BACKGROUND Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea. METHODS We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea–hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guideline-based medical treatment alone (control). The primary end point in the time-to-event analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure. RESULTS In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P = 0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P = 0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P = 0.006). CONCLUSIONS Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy.
Aim: Evaluation of the prevalence and nature of sleep-disordered breathing (SDB) in patients with symptomatic chronic heart failure (CHF) receiving therapy according to current guidelines. Methods and results: We prospectively screened 700 patients with CHF (NYHA class ≥ II, LV-EF ≤ 40%) for SDB using cardiorespiratory polygraphy (Embletta™). Furthermore, echocardiography, cardiopulmonary exercise and 6-min walk testing were performed. Medication included ACE-inhibitors and/or AT1-receptor blockers in at least 94%, diuretics in 87%, β-blockers in 85%, digitalis in 61% and spironolactone in 62% of patients.SDB was present in 76% of patients (40% central (CSA), 36% obstructive sleep apnoea (OSA)). CSA patients were more symptomatic (NYHA class 2.9 ± 0.5 vs. no SDB 2.57 ± 0.5 or OSA 2.57 ± 0.5; p b 0.05) and had a lower LV-EF (27.4 ± 6.6% vs. 29.3 ± 2.6%, p b 0.05) than OSA patients. Oxygen uptake (VO 2 ) was lowest in CSA patients: predicted peak VO 2 57 ± 16% vs. 64 ± 18% in OSA and 63 ± 17% in no SDB, p b 0.05. 6-min walking distances were 331 ± 111 m in CSA, 373 ± 108 m in OSA and 377 ± 118 m in no SDB (p b 0.05). Conclusions: This study confirms the high prevalence of SDB, particularly CSA in CHF patients. CSA seems to be a marker of heart failure severity.
This study tested the effectiveness of the AutoSet self-titrating nasal continuous positive airway pressure (nCPAP) system in treating obstructive sleep apnea (OSA), and choosing a suitable pressure for subsequent conventional fixed-pressure nCPAP therapy. Twenty-one adult men with untreated OSA were studied with full polysomnography on each of four nights: diagnostic, manual and AutoSet nCPAP titration (in random order), and conventional fixed-pressure nCPAP at the pressure recommended by the AutoSet titration. Titration was satisfactorily performed in 20 of 21 subjects. Severe mask leak prevented automated titration in one subject and caused transient unnecessary increases in pressure in three subjects. In the 20 subjects, respiratory disturbance index (RDI) was 60.3 +/- 5.7 events/h (mean +/- SEM) on the diagnostic night. RDI was lower with manual titration (10.1 +/- 3.0, p < 0.001), and lower still with Autoset (2.8 +/- 0.9, p < 0.01) and fixed pressure (2.5 +/- 0.7, p = ns versus AutoSet) nCPAP. There were similar changes in the arousal index, which was 52.7 +/- 4.6 events/h on the diagnostic night, 14.2 +/- 2.4 with manual titration and 8.9 +/- 0.9 with AutoSet titration, and 9.5 +/- 1.0 on the night of conventional fixed-pressure CPAP (p < 0.001 versus diagnostic). We conclude that the AutoSet system is suitable for automated nCPAP pressure titration.
The plasma level of fibrinogen is felt to be an independent risk factor for vascular events. Obstructive sleep apnea (OSA) has a high prevalence in patients with stroke and may also be an independent risk factor. The aim of our study was to determine the association between OSA and plasma levels of fibrinogen in patients with stroke. Polysomnography was performed during neurological rehabilitation in 113 patients (82 men, 31 women, age 58 +/- 11.1 yr, mean +/- SD) with ischemic stroke. OSA was absent (RDI < 5) in 44 patients, 42 had mild OSA (5 < or = RDI < 20), and 27 had moderate to severe OSA (RDI > or = 20). Parameters of OSA (respiratory disturbance index [RDI], oxygen indices) were correlated to plasma levels of fibrinogen, measured in the morning after admission to rehabilitation. Fibrinogen was positively correlated with RDI (r = 0.24, p = 0.007), duration of the longest apnea (r = 0.18, p = 0.049), and negatively correlated with several oxygen indices including average minimal oxygen saturation (r = -0.41, p < 0.001). Correlation coefficients were slightly higher when excluding patients with stroke of presumed cardiac origin. Multiple linear regression identified minimal mean oxygen saturation and sex as independent predictors of fibrinogen level. The correlation between severity of coexisting OSA and fibrinogen level in patients with stroke suggests a possible pathophysiological mechanism for an increased risk of stroke in patients with OSA.
Sleep-disordered breathing (SDB) in the form of obstructive sleep apnea is a possible risk factor for stroke. We carried out a cross-sectional survey out in a rehabilitation center among patients with first-ever stroke to further determine the incidence and types of SDB and its relationship to known risk factors for stroke. Full polysomnography was performed in 147 consecutive patients (95 men, 52 women, age 61+/-10 years) admitted to our neurological Rehabilitation Department 46+/-20 days after first-ever stroke. Subjective sleepiness (Epworth Sleepiness Scale), vascular risk factors, anthropometric data, and polysomnographic findings were compared between stroke patients with varying degrees of SDB. With a cutoff point for the respiratory disturbance index (RDI) of 5, 10, 15, or 20 the respective prevalence of SDB was 61%, 44%, 32%, and 22%. The type of SDB was generally obstructive, with dominant central apneas in only 6% of patients. Patients with an RDI of 20 or higher had less REM sleep, thicker necks, and a more central type of obesity. Even in patients with an RDI of 20 or higher subjective sleepiness, although higher than in those without SDB, was not a predominant symptom. Snoring and anthropometric data suggest that obstructive SDB may have existed prior to stroke. The prevalence of hypertension and coronary heart disease were higher among stroke patients with an RDI of 20 or higher than in those without SDB. We conclude that the prevalence of SDB among patients with stroke is high. Examination of stroke should include screening for SDB.
Vital capacity correlates with respiratory muscle function in AMD. Diaphragm weakness is the major cause of SDB and RF. SDB and nocturnal hypoventilation are predictable from daytime function tests.
PCI at a moderate dose reduced brain metastases in LAD-NSCLC to a clinically significant extent, comparable to that in limited-disease small-cell lung cancer. Late toxicity to normal brain was acceptable. This study supports the use of PCI within intense protocols for LAD-NSCLC, particularly in patients with favorable prognostic factors.
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