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.     

Periodicity of obstructive sleep apnea in patients with and without heart failure

STUDY OBJECTIVE: To determine whether the duration of the apnea-hyperpnea cycle is longer in patients with congestive heart failure (CHF) and obstructive sleep apnea (OSA) than in patients with OSA alone, and whether this is related to prolonged circulation time. DESIGN: Retrospective study. SETTING: Sleep laboratory of a university teaching hospital.Patients and intervention: Male patients with OSA and CHF (n = 22) or without CHF (n = 18) underwent overnight polysomnography. MEASUREMENTS AND RESULTS: Hyperpnea duration, time to peak tidal volume (Vt), and lung-to-ear circulation time (LECT) were measured in all patients. Compared to the non-CHF patients, those with CHF had significantly longer hyperpneas (25.7 +/- 7.8 s vs 17.6 +/- 5.6 s, p < 0.001) and LECT (14.9 +/- 3.4 s vs 9.0 +/- 1.8 s, p < 0.001) [mean +/- SD]. There was also a significant relationship between LECT and hyperpnea duration (r = 0.67, p < 0.001). CONCLUSION: In patients with CHF, prolonged lung-to-chemoreceptor circulation time influences the cycling characteristics of OSA such that it prolongs hyperpnea and sculpts a pattern resembling Cheyne-Stokes respiration. These findings further suggest that the increased tendency to periodic breathing in CHF may predispose to, or alter the physiologic manifestations of OSA.     

Central sleep apnea in patients with congestive heart failure

Central apnea during sleep represents a manifestation of breathing instability in many clinical conditions of varied etiologies. Central apnea is the result of transient cessation of ventilatory motor output, which represents that inhibitory influences favoring instability predominate over excitatory influence favoring stable breathing. This article will review the determinants of central apnea, the specific features of CHF-related central apnea, and outline a management approach     

Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea

Sympathetic activation and sleep apnea are present in most patients with symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with normal systolic function, this increase persists after waking. Whether coexisting sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that its presence exerts additive effects on MSNA during wakefulness. Overnight sleep studies and morning MSNA recordings were performed on 60 subjects with ejection fraction <45%. Of these, 43 had an apnea-hypopnea index > or =15 per hour. Subjects with and subjects without sleep apnea were similar for age, ejection fraction, HF etiology, body mass index, blood pressure, and heart rate. Daytime MSNA was significantly higher in those with sleep apnea (76+/-2 versus 63+/-4 bursts per 100 heartbeats [mean+/-SEM], P=0.005; 58+/-2 versus 50+/-3 bursts/min, P=0.037), irrespective of its etiology (the mean difference for central sleep apnea was 17 bursts per 100 heartbeats; n=14; P=0.006; and for obstructive sleep apnea, 11 bursts per 100 heartbeats; n=29; P=0.032). In a subgroup (n=8), treatment of obstructive sleep apnea lowered MSNA by 12 bursts per 100 heartbeats (P=0.003). Convergence of independent excitatory influences of HF and sleep apnea on central sympathetic neurons results in higher MSNA during wakefulness in HF patients with coexisting sleep apnea. This additional stimulus to central sympathetic outflow may accelerate the progression of HF; its attenuation by treatment of sleep apnea represents a novel nonpharmacological opportunity.     

Central sleep apnea is a predictor of cardiac readmission in hospitalized patients with systolic heart failure

BackgroundHospitalized heart failure patients have a high readmission rate. We sought to determine the independent risk due to central sleep apnea (CSA) of readmission in patients with systolic heart failure (SHF).Methods and ResultsThis was a prospective observational cohort study of hospitalized patients with SHF. Patients underwent sleep studies during their hospitalization and were followed for 6 months to determine their rate of cardiac readmissions; 784 consecutive patients were included; 165 patients had CSA and 139 had no sleep-disordered breathing (SDB); the remainder had obstructive sleep apnea (OSA). The rate ratio for 6 months' cardiac readmissions was 1.53 (95% confidence interval 1.1–2.2; P = .03) in CSA patients compared with no SDB. This rate ratio was adjusted for systolic function, type of cardiomyopathy, age, weight, sex, diabetes, coronary disease, length of stay, admission sodium, creatinine, hemoglobin, blood pressure, and discharge medications. Severe OSA was also an independent predictor of readmissions with an adjusted rate ratio of 1.49 (P = .04).ConclusionIn this first evaluation of the impact of SDB on cardiac readmissions in heart failure, CSA was an independent risk factor for 6 months' cardiac readmissions. The effect size of CSA exceeded that of all known predictors of heart failure readmissions.     

