The breathing process possesses a complex variability caused in part by the respiratory central pattern generator in the brainstem; however, it also arises from chemical and mechanical feedback control loops, network reorganization and network sharing with nonrespiratory motor acts, as well as inputs from cortical and subcortical systems. The notion that respiratory fluctuations contain hidden information has prompted scientists to decipher respiratory signals to better understand the fundamental mechanisms of respiratory pattern generation, interactions with emotion, influences on the cortical neuronal networks associated with cognition, and changes in variability in healthy and disease-carrying individuals. Respiration can be used to express and control emotion. Furthermore, respiration appears to organize brain-wide network oscillations via cross-frequency coupling, optimizing cognitive performance. With the aid of information theory-based techniques and machine learning, the hidden information can be translated into a form usable in clinical practice for diagnosis, emotion recognition, and mental conditioning.

A dilemma faced by health-care administrators is that need greatly outstrips capacity for diagnosing and treating sleep apnea, with such decisions carrying significant economic consequences. Our objective was to develop an economic model to estimate the relative costs of 4 approaches for diagnosis and initial treatment of sleep apnea.

The analysis consisted of developing a mathematical model depicting possible diagnostic and treatment approaches to the care of patients with sleep apnea; developing 4 clinical scenarios to describe distinct approaches to the management of sleep apnea patients (in-laboratory, unattended, direct-to-autotitrating PAP [auto-PAP], and mixed); and identifying costs associated with each scenario. We created a hypothetical cohort of 1,000 patients with 85% prevalence of sleep apnea to generate cost estimates.

The driver of per-patient costs was the total number of sleep studies, which varied widely across scenarios: from 425 for the direct-to-auto-PAP approach to 1,441 in the unattended approach. The scenarios also differed in per-patient costs: Per-patient costs excluding facility startup costs were $456 for direct-to-auto-PAP, $913 for in-laboratory, $991 for mixed, and $1,090 for unattended.

Approaches to diagnosing and treating sleep apnea that emphasized early application of auto-PAP had lower per-patient costs.

Sleep-disordered breathing (SDB) is a highly prevalent condition, and is associated with many debilitating chronic diseases. The role of untreated obstructive sleep apnea (OSA) in arterial hypertension has been recognized in international guidelines. Treatment with continuous positive airway pressure (CPAP) is associated with clinically-relevant reductions in blood pressure. In heart failure (HF), SDB is associated with worse prognosis and increased mortality. Major HF guidelines recommend that patients should be treated for sleep apnea to improve their HF status. Severe OSA increases the risk of arrhythmias, including atrial fibrillation, influences risk management in stroke, and is highly prevalent in patients with type 2 diabetes. Effective treatment with CPAP improves the success of antiarrhythmic interventions, improves outcomes in stroke and reduces hyperglycemia in diabetes. Patients with coronary artery disease also have a high prevalence of SDB, which is independently associated with worse outcomes. The role of CPAP for secondary cardiovascular prevention remains to be determined. Data from large, well-conducted clinical trials have shown that noninvasive ventilation, targeted to markedly reduce hypercapnia, significantly improves survival and reduces readmission in stable hypercapnic chronic obstructive pulmonary disease. The association of SDB with chronic diseases contributes to the high healthcare costs incurred by SDB patients. SDB also has an important negative impact on quality of life, which is reversed by CPAP treatment. The high prevalence of SDB, and its association with diseases that cause significant morbidity and mortality, suggest that the diagnosis and management of SDB is an important therapeutic goal. First, adherent CPAP treatment significantly improves the quality of life of all patients with SDB; second, it eliminates the negative impact of untreated SDB on any associated chronic diseases; and third, it significantly reduces the increased costs of all hospital and medical services directly associated with untreated SDB. In short, the recognition and treatment of SDB is vital for the continued health and wellbeing of individual patients with SDB.

Heart failure (HF) is a life-threatening disease and is a growing public health concern. Despite recent advances in pharmacological management for HF, the morbidity and mortality from HF remain high. Therefore, non-pharmacological approaches for HF are being developed. However, most non-pharmacological approaches are invasive, have limited indication and are considered only for advanced HF. Accordingly, the development of less invasive, non-pharmacological approaches that improve outcomes for patients with HF is important. One such approach may include positive airway pressure (PAP) therapy. In this review, the role of PAP therapy applied through mask interfaces in the wide spectrum of HF care is discussed.

To evaluate the effect of respiratory scoring criteria on diagnosis and classification of sleep disordered breathing (SDB) in chronic heart failure (CHF).

Cross-sectional observational study.

Heart failure and general cardiology clinics at two London hospitals.

One hundred eighty stable patients with CHF and a median age of 69.6 y, 86% male.

SDB was diagnosed by polysomnography. The apnea-hypopnea index (AHI) was initially scored using a conservative hypopnea definition of a ≥ 50% decrease in nasal airflow with a ≥ 4% oxygen desaturation. The AHI was rescored with hypopnea defined according to the American Academy of Sleep Medicine (AASM) alternative scoring rule, requiring an associated ≥ 3% oxygen desaturation or arousal. SDB was defined as AHI ≥ 15/h. Diagnosis and classification of SDB as obstructive sleep apnea (OSA) or central sleep apnea (CSA) with each rule were compared. The effect of mixed apneas on classification of SDB as CSA or OSA was also investigated.

Median AHI increased from 9.3/h to 13.8/h (median difference 4.6/h) when the AASM alternative rule was used to score hypopneas. SDB prevalence increased from 29% to 46% with the alternative scoring rule (P < 0.001). Classification of SDB as OSA or CSA was not significantly altered by hypopnea scoring rules or the categorization of mixed apneas.

