睡眠呼吸障碍对慢性心力衰竭的影响

睡眠呼吸障碍在慢性心力衰竭中的发病率远高于普通人群，睡眠呼吸障碍对慢性心力衰竭的转归有相当重要的影响。正确认识两者的关系，并给予恰当的处理有着十分重要的意义。     

Short-term effects of cardiac resynchronization therapy on sleep-disordered breathing in patients with systolic heart failure

OBJECTIVES: We evaluated the short-term effect of cardiac resynchronization therapy (CRT) on sleep apnea in patients with systolic heart failure. BACKGROUND: Sleep-disordered breathing is common in patients with left ventricular systolic dysfunction. METHODS: Twelve patients (mean [+/-SE] age, 59.6+/-7.8 years; mean left ventricular ejection fraction, 28.0+/-2.8%) with an implanted atrial-synchronized biventricular pacemaker for the treatment of left ventricular systolic dysfunction were selected and studied. Each subject underwent polysomnography on 3 consecutive nights with CRT on the first night, CRT off the second night, and CRT on the third night. Echocardiography was performed prior to each polysomnogram. RESULTS: The central sleep event index (ie, the number of central sleep apneas [CSAs] and hypopneas per hour of sleep) score was lower with CRT compared to that without CRT (mean central sleep event index score with CRT on, 6.9+/-1.7 events per hour of sleep; mean central sleep event index score with CRT off, 14.3+/-2.9 events per hour of sleep; mean central sleep event index score with CRT on, 8.1+/-1.5 events per hour of sleep; p<0.001). Similarly, the cumulative duration of central sleep events (the number of minutes per hour of sleep during CRT) was one half that observed without CRT (CRT on, 2.8+/-0.7 min per hour of sleep; CRT OFF 6.2+/-1.2 min per hour of sleep; CRT ON 3.1+/-0.7 min per hour of sleep; p<0.001). There was a significant correlation between mitral regurgitant volume and central sleep event index on all three nights (r>or=0.77; p<0.01). CONCLUSIONS: CRT reduces CSA severity in the short term. This reduction correlated significantly with the CRT-mediated reduction of mitral regurgitation.     

Advances in the management of sleep-disordered breathing in heart failure

Obstructive (OSA) and central sleep apnea (CSA) are very common in patients with congestive heart failure (CHF). This is clearly a risk factor for worsening the prognosis of patients. Treatment of sleep apnea in these patients may stop disease progression. Modern therapy, primarily central sleep apnea, is provided by adaptive servoventilation (ASV). Short-term randomized trials have demonstrated that treatment with ASV increased ejection fraction (EF), reduces sympathetic activity and blood pressure. Unfortunately, there is not enough data on whether there are effects on mortality and morbidity. Studies of this issue, such as SERVE-HF and ADVENT-HF, are currently in progress and results are expected. There are other forms of therapy of OSA like CPAP, oxygen, theophylline, acetazolamide, heart synchronisation therapy and transplantation. In patients with a predominance of OSA, in addition to previous methods, there are other recommended forms of therapy like appropriate weight loss, orthodontic appliances and surgical treatment.     

Hypotensive effects of positive airway pressure ventilation in heart failure patients with sleep-disordered breathing

Introduction

Obstructive sleep apnoea (OSA) as well as central sleep apnoea (CSA) are highly prevalent in heart failure (HF) patients. Positive airway pressure (PAP) therapy is usually intended to treat OSA and CSA. The aim of the present study was to investigate immediate hemodynamic effects of PAP therapy in these patients.

Materials and methods

In 61 consecutive HF patients (NYHA????II, EF????45%) with moderate to severe OSA or CSA (AHI????15/h) blood pressure (BP) and heart rate (HR) response to PAP therapy initiation was investigated during mask fitting with patients being awake and in supine position. While applying an endexspiratory pressure of 5.8?±?0.9?cm H₂O, there was a significant decrease in systolic (?8.9?±?12.1?mmHg, p?p?p?=?n.s.).

