Lateral Sleeping Position Reduces Severity of Central Sleep Apnea / Cheyne- Stokes Respiration

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1 Lateral Sleeping Position Reduces Severity of Central Sleep Apnea / Cheyne- Stokes Respiration Irene Szollosi BSc, ; Teanau Roebuck BAppl Sc ; Bruce Thompson PhD ; Matthew T Naughton MD, Department of Allergy Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia Introduction: The influence of sleeping position on obstructive sleep apnea severity is well established. However, in central sleep apnea with Cheyne Stokes respiration (CSA-CSR) in which respiratory-control instability plays a major pathophysiologic role, the effect of position is less clear. Study Objectives: To examine the influence of position on CSA-CSR severity as well as central and mixed apnea frequency. Methods: Polysomnograms with digitized video surveillance of 0 consecutive patients with heart failure and CSA-CSR were analyzed for total apnea-hypopnea index, mean event duration, and mean oxygen desaturation according to sleep stage and position. Position effects on mixed and central apnea index, mean apnea duration, and mean desaturation were also examined in non-rapid eye movement sleep. Results: Data are presented as mean ± SEM unless otherwise indicated. Group age was 9.9 ±.3 years, and total apnea-hypopnea index was 6.4 ± 3.0 events per hour. Compared with supine position, lateral position reduced the apnea-hypopnea index in all sleep stages (Stage, 4.7 ± 4. events per hour vs 7. ± 4. events per hour [p <.00]; Stage, 43.3 ± 6. events per hour vs 4.4 ± 3.6 events per hour [p <.00]; slowwave sleep,.9 ± 6.4 events per hour vs.4 ±.9 events per hour [p <.0]; rapid eye movement sleep, 38.0 ± 7.3 events per hour vs.0 ± 3.0 events per hour [p <.00]). Lateral position attenuated apnea and hypopnea associated desaturation (supine 4.7% ± 0.3%, lateral 3.0% ± 0.4%; p <.00) with no difference in event duration (supine.7 ±.8 seconds, lateral 6.9 ± 3.4 seconds; p =.9). Mixed apneas were longer than central (9. ±. seconds and 9.3 ±. seconds; p <.00) and produced greater desaturation (6.% ± 0.% and 4.% ± 0.%, p =.003). Lateral position decreased desaturation independent of apnea type (supine.4% ± 0.%, lateral 3.9% ± 0.4%; p =.003). Conclusions: Lateral position attenuates severity of CSA-CSR. This effect is independent of postural effects on the upper airway and is likely to be due to changes in pulmonary oxygen stores. Further studies are required to investigate mechanisms involved. Keywords: Central sleep apnea, body position, ventilatory control Citation: Szollosi I; Roebuck T; Thompson B et al. Lateral Sleeping Position Reduces Severity of Central Sleep Apnea / Cheyne-Stokes Respiration. SLEEP 006;9(8):04-0. INTRODUCTION Disclosure Statement This was not an industry supported study. Dr. Naughton is on the medical advisory board of ResMed Inc. Ms. Szollosi, Roebuck, and Dr. Thompson have indicated no financial conflicts of interest. Submitted for publication November 6, 00 Accepted for publication March, 006 Address correspondence to: Matthew T. Naughton, Alfred Hospital, PO Box 3, Prahran, Victoria, 38, Australia; Tel: ; Fax: ; m.naughton@alfred.org.au SLEEP, Vol. 9, No. 8, SLEEP-RELATED BREATHING DISTURBANCES OCCUR IN UP TO 0% OF PATIENTS WITH HEART FAILURE, WITH 40% EXHIBITING CENTRAL SLEEP APNEA and Cheyne- Stokes respiration (CSA-CSR) and a further 0% of patients exhibiting obstructive sleep apnea hypopnea syndrome (OSAHS). CSA-CSR is attributed to respiratory-control instability in which periodic hyperventilation drives PaCO below the apneic threshold, such that central drive and efferent output to the respiratory pump muscles are transiently reduced or absent. Proposed mechanisms for hyperventilation include stimulation of pulmonary vagal afferents secondary to pulmonary congestion and heightened sympathetic activation. 3,4 Increased chemosensitivity of the central and peripheral chemoreceptors and the underlying increase in circulation time associated with heart failure,6 predisposes to ventilatory instability that manifests as CSA-CSR. OSAHS is a known independent risk factor for the development of cardiovascular disease, 7 occurring in % to 4% of the general adult population. 8 Upper-airway instability during sleep and an inadequate capacity of upper-airway musculature to maintain airway patency is thought to be the main pathophysiologic event, with respiratory-control instability (loop gain) playing a potential role in some patients. 9,0 It has been established that OSAHS severity as measured by the apnea-hypopnea index (AHI) is increased in the supine position. Even in nonpositional OSAHS, the duration of respiratory events and the consequent hypoxemia is more marked in the supine position. This effect is attributed to gravitational effects on the upper airway 3 leading to increased upper-airway collapsibility while supine. In support of this, Penzel et al confirmed that body position has a significant impact on the pharyngeal critical closing pressure, an objective measure of upper-airway collapsibility. 