Prevalence of Restless Legs Syndrome and Its Effects on Sleep and Health-Related Quality of Life in Patients With Heart Failure.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder characterized by leg restlessness and dysesthesia. Although the relationship between RLS and heart failure (HF) has been reported, the prevalence and clinical significance of RLS in patients with HF remain to be elucidated. METHODS AND RESULTS: We enrolled consecutive patients with HF who were admitted to our institutions. RLS was diagnosed using the International Restless Legs Syndrome Study Group criteria. Subjective sleepiness, sleep quality, and quality of life (QoL) were assessed using the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and 8-item Short Form (SF-8), respectively. Among the 133 patients, 18 (13.6%) had RLS and were younger than those without RLS (62.4±13.4 vs 70.0±12.2, P = .017). The RLS group had significantly disrupted sleep quality and QoL, with greater PSQI score (8.0±3.2 vs 5.9±3.3, P = .015) and lower SF-8 physical component summary (PCS) score (35.6±6.5 vs 40.7±9.5, P = .031), despite similar ESS and SF-8 mental component summary scores. In the multivariable regression analysis, RLS was associated with greater PSQI (ß=0.211; P = .014) and lower PCS score (ß=-0.177; P = .045). CONCLUSION: In the patients with HF, RLS was prevalent, and sleep quality and QoL may be disrupted by RLS.

Impact on Clinical Outcomes of Periodic Leg Movements During Sleep in Hospitalized Patients Following Acute Decompensated Heart Failure.

BACKGROUND: Periodic leg movements during sleep (PLM) are characterized by regularly recurring movement of the legs during sleep. Although PLM is common and a predictor of death in patients with chronic heart failure, the clinical significance of PLM in hospitalized patients with a reduced left ventricular ejection fraction (LVEF) following acute decompensated heart failure (ADHF) remains unknown.Methods and Results:After initial improvement of acute signs and symptoms of ADHF, 94 consecutive patients with reduced LVEF who underwent polysomnography were enrolled. They were divided into 2 groups based on the presence or absence of severe PLM defined as PLM index ≥30. The risks for clinical events, composite of all-cause death and rehospitalization, were assessed using a stepwise multivariable Cox proportional model including variables showing P<0.10 in univariate analyses. Severe PLM was observed in 21 patients (22%). At a median follow-up of 5.2 months, 30 patients experienced clinical events (32%). In the multivariable analysis, the presence of severe PLM was significantly associated with increasing clinical events (hazard ratio, 2.16; 95% confidence interval, 1.03-4.54; P=0.042) independent of hemoglobin level and the severity of sleep-disordered breathing. CONCLUSIONS: In hospitalized patients with systolic dysfunction following ADHF, severe PLM was prevalent and significantly associated with increased risk of death and/or rehospitalization.

Bradyarrhythmias may induce central sleep apnea in a patient with obstructive sleep apnea.

The relationship between central sleep apnea (CSA) and bradyarrhythmia remains unclear. We report the case of a 70-year-old man with severe obstructive sleep apnea and bradyarrhythmia due to sick sinus syndrome in whom concomitant CSA was alleviated after pacemaker implantation.

Impact of sleep-disordered breathing on overnight changes in arterial stiffness in patients with acute heart failure.

