Sleep apnoea in heart failure.

Studies from the USA have reported that sleep apnoea is common in congestive heart failure (CHF), with Cheyne-Stokes respiration (CSR) being the most frequent type of sleep-disordered breathing (SDB) in these patients. Within the present study, the authors sought to assess the prevalence and type of SDB among CHF patients in Germany. A total of 203 CHF patients participated in this prospective multicentre study. All patients were stable in New York Heart Association classes II and III and had a left ventricular ejection fraction (LVEF)<40%. The patients were investigated by polygraphy and all data were centrally analysed. Patient enrolment was irrespective of sleep-related symptoms. The majority of patients were male with a mean age of 65 yrs and hospitalised. Of the 203 patients, 145 (71%) had an apnoea/hypopnoea index>10.h(-1), obstructive sleep apnoea (OSA) occurred in 43% (n=88) and CSR in 28% (n=57) of patients. The prevalence of sleep-disordered breathing is high in patients with stable severe congestive heart failure from a European population. As sleep-disordered breathing may have a negative impact on the prognosis of congestive heart failure, a sleep study should be performed in every patient with congestive heart failure and a left ventricular ejection fraction of <40%. This diagnostic approach should probably be adopted for all of these patients irrespective of the presence of sleep-related symptoms.     

Cheyne-Stokes Respiration in Patients with Heart Failure

Cheyne-Stokes respiration (CSR) is a form of central sleep-disordered breathing (SDB) in which there are cyclical fluctuations in breathing that lead to periods of central apneas/hypopnea, which alternate with periods of hyperpnea. The crescendo–decrescendo pattern of respiration in CSR is a compensation for the changing levels of blood oxygen and carbon dioxide. Severe congestive heart failure seems to be the most important risk factor for the development of CSR. A number of pathophysiologic changes, such as sleep disruption, arousals, hypoxemia-reoxygenation, hypercapnia/hypocapnia, and changes in intrathoracic pressure have harmful effects on the cardiovascular system, and the presence of CSR is associated with increased mortality and morbidity in subjects with variable degrees of heart failure. The management of CSR involves optimal control of underlying heart failure, oxygen therapy, and positive airway pressure support. In this review, we initially define and describe the epidemiology of central sleep apnea (CSA) and CSR, its pathogenesis, clinical presentation, diagnostic methods, and then discuss the recent developments in the management in patients with heart failure.     

Sleep-disordered breathing in patients with decompensated heart failure

Sleep-disordered breathing (SDB) has a higher prevalence in patients with heart failure than in the general middle-aged population. Obstructive sleep apnea (OSA), one of the forms of SBD, promotes poorly controlled hypertension, coronary events, and atrial fibrillation events that can lead to acutely decompensated heart failure (ADHF), and evidence suggests that untreated OSA increases mortality in patients with heart failure. Cheyne–Stokes respiration and central sleep apnea (CSA) have long been associated with heart failure and, in many patients, can coexist with OSA. In this article, we propose a systematic approach to diagnose and treat OSA in patients with ADHF based on current evidence.     

Reversal of nocturnal periodic breathing in primary pulmonary hypertension after lung transplantation

Nocturnal periodic breathing (PB) closely resembling Cheyne-Stokes respiration in congestive heart failure has been reported to occur in end-stage primary pulmonary hypertension (PPH). We herein describe the clinical course of a 56-year-old female patient with PPH and severe hypoxemia, hypocapnia, and right ventricular compromise in whom sleep-disordered breathing (SDB) resolved after successful double-lung transplantation. This case illustrates the crucial roles of blood gas alterations and hemodynamic impairment in the emergence of PB in PPH, and is in favor of a genuine association between advanced right heart failure and the development of SDB.     

Diagnosis and treatment of sleep apnea in heart disease

Opinion statement One of the most common yet unidentified conditions in heart disease is sleep-disordered breathing (SDB). Although it is most prevalent in patients with heart failure, it has been epidemiologically and pathophysiologically linked to ischemic heart disease, hypertension, sudden cardiac death, atrial fibrillation, and stroke. There are two primary SDB syndromes: obstructive sleep apnea (OSA) and central sleep apnea (CSA; also known as Cheyne-Stokes respiration). The pathophysiologic mechanisms that underlie these disorders appear to be distinct but both involve recurrent cycles of excessive sympathetic activation, hypoxemias and hypercapnias, and increases in ventricular wall stress. Signs and symptoms may include daytime somnolence, snoring, difficult-to-control hypertension, and refractory arrhythmias or angina. In heart failure, half of patients will have SDB and most patients will exhibit evidence of both OSA and CSA, although one or the other may predominate. The current standard diagnostic method is overnight laboratory polysomnography. Primary therapies for OSA include lifestyle changes, various facial and oral appliances, head and neck surgery, and continuous positive airway pressure (CPAP). CPAP is the most effective form of therapy for OSA, with few side effects, but is limited by compliance because of comfort-related issues. In patients with cardiovascular disease who predominantly suffer from OSA, treatment recommendations should be based on current guidelines for OSA. For patients with heart failure with predominant CSA, the current cornerstone of therapy is the optimization of medical therapy and resynchronization therapy when indicated. When SDB persists despite optimal medical management, referral to a sleep medicine consultant should be considered.     

