Clodagh M. Ryan

Suppression of Central Sleep Apnea by Continuous Positive Airway Pressure and Transplant-Free Survival in Heart Failure A Post Hoc Analysis of the Canadian Continuous Positive Airway Pressure for Patients With Central Sleep Apnea and Heart Failure Trial (CANPAP)

Background— In the main analysis of the Canadian Continuous Positive Airway Pressure (CPAP) for Patients with Central Sleep Apnea (CSA) and Heart Failure Trial (CANPAP), CPAP had no effect on heart transplant–free survival; however, CPAP only reduced the mean apnea-hypopnea index to 19 events per hour of sleep, which remained above the trial inclusion threshold of 15. This stratified analysis of CANPAP tested the hypothesis that suppression of CSA below this threshold by CPAP would improve left ventricular ejection fraction and heart transplant–free survival. Methods and Results— Of the 258 heart failure patients with CSA in CANPAP, 110 of the 130 randomized to the control group and 100 of the 128 randomized to CPAP had sleep studies 3 months later. CPAP patients were divided post hoc into those whose apnea-hypopnea index was or was not reduced below 15 at this time (CPAP-CSA suppressed, n=57, and CPAP-CSA unsuppressed, n=43, respectively). Their changes in left ventricular ejection fraction and heart transplant–free survival were compared with those in the control group. Despite similar CPAP pressure and hours of use in the 2 groups, CPAP-CSA–suppressed subjects experienced a greater increase in left ventricular ejection fraction at 3 months (P=0.001) and significantly better transplant-free survival (hazard ratio [95% confidence interval] 0.371 [0.142 to 0.967], P=0.043) than control subjects, whereas the CPAP-CSA–unsuppressed group did not (for left ventricular ejection fraction, P=0.984, and for transplant-free survival, hazard ratio 1.463 [95% confidence interval 0.751 to 2.850], P=0.260). Conclusions— These results suggest that in heart failure patients, CPAP might improve both left ventricular ejection fraction and heart transplant–free survival if CSA is suppressed soon after its initiation.

Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea

Background: Obstructive sleep apnoea (OSA) elicits a number of cardiovascular perturbations that could lead acutely or chronically to increased ventricular ectopy in patients with heart failure (HF). We tested the hypothesis that treatment of OSA with continuous positive airway pressure (CPAP) in patients with HF would reduce the frequency of ventricular premature beats (VPBs) during sleep in association with reduced sympathetic nervous system activity. Methods: Following optimisation of medical treatment, 18 HF patients with OSA and >10 VPBs per hour of sleep were randomised to a control group (n = 8) or a treatment group who received CPAP (n = 10). The frequency of VPBs and urinary norepinephrine (noradrenaline) concentrations during total sleep time were determined at baseline and after 1 month. Results: Control patients did not experience any significant changes in apnoea-hypopnoea index (AHI), mean nocturnal O2 saturation, or the frequency of VPBs. In contrast, there was a significant reduction in AHI (p<0.001), an increase in minimum O2 saturation (p = 0.05), a reduction in urinary norepinephrine concentrations (p = 0.009), and a 58% reduction in the frequency of VPBs during total sleep (from mean (SE) 170 (65) to 70 (28) per hour, p = 0.011) after 1 month of CPAP treatment. Conclusions: In patients with HF, treatment of co-existing OSA by CPAP reduces the frequency of VPBs during sleep. These data suggest that reductions in VPBs and other ventricular arrhythmias through treatment of OSA might improve the prognosis in patients with HF.

Alterations in upper airway cross-sectional area in response to lower body positive pressure in healthy subjects

Background: Fluid accumulation in the neck during recumbency might narrow the upper airway (UA) and thereby contribute to its collapse in patients with obstructive sleep apnoea (OSA). It is hypothesised that acute fluid shifts from the legs to the upper body in healthy subjects would increase neck circumference and reduce the cross-sectional area of the UA (UA-XSA). Methods: In 27 healthy non-obese subjects of mean (SE) age 39 (3) years and body mass index 23.2 (0.6) kg/m2 studied while supine, leg fluid volume was measured using bioelectrical impedance, neck circumference using a mercury strain gauge and mean UA-XSA between the velum and the glottis using acoustic pharyngometry at end expiration. Measurements were made at baseline after which subjects were randomly assigned to a 5 min time control period or to a 5 min application of lower body positive pressure (LBPP) at 40 mm Hg by anti-shock trousers, separated by a 15 min washout period. Subjects then crossed over to the opposite arm of the study. Results: Compared with control, application of LBPP significantly reduced leg fluid volume (p<0.001) and increased neck circumference (p<0.001), both at 1 min and 5 min, and reduced UA-XSA after both 1 min (−0.15 cm2; 95% CI −0.23 to −0.09, p<0.001) and 5 min (−0.20 cm2; 95% CI −0.33 to −0.09, p<0.001). Conclusion: In healthy subjects, displacement of fluid from the legs by LBPP causes distension of the neck and narrowing of the UA lumen. Fluid displacement from the lower to the upper body while recumbent may contribute to pharyngeal narrowing and obstruction to airflow in patients with OSA. This may have particular pathological significance in oedematous states such as heart and renal failure.