Results

At least a transient drop in mean arterial pressure ??70?mmHg was seen in 10% of these patients. Logistic regression analysis revealed a significant impact of baseline BP on potential BP drops: lower baseline BP was associated with BP drops.

Conclusion

PAP therapy may cause unexpected hypotension especially in patients with low baseline BP as seen in HF patients treated according to current guidelines. Whether these hypotensive effects sustain, cause any harm to the patients and/or is responsible for non-acceptance or non-adherence of PAP therapy needs to be determined.     

Classification of sleep-disordered breathing

Increasing recognition of sleep-disordered breathing (SDB) and its morbidity have prompted reevaluation of techniques to identify respiratory events during sleep. The present study was designed to evaluate the utility of various metrics of SDB and to identify the optimal respiratory metric that objectively correlates to symptoms of excessive daytime somnolence (EDS). Metrics were derived from combinations of conventional apnea/hypopnea, flow limitation events (transient elevated upper airway resistance identified by characteristic flattening on the flow/time tracing, using a noninvasive nasal cannula technique), desaturation, and arousal. A total of 137 subjects underwent clinical evaluation and nocturnal polysomnogram. In 34 randomly selected subjects, the best metrics for discriminating between 13 subjects with no EDS/snoring and 21 patients with EDS and snoring were identified by receiver operator curve analysis. Of the metrics and cut points tested, a total respiratory disturbance index (RDI(Total), sum of apneas, hypopnea, and flow limitation events) of 18 events/h was found to have the best discriminant ability (100% sensitivity and 96% specificity). Prospective testing of this metric was then performed with the remaining 103 subjects (14 nonsnoring non-EDS, 21 snoring non-EDS, 68 snoring with EDS). Using this cutoff of 18 events/h, we obtained 71% sensitivity and 60% specificity for identifying subjects with EDS. We conclude that, in subjects with upper airway dysfunction, an index that incorporates all respiratory events provides the best quantitative physiological correlate to EDS.     

Multi-modal ECG Holter system for sleep-disordered breathing screening

Background

The high prevalence of sleep disordered breathing (SDB) among heart diseases patients becomes increasingly recognized. A reliable exploring tool of SDB well adapted to cardiologists practice would be very useful for the management of these patients.

Methods

We assessed a novel multi-modal electrocardiogram (ECG) Holter which incorporated both thoracic impedance and pulse oximetry signals. We compared in a home setting, a standard condition for Holter recordings, results from the novel device to a classical ambulatory polygraph in subjects with suspected SDB. The analysis of cardiac arrhythmias in relationship with SDB is also presented. A total of 118 patients clinically suspected of having SDB were evaluated (mean age 57?±?14?years, mean body mass index [BMI] 32?±?6?kg/m²). The new device allows calculating a new index called thoracic impedance (TI) disturbance index (TIDI+) evaluated from TI and SpO₂ signals recorded from a Holter monitor.

Results

In the population under study, 93% had more than 70% of usable TI signal and 95% had more than 90% for SpO₂ during sleep time recording. Screening performance results based on automatic analysis is accurate: TIDI?+?demonstrates a high level of sensitivity (96.8%), specificity (72.3%) as well as positive (82.4%) and negative (94.4%) predictive value for the detection of SDB. Moreover, detection of SDB periods permits us to observe a possible respiratory association of several nocturnal arrhythmias.

Conclusions

The multi-modal Holter should be considered as a valuable evaluating tool for SDB screening and as a case selection technique for facilitating access to a full polysomnography for severe cases. Moreover, it offers a unique opportunity to study arrhythmia consequences with both respiratory and hypoxia disturbances.     