Cardiovascular diseases in obstructive sleep apnea

Obstructive sleep apnea (OSA) affects approximately 5% of women and 15% of men in the middle-aged adults, and associated with adverse health outcomes. Cardiovascular disturbances are the most serious complications of OSA. These complications include heart failure, left/right ventricular dysfunction, acute myocardial infarction, arrhythmias, stroke, systemic and pulmonary hypertension. All these cardiovascular complications increase morbidity and mortality of OSA. Several epidemiologic studies have demonstrated that sleep related breathing disorders are an independent risk factor for hypertension, probably resulting from a combination of intermittent hypoxia and hypercapnia, arousals, increased sympathetic activity, and altered baroreflex control during sleep. Arterial hypertension, obesity, diabetes mellitus and coronary artery disease (CAD) which are independent predictors of left ventricular dysfunction, often have co-existence with OSA. Especially severe OSA patients having diastolic dysfunction might have an increased risk of heart failure, since diastolic dysfunction might be combined with systolic dysfunction. Early recognition and appropriate therapy of ventricular dysfunction is advisable to prevent further progression to heart failure and death. Patients with acute myocardial infarction, especially if they had apneas and hypoxemia without evident heart failure should be evaluated for sleep disorders. So, patients with CAD should be evaluated for OSA and vice versa. Early recognition and treatment of OSA may improve cardiovascular functions. Continuous positive airway pressure (CPAP) applied by nasal mask, is still the gold standard method for treatment of the disease and prevention of complications.     

Deleterious effects of sleep-disordered breathing on the heart and vascular system

Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing, affecting 5-15% of the population. It is characterized by intermittent episodes of partial or complete obstruction of the upper airway during sleep that disrupts normal ventilation and sleep architecture, and is typically associated with excessive daytime sleepiness, snoring, and witnessed apneas. Patients with obstructive sleep apnea present risk to the general public safety by causing 8-fold increase in vehicle accidents, and they may themselves also suffer from the physiologic consequences of OSA; these include hypertension, coronary artery disease, stroke, congestive heart failure, pulmonary hypertension, and cardiac arrhythmias. Of these possible cardiovascular consequences, the association between OSA and hypertension has been found to be the most convincing. Although the exact mechanism has not been understood, there is some evidence that OSA is associated with frequent apneas causing mechanical effects on intrathoracic pressure, cardiac function, and intermittent hypoxemia, which may in turn cause endothelial dysfunction and increase in sympathetic drive. Therapy with continuous positive airway pressure has been demonstrated to improve cardiopulmonary hemodynamics in patients with OSA and may reverse the endothelial cell dysfunction. Despite the availability of diagnostic measures and effective treatment, many patients with sleep-disordered breathing remain undiagnosed. Therefore, OSA continues to be a significant health risk both for affected individuals and for the general public. Awareness and timely initiation of an effective treatment may prevent potential deleterious cardiovascular effects of OSA.     

Cheyne-Stokes respiration as an additional risk factor for pulmonary hypertension in a boy with trisomy 21 and atrioventricular septal defect

Central ventilation disorders(1) and airway obstruction(2) with chronic hypoxemia are causally related to cor pulmonale. Pulmonary vascular resistance is often reversible, and hypoxic pulmonary hypertension often responds to treatment with supplemental oxygen. Oxygen therapy during sleep may be useful as a temporary palliative treatment in children with obstructive sleep apnea syndrome (3) and Cheyne-Stokes respiration (CSR) in congestive heart failure(4). This type of sleep-related breathing disorder is characterized by periodic crescendo-decrescendo alterations in tidal volume. Proposed mechanism include an increased central nervous system sensitivity to changes in arterial PCO2 and PO2, a decrease in total body stores of CO2 and O2 with resulting instability in arterial blood gas tensions in response to changes in ventilation, and an increased circulatory time. Clinical features of obstructive and central sleep-related breathing disorders include daytime somnolence, unusual breathing patterns, failure to thrive, and cyanosis masquerading as cyanotic congenital heart disease(2). Down syndrome is often associated with cardiac malformations, left to right shunt, and the development of pulmonary hypertension(5). However, this may be exacerbated by sleep-related breathing disorders, as illustrated in the following case report.     

