By John D. Zoidis, MD

Patients with long-standing congestive heart failure (CHF) may suffer from respiratory muscle weakness,^1-4 which is usually due to the structural and functional abnormalities of skeletal muscle that can result from an inadequate energy supply.^5-7 Although drug therapy is often effective for treating CHF, the effects of drug therapy for CHF on respiratory muscle strength are not fully understood. Numerous studies have shown that patients with CHF may benefit considerably from continuous positive airway pressure (CPAP) applied via a nasal mask.

Therapeutic Rationale
In patients with CHF, nasal CPAP has been shown to augment cardiac output, reduce myocardial oxygen consumption, and unload inspiratory muscles by reducing pleural pressure swings.^8,9 Furthermore, nightly applications of nasal CPAP to patients with CHF and obstructive sleep apnea (OSA) may lead to increased left ventricular ejection fraction (LVEF) and reduced dyspnea.^10,11 CPAP also reduces left ventricular preload and afterload by decreasing left-ventricular transmural pressures during systole and diastole,^12,13 thereby improving the mechanical efficiency of the failing heart.

Preload, Afterload, and Ventricular Function
CPAP can have beneficial hemodynamic effects in patients with CHF. In the normal heart, cardiac output depends largely on preload, and CPAP decreases cardiac output by reducing left-ventricular preload without affecting afterload. In patients with CHF, however, because cardiac output is relatively insensitive to changes in preload (but very sensitive to changes in afterload), CPAP-induced reductions in left-ventricular transmural pressure can augment cardiac output.^14,15 In the early 1980s, Pinsky and colleagues¹⁶ showed that in patients with CHF, intermittent elevations in intrathoracic pressure can improve cardiac output. Subsequent investigations¹⁷ confirmed these findings and showed that CPAP causes a dose-dependent augmentation in cardiac output when applied acutely to patients with stable CHF and elevated pulmonary capillary wedge pressure,⁸ and may improve cardiac index when given to patients with acute cardiogenic pulmonary edema.

Patients with heart failure and systolic dysfunction may develop disordered breathing during sleep. Repeated episodes of apnea and hypopnea may result in desaturation and arousals, which could adversely affect left ventricular function. Javaheri¹⁸ performed a study to determine the short-term effects of CPAP on sleep-disordered breathing and its consequences in heart failure patients. He prospectively studied 29 male patients whose initial polysomnograms showed 15 or more episodes of apnea and hypopnea per hour; 21 patients had predominately central and eight patients had OSA. All were treated with CPAP during the subsequent night. In 16 patients, CPAP resulted in virtual elimination of disordered breathing. In these patients, the mean apnea-hypopnea index (AHI), arousal index due to disordered breathing, and percent of total sleep time below saturation of 90% decreased significantly, and lowest saturation increased significantly with CPAP. In 13 patients who did not respond to CPAP, these values did not change significantly. In patients whose sleep apnea responded to CPAP, the number of hourly episodes of nocturnal premature ventricular contractions and couplets decreased. In contrast, in patients whose sleep apnea did not respond to CPAP, ventricular arrhythmias did not change significantly. Overall, first-night nasal CPAP eliminated disordered breathing and reduced ventricular irritability in 55% of patients with heart failure and sleep apnea.

Cardiac Mortality and Cardiac Transplantation Rate
CPAP also improves cardiac function in patients with CHF who also have Cheyne-Stokes respiration and central sleep apnea. Sin and colleagues¹⁹ conducted a randomized, controlled trial in which 66 patients with CHF (29 with and 37 without central sleep apnea) were randomized to either a group that received CPAP nightly or to a control group. Change in LVEF from baseline to 3 months and the combined mortality-cardiac transplantation rate over the median 2.2-year follow-up period were compared between the CPAP-treated and control groups. For the entire group of patients, CPAP had no significant effect on LVEF, but it was associated with a 60% relative risk reduction in mortality-cardiac transplantation rate in patients who complied with CPAP therapy. Stratified analysis of patients with and without central sleep apnea revealed that those with central sleep apnea experienced both a significant improvement in LVEF at 3 months and a relative risk reduction of 81% in the mortality-cardiac transplantation rate of those who used CPAP. CPAP had no significant effect on either of these outcomes in patients without central sleep apnea. The investigators concluded that CPAP improves cardiac function in CHF patients with central sleep apnea, but not in those without it. These findings also suggest that CPAP can reduce the combined mortality-cardiac transplantation rate in CHF patients with central sleep apnea who comply with therapy.

