This Article Abstract Full Text (PDF) All Versions of this Article: 107/15/1998    most recent 01.CIR.0000065227.04025.C2v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arzt, M. Articles by Pfeifer, M. Search for Related Content PubMed PubMed Citation Articles by Arzt, M. Articles by Pfeifer, M. Pubmed/NCBI databases Medline Plus Health Information Heart Failure Related Collections Exercise testing

(Circulation. 2003;107:1998.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Enhanced Ventilatory Response to Exercise in Patients With Chronic Heart Failure and Central Sleep Apnea

Michael Arzt, MD; Martina Harth, MD; Andreas Luchner, MD; Frank Muders, MD; Stephan R. Holmer, MD; Friedrich C. Blumberg, MD; Günter A.J. Riegger, MD; Michael Pfeifer, MD

From the Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Germany.

Correspondence to Dr Michael Arzt, Department of Internal Medicine II, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93042 Regensburg, Germany. E-mail michael.arzt{at}klinik.uni-regensburg.de

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background— In patients with chronic heart failure (CHF), central sleep apnea (CSA) and enhanced ventilatory response (E/CO₂ slope) to exercise are common. Both breathing disorders alone indicate poor prognosis in CHF. Although augmented chemosensitivity to CO₂ is thought to be one important underlying mechanism for both breathing disorders, it is unclear whether both breathing disorders are related closely in patients with CHF.

Methods and Results— We investigated 20 CHF patients with clinically important CSA (apnea-hypopnea-index (AHI), number of episodes per hour 15) and 10 CHF patients without CSA. Patients with and without CSA did not differ with respect to exercise capacity (peak O₂, 63.4±3.4% versus 60.8±4.4% of predicted value; P=0.746) and left ventricular ejection fraction (LVEF, 31±2% versus 31±3%; P=0.948). The AHI was not correlated with exercise capacity (peak O₂, percent of predicted value; P=0.260) and LVEF (percent, P=0.886). In contrast, the positive correlation of the E/CO₂ slope, determined by cardiopulmonary exercise testing, with the AHI was highly significant (P<0.001). The E/CO₂ slope was significantly increased in patients with CSA compared with those without CSA (29.7 versus 24.9; P<0.001).

Conclusions— The ventilatory response to exercise is significantly augmented in CHF patients with CSA compared with those without. In contrast to peak O₂ and LVEF, the E/CO₂ slope is strongly related to the severity of CSA in patients with CHF, which underscores an augmented chemosensitivity to CO₂ as a common underlying pathophysiological mechanism.

Key Words: heart failure • sleep • exercise • ventilation

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Cheyne-Stokes respiration is a common,^1,2 still underestimated breathing disorder in patients with chronic heart failure (CHF). It is characterized by periodic breathing with recurrent episodes of apnea or hypopnea alternating with hyperpnea and occurs in awake conditions as well as during sleep.^2,3 The resulting oxyhemoglobin desaturations and excessive arousals lead to severe disturbances in autonomic and cardiac function, including atrial fibrillation, ventricular arrhythmias, and sudden cardiac death.^4–7

Interestingly, CHF patients with nocturnal CSA have an increased mortality rate compared with CHF patients without CSA with a similar degree of ventricular dysfunction.⁶ Identification of heart failure patients with CSA is impeded by several factors. CHF patients with CSA often lack typical clinical symptoms of sleep apnea, because frequency of daytime sleepiness and snoring does not differ between CHF patients with and without CSA.² A high prevalence of CHF contrasts the limited resources of available laboratories for sleep studies. Nevertheless, diagnosing CSA in CHF patients may be highly important because of growing evidence for beneficial effects of an additional treatment with continuous positive airway pressure on cardiac function and the combined mortality-cardiac transplantation rate.⁸

A key mechanism for Cheyne-Stokes respiration in patients with CHF is the hypersensitivity to the partial pressure of carbon dioxide (PCO₂).^9–12 In these patients, a rise in PCO₂, within the scope of physiological fluctuations, leads to a reflectory excessive hyperventilation driving the PCO₂ under the apneic threshold. In this way, cycles of central apnea and hyperventilation recur alternatingly.¹⁰ Controlled by the same feedback mechanism between PCO₂ and ventilatory drive, the chemoreceptor gain for the PCO₂ in CHF patients also leads to an augmented ventilatory response to exercise as a reaction to the rising PCO₂ levels.^13,14 The ventilatory response can be measured best as a steep slope of the increase in ventilation with respect to CO₂ output (E/CO₂ slope).^15,16