Sleep disordered breathing in the elderly

Sleep disordered breathing (SDB), i.e., obstructive, central or mixed sleep apneas, has been recognized as a common occurrence in the elderly. Aging is per se associated with a decrease in the quality of sleep; SDB may further disrupt the sleep architecture in older subjects. The prevalence of obstructive sleep apnea (OSA) increases with aging; available studies report prevalence rates of 11-62%. Furthermore, OSA has been associated with increased mortality in older adults. Central apneas and periodic breathing occur with increased frequency either in subjects with neurological disorders such as infarction, tumor, sequelae of infection, diffuse encephalopathies, or in chronic heart failure. Patients with cerebrovascular disease (stroke, or transient ischemic attacks) have a markedly high prevalence of SDB, mainly OSA. In these patients, SDB is associated with a poorer functional prognosis at 3 and 12 months after the acute event, and a higher mortality. The clinical impact of SDB on cognitive function appears to be modest in patients without dementia, although there is a moderate increase in daytime sleepiness. In Alzheimer's disease (AD) however, SDB occurs more frequently than in non-demented older subjects, and its severity is correlated with the degree of cognitive impairment. The hypothesis of a causal relationship between AD and SDB remains a subject of controversy. The possibility of SDB should be considered in the elderly in the differential diagnosis of "reversible dementias", increased daytime sleepiness, or unexplained right-sided heart failure.     

Sleep Disordered Breathing in Patients with Heart Failure: Pathophysiology and Management

Sleep disordered breathing (SDB) is common in heart failure patients across the range of ejection fractions and is associated with adverse prognosis. Although effective pharmacologic and device-based treatment of heart failure may reduce the frequency or severity of SDB, heart failure treatment alone may not be adequate to restore normal breathing during sleep. Continuous positive airway pressure (CPAP) is the major treatment for SDB in heart failure, especially if obstructive rather than central sleep apnea (CSA) predominates. Adequate suppression of CSA by PAP is associated with a heart transplant-free survival benefit, although randomized trials are ongoing. Bilevel PAP (BPAP) may be as effective as CPAP in treating SDB and may be preferable over CPAP in patients who experience expiratory pressure discomfort. Adaptive (or auto) servo-ventilation (ASV), which adjusts the PAP depending on the patient’s airflow or tidal volume, may be useful in congestive heart failure patients if CPAP is ineffective. Other therapies that have been proposed for SDB in congestive heart failure include nocturnal oxygen, CO₂ administration (by adding dead space), theophylline, and acetazolamide; most of which have not been systematically studied in outcome-based prospective randomized trials.     

Underrated value of repeated right heart catheterization in pulmonary hypertension with heart failure—a case of persisted pulmonary arterial hypertension after treatment for biventricular failure

Pulmonary hypertension (PH) is a common complication of left heart disease and its presence in patients with heart failure predicts worse clinical outcomes. Specific agents targeting pulmonary arterial hypertension (PAH) have been developed over the last few years, but the efficacy of these agents in pulmonary hypertension due to left heart disease (PH-LHD) is uncertain. We report a case of idiopathic pulmonary arterial hypertension (IPAH) initially presented with biventricular failure, which was misdiagnosed as PH-LHD. A 31-year-old man who had a history of recurrent hemoptysis was referred to our center with biventricular failure. Right heart catheterization (RHC) showed elevated mean pulmonary arterial pressure (mPAP) and pulmonary capillary wedge pressure (PCWP). He was diagnosed as having PH-LHD, specifically combined post-capillary and precapillary PH (CpcPH). We treated him for 2 years with diuretics, a beta blocker, an angiotensin-converting enzyme (ACE) inhibitor, and sildenafil, which was added to treat CpcPH. A follow-up echocardiography showed that biventricular function had improved, but not PH. A second RHC revealed elevated mPAP and normal PCWP, which made us change the diagnosis to IPAH. In conclusion, it is important to perform repeated RHC in CpcPH patients after the improvement of left heart dysfunction to distinguish CpcPH from IPAH.     