Genomics of sleep-disordered breathing

The technologies of genomics and proteomics are powerful tools for discovering novel gene and protein expression responses to disease. Considerable evidence indicates that a genetic basis exists to the causes of sleep-disordered breathing, in particular its most common form of obstructive sleep apnea (OSA), which is characterized by periods of intermittent hypoxia and disrupted sleep. However, the genetic contribution to the pathogenesis of OSA has largely been determined using traditional genetic approaches of family, twin, and linkage studies in clinical populations and quantitative trait loci and targeted gene procedures in animal models of OSA. In contrast to the pathogenesis of OSA, the consequences or sequelae of OSA are highly amenable to genomic and proteomic approaches. Animal studies have assessed changes in gene and protein expression in multiple organ systems in response to intermittent hypoxia and sleep deprivation and uncovered novel gene activation paradigms. The first tentative steps have been made toward applying proteomic analyses of blood and urine from patients with OSA as a potential screening tool for diagnosis in the clinical setting. It is anticipated that genomic and proteomic technologies will become increasingly used in the area of OSA with the unprecedented access to tissue in procedures such as bariatric surgery. OSA represents a severe insult to the oxygenation of tissues and the homeostasis of sleep, and genomic and proteomic approaches hold promise for defining previously unexplored mechanisms and pathways that lead to downstream pathologies, including hypertension, insulin resistance, and neurocognitive dysfunction.     

Cardiovascular diseases and sleep-disordered breathing

About 1.9 % of the population suffer from an obstructive sleep apnea syndrome (OSAS). At the age of between 30 and 60 years it occurs in 3 %. Patients with OSAS develop more frequently such disorders as arteriosclerosis, cardiac arrhythmias and arterial hypertension. A host of pathophysiological changes can be diagnosed. The elevated sympathic activity, recurrent hypoxemias, stress, disturbances in the microvascular milieu, endothelial dysfunction, elevated oxidative capacity as well as a reduced vascular reagibility are deemed to be factors connected to arteriosclerosis. Different biochemical markers, which are seen as risk factors or as markers of cardiovascular diseases, are altered in patients with OSAS (high-sensitive CRP, Interleukin(IL)-6, IL-8, IL-10, TNF-alpha, VGEF, ICAM-1, VCAM-1 and L-Selectin). Patients with OSAS exhibit signs of an impaired insulin sensitivity. Disturbances in microcirculation are also evident. Patients with OSAS have, compared to patients without sleep apnea, elevated blood pressure measurements, even given other common risk factors. The incidence of coronary heart diseases is increased in patients with OSAS. Morbidity and mortality, especially of arteriosclerotic diseases are elevated. Many of the aforementioned disturbances can be improved by a CPAP-therapy.     

Autonomic abnormalities in congestive heart failure patients with sleep-disordered breathing

BackgroundThe increasing prevalence of chronic heart failure is affecting patients' longevity, quality of life, and health resources, despite advances in management. Recognizing and treating comorbid illnesses is critical. Risk factors such as hypertension and diabetes are treated, but less importance is placed on the role of sleep apnea in heart failure.Methods and ResultsThere is a discrepancy between the growing evidence on the potential adverse influence of sleep apnea on heart failure (and vice versa) and incorporating its treatment as part of the management strategy for chronic heart failure. Apneic episodes during sleep can lead to profound disturbances to the sympathetic and parasympathetic nervous system.ConclusionsThis review explores the impact of sleep disordered breathing in patients with chronic heart failure, focusing on the autonomic nervous system.     

