Intermittent Versus Sustained Hypoxemia from Sleep-disordered Breathing: Outcomes in Patients with Chronic Lung Disease and High Altitude.

In a variety of physiologic and pathologic states, people may experience both chronic sustained hypoxemia and intermittent hypoxemia ("combined" or "overlap" hypoxemia). In general, hypoxemia in such instances predicts a variety of maladaptive outcomes, including excess cardiovascular disease or mortality. However, hypoxemia may be one of the myriad phenotypic effects in such states, making it difficult to ascertain whether adverse outcomes are primarily driven by hypoxemia, and if so, whether these effects are due to intermittent versus sustained hypoxemia.

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

Sleep Apnea and Heart Failure-Current State-of-The-Art.

Sleep-disordered breathing (SDB), including obstructive and central sleep apnea, significantly exacerbates heart failure (HF) through adverse cardiovascular mechanisms. This review aims to synthesize existing literature to clarify the relationship between SDB and HF, focusing on the pathophysiological mechanisms, diagnostic challenges, and the effectiveness of treatment modalities like continuous positive airway pressure (CPAP) and adaptive servo-ventilation ASV. We analyzed peer-reviewed articles from 2003 to 2024 sourced from PubMed, EMBASE, Scopus, and Web of Science databases. The prevalence of SDB in HF patients is high, often underdiagnosed, and underappreciated. Management strategies, including CPAP and ASV, have been shown to mitigate symptoms and improve cardiac function. However, despite the availability of effective treatments, significant challenges in screening and diagnosis persist, affecting patient management and outcomes. DB significantly impacts HF prognosis. Enhanced screening strategies and broader utilization of therapeutic interventions like CPAP and ASV are essential to improve the management and outcomes of HF patients with concomitant SDB. Future research should focus on refining diagnostic and treatment protocols to optimize care for HF patients with SDB.

Hypoxic and Autonomic Mechanisms from Sleep-Disordered Breathing Leading to Cardiopulmonary Dysfunction.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. Its prevalence has increased due to increasing obesity and improved screening and diagnostic strategies. OSA overlaps with cardiopulmonary diseases to promote intermittent hypoxia and autonomic dysfunction. Intermittent hypoxia increases the risk for oxidative stress and inflammation, which promotes endothelial dysfunction and predisposes to atherosclerosis and other cardiovascular complications. OSA is associated with an increased sympathetic nervous system drive resulting in autonomic dysfunction leading to worsening of cardiopulmonary diseases. Cardiovascular diseases are observed in 40% to 80% of OSA patients. Therefore, it is essential to screen and treat cardiovascular diseases.

Risk factors of sleep-disordered breathing and poor asthma control in children with asthma.

BACKGROUND: Sleep-disordered breathing (SDB) may lead to poor asthma control in children. OBJECTIVE: To identify risk factors of SDB in children with asthma and assess its impact on asthma control. METHODS: In this cross-sectional study, we collected data of outpatients with asthma at the Children's Hospital of Chongqing Medical University from June 2020 to August 2021. The Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder and the age-appropriate asthma control tests Childhood Asthma Control Test and Test for Respiratory and Asthma Control in Kids were completed. RESULTS: We enrolled 397 children with a male-to-female ratio of 1.7:1 and a mean age of 5.70 ± 2.53 years. The prevalence of SDB was 21.6%. Allergic rhinitis (odds ratio OR = 3.316), chronic tonsillitis (OR = 2.246), gastroesophageal reflux (OR = 7.518), adenoid hypertrophy (OR = 3.479), recurrent respiratory infections (OR = 2.195), and a family history of snoring (OR = 2.048) were risk factors for the development of combined SDB in children with asthma (p < 0.05). Asthma was poorly controlled in 19.6% of the children. SDB (OR = 2.391) and irregular medication use (OR = 2.571) were risk factors for poor asthma control (p < 0.05). CONCLUSIONS: Allergic rhinitis, chronic tonsillitis, gastroesophageal reflux, adenoid hypertrophy, recurrent respiratory infections, and a family history of snoring were independent risk factors for the development of SDB in children with asthma. SDB and irregular medication use were independent risk factors for poor asthma control.

Effects of sleep-disordered breathing on serum lipid levels in children:a case control study.