Cardiovascular abnormalities in sleep-disordered breathing

The role of sleep-disordered breathing (SDB) in the development of persistent daytime pulmonary hypertension (PH) and cor pulmonale is controversial and has not been extensively studied. In this review we discuss the physiological changes that occur during SDB in the cardiovascular system, as well as review the most recent literature examining the relationship between SDB and PH/cor pulmonale. The literature suggests that much of the PH and right heart dysfunction seen in SDB is related to concurrent obesity and underlying lung disease, although it does appear that isolated SDB (in the form of obstructive sleep apnea) may be responsible for a small but significant degree of PH. The clinical consequences of this, however, remain unclear.     

Influence of obstructive sleep apnea and treatment with continuous positive airway pressure on fractional flow reserve measurements for coronary lesion assessment

Obstructive sleep apnea (OSA) and sleep‐disordered breathing have been implicated in the progression of cardiovascular disease and with increased risk of coronary artery disease, congestive heart failure, and stroke. Fractional flow reserve (FFR) is used to evaluate the physiological significance of coronary artery stenosis, and this technique is largely thought to be independent of systemic hemodynamic changes. Herein, we describe a case of OSA and sleep‐disordered breathing cyclically altering FFR measurements from normal to abnormal in a patient with coronary artery disease. More specifically, we show that the abnormal FFR across a coronary lesion in a patient with sleep disordered apnea improves (to a normal threshold) with the initiation of continuous positive airway pressure (CPAP). This finding may have implications for the mechanisms of cardiac dysfunction in patients with OSA. © 2009 Wiley‐Liss, Inc.     

Atrial fibrillation and sleep-disordered breathing

Atrial fibrillation (AF) is a common supraventricular arrhythmia that increases in prevalence with increasing age and in the presence of comorbidities such as heart failure (HF). AF increases the risk of a number of serious complications, including stroke and HF. As a result, the rate of hospitalization is high, making AF a costly disease. Treatment strategies for AF are broadly based around rate and rhythm control, either pharmacological or mechanical. There appear to be a number of links between sleep-disordered breathing (SDB) and AF, although further studies are needed to fully understand the physiological mechanisms that link these conditions. Patients with AF and SDB share a number of risk factors and comorbidities, including age, male sex, hypertension, congestive HF and coronary artery disease (CAD), and the prevalence of SDB in AF is higher than in the general population. Prevalence rates of obstructive sleep apnea (OSA) in patients with AF have been reported to range from 21% to just over 80%. The prevalence of central sleep apnea (CSA) in patients with AF is less well defined, but appears to be particularly high in patients who also have HF and a reduced left ventricular ejection fraction (LVEF). The frequency of apneas can be reduced by effective treatment of AF, while co-existing OSA reduces the effectiveness of treatments for AF and there is an increased risk of arrhythmia recurrence in the presence of SDB. Treating OSA with continuous positive airway pressure (CPAP) therapy has shown the potential to decrease the incidence of AF, improve the effectiveness of AF interventions, and decrease the risk of arrhythmia recurrence, although data from large randomized, controlled clinical trials are lacking. Based on available data, inclusion of SDB recognition and management strategies as part of AF management appears to have the potential to reduce the impact of this arrhythmia at both the individual and societal levels, and has been recognized as important in recent guidelines.     

Sleep-disordered breathing in acute decompensated heart failure

Sleep-disordered breathing (SDB), including obstructive sleep apnea (OSA) and central sleep apnea (CSA), is highly prevalent and frequently unrecognized in patients with chronic heart failure (HF). Untreated SDB may worsen acute decompensation of HF and delay recovery by increasing vascular inflammation and oxidative stress, impeding control of the blood pressure, and promoting arrhythmias. Untreated OSA doubles the risk for developing HF, and patients with HF who develop OSA are thought to have a worse prognosis than patients with HF alone. Similar to the findings in the general population, treatment of OSA appears to reduce cardiovascular morbidity and mortality in HF. The presence of CSA is associated with increased mortality in HF patients. Efficacious suppression of central sleep apnea with continuous positive airway pressure therapy may reduce mortality in HF.     

Right and left ventricular functional impairment and sleep apnea.

