 95.(5.5) 9.3(.5) (15) (17) 3 Granton (.) 5() 1 1.9(1.9) 5.(1.) 9(11) 35(11) 3 Naughton 5.1(3) 5(3.) (.) 7(1.) 5(.3) 51.(11.) 1 Naughton (3.) 5.(3.) 1 1 (1.5) 7.1(1.5) 3.(.3) 51.(11.) 1 Naughton 1995 A 1 1.1(.9) 37.3(7.) 1 Tkacova (1.9) 5.(.) 1 1.(1.) 5.1(1.) 5.(.9) 33.7(.5) 3 Sin.() 55.(11.1) 1 1.(1.9) 33.(.) 3 Egea (.9) 3(1.) (.) 3.5(1.) 3(.) 1(5.) 3 Ferrier 5.5(11.).3(.3).9 3.3(.7) 7(3.) Kaneko (.5) 55.(3.) (1.) 3.(.5) 37.1(.) 5.(5.3) 1 Kasai 59.(1.7) 59.(1.) (5.7).9(.5) 5.1(1.9) 3.(1) 5 Mansfield 57.(1.7) 57.5(1.) (.9) 3.(1.).3(.).1(3.9) 3 Ryan 5 57.(.).3(.1) (1.3) 35.1(3.7) 9.3(.) 57.9(5.5) 1 Usui 5 55() 5.(.1) (1.5) 31.3(1.) 1 Wang 7 53.(9.) 5.5(1) 1 3.3(.5) 3.1(5.) 3.(15.9) 3.(1.3) Abbreviations: AHI, Apnea-hypopnea index; BMI, Body mass index; DBP, Diastolic blood pressure; LVEF, Left ventricular ejection fraction; SBP, Systolic blood pressure. Table 3. Cardiac parameters reported by included studies SBP SBP mean(sd) DBP DBP mean HR HR mean LVEF Mean mean Bradley 5.(7.9).(7.) Granton 199 ().(3.) Naughton 17.3(1.) 1.7(.) Naughton () 11(7) 75() 7() () 71(3) 1.(3.) 19.7(.7) Naughton 1995 A 1.3(1.) 19.(.) 75.(3.1) 73(3.) 79.3() 7(3.) 17(3) 19.() Tkacova (1.5) 111.(.) 7.9(.3).1(.) 7.(.9) 3.(.).(.).(3.) Sin.(11.3) 19.(9) Egea 13(3.7) 1(.9) 7(.3) 75(.1) (.5).1(1.5) Ferrier 13(1) 135() (9) 77(11) 35.9(.1) 35.9(7.) Kaneko 3 1() 1(7) () () (3) 7() 5(.).5(1.) Kasai 13.7(13) 13(7) 7.9(1.3) 79.9(7) 7(11) 7.(.5) 3.(1) 35(7.1) Mansfield 37.3(.1) 33.7(.) Ryan 5 1.7(5.) 139(5.5).(3) 9.9(.3).1(.1) 7.5(3.) 7.(3.) 3.1(3) Usui (5.) 11.(9.) 7.9(5.1).(.1).(.3) 7.7(3.) 3.1(3.).(3) Wang 7 3.9(.) 5.(.7) Clin. Cardiol. 37, 1, 57 5 (1) DOI:1.1/clc.1 13 Wiley Periodicals, Inc.

5 Figure 3. Forest plot of the effect of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea on left ventricular ejection fraction in patients with central sleep apnea or Cheyne-Stokes respiration. Abbreviations: CI, confidence interval; EF, ejection fraction; IV, inverse variance; SD, standard deviation. Figure. Forest plot of the effect of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) on left ventricular ejection fraction in patients with predominantly OSA. Abbreviations: CI, confidence interval; EF, ejection fraction; IV, inverse variance; SD, standard deviation. Regression: EF change and Age Regression: EF change and BMI Predicted Mean change in LVEF Linear (Predicted Mean change in LVEF) Predicted Mean change in LVEF Linear (Predicted Mean change in LVEF) Age 1 3 BMI Figure 5. Effect of age on change in Ejection fraction with CPAP treatment for OSA- Regression analysis. Figure. Effect of BMI on change in Ejection fraction with CPAP treatment for OSA- Regression analysis. model. This result significantly favored the use of CPAP therapy (Figure 3). Effect of CPAP on LVEF With Predominantly OSA Group (>5% OSA) had studies with pooled analysis for LVEF showing heterogeneity with an I value of 7% (P =.1). The pooled mean difference was found to be 5., with a 95% CI of 3.1 to 7.3 using the random effects model. This result significantly favored the use of CPAP therapy (Figure ). Regression Analysis for LVEF Regression analysis for age, body mass index, and AHI for change in ejection fraction with CPAP treatment for OSA did not show a significant effect of these parameters on LVEF change (P =.1,.55,.7, respectively) (Figures 5 7). Regression: EF change and AHI AHI Mean change in LVEF Predicted Mean change in LVEF Linear (Predicted Mean change in LVEF) Figure 7. Effect of AHI on change in Ejection fraction with CPAP treatment for OSA- Regression analysis. Effect of CPAP on Diastolic Blood Pressure Six studies were pooled for the analysis of diastolic blood pressure. Heterogeneity analysis resulted in an I value of Clin. Cardiol. 37, 1, 57 5 (1) 1 DOI:1.1/clc.1 13 Wiley Periodicals, Inc.