Hypopnea scoring rules can significantly influence the apnea-hypopnea index and diagnosis of sleep disordered breathing in chronic heart failure but do not alter the classification as obstructive sleep apnea or central sleep apnea. Standardization of hypopnea scoring rules is important to ensure consistency in diagnosis of sleep disordered breathing in chronic heart failure patients.

Sleep-disordered breathing (SDB) causes hypoxemia, negative intrathoracic pressure, and frequent arousal, contributing to increased cardiovascular disease mortality and morbidity. Obstructive sleep apnea syndrome (OSAS) is linked to hypertension, ischemic heart disease, and cardiac arrhythmias. Successful continuous positive airway pressure (CPAP) treatment has a beneficial effect on hypertension and improves the survival rate of patients with cardiovascular disease. Thus, long-term compliance with CPAP treatment may result in substantial blood pressure reduction in patients with resistant hypertension suffering from OSAS. Central sleep apnea and Cheyne-Stokes respiration occur in 30-50% of patients with heart failure (HF). Intermittent hypoxemia, nocturnal surges in sympathetic activity, and increased left ventricular preload and afterload due to negative intrathoracic pressure all lead to impaired cardiac function and poor life prognosis. SDB-related HF has been considered the potential therapeutic target. CPAP, nocturnal O2 therapy, and adaptive servoventilation minimize the effects of sleep apnea, thereby improving cardiac function, prognosis, and quality of life. Early diagnosis and treatment of SDB will yield better therapeutic outcomes for hypertension and HF.

Obstructive sleep apnea and central sleep apnea increase risk of mortality in patients with heart failure (HF), possibly because of hemodynamic compromise during sleep. However, beat-to-beat stroke volume (SV) has not been assessed in response to obstructive and central events during sleep in patients with HF. Because obstructive events generate negative intrathoracic pressure that reduces left ventricular (LV) preload and increases afterload, but central events do not, obstructive events should lead to greater hemodynamic compromise than central events.

To determine the effects of obstructive and central apneas and hypopneas during sleep on SV in patients with HF.

Patients with systolic HF (LV ejection fraction ≤ 45%) and sleep apnea underwent beat-to-beat measurement of SV by digital photoplethysmography during polysomnography. Change in SV from before to the end of obstructive and central respiratory events was calculated and compared between these types of events.

Changes in SV were assessed during 252 obstructive and 148 central respiratory events in 40 patients with HF. Whereas SV decreased by 6.8 (±8.7)% during obstructive events, it increased by 2.6 (±5.4)% during central events (P < 0.001 for difference). For obstructive events, reduction in SV was associated independently with LV ejection fraction, duration of respiratory events, and degree of oxygen desaturation.

In patients with HF, obstructive and central respiratory events have opposite hemodynamic effects: whereas obstructive sleep apnea appears to have an adverse effect on SV, central sleep apnea appears to have little or slightly positive effects on SV. These observations may have implications for therapeutic approaches to these two breathing disturbances.

The Canadian Thoracic Society (CTS) published an executive summary of guidelines for the diagnosis and treatment of sleep disordered breathing in 2006⁄2007. These guidelines were developed during several meetings by a group of experts with evidence grading based on committee consensus. These guidelines were well received and the majority of the recommendations remain unchanged. The CTS embarked on a more rigorous process for the 2011 guideline update, and addressed eight areas that were believed to be controversial or in which new data emerged. The CTS Sleep Disordered Breathing Committee posed specific questions for each area. The recommendations regarding maximum assessment wait times, portable monitoring, treatment of asymptomatic adult obstructive sleep apnea patients, treatment with conventional continuous positive airway pressure compared with automatic continuous positive airway pressure, and treatment of central sleep apnea syndrome in heart failure patients replace the recommendations in the 2006⁄2007 guidelines. The recommendations on bariatric surgery, complex sleep apnea and optimum positive airway pressure technologies are new topics, which were not covered in the 2006⁄2007 guidelines.

An 80-year-old man with severe central sleep apnea due to Cheyne-Stokes breathing (AHI 41.2) caused by severe cardiac failure underwent a trial of adaptive servo-ventilation (ASV) by full face mask after failure of a fixed CPAP trial. Recommended procedure was closely followed and the ASV device activated normally during central apneas. Initial settings were EEP 5, PSmin 3, PSmax 15 on room air. The device did not capture the thorax or abdomen, as shown by lack of change in respiratory inductive plethysmography, despite expected mask pressure waveforms. Snoring was also detected during apneas with device activation. Desaturation continued, followed by arousals during hyperpnea. On the device, the patient clearly slept for 1-3 epochs during the central apneas only to awaken during hyperpnea. We hypothesize that the failure to capture may have resulted from "reverse" obstructive apnea, possibly due to glottic closure during ASV activation. We suggest that earlier manual adjustments to ASV in cases such as ours, prior to waiting for the recommended 20 to 40 min of sleep, may be appropriate in selected patients. We also consider additional interventions that may increase the likelihood of a successful trial.