Obstructive sleep apnea may contribute to the development of pulmonary hypertension and RVF primarily through pulmonary vasoconstriction secondary to hypoxia. Several recent studies indicate, however, that intermittent apnea-related hypoxia is not sufficient to cause sustained pulmonary hypertension. These studies have been consistent in showing that pulmonary hypertension and RVF are almost invariably seen in the presence of diurnal hypoxia. Sustained pulmonary hypertension, therefore, appears to be associated with sustained hypoxia as is the case in COPD. Patients with OSA who have hypoxia while awake are, as a rule, obese and have mild-to-moderate diffuse obstructive airways disease. Thus, most cases of pulmonary hypertension in association with OSA result from a combination of OSA, obesity, and diffuse obstructive airways disease, a so-called overlap syndrome. However, from the therapeutic viewpoint, it is apparent that treatment of OSA by NCPAP or tracheostomy, in such cases, is usually sufficient to reverse pulmonary hypertension and RVF. More recent work has provided strong evidence that OSA can play a role in the pathogenesis of LV heart failure in patients with CHF of otherwise unknown etiology. It is likely that this occurs through a combination of increased LV afterload related to exaggerated negative Pit swings during obstructive apneas, to intermittent hypoxia, and to chronically elevated sympathoadrenal activity. Reversal of OSA by NCPAP in these patients may relieve LV heart failure. These findings add a new dimension to our understanding of the pathophysiologic effects of OSA on the cardiovascular system by demonstrating that the LV is a structure that may suffer functional impairment secondary to the stresses imposed by OSA. Finally, it has now become apparent that CSR in patients with CHF can cause symptoms of a sleep apnea syndrome when associated with intermittent hypoxia and arousals from sleep. Reversal of CSR during sleep by NCPAP can lead to alleviation of these symptoms and possibly to reduced cardiac dyspnea and LV systolic function as well. Taken together, this suggests that much more extensive use of polysomnography may be warranted in the investigation of cardiovascular disease. The reasons are compelling: sleep apnea disorders are common and eminently treatable conditions whose reversal can result in improved right and left heart function and symptomatic improvement in patients with impaired myocardial function.     

Effects of intermittent hypoxia on pulmonary haemodynamics: animal models versus studies in humans.

The aim of this review was to analyse the effects of intermittent hypoxia (IH) on pulmonary haemodynamics, comparing results of animal experiments with results of clinical studies. In animal investigations even short hypoxic exposure, continuously or in short repeated episodes mimicking obstructive sleep apnoea (OSA), leads to pulmonary artery remodelling and to pulmonary hypertension (PH). Results of investigations on effects of nocturnal IH on pulmonary haemodynamics in patients with chronic obstructive pulmonary disease (COPD) are discordant. Earlier studies reported the development of mild PH in subjects desaturating during sleep, while more recent investigations did not confirm those findings. Alveolar IH developing during apnoeic episodes during sleep in OSA patients is a disease-induced model to study its effects on pulmonary haemodynamics. In the majority of studies in OSA patients pulmonary arterial pressure remained within normal values. PH was found in patients with OSA accompanied by COPD and/or extreme obesity. People commuting between lowland and high altitude due to their employment, are also repeatedly exposed to IH. Results of clinical investigations suggest that it did not lead to the development of permanent PH. The mechanisms of discrepancies between effects of intermittent hypoxia in animal models and in humans remain to be studied.     

Sleep disorders in patients with congestive heart failure

PURPOSE OF REVIEW: This review of recent literature pertains to the growing evidence that obstructive sleep apnea contributes to the development of systemic hypertension and congestive heart failure. RECENT FINDINGS: There is irrefutable evidence that OSA causes systemic hypertension and that continuous positive airway pressure (CPAP) treatment of OSA causes a reduction in blood pressure. Moreover there is evidence that untreated OSA is associated with left ventricular diastolic and systolic failure and that treatment with CPAP improves systolic function. SUMMARY: OSA should be considered in patients with systemic hypertension or heart failure.     

Can heart rate variation rule out sleep-disordered breathing in heart failure?

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne-Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF. In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles. Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea-hypopnoea index>20 events.h-1 and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea-hypopnoea cut-off of 30 events.h-1. In conclusion, these results suggest that spectral analysis of heart rate may be useful as a "rule-out test" for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.     

Kardiale Auswirkungen der obstruktiven Schlafapnoe

Sleep disordered breathing, especially obstructive sleep apnea, are common in cardiovascular disease. Negative hemodynamic effects are mediated by nocturnal ischemia and intrathoracal pressure swings. Therefore “therapy resistant” arterial hypertension and congestive heart failure, as well as atrial fibrillation or sleep associated bradycardia are suggestive of sleep disordered breathing. Further on, clinical course of coronary artery disease seems to be influenced by nocturnal breathing disorders. Application of continuous positive airway pressure (CPAP) is effective in most of the patients and attenuates cardiodepressive hemodynamic effects of obstructive sleep apnea.