Hypoglycaemia in hospitalized patients with or without heart failure

Hospitalized patients with heart failure (HF) undergoing bedside glucose monitoring with subcutaneous insulin orders were retrospectively identified over 2 years. Hypoglycaemia was defined as any glucose value <3.9 mmol/L (70 mg/dL) within 24 hours of admission (Hypo_1day) or throughout the hospitalization (Hypo_T) or any glucose value <2.2 mmol/L (40 mg/dL) throughout the hospitalization (Hypo_Severe). A total of 13 424 patients were included, of whom 2484 had HF. Patients with HF were more likely to have Hypo_1day (9.1% vs 7.0%, P = .0003), Hypo_T (28% vs 18.5%, P < .0001), or Hypo _Severe (3.4% vs 2.1%, P = .0001). After controlling for other variables, the odds of Hypo_1day were similar between the HF and non‐HF groups (odds ratio [OR] 1.14, 95% CI 0.94‐1.39, P = .18, fully adjusted model), slightly lower for Hypo_T (OR 0.85, 95% CI 0.73‐0.99, P = .03, fully adjusted model), and similar for Hypo_Severe (OR 1.25, 95% CI 0.91‐1.70, P = .17). Hypo_1day, Hypo_T and Hypo_Severe were all associated with increased mortality; there was no evidence of an interaction by HF status. Hypoglycaemia occurred at a similar or lower frequency in hospitalized patients with HF compared to those without HF. Hypoglycaemia was associated with increased hospital mortality, regardless of HF status.     

Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea

OBJECTIVES: To determine the acute effects of continuous positive airway pressure (CPAP) on baroreceptor reflex sensitivity (BRS) for heart rate during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). DESIGN AND METHODS: In eight CHF patients with OSA not previously treated with CPAP, spontaneous BRS was assessed during overnight polysomnography prior to the onset of sleep, and during stage 2 non-rapid eye movement sleep (NREM) before, during and after application of CPAP. RESULTS: CPAP alleviated OSA and acutely increased the slope of BRS (median, 25%,75%) [from 3.9 (3.5, 4.8) to 6.2 (4.6, 26.2) ms/mmHg, P<0.05]. Increases in the slope of BRS persisted following withdrawal of CPAP [4.9 (4.3, 6.9) ms/mmHg, P<0.05]. CPAP also lowered heart rate (from 81.3 +/- 4.9 to 76.0 +/- 5.7 bpm, P< 0.05), an effect which persisted after its withdrawal (76.7 +/- 5.7 bpm, P < 0.05). Systolic blood pressure at the midpoint of the pressure range of BRS sequences fell while on CPAP (from 139 +/- 8 to 120 +/- 7 mmHg, P < 0.05), and remained lower following CPAP withdrawal (124 +/- 9 mmHg, P < 0.05). CONCLUSIONS: In CHF patients with OSA, CPAP increases acutely BRS during sleep, lowers heart rate and resets the operating point for BRS to a lower blood pressure. These effects of CPAP persist after its withdrawal, suggesting that nocturnal CPAP therapy may cause sustained improvement in the neural control of heart rate.     

Effects of nocturnal oxygen therapy in patients with chronic heart failure and central sleep apnea: CHF-HOT study

It was previously reported that nocturnal home oxygen therapy (HOT) significantly improved not only sleep disordered breathing (SDB), but also quality of life (QOL) and left ventricular ejection fraction (LVEF) in two trials. To strengthen the statistical reliability of the above efficacies of HOT and to assess the effects of 12-week nocturnal HOT on suppression of ventricular arrhythmias, we combined the two trials and undertook a post hoc analysis. Ninety-seven patients with chronic heart failure (CHF) and central sleep apnea were assigned to receive HOT (45 patients) or not (52 patients). HOT resulted in greater reduction in the apnea–hypopnea index (AHI) (?11.4 ± 11.0 vs. ?0.2 ± 7.6 events/h, p < 0.01), which is associated with greater improvement in the Specific Activity Scale (0.8 ± 1.2 vs. 0.0 ± 0.6, p < 0.01), New York Heart Association (NYHA) functional class (p < 0.01), and LVEF (p = 0.06). Median number of premature ventricular contraction (PVC) at baseline was 17 beats per hour in both the HOT and the control groups. Overall improvements of PVCs were not different either in the HOT group or in the control. However, in 12 patients with NYHA >III and AHI >20 events/h, PVC was significantly improved by HOT with a marked reduction in AHI and a substantial increase in LVEF. In conclusion, among patients with CHF and CSA, HOT improves SDB, QOL, and cardiac function. The effectiveness of HOT for ventricular arrhythmias was not observed in the overall analysis, but only in a limited number of patients with severe CHF and SDB. To clarify the effects of HOT on ventricular arrhythmias in patients with CHF and SDB, a further study is needed.     