4 In addition, the optimal continuous positive airway pressure required to treat OSAHS has been demonstrated to be approximately cmh O higher in the supine position compared with the lateral. The impact of position in CSA-CSR is less clear. Recently, it has been reported that patients with heart failure have a preference for the lateral sleeping position 6 and, furthermore, that the right lateral decubitus position is preferred over the left lateral decubitus position. 7 In addition, Sahlin et al have shown that central AHI is increased during supine sleep compared with nonsupine sleep. 8 However, previous investigators have also observed that upper-airway instability is common during CSA-CSR, with many patients exhibiting mixed apneas in which pharyngeal occlusion prevents the immediate resumption of airflow when ventilatory effort returns. 9,0 It remains unclear whether upper-airway col-

2 Figure Representative polygraph from subject, showing classification of central, mixed, and obstructive apneas while supine. lapse favored by the supine position is important in the initiation or propagation of CSA-CSR. Our primary aims were to assess the effect of position on the severity of CSA-CSR, as measured by AHI, respiratory-event duration, and hypoxemia associated with events, while controlling for sleep-stage effects. Secondary aims were to examine whether mixed apneas during CSA-CSR were more severe than central apneas in terms of duration and desaturation. Finally, we wished to examine whether the increase in respiratory-control instability observed in the supine position is associated with an increase in mixed-apnea frequency, reflecting an increased contribution of upper-airway collapse to the development of ventilatory instability. METHODS Consecutive patients aged 8 to 80 years with stable congestive heart failure, as defined by a past episode of acute cardiogenic pulmonary edema, no hospital admission for more than 3 months, left ventricular ejection fraction less than 4%, and New York Heart Association class or worse despite optimal medical management, who were referred to our institution s heart failure program were assessed. Exclusion criteria included pregnancy and significant pulmonary, renal, or neurologic disease. All patients provided written informed consent, and data were collected prospectively. Twenty consecutive patients with continuous digital video surveillance during polysomnography with predominantly CSA- CSR and who spent at least 30 minutes sleeping in the supine and lateral positions were analyzed for the effects of position on CSA- CSR severity. Patients were not selected on the basis of positional CSA-CSR. Measurements included electroencephalogram (C4- A, C3-A, O-A, O-A), EOG, submental electromyogram, electrocardiogram, oronasal flow measured with thermistor and nasal pressure cannula (Pro-Tech Services, Mukilteo,WA), ribcage and abdominal effort measured by piezoelectric sensors, calibrated body position sensor, SpO with -second averaging time (Oxypleth, Novametrix, Wallingford, CT), esophageal pressure manometry (Millar Instruments, Houston,TX), and snoring sound. All signals were stored onto a computerized polysomnographic data acquisition and analysis system (Compumedics E- series, Abbottsford, Australia). In order for lateral position to be confirmed, patients had to have shoulder elevated visually on the digitized video and the position sensor reading either left or right position; supine sleep required both shoulders to be in contact with the bed on video and confirmed with position sensor. Sleep stages were manually scored as previously described. Apneas were scored in the absence of oronasal flow in both the thermistor and nasal cannula signals obstructive if continued effort persisted in the ribcage and abdominal bands or esophageal pressure, central in the absence of ventilatory effort, and mixed if there was an absence of oronasal flow when ventilatory effort resumed. Hypopneas were scored on the basis of a 0% or greater reduction in oronasal flow associated with a % desaturation and/or arousal obstructive in the event of paradoxical motion in the effort bands or increasing esophageal pressure amplitude and central if ribcage and abdominal effort remained in phase or esophageal pressure swings decreased. Examples of central, mixed, and obstructive apneas are shown in Figure. CSA-CSR was defined as an AHI greater than events per hour, with fewer than % of events being obstruc- SLEEP, Vol. 9, No. 8,

