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* From the Physiological Sciences Graduate Program (Ms. Wittmer and Ms. Simoes), Biomedical Center, Federal University of Espirito Santo; and Emescam College of Health Sciences of Vitoria (Drs. Sogame and Vasquez), Vitoria, Brazil.
Correspondence to: Elisardo C Vasquez, PhD, Physiological Sciences Graduate Program, Biomedical Center, Federal University of Espirito Santo, Av. Marechal Campos 1468, Vitoria, 29042–755 ES, Brazil; e-mail: evasquez{at}terra.com.br
Abstract
Study objectives: Continuous positive airway pressure (CPAP) has been used to improve cardiopulmonary function and reduce pulmonary edema symptoms in patients with congestive heart failure (CHF). The objective of this study was to evaluate the efficacy of CPAP therapy on pulmonary function and exercise tolerance in patients with CHF.
Design: Prospective blind randomized clinical study.
Participants: Twenty-four patients with class II or III CHF and dilated cardiomyopathy were randomly assigned to 30 min of CPAP therapy and respiratory exercises (CPAP group) or respiratory exercise only (control group) once a day for 14 days.
Measurements and results: Evaluation of pulmonary function was performed measuring FEV1 and FVC. Exercise tolerance was assessed measuring the distance walked during the 6-min walking test (6MWT). These parameters were measured before treatment and 4 days, 9 days, and 14 days later. CPAP therapy caused a progressive increase (p < 0.05) in both FVC (maximum of 16% after 9 days) and FEV1 (maximum of 14% after 14 days) compared to basal values, without significant changes in the control group. The 6MWT showed a progressive improvement in the distance walked in the CPAP group, reaching approximately 28% above the basal values in the CPAP group and without significant changes in the control group.
Conclusions: These data show that the use of CPAP therapy for 2 weeks on a daily basis is able to enhance pulmonary function and consequently improve the tolerance to physical activities in patients with CHF. The clinical implication of this finding is that CPAP therapy could potentially be used as an adjunct to the treatment of CHF patients.
Key Words: continuous positive airway pressure ventilation • exercise tolerance • FVC • heart failure • pulmonary function test
Congestive heart failure (CHF) resulting from dilated cardiomyopathy is a serious disease associated with excessive morbidity and mortality and of elevated costs to health-care plans and the government. Despite advances in the pharmacologic therapy for CHF, the mortality from this disease remains very high. A consequence of the CHF is an extensive fluid accumulation in the lungs (pulmonary edema), which results in muscle fatigue or dyspnea symptoms when performing routine activities and progressing to dyspnea at rest.12
Oxygen supplementation and administration of drugs are commonly used as an attempt to decrease lung edema and improve myocardial performance in patients with CHF,3 but severe respiratory failure develops in many patients and requires intubation and mechanical ventilation. An additive approach that has long been used to improve pulmonary function in these patients is the use of continuous positive airway pressure (CPAP) delivered through a tight-fitting nasal or oronasal mask.4 The main direct benefits of CPAP include improvement in oxygenation, a decrease in respiratory work, and decrease in left ventricular preload and afterload.345
It is reasonable that the increase in cardiac and respiratory function may result in beneficial effects on the exercise capacity in CHF patients, as reported by Nanas et al.6 However, it has not yet been investigated if the improvement of pulmonary function through CPAP therapy affects the tolerance to physical exercise in CHF patients. Considering that any intervention that favorably alters integrated cardiopulmonary function should improve exercise endurance, this study was designed to determine the effects of CPAP therapy on the pulmonary function and its contribution to exercise tolerance in patients with CHF.