BACKGROUND: Sleep-disordered breathing (SDB) during childhood is common and includes a range of breathing abnormalities that range from primary snoring (PS) to obstructive sleep apnea syndrome (OSAS).Studies have shown that not only OSAS, but also PS, which is originally considered harmless, could cause cardiovascular, cognitive, behavioral, and psychosocial problems. Many researches are focused on the relation of OSA and serum lipid levels. However, little studies are focused on PS and serum lipid levels in children.We evaluated whether serum lipid (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)) concentrations were associated with specific components of SDB, including indices of oxygen reduction index, lowest oxygen saturation, mean oxygen saturation. And we explored whether serum lipid levels were associated with different degree sleep disordered (PS and OSA group) and obese. METHODS: This was a cross-sectional study. Children who were complained by their guardians with habitual snoring and(or) mouth breathing were collected in the SDB group. Normal children without sleep problem were matched in the control group. Subjects in the SDB group underwent polysomnography. The serum lipid profiles of all the children included TC, TG, HDL-C and LDL-C concentrations were measured by appropriate enzymatic assays. RESULTS: A total of 241 with Apnea/Hypopnea Index ≥ 5 (AHI) were assigned to the OSAS group and the remaining 155 with normal AHI were assigned to the PS group. The values of TC, TG, LDL-C and LDL/HDL were significantly higher in the OSAS group than in the PS group, and the values in the PS group were significantly higher than the control group. Multiple regression analysis revealed serum TG only correlated negatively with lowest oxygen saturation. Body mass index-z score has a positive effect on TG in all the 1310 children (P = 0.031) and in SDB 396 children(P = 0.012). The level of serum TG in obese group was significantly higher than that in non-obese group. CONCLUSIONS: SDB had a very obvious effect on blood lipids, whereas PS without apnea and hypoxia. Obese only affects the aggregation of TG. TRIAL REGISTRATION: ChiCTR1900026807(2019.10.23).

Sleep apnea, the risk of out-of-hospital cardiac arrest, and potential benefits of continuous positive airway pressure therapy: A nationwide study.

OBJECTIVE: Patients with sleep apnea (SA) are at increased cardiovascular risk. However, little is known about the risk of out-of-hospital cardiac arrest (OHCA) in patients with SA. Therefore, we studied the relation between SA patients who did and did not receive continuous positive airway pressure (CPAP) therapy with OHCA in the general population. METHODS: Using nationwide databases, we conducted a nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date matched non-OHCA-controls from the general population. Conditional logistic regression models with adjustments for well-known OHCA risk factors were performed to generate odds ratio (OR) of OHCA comparing patients with SA receiving and not receiving CPAP therapy with individuals without SA. RESULTS: We identified 46,578 OHCA-cases and 232,890 matched non-OHCA-controls [mean: 71 years, 68.8% men]. Compared to subjects without SA, having SA without CPAP therapy was associated with increased odds of OHCA after controlling for relevant confounders (OR:1.20, 95%-Cl:1.06-1.36), while having SA with CPAP therapy was not associated with OHCA (OR:1.04, 95%-Cl:0.93-1.36). Regardless of CPAP therapy, age and sex did not significantly influence our findings. Our findings were confirmed in: (I) patients with neither ischemic heart disease nor heart failure (untreated SA, OR:1.24, 95%-CI:1.04-1.47; SA with CPAP, OR:1.08, 95%-CI:0.93-1.25); and (II) in patients without cardiovascular disease (untreated SA, OR:1.33, 95%-CI:1.07-1.65; SA with CPAP, OR:1.14, 95%-CI:0.94-1.39). CONCLUSION: SA not treated with CPAP was associated with OHCA, while no increased risk of OHCA was found for SA patients treated with CPAP.

A pilot observation using ultrasonography and vowel articulation to investigate the influence of suspected obstructive sleep apnea on upper airway.