Overnight increases in arterial stiffness associated with sleep-disordered breathing may adversely affect patients with acute heart failure. Thus, we investigated overnight changes in arterial stiffness and their association with sleep-disordered breathing in patients hospitalized for acute heart failure. Consecutive patients with acute heart failure were enrolled. All participants underwent overnight full polysomnography following the initial improvement of acute signs and symptoms of acute heart failure. The arterial stiffness parameter, cardio-ankle vascular index (CAVI), was assessed before and after polysomnography. Overall, 60 patients (86.7% men) were analyzed. CAVI significantly increased overnight (from 8.4 ± 1.6 at night to 9.1 ± 1.7 in the morning, P < 0.001) in addition to systolic and diastolic blood pressure (from 114.1 mmHg to 121.6 mmHg, P < 0.001; and from 70.1 mmHg to 78.2 mmHg, P < 0.001, respectively). Overnight increase in CAVI (ΔCAVI ≥ 0) was observed in 42 patients (70%). The ΔCAVI ≥ 0 group was likely to have moderate-to-severe sleep-disordered breathing (i.e., apnea-hypopnea index ≥15, 55.6% vs 80.9%, P = 0.047) and greater obstructive respiratory events (29.4% vs 58.5%, P = 0.041). In multivariable analysis, moderate-to-severe sleep-disordered breathing and greater obstructive respiratory events were independently correlated with an overnight increase in CAVI (P = 0.033 and P = 0.042, respectively). In patients hospitalized for acute heart failure, arterial stiffness, as assessed by CAVI, significantly increased overnight. Moderate-to-severe sleep-disordered breathing and obstructive respiratory events may play an important role in the overnight increase in cardio-ankle vascular index.

Cross-Sectional Relationship Between Atrial Conduction Delay and Arterial Stiffness in Patients with Obstructive Sleep Apnea.

Aim: Prolonged P-wave duration (PWD), which indicates atrial conduction delay, is a potent precursor of atrial fibrillation (AF) that may be induced by obstructive sleep apnea (OSA). The cardio-ankle vascular index (CAVI), which is an arterial stiffness parameter, is elevated in patients with OSA; moreover, an increased CAVI is associated with atrial conduction delay through left atrium enlargement in association with left ventricular diastolic dysfunction. We aimed to examine the relationship between the CAVI and PWD in patients with OSA. Methods: We included patients with a sinus rhythm who underwent overnight polysomnography. We measured the PWD and CAVI on standard 12-lead electrocardiograms; further, we analyzed the relationship between PWD and CAVI. Results: We analyzed data from 300 participants (men, 89.0%; mean age, 52.3 ± 13.1 years; and body mass index, 26.2 ± 3.9 kg/m2). The mean PWD was 104.4 ± 10.4 ms while the mean CAVI was 7.5 ± 1.5. PWD was significantly correlated with CAVI (r = 0.478, p < 0.001); additionally, PWD and CAVI were directly associated with OSA severity (p = 0.002 and p = 0.002, respectively). Multivariate regression analysis revealed an independent significant correlation of PWD and CAVI with OSA severity. Conclusion: In patients with OSA, an increase in arterial stiffness is associated with atrial conduction delay.

Utility of cyclic variation of heart rate score as a screening tool for sleep-disordered breathing in patients with heart failure.

STUDY OBJECTIVES: Patients with sleep-disordered breathing have cyclic variation of heart rate (CVHR) in response to respiratory events. However, limited data are available regarding the utility of CVHR as a screening tool for sleep-disordered breathing in patients with mixed heart failure (HF) and those without HF. METHODS: We enrolled consecutive patients with and without HF who underwent full polysomnographies with simultaneous Holter electrocardiogram monitoring. We determined the temporal position of the individual dips comprising the CVHR score using time-domain methods. RESULTS: The data of 101 patients, including 70 with and 31 without HF, were analyzed. The CVHR score was significantly correlated with the apnea-hypopnea index (r = .667, P < .001) and limits of agreement between the apnea-hypopnea index and CVHR score were -21.8 to 35.2. The receiver operating characteristic analysis demonstrated that the CVHR score (best cut-off of 23.5 events/h) identified severe sleep-disordered breathing with a sensitivity of 83.3%, specificity of 79.5%, and the area under the curve of 0.856. In addition, there was no interaction between the presence or absence of HF and the apnea-hypopnea index-CVHR score relationship (P = .323). CONCLUSIONS: The CVHR score, determined by Holter electrocardiogram monitoring, is a useful tool for evaluating sleep-disordered breathing even in patients with mixed HF and patients without HF. CITATION: Yatsu S, Kasai T, Naito R, et al. Utility of cyclic variation of heart rate score as a screening tool for sleep-disordered breathing in patients with heart failure. J Clin Sleep Med. 2021;17(11):2187-2196.