Materials and Methods
Subjects
The procedures used in this study were in accordance with the recommendations of the Helsinski Declaration of 1975. All subjects provided written informed consent before entry, and the protocol was approved by the Ethics Committee at the College of Health Sciences of Vitoria. We recruited consecutive patients who were admitted to the hospital for treatment of CHF. Patients were eligible to participate if they had a clinical diagnosis of New York Heart Association class II or III CHF. Patients were excluded from participating in the study if they had one or more of the following conditions: (1) unstable angina; (2) atrial fibrillation or third-degree atrioventricular blockade; (3) myocardial infarction; (4) cardiac surgery within 1 year prior to study entry; (5) pulmonary disease; (6) radiologic signs of pleural effusion; (7) use of bronchodilators; (8) pregnancy; (9) frequent vomiting; (10) smokers; (11) unable to successfully complete the walking test; and (12) < 30 years old and > 80 years old.
After a clinical examination, which included echocardiography, ECG, and chest radiography by an independent physician who acted on clinical judgment alone, 24 patients were randomly assigned to the CPAP group or the control group. During the study, two patients were excluded: one because angina pectoris developed during the walking test, and the other because of CPAP therapy intolerance.
Spirometry
Routine spirometry was performed following the standardization of the American Thoracic Society.7 Pulmonary function testing included measurement of FEV1, FVC, and FEV1/FVC ratio. Measurements were obtained in the sitting position with a closed-circuit spirometer (Respiradyne II Plus; Kendall Healthcare Products Company; Mansfield, MA). Predicted values for FEV1, FVC, and FEV1/FVC ratio were calculated using reference values of Knudson et al.8
Six-Minute Walk Test
The 6-min walk test (6MWT) was performed in an indoor, 25-m long corridor, according to the suggestions from Guyatt et al.9 In brief, the patients were asked to walk at their highest rate from one end of the corridor to the other end as many times as possible within the established time of 6 min. The test was performed under the control of a therapist who encouraged the patients with phrases like "you are doing well" or "you are doing a good job; keep going." At the end of the 6-min period, the therapist measured the distance walked by the patient.
Respiratory Exercises
Patients in the sitting position were subjected to three different respiratory exercises, each exercise repeated 10 times. First, slow inspiration through the nose was performed up to the maximum to reach total lung capacity, followed by a brief expiration through the mouth and another maximum inspiration followed by a complete expiration. Second, inspiration through the nose was performed up to approximately one half of total lung capacity, followed by a brief expiration through the mouth, another inspiration up to approximately two thirds of the total lung capacity followed by a brief expiration, and finally an inspiration up to the total lung capacity followed by a prolonged expiration. Third, brief and consecutive inspirations were performed through the nose until total lung capacity was reached, followed by a prolonged expiration through the mouth.
Walking Exercise
All patients were asked to walk 100 m/d at a slow pace under the control of a therapist.
CPAP Therapy
CPAP was applied through a tight-fitting nasal mask (Sollo; Sao Paulo, Brazil) breathing at pressure of 8 cm H2O with the mouth closed for a 30-min period every morning while awake and in the sitting position.
BP, Heart Rate, and Hemoglobin Saturation With Oxygen Measurements
Systolic and diastolic arterial BP were measured with a validated automatic sphygmomanometer (model HEM-705CP; Omron; Chicago, IL) with the patient at rest and in a sitting position following the IV Brazilian guidelines in arterial hypertension.10 Heart rate was measured using a portable monitor (model A1; Polar Electro; Lake Success, NY) positioned around the patient’s thorax. Peripheral hemoglobin oxygen saturation was measured through a fingertip pulse oximeter (Onyx; Nonin Medical; Plymouth, MN).
Experimental Protocol
All patients were initially subjected to a physical evaluation and also evaluation of arterial pressure, heart rate, hemogram, respiratory frequency, and peripheral hemoglobin oxygen saturation, After that, patients were allocated to daily CPAP therapy plus respiratory and walking exercises (CPAP group, n = 12) or respiratory and walking exercises (control group, n = 10) in a blind randomized, prospective study design. Spirometry and 6MWTs were performed by an independent investigator 1 day before treatment (day 0) and at the fourth, ninth, and 14th days of treatment, and all other parameters were measured every day in both groups.
