Predictors of long-term adherence to continuous positive airway pressure in patients with obstructive sleep apnea and cardiovascular disease.

STUDY OBJECTIVES: Poor adherence to continuous positive airway pressure (CPAP) commonly affects therapeutic response in obstructive sleep apnea (OSA). We aimed to determine predictors of adherence to CPAP among participants of the Sleep Apnea and cardioVascular Endpoints (SAVE) trial. METHODS: SAVE was an international, randomized, open trial of CPAP plus usual care versus usual care (UC) alone in participants (45-75 years) with co-occurring moderate-to-severe OSA (≥12 episodes/h of ≥4% oxygen desaturation) and established cardiovascular (CV) disease. Baseline sociodemographic, health and lifestyle factors, OSA symptoms, and 1-month change in daytime sleepiness, as well as CPAP side effects and adherence (during sham screening, titration week, and in the first month), were entered in univariate linear regression analyses to identify predictors of CPAP adherence at 24 months. Variables with p <0.2 were assessed for inclusion in a multivariate linear mixed model with country, age, and sex included a priori and site as a random effect. RESULTS: Significant univariate predictors of adherence at 24 months in 1,121 participants included: early adherence measures, improvement in daytime sleepiness at 1 month, fixed CPAP pressure, some measures of OSA severity, cardiovascular disease history, breathing pauses, and very loud snoring. While observed adherence varied between countries, adherence during sham screening, initial titration, and the first month of treatment retained independent predictive value in the multivariate model along with fixed CPAP pressure and very loud snoring. CONCLUSIONS: Early CPAP adherence had the greatest predictive value for identifying those at highest risk of non-adherence to long-term CPAP therapy. CLINICAL TRIAL REGISTRATION: SAVE is registered with clinicaltrials.gov (NCT00738179).

Co-morbid OSA and insomnia increases depression prevalence and severity in men.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) and insomnia coexist in clinical populations but prevalence in the community and risk factors remain largely unknown. We examined the prevalence and profile of previously undiagnosed co-morbid OSA and insomnia symptoms (COMISA) in community-dwelling men. METHODS: Men (n = 700, aged 58.5 ± 11.0 (mean ± SD) years) without a prior diagnosis of OSA completed full at-home unattended polysomnography, the Pittsburgh Sleep Quality Index and 36-item short form (SF-36) survey (2007-2012). Insomnia symptoms included difficulty initiating/maintaining sleep in the presence of daytime fatigue (DIMS-F). Depressive symptoms were assessed using the Beck Depression Inventory-1A, Centre for Epidemiological Studies Depression Scale and Patient Health Questionnaire-9 (PHQ-9) (2007-2010). Univariate (χ2 and analysis of variance (ANOVA)) and multiple linear regressions were used to compare data from four groups of individuals: neither disorder; previously undiagnosed OSA (apnoea-hypopnoea index ≥ 10) or DIMS-F alone; and COMISA. RESULTS: COMISA prevalence was 6.7%. Depression prevalence (COMISA, 42.6%; DIMS-F, 21.6%; OSA, 8.4%, χ2 = 71.6, P < 0.00) and symptom scale scores (e.g. PHQ-9 mean ± SD: 16.1 ± 5.5 c.f. DIMS-F: 14.0 ± 4.9, P < 0.01 and OSA: 11.4 ± 3.0, P = 0.01) were highest in men with COMISA. In COMISA, respiratory and arousal indices were similar to those observed in OSA whilst reductions in subjective sleep and day dysfunction scores were similar to DIMS-F. After adjustment, predicted mean depression scores were all higher in DIMS-F and COMISA using linear regression (e.g. PHQ-9 ß (95% CI): DIMS-F: 2.3 (1.2, 3.5); COMISA: 4.1 (3.0, 5.1)). CONCLUSION: Men with COMISA have a greater prevalence, and severity, of depression than men with only one disorder.

Novel mechanisms in the pathogenesis of atrial fibrillation: practical applications.

Intensive research over the last few decades has seen significant advances in our understanding of the complex mechanisms underlying atrial fibrillation (AF). The epidemic of AF and related hospitalizations has been described as a 'rising tide' with estimates of the global AF burden showing no sign of retreat. There is urgency for effective translational programs in this field to facilitate more individualized and targeted therapy to modify the abnormal atrial substrate responsible for the perpetuation of this arrhythmia. In this review, we chose to focus on several novel aspects of AF pathogenesis whereby practical applications in clinical practice are currently available or potentially not too far away. Specifically, we explored the contribution of atrial fibrosis, epicardial adipose tissue, autonomic nervous system, hyper-coagulability, and focal drivers to adverse atrial remodelling and AF persistence. We also highlighted the potential practical means of monitoring and targeting these factors to achieve better outcomes in patients suffering from this debilitating illness. Emerging data also support a new paradigm for targeting AF substrate with aggressive risk factor management. Finally, multi-disciplinary integrated care approach has shown great promise in improving cardiovascular outcomes of patients with AF along with potential cost savings.

Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study.

BACKGROUND: The long-term outcome of atrial fibrillation (AF) ablation demonstrates attrition. This outcome may be due to failure to attenuate the progressive substrate promoted by cardiovascular risk factors. OBJECTIVES: The goal of this study was to evaluate the impact of risk factor and weight management on AF ablation outcomes. METHODS: Of 281 consecutive patients undergoing AF ablation, 149 with a body mass index ≥27 kg/m(2) and ≥1 cardiac risk factor were offered risk factor management (RFM) according to American Heart Association/American College of Cardiology guidelines. After AF ablation, all 61 patients who opted for RFM and 88 control subjects were assessed every 3 to 6 months by clinic review and 7-day Holter monitoring. Changes in the Atrial Fibrillation Severity Scale scores were determined. RESULTS: There were no differences in baseline characteristics, number of procedures, or follow-up duration between the groups (p = NS). RFM resulted in greater reductions in weight (p = 0.002) and blood pressure (p = 0.006), and better glycemic control (p = 0.001) and lipid profiles (p = 0.01). At follow-up, AF frequency, duration, symptoms, and symptom severity decreased more in the RFM group compared with the control group (all p < 0.001). Single-procedure drug-unassisted arrhythmia-free survival was greater in RFM patients compared with control subjects (p < 0.001). Multiple-procedure arrhythmia-free survival was markedly better in RFM patients compared with control subjects (p < 0.001), with 16% and 42.4%, respectively, using antiarrhythmic drugs (p = 0.004). On multivariate analysis, type of AF (p < 0.001) and RFM (hazard ratio 4.8 [95% confidence interval: 2.04 to 11.4]; p < 0.001) were independent predictors of arrhythmia-free survival. CONCLUSIONS: Aggressive RFM improved the long-term success of AF ablation. This study underscores the importance of therapy directed at the primary promoters of the AF substrate to facilitate rhythm control strategies.

Sleep disordered breathing and chronic respiratory failure in patients with chronic pain on long term opioid therapy.

STUDY OBJECTIVES: The use of opioid medication for chronic pain has been increasing. The main aim of this study was to assess how many patients on opioids for chronic pain had sleep disordered breathing (SDB) and the type of SDB. The impact of these medications on daytime arterial blood gas (ABG) measurements and psychomotor vigilance was also studied. METHODS: Twenty-four patients (aged 18-75 years) on long-term opioids were prospectively recruited. Patients underwent home polysomnogram (PSG), psychomotor vigilance testing (PVT), and awake daytime ABG. Overnight PSG findings were compared to those of patients matched for age, sex, and BMI referred to our sleep service for evaluation of SDB. PVT results in the patient cohort were compared to PVT in healthy controls. RESULTS: Forty-six percent of opioid patients had severe SDB as defined by an apnea hypopnea index (AHI) > 30/h. The severity of SDB was similar in opioid-treated pain clinic patients and sleep clinic patients (mean ± SD AHI: Opioid-treated patients 32.7 ± 25.6; Sleep Study comparator group 28.9 ± 24.6, p = 0.6). Opioid patients had a higher frequency of central apneas and a lower arousal index (CAI: 3.9 ± 8.3 vs. 0.3 ± 0.5 events/h; p = 0.004, AI 8.0 ± 4.1 vs. 20.1 ± 13.8, p < 0.001). Pain clinic patients had impaired gas exchange during sleep and wakefulness. Nine of 20 (45%) had daytime hypercapnia, indicating a surprising number were in chronic respiratory failure. Morphine equivalent doses correlated with the severity of SDB. PVT was impaired when compared to a healthy PVT comparator group (RT: Opioid-treated patients 0.43 ± 0.27: Healthy PVT comparator group 0.28 ± 0.03 sec; p < 0.001). CONCLUSIONS: Patients on long-term opioids frequently have severe SDB, which in part is central in origin. PVT was markedly impaired. Half of the patients studied have evidence of chronic ventilatory failure. COMMENTARY: A commentary on this article appears in this issue on page 853

Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial.