Influence of Continuous Positive Airway Pressure on Outcomes of Rehabilitation in Stroke Patients With Obstructive Sleep Apnea

Background and Purpose— In stroke patients, obstructive sleep apnea (OSA) is associated with poorer functional outcomes than in those without OSA. We hypothesized that treatment of OSA by continuous positive airway pressure (CPAP) in stroke patients would enhance motor, functional, and neurocognitive recovery. Methods— This was a randomized, open label, parallel group trial with blind assessment of outcomes performed in stroke patients with OSA in a stroke rehabilitation unit. Patients were assigned to standard rehabilitation alone (control group) or to CPAP (CPAP group). The primary outcomes were the Canadian Neurological scale, the 6-minute walk test distance, sustained attention response test, and the digit or spatial span-backward. Secondary outcomes included Epworth Sleepiness scale, Stanford Sleepiness scale, Functional Independence measure, Chedoke McMaster Stroke assessment, neurocognitive function, and Beck depression inventory. Tests were performed at baseline and 1 month later. Results— Patients assigned to CPAP (n=22) experienced no adverse events. Regarding primary outcomes, compared to the control group (n=22), the CPAP group experienced improvement in stroke-related impairment (Canadian Neurological scale score, P<0.001) but not in 6-minute walk test distance, sustained attention response test, or digit or spatial span-backward. Regarding secondary outcomes, the CPAP group experienced improvements in the Epworth Sleepiness scale (P<0.001), motor component of the Functional Independence measure (P=0.05), Chedoke-McMaster Stroke assessment of upper and lower limb motor recovery test of the leg (P=0.001), and the affective component of depression (P=0.006), but not neurocognitive function. Conclusions— Treatment of OSA by CPAP in stroke patients undergoing rehabilitation improved functional and motor, but not neurocognitive outcomes. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00221065.

Dissociation of Obstructive Sleep Apnea From Hypersomnolence and Obesity in Patients With Stroke

Background and Purpose— Obstructive sleep apnea (OSA) is seldom considered in the diagnostic investigation in the poststroke period although it is a stroke risk factor and has adverse prognostic implications after stroke. One reason might be that widely used clinical criteria for detection of OSA in the general community are not applicable in patients with stroke. We hypothesized that patients with stroke report less sleepiness and are less obese than subjects from a community sample with the same severity of OSA. Methods— We performed polysomnography in 96 consecutive patients with stroke admitted to a stroke rehabilitation unit and in a community sample of 1093 subjects without a history of stroke. We compared the degrees of subjective sleepiness assessed by the Epworth Sleepiness Scale and body mass index between the 2 samples according to OSA categories assessed by the frequency of apneas and hypopneas per hour of sleep (<5, no OSA; 5 to <15 mild OSA; and ≥15, moderate to severe OSA). Results— Compared with the community sample, patients with stroke with OSA had significantly lower Epworth Sleepiness Scale scores and body mass index for mild OSA (Epworth Sleepiness Scale 9.3±0.3 versus 5.6±0.5, P<0.001 and body mass index 33.1±0.5 versus 28.5±1.1, P<0.048) and for moderate to severe OSA (Epworth Sleepiness Scale 9.7±0.4 versus 7.1±0.9, P=0.043 and body mass index 36.4±0.8 versus 27.2±0.8 kg/m2, P<0.025). Conclusions— For a given severity of OSA, patients with stroke had less daytime sleepiness and lower body mass index than subjects without stroke. These factors may make the diagnosis of OSA elusive in the poststroke period and preclude many such patients from the potential benefits of OSA therapy.

Sleep Apnea and Stroke

Stroke is the second leading cause of death worldwide and often has devastating consequences for affected individuals in terms of chronic disability. Traditional risk factors such as age, male sex, ethnicity, hypertension, and atrial fibrillation explain 60%-80% of the risk of stroke. Obstructive sleep apnea (OSA) is highly prevalent in individuals who have had a stroke and its emerging role as a potential modifiable risk factor for stroke has been recognized in the most recent American Heart Association stroke guidelines, which recommend consideration of screening for and treatment of OSA in this regard. In this article we provide an overview of the current evidence-based knowledge related to stroke and sleep apnea. The main focus of this article is key pathophysiological mechanisms by which OSA might increase the risk for stroke. The effect of OSA on stroke outcomes and the efficacy of treatment of OSA on these outcomes is also discussed.