The International Classification of Sleep Disorders, Second Edition (ICSD-2) distinguishes 5 subtypes of central sleep apnea syndromes (CSAS) in adults. Review of the literature suggests that there are two basic mechanisms that trigger central respiratory events: (1) post-hyperventilation central apnea, which may be triggered by a variety of clinical conditions, and (2) central apnea secondary to hypoventilation, which has been described with opioid use. The preponderance of evidence on the treatment of CSAS supports the use of continuous positive airway pressure (CPAP). Much of the evidence comes from investigations on CSAS related to congestive heart failure (CHF), but other subtypes of CSAS appear to respond to CPAP as well. Limited evidence is available to support alternative therapies in CSAS subtypes. The recommendations for treatment of CSAS are summarized as follows: CPAP therapy targeted to normalize the apnea-hypopnea index (AHI) is indicated for the initial treatment of CSAS related to CHF. (STANDARD)Nocturnal oxygen therapy is indicated for the treatment of CSAS related to CHF. (STANDARD)Adaptive Servo-Ventilation (ASV) targeted to normalize the apnea-hypopnea index (AHI) is indicated for the treatment of CSAS related to CHF. (STANDARD)BPAP therapy in a spontaneous timed (ST) mode targeted to normalize the apnea-hypopnea index (AHI) may be considered for the treatment of CSAS related to CHF only if there is no response to adequate trials of CPAP, ASV, and oxygen therapies. (OPTION)The following therapies have limited supporting evidence but may be considered for the treatment of CSAS related to CHF after optimization of standard medical therapy, if PAP therapy is not tolerated, and if accompanied by close clinical follow-up: acetazolamide and theophylline. (OPTION)Positive airway pressure therapy may be considered for the treatment of primary CSAS. (OPTION)Acetazolamide has limited supporting evidence but may be considered for the treatment of primary CSAS. (OPTION)The use of zolpidem and triazolam may be considered for the treatment of primary CSAS only if the patient does not have underlying risk factors for respiratory depression. (OPTION)The following possible treatment options for CSAS related to end-stage renal disease may be considered: CPAP, supplemental oxygen, bicarbonate buffer use during dialysis, and nocturnal dialysis. (OPTION) .

Central sleep apnea (CSA) occurs in clinical situations that induce hypocapnia and respiratory instability during sleep. This is true, not only in heart failure patients, but also in patients suffering from neurological diseases and idiopathic CSA. Adaptive Servo Ventilation (ASV) is frequently prescribed in France for the treatment of CSA, but only a few studies have evaluated ASV treatment with regards to long term effectiveness and compliance.

Retrospective chart review in two French centers of the outcome of 74 CSA patients treated by ASV with a mean follow up on ASV of 36±18 months.

Thirty-three of the 74 patients suffered from CSA related to heart failure (HF), whereas the 41 others exhibited CSA mainly associated with neurological disorders or idiopathic CSA. Mean ASV compliance was 5.2±2.6 and 5.9±2.9h per night in cardiac failure and non-cardiac failure patients, respectively. All patients significantly improved their apnea+hypopnea index (from 47.4±19.8 to 6.9±9.3/h [p<0.001]) and mean nocturnal SaO(2) (from 92.1±2.6% to 93.6±3.2% [p<0.001]). The Epworth sleepiness scale score was reduced from 10.2±5.2 to 6.5±3.9 (p<0.01) in compliant patients but not in non-compliant patients (less than 3h per night). Moreover, compliant cardiac failure patients demonstrated a significant improvement in their NYHA score [p<0.05]. Lastly, ASV significantly reduced chronic hyperventilation as assessed by blood gases.

Our findings suggest that ASV is well tolerated and effective for most patients with hypocapnic central sleep apnea and chronic hyperventilation.

New approaches are needed to treat patients with stroke. Among acute ischemic stroke patients, our primary objectives were to describe the prevalence of sleep apnea and demonstrate the feasibility of providing auto-titrating continuous positive airway pressure (auto-CPAP). A secondary objective was to examine the effect of auto-CPAP on stroke severity.

Stroke patients randomized to the intervention group received 2 nights of auto-CPAP, but only those with evidence of sleep apnea received auto-CPAP for the remainder of the 30-day period. Intervention patients received polysomnography 30 days post-stroke. Control patients received polysomnography at baseline and after 30 days. Acceptable auto-CPAP adherence was defined as ≥ 4 h/night for ≥ 75% nights. Change in stroke severity was assessed comparing the NIH Stroke Scale (NIHSS) at baseline versus at 30 days.

The 2 groups (intervention N = 31, control N = 24) had similar baseline stroke severity (both median NIHSS, 3.0). Among patients with complete polysomnography data, the majority had sleep apnea: baseline, 13/15 (86.7%) control patients; 30 days, 24/35 (68.6%) control and intervention patients. Intervention patients had greater improvements in NIHSS (-3.0) than control patients (-1.0); P = 0.03. Among patients with sleep apnea, greater improvement was observed with increasing auto-CPAP use: -1.0 for control patients not using auto-CPAP; -2.5 for intervention patients with some auto-CPAP use; and -3.0 for intervention patients with acceptable auto-CPAP adherence.

The majority of acute stroke patients had sleep apnea. Auto-CPAP was well tolerated, appears to improve neurological recovery from stroke, and may represent a new therapeutic approach for selected patients with acute cerebral infarction.

Clinical observations have linked sleep-disordered breathing to cardiovascular morbidity and mortality, and especially to coronary artery disease.

The study was undertaken to determine the prevalence of sleep-disordered breathing in consecutive patients referred for angina evaluation, and analyzed the parameters influencing the severity of sleep-disordered breathing.

In all, 68 consecutive patients (53 men, 15 women, aged 63.4 +/- 10.0 years) referred for angina evaluation were studied. Coronary angiography, selective left ventriculography, and a polygraphic study with a validated six-channel monitoring device were performed. Full-night polysomnography was used to reevaluate patients with an apnea/hypopnea index > or = 10/h.