Both CSA and augmented E/CO₂ slope to exercise are predictors of poor prognosis.^6,7,15,17 However, no study has shown association between the E/CO₂ slope and the severity of CSA. Therefore, we tested the hypothesis of whether CHF patients with CSA have an augmented E/CO₂ slope to exercise compared with those without CSA. Furthermore, we compared the association of the E/CO₂ slope, peak O₂, and left ventricular ejection fraction (LVEF) with the severity of CSA in CHF patients to elucidate the influence of chemosensitivity to CO₂, exercise capacity, and cardiac function on CSA.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patients
A total of 104 consecutive ambulatory patients with CHF (file information) were screened for CSA. Thirty-two CHF patients had CSA (apnea-hypopnea-index [AHI], number of episodes per hour 15), and 72 did not have CSA. The first 25 of the CHF patients with CSA were evaluated with the present study protocol. Because of the study protocol, 4 patients had to be excluded because of restrictive or obstructive ventilatory disorders and 2 patients were excluded because they had LVEF >45%. All 72 patients without CSA were asked to repeat the sleep study and to perform the rest of the study protocol. Sixteen patients gave written informed consent to perform the study. One had CSA and was assigned to the group of CHF with CSA. Of the remainder, 2 had LVEF >45% in the study echocardiography and 3 had obstructive ventilatory disorder and were excluded from additional analysis.

The study protocol included cardiopulmonary exercise test, ambulatory sleep apnea screening, polysomnographic studies, lung function test, and echocardiography. Cardiopulmonary exercise test and the sleep studies were done by 2 different investigators blinded to the clinical data. All patients gave written informed consent to perform the study protocol, which had been approved by the ethics committee of our institution.

Inclusion criteria were CHF attributable to ischemic, hypertensive, or idiopathic dilated cardiomyopathy with a LVEF <45%, as determined by resting echocardiography according to the guidelines of the American Society of Echocardiography¹⁸ by a single cardiologist who was blinded to the clinical data. Patients (NYHA functional class II and III) were stable over the last 3 months, documented by stable cardiac medication and no hospital admissions. Exclusion criteria were a history of unstable angina, cardiac surgery, or documented myocardial infarction within 90 days of entry into study. Restrictive and obstructive ventilatory disorders (vital capacity and total lung capacity <80% of predicted value, FEV₁ <80% of predicted value, and FEV₁/VC <70% of predicted value) were exclusion criteria.

Exercise Testing
To assess exercise capacity and ventilatory efficiency, patients underwent exercise testing with respiratory gas exchange analysis (Oxycon Champion; Jaeger-Toennies). Special effort was taken to perform symptom-limited exercise testing. Peak O₂ was measured and expressed as absolute value and as percent predicted from the individual age, sex, and body weight–corrected mean normal values.¹⁹ The E/CO₂ slope was calculated in every subject as the slope of the regression line relating ventilation (E) to CO₂ output (CO₂) during exercise testing and was used as an index of the ventilatory response to exercise. The ratio of E and CO₂ reveals a linear relationship over a wide range; the nonlinear part of this relationship after onset of acidotic drive to ventilation was excluded.²⁰

Sleep Apnea Screening
Ambulatory sleep apnea screening was performed using a portable computerized sleep apnea diagnosis set (SOMNOcheck effort; Weinmann). Thoracoabdominal excursions were measured qualitatively by an effort sensor (Piezo sensor; value range, 8 Bit) placed over the rib cage and abdomen. The SOMNOcheck system also includes 3 thermistors (value range, 8 Bit) to monitor oronasal airflow, a microphone for recording snoring sounds, and a sensor for detecting the position of the patient. Arterial-blood oxyhemoglobin saturation was recorded by a pulse oximeter. These data were recorded and analyzed using a computer-assisted procedure followed by blinded manual review of the collected data (Weinmann).