6 1% (P <.1) that demonstrated homogeneity between studies. The pooled mean difference was found to be 1.7, with a 95% CI of 3.9 to.5 using the fixed effects model. This result significantly favored the use of CPAP therapy (Figure ). Effect of CPAP on Systolic Blood Pressure Six studies were pooled for the analysis of systolic blood pressure. Heterogeneity analysis resulted in an I value of % (P <.1) that demonstrated heterogeneity between studies. The pooled mean difference was found to be.5, with a 95% CI of 1.11 to.1 using the random effects model. This result was not associated with any significant improvement with the use of CPAP therapy (Figure 9). Effect of CPAP on Heart Rate Five studies were pooled for the analysis of heart rate. Heterogeneity analysis resulted in an I value of 7% (P <.1) that demonstrated heterogeneity between studies. The pooled mean difference was found to be 5.9, with a 95% CI of 1.1 to 1.7 using the random effects model. This result significantly favored the use of CPAP therapy (Figure 1). Effect of CPAP on Mortality Four studies were pooled for the analysis of mortality. Heterogeneity analysis resulted in an I value of 55% (P =.) that demonstrated homogeneity between studies. The pooled OR was found to be.3, with a 95% CI of. to 1. using the Mantel-Haenszel fixed effects model. This result was not associated with any significant improvement with the use of CPAP therapy (Figure 11). Discussion This meta-analysis shows that in patients with heart failure and SDB, CPAP therapy was associated with a significant improvement in LVEF, diastolic blood pressure, heart rate, and mortality. There was an insignificant improvement in systolic blood pressure associated with CPAP therapy as well. The American Heart Association/American College of Cardiology recommends adequate testing and diagnosis of sleep apnea in patients with heart failure. Sleep apnea remains undiagnosed in a vast majority of the population, and patients with undiagnosed sleep apnea have been reported to have increased medical costs than age- and sex-matched individuals. 7 Various mechanisms have been proposed to explain the beneficial effects of CPAP therapy in patients with sleep apnea and heart failure. Patients with OSA have increased sympathetic activity, and studies have found lower plasma catecholamine levels after CPAP therapy.,9 Some studies also measured urinary catecholamine levels and found decreased levels in patients treated with CPAP therapy. 9,1 Though other studies reported no significant change in urinary catecholamine levels in patients with heart failure treated with CPAP therapy, compliance with CPAP treatment was lower in these studies. 11 We did not analyze this end point due to the low number of patients for whom data were reported. Improved LVEF has also been reported with CPAP treatment in OSA patients with heart failure. 3,1 15 Improved LVEF has also been reported in patients with CSA. 5,9,1,17 In 1 study of patients with SDB, a trend in improvement of LVEF was seen with the use of CPAP therapy. 1 This study did not report outcomes separately in patients with Figure. Forest plot of the effect of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) on diastolic blood pressure (DBP) in patients with OSA. Abbreviations: CI, confidence interval; IV, inverse variance; SD, standard deviation. Figure 9. Forest plot of the effect of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) on systolic blood pressure (SBP) in patients with OSA. Abbreviations: CI, confidence interval; IV, inverse variance; SD, standard deviation. Clin. Cardiol. 37, 1, 57 5 (1) DOI:1.1/clc.1 13 Wiley Periodicals, Inc.