Sleep-disordered breathing as defined by an apnea/hypopnea index > or = 10/h was found in 30.9% of patients; its prevalence was not increased in patients with and without coronary artery disease (26.5 vs. 42.1%). Multiple stepwise linear regression analysis revealed that the severity of sleep-disordered breathing was significantly and independently associated with left ventricular ejection fraction (r = -0.38; p = 0.002), but not with age, body mass index, gender, diabetes mellitus, hypertension, hyperuricemia, hypercholesterolemia, smoking habits, or coronary artery disease. In this group of patients, multiple logistic regression analysis could not demonstrate sleep-disordered breathing to be an independent predictor of coronary artery disease.

Sleep-disordered breathing is common in patients referred for angina evaluation. The degree of sleep-disordered breathing is mainly determined by the extent of left ventricular dysfunction.

In patients with congestive heart failure, sleep disordered breathing occurs commonly and is associated with an increased mortality. In addition to central sleep apnea (Cheyne-Stokes respiration), obstructive sleep apnea is more prevalent in patients with congestive heart failure than in the general population. As a result, a number of treatments have been investigated, with varying results. While many therapies may improve the severity of sleep disordered breathing, only positive pressure ventilation has been shown to improve cardiac function. Newer forms of positive pressure ventilation, such as adaptive servo-ventilation, appear to be even more effective at correcting central sleep apnea. Whether any of these treatments have an effect on transplant-free survival is presently unknown and awaits further study.

Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is associated with a poor prognosis in patients with heart failure (HF). However, some patients do not respond to continuous positive airway pressure (CPAP), so other therapeutic modalities should be considered, such as bi-level positive airway pressure (PAP), which also assists respiration and might be effective for such patients.

The 20 patients with HF because of left ventricular systolic dysfunction were assessed: 8 had ischemic etiology, and all had severe CSA according to the apnea - hypopnea index (AHI) determined by polysomnography. All diagnosed patients underwent repeat polysomnography using CPAP. The AHI improved significantly in 11 (AHI <15), but only slightly in 9, in whom the AHI remained high (>or=15). Bi-level PAP titration significantly improved the AHI in the latter group. Those who were unresponsive to CPAP had significantly lower PaCO(2), higher plasma brain natriuretic peptide (BNP), longer mean duration of CSR and fewer obstructive episodes than CPAP responders. After 6 months of positive airway support with either CPAP (n=9) or bi-level PAP (n=7), BNP levels significantly decreased and left ventricular ejection fraction significantly increased.

Bi-level PAP could be an effective alternative for patients with HF and pure CSR-CSA who are unresponsive to CPAP.

There is no universally accepted method to determine effective therapy for central sleep apnea (CSA). Continuous positive airway pressure (CPAP) applied acutely most often does not eliminate apneas and hypopneas. We hypothesized that the application of two or more therapeutic modalities after the diagnostic phase of polysomnography, a multi-modality titration study (MMTS), would identify a successful CSA treatment more often than a standard split-night study (SNS) and obviate the need for additional polysomnograms to determine a successful therapy. We retrospectively analyzed polysomnograms of patients diagnosed with CSA at our Sleep Disorders Center. We defined a therapy trial that resulted in an apnea-hypopnea index < 10 with at least one treatment modality as a therapeutic success. One hundred fifteen patients with CSA were studied. Sixty-six patients (57.4%) underwent a SNS, and 49 patients (42.6%) underwent a MMTS. SNS yielded only 8/66 (12.1%) successes on the first night, whereas a MMTS yielded 19/49 (38.8%) successes (p = 0.001, two-tailed Fishers exact). Patients who underwent a SNS eventually had similar rate of success as patients studied with MMTS (60.6 vs 63.3%, NS), but required more testing. Adaptive servo-ventilation was the most successful modality tested, yielding 36/46 (78.3%) successes. Trials of additional modalities following a failed trial of CPAP often produce a successful option that may guide therapy in patients with CSA. This approach may lead to establishing the diagnosis and treatment plans faster, while reducing unnecessary testing.

Cardiovascular and cerebrovascular diseases are the most common diseases in industrialized societies. The main objectives of this article were to summarize the physiological effects of sleep apnea on the circulatory system and to review how treatment of this condition influences cardiovascular disease. Acute sleep apnea has a number of hemodynamic consequences, such as pulmonary and systemic hypertension, increased ventricular afterload and reduced cardiac output, all of which result from sympathetic stimulation, arousal, alterations in intrathoracic pressure, hypoxia and hypercapnia. When chronic, sleep apnea-hypopnea syndrome is associated with systemic hypertension, ischemic heart disease, congestive heart failure, and Cheyne-Stokes respiration in patients with congestive heart failure. Nocturnal treatment with continuous positive airway pressure decreases both the number of central apneic episodes and blood pressure in patients with sleep apnea-hypopnea syndrome and arterial hypertension.

Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in congestive heart failure (CHF) is generally considered a poor prognostic indicator, but treatment of CSR-CSA using an adaptive servo-ventilation (ASV) device has been developed. This is the first evaluation of its use in the management of CSR-CSA in Japanese CHF patients.