Effectiveness of short-term treatment with nocturnal oxygen therapy for central sleep apnea in patients with congestive heart failure

OBJECTIVES. To evaluate the short term effects of inhalation of oxygen at night in 51 patients with congestive heart failure (CHF) and sleep apnea syndrome (SAS). METHODS. Fifty-one patients with stable CHF (31 males, 20 females, mean age 79.0 +/- 11.9 years; brain natriuretic peptide level of > 100 pg/ml) were evaluated between September 2003 and August 2004, using a Morpheus monitor. The complication rate of SAS in patients with CHF was assessed and apnea hypopnea index, oxygen desaturation index 3%, heart rate, and autonomic nerve activity under room air compared to supplemental O2 (2 l/min) over two consecutive nights. RESULTS. Thirty-eight (75%)of the CHF patients had SAS. Of these SAS patients, 49% suffered from central SAS and 51% had obstructive SAS. Apnea hypopnea index and oxygen desaturation index 3% improved remarkably with supplemental oxygen (p < 0.001), in particular, the central SAS group demonstrated prominent improvement (p < 0.001). Obstructive SAS patients exhibited no significant changes (p = 0.3356), but tended to exacerbate the episodes of sleep apnea. Total heart rate was decreased (p = 0.0079). Nevertheless, heart rate variability analysis showed little effect of nocturnal oxygen therapy on the autonomic nervous system during sleeping. CONCLUSIONS. Nocturnal oxygen therapy improved the number of sleep apnea episodes and decreased total heart rate during sleep time for the CHF patients with central SAS, despite little influence on the autonomic nervous system, based upon assessment of heart rate variability. Obstructive SAS might exacerbate the episodes of sleep apnea.     

Measurement of dyspnea in patients with obstructive sleep apnea

Purpose

Patients with obstructive sleep apnea (OSA) frequently complain of exertional dyspnea. We aimed to assess its related factors and the significance of its measurement in OSA.

Methods

We evaluated 301 subjects with suspected OSA for dyspnea during activities of daily living using the Medical Research Council (MRC) scale. We analyzed the relationships between MRC grades and various subjective and objective indices. Further, the relationship of disease severity based on the apnea/hypopnea index (AHI) with these indices was examined. Results were compared between those obtained using MRC grades and the AHI.

Results

Of 301 subjects, 265 were diagnosed with OSA. Their MRC scores were worse than in non-OSA patients. Among OSA patients, 125 had MRC grade 1 (mild), 121 had MRC grade 2 (moderate), and 19 had MRC grade 3 or more (severe) dyspnea. Various measurements differed significantly between groups categorized according to the MRC scale although determinants between mild and moderate groups and between moderate and severe groups differed. AHI categorizations were not significantly related to patient-reported measurements such as the Medical Outcomes Study 36-item short form, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale scores, unlike categorization based on the MRC scale.

Conclusions

Dyspnea is an important outcome in OSA although dyspnea in OSA patients is unrelated to the sleep disorder per se. Measurement of dyspnea in patients with OSA might provide further insights into the health of these patients and clinical manifestations of this disease.     

阻塞性睡眠呼吸暂停综合征老年患者血管内皮功能变化及其与冠心病的关系

目的　探讨老年阻塞性睡眠呼吸暂停综合征 (OSAS)患者血管内皮功能变化与冠心病 (CHD)的内在联系。方法　随机选择 31例无OSAS、无心血管疾病的老年单纯鼾症者为对照组 ,4 5例老年中、重度OSAS患者为OSAS组 ,OSAS组内又分为有CHD(16例 )和无CHD(2 9例 )两个亚组。测定和比较组间的血浆一氧化氮 (NO)、内皮素 (ET)及其比值的动态变化及OSAS组内CHD有无的区别。结果　与对照组相比 ,OSAS组患者的NO水平明显降低〔(2 7.6 9± 9.17)vs(6 1.90± 13.4 7) μmol/L〕 ,ET水平明显增高〔(5 8.0 8± 14 .2 1)vs (34.77± 8.2 3)ng/L〕 ,NO/ET比值明显下降〔(0 .4 7± 0 .18)vs (1.72± 0 .97) ,均P <0 .0 1)〕。CHD的发生率在OSAS组达 35 .6 %。与对照组相比 ,OSAS组中不伴CHD者降低的NO水平 (35 .5 3± 9.39) μmol/L、升高的ET水平 (47.78± 11.13)ng/L和下降的NO/ET比值 (0 .75± 0 .13)已有显著性差异 (P <0 .0 5 ) ;伴有CHD者的NO水平 (2 2 .17± 8.76 )μmol/L、ET水平 (6 9.14± 12 .17)ng/L和NO/ET比值 (0 .32± 0 .14 )较对照组相差更为明显 (P <0 .0 1)。结论　OSAS老年患者存在明显的血管内皮功能障碍 ,尤以CHD者为甚 ,血管内皮功能损伤可能是OSAS患者并发CHD的原因     