7 Figure 1. Forest plot of the effect of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) on heart rate (HR) in patients with OSA. Abbreviations: CI, confidence interval; IV, inverse variance; SD, standard deviation. Figure 11. Forest plot of the effect of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) on mortality in patients with OSA. Abbreviations: CI, confidence interval; M-H, Mantel-Haenszel. CSA, though a significant improvement in LVEF was noted in the OSA group. CPAP therapy was also associated with improved ejection fraction in patients with CSB. 19, Our study found a significant increase in LVEF in patients with SDB and heart failure. Apart from heart failure, OSA has also been reported to be associated with other cardiovascular diseases. Almost half of all patients with OSA have systemic hypertension; consequently, OSA is now considered to be a risk factor for hypertension. 1 Various studies have demonstrated the association between OSA and hypertension.,3 Several studies, some of which did not meet the criteria of inclusion in our analysis, have reported effects of CPAP therapy on systolic, diastolic, and arterial hypertension in patients with SDB. 3,9,11 1,1, Compliance with the use of CPAP therapy has also been reported to modify its efficacy on reducing blood pressure, which again demonstrates that CPAP therapy might have a positive effect on improvement of blood pressure. However, some studies found no change in blood pressure in OSA patients before and after CPAP therapy. Our analysis found a significant decrease in diastolic blood pressure and an insignificant decrease in systolic blood pressure associated with CPAP therapy. OSA causes increased sympathetic activity that may predispose the patient to increased automaticity and tachycardia. 7 Some studies have found that CPAP therapy decreases heart rate in patients with SDB. 3,9,13,1, Our study found that CPAP therapy is associated with a significant reduction in heart rate. Several studies have demonstrated the association between untreated OSA and mortality. 3 CPAP therapy has been demonstrated to reduce the mortality in heart failure patients with OSA in some studies. 1,33 No improvement in overall survival was reported with CPAP treatment in CSA patients with heart failure. 5 CPAP therapy was also associated with a trend toward improved combined mortality cardiac transplantation rate in patients with CSB. 19 Our study analyzed the effect of CPAP therapy on mortality and found it to be associated with a lower risk of allcause mortality. This meta-analysis suggests improvement in cardiac outcomes in patients with heart failure with treatment for coexistent sleep apnea by CPAP. Because improvement in heart function improves SDB, especially CSA, destination therapies for heart failure (left ventricular assist device or cardiac transplantation) may improve sleep apnea-hypopnea syndrome. This study is limited by issues inherent in metaanalyses. Heterogeneity was present in the following end points: LVEF, systolic blood pressure, and heart rate. This heterogeneity is the result of variation in the effect size of included studies rather than differences in individual study methodology. A random effects model was used in the analysis of these end points to adjust for the heterogeneity. Analysis of publication bias demonstrates the lack of small studies showing negative results for LVEF. Analysis of publication bias for the other end points could not be formally done due to the number of pooled studies being <1 for these end points. Included subjects in studies had different stages of heart failure and different functional classes of heart failure, and moreover duration of therapy. The duration of therapy and background medical therapy were not considered in the review of studies, and this may have caused a bias in the end results. Also, all of the end points studied in this meta-analysis were not prespecified end points in the original studies, which may have been a source of bias. Another limitation of the study is that all studies in this analysis had patients with severe SDB, and the results obtained may not be applicable to patients with mild or moderate SDB. Lack Clin. Cardiol. 37, 1, 57 5 (1) 3 DOI:1.1/clc.1 13 Wiley Periodicals, Inc.

8 SE() SE() 1 of blinding in most of the studies may have been another source of bias. Additionally, there is always an inherent risk of overestimation of effect size in meta-analyses, which cannot be excluded in this analysis. Funnel plot analysis demonstrates that moderate size studies seem to have the greatest impact on the outcomes reported in this analysis (Figure 1). The moderate-size studies tended to favor the use of CPAP on studied end points more than largersize studies. Despite some of the listed shortcomings, a sensitivity analysis was conducted, which validated the robustness of the analysis and the methodology schema selected SE() SE() Conclusion In this meta-analysis, CPAP therapy was associated with improvements in cardiovascular end points such as LVEF, diastolic blood pressure, and heart rate in patients with SDB and systolic heart failure. This study also demonstrates the need for additional studies to better demonstrate the effect of CPAP therapy on other cardiovascular end points in patients with SDB and heart failure. Both large and small studies are needed. There is a need for studies with negative results to also be published to decrease the publication bias present in these end points SE() 1 1 SE() SE(log[OR]) OR Figure 1. All funnel plots. Abbreviations:, mean difference; OR, odd ratio; SE, standard error. References 1. Wang H, Parker JD, Newton GE, et al. Influence of obstructive sleep apnea on mortality in patients with heart failure. JAmColl Cardiol. 7;9: Sin DD, Fitzgerald F, Parker JD, et al. Risk factors for central and obstructive sleep apnea in 5 men and women with congestive heart failure. Am J Respir Crit Care Med. 1999; 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. 3;3: Javaheri S, Caref EB, Chen E, et al. Sleep apnea testing and outcomes in a large cohort of Medicare beneficiaries with newly diagnosed heart failure. Am J Respir Crit Care Med. 11;13: Bradley TD, Logan AG, Kimoff RJ, et al. Continuous positive airway pressure for central sleep apnea and heart failure. NEnglJ Med. 5;353: Somers VK, White DP, Amin R, et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation. ;11: Kapur V, Blough DK, Sandblom RE, et al. The medical cost of undiagnosed sleep apnea. Sleep. 1999;: Somers VK, Dyken ME, Clary MP, et al. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;9: Naughton MT, Benard DC, Liu PP, 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;15: Mansfield DR, Gollogly NC, Kaye DM, et al. Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med. ;19: Ferrier KA, Neill AM, O Meeghan T, et al. Continuous positive airway pressure in heart failure patients with obstructive sleep apnoea. Intern Med J. ;3:9 3. Clin. Cardiol. 37, 1, 57 5 (1) DOI:1.1/clc.1 13 Wiley Periodicals, Inc.

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