Timing of Nocturnal Ventricular Ectopy in Heart Failure Patients With Sleep Apnea

BACKGROUND Ventricular ectopy is frequent in heart failure (HF) patients with sleep apnea. A previous report indicated that in HF patients, ventricular premature beats (VPB) occurred more frequently during episodes of recurrent central sleep apnea (CSA) than during normal breathing, and their frequency was greater during hyperpnea than during apnea. We hypothesized that, because respiratory stimuli that might provoke ventricular ectopy are stronger during obstructive apneas than during central apneas, in contrast to CSA, VPBs would be more frequent during apnea than hyperpnea in HF patients with obstructive sleep apnea (OSA). METHODS HF patients in sinus rhythm who have OSA or CSA (apnea-hypopnea index, > or = 15 events per hour) and with > 30 VPBs per hour were matched for severity of cardiac dysfunction and sleep apnea. The frequency of VPBs was then assessed during stage 2 sleep during the apneic and the hyperpneic phases of recurrent obstructive or central apneas. RESULTS VPBs occurred more frequently during the apneic phase than during the hyperpneic phase in patients with OSA. In contrast, VPBs occurred more frequently during the hyperpneic phase than the apneic phase in patients with CSA. There was no difference in the degree of apnea-related oxygen desaturation between central and obstructive apneas. CONCLUSIONS In patients with HF, nocturnal ventricular ectopy oscillates in time with oscillations in ventilation, with VPBs occurring predominantly during apneas in patients with OSA, but during hyperpneas in patients with CSA. This difference in VPB timing between OSA and CSA may be attributable to the differences in timing of arrhythmic stresses in these patients.

Mechanisms of sleep-disordered breathing: causes and consequences.

Obstructive sleep apnea (OSA) is very common in the general population and is characterized by ineffective inspiratory efforts against a collapsed upper airway during sleep. Collapse occurs mainly at the level of the velopharynx and oropharynx due to a combination of predisposing anatomy and the withdrawal of pharyngeal dilator activity during sleep. Central sleep apnea (CSA) is a manifestation of chemoreflex control instability, leading to periods of inadequate respiratory drive sufficient to trigger breathing, usually alternating with periods of hyperventilation. While both forms of apnea are the result of differing pathophysiology, it has become increasingly clear that OSA and CSA often coexist in the same patient, the existence of one can predispose to the other, and that the two are not as distinct as previously thought. Both OSA and CSA exert a number of acute deleterious effects including intermittent hypoxia, arousals from sleep, and swings in negative intrathoracic pressure, which in turn lead to chronic physiologic consequences such as autonomic dysregulation, endothelial dysfunction, and cardiac remodeling. These underlying pathophysiological mechanisms provide a framework for understanding why OSA and CSA may predispose to cardiovascular diseases like ischemic heart disease and stroke.

Sleep disordered breathing in group 1 pulmonary arterial hypertension.

STUDY OBJECTIVES To determine the prevalence and clinical predictors of sleep disordered breathing (SDB) and impact on outcomes in a cohort of patients with WHO group 1 pulmonary arterial hypertension (PAH). METHODS A retrospective, cross-sectional review of 52 consecutive subjects with known WHO group 1 PAH referred for assessment of possible SDB. Subjects had overnight polysomnography within 6 months of right heart catheterization performed as part of a routine clinical protocol. RESULTS SDB was present in 71% of the PAH patients: 56% had OSA and 44% CSA. Older age and subjective sleepiness as assessed by the Epworth Sleepiness Scale score > 10 were predictive of SDB. A high prevalence of OSA occurred in both male (50%) and female (60%) subjects. No differences in cardiopulmonary hemodynamics or survival between those with and without SDB were observed. CONCLUSIONS This high prevalence of SDB in the PAH population suggests that systematic screening and testing is important in this group. Further studies are necessary to determine the pathophysiological effect of SDB and potential impact of SDB treatment in this population. CITATION Minic M; Granton JT; Ryan CM. Sleep disordered breathing in group 1 pulmonary arterial hypertension.

Design of the effect of adaptive servo-ventilation on survival and cardiovascular hospital admissions in patients with heart failure and sleep apnoea: the ADVENT-HF trial

Both types of sleep‐disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo‐ventilation (ASV) in such patients reduces morbidity and mortality.