Dai Yumino

Nocturnal Rostral Fluid Shift A Unifying Concept for the Pathogenesis of Obstructive and Central Sleep Apnea in Men With Heart Failure

Background— Obstructive sleep apnea (OSA) and central sleep apnea are common in patients with heart failure. We hypothesized that in such patients, severity of OSA is related to overnight rostral leg fluid displacement and increase in neck circumference, severity of central sleep apnea is related to overnight rostral fluid displacement and to sleep Pco2, and continuous positive airway pressure alleviates OSA in association with prevention of fluid accumulation in the neck. Methods and Results— In 57 patients with heart failure (ejection fraction ≤45%), we measured change in leg fluid volume and neck circumference before and after polysomnography, and we measured transcutaneous Pco2 during polysomnography. Patients were divided into an obstructive-dominant group (≥50% of apneas and hypopneas obstructive) and a central-dominant group (>50% of events central). Patients with OSA received continuous positive airway pressure. In obstructive-dominant patients, there were inverse relationships between overnight change in leg fluid volume and both the overnight change in neck circumference (r=−0.780, P<0.001) and the apnea-hypopnea index (r=−0.881, P<0.001) but not transcutaneous Pco2. In central-dominant patients, the overnight reduction in leg fluid volume correlated inversely with the apnea-hypopnea index (r=−0.919, P<0.001) and the overnight change in neck circumference (r=−0.568, P=0.013) and directly with transcutaneous Pco2 (r=0.569, P=0.009). Continuous positive airway pressure alleviated OSA in association with prevention of the overnight increase in neck circumference (P<0.001). Conclusions— Our findings suggest that nocturnal rostral fluid shift is a unifying concept contributing to the pathogenesis of both OSA and central sleep apnea in patients with heart failure.

Relationship between Overnight Rostral Fluid Shift and Obstructive Sleep Apnea in Nonobese Men

RATIONALE The cause of increased pharyngeal collapsibility in patients with obstructive sleep apnea is incompletely understood. In awake healthy subjects, we showed that fluid displacement from the legs into the neck induced by lower body positive pressure reduces upper airway size and increases its collapsibility. Prolonged sitting leads to dependent fluid accumulation in the legs. OBJECTIVES To test the hypotheses that the apnea-hypopnea index (AHI) during sleep will be related to the amount of fluid spontaneously displaced from the legs overnight, and that this will, in turn, be related to the time spent sitting the previous day. METHODS In 23 nonobese healthy men referred for sleep studies for suspected obstructive sleep apnea, we assessed the changes in leg fluid volume and in neck circumference from the beginning to the end of the night, and the time spent sitting during the previous day. MEASUREMENTS AND MAIN RESULTS The overnight change in leg fluid volume correlated strongly with the AHI (r = -0.773, P < 0.001), the change in neck circumference (r = -0.792, P < 0.001), and the time spent sitting (r = -0.588, P = 0.003). Multivariate analysis showed that the only significant independent correlates of the AHI were the overnight changes in leg fluid volume and neck circumference, which together explained 68% of the variability in the AHI among subjects. CONCLUSIONS These novel findings suggest that overnight rostral fluid displacement from the legs, related to prolonged sitting, may play a previously unrecognized role in the pathogenesis of obstructive sleep apnea in nonobese men that is independent of body weight.

Acute decompensated heart failure syndromes (ATTEND) registry. A prospective observational multicenter cohort study: Rationale, design, and preliminary data

Acute heart failure syndromes (AHFS) are likely to increase in the future, and the high readmission rate of patients with AHFS is an important issue in Western countries. However, there are very few published epidemiological studies on AHFS in the Asia Pacific region. Because AHFS are heterogeneous, the characteristics, clinical profile, and management of AHFS should be clarified in an epidemiological study. The acute decompensated heart failure syndromes (ATTEND) registry is a prospective, observational, multicenter cohort study being performed in Japan and is the first epidemiological study of AHFS in the Asia Pacific region. This study is designed to investigate several aspects of AHFS as follows: (1) the registry allows patient-based data collection for precise evaluation of patient characteristics and short-term outcomes, including the readmission rate; (2) confirmation of clinical assessments can be performed, and new clinical assessments can be created; and (3) feedback allows the modification of guidelines for clinical management. The present report describes the clinical characteristics of patients with AHFS in Japan based on the preliminary data collected in this study, and the similarities and differences in characteristics of these patients compared with those in Western countries. Although most of the patient characteristics did not differ from those reported in Western studies, there are some unique findings in this study, including a high rate of treatment with carperitide (69.4%) and angiotensin II receptor blockers (53.9%) at discharge and a longer hospital stay (median 21 days). The ATTEND registry is designed to provide valuable information to clarify the characteristics of patients with AHFS to improve their management.