Atrial fibrillation and sleep-disordered breathing

Atrial fibrillation (AF) is a common supraventricular arrhythmia that increases in prevalence with increasing age and in the presence of comorbidities such as heart failure (HF). AF increases the risk of a number of serious complications, including stroke and HF. As a result, the rate of hospitalization is high, making AF a costly disease. Treatment strategies for AF are broadly based around rate and rhythm control, either pharmacological or mechanical. There appear to be a number of links between sleep-disordered breathing (SDB) and AF, although further studies are needed to fully understand the physiological mechanisms that link these conditions. Patients with AF and SDB share a number of risk factors and comorbidities, including age, male sex, hypertension, congestive HF and coronary artery disease (CAD), and the prevalence of SDB in AF is higher than in the general population. Prevalence rates of obstructive sleep apnea (OSA) in patients with AF have been reported to range from 21% to just over 80%. The prevalence of central sleep apnea (CSA) in patients with AF is less well defined, but appears to be particularly high in patients who also have HF and a reduced left ventricular ejection fraction (LVEF). The frequency of apneas can be reduced by effective treatment of AF, while co-existing OSA reduces the effectiveness of treatments for AF and there is an increased risk of arrhythmia recurrence in the presence of SDB. Treating OSA with continuous positive airway pressure (CPAP) therapy has shown the potential to decrease the incidence of AF, improve the effectiveness of AF interventions, and decrease the risk of arrhythmia recurrence, although data from large randomized, controlled clinical trials are lacking. Based on available data, inclusion of SDB recognition and management strategies as part of AF management appears to have the potential to reduce the impact of this arrhythmia at both the individual and societal levels, and has been recognized as important in recent guidelines.     

Cerebrovascular diseases and sleep-disordered breathing

Sleep-disordered breathing (SDB) is more probably the cause rather than the consequence of stroke because: apneas are essentially obstructive rather than central, the frequency of SDB is not different between transient ischemic attack and cerebral infarction; and previous excessive daytime sleepiness is significantly more frequent among stroke patients with SDB than those without. The presence of SDB in stroke patients could lead to a poor outcome. Pathophysiological relationships between strokes and SDB are multiple. Experimental and clinical studies have shown that both short- and long-term factors may play a role in increasing the susceptibility to stroke in patients with obstructive sleep apnea syndrome. The former include changes in cerebral hemodynamics, hematologic alterations, and cardiocirculatory dysfunctions that typically and repeatedly occur during apnea episodes and also may persist during wakefulness. Regarding long-term factors, some changes in the anatomical characteristics of carotid arteries wall have been recognized in SDB patients. This finding seems to suggest that the link between SDB and cerebrovascular disease might be explained, at least in part, by an increase in the progression of the atherosclerosis process involving cerebral vessels. There are several practical implications from the demonstrated significant role of sleep apnea in increasing the predisposition to developing stroke. Specific investigation is fundamental in the presence of a clinical suspect of SDB, especially in patients with history of transient ischemic attacks and stroke. Specific treatment of SDB may reduce the possibility of further cerebrovascular disturbances.     

Association of sleep-disordered breathing and ventricular arrhythmias in patients without heart failure

The prevalence and characteristics of sleep-disordered breathing (SDB) in patients with ventricular arrhythmias, such as premature ventricular complexes and ventricular tachycardia, are unknown. Therefore, this study was conducted to evaluate the prevalence of SDB in patients with severe ventricular arrhythmias and normal left ventricular (LV) function. Thirty-five patients (63% men, mean age 57.4 +/- 13.8 years) underwent a sleep study. All patients had ventricular tachycardia or frequent premature ventricular complexes (>or=300/hour) and had been referred to the cardiology department for medication, catheter ablation therapy, or the implantation of a cardioverter-defibrillator. Patients with heart failure with LV ejection fractions <50% were excluded; in the remaining patients, the mean LV ejection fraction was 63.9 +/- 8.0%. Twenty-one patients (60%) had SDB with apnea-hypopnea indexes >or=5/hour, and the average apnea-hypopnea index was 22.7 +/- 17.9/hour. Twelve patients (34%) had moderate to severe SDB, with an average apnea-hypopnea index of 33.6 +/- 16.6/hour. Central dominant sleep apnea was evident in 3 patients with SDB. The average age and body mass index were significantly higher in patients with SDB than in those without SDB (age 62.0 +/- 12.8 vs 50.6 +/- 12.7 years, body mass index 26.3 +/- 4.0 vs 21.2 +/- 2.0 kg/m2). In conclusion, this study found a high prevalence of SDB in patients with ventricular arrhythmias and normal LV function.     