3 AHI (events/h) Table Subject Characteristics Age, y Sex Men Women CHF etiology IHD DCM HOCM ECG Rhythm SR AF Paced NYHA II III IV Echo FS, % LVEF, % BMI, kg/m ESS AHI, events/h Total Central Mixed Obstructive TST, h SpO, % Mean Min PtcCO, mm Hg Max Mean Min Sleep Stage (%TST) Position (%TST) Supine Left Right (.3) 60 8 * 0 * # 0 0 * p <.00, # p < (.) 6. (.) 6. (0.8) 7.4 (0.8) Figure Apnea-hypopnea index (AHI) by sleep stage and sleeping position inclusive of all central and mixed events. Right and left positions combined into a single lateral position. refers to slow wave sleep;, rapid eye movement sleep. Note significant reduction in AHI with lateral compared to supine positon in all sleep stages. gen desaturation, mean minimum saturation, and mean baseline SpO were calculated (excluding obstructive events) for each subject in each combination of sleep stage and position. The baseline SpO was calculated as the sum of the minimum saturation and the desaturation associated with each respiratory event and, thus, reflects the oxygen saturation in each sleep stage and position, excluding the dips in saturation occurring with respiratory events. Mixed and central apnea contribution to the apnea index was examined in the supine and lateral positions with the left and right positions combined during non-rapid eye movement (N) sleep. Apnea index, mean duration, and mean desaturation associated with central and mixed apneas was calculated for each subject in the supine and lateral positions. Preliminary analysis revealed no differences between right and left positions for any of the outcome variables of interest, consistent with previous observations.7 As such, data from the right and left positions were combined into a single lateral position for analysis. AHI and ArI were not normally distributed; therefore, we used a negative binomial regression model to analyze the number of events per time in each sleep stage and body position. All other outcome variables for the group (i.e., mean event duration, desaturation, and minimum and baseline saturation) were normally distributed with equal variances across groups; therefore, we used linear regression to assess the influence of sleep stage and position. Similarly, the apnea index was analyzed using negative binomial regression to assess the influence of apnea type and position on the number of events per time; linear regression was used to assess influence of apnea type and position on mean duration and mean desaturation associated with events. All analyses were performed with robust standard errors adjusted for clustering by subject using Stata9 (StataCorp LP, College Station, TX). Data presented as mean ± SEM. 6.4 (3.0). (.7) 3. (.6). (0.4).0 (0.3) 96. (0.3) 86.6 (.3) 48.3 (.4) 43.6 (.) 38.9 (.6) 6. (.9).3 (.8) 4. (.7) 8. (.9) 39. (.0) 3. (.) 37. (6.7) Data presented as mean (SEM). CHF refers to congestive heart failure; ECG electrocardiogram; IHD ischemic heart disease; DCM, dilated cardiomyopathy; HOCM, hypertrophic obstructive cardiomyopathy; SR, sinus rhythm; AF, atrial fibrillation and flutter; NHYA, New York Heart Association classification; FS, fractional shortening measured by echocardiography; LVEF, left ventricular ejection fraction measured gated blood pool scan; BMI, body mass index; ESS, Epworth Sleepiness Scale score; AHI, apnea-hypopnea index; TST, total sleep time;, slow-wave sleep;, rapid eye movement sleep). tive in nature. Arousals were scored according to American Sleep Disorders Association criteria.3 Sleep-stage, respiratory-event, and arousal information was exported for manual analysis. RESULTS The group of patients studied were typical of a heart failure population with a mean age of 9.9 ±.3 years, male predominance, sinus rhythm in approximately 0% and atrial fibrillation or pacemaker in approximately 0%, mean left ventricular ejection fraction (via 99Tc equilibrium radionuclide angiography) 6.% ± Statistical Analyses To determine the influence of position on CSA-CSR severity, all obstructive events were removed from further analysis. AHI, Arousal Index (ArI), mean respiratory event duration, mean oxysleep, Vol. 9, No. 8, 006 Downloaded from supine lateral * 047 Influence of Position on CSA-CSR Severity Szollosi et al

4 DESATURATION % * *.09]). The mean duration of events for all subjects was 6. ±.0 seconds (supine.7 ±.8 seconds and lateral 6.9 ± 3.4 seconds) and was not significantly influenced by either sleep stage or sleeping position. The desaturation and minimum saturation were significantly influenced by position in Stage and Stage sleep, during which 9% and % of events occurred, respectively (Figure 3). The lateral position was associated with decreased apnea-hypopnea related hypoxemia during Stage and Stage sleep. The differences were not statistically significant in and sleep, probably due to the relatively small numbers of events occurring in these sleep stages (0% of all events). There was no significant influence of sleep stage or position on baseline SpO (supine 96.8% ± 0.3% and lateral 97.4% ± 0. %). The supine position was associated with a significantly greater total apnea index compared with the lateral position (9.0 ± 4.9/ hour and 7.0 ±.9/hour; p <.00). This increase in the supine apnea index was driven by significant increases in both central and mixed events; however, the proportion of central versus mixed events remained similar in both positions (supine 7:9 and lateral 69:3, p = NS). During N sleep, mixed apneas were of longer duration than central apneas (9. ±. and 9.3 ±. seconds; p <.00) and resulted in greater desaturation (6.