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.     

Effectiveness of adaptive servo-ventilation

Adaptive servo-ventilation (ASV) has been developed as a specific treatment for sleep-disordered breathing, in particular Cheyne-Stokes respiration with central sleep apnea (CSA). Heart failure patients often have sleep-disordered breathing, which consists of either obstructive sleep apnea (OSA) or CSA. Other medical conditions, such as stroke, acromegaly, renal failure, and opioid use may be associated with CSA. Continuous positive airway pressure (CPAP) therapy is widely used for patients with OSA, but some of these patients develop CSA on CPAP, which is called treatment-emergent CSA. CPAP can be useful as a treatment for these various forms of CSA, but it is insufficient to eliminate respiratory events in approximately half of patients with CSA. As compared to CPAP, ASV may be a better option to treat CSA, with sufficient alleviation of respiratory events as well as improvement of cardiac function in heart failure patients. In patients without heart failure, ASV can also alleviate CSA and relieve their symptom. Recently, ASV has been widely used for patients with various forms of CSA. ASV may be also used in the setting without CSA, but it should be assessed more carefully. Clinicians should have a better understanding of the indications for ASV in each setting.     

Respiratory sleep disorders in patients with congestive heart failure

Respiratory sleep disorders (RSD) occur in about 40-50% of patients with symptomatic congestive heart failure (CHF). Obstructive sleep apnea (OSA) is considered a cause of CHF, whereas central sleep apnea (CSA) is considered a response to heart failure, perhaps even compensatory. In the setting of heart failure, continuous positive airway pressure (CPAP) has a definite role in treating OSA with improvements in cardiac parameters expected. However in CSA, CPAP is an adjunctive therapy to other standard therapies directed towards the heart failure (pharmacological, device and surgical options). Whether adaptive servo controlled ventilatory support, a variant of CPAP, is beneficial is yet to be proven. Supplemental oxygen therapy should be used with caution in heart failure, in particular, by avoiding hyperoxia as indicated by SpO₂ values >95%.     

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.     

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.     

Evaluation and Treatment of Central Sleep Apnea in Patients with Heart Failure

Sleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF). Prevalence of the most common subtypes of SDB, central sleep apnea (CSA) and obstructive sleep apnea (OSA), is increasing, which is concerning due to the association of SDB with increased mortality in patients with HF. Despite an increasing burden of CSA in HF, it is difficult to detect using current diagnostic tools and the treatment modalities are limited by variable efficacy and patient adherence. Though positive airway pressure therapies remain the cornerstone of OSA treatment, the management of CSA in the setting of HF continues to evolve. The association of the presence of CSA with worse prognosis in HF patients warrants the need for routine screening for signs and symptoms of CSA in this population. In this review, we examine the connection between CSA and HF, and highlight advancements in timely diagnostics, treatment modalities, and strategies to promote facilitation of compliance in this high-risk cohort.     

Detektion und Therapie respiratorischer Störungen durch implantierbare (kardiale) Devices

Sleep-disordered breathing (SDB) represents a common comorbidity in cardiac patients. The prevalence of obstructive sleep apnea (OSA) and central sleep apnea (CSA) is very high, particularly in patients with heart rhythm disorders and heart failure (HF). Patients with pacemakers (PM) and implantable defibrillators (ICD) including cardiac resynchronization therapy (CRT) show SDB prevalences up to 75%. However, some modern PM, ICD and CRT devices allow the detection of SDB via transthoracic impedance analysis with high sensitivity compared to polysomnographic (PSG) controls. Thus, this method could be of relevance in screening and monitoring SDB in patients with implantable cardiac devices. Preliminary studies demonstrated the possibility to treat OSA in selected patients by stimulation of the cranial nerves, especially the hypoglossal nerve. However, this requires extensive diagnostics and advanced surgical approaches including many medical disciplines and is not part of this review article. However, unilateral and transvenous stimulation of the phrenic nerve to treat central sleep apnea and Cheyne-Stokes respiration in HF patients in particular can be performed by cardiologists. This article summarizes preliminary data on the results of this promising therapy.     

Sleep apnea and heart failure

Sleep apnea is frequently observed in patients with heart failure (HF). In general, sleep apnea consists of two types: obstructive and central sleep apnea (OSA and CSA, respectively). OSA results from upper airway collapse, whereas CSA arises from reductions in central respiratory drive. In patients with OSA, blood pressure is frequently elevated as a result of sympathetic nervous system overactivation. The generation of exaggerated negative intrathoracic pressure during obstructive apneas further increases left ventricular (LV) afterload, reduces cardiac output, and may promote the progression of HF. Intermittent hypoxia and post-apneic reoxygenation cause vascular endothelial damage and possibly atherosclerosis and consequently coronary artery disease and ischemic cardiomyopathy. CSA is also characterized by apnea, hypoxia, and increased sympathetic nervous activity and, when present in HF, is associated with increased risk of death. In patients with HF, abolition of coexisting OSA by continuous positive airway pressure (CPAP) improves LV function and may contribute to the improvement of long-term outcomes. Although treatment options of CSA vary compared with OSA treatment, CPAP and other types of positive airway ventilation improve LV function and may be a promising adjunctive therapy for HF patients with CSA. Since HF remains one of the major causes of mortality in the industrialized countries, the significance of identifying and managing sleep apnea should be more emphasized to prevent the development or progression of HF.     