Four CHF patients with CSR-CSA that was unresponsive to conventional positive airway pressure (CPAP) underwent 3 nights of polysomnography: baseline, CPAP or bi-level PAP, and on the ASV. The apnea - hypopnea index (AHI) and central-AHI (CAHI) were markedly improved on ASV (AHI 62.7+/-10.1 to 5.9+/-2.2 /h, p=0.0006, CAHI 54.5+/-6.7 to 5.6+/-2.3 /h, p=0.007). In addition, the sleep quality improved significantly on ASV, including arousal index (62.0+/-10.5 to 18.7 +/-6.2 /h, p=0.012), percentage of slow-wave sleep (2.6+/-2.6 to 19.4+/-4.8 %, p=0.042).

ASV markedly improved CSR-CSA in patients with CHF. It is a promising treatment for Japanese patients with CHF.

Obstructive and central sleep apnea are common in heart failure, and may participate in its progression by exposing the heart to intermittent hypoxia, increased preload and afterload, sympathetic activation, and vascular endothelial dysfunction. Treatment of sleep apnea in patients with heart failure may reverse these detrimental effects, in addition to alleviating symptoms of sleep apnea. In patients with heart failure and obstructive sleep apnea, short-term randomized trials have demonstrated that continuous positive airway pressure (CPAP) improves cardiac function, and lowers sympathetic activity and blood pressure. However, there are no data on whether treating obstructive sleep apnea in patients with heart failure improves morbidity and mortality. Various treatments have been tested in heart failure patients with central sleep apnea, particularly oxygen and CPAP. Both reduce the frequency of central respiratory events, and lower sympathetic activity. In addition, CPAP improves cardiac function. However, the largest randomized trial did not demonstrate any beneficial effect of CPAP on the rate of mortality and cardiac transplantation (32 vs. 32 events in the control and treatment groups, respectively; p=0.54), but ultimately lacked power to conclude with certainty whether CPAP has an effect on morbidity and mortality in such patients. Thus, although there are data to indicate that treating both obstructive and central sleep apnea in patients with heart failure improves cardiovascular function, larger randomized trials involving interventions such as oxygen, CPAP, or other forms of positive airway pressure will be required to determine whether treating these sleep-related breathing disorders reduces clinically important outcomes such as morbidity and mortality.

Central sleep apnoea (CSA) is highly prevalent in the evolutionary course of chronic heart failure. Such a ventilatory pattern during sleep is independently associated with poor prognosis in people with congestive heart failure. Chronic hyperventilation and daytime hypocapnia are the main mechanisms underlying the frequent association between CSA and cardiac failure. Simplified diagnostic strategies allowing easier recognition of CSA among people with severe heart failure are obviously needed but remain to be validated. Treatment of CSA is essentially aimed at improving cardiac function. When CSA persists, after appropriate adjustment of medication and resynchronisation therapy when indicated, specific ventilatory support during sleep should be considered. Continuous positive airway pressure (CPAP), oxygen, adaptive Servo-ventilation (ASV) and non-invasive ventilation have been proposed. Large randomised trials demonstrating survival and time free from heart transplantation are lacking.

Sleep-disordered breathing (SDB) has a potential role in the pathogenesis of congestive heart failure (CHF). High rates of central sleep apnea (CSA) are found in patients with severe CHF, and equal proportions of obstructive sleep apnea (OSA) and CSA in are found CHF patients referred to sleep clinics. The prevalence, type, and severity of SDB in unselected stable outpatients with CHF are unknown.

To determine the frequency and type of SDB in stable CHF outpatients and to examine the relationship between indexes of SDB and impaired cardiac function.

Fifty-three of 87 eligible outpatients (left ventricular ejection fraction [LVEF] < 45%) were predominantly male (77%), with an average age of 60.1 +/- 9.8 years, mean body mass index of 27.9 +/- 5.3 kg/m2, and mean LVEF of 34.0 +/- 8.5% (+/- SD).

Polysomnography, clinical questionnaire, echocardiography, urinary catecholamines, and amino-terminal fragment of pro-brain natriuretic peptide (NT-BNP).

SDB (apnea-hypopnea index >10 events/h) was demonstrated in 36 patients (68%) including two subgroups: OSA (n = 28, 53%) and CSA (n = 8, 15%). SDB was associated with atrial fibrillation (0% vs 28%, p = 0.02), more severe oxyhemoglobin desaturation (percentage of time with oxygen saturation < 90%: 0.4% vs 7.9%, p = 0.003), sleep disruption (p = 0.003), and higher urinary noradrenaline levels (p = 0.013) in OSA patients and CSA patients, respectively. Subjective sleepiness (Epworth sleepiness scale, 7.5 vs 8.5; p = 0.11), indexes of impaired cardiac function including Minnesota Living With Heart Failure Questionnaire scores, shuttle walk distance, and NT-BNP levels were not related to the presence of SDB (p > 0.05). CSA patients had lower LVEF (p = 0.0013).

SDB is very common in stable outpatients with CHF, and in our sample OSA predominates. Atrial fibrillation and severe left ventricular impairment increased the likelihood of SDB (particularly CSA), whereas symptom severity, subjective daytime sleepiness, exercise capacity, and NT-BNP levels did not. If specific therapy for SDB such as continuous positive airway pressure can be shown to improve major cardiovascular end points, these results support screening of clinically stable CHF patients.

Cheyne - Stokes respiration with central sleep apnea (CSR-CSA) contributes to the poor prognosis in patients with congestive heart failure (CHF). Bi-level positive airway pressure (bi-level PAP) may be an effective alternative for treating CSR-CSA and CHF.