% ± 0.% and 4.% ± 0.%; p =.003) and lower minimum SpO (9.% ± 0.6% and 9.9% ± 0.6%; p =.039). Similar to the apnea-hypopnea results, there was no influence of position on apnea duration; however, the supine position was associated with significantly greater desaturations independent of apnea type (supine.4% ± 0.% and lateral 3.9% ± 0.4%, p =.003). 0 supine lateral MINIMUM SpO % * * * p <.00 Figure 3 Influence of body position on (a) oxygen desaturation and (b) minimum oxygen saturation associated with respiratory events. refers to slow wave sleep;, rapid eye movement sleep. Note significantly greater desaturation and lower minimum SpO in the supine compared with lateral position in Stage and Stage sleep, where the majority of events occurred..%, and fractional shortening (via transthoracic echocardiography) 8.% ±.%. The overall AHI was 6.4 ± 3.0 events per hour; central, mixed and obstructive AHI were.±.7, 3.±.6, and.±0.4 events per hour, respectively (Table ). Six of 0 patients tolerated the esophageal pressure manometer. A total of 36 central and mixed events during 996 minutes of sleep were analyzed from polygraphs of 0 patients. Mean time spent sleeping supine was 8.7 ± 7.4 minutes, left lateral was 6.4 ± 7.3 minutes, and right lateral was.7 ±.6 minutes. The AHI was significantly influenced by both sleep stage and position (Figure ). AHI showed a progressive decrease from Stage to Stage to slow-wave sleep () (all p <.00); respiratory events persisted during rapid eye movement () sleep, with greater frequency than during (p <.0) but with lower frequency than during Stage sleep (p <.00). Position had a significant influence on AHI, independent of sleep-stage effects. The lateral position was associated with significant reduction in AHI compared with supine in all sleep stages (Stage, 4.7 ± 4. events per hour vs 7. ± 4. events per hour [p <.00]; Stage, 43.3 ± 6. events per hour vs 4.4 ± 3.6 events per hour [p <.00];,.9 ± 6.4 events per hour vs.4 ±.9 events per hour [p <.0];, 38.0 ± 7.3 events per hour vs.0 ± 3.0 events per hour [p <.00]). Similarly, the ArI decreased from Stage to Stage and with a small rise in ; however, the decrease in ArI observed in the lateral position reached statistical significance only during Stage sleep (Stage, 46.3 ± 4.9 events per hour vs 4.3 ±.7 events per hour [p =.]; Stage, 8. ±.8 events per hour vs.6 ±. events per hour [p <.0];,.7 ±. events per hour vs.8 ± 0.7 events per hour [p =.4];,. ± 3.4 events per hour vs 9.7 ±. events per hour [p = SLEEP, Vol. 9, No. 8, 006 Downloaded from DISCUSSION There are important novel observations that have emerged from this detailed study of CSA-CSR in patients with heart failure. First, compared with the supine position, the lateral position is associated with reduced apnea-hypopnea related hypoxemia despite respiratory events of similar duration in addition to a more than 0% reduction in AHI. Second, mixed apneas were of longer duration and produced greater desaturation than central apneas; however, the ratio of mixed to central apneas was unchanged by the move from supine to lateral position (~30:70 ratio). These novel findings would suggest that the effect of posture on respiratory-control instability during sleep is more likely to be due to supine reductions in pulmonary oxygen stores rather than increases in upper-airway instability in this patient group. Our findings support recently published articles in which the importance of sleeping posture in patients with heart failure was highlighted. We have confirmed the findings of Sahlin et al, who reported a higher central AHI in the supine compared with nonsupine position (4 and 6 events per hour) in a group of 0 patients.8 Similarly, Leung and coworkers reported a voluntary predisposition to sleep in the right lateral decubitus position compared to the left lateral decubitus position in 7 patients with heart failure. Of note, Leung reported the AHI and mean and minimum SpO values to be similar in the left and right lateral positions.7 As well as confirming these previous findings, the present study extends upon these previous observations. Importantly, we have shown that the severity of CSA-CSR, as assessed by the magni048 Influence of Position on CSA-CSR Severity Szollosi et al