Standard definitions were used to describe and score the sleep-related breathing disorders. An episode of apnea was defined as a cessation of inspiratory airflow for 10 seconds. In case of CSA also, the excursions of the rib cage and abdomen cease, whereas in obstructive apnea, despite breathing excursions of rib cage and abdomen, oronasal airflow is absent.^2,21 Hypopnea was defined as a >50% reduction of airflow or thoracoabdominal excursions lasting at least 10 seconds, resulting in a 4% drop in arterial oxyhemoglobin saturation.^2,21 The AHI describes the number of episodes of apnea and hypopnea per hour. Clinically important CSA was defined as an AHI of 15 episodes per hour^2,21 with obstructive sleep apnea events <25% of total AHI.

Although previous studies showed excellent agreement in determination of the AHI using portable computerized polysomnography compared with laboratory-based polysomnography,^22–24 the patients diagnosed with clinically important CSA with the portable system also underwent laboratory-based polysomnography (Brainlap, Schwarzer), where the diagnosis of an AHI 15 and obstructive sleep apnea events <25% of total AHI were confirmed.

Statistical Analysis
All data were analyzed by a computer program (SPSS, version 10.0). To assess differences between patients with and without CSA, the Mann-Whitney U test was used. A ² analysis was used to analyze proportions. All values are reported as mean±SEM. A 2-sided P<0.05 was considered to indicate statistical significance. To calculate the relationship between the apnea indices, the E/CO₂ slope, the peak O₂, the peak oxygen pulse, and the Epworth sleepiness scale, the Spearman rank correlation was used. Receiver operator characteristic analysis was carried out to determine sensitivity, specificity, positive predictive value, and negative predictive value to several cutoff values of the E/CO₂ slope and parameters of exercise capacity and cardiac function for detecting clinically important CSA (AHI 15).

	Results

Top Abstract Introduction Methods Results Discussion References

 
Characteristics of Patients
The AHI, the apnea index, and the hypopnea index were significantly elevated in the patients who did meet the criteria of CSA compared with those without CSA (Table 1). In contrast, the Epworth sleepiness scale indicated no statistically significant difference between groups (Table 1) and did not correlate with the AHI (Figure 1).

View this table: [in this window] [in a new window]   TABLE 1. Characteristics of CHF Patients With and Without Central Sleep Apnea

View larger version (27K): [in this window] [in a new window]   Figure 1. Linear regression between the Epworth sleepiness scale (n=29), the LVEF (%, n=30), the peak O2 (percent of predicted value, n=30) and the peak O2/HR (percent of predicted value, n=30) with respect to the AHI in patients with congestive heart failure. HR indicates heart rate.

The patients in the CSA group were significantly older than those without CSA (Table 1). Patients in the 2 groups were similar with respect to their medications (Table 1). In both groups, 60% had an implanted cardioverter defibrillator. The patients without CSA all had sinus rhythm, whereas in the group with CSA, 20% of the patients had atrial fibrillation (Table 1) and 25% had nocturnal pacing.

Exercise Capacity
Mean LVEF was similar in CHF patients with CSA and without CSA (Table 1). In addition, the clinical performance expressed by the NYHA functional class showed no significant differences (Table 1).

The parameters of the cardiopulmonary exercise test, which are related to exercise capacity and cardiac stroke volume, were not statistically different between the 2 groups and included mean peak O₂, the peak O₂ expressed as percent of predicted value, the mean oxygen pulse, and the mean oxygen pulse expressed as percent of predicted value (Table 1).

Linear regression analysis revealed that LVEF, the peak O₂ (percent of predicted values), and the oxygen pulse (percent of predicted values) were not correlated with the AHI (Figure 1).

Ventilatory Response to Exercise
In CHF patients with CSA, the ventilatory response to exercise, determined by the slope of the relationship between ventilation and CO₂ output (E/CO₂ slope), was highly significantly increased compared with CHF patients without CSA (29.7±0.9 versus 24.9±0.6; P<0.001; Figure 2). This difference remained highly significant when the E/CO₂ slope was adjusted for sex and age (percent of predicted values, 104.9±3.2% with CSA versus 91.4±3.1% without; P=0.004).