Sympathetic Nerve Activity
Heindl and colleagues²⁰ performed an observational study to test the hypothesis that the short-term application of CPAP increases muscle sympathetic nerve activity in patients with CHF. They recruited 10 patients with CHF and 10 healthy subjects matched for age, sex, and weight. Outcome assessments—which included muscle sympathetic nerve activity (assessed by microneurography of the peroneal nerve), blood pressure, heart rate, minute ventilation, transcutaneous oxygen saturation, and end-tidal pCO2—were measured during normal breathing, mask breathing, and CPAP at 5 and 10 cm H2O. CPAP induced an increase in muscle sympathetic nerve activity and blood pressure in both the patients and the control subjects. In the patients, mean sympathetic nerve activity increased from 43 bursts/min during mask breathing to 47 bursts/min at CPAP 10 cm H2O (P=0.03). Mean blood pressure increased from 80 mm Hg to 86 mm Hg (P< 0.001). Mean oxygen saturation improved during CPAP in the patients, from 95.7% to 96.6% (P=0.004), and remained stable in the control group. There was no effect of CPAP on minute ventilation or heart rate. The investigators concluded that in patients with CHF, short-term CPAP elicits sympathetic activation, probably because of unloading of the aortic or cardiopulmonary baroreceptors.

Respiratory Muscles
In patients with CHF, shortness of breath is often a disabling symptom. Although a number of factors may contribute to dyspnea in CHF, there is a growing awareness of the etiologic role of respiratory muscle weakness and dysfunction. Hammond and colleagues⁴ compared handgrip force, maximal inspiratory pressure, and maximal expiratory pressure in CHF patients and healthy subjects. They found that maximum static respiratory pressures, which were used as measures of respiratory muscle strength, were disproportionately reduced in CHF patients. Another study performed by McParland and colleagues²¹ confirmed this finding. These investigators measured maximum inspiratory and expiratory mouth pressures as indices of respiratory muscle strength, as well as baseline dyspnea index, in nine patients with stable CHF and nine age- and sex-matched healthy control subjects. The CHF patients, when compared with their matched control subjects, had reduced inspiratory and expiratory muscle strength, and both inspiratory and expiratory muscle strength correlated significantly with degree of dyspnea during daily activity. Inspiratory muscle strength accounted for all of the variance in dyspnea that was correlated with respiratory muscle strength when the relative contributions of inspiratory and expiratory muscle strength were examined. There was no correlation between lung volumes or spirometry and dyspnea in the heart failure patients. These findings indicate that patients with stable CHF have inspiratory and expiratory muscle weakness. In a randomized, controlled study of patients with CHF and central sleep apnea, nightly application of CPAP over a 3-month period resulted in an improvement of inspiratory muscle strength, along with alleviation of fatigue and dyspnea.²²

Strategies to Increase Compliance
Despite the positive aspects of CPAP, compliance can be difficult to achieve. CPAP can cause nasal congestion, claustrophobic sensations, and other side effects. Sin and colleagues²³ studied patients with sleep apnea to determine short-term and long-term compliance with this treatment, baseline predictors for long-term CPAP compliance, and whether CPAP use provides sustained improvement in daytime sleepiness. The design was a prospective, longitudinal study of patients referred to a university sleep disorders center; 296 patients with moderate-to-severe obstructive sleep apnea, as defined by an AHI of 20 or more events per hour on polysomnography, were enrolled. Participants were provided with a CPAP device that contained a computer chip for monitoring compliance. They were informed that noncompliance would result in the loss of the machine. Within the first week of the study, patients began making daily telephone contact with a CPAP clinic nurse and were followed up in the office at 2 weeks, 4 weeks, 3 months, and 6 months. During each follow-up visit, patients were asked to complete a questionnaire regarding their degree of daytime sleepiness. Compliance rates (defined as use of the CPAP machine for 3.5 hours or longer per day) were at or above the 80% mark at each of the follow-up visits. The daytime sleepiness score improved over the entire follow-up period, with the lowest score occurring at 6 months. Three variables were found to correlate with increased use of CPAP—female gender, increased age, and reduction of daytime sleepiness scores. The investigators concluded that a population-based CPAP program consisting of consistent follow-up, “troubleshooting,” and regular feedback to both patients and physicians can achieve CPAP compliance rates of >85% over a 6-month period.

Conclusion
A growing body of evidence suggests that patients with CHF may benefit considerably from CPAP applied via a nasal mask. Sleep-related breathing disorders are particularly prevalent in the CHF population, and CPAP may provide the additional benefit of improving cardiac function and alleviating CHF symptoms in these patients. Sleep specialists should encourage compliance with the prescribed CPAP regimen.

John D. Zoidis, MD, is a contributing writer for Sleep Review.

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