5 tude of hypoxemia but not of event duration, is also reduced in the lateral position. This observation offers valuable insights into the pathogenesis of CSA-CSR, namely that the supine increase in CSA-CSR occurs in the presence of reduced oxygen stores. The pathogenesis of CSA-CSR has been explained by instability in the metabolic control of ventilation. Recently, this hypothesis has also been applied to explain the pathogenesis of OSAHS, with some studies reporting that patients with OSAHS also have an underlying instability in ventilatory control. 9,0 In terms of control theory, a negative feedback loop, such as the metabolic control of ventilation, will exhibit unstable behavior if the loop gain of the system exceeds. If the loop gain is less than, any disturbance causing changes in blood gases will be dampened out, and ventilation will return to a stable pattern. Simplistically, there are 3 factors that can contribute to increasing loop gain and the development of oscillatory behavior in ventilatory control, namely, increased circulation time, increased sensitivity of chemoreceptors (controller gain), and decreases in lung volume (plant gain). 4, The limited evidence for each of these 3 factors is discussed in the context of transverse postural changes. Although this study was not designed to identify which of these mechanisms may be influenced by postural changes during sleep, our results provide indirect evidence that the increase in supine AHI in this patient group occurred in the presence of decreased oxygen stores/lung volumes, as reflected by the greater degree of hypoxemia occurring with events of similar duration in the supine position. The influence of transverse gravitational effects on hemodynamics in humans are few and, to date, have only been conducted during wakefulness. Pump et al reported that, in healthy subjects, the left lateral posture increases left atrial diameter, facilitates venous return, and decreases mean systemic arterial pressure; however, the right lateral posture was not examined. 6 The importance of posture on sleep-disordered breathing is also highlighted by observations that both central and obstructive apneas are decreased during microgravity conditions. 3 Postural hemodynamic changes during sleep may therefore be important in the setting of heart failure. Increased venous return in the lateral position may contribute to maintaining increased cardiac output, decreasing circulation time, and thus favoring ventilatory stability. Postural changes in lung volume in the transverse plane are also not well documented. In a study by Hurewitz et al, which assessed regional ventilation in obese and nonobese controls, the lateral decubitus position was associated with an increase in functional residual capacity of approximately 60 ml, compared with the supine position in the control subjects. 7 However, the numbers were small (n = 3) and generalizations thus difficult to make. Patients with heart failure are known to have decreased lung volumes due to pulmonary congestion with or without enlargement of the heart within the thorax. 8 Recently, it has also been observed that, during CSA-CSR, fluctuations in end-expiratory lung volume occur with changes in tidal volume. 9 Decreases in lung volume, and therefore oxygen stores, favors the development of CSA-CSR as the ability of the lungs to buffer changes in blood gases is reduced, leading to an increase in plant gain. A small reduction of lung volume that may occur from the lateral to supine position may therefore be an important mechanism that would explain the supine increase in AHI that we and others have observed. Given that we found a greater degree of hypoxemia resulting from respiratory events in the supine position, without any differences in the duration of events, lung-volume changes are likely to be involved in explaining positional changes in ventilatory stability. Further indirect evidence to support the importance of lung-volume changes come from studies investigating the efficacy of continuous positive airway pressure (CPAP) and supplemental oxygen in the treatment of CSA-CSR secondary to heart failure. Application of CPAP has been equally effective in reducing AHI and ArI, as compared with the administration of supplemental oxygen. 30,3 CPAP is known to increase lung volumes, 3 and both forms of treatment acutely reduce hypoxemia through increasing total body oxygen stores, 33 thus favoring the development of ventilatory stability. Furthermore, CPAP as well as supplemental oxygen have been shown to improve left ventricular ejection fraction after a 3-month treatment period. 4,34 Thus, the importance of reductions in lung volume and its effect on reducing oxygen stores may be underestimated in the pathogenesis of CSA-CSR. At present, there have been no studies that have investigated the influence of transverse postural changes in chemoreceptor sensitivity; thus we cannot rule out this mechanism as playing a role in explaining the increase in AHI observed in the supine position. However, this is unlikely given that supine to upright changes in chemoreceptor sensitivity to CO have not been observed in normal subjects. 