View larger version (11K): [in this window] [in a new window]   Figure 2. The individual and mean values of the E/CO2 slope of patients with CHF without (no CSA, n=10) and with central sleep apnea (CSA, n=20).

A highly significant correlation between ventilatory response to exercise (E/CO₂ slope) and the AHI for CHF patients with and without CSA (r=0.613; P<0.001) was observed (Figure 3). Most importantly, these results remain highly significant after adjustment for gender and age (r=0.531; P=0.003; Figure 3).

View larger version (15K): [in this window] [in a new window]   Figure 3. Linear regression between the E/CO2 slope and the AHI in patients with CHF: E/CO2 slope (n=30); E/CO2 slope (percent of predicted value, n=30).

Predictive Values of the E/CO₂ Slope to Detect Central Sleep Apnea in CHF Patients
There is only little overlap between individual values of the E/CO₂ slope of CHF patients with and without CSA (Figure 2). In addition, after adjusting for sex and age, the E/CO₂ slope has high predictive values for detection of AHI 15 in the present study population (Table 2).

View this table: [in this window] [in a new window]   TABLE 2. Predictive Values of E/CO2 Slope, Left Ventricular Ejection Fraction, Peak O2, Peak Oxygen Pulse, Epworth Sleepiness Scale, and Resting Partial Pressure for CO2 for Detection of Central Sleep Apnea

Compared with parameters related to exercise capacity and functional classification of patients with CHF (peak O₂, peak oxygen pulse, and LVEF), the E/CO₂ slope reaches a high area under the receiver operator characteristic curve for detection of clinically important CSA in CHF patients (Table 2). Neither the history of daytime sleepiness (Epworth sleepiness scale) nor resting arteriocapillary and end-tidal carbon dioxide were suitable for detecting CSA in CHF patients (Table 2). Resting arteriocapillary and end-tidal partial pressures for CO₂ did not significantly differ in CHF patients with and without CSA (Table 1).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The major finding of this study is the highly augmented E/CO₂ slope in CHF patients with CSA compared with those without and the close correlation of the E/CO₂ slope with the AHI, indicating CSA. In contrast to the E/CO₂ slope, parameters of exercise capacity and cardiac function (peak O₂, oxygen pulse, and LVEF) were not related to central sleep apnea.

Thus, these results support the pathophysiological concept that it is common in CHF patients to have an augmented peripheral and central chemosensitivity to carbon dioxide.^{5,10,13,14,15} It is known that CHF patients with CSA have an increased ventilatory response to carbon dioxide^5,10 and that the degree of carbon dioxide hypersensitivity correlates with the AHI.⁵ The elevated chemoreceptor responsiveness destabilizes the respiratory control system by increasing the tendency to hyperventilate, thus precipitating ventilatory overshoot,²⁵ and leads to oscillatory breathing patterns in CHF patients even during wakefulness.²⁵

Exercise in healthy individuals also leads to an augmentation of chemosensitivity, which could be explained by rising catecholamine levels during exercise.²⁶ Interestingly, chemosensitivity to hypercapnia and hypoxia during exercise were shown to be augmented in patients with CHF compared with healthy control subjects.¹⁴ Hypercapnic chemosensitivity assessed by the Read’s rebreathing method²⁹ was significantly correlated to ventilatory response to exercise (E/CO₂-slope) in healthy subjects^14,28,29 and patients with CHF.^13,14

In addition to the pathophysiological link, severity of CSA and the E/CO₂ slope share the attribute to be predictors of poor prognosis in patients with CHF.^6,7,15,17 Lanfranchi et al⁶ determined the AHI to be a powerful predictor of cardiac mortality, independently of clinical and echocardiographic data. In addition, CHF patients with preserved exercise capacity (peak O₂ 18 mL · kg^-1min^-1) can have a remarkably enhanced ventilatory response to exercise associated with poor prognosis.¹⁵ Ponikowsky et al¹⁵ and Kleber et al¹⁷ even concluded that the E/CO₂ slope is a better prognostic parameter for CHF patients than the peak oxygen consumption, which is presently accepted as the best single measure of prognosis in ambulatory patients with severe heart failure.^30,31