Fourteen patients with CSR-CSA were divided into 2 groups, a control group that included 7 patients who decided to receive only conventional medications and a group of 7 patients that received bi-level PAP. Left ventricular ejection fraction (LVEF), mitral regurgitation (MR) area, plasma brain natriuretic peptide (BNP) concentration and the New York Heart Association (NYHA) functional class were evaluated initially (baseline) and 3 months later. In the control group, there were no significant changes in cardiac function during the study period. In contrast, in the group that received bi-level PAP, there were significant improvements in LVEF (from 36.3+/-2.9% to 46.0+/-4.0%, p = 0.02), MR area (from 30.4+/-7.6% to 20.0+/-5.1%, p = 0.02), BNP (from 993.6+/-332.0 pg/ml to 474.0+/-257.6 pg/ml, p = 0.02) and NYHA functional class (from 3.1+/-0.1 to 2.1+/-0.1, p = 0.03).

Treatment with bi-level PAP improved cardiac functions in CHF patients with CSR-CSA.

Cheyne-Stokes respiration is a form of periodic breathing in which central apneas and hypopneas alternate with periods of hyperventilation, producing a waxing and waning pattern of tidal volume. This review focuses on the causes and consequences of Cheyne-Stokes respiration in patients with congestive heart failure, in whom the prevalence is strikingly high and ranges from 30% to 50%. Several factors have been implicated in the genesis of Cheyne-Stokes respiration, including low cardiac output and recurrent hypoxia. The key pathophysiological mechanism triggering Cheyne-Stokes respiration is hyperventilation and low arterial CO2 (PaCO2) that when below the apneic threshold triggers a central apnea. Hyperventilation is associated with pulmonary congestion, and Cheyne-Stokes respiration is more prone to occur during sleep, when the respiratory system is mainly dependent on chemical control. It is associated with recurrent dips in oxygen saturation and arousals from sleep, with oscillations in blood pressure and heart rate, sympathetic activation and increased risk of ventricular tachycardia. Cheyne-Stokes respiration is an independent marker of poor prognosis and may participate in a vicious cycle, further stressing the failing heart.

Chronic heart failure (CHF) is a common condition and is associated with excess morbidity and mortality, in spite of the many advances in its treatment. Chronic stable heart failure is also associated with an increased incidence of sleep-related breathing disorders, such as central sleep apnoea (CSA) and Cheyne Stokes respiration (CSR). Continuous positive airways pressure (CPAP) has been shown to alleviate the symptoms of CHF, improve left ventricular function and oxygenation. To a certain extent, CPAP also abolishes sleep-related breathing disorders in patients with chronic heart failure. In patients with acute pulmonary oedema, the use of positive pressure ventilation improves cardiac haemodynamic indices, as well as symptoms and oxygenation, and is associated with a lower need for intubation. However, some studies have cast doubts about its safety and suggest a higher rate of myocardial infarction associated with its use. In our opinion, non-invasive positive pressure ventilation and CPAP offers an adjunctive mode of therapy in patients with acute pulmonary oedema and chronic heart failure, who may not be suitable for intubation and in those not responsive to conventional therapies. Non-invasive ventilation also helps to improve oxygenation in those patients with exhaustion and respiratory acidosis. Many trials are still ongoing and the results of these studies would throw more light on the present role of non-invasive ventilation in the management of CHF.

This study was done to evaluate whether cardiac dysfunction or abnormal measurements on cardiopulmonary exercise testing (CPET) can be improved after 2 months of nasal CPAP treatment. Twenty patients with moderate or severe OSAS received nasal CPAP treatment. All subjects also underwent blood pressure, simple spirometric, and arterial blood gas (ABG) measurements; cardiac evaluation by radionuclide scanning and CPET; and an overnight polysomnography sleep study before and after nasal CPAP treatment. No difference in left ventricular ejection fraction (LVEF) was found after 2 months of nasal CPAP treatment, but higher right ventricular ejection fraction (RVEF), VO2peak, VO2peak/kg and workpeak were observed. After 2 months of nasal CPAP treatment, these patients had a lower breathing reserve and a greater increase in anaerobic threshold and oxygen pulse. Moderate to severe OSAS patients before nasal CPAP treatment had abnormal CPET as reflected by lower RVEF, VO2peak/kg, workpeak, anaerobic threshold and oxygen pulse. These abnormalities can be improved after 2 months of nasal CPAP treatment.

Daytime CPAP titration studies with full polysomnography have been successfully performed in patients with severe sleep apnea-hypopnea syndrome (SAHS). The implementation of daytime studies in unselected SAHS patients could help to reduce the waiting lists for CPAP titrations. The main purpose of this study was to compare the effectiveness of conventional versus manual or automatic daytime CPAP titration in unselected patients with SAHS. Ninety-three consecutive patients with SAHS in whom CPAP was indicated were assigned to conventional titration or to manual or automatic (AutoSet) daytime CPAP titration, after sleep deprivation. The number of valid studies, sleep architecture, final pressure selected and mean pressure in the different sleep stages were compared. Changes in sleepiness (Epworth sleepiness score) and hours of CPAP use were assessed after 3 months of treatment. Four patients did not sleep (3 AutoSet, 1 conventional daytime groups). Sleep latency was shorter during automatic daytime titration whereas REM latency was shorter in daytime studies; the percentage of sleep stages was similar during all types of titration. CPAP requirements were significantly higher during REM sleep in conventional and manual daytime titrations while mean pressure was unchanged throughout sleep stages during AutoSet titration. CPAP pressure selected with conventional or daytime manual titration (7.5(2.2) cm H2O and 7.4(1.5) cm H2O, ns) were significantly lower (P< 0.001) than with AutoSet (9.4(1.6) cm H20. All groups showed similar decrease of sleepiness and hours of use of CPAP at 3 months of follow-up. Automatic and manual daytime PSG studies after sleep deprivation are useful for CPAP titration in unselected patients with SAHS. Pressure selected with AutoSet is significantly higher than with conventional daytime or nighttime titration, although not significant in terms of treatment compliance and symptom improvement.