Sleepiness and sleep in patients with both systolic heart failure and obstructive sleep apnea

BACKGROUND: Adverse effects of obstructive sleep apnea (OSA), including sleep deprivation, can contribute to the progression of heart failure. The usual indication to diagnose and treat sleep apnea is subjective sleepiness. Previous studies suggest that patients with both heart failure and obstructive sleep apnea often do not complain of sleepiness, albeit their sleep time may be reduced. Therefore, we tested the hypothesis that patients with heart failure have less sleepiness and sleep less compared with subjects without heart failure for a given severity of OSA. METHODS: Sleepiness assessed with the Epworth Sleepiness Scale and sleep structure measured with polysomnography were compared among 155 consecutive patients with heart failure and from a random community sample (n = 1139) according to categories of the apnea-hypopnea index (<5, no OSA; 5-14, mild OSA; and > or =15, moderate to severe OSA). RESULTS: Compared with the community sample, for any given severity of OSA, patients with heart failure had lower mean +/- SE Epworth Sleepiness Scale scores (7.1 +/- 0.4 vs 8.3 +/- 0.2 [P = .005]; 6.7 +/- 0.7 vs 9.2 +/- 0.3 [P < .001]; and 7.8 +/- 0.7 vs 9.8 +/- 0.4 [P = .01]), indicating less sleepiness despite sleeping less (total sleep time mean +/- SE [in minutes]: 306 +/- 7 vs 384 +/- 2, 295 +/- 19 vs 384 +/- 5, and 285 +/- 13 vs 359 +/- 7 for no, mild, and moderate to severe OSA, respectively; P < .001 for all comparisons). CONCLUSIONS: Patients with heart failure have less subjective daytime sleepiness compared with individuals from a community sample, despite significantly reduced sleep time, whether or not they have OSA. In patients with heart failure, the absence of subjective sleepiness is not a reliable means of ruling out OSA.     

Obstructive sleep apnea presenting with nocturnal angina, heart failure, and near-miss sudden death

An obese woman with a one-year history of episodic nocturnal chest pain was admitted because of shock and pulmonary edema. A clinical diagnosis of acute myocardial infarction and cardiogenic shock was made. She was ventilated and successfully resuscitated. Subsequent investigations showed no evidence of cardiac dysfunction or coronary disease, but sleep study confirmed the diagnosis of obstructive sleep apnea syndrome (OSAS). We suggest that the nocturnal angina and heart failure in this patient might have resulted from extreme hypoxemia produced by OSAS. This case raised the possibility that the high cardiovascular mortality rate reported in OSAS might not necessarily relate to underlying coronary artery disease. Further investigations are required to delineate the true incidence of coronary disease in patients with OSAS.     

Dissociation between hemodynamic changes and symptom improvement in patients with advanced congestive heart failure

BACKGROUND: Changes in hemodynamic measures often serve as surrogate end points in efficacy trials for advanced heart failure, although there are few objective data to support this practice. AIMS: We compared changes in hemodynamic variables vs. changes in symptoms of decompensated heart failure in patients enrolled in a randomized trial. METHODS: We studied 201 patients with New York Heart Association (NYHA) class IIIb or IV heart failure and ejection fraction < or = 25% for > or = 3 months. Patients underwent continuous monitoring by pulmonary-artery catheter during inpatient drug administration. We assessed the relations of changes in hemodynamic variables (baseline minus final measure) to changes at 2 weeks in congestive heart failure symptoms, NYHA class, Yale Dyspnea-Fatigue Index (YDFI) score, and distance achieved in a 6-min walk. RESULTS: No hemodynamic measure significantly predicted either symptom score or NYHA classification. Mean pulmonary artery pressure and pulmonary capillary wedge pressure did show some relation to change in YDFI score in univariable, but not multivariable, analysis. No hemodynamic measure correlated significantly with changes in distance achieved in the 6-min walk test. CONCLUSION: We noted no significant association between improved hemodynamics and improved symptoms in patients with advanced heart failure. Other measures may need to be evaluated as surrogate end points in future trials.     