IMPORTANCE: Obesity is a risk factor for atrial fibrillation. Whether weight reduction and cardiometabolic risk factor management can reduce the burden of atrial fibrillation is not known. OBJECTIVE: To determine the effect of weight reduction and management of cardiometabolic risk factors on atrial fibrillation burden and cardiac structure. DESIGN, SETTING, AND PATIENTS: Single-center, partially blinded, randomized controlled study conducted between June 2010 and December 2011 in Adelaide, Australia, among overweight and obese ambulatory patients (N = 150) with symptomatic atrial fibrillation. Patients underwent a median of 15 months of follow-up. INTERVENTIONS: Patients were randomized to weight management (intervention) or general lifestyle advice (control). Both groups underwent intensive management of cardiometabolic risk factors. MAIN OUTCOMES AND MEASURES: The primary outcomes were Atrial Fibrillation Severity Scale scores: symptom burden and symptom severity. Scores were measured every 3 months from baseline to 15 months. Secondary outcomes performed at baseline and 12 months were total atrial fibrillation episodes and cumulative duration measured by 7-day Holter, echocardiographic left atrial area, and interventricular septal thickness. RESULTS: Of 248 patients screened, 150 were randomized (75 per group) and underwent follow-up. The intervention group showed a significantly greater reduction, compared with the control group, in weight (14.3 and 3.6 kg, respectively; P < .001) and in atrial fibrillation symptom burden scores (11.8 and 2.6 points, P < .001), symptom severity scores (8.4 and 1.7 points, P < .001), number of episodes (2.5 and no change, P = .01), and cumulative duration (692-minute decline and 419-minute increase, P = .002). Additionally, there was a reduction in interventricular septal thickness in the intervention and control groups (1.1 and 0.6 mm, P = .02) and left atrial area (3.5 and 1.9 cm2, P = .02). CONCLUSIONS AND RELEVANCE: In this study, weight reduction with intensive risk factor management resulted in a reduction in atrial fibrillation symptom burden and severity and in beneficial cardiac remodeling. These findings support therapy directed at weight and risk factors in the management of atrial fibrillation. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12610000497000.

How to assess, diagnose, refer and treat adult obstructive sleep apnoea: a commentary on the choices.

Obstructive sleep apnoea (OSA) determined by polysomnography is highly prevalent, affecting about 25% of men and 10% of women in the United States, although most have few or no symptoms. Symptomatic moderate to severe OSA has major health implications related to daytime sleepiness, such as increased accidents, altered mood and loss of productivity in the workplace. Severe OSA may increase the risk of cardiovascular disease independent of daytime sleepiness. A major challenge is to correctly identify, from the large community pool of disease, people with symptoms and those at risk of long-term complications. For treatment plans to achieve quality patient outcomes, clinicians must have a clear understanding of patients' symptoms and their motivations for presentation, and be knowledgeable about the evidence surrounding the health risks of OSA and the relative merits of the various diagnostic and treatment options available. The diagnosis of OSA represents a teachable moment to target adverse lifestyle factors such as excessive weight, excessive alcohol consumption and smoking, which may be contributing to OSA and long-term cardiometabolic risk. OSA assessment and management has traditionally involved specialist referral and in-laboratory polysomnography. However, these services may not always be easy to access. Controlled studies have shown that patients with a high pretest probability of symptomatic, moderate to severe OSA can be managed well in primary care, or by skilled nurses with appropriate medical backup, using simplified ambulatory models of care. The future of sleep apnoea assessment and management will likely include models of care that involve early referral to specialists of patients with complex or atypical presentations, and an upskilled and supported primary care workforce to manage symptomatic, uncomplicated, high pretest probability disease.

Obstructive sleep apnoea in adults: a common chronic condition in need of a comprehensive chronic condition management approach.

Obstructive sleep apnoea (OSA) is a common disorder that has all the characteristics of a chronic condition. As with other chronic conditions, OSA requires ongoing management of treatments and problems, such as residual symptoms, deficits and co-morbidities. Also, many OSA patients have modifiable lifestyle factors that contribute to their disease, which could be improved with intervention. As health systems are in the process of developing more comprehensive chronic care structures and supports, tools such as chronic condition management programs are available to enable OSA patients and their health care providers to further engage and collaborate in health management. This review explains why the OSA patient group requires a more comprehensive approach to disease management, describes the chronic care model as a platform for management of chronic conditions, and assesses the suitability of particular chronic disease management programs in relation to the needs of the OSA population. Implementation of an evidence-based health-professional-led chronic condition management program into OSA patient care is likely to provide a context in which health risks are properly acknowledged and addressed. Such programs present an important opportunity to enable more optimal health outcomes than is possible by device-focused management alone.