Failure to employ suitable measures before administering full anesthesia to patients with obstructive sleep apnea (OSA) who are undergoing surgery may lead to developing complications after surgery. Therefore, it is very important to screen OSA before performing a surgery, which is currently done by subjective questionnaires such as STOP-Bang, Berlin scores. These questionnaires have 10-36% specificity in detecting sleep apnea, along with no information given on anatomy of upper airway, which is important for intubation. To address these challenges, we performed a pilot study to understand the utility of ultrasonography and vowel articulation in screening OSA. Our objective was to investigate the influence of OSA risk factors in vowel articulation through ultrasonography and acoustic features analysis. To accomplish this, we recruited 18 individuals with no risk of OSA and 13 individuals with high risk of OSA and asked them to utter vowels, such as /a/ (as in "Sah"), /e/ (as in "See"). An expert ultra-sonographer measured the parasagittal anterior-posterior (PAP) and transverse diameter of the upper airway. From the recorded vowel sounds, we extracted 106 features, including power, pitch, formant, and Mel frequency cepstral coefficients (MFCC). We analyzed the variation of the PAP diameters and vowel features from "See: /i/" to "Sah /a/" between control and OSA groups by two-way repeated measures ANOVA. We found that, there was a variation of upper airway diameter from "See" to "Sah" was significantly smaller in OSA group than control group (OSA: ∆12.8 ± 5.3 mm vs. control: ∆22.5 ± 3.9 mm OSA, p < 0.01). Moreover, we found several vowel features showed the exact same or opposite trend as PAP diameter variation, which led us to build a machine learning model to estimate PAP diameter from vowel features. We found a correlation coefficient of 0.75 between the estimated and measured PAP diameter after applying four estimation models and combining their output with a random forest model, which showed the feasibility of using acoustic features of vowel sounds to monitor upper airway diameter. Overall, this study has proven the concept that ultrasonography and vowel sounds analysis may be useful as an easily accessible imaging tool of upper airway.

[Sleep apnea and ocular diseases].

Sleep apnea presents as recurrent respiratory arrests or shallow breathing during sleep, resulting in decreased oxygen saturation and sleep disruption. Among its various types, obstructive sleep apnea is the most common. Over the past few decades, the prevalence of sleep apnea has been on the rise, drawing increasing attention, particularly with the growing obesity and aging population. Prolonged exposure to a hypoxic environment due to sleep apnea not only damages multiple systems throughout the body but may also pose a threat to vision. Examining the relationship between sleep apnea and ocular diseases, along with exploring its pathogenesis, has become a prominent research topic in recent years. This article provides a comprehensive review of the existing literature concerning the correlation between sleep apnea and ocular diseases such as glaucoma, optic nerve diseases, retinal and choroidal diseases, and anterior eye segment diseases. In clinical practice, prioritizing early screening and treatment for sleep apnea is crucial to prevent the worsening of associated ophthalmic conditions.

Sleep traits and associated factors among people living with HIV/AIDS in Iran: a two-step clustering analysis.

Sleep plays an essential role in improving the quality of life of people living with HIV (PLWH); however, sleep traits in this population are not well studied. This study aims to evaluate the sleep traits and related associated factors among PLWH in Iran. A nationwide cross-sectional study was conducted with 1185 PLWH who attended Voluntary Counseling and Testing centers in 15 provinces in Iran between April 2021 and March 2022. The Berlin Obstructive Sleep Apnea questionnaire, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Insomnia Severity Index were used. A two-step clustering method was employed to identify the number of sleep clusters in PLWH. Prevalence of poor sleep quality, sleepiness and insomnia were 49.6%, 21.15% and 42.7% respectively. Three sleep trait clusters were identified: I. minor sleep problems (45.6%); II. Snoring & sleep apnea (27.8%), and III. poor sleep quality and insomnia (26.7%). Age (Odds Ratio (OR) 1.033, 95% Confidence Interval (CI) 1.017-1.050), academic education (OR 0.542, 95% CI 0.294-0.998) and HIV duration were associated with being in Snoring & sleep apnea cluster, while age (OR = 1.027, 95% CI 1.009-1.040) was associated with being in Poor sleep quality and insomnia cluster. PLWH with depression had higher odds of being in Poor sleep quality and insomnia cluster, and those with anxiety had higher odds of being in Snoring & sleep apnea cluster and Poor sleep quality and insomnia cluster. A significant proportion of PLWH have poor sleep quality, sleepiness, and insomnia. The identification of three distinct sleep trait clusters underscores the need for increased attention and tailored interventions to address the specific sleep issues experienced by PLWH.

The epidemiological characteristics of sleep disordered breathing in congestive heart failure: A prospective, single centre study in Southeast Asia.

BACKGROUND: The presence of sleep-disordered breathing (SDB) in congestive heart failure (CHF) is associated with poor prognosis and is underdiagnosed despite advances in CHF management. The prevalence of SDB in CHF remains understudied in South East Asia. METHODS: A prospective, observational single-centre study was conducted where 116 consecutive patients in a specialised heart failure clinic underwent level 1, attended polysomnography (PSG). RESULTS: The prevalence of SDB was 78% using the apnoea-hypopnea index (AHI), AHI ⩾ 5/h threshold, and 59% with the AHI ⩾ 15/h threshold. Obstructive sleep apnoea (OSA) was the predominant type of SDB and was associated with increased body mass index and neck circumference. STOP-BANG was predictive of SDB, especially in men. Central sleep apnoea (CSA) patients had worse sleep indexes and lower awake arterial carbon dioxide. SDB was also homogenously present in preserved ejection fraction (EF) CHF. CONCLUSION: Most of the CHF patients were found to have SDB with the utility of PSG. Local CHF guidelines should include sleep testing for all patients with CHF.The study is registered on ClinicalTrials.gov (NCT05332223) as 'The Epidemiological Characteristics of SDB in Patients with Reduced or Preserved EF CHF'.