Prevalence and Significance of Restless Legs Syndrome in Patients With Coronary Artery Disease.

Restless legs syndrome (RLS), characterized by leg restlessness and dysesthesia predominantly at night and at rest, disrupts sleep and quality of life. The reported prevalence of RLS is 2% to 5%. Although a relation between RLS and coronary artery disease has been suggested, the prevalence and clinical significance of RLS in coronary artery disease patients remain unknown. We enrolled coronary artery disease patients who underwent percutaneous coronary intervention. Patients with RLS were identified according to international criteria. Subjective sleepiness, sleep quality, and health-related quality of life were assessed using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Short Form-8, respectively. Among 326 patients with coronary artery disease, 26 (8.0%) had RLS. There were no significant differences in characteristics between patients with and without RLS. Sleep quality and quality of life were more disrupted in patients with RLS (Pittsburgh Sleep Quality Index score, 7.4 ± 2.4 vs 5.6 ± 2.5, p <0.001; physical component summary and mental component summary scores of Short Form-8, 39.6 ± 1.8 vs 43.5 ± 0.5, p = 0.042 and 45.2 ± 8.4 vs 48.4 ± 7.4, p = 0.037, respectively), despite no significant difference in Epworth Sleepiness Scale score (8.2 ± 5.1 vs 7.1 ± 4.8, p = 0.293). In multiple linear regression analyses, RLS was independently associated with Pittsburgh Sleep Quality Index (ß = 0.174, p <0.001), physical component summary (ß = -0.127, p = 0.029), and mental component summary (ß = -0.113, p = 0.042) scores. In conclusion, in patients with coronary artery disease, the prevalence of RLS was relatively high compared to that reported in the general population. The presence of RLS was associated with disrupted sleep quality and health-related quality of life in coronary artery disease patients.

Age-stratified sex differences in polysomnographic findings and pharyngeal morphology among children with obstructive sleep apnea.

BACKGROUND: Childhood obstructive sleep apnea (OSA) has important implications for growth, learning, behavior, cognition and cardiovascular health as well as snoring and OSA in adulthood. In this study, we elucidated the sex differences in polysomnographic (PSG) findings and pharyngeal radiographic data in pediatric OSA patients. METHODS: Sixty three children (age between 3 and 15 years old) with OSA [defined as apnea-hypopnea index (AHI) ≥1/h by polysomnography] were enrolled. Lateral neck radiographs were obtained from the patients. All subjects were separated by age: pre-adolescent group (3-8 years old) and adolescent group (9-15 years old). RESULTS: Overall, 45 patients in the pre-adolescent group (33 boys and 12 girls) and 18 patients in the adolescent group (10 boys and 8 girls) were enrolled, and sex differences were compared in each group. We found sex differences in craniofacial features and severity of OSA in the adolescent group, in which girls with OSA had more upper airway space, in addition to lower AHI, lower 3% oxygen desaturation index (ODI), higher minimum SO2 and better sleep efficiency than the boys. CONCLUSIONS: The present study found revealed sex differences in pediatric OSA patients in the adolescent group. Girls in the adolescent group had more upper airway space in addition to lower AHI, lower 3% ODI, higher minimum SO2 and better sleep efficiency than boys.

Prevalence and Clinical Correlates of Sleep-Disordered Breathing in Patients Hospitalized With Acute Decompensated Heart Failure.