Sleep disturbances are common in critically ill patients and contribute to morbidity. Environmental factors, patient care activities and acute illness are all potential causes of disrupted sleep. Additionally, it is important to consider drug therapy as a contributing factor to this adverse experience, which patients perceive as particularly stressful. Sedative and analgesic combinations used to facilitate mechanical ventilation are among the most sleep disruptive drugs. Cardiovascular, gastric protection, anti-asthma, anti-infective, antidepressant and anticonvulsant drugs have also been reported to cause a variety of sleep disorders. Withdrawal reactions to prescribed and occasionally recreational drugs should also be considered as possible triggers for sleep disruption. Tricyclic antidepressants and benzodiazepines are commonly prescribed in the treatment of sleep disorders, but have problems with decreasing slow wave and rapid eye movement sleep phases. Newer non-benzodiazepine hypnotics offer little practical advantage. Melatonin and atypical antipsychotics require further investigation before their routine use can be recommended.

Sleep apnoea is associated with increased mortality and morbidity. The treatment goal is to reduce the neurocognitive and cardiovascular sequelae. CPAP therapy in sleep apnoea is discussed in two parts in the article. The first part will consider CPAP therapy in the more common form of sleep apnoea (i.e. obstructive or mixed sleep apnoea) and the second part will consider CPAP therapy in central sleep apnoea. Alternative positive airway pressure modalities are discussed. CPAP therapy has been extensively studied and it remains the mainstay of treatment in obstructive sleep apnoea, as it is still the most consistently efficacious and safe option. However, its major disadvantage is that it does not confer a cure to this disorder and hence therapy is generally life long with its usual treatment compliance problems. As such, there are continuous improvement strategies. The role of CPAP therapy in central sleep apnoea is more limited. There has been increasing data on the beneficial effect of CPAP on central sleep apnoea/Cheyne-Stokes respiration in congestive heart failure. Evidence for CPAP therapy in sleep apnoea has evolved significantly over the last decade. However, more research and publication of large-scale long-term randomized trials of treatment in sleep apnoea to assess patient-orientated outcomes and preferences are necessary.

Sleep-disordered breathing may adversely affect heart function, and thereby contribute to the progression of heart failure. A study was undertaken in patients with idiopathic cardiomyopathy to document the characteristics of sleep-disordered breathing.

Thirty-five patients with a diagnosis of idiopathic cardiomyopathy, comprising 20 patients with dilated cardiomyopathy (DCM) and 15 patients with hypertrophic cardiomyopathy (HCM), underwent overnight polysomnography. Of these 35, 16 (80%) of the DCM patients and 7 (47%) of the HCM patients had sleep-disordered breathing. Central sleep apnea-hypopnea syndrome (CSAHS) was seen in 10 DCM patients, but not in the HCM patients, and obstructive sleep apnea-hypopnea syndrome (OSAHS) was seen in 6 DCM patients and 7 HCM patients. CSAHS was seen in DCM patients with a low left ventricular ejection fraction. HCM patients with OSAHS had a significantly greater body mass index (BMI) than those without OSAHS and CSAHS (27.6 +/- 3.8 vs 22.0 +/- 4.0 kg/m2, p<0.05). DCM patients with OSAHS had a larger BMI than those with CSAHS (29.3 +/- 5.8 vs 24.2 +/- 4.0 kg/m2, p<0.05) and those without OSAHS and CSAHS (29.3 +/- 5.8 vs 21.3 +/- 3.1 kg/m2, p<0.05).

Sleep-disordered breathing is common in patients with idiopathic cardiomyopathy; half of DCM patients had CSAHS, which was closely associated with obesity.

To examine the association of sleep apnea with heart disease.

Prospective study.

Medical wards at the Veterans Affairs San Diego Healthcare System.

Three hundred fifty-three randomly selected inpatient men.

Sleep was recorded for 2 nights in the hospital. Medical conditions were obtained from hospital medical records. Cox proportional hazards analyses indicated that patients with congestive heart failure (CHF) plus central sleep apnea (CSA) had shorter survival than those with just CHF, just sleep apnea (obstructive or central), or neither. Survival for those with obstructive sleep apnea (OSA) or CSA and no CHF was no different than for those with neither disorder. Follow-up analysis showed that for those with no CHF, neither CSA nor OSA shortened survival (p > 0.80). For those with CHF, having CSA shortened the life span with a hazard ratio of 1.66 (p = 0.012), but having OSA had no effect. Patients with CHF had more severe sleep apnea than those with no heart disease.

This study does not clarify the issues of cause and effect, but does reinforce the strong associations between sleep apnea and heart disease in elderly men. These data suggest that people with coronary disease should be regarded as a risk group for sleep apnea.

The mechanism(s) by which nasal continuous positive airway pressure (CPAP) is effective in the treatment of Cheyne-Stokes respiration (CSR) in patients with congestive heart failure (CHF) remains uncertain, and may involve an increase in total oxygen body stores (dampening), changes in central and peripheral controller gain, and/or improvement in cardiac function. The purpose of this study was to evaluate the effects of nasal CPAP on total oxygen stores, as measured by the rate of fall of arterial oxyhemoglobin saturation (dSaO(2)/dt), to determine if dampening may play a role in the attenuation of CSR in patients with CHF.