Advances in the management of sleep-disordered breathing in heart failure

Obstructive (OSA) and central sleep apnea (CSA) are very common in patients with congestive heart failure (CHF). This is clearly a risk factor for worsening the prognosis of patients. Treatment of sleep apnea in these patients may stop disease progression. Modern therapy, primarily central sleep apnea, is provided by adaptive servoventilation (ASV). Short-term randomized trials have demonstrated that treatment with ASV increased ejection fraction (EF), reduces sympathetic activity and blood pressure. Unfortunately, there is not enough data on whether there are effects on mortality and morbidity. Studies of this issue, such as SERVE-HF and ADVENT-HF, are currently in progress and results are expected. There are other forms of therapy of OSA like CPAP, oxygen, theophylline, acetazolamide, heart synchronisation therapy and transplantation. In patients with a predominance of OSA, in addition to previous methods, there are other recommended forms of therapy like appropriate weight loss, orthodontic appliances and surgical treatment.     

Sleep Apnea in Heart Failure

Purpose of review

In this review, we discuss the current treatment options for sleep-disordered breathing (SDB) in patients with heart failure (HF). We address the role of positive airway pressure (PAP) devices and other emerging therapies. The review includes discussion of recent trials that reported negative consequences for the PAP devices in patients with heart failure.

Recent findings

Optimal guideline-directed medical therapies of HF and PAP devices have been the mainstay treatments for HF patients with SDB. Recently, randomized controlled trials (RCTs) evaluated the effect of PAP on clinical outcomes in patients with cardiovascular (CV) disease and heart failure and found no benefit in decreasing fatal and non-fatal CV events. The Sleep Apnea Cardiovascular Endpoints (SAVE) trial evaluated continuous positive airway pressure (CPAP) ventilation in patients with CV disease and obstructive sleep apnea (OSA) and did not observe any improvement in CV effect. In patients with HF and central sleep apnea (CSA), adaptive servo-ventilation (ASV) was hypothesized to help HF outcomes, but the Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure (SERVE-HF) trial did not show any mortality benefit. Instead, the trial suggested an increase in all-cause and CV mortality in the treatment arm.

Summary

currently, studies have not shown the use of PAP therapy to improve any risks of CV outcomes or death in HF patients with sleep apnea, but some associations with improvements in symptoms from OSA have been observed.

     

Does Treating Sleep Apnea Reduce Heart Failure Risks?

Sleep-disordered breathing (SDB) is the most common comorbidity in heart failure (HF) patients. SDB, including both central sleep apnea (CSA) and obstructive sleep apnea (OSA), affects up to 70 % of all heart patients. Numerous studies have identified intermittent hypoxia, oxidative stress, and sympathetic activation as the main pathways through which SDB exerts its negative cardiovascular consequences. The etiological relation between SDB and HF is complex and multi-layered. On one level, SDB contributes to the progression of cardiovascular disease (CVD) into HF; on another level, SDB is a consequence of severe advanced HF. At all stages of CVD, SDB likely contributes to the acceleration of disease progression into end-stage process including advanced HF, stroke, and death. Figure 1 describes the role of OSA in the progression of CVD risk status, the role of CSA in end-stage CVD (including HF) and the reciprocal relationship between advanced CVD and SDB. Current evidence supports that SDB treatment improves several physiological parameters and disease markers in patients with CVD and likely decreases the progression into HF. In patients with established HF, available evidence supports that untreated SDB is independently associated with negative consequences in heart failure. However, there are insufficient studies in support of a conclusion that treatment of SDB changes important HF outcomes. In particular, there are no adequately powered randomized controlled trials demonstrating improvement in mortality, admissions, or cardiac function in HF patients with SDB therapy. However, treatment of SDB is largely safe, associated with critical functional benefits, and is increasingly better tolerated, allowing for decision-making processes that favor treatment.     