Identification of high-risk CHF patients with central sleep apnea and cardiopulmonary reflex instability is important, because these patients could benefit from various forms of positive airway pressure, including continuous positive airway pressure (CPAP), bilevel, and adaptive pressure support servo-ventilation therapy.²⁵ CPAP is the therapy that was tested most extensively.²⁵ This respiratory support therapy is able to improve cardiac function and quality of life and can reduce hospital admissions.^3,8 The findings of Sin et al⁸ indicate that CPAP therapy may improve mortality and transplant-free survival in patients with central sleep apnea but not in patients without.

For diagnosing CSA in CHF patients, polysomnography screening is necessary. But because of the high prevalence of CHF, resources of sleep laboratories do not meet the need for large-scale screening. Although the prevalence of CSA is higher in CHF patients with low exercise capacity and higher NYHA functional class,^2,6 these parameters are not valid as preselection criteria. We found, similar to other investigators, that exercise capacity and cardiac function are not compellingly associated with the severity of CSA in CHF patients.^7,12,32 Alternatively, predicting for CSA could be the E/CO₂ slope, which is easy to obtain in a cardiopulmonary exercise test as a part of the routine workup of patients with CHF, even under submaximal exercise, when maximal exercise is contraindicated or not achievable.^17,33 As a consequence of the close correlation of the E/CO₂ slope with the AHI in our study, one can conclude that a high E/CO₂ slope in patients with CHF should lead to complete laboratory sleep analysis.

A limitation of the present study is that correlations and predictive values were calculated in a study population of 30 CHF patients, excluding all patients with concomitant diseases that could influence the prevalence of CSA and ventilatory response to exercise. Thus, care must be taken to extrapolate our findings to a broader spectrum of patients, and the data should be confirmed in a larger study on unselected CHF patients. After exclusion of patients with ventilatory disorders, the study population was well matched according to sex, body mass index, pulmonary function, arteriocapillary partial pressure of carbon dioxide,^5,10 and presence of implanted cardioverter defibrillator.³⁴ Similar to former studies comparing CHF patients with and without CSA, patients with CSA were significantly older.^5,10 Because both parameters, in particular, the ventilatory response to exercise, are age-related, analyses of this study were performed on age-adjusted variables, which showed similar results as the results from unadjusted variables.

Three conclusions may be drawn from this study. First, the present data emphasize that the severity of central sleep apnea and ventilatory response to exercise in CHF patients are not related to peak exercise capacity and cardiac function. Second, the E/CO₂ slope, as an indicator of ventilatory response to exercise, is highly augmented in CHF patients with CSA compared with those without. Third, because of their close positive correlation, the E/CO₂ slope could be helpful for the decision of whether CHF patients should receive full laboratory sleep analysis.

Received December 16, 2002; accepted February 7, 2003.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Javaheri S. Central sleep apnea-hypopnea syndrome in heart failure: prevalence, impact, and treatment. Sleep. 1996; 19: S229–S231.[Medline] [Order article via Infotrieve]

2. Javaheri S, Parker TJ, Liming JD, et al. Sleep apnea in 81 ambulatory male patients with stable heart failure. Circulation. 1998; 97: 2154–2159.[Abstract/Free Full Text]

3. Naughton MT, Bernard DC, Liu P, et al. Effects of nasal CPAP on sympathic activity in patients with heart failure and central sleep apnea. Am J Respir Crit Care Med. 1995; 152: 473–479.[Abstract]

4. Narkiewicz K, Pesek CA, van de Borne PJ, et al. Enhanced sympathetic and ventilatory response to central chemoreflex activation in heart failure. Circulation. 1999; 100: 262–267.[Abstract/Free Full Text]

5. Javaheri S, Corbett WS. 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.[Abstract/Free Full Text]

6. Lanfranchi PA, Braghiroli A, Bosimini E, et al. Prognostic value of nocturnal Cheyne-Stokes respiration in chronic heart failure. Circulation. 1999; 99: 1435–1440.[Abstract/Free Full Text]

