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BTG – Obstructive Sleep Apnea Exacerbates Heart Failure – Continuous Positive Airway Pressure May Reverse Cardiomyopathy

Published Online: June 4th 2011
Authors: Ralph A Pascualy
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Abstract:
Overview

Obstructive sleep apnea (OSA) occurs in about one-third of heart-failure patients, and its presence is associated with poor outcome.1 The Sleep Heart Health Study (SHHS) has found that OSA patients are at 2.38 times greater risk of heart failure.2 OSA may worsen heart failure in the following ways:3,4 inflammatory and oxidative—hypoxia, serum inflammatory, and oxidative markers (high sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor (PAI)-1); neurohumoral—arousal index, arousals per hours sleep and sympathetic activation (elevated urinary catecholamines); mechanical—repetitive bouts of negative intra-thoracic pressure and greater left ventricular muscle stress; thrombotic—increased levels of clotting factors and platelet aggregation; and endothelial— increased markers for endothelial dysfunction and injury.

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Both untreated OSA patients and heart failure patients are at increased risk of nocturnal death from cardiac ischemia and ventricular arrhythmia. Ryan et al. studied the interaction between OSA and ventricular arrhythmia in heart failure patients.5 They tested the effects of continuous positive airway pressure (CPAP) therapy on ectopic ventricular arrhythmias in a randomized controlled trial of 18 heart failure patients who had >10 ventricular ectopies per hour of sleep.Ventricular premature beats (VPB) were counted if they were premature, =0.12 seconds in duration, morphologically different to those arising from sinus beats, and had no premature P wave. Couplets and ventricular tachycardia were few and were not analyzed.

The CPAP-treated heart failure patients experienced a 58% reduction in VPBs (see Figure 1), as well as a reduction in daytime systolic pressure (by 4.6mmHg) and increased left ventricular ejection fraction and overnight urinary norepinephrine. It should be noted that this was a small study, and that the occurrence of ventricular extrasystoles does not in itself portend a life-threatening condition.Another recent study compared the effects of a month of CPAP treatment with medical treatment alone in patients with OSA and co-existing heart failure.6 Both the CPAP and the control patients were receiving optimal medical therapy. In the CPAP group,OSA was eliminated and there were significant reductions in mean daytime systolic blood pressure (p=0.02), heart rate (p=0.007), and left ventricular end-systolic dimension (p=0.009). There was also improved left ventricular ejection fraction, from 25% to 33.8% (p<0.001).This effect has been confirmed by a similar, larger study.7

CPAP May Provide Clear Cardiovascular Benefits to Cardiac Patients
In addition to reducing the detrimental effects of OSA, CPAP may also benefit the cardiac patient by: eliminating the exaggerated negative intra-thoracic pressure that occurs during apnea events, thereby reducing the left ventricle transmural pressure gradient and improving left ventricular ejection fraction and venous return; increasing lung volume and assisting inspiratory muscle function; reducing hypoxia and normalizing the balance of oxygen demand and supply to the heart; eliminating the pressor effect of hypoxia, hypercapnia and arousal, and the downward resetting of sympathetic outflow, thus reducing nocturnal catecholamine levels; and reducing both nocturnal and daytime blood pressure and heart rate.

CPAP May Also Playa Preventive Role
Young middle-aged OSA patients who have no other signs of cardiovascular disease show significant early signs of atherosclerosis. These signs are proportionate to the severity of their OSA.8 This suggests that OSA may play an independent role in the early pathophysiology of atherosclerosis, and that early CPAP treatment may ameliorate its progression.Kaneko points out that medical therapy alone does not improve any of the nocturnal effects of OSA—intermittent hypoxia, impairment of cardiac output, myocardial ischemia, and sympathetic pressor effects—to the same degree as CPAP.6 Furthermore, he suggests that long-term CPAP use may actually foster a sustained improvement in cardiac betaadrenergic function and myocardial contractility.

Figure 1: CPAP Treatment Reduces Arrhythmia in Obstructive Sleep Apnea Patients
CPAP = continuous positive airway pressure, NREM = non-rapid eye movement, REM = rapid eye movement, VPB = ventricular pressure beats.

Conclusion
Obstructive sleep apnea is a treatable condition that is associated with congestive heart failure, as well as with cardiovascular morbidity in general. Treatment with CPAP may ameliorate these conditions. CPAP should be considered especially useful in cases of difficult-to-treat and drug-resistant end-stage cardiovascular disease The studies cited in this review strongly support the notion that reduction in the severity of a patient’s obstructive sleep apnea, specifically via CPAP, is strongly correlated with increased cardiac health. Despite the recognition of this encouraging benefit to OSA patients, the global pharmacoeconomic benefit of CPAP may be limited due to the extremely poor compliance rates associated with its use. Recent estimates indicate that less than 10% of OSA sufferers remain minimally CPAP compliant six months after their formal diagnosis. Recognizing a critical need for alternatives to CPAP for the treatment of obstructive sleep apnea, a number of pharmaceutical companies, including Cypress Bioscience, Organon, and BTG have initiated investigation of various potential pharmacologic alternatives to the CPAP device.The idea of a once-a-day tablet to treat sleep apnea has obvious advantages over CPAP and would presumably be welcomed by many current OSA sufferers and unsatisfied CPAP users. If successfully developed, a drug that is both safe and effective in treating obstructive sleep apnea also has the potential to have significant clinical and economic benefit in the growing population of heart failure patients and in the broader cardiovascular patient population.

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