The significance and outcome of continuous positive airway pressure-related central sleep apnea during split-night sleep studies

OBJECTIVE: To determine whether central sleep apnea (CSA) occurring during continuous positive airway pressure (CPAP) titration in patients with obstructive sleep apnea (OSA) reflects subclinical congestive heart failure (CHF), and whether these events will improve with CPAP therapy. DESIGN: Cross-sectional analysis of patients with suspected sleep-related breathing disorders referred for split-night polysomnography PATIENTS AND METHODS: Forty-two OSA patients with and without CPAP-related CSA were analyzed. All CSA patients (n = 21) and control subjects (n = 21) underwent echocardiography, pulmonary function testing, and arterial blood gas (ABG) analysis. Repeat polysomnography with CPAP was performed 2 to 3 months after adequate CPAP therapy in CSA group patients. RESULTS: Demographic, Epworth sleepiness scale, pulmonary function test, ABG, and baseline diagnostic polysomnography findings were similar in both groups. There was no difference in the prevalence of subclinical left ventricular systolic dysfunction in the CSA group vs the control group. CSA patients had decreased sleep efficiency (SE), increased sleep stage 1 percentage, sleep stages shift, wake time after sleep onset (WASO), and total arousals compared to control subjects. Twelve of 14 patients (92%) in the CSA group demonstrated complete or near-complete resolution of CSA events on follow-up polysomnography and showed improvement in SE, WASO, and total arousals compared to their baseline study. CONCLUSIONS: CSA events occurring during CPAP titration are transient and self-limited. They may be precipitated by the sleep fragmentation associated with initial CPAP titration and are not associated with an increased prevalence of occult CHF compared to OSA patients without CPAP-related CSA.     

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.     

Central sleep apnea is a predictor of cardiac readmission in hospitalized patients with systolic heart failure

BackgroundHospitalized heart failure patients have a high readmission rate. We sought to determine the independent risk due to central sleep apnea (CSA) of readmission in patients with systolic heart failure (SHF).Methods and ResultsThis was a prospective observational cohort study of hospitalized patients with SHF. Patients underwent sleep studies during their hospitalization and were followed for 6 months to determine their rate of cardiac readmissions; 784 consecutive patients were included; 165 patients had CSA and 139 had no sleep-disordered breathing (SDB); the remainder had obstructive sleep apnea (OSA). The rate ratio for 6 months' cardiac readmissions was 1.53 (95% confidence interval 1.1–2.2; P = .03) in CSA patients compared with no SDB. This rate ratio was adjusted for systolic function, type of cardiomyopathy, age, weight, sex, diabetes, coronary disease, length of stay, admission sodium, creatinine, hemoglobin, blood pressure, and discharge medications. Severe OSA was also an independent predictor of readmissions with an adjusted rate ratio of 1.49 (P = .04).ConclusionIn this first evaluation of the impact of SDB on cardiac readmissions in heart failure, CSA was an independent risk factor for 6 months' cardiac readmissions. The effect size of CSA exceeded that of all known predictors of heart failure readmissions.     

Reliability and accuracy of sleep apnea scans in novel cardiac resynchronization therapy devices: an independent report of two cases

Pacemaker apnea scan algorithms are able to screen for sleep apnea. We investigated whether these systems were able to accurately detect sleep-disordered breathing (SDB) in two patients from an outpatient clinic. The first patient suffered from ischemic heart failure and severe central sleep apnea (CSA) and underwent adaptive servoventilation therapy (ASV). The second patient suffered from dilated cardiomyopathy and moderate obstructive sleep apnea (OSA). Pacemaker read-outs did not match polysomnography (PSG) recordings well and overestimated the apnea–hypopnea index. However, ASV therapy-induced SDB improvements were adequately recognized by the apnea scan of the Boston Scientific INVIVE® cardiac resynchronization therapy pacemaker. Detection of obstructive respiratory events using impedance-based technology may underestimate the number of events, as frustrane breathing efforts induce impedance changes without significant airflow. By contrast, in the second case, apnea scan overestimated the number of total events and of obstructive events, perhaps owing to a very sensitive but less specific hypopnea definition and detection within the diagnostic algorithm of the device. These two cases show that a pacemaker apnea scan is able to reflect SDB, but PSG precision is not met by far. The device scan revealed the decline of SDB through ASV therapy for CSA in one patient, but not for OSA in the second case. To achieve reliable monitoring of SDB, further technical developments and clinical studies are necessary.     

Pulmonary hypertension and sleep-related breathing disorders

Pulmonary hypertension (PH), i. e. an increase of mean pulmonary artery pressure above 20 mm Hg under resting conditions, can be observed in different forms of sleep-disordered breathing (SDB). In obstructive sleep apnea (OSA) the apnea-associated triggers of hypoxia and intrathoracic pressure swings lead to repetitive rises of pulmonary artery pressure during sleep. In 20 - 30 % of these patients daytime PH occurs. PH in the setting of OSA is usually mild and rarely causes clinically evident cor pulmonale. Effective CPAP therapy has a beneficial influence on pulmonary hemodynamics in OSA. Severe congestive heart failure (i. e. with a LVEF < 40 %) might provoke pulmonary venous hypertension and thereby stimulation of pulmonary stretch and irritant receptors. The ensuing hyperventilation leads to a decrease of pCO (2) levels below the apneic threshold and thus contributes to the emergence of Cheyne Stokes respiration (CSR) in up to one half of the affected patients. Patients suffering from advanced idiopathic pulmonary arterial hypertension (IPAH) might show a similar breathing pattern while asleep. Possible pathogenetic factors of the nocturnal periodic breathing occurring in end-stage IPAH are prolonged circulation times and hypocapnia. In conclusion, SDB might cause PH (OSA-associated PH). On the other hand, PH might lead to the development of SDB (CSR in congestive heart failure, periodic breathing in IPAH).     