Comorbidities associated with adult asthma: a population-based matched cohort study in Finland.

BACKGROUND: Asthma is a common chronic disease characterised by variable respiratory symptoms and airflow limitation, affecting roughly 4%-10% of the adult population. Adult asthma is associated with higher all-cause mortality compared to individuals without asthma. In this study, we investigate the comorbidities that may affect the management of asthma. METHODS: Total of 1648 adults with asthma and 3310 individuals without asthma aged 30-93 were matched with age, gender and area of residency, and followed from 1 January 1997 to 31 December 2013. Baseline information was collected with questionnaires 1997 and follow-up register data from the national discharge registry Finnish Institute for Health and Welfare. Data included diagnoses from outpatient care and day surgery of specialised health care, and data from inpatient care of specialised and primary health care. We included all main diagnoses that had at minimum 200 events and number of diagnoses based on their common appearance with adult asthma. RESULTS: The mean follow-up time varied between 14.2 and 15.1 years, and age at the time of enrolment was 53.9 years for subjects without asthma and 54.4 years for patients with asthma. Chronic obstructive pulmonary disease was 10 times more common among asthmatics. Risk of acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis and vocal cord dysfunction was fourfold and risk of pneumonia, and chronic rhinosinusitis was 2.5 times more common among asthmatics. Sleep apnoea, gastro-oesophageal reflux disease, diabetes, allergic rhinitis and dysfunctional breathing were twofold and cataract nearly twofold higher in the asthmatic group. Adult asthma was also significantly associated with musculoskeletal diseases, incontinence and bronchiectasis. CONCLUSIONS: The most common and most severe comorbidity of adult asthma in this study was chronic obstructive pulmonary disease. Other common comorbidities of adult asthma include acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, allergic rhinitis, dysfunctional breathing, diabetes, pneumonia, sleep apnoea and gastro-oesophageal reflux disease.

Nomogram for predicting moderate-to-severe sleep-disordered breathing in patients with acute ischaemic stroke: a retrospective cohort study.

OBJECTIVES: Moderate-to-severe sleep-disordered breathing (SDB) is prevalent in patients with acute ischaemic stroke (AIS) and is associated with an increased risk of unfavourable prognosis. We aimed to develop and validate a reliable scoring system for the early screening of moderate-to-severe SDB in patients with AIS, with the objective of improving the management of those patients at risk. STUDY DESIGN: We developed and validated a nomogram model based on univariate and multivariate logistic analyses to identify moderate-to-severe SDB in AIS patients. Moderate-to-severe SDB was defined as an apnoea-hypopnoea index (AHI) ≥15. To evaluate the effectiveness of our nomogram, we conducted a comparison with the STOP-Bang questionnaire by analysing the area under the receiver operating characteristic curve. SETTING: Large stroke centre in northern Shanghai serving over 4000 inpatients, 100 000 outpatients and emergency visits annually. PARTICIPANTS: We consecutively enrolled 116 patients with AIS from the Shanghai Tenth People's Hospital. RESULTS: Five variables were independently associated with moderate-to-severe SDB in AIS patients: National Institutes of Health Stroke Scale score (OR=1.20; 95% CI 0.98 to 1.47), neck circumference (OR=1.50; 95% CI 1.16 to 1.95), presence of wake-up stroke (OR=21.91; 95% CI 3.08 to 156.05), neuron-specific enolase level (OR=1.27; 95% CI 1.05 to 1.53) and presence of brainstem infarction (OR=4.21; 95% CI 1.23 to 14.40). We developed a nomogram model comprising these five variables. The C-index was 0.872, indicated an optimal agreement between the observed and predicted SDB patients. CONCLUSIONS: Our nomogram offers a practical approach for early detection of moderate-to-severe SDB in AIS patients. This tool enables individualised assessment and management, potentially leading to favourable outcomes.

The association between the effective apnea-hypopnea index and blood pressure reduction efficacy following CPAP/oxygen treatment.