阻塞性睡眠呼吸暂停患者残余嗜睡与中枢性睡眠呼吸暂停事件的相关性

目的 探讨阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome,OSAS)患者连续气道正压通气(continuous positive airway pressure,CPAP)治疗后残余嗜睡与中枢性睡眠呼吸暂停(central sleep apnea,CSA)事件的相关性以及匹配伺服通气(adaptive Bervo-ventilation,ASV)对CSA相关残余嗜睡的影响. 方法 选择正规使用CPAP治疗且排除其他嗜睡相关疾病的中、重度OSAS患者50例,分为残余嗜睡组(26例)和无残余嗜睡的对照组(24例).2组患者均先后接受自动CPAP治疗1个月和ASV治疗1周.分别比较2组患者治疗前、自动CPAP治疗时及ASV治疗时睡眠期的中枢性睡眠呼吸暂停指数(central sleep apnea index,CSAI),微觉醒指数(micro-arousal index,MAI)等多导睡眠监测参数及白天Epworth嗜睡评分(ESS),采用酶联免疫吸附试验测定肿瘤坏死因子a(tumor necrosis factor-a,TNF-a).两组间比较采用t检验,组内比较使用单因素方差分析,组内3个阶段两两比较采用q检验,两变量相关分析采用Pearson相关检验. 结果 治疗前2组呼吸暂停低通气指数(apnea hypoapnea index,AHI)、MAI、最低SpO2、ESS评分及血浆TNF-a水平组间比较差异没有统计学意义(t值分别为0.630、1.223、0.691、0.764和0.192,均P>0.05),但残余嗜睡组患者的CSAJ(14.39±4.21)次/h显著高于对照组[(8.58±5.75)次/h,t=4.097,P＜0.05].自动CPAP治疗1个月时2组的AHI、CSM、MAI和ESS评分均明显低于治疗前(g值为0.87～112.55,均P.＜0.05),但残余嗜睡组CSAI、MAI及ESS评分明显高于对照组[CSM:(7.19±1.75)次/h,(3.37±1.04)次/h,t=9.473,P＜O.05;MAI:(9.00±1.95)次/h,(2.36 4-0.66)次/h,f=14.385,P＜0.05;ESS:(9.54 4-0.51)分,(5.42±1.32)分,t=2.857,P＜0.05].ASV治疗时残余嗜睡组与对照组的CSAI、MAI及白天ESS评分均进一步下降,尤以残余嗜睡组的下降更为明显.此外残余嗜睡组内血浆TNF-a水平与治疗前(17.2±3.3)残余嗜睡,μg/L相比,自动CPAP治疗时(16.5 4-3.6)μg/L无明显下降(q值为11.696,P>0.05),但在ASV治疗时(12.6±3.4)μg/L与治疗前相比显著降低(q值为11.696,P＜0.05).血浆TNF-a水平与ESS评分呈显著正线性相关(r=0.503,P＜0.01),与MAI亦呈显著正相关(r=0.545,P＜0.01). 结论 经自动CPAP治疗后OSAS患者的残余嗜睡与治疗前、中存在的CSA事件频率有关.ASV在显著降低CSAI的同时也明显改善了提示ASV可有效治疗OSAS患者的残余嗜睡.TNF-a也与残余嗜睡患者的嗜睡程度相关,可能参与了残余嗜睡的发生.     

Treatment of Cheyne-Stokes respiration-central sleep apnea in patients with heart failure

Sleep disordered breathing including obstructive sleep apnea (OSA) and central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR) is often accompanied by heart failure. Treatment of OSA centered on continuous positive airway pressure (CPAP) is established. However, treatment of CSR-CSA is still controversial. Since CSR-CSA occurs as a consequence of heart failure, optimization of heart failure is essential to treat CSR-CSA. For treatment directed at CSR-CSA itself, a variety of treatment approaches including night oxygen therapy and noninvasive positive pressure ventilation have been applied. Among them, night oxygen therapy improves patients' symptoms, quality of life (QOL), and left ventricular function, but had yet been shown to improve clinical outcome. For CPAP, there are responders and non-responders and for responders CPAP can also improve survival. Adaptive servo-ventilation (ASV), which most effectively treats CSR-CSA, improves exercise capacity, QOL, and cardiac function. Recent reports suggested ASV may also prevent cardiac events in patients with heart failure. However, further studies are needed to conclude that this treatment improves patient survival.