Lower body positive pressure increases upper airway collapsibility in healthy subjects

We previously showed that rostral fluid displacement by lower body positive pressure (LBPP) narrows the upper airway (UA) and increases UA resistance, but effects on UA collapsibility remained unknown. To test if LBPP increases UA collapsibility, 13 healthy men were randomized into a control or LBPP arm then crossed over into the other arm with a 30-min washout in between. LBPP was applied by inflating anti-shock trousers wrapped around both legs to 40 mmHg. UA collapsibility was assessed by determining UA critical closing pressure (P crit) during application of different negative airway pressures. P crit and leg fluid volume were measured at baseline and after 5 min during both periods. LBPP caused a significant increase in P crit associated with a reduction in leg fluid volume. We conclude that rostral fluid displacement by LBPP increases UA collapsibility in healthy men, suggesting that fluid shift into the neck could increase UA collapsibility during sleep and thereby predispose patients with fluid overload states to obstructive sleep apnea.

Relationship between sleep apnoea and mortality in patients with ischaemic heart failure

Objective: To determine whether the influence of sleep apnoea (SA) on the risk of death differs in patients with ischaemic and in those with non-ischaemic heart failure (HF). Design: Prospective observational study. Patients: Consecutive patients with HF with left ventricular ejection fraction ⩽45% newly referred to the HF clinic between 1 September 1997 and 1 December 2004. Main outcome measures: Patients underwent sleep studies and were divided into those with moderate to severe SA (apnoea–hypopnoea index ⩾15/h of sleep) and those with mild to no SA (apnoea–hypopnoea index <15/h of sleep). They were followed up for a mean of 32 months to determine all-cause mortality rate. Results: Of 193 patients, 34 (18%) died. In the ischaemic group, mortality risk adjusted for confounding factors was significantly higher in those with SA than in those without it (18.9 vs 4.6 deaths/100 patient-years, hazards ratio (HR) = 3.03, 95% CI 1.04 to 8.84, p = 0.043). In contrast, in the non-ischaemic HF group, there was no difference in adjusted mortality risk between those with, and those without, SA (3.9 vs 4.0 deaths/100 patient-years, p = 0.929). Conclusions: In patients with HF, the presence of SA is independently associated with an increased risk of death in those with ischaemic, but not in those with non-ischaemic, aetiology. These findings suggest that patients with ischaemic cardiomyopathy are more susceptible to the adverse haemodynamic, autonomic and inflammatory consequences of SA than are those with non-ischaemic cardiomyopathy.

Impact of Sleep-Disordered Breathing on Life-Threatening Ventricular Arrhythmia in Heart Failure Patients With Implantable Cardioverter-Defibrillator

It was recognized that sleep-disordered breathing (SDB) is associated with cardiac arrhythmia and sudden cardiac death. However, it was unclear whether the presence of SDB increased the risk of life-threatening ventricular arrhythmia in patients with heart failure (HF) with an implantable cardioverter-defibrillator (ICD). Seventy-one patients with HF and an ICD who were followed up for 180 days after a sleep study were prospectively studied. All patients had an ejection fraction <or=35%. SDB was defined as an apnea-hypopnea index >or=10 events/hour on the sleep study. The frequency of appropriate ICD therapy and the day-night pattern of ICD therapies were compared between patients with and without SDB. SDB was diagnosed in 47 of 71 patients (66%). There were no statistical differences between patients with and without SDB in baseline cardiac function. However, appropriate ICD therapies occurred more frequently in patients with (43%) than without SDB (17%; p = 0.029). On multivariate analysis, the presence of SDB was an independent predictor for appropriate ICD therapy (hazard ratio 4.05, 95% confidence interval 1.20 to 13.65, p = 0.015). Moreover, the rate of total ICD therapy from midnight to 6 A.M. was significantly higher in patients with (34%) than without SDB (13%; p = 0.046). In conclusion, in patients with HF with an ICD, the presence of SDB was common and an independent predictor of life-threatening ventricular arrhythmias that were more likely to occur during sleep.