Obstructive sleep-disordered breathing and plasma levels of vascular endothelial growth factor in children

Vascular endothelial growth factor (VEGF) may be one of the pathophysiologic links in the association between obstructive sleep apnea-hypopnea and cardiovascular disease. Morning serum VEGF levels are increased in children with obstructive sleep apnea. However, release of VEGF by platelets and leukocytes during blood clotting may affect its concentration in serum. In the present study, VEGF levels were measured in children with and without habitual snoring using plasma specimens. Evening and morning plasma VEGF concentrations were determined in: (i) 20 children with habitual snoring and apnea-hypopnea index (AHI)5 episodes/h (median age 5; range 1.9-13 years); (ii) 55 children with snoring and AHI<5 episodes/h (median age 6; 2-13 years); and (iii) 25 controls without snoring (median age 6.5; 3-13 years). No differences were identified between the three study groups regarding evening [median 2.5 (range 2.5-174.5) versus 22.5 (2.5-159.4) versus 26.8 (2.5-108) pg/mL; P>0.05] and morning VEGF levels [median 7.7 (range 2.5-120.5) versus 25.1 (2.5-198.4) versus 48.4 (2.5-147.7) pg/mL; P>0.05]. AHI and % sleep time with oxygen saturation of hemoglobin less than 90% were not significant predictors of log-transformed morning VEGF concentrations (P>0.05). In summary, both evening and morning plasma VEGF levels were similar in children with obstructive sleep-disordered breathing of variable severity and in controls without snoring. VEGF may not play an important pathophysiologic role in all cases of obstructive sleep-disordered breathing in childhood.     

Epidemiology and pathogenesis of sleep-disordered breathing

Sleep-disordered breathing is common in the general population, but the observed prevalence depends on the criteria used to establish the diagnosis. Obesity is a strong risk factor, but other conditions such as allergic upper and lower airways disease may also be important. Differences in risk between the sexes and ethnic groups appear to be present even after established risk factors have been considered. The pathogenesis is likely mutifactorial with anatomic and physiologic factors of varying importance in different individuals. The natural history is uncertain, but without treatment or reduction in risk factors, some progression is likely. Ongoing epidemiologic investigations such as the Sleep Heart Health Study are beginning to provide important information on these questions.     

Association of hypertension and sleep-disordered breathing

BACKGROUND: To our knowledge, the association between sleep-disordered breathing (SDB) and hypertension has not been evaluated in subjects from the general population with a wide age range while adjusting for the possible confounding factors of age, body mass index, sex, menopause and use of hormone replacement therapy, race, alcohol use, and smoking. METHODS: In the first phase of this study, we interviewed 4364 men and 12,219 women, aged 20 to 100 years. In the second phase of this study, 741 men and 1000 women, previously interviewed, were selected based on the presence of risk factors for SDB (snoring, daytime sleepiness, obesity, hypertension, and, for women, menopause). Each subject selected for the second phase of the study provided a comprehensive history, underwent a physical examination, and was evaluated for 1 night in the sleep laboratory. In terms of severity of SDB, 4 groups were identified: moderate or severe (obstructive apnea/hypopnea index > or =15.0), mild (snoring and an obstructive apnea/hypopnea index of 0.1-14.9), snoring, and no SDB, the control group. RESULTS: Sleep-disordered breathing was independently associated with hypertension when potential confounders were controlled for in the logistic regression analysis. The strength of this association decreased with age and was proportional to the severity of SDB. In the best-fitted model, neither sex nor menopause changed the relationship between hypertension and SDB. CONCLUSIONS: In the results of this study, SDB, even snoring, was independently associated with hypertension in both men and women. This relationship was strongest in young subjects, especially those of normal weight, a finding that is consistent with previous findings that SDB is more severe in young individuals.