Obstructive sleep apnea syndrome

Obstructive sleep apnea (OSA) syndrome is a common but often unrecognized disorder caused by pharyngeal collapse during sleep and characterized by frequent awakenings, disrupted sleep and consequent excessive daytime sleepiness. With the increasing epidemic of obesity, the most important risk factor for OSA, prevalence of the disease will increase over the coming years thus representing an important public-health problem. In fact, it is now recognized that there is an association between OSA and hypertension, metabolic syndrome, diabetes, heart failure, coronary artery disease, arrhythmias, stroke, pulmonary hypertension, neurocognitive and mood disorders. Diagnosis is based on the combined evaluation of clinical manifestations and objective sleep study findings. Cardinal symptoms include snoring, sleepiness and significant reports of sleep apnea episodes. Polysomnography represents the gold standard to confirm the clinical suspicion of OSA syndrome, to assess its severity and to guide therapeutic choices. Behavioral, medical and surgical options are available for the treatment. Continuous positive airway pressure (CPAP) represents the treatment of choice in most patients. CPAP has been demonstrated to be effective in reducing symptoms, cardiovascular morbidity and mortality and neurocognitive sequelae, but it is often poorly tolerated. The results of clinical studies do not support surgery and pharmacological therapy as first-line treatment, but these approaches might be useful in selected patients. A better understanding of mechanisms underlying the disease could improve therapeutic strategies and reduce the social impact of OSA syndrome.     

Treatment of Cheyne-Stokes respiration-central sleep apnea in patients with heart failure

Sleep disordered breathing including obstructive sleep apnea (OSA) and central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR) is often accompanied by heart failure. Treatment of OSA centered on continuous positive airway pressure (CPAP) is established. However, treatment of CSR-CSA is still controversial. Since CSR-CSA occurs as a consequence of heart failure, optimization of heart failure is essential to treat CSR-CSA. For treatment directed at CSR-CSA itself, a variety of treatment approaches including night oxygen therapy and noninvasive positive pressure ventilation have been applied. Among them, night oxygen therapy improves patients' symptoms, quality of life (QOL), and left ventricular function, but had yet been shown to improve clinical outcome. For CPAP, there are responders and non-responders and for responders CPAP can also improve survival. Adaptive servo-ventilation (ASV), which most effectively treats CSR-CSA, improves exercise capacity, QOL, and cardiac function. Recent reports suggested ASV may also prevent cardiac events in patients with heart failure. However, further studies are needed to conclude that this treatment improves patient survival.     

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.     

Sleep apnea and cardiovascular risk

Sleep apnea is evident in approximately 10% of adults in the general population, but in certain cardiovascular diseases, and in particular those characterized by sodium and water retention, its prevalence can exceed 50%. Although sleep apnea is not as yet integrated into formal cardiovascular risk assessment algorithms, there is increasing awareness of its importance in the causation or promotion of hypertension, coronary artery disease, heart failure, atrial arrhythmias, and stroke, and thus, not surprisingly, as a predictor of premature cardiovascular death.Sleep apnea manifests as two principal phenotypes, both characterized by respiratory instability: obstructive (OSA), which arises when sleep-related withdrawal of respiratory drive to the upper airway dilator muscles is superimposed upon a narrow and highly compliant airway predisposed to collapse, and central (CSA), which occurs when the partial pressure of arterial carbon dioxide falls below the apnea threshold, resulting in withdrawal of central drive to respiratory muscles.The present objectives are to: (1) review the epidemiology and patho-physiology of OSA and CSA, with particular emphasis on the role of renal sodium retention in initiating and promoting these processes, and on population studies that reveal the long-term consequences of untreated OSA and CSA; (2) illustrate mechanical, autonomic, chemical, and inflammatory mechanisms by which OSA and CSA can increase cardiovascular risk and event rates by initiating or promoting hypertension, atherosclerosis, coronary artery disease, heart failure, arrhythmias, and stroke; (3) highlight insights from randomized trials in which treating sleep apnea was the specific target of therapy; (4) emphasize the present lack of evidence that treating sleep apnea reduces cardiovascular risk and the current clinical equipoise concerning treatment of asymptomatic patients with sleep apnea; and (5) consider clinical implications and future directions of clinical research and practice.