3,36 Previous investigators have reported that upper-airway collapse is common during CSA-CSR 9,0 and that the tendency for upper-airway collapse is enhanced in the supine position in patients with OSAHS. 4 This observation, together with evidence that upper-airway collapse is common during CSA-CSR, may make it plausible that an obstructive component during CSA- CSR may be important in explaining the increased frequency of respiratory events in the supine position. It has also been reported that fluctuations in state changes, such as those that occur as a consequence of the arousal response, illicit changes in chemoreceptor sensitivity and that involvement of the peripheral chemoreceptors amplifies the state-related changes in ventilation. 37 During sleep, chemoreceptor sensitivity is blunted to both hypoxic and hypercapnic stimuli. 38,39 The arousal response or the wakefulness drive is thus associated with an increase in chemoreceptor sensitivity. It is possible that as the supine position favors upper-airway collapse, it would lead to longer apneas and a greater degree of oxygen desaturation. The resultant increase in hypoxic drive, together with an increased sensitivity of chemoreceptors associated with the arousal response, may be associated with an exaggerated ventilatory response and be an important mechanism that promotes respiratory instability. To address this question, we have examined the prevalence of upper-airway collapse that resulted in mixed apneas during CSA- CSR in both supine and lateral positions during N sleep. We have limited this part of the analysis to include only apneas because the subclassification of hypopneas into central and mixed is difficult, even with the presence of esophageal pressure measurement in a subgroup of our patients. Mixed apneas were found to be longer in duration and resulted in a greater degree of hypoxemia than did central apneas. For both duration and desaturation, this effect was independent of position; however, desaturation associated with mixed and central apneas was further increased in the supine position. Importantly, the proportion of central and mixed apneas was similar in both positions; therefore, we believe that mechanisms other than upper-airway collapse are responsible for the increased ventilatory instability that we have found in the SLEEP, Vol. 9, No. 8,

6 supine position. Our findings give indirect support that lung-volume reductions may be more important than previously thought in the pathophysiology of CSA-CSR. It is likely that changes in lung volume occur in association with postural changes in the transverse plane; however, we cannot rule out that changes in cardiac chamber dimensions, cardiac filling, cardiac output, or other hemodynamic variables affecting circulation time, as well as changes in chemoreceptor sensitivity, may also contribute to ventilatory instability in the supine position. It is also possible that active or passive collapse of the upper airway may be occurring during central apneas. In summary, this study has shown that the lateral position is associated with a greater than 0% reduction in the AHI and the apnea index independent of sleep-stage effects. These reductions are of similar magnitude to those observed with application of CPAP. 4 Although event duration is not influenced by position, hypoxemia is attenuated in the lateral position, suggesting that postural changes in lung volume may be responsible for postural changes in ventilatory instability. Thus, changes in loop gain rather than upper-airway collapse are likely to cause the increase in AHI observed in the supine position in patients with heart failure and CSA-CSR. Because the prevalence of CSA-CSR is common in patients with heart failure, avoiding the supine position during sleep may be important in altering the expression of ventilatory instability in this patient group. This may have profound effects on sleep quality by promoting consolidation of sleep architecture and by reducing hypoxic damage, sympathetic nervous system activation, and consequent cardiovascular morbidity. However, further studies are required to identify precise mechanisms involved and whether a simple therapeutic intervention such as avoidance of the supine position during sleep can contribute to improvements in quality of life and survival. Finally, this study highlights that AHI during CSA-CSR, as in obstructive sleep apnea, is highly dependent on body position and sleep stage. The weak correlation between AHI and morbidity in many studies 40 may in part be explained by the shifting expression of ventilatory instability caused by positional influences. REFERENCES. Javaheri S, Parker T, Liming J, et al. Sleep apnea in 8 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations. Circulation 998;97:4-9.. Churchill ED, Cope O. The rapid shallow breathing resulting from pulmonary congestion and edema. J Exp Med 99;49: Mansfield D, Kaye DM, Brunner La Rocca H, Solin P, Esler MD, Naughton MT. 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