BACKGROUND: Limited data are available regarding the presence of sleep-disordered breathing (SDB) assessed using polysomnography in patients hospitalized with left ventricular (LV) systolic dysfunction after acute decompensated heart failure (ADHF). We investigated the prevalence and clinical correlates of SDB in patients hospitalized with ADHF and LV systolic dysfunction. METHODS: Prospectively collected data from 105 consecutive patients with an LV ejection fraction < 50% who were hospitalized with ADHF from May 2012 to July 2014 were retrospectively assessed. Polysomnography was performed during the initial hospitalization after the initial improvement in ADHF acute signs and symptoms. The apnea-hypopnea index (AHI), including obstructive or central AHI, was computed as a severity of obstructive or central sleep apnea. Echocardiography and blood sampling for various parameters, such as B-type natriuretic peptide level, were performed systematically. RESULTS: The proportions of patients with an AHI ≥ 5 events per hour and those with an AHI ≥ 15 events per hour were 93% and 69%, respectively, and central sleep apnea was predominant (66% and 44%, respectively). In the multivariate analysis, only body mass index (BMI) was independently correlated with AHI, whereas age, BMI, and E/e' level were independently correlated with obstructive AHI. In addition, use of loop diuretics and E/e' level were independently correlated with central AHI. CONCLUSIONS: SDB determined using polysomnography was common in hospitalized patients with ADHF and LV systolic dysfunction. Age, BMI, and E/e' levels were significantly correlated with obstructive sleep apnea severity, whereas E/e' levels and use of loop diuretics were significantly correlated with central sleep apnea severity.

Change in type of sleep-disordered breathing from predominant central to obstructive sleep apnea following coronary artery bypass grafting.

We report the case of a 67-year-old overweight man with reduced left ventricular ejection fraction (LVEF) due to myocardial infarction. He had an implantable cardioverter defibrillator (ICD) for frequent episodes of ventricular tachyarrhythmia and was initiated into adaptive-servo ventilation therapy for severe central sleep apnea (CSA), which was not suppressed by continuous positive airway pressure (CPAP). Since he still had several episodes of appropriate ICD therapies, coronary angiogram was performed, and severe three-vessel disease was found. He then underwent coronary artery bypass grafting (CABG). After CABG, his LVEF did not improve (from 29 to 25%); however, the B-type natriuretic peptide level decreased (from 560 to 330 pg/mL). Although the apnea-hypopnea index did not change (49.4 before and 55.1/h after CABG), his CSA converted to predominant obstructive sleep apnea accompanied by a shortening of the lung-to-finger circulation time (from 43 to 29 s) 2 weeks after CABG, which was completely suppressed by CPAP. .

Acute Effects of Positive Airway Pressure on Functional Mitral Regurgitation in Patients with Systolic Heart Failure.

Background: Acute effects of positive airway pressure (PAP) [including continuous PAP (CPAP) and adaptive servo-ventilation, an advanced form of bi-level PAP] on functional mitral regurgitation (fMR) in patients with heart failure (HF) with left ventricular (LV) systolic dysfunction remain unclear. Thus, whether PAP therapy reduces fMR in such patients with HF was investigated. Methods and Results: Twenty patients with HF and LV systolic dysfunction defined as LV ejection fraction (LVEF) <50% (14 men; mean LVEF, 35.0 ± 11.5%) with fMR underwent echocardiography during 10-min CPAP (4 and 8 cm H2O) and adaptive servo-ventilation. For fMR assessment, MR jet area fraction, defined as the ratio of MR jet on color Doppler to the left atrial area, was measured. The forward stroke volume (SV) index (fSVI) was calculated from the time-velocity integral, cross-sectional area of the aortic annulus, and body surface area. fMR significantly reduced on CPAP at 8 cm H2O (0.30 ± 0.12) and adaptive servo-ventilation (0.29 ± 0.12), compared with the baseline phase (0.37 ± 0.12) and CPAP at 4 cm H2O (0.34 ± 0.12) (P < 0.001). The fSVI did not change in any of the PAP sessions (P = 0.888). However, significant differences in fSVI responses to PAP were found between sexes (P for interaction, 0.006), with a significant reduction in fSVI in women (P = 0.041) and between patients with baseline fSVI ≥ and < the median value (27.8 ml/m2, P for interaction, 0.018), with a significant fSVI reduction in patients with high baseline fSVI (P = 0.028). In addition, significant differences were found in fSVI responses to PAP between patients with LV end-systolic volume (LVESV) index ≥ and < the median value (62.0 ml/m2, P for interaction, 0.034), with a significant fSVI increase in patients with a high LVESV index (P = 0.023). Conclusion: In patients with HF, LV systolic dysfunction, and fMR, PAP can alleviate fMR without any overall changes in forward SV. However, MR alleviation due to PAP might be associated with a decrease in forward SV in women with high baseline SV, whereas MR alleviation due to PAP might be accompanied by increased forward SV in patients with a dilated LV.