Prospective controlled trial.

University hospital.

Nine male patients (mean +/- SD age, 59 +/- 8 years) with CHF and a mean left ventricular ejection fraction (LVEF) of 16 +/- 4%.

All patients had known CSR, as identified on a baseline polysomnographic study. Patients then underwent repeat polysomnography while receiving nasal CPAP (9 +/- 0.3 cm H(2)O). The polysomnography consisted of recording of breathing pattern, pulse oximetry, and EEG. dSaO(2)/dt was measured as the slope of a line drawn adjacent to the falling linear portion of the arterial oxygen saturation (SaO(2)) curve associated with a central apnea. All patients underwent echocardiography and right-heart catheterization within 1 month of the study to measure LVEF and cardiac hemodynamics, respectively.

There was a significant decrease in the apnea-hypopnea index (AHI) with nasal CPAP, from 44 +/- 27 events per hour at baseline to 15 +/- 24 events per hour with nasal CPAP (p = 0.004). When compared to baseline, dSaO(2)/dt significantly decreased with nasal CPAP from 0.42 +/- 0.15% to 0.20 +/- 0.07%/s (p < 0.001). The postapneic SaO(2), when compared to baseline, significantly increased with nasal CPAP, from 87 +/- 5% to 91 +/- 4% (p < 0.05). The preapneic SaO(2) did not significantly change, from a baseline of 96 +/- 2% to 96 +/- 3% with nasal CPAP (p = 0.8). When compared to baseline, the apnea duration and heart rate did not change with nasal CPAP. While there was a significant correlation noted between baseline postapneic SaO(2) and dSaO(2)/dt (r = 0.8, p = 0.02), no correlation was seen between baseline preapneic SaO(2) and dSaO(2)/dt (r = 0.1, p = 0.7). A significant correlation was noted between baseline dSaO(2)/dt and the AHI (r = 0.7, p = 0.02). With CPAP, there was a significant correlation noted between dSaO(2)/dt and the AHI (R = 0.7, p = 0.04), but no correlation was noted between dSaO(2)/dt and postapneic SaO(2) (R = 0.1, p = 0.8).

Nasal CPAP significantly decreases dSaO(2)/dt and thus increases total body oxygen stores in patients with CSR and CHF. By increasing oxygen body stores, dampening may be one of the mechanisms responsible for the attenuation of CSR seen with nasal CPAP.

Nasal continuous positive airway pressure therapy has recently been studied as a nonpharmacologic adjunct to congestive heart failure therapy. In patients with congestive heart failure, it was reported that continuous positive airway pressure therapy for the condition Cheyne-Stokes respiration with central sleep apnea led to long-term improvements in cardiac function and alleviation of heart failure symptoms. Cheyne-Stokes respiration with central sleep apnea is a frequent breathing disorder well described in patients with congestive heart failure, and is an associated risk factor for increased cardiovascular morbidity and mortality. These apneas cause an increase in sympathetic nervous system activity, which would maintain afterload at a high level or tend to increase it with time, leading to further compromise of ejection fraction. Continuous positive airway pressure appears to benefit the failing heart by increasing intrathoracic pressure, which is believed to cause an increase in cardiac output by decreasing the pressure gradient across the heart wall and allowing the left-ventricular end diastolic volume to decrease, thereby reducing the afterload. This beneficial "resting" of the heart has been documented to increase left-ventricular ejection fraction, increase cardiac index, improve inspiratory muscle strength, lower blood pressure and heart rate, decrease plasma and overnight urinary levels of norepinephrine, lower levels of atrial natriuretic peptide and endothelin-1, and increase heart rate variability. Other benefits include improvement in New York Heart Association functional class status and improvement in dyspnea.

Cheyne-Stokes respiration is known to be associated with severe left heart failure. Because of severe desaturation, sleep fragmentation, arousals, and an increase in sympathetic activity, Cheyne-Stokes respiration may lead to a further impairment of cardiac function and to a worsening of quality of life. Although the pathology of Cheyne-Stokes respiration is not fully understood, enhanced chemoreceptor sensitivity, prolonged circulation time, as well as decreased pulmonary gas stores and increased ventilatory drive may be contributing factors. Therapeutic options include the improvement of cardiac failure; medical treatment, such as using theophylline; continous positive airway pressure ventilation; and low-flow oxygen supply. Because of severe cardiac insufficiency, change of endothoracic pressure may worsen the hemodynamic situation in some patients. Therefore, this form of treatment has to be used carefully. Another possible treatment is a low-flow oxygen supply, which will prevent severe desaturations. This therapeutic approach might be a good alternative to noninvasive ventilation. However, it is controversial whether oxygen supply will improve quality of sleep of the patients, even in long-term treatment.

Congestive heart failure (CHF) is a serious medical condition frequently associated with sleep-related breathing disorders, which remain underdiagnosed and undertreated. Recent studies have provided important insight into the pathophysiology of sleep apnea syndrome in patients with CHF, with potential therapeutic implications. In addition to abolition of sleep apnea, continuous positive airway pressure (CPAP) treatment can improve cardiac function and relieve symptoms of CHF. Postulated mechanisms include beneficial hemodynamic effects on ventricular remodeling, unloading of fatigued respiratory muscles, and neurohormonal modulation. Although medium-term studies using CPAP to treat sleep-related breathing disorders associated with CHF have been encouraging, more definitive data from ongoing large clinical trials are necessary to clarify its therapeutic role.