BACKGROUND: The effect of sleep apnea treatment on reducing cardiovascular disease risk remains inconclusive. This study aims to assess if the effective apnea hypopnea index (eAHI), a measure of residual sleep apnea burden post-treatment, is a factor in determining blood pressure (BP) response to continuous positive airway pressure therapy. The eAHI integrates time on therapy, residual apnea, and % of sleep time untreated. METHODS: A secondary analysis of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a randomized, controlled, parallel group assessment of continuous positive airway pressure (CPAP), oxygen and sleep hygiene. The Delta-AHI (▲AHI) was defined as the difference between baseline AHI and effective AHI at 12 weeks. Logistic and linear regression models estimated the predictors for nocturnal systolic BP change following sleep apnea therapy. RESULTS: One hundred and sixty-nine subjects with a mean age of 62.82 ± 6.99 years were included in the final analysis. Fifty subjects had ▲AHI ≤8/hour of sleep and 119 subjects were higher. After adjustment, baseline mean nighttime systolic blood pressure (OR 1.036, 95% CI 1.015-1.058, p: 0.001) and ▲AHI ≥8/hour (OR 2.406, 95% CI 1.116-5.185, p:0.025) were independent predictors for mean nighttime systolic blood pressure change >3 mm Hg. The higher effective AHI was negatively related with BNP (ß: -2.564, SE: 1.167, p: 0.029) and positively related with troponin change (ß: 0.703, SE: 0.256, p: 0.007). CONCLUSION: The ▲AHI was an independent predictor of the blood pressure response to sleep apnea treatment. REGISTER NUMBER: NCT01086800.

Implication of sleep apnea for cardiac remodeling in patients with hypertrophic cardiomyopathy.

OBJECTIVES: Cardiac remodeling is a life-long process in hypertrophic cardiomyopathy (HCM), and if uncontrolled, would cause substantial morbidity and mortality. Sleep apnea (SA) is a common comorbidity in HCM. This study aimed to investigate the relationship between SA and cardiac remodeling in a large series of patients with HCM. METHODS: A total of 606 patients with HCM who underwent sleep evaluations at Fuwai Hospital were included. Parameters of cardiac remodeling were evaluated by echocardiographic studies. RESULTS: SA was present in 363 (59.9%) patients. Left ventricular (LV) end-diastolic diameter (P < 0.001), left atrial (LA) diameter (P = 0.024), ascending aortic diameter (P < 0.001) all increased and maximal end-diastolic wall thickness (P < 0.001) decreased with the severity of SA. After adjustment for sex, age, body mass index, hypertension, hyperlipidemia, diabetes, coronary artery disease and cigarette use, log (apnea-hypopnea index+1) was independently correlated with increasing LV end-diastolic diameter (ß = 0.729, P = 0.003) and deceasing maximal end-diastolic wall thickness (ß = -0.503, P = 0.009). Log (percentage of total sleep time spent with oxygen saturation<90% + 1) was independently correlated with increasing LV end-diastolic diameter (ß = 0.609, P = 0.004) and LA diameter (ß = 0.695, P = 0.006). Severity of SA (severe SA with odds ratio, 2.38; 95% CI, 1.20-4.70; P = 0.013), log (apnea-hypopnea index+1) (OR, 1.28; 95% CI, 1.01-1.63; P = 0.045) and log (percentage of total sleep time spent with oxygen saturation<90% + 1) (OR, 1.31; 95% CI, 1.08-1.59; P = 0.006) were also independently associated with LV enlargement. CONCLUSIONS: Severity of SA is independently associated with cardiac remodeling indicating a trend toward enlarged chamber size and thinned wall. Clinical trials are required to determine whether treatment of SA improves cardiac remodeling and long-term outcomes in patients with HCM.

Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial

BACKGROUND: In patients with heart failure and reduced ejection fraction, sleep-disordered breathing, comprising obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is associated with increased morbidity, mortality, and sleep disruption. We hypothesised that treating sleep-disordered breathing with a peak-flow triggered adaptive servo-ventilation (ASV) device would improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction. METHODS: We conducted a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial of peak-flow triggered ASV in patients aged 18 years or older with heart failure and reduced ejection fraction (left ventricular ejection fraction ≤45%) who were stabilised on optimal medical therapy with co-existing sleep-disordered breathing (apnoea-hypopnoea index [AHI] ≥15 events/h of sleep), with concealed allocation and blinded outcome assessments. The trial was carried out at 49 hospitals in nine countries. Sleep-disordered breathing was stratified into predominantly OSA with an Epworth Sleepiness Scale score of 10 or lower or predominantly CSA. Participants were randomly assigned to standard optimal treatment alone or standard optimal treatment with the addition of ASV (1:1), stratified by study site and sleep apnoea type (ie, CSA or OSA), with permuted blocks of sizes 4 and 6 in random order. Clinical evaluations were performed and Minnesota Living with Heart Failure Questionnaire, Epworth Sleepiness Scale, and New York Heart Association class were assessed at months 1, 3, and 6 following randomisation and every 6 months thereafter to a maximum of 5 years. The primary endpoint was the cumulative incidence of the composite of all-cause mortality, first admission to hospital for a cardiovascular reason, new onset atrial fibrillation or flutter, and delivery of an appropriate cardioverter-defibrillator shock. All-cause mortality was a secondary endpoint. Analysis for the primary outcome was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01128816) and the International Standard Randomised Controlled Trial Number Register (ISRCTN67500535), and the trial is complete. FINDINGS: The first and last enrolments were Sept 22, 2010, and March 20, 2021. Enrolments terminated prematurely due to COVID-19-related restrictions. 1127 patients were screened, of whom 731 (65%) patients were randomly assigned to receive standard care (n=375; mean AHI 42·8 events per h of sleep [SD 20·9]) or standard care plus ASV (n=356; 43·3 events per h of sleep [20·5]). Follow-up of all patients ended at the latest on June 15, 2021, when the trial was terminated prematurely due to a recall of the ASV device due to potential disintegration of the motor sound-abatement material. Over the course of the trial, 41 (6%) of participants withdrew consent and 34 (5%) were lost to follow-up. In the ASV group, the mean AHI decreased to 2·8-3·7 events per h over the course of the trial, with associated improvements in sleep quality assessed 1 month following randomisation. Over a mean follow-up period of 3·6 years (SD 1·6), ASV had no effect on the primary composite outcome (180 events in the control group vs 166 in the ASV group; hazard ratio [HR] 0·95, 95% CI 0·77-1·18; p=0·67) or the secondary endpoint of all-cause mortality (88 deaths in the control group vs. 76 in the ASV group; 0·89, 0·66-1·21; p=0·47). For patients with OSA, the HR for all-cause mortality was 1·00 (0·68-1·46; p=0·98) and for CSA was 0·74 (0·44-1·23; p=0·25). No safety issue related to ASV use was identified. INTERPRETATION: In patients with heart failure and reduced ejection fraction and sleep-disordered breathing, ASV had no effect on the primary composite outcome or mortality but eliminated sleep-disordered breathing safely.

Association of Sex With Cardiovascular Outcomes in Heart Failure Patients With Obstructive or Central Sleep Apnea.

BACKGROUND: This study investigated the association of sex with cardiovascular outcomes in a prospective cohort of patients with heart failure (HF) with obstructive sleep apnea or central sleep apnea. METHODS AND RESULTS: Patients were screened for sleep apnea on admission using multichannel cardiopulmonary monitoring from May 2015 to July 2018. The primary outcome was a composite of cardiovascular death or unplanned hospitalization for worsening HF. Ultimately, 453 patients with HF with obstructive sleep apnea or central sleep apnea were included; 71 (15.7%) and 382 (84.3%) were women and men, respectively. During a median follow-up of 2.33 years, 248 (54.7%) patients experienced the primary outcome. In the overall population, after adjusting for potential confounders, women had an increased risk of the primary outcome (66.2% versus 52.6%; hazard ratio [HR], 1.47 [95% CI, 1.05-2.04]; P=0.024) and HF rehospitalization (62.0% versus 46.6%; HR, 1.55 [95% CI, 1.10-2.19]; P=0.013) compared with men but a comparable risk of cardiovascular death (21.1% versus 23.3%; HR, 0.78 [95% CI, 0.44-1.37]; P=0.383). Likewise, in patients with HF with obstructive sleep apnea, women had a higher risk of the primary outcome (81.8% versus 46.3%, HR, 2.37 [95% CI, 1.28-4.38]; P=0.006) and HF rehospitalization (81.8% versus 44.7%, HR, 2.46 [95% CI, 1.32-4.56], P=0.004). However, in patients with HF with central sleep apnea, there was no statistically significant difference between women and men. CONCLUSIONS: In hospitalized patients with HF, female sex was associated with an increased risk of the primary outcome and HF rehospitalization, especially in those with obstructive sleep apnea. Screening for sleep apnea should be emphasized to improve the prognosis. REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.