Statistical Analysis
All data are expressed as mean ± SEM. Means of groups were compared by two-way analysis of variance (ANOVA) for repeated measurements followed by the post hoc Tukey/Kramer test. A Student t test was used for comparisons of two means when appropriate. The relative changes in the FVC, FEV1, and 6MWT distance were determined as follows: 
% = ([posttreatment value – pretreatment value]/pretreatment value) x 100; p < 0.05 was considered significant.
Results
Subject Characteristics
Eleven patients included in this analysis were in New York Heart Association class II (CPAP group, n = 5; control group, n = 6), and 11 patients were in class III (CPAP group, n = 5; control group, n = 6). The characteristics of the patients are shown in Table 1
. CPAP and control groups were comparable in age, body mass index, heart rate, systolic and diastolic arterial BP, respiratory rate, and hemoglobin saturation with oxygen. Although patients were randomly allocated in each group, the left ventricular ejection fraction was 8% higher in the CPAP group than in the control group.
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As shown in Table 2
, all the patients from CPAP and control groups had a left ventricular ejection fraction 
45% and dilated cardiomyopathy associated with valvular diseases. All patients from both groups were receiving medication, as shown in Table 3
.
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Effects of CPAP
The group treated with CPAP showed a progressive increase in FVC, reaching a maximum of 16% of the basal value on the ninth day of treatment without additional improvement on the 14th day of treatment, in contrast with the control group, which showed no significant improvement at any time point (Fig 1
). Similarly, FEV1 values progressively increased and reached a maximum of 14% on the 14th day of CPAP treatment, without any significant change in the control group (Fig 2
). At the end of experiments, three patients from CPAP group and one patient from the control group changed from a restrictive to a normal spirometric pattern. However, no changes of pattern were observed in those patients with a previous diagnosis of airway obstruction. As summarized in Figure 3
, the 6MWT showed a progressive improvement in the distance walked in the CPAP group, reaching approximately 28% above basal values at the end of treatment, but no significant changes were observed in the control group.
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Reduced exercise capacity is one of the characteristics of patients with CHF and is correlated with abnormal respiratory function, as noted in this study, and involves several other mechanisms, including impaired tissue oxygen extraction1112; abnormalities in skeletal muscle metabolism and structure,121314 and reduced skeletal muscle blood flow during exercise1213; hyperventilation caused by elevated physiologic dead space in the edematous lung1213; reduced myocardial ß-adrenoceptor density and sensitivity1213; chronotropic failure12131415; and diastolic dysfunction.15 It is interesting that CHF patients show persistent physical limitations after heart transplantation, probably due to increased vasoconstriction drive to skeletal muscles.16 In the current study, we have demonstrated that CPAP therapy for 2 weeks increased the pulmonary function of patients with CHF, consequently improving their tolerance to physical activities.
Approximately 80% of the patients with CHF showed a restrictive spirometric pattern, which has been mainly attributed to extravascular volume expansion and fluid accumulation in interstitial compartments of the lungs associated with increased heart size, and consequently reduced lung compliance.11718 The accumulation of interstitial fluid leads the alveoli to flood and results in a deficient alveolar gas exchanging of the lungs with several consequences, including the manifestation of muscle weakness and dyspnea.19
Some studies34 indicate that the use of CPAP may improve the cardiac and pulmonary function and relieve the symptoms of patients with CHF. In this study, CPAP therapy caused a progressive and significant improvement of the FVC and FEV1 in patients with CHF compared to the control group. The effects of CPAP could be because this therapy increases functional residual capacity and opens collapsed or underventilated alveoli, thus decreasing right-to-left intrapulmonary shunt, improving oxygenation and lung compliance.4