7. Hanly PJ, Zuberi-Khokhar NS. Increased mortality associated with Cheyne-Stokes respiration in patients with congestive heart failure. Am J Respir Crit Care Med. 1996; 153: 272–276.[Abstract]

8. Sin DD, Logan AG, Fitzgerald FS, et al. Effects of continuous positive airway pressure in cardiovascular outcomes in heart failure patients with and without Cheyne-Stokes respiration. Circulation. 2000; 102: 61–66.[Abstract/Free Full Text]

9. Solin P, Roebuck T, Johns DP, et al. Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure. Am J Respir Crit Med. 2000; 162: 2194–2200.[Abstract/Free Full Text]

10. Javaheri S. A mechanism of central sleep apnea in patients with heart failure. N Engl J Med. 1999; 341: 949–954.[Abstract/Free Full Text]

11. 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.[Abstract/Free Full Text]

12. Naughton M, Benard D, Tam A, et al. Role of hyperventilation in the pathogenesis of central sleep apneas in patients with chronic heart failure. Am Rev Respir Dis. 1993; 148: 330–338.[Medline] [Order article via Infotrieve]

13. Ponikowsky P, Chua TP, Piepoli M, et al. Augmented peripheral chemosensitivity as a potential input to baroreflex impairment and autonomic imbalance in chronic heart failure. Circulation. 1997; 96: 2586–2594.[Abstract/Free Full Text]

14. Chua TP, Clark AL, Amadi AA, et al. Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol. 1996; 27: 650–657.[Abstract]

15. Ponikowski P, Francis DP, Piepoli MF, et al. Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation. 2001; 103: 967–972.[Abstract/Free Full Text]

16. Johnson RL. Gas exchange efficiency in congestive heart failure. Circulation. 2000; 101: 2774–2776.[Free Full Text]

17. Kleber FX, Vietzke G, Wernecke KD, et al. Impairment of ventilatory efficiency in heart failure: prognostic impact. Circulation. 2000; 101: 2803–2809.[Abstract/Free Full Text]

18. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography: American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989; 2: 358–367.[Medline] [Order article via Infotrieve]

19. Hansen JE, Sue DY, Wassermann K. Predicted values for clinical exercise testing. Am Rev Respir Dis. 1984; 129: S49–S55.[Medline] [Order article via Infotrieve]

20. Habedank D, Reindl I, Vietzke G, et al. Ventilatory efficiency and exercise tolerance in 101 healthy volunteers. Eur J Appl Physiol Occup Physiol. 1998; 77: 421–426.[CrossRef][Medline] [Order article via Infotrieve]

21. American Thoracic Society. Indications and standards for cardiopulmonary sleep studies. Am Rev Respir Dis. 1989; 139: 559–568.[Medline] [Order article via Infotrieve]

22. Kapur VK, Rapoport DM, Sanders MH, et al. Rates of sensor loss in unattended home polysomnography: the influence of age, gender, obesity, and sleep-disordered breathing. Sleep. 2000; 23: 682–688.[Medline] [Order article via Infotrieve]

23. Mykytyn IJ, Sajkov D, Neill AM, et al. Portable computerized polysomnography in attended and unattended settings. Chest. 1999; 115: 114–122.[Abstract/Free Full Text]

24. Orr WC, Eiken T, Pegram V, et al. A laboratory validation study of a portable system for remote recording of sleep-related respiratory disorders. Chest. 1994; 105: 160–162.[Abstract/Free Full Text]

25. Leung RS, Bradley TD. State of the art: sleep apnea and cardiovascular disease. Am J Respir Crit Care Med. 2001; 164: 2147–2165.[Free Full Text]

26. Weil JV, Byrne-Quinn E, Sodal IE, et al. Augmentation of chemosensitivity during mild exercise in normal man. J Appl Physiol. 1972; 33: 813–819.[Free Full Text]

27. Deleted in proof.

28. Martin BJ, Weil JV, Sparks KE, et al. Exercise ventilation correlates positively with ventilatory chemoresponsiveness. J Appl Physiol. 1978; 45: 557–564.[Abstract/Free Full Text]

29. Read DJC. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med. 1967; 16: 20–32.[Medline] [Order article via Infotrieve]