Adaptive servo-ventilation in cardiac function and neurohormonal status in patients with heart failure and central sleep apnea nonresponsive to continuous positive airway pressure.

OBJECTIVES: The aim of this study was to investigate whether effective suppression of central sleep apnea (CSA) by adaptive servo-ventilation (ASV) improves underlying cardiac dysfunction among patients with heart failure (HF) in whom CSA was not effectively suppressed by continuous positive airway pressure (CPAP). BACKGROUND: The presence of CSA in HF is associated with a poor prognosis, whereas CPAP treatment improves HF. However, in a large-scale trial, CPAP failed to improve survival, probably due to insufficient CSA suppression. Recently, ASV was reported as the most effective alternative to CSA suppression. However, the effects of sufficient CSA suppression by ASV on cardiac function are unknown. METHODS: Patients with New York Heart Association class ≥II HF, left ventricular ejection fraction <50%, and CSA that was unsuppressed (defined as an apnea-hypopnea index ≥15) despite ≥3 months of CPAP were randomly assigned to receive ASV in either CPAP mode or ASV mode. RESULTS: Of 23 patients enrolled, 12 were assigned to the ASV-mode group and 11 were assigned to the CPAP-mode group. Three months after randomization, the ASV mode was significantly more effective in suppressing the apnea-hypopnea index (from 25.0 ± 6.9 events/h to 2.0 ± 1.4 events/h; p < 0.001) compared to the CPAP mode. Compliance was signi-ficantly greater with the ASV mode than with the CPAP mode. Improvement in left ventricular ejection fraction was greater with the ASV mode (32.0 ± 7.9% to 37.8 ± 9.1%; p < 0.001) than with the CPAP mode. CONCLUSIONS: Patients with HF and unsuppressed CSA despite receiving CPAP may receive additional benefit by having CPAP replaced with ASV. Additionally, effective suppression of CSA may improve cardiac function in HF patients.

Change in cardio-ankle vascular index by long-term continuous positive airway pressure therapy for obstructive sleep apnea.

BACKGROUND: It has been reported that patients with obstructive sleep apnea (OSA) have an elevated arterial stiffness, and alleviation of OSA by continuous positive airway pressure (CPAP) might attenuate this. Recently, the cardio-ankle vascular index (CAVI) has been reported to be a highly reproducible arterial stiffness parameter in OSA patients. However, the change in CAVI that occurs following long-term CPAP treatment for OSA remains unclear. METHODS: Patients with moderate-to-severe OSA were enrolled. Changes in CAVI at 1 and 12 months after CPAP initiation (ΔCAVI(1) and ΔCAVI(12), respectively) were assessed. Factors associated with ΔCAVI(1) and ΔCAVI(12) were determined by multivariable regression analyses. RESULTS: Thirty subjects were assessed. CAVI was significantly reduced at 1 month compared with the baseline from 7.80 ± 1.19 to 7.56 ± 1.08 (p = 0.013). A non-significant reduction was observed at 12 months (7.72 ± 1.18, p = 0.365 versus baseline) and CAVI had actually increased compared with that measured at 1 month. In multivariable analyses, ΔCAVI(1) was inversely correlated with CPAP usage (coefficient: -0.500, p = 0.006) and was directly correlated with the change in the ratio of low frequency to high frequency in heart rate variability (coefficient: 0.607, p < 0.001), whereas ΔCAVI(12) was related to the use of angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II-receptor blockers (ARB; coefficient: 0.464, p = 0.013), was directly correlated with the change in hemoglobin A1c levels (coefficient: 0.644, p < 0.001), and was inversely correlated with the change in CPAP usage (coefficient: -0.380, p = 0.046). CONCLUSIONS: CAVI was significantly reduced by short-term CPAP and then slightly increased from 1 to 12 months, which was probably due to natural progression associated with the aging process. However, long-term CPAP treatment had the beneficial effect of maintaining CAVI below baseline levels when associated with the use of ACE-I/ARB, the control of blood glucose and the CPAP compliance.