Differing Effects of Obstructive and Central Sleep Apneas on Stroke Volume in Patients with Heart Failure

RATIONALE Obstructive sleep apnea and central sleep apnea increase risk of mortality in patients with heart failure (HF), possibly because of hemodynamic compromise during sleep. However, beat-to-beat stroke volume (SV) has not been assessed in response to obstructive and central events during sleep in patients with HF. Because obstructive events generate negative intrathoracic pressure that reduces left ventricular (LV) preload and increases afterload, but central events do not, obstructive events should lead to greater hemodynamic compromise than central events. OBJECTIVES To determine the effects of obstructive and central apneas and hypopneas during sleep on SV in patients with HF. METHODS Patients with systolic HF (LV ejection fraction ≤ 45%) and sleep apnea underwent beat-to-beat measurement of SV by digital photoplethysmography during polysomnography. Change in SV from before to the end of obstructive and central respiratory events was calculated and compared between these types of events. MEASUREMENTS AND MAIN RESULTS Changes in SV were assessed during 252 obstructive and 148 central respiratory events in 40 patients with HF. Whereas SV decreased by 6.8 (±8.7)% during obstructive events, it increased by 2.6 (±5.4)% during central events (P < 0.001 for difference). For obstructive events, reduction in SV was associated independently with LV ejection fraction, duration of respiratory events, and degree of oxygen desaturation. CONCLUSIONS In patients with HF, obstructive and central respiratory events have opposite hemodynamic effects: whereas obstructive sleep apnea appears to have an adverse effect on SV, central sleep apnea appears to have little or slightly positive effects on SV. These observations may have implications for therapeutic approaches to these two breathing disturbances.

Difference in upper airway collapsibility during wakefulness between men and women in response to lower-body positive pressure.

Fluid shift from the legs to the neck induced by LBPP (lower-body positive pressure) increases UA (upper airway) collapsibility in healthy men. Rostral fluid displacement during recumbency may therefore contribute to the pathogenesis of OSA (obstructive sleep apnoea). There is a higher prevalence of OSA in men than in women. We therefore hypothesized that UA collapsibility increases more in men in response to rostral fluid displacement than in women. UA collapsibility was assessed in healthy, non-obese men and women while awake by determining UA Pcrit (critical closing pressure) during application of different suction pressures to the UA. Subjects were randomized to 5 min control or LBPP arms after which they crossed-over into the other arm following a 30 min washout. LBPP was applied by inflating anti-shock trousers wrapped around both legs to 40 mmHg. Pcrit, leg fluid volume and neck circumference were measured at baseline and after 5 min of both control and LBPP periods. LBPP caused a decrease in leg fluid volume and an increase in neck circumference that did not differ between men and women. However, compared with the control period, LBPP induced a much greater increase in Pcrit in men than in women (7.2+/-1.8 compared with 2.0+/-1.5 cm H2O, P=0.035). We conclude that rostral fluid displacement by LBPP increases UA collapsibility more in healthy, non-obese men than in women. This may be one mechanism contributing to the higher prevalence of OSA in men than in women.

Hyponatremia and In-Hospital Mortality in Patients Admitted for Heart Failure (from the ATTEND Registry)

Hyponatremia is known to be a poor prognostic factor in patients hospitalized with heart failure (HF), however not well studied in Japan. The aims of this study were to characterize hyponatremic hospitalized patients with HF and to clarify the relations between hyponatremia and detailed in-hospital outcomes in Japan. Among 4,837 hospitalized patients with HF enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, patient characteristics and in-hospital mortality in those with hyponatremia were examined. Hyponatremia (sodium <135 mEq/L) was observed in 11.6% of patients. Patients with hyponatremia were of similar age, included fewer men, and had a higher proportion of previous hospitalizations for HF compared to those with normonatremia. On admission, lower heart rates and blood pressures and higher brain natriuretic peptide levels were observed in patients with hyponatremia. During hospitalization, inotrope levels and mechanical device use were significantly higher in patients with hyponatremia. Rates of all-cause and cardiac death were significantly higher in patients with hyponatremia, 15.0% and 11.4%, respectively, compared to 5.3% and 3.6%, respectively, in those with normonatremia. In hyponatremic hospitalized patients with HF, cardiac death accounted for 76.2% of all-cause death. In conclusion, the present study demonstrates that in Japan hyponatremia in patients hospitalized with HF is relatively common and is associated with a very high in-hospital mortality.

Obstructive sleep apnea is associated with greater thoracic aortic size.

To the Editor: Obstructive sleep apnea (OSA), characterized by partial or complete occlusion of the pharynx during sleep, results in persistent inspiratory effort and interruption of airflow. During each episode of apnea, OSA patients develop increased transmural pressure in the aortic wall.