It is well known that exercise limitation frequently observed in patients with CHF is multifactorial and includes abnormal ventilatory responses.20 The 6MWT has been used to evaluate functional capacity in symptomatic CHF patients.2122 In a recent systematic review, Olsson et al23 concluded that although there is uncertainty about the utility of this test for the evaluation of pharmacologic therapy, the 6MWT may be of greater value in patients with advanced CHF, in whom it may function as a maximal exercise test. A possible disadvantage of using the 6MWT as an outcome measure in studies of CHF treatment is that the verbal encouragement of the person administering the test could affect the distance walked by the patient.23 The advantages of the 6MWT rather than the bicycle or treadmill exercise are that the test is simple, inexpensive, and easily performed; a more natural form of exercise that may better reflect daily activity; and has important prognostic information.212223 In this study, the physical limitation in patients with CHF was confirmed through the 6MWT, observing that most patients showed muscle weakness and dyspnea during the test and hardly completed the test. It is reasonable to assume that the improvement of the pulmonary function and associated symptoms caused by the CPAP therapy contributed to the progressive increase in the distance walked in the 6MWT by patients with CHF in our study. However, we may consider that other investigators have shown that the improvement of exercise tolerance in CHF patients could also be due to the beneficial effects of CPAP therapy on other parameters. It has been shown that CPAP application causes significant improvements in cardiac function of CHF patients, including reduction in left ventricular preload24 and afterload,25 augmented left ventricular ejection fraction,26 reduction in mitral regurgitant fraction,26 and in myocardial oxygen consumption plus carbon dioxide production.27 These improvements in cardiovascular function could be as a consequence of the CPAP-induced increase in intrathoracic pressure.24252628 Other beneficial cardiovascular effects of CPAP on CHF patients have been reported, including inhibition of cardiac sympathetic nervous activity,27 and reduction in plasma atrial natriuretic peptide concentration.26 It is interesting that in this study, we observed a substantial improvement in pulmonary function and 6MWT distance even after short-term CPAP therapy. Our findings are in agreement with others242729 showing beneficial effects of short-term CPAP therapy in CHF patients. Based on other studies,272930 we speculate that among possible mechanisms could account for some of the favorable effects of short-term CPAP on pulmonary function and 6MWT distance in CHF patients are decreases of cardiac sympathetic nervous activity,30 myocardial work and oxygen consumption,27 mitral regurgitation,29 and improvement of ejection fraction.29 Although the patients were randomly allocated in the CPAP or control groups, we cannot rule out the possibility that the pretreatment value of the left ventricular ejection fraction 8% higher in the CPAP group could additionally contributed to the improvement of cardiopulmonary function and tolerance to physical exercise in this group.
CHF is commonly treated with pharmacologic approaches, and the drugs used could influence the tolerance to physical exercise.31323334 It is interesting that in this study, most of the patients receiving drug therapy were receiving diuretics, digitalis glycosides, and angiotensin-converting enzyme inhibitors rather than ß-blockers, which is not considered a standard practice currently. However, we did not interfere with the clinical medications that were prescribed. Based on other studies,323335 we speculate that the beneficial effects of CPAP therapy on tolerance to physical exercise could be exacerbated if the patients were mainly receiving medication with ß-blockers, which are known to improve cardiac function and exercise tolerance in CHF patients. Although in our study all patients were receiving cardiovascular medication, the class and dosage of medication were not changed during the 14 days of the study.
Our study has some limitations. Although our data show that CPAP treatment improved exercise tolerance, we do not know if this was caused only by the improvement of the pulmonary function or/and by hemodynamic changes, since the patients were not submitted to an echocardiographic evaluation at the end of the experiments. Another limitation was the fact that the number of patients with anemia was not exactly the same in both groups, which could have affected the tolerance to physical exercise.
In conclusion, these data show that the use of nasal CPAP significantly improves pulmonary function and, consequently, also improved the tolerance to the physical activities of CHF patients. The clinical implication of our findings is that the use of noninvasive CPAP for 30 min/d could potentially be used as an adjunct to the treatment of CHF patients.
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Abbreviations: ANOVA = analysis of variance; 6MWT = 6-min walk test; CHF = congestive heart failure; CPAP = continuous positive airway pressure
The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/orgainzations whose products or services may be discussed in this article.
Received for publication October 4, 2005. Accepted for publication January 11, 2006.
References
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