Plasma pentraxin3 and arterial stiffness in men with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) induces inflammation and vascular damage that might contribute to an increased risk of cardiovascular disease (CVD). However, the mechanisms linking OSA and CVD are not fully understood. Pentraxin3 may play a significant role in vascular inflammation and damage. Currently, there is lack of data on pentraxin3 and its role in vascular damage associated with OSA. METHODS: We enrolled 50 males with OSA and 25 controls matched for age and body mass index (BMI). Patients with OSA were further divided into mild and moderate to severe groups. We measured plasma pentraxin3 and evaluated vascular damage using an arterial stiffness parameter--the cardio-ankle vascular index (CAVI)--in all subjects. In the moderate to severe OSA group, pentraxin3 and CAVI were repeatedly measured following continuous positive airway pressure (CPAP) therapy for 1 month. RESULTS: Pentraxin3 levels in the moderate-to-severe OSA group were significantly higher than those in the mild OSA and control groups, with median levels (25th-75th percentile) of 2.36 (1.79-2.78), 1.63 (1.15-2.05), and 1.53 (1.14-2.04) ng/ml, respectively (P < 0.01). Pentraxin3 level was independently correlated with CAVI (coefficient, 0.34 P < 0.01). In the moderate-to-severe OSA group, pentraxin3 and CAVI levels were significantly reduced (P < 0.01 and P = 0.04, respectively) after 1 month of CPAP therapy. CONCLUSIONS: Plasma pentraxin3 and arterial stiffness levels in the moderate-to-severe OSA group were greater than the corresponding levels in patients without OSA. However, pentraxin3 level can be managed by CPAP therapy for OSA.

Establishment of the cardio-ankle vascular index in patients with obstructive sleep apnea.

BACKGROUND: An arterial stiffness parameter, the cardio-ankle vascular index (CAVI), has been developed. CAVI is adjusted for BP and can be used to measure arterial stiffness with little influence of BP. The purpose of this study was to evaluate the reproducibility, validity, and clinical usefulness of CAVI among patients with obstructive sleep apnea (OSA), who often have elevated BP during measurement. METHODS: Overall, 543 consecutive patients with OSA were studied. CAVI was automatically calculated from the pulse volume record, BP, and the vascular length from the heart to the ankle. First, CAVI was measured three times on different days in 25 patients to evaluate its reproducibility. Second, the correlation between CAVI and BP was assessed. Third, patients were classified into two groups (mild OSA or moderate-to-severe OSA), and the CAVIs of these groups were compared. Fourth, the correlation between CAVI and carotid intima-media thickness (IMT) was also assessed in 74 patients. RESULTS: The mean coefficient of variation was 2.8. CAVI demonstrated weak or no correlations with BP (with systolic BP, r = 0.184; with diastolic BP, r = 0.223). Patients with moderate-to-severe OSA (n = 469) had a significantly greater CAVI than patients with mild OSA (p = 0.034). CAVI was positively correlated with IMT (r = 0.487). CONCLUSIONS: The measurement of CAVI demonstrated good reproducibility and was not affected by the BP during measurement. Additionally, CAVI was positively correlated with another arteriosclerosis indicator. CAVI was higher in patients with more severe OSA and is regarded as a clinically useful index for the progression of vascular damage.