30. Mancini DM, LeJemtel T, Aaronson K. Peak VO₂, a simple yet enduring standard. Circulation. 2000; 101: 1080–1082.[Free Full Text]

31. Mancini DM, Eisen H, Kussmaul W, et al. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation. 1991; 83: 778–786.[Abstract/Free Full Text]

32. 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.[Abstract/Free Full Text]

33. Paradaens K, Van Cleemput J, Vanhaeke J, et al. Peak oxygen uptake better predicts outcome than submaximal respiratory data in heart transplant candidates. Circulation. 2000; 101: 1152–1157.[Abstract/Free Full Text]

34. Garrigue S, Bordier P, Jais P, et al. Benefit of atrial pacing in sleep apnea syndrome. N Engl J Med. 2002; 346: 404–412.[Abstract/Free Full Text]

This article has been cited by other articles:

				T. E. Vanhecke, B. A. Franklin, K. C. Zalesin, R. B. Sangal, A. T. deJong, V. Agrawal, and P. A. McCullough Cardiorespiratory Fitness and Obstructive Sleep Apnea Syndrome in Morbidly Obese Patients Chest, September 1, 2008; 134(3): 539 - 545. [Abstract] [Full Text] [PDF]

				I. Szollosi, B. R. Thompson, H. Krum, D. M. Kaye, and M. T. Naughton Impaired Pulmonary Diffusing Capacity and Hypoxia in Heart Failure Correlates With Central Sleep Apnea Severity Chest, July 1, 2008; 134(1): 67 - 72. [Abstract] [Full Text] [PDF]

				L. J. Olson and V. K. Somers Treating Central Sleep Apnea in Heart Failure: Outcomes Revisited Circulation, June 26, 2007; 115(25): 3140 - 3142. [Full Text] [PDF]

				A. Vazir, P.C. Hastings, M. Dayer, H.F. McIntyre, M.Y. Henein, P.A. Poole-Wilson, M.R. Cowie, M.J. Morrell, and A.K. Simonds A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction Eur J Heart Fail, March 1, 2007; 9(3): 243 - 250. [Abstract] [Full Text] [PDF]

				M. Arzt and T. D. Bradley Treatment of Sleep Apnea in Heart Failure Am. J. Respir. Crit. Care Med., June 15, 2006; 173(12): 1300 - 1308. [Abstract] [Full Text] [PDF]

				M. Arzt, M. Schulz, R. Wensel, S. Montalvan, F. C. Blumberg, G. A. J. Riegger, and M. Pfeifer Nocturnal Continuous Positive Airway Pressure Improves Ventilatory Efficiency During Exercise in Patients With Chronic Heart Failure Chest, March 1, 2005; 127(3): 794 - 802. [Abstract] [Full Text] [PDF]

				J-L. Pepin, P. Defaye, S. Garrigue, Y. Poezevara, and P. Levy Overdrive atrial pacing does not improve obstructive sleep apnoea syndrome Eur. Respir. J., February 1, 2005; 25(2): 343 - 347. [Abstract] [Full Text] [PDF]

				A.-M. Sinha, E. C. Skobel, O.-A. Breithardt, C. Norra, K. U. Markus, C. Breuer, P. Hanrath, and C. Stellbrink Cardiac resynchronization therapy improves central sleep apnea and Cheyne-Stokes respiration in patients with chronic heart failure J. Am. Coll. Cardiol., July 7, 2004; 44(1): 68 - 71. [Abstract] [Full Text] [PDF]

				J. D Lowman Jr, A. Y. Jones, E. Dean, and C. C. Chow Breathing Exercises for Patients With COPD: To Teach or Not to Teach Physical Therapy, October 1, 2003; 83(10): 948 - 951. [Full Text]

This Article Abstract Full Text (PDF) All Versions of this Article: 107/15/1998    most recent 01.CIR.0000065227.04025.C2v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arzt, M. Articles by Pfeifer, M. Search for Related Content PubMed PubMed Citation Articles by Arzt, M. Articles by Pfeifer, M. Pubmed/NCBI databases Medline Plus Health Information Heart Failure Related Collections Exercise testing