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The ACUTE HF score is a simple risk score that predicts the prognosis of patients with acute heart failure (HF) using clinical and echocardiographic parameters. As this score was developed for a small European population, we aimed to validate this score in an external population.This retrospective observational cohort analysis included patients hospitalized with acute HF during 2015-2019. Of 744 patients, 703 patients with available ACUTE HF scores were analyzed (75 ± 13 years; 61% male; left ventricular ejection fraction [LVEF] 49 ± 17%). Approximately one-third (34.4%) of the patients had reduced LVEF (40%), and 51.4% exhibited preserved LVEF (≥50%). During a median follow-up of 452 days, primary and secondary outcomes were observed in 110 and 204 patients, respectively. The ACUTE HF score successfully stratified patients for primary (all-cause mortality) and secondary endpoints (a composite of all-cause mortality and heart failure rehospitalization) in Kaplan-Meier analyses (log-rank test, P 0.001). Multivariable Cox proportional hazards models showed that the score was significantly independently associated with both primary and secondary endpoints after adjusted by covariates (P 0.001).We validated the risk prediction ability of ACUTE HF score in an Asian population. This score may be applicable in clinical practice.

Renal dysfunction includes glomerular dysfunction (GD) and tubular dysfunction (TD); however, there is limited information regarding the prevalence, coexistence, and prognostic relevance of TD and GD among patients with acute heart failure (AHF).Methods and Results:This study reviewed 489 patients with AHF who had undergone testing at the time of their admission to identify GD (estimated glomerular filtration rate60 mL/min/1.73 mAs a significant proportion of patients with AHF had isolated TD and an increased risk of mortality, patients with AHF should be screened for TD even if they do not have GD.

Identifying patients at risk for poor clinical outcomes following acute heart failure (AHF) is essential. However, data regarding the prognostic effect of sleep-disordered breathing (SDB) and treatment with positive airway pressure (PAP) on clinical outcomes of hospitalized patients following AHF is lacking. This study investigated the prognostic effect of SDB, PAP treatment, and compliance with PAP treatment on patient clinical outcomes. Polysomnography was performed in hospitalized patients whose left ventricular ejection fraction was

Background Astaxanthin has a strong antioxidant effect. We recently demonstrated that following 3-month astaxanthin supplementation, cardiac contractility and exercise tolerance improved, possibly through the suppression of oxidative stress in a small pilot study involving patients with heart failure with left ventricular systolic dysfunction. This is a sub-study of our pilot study to investigate whether improvements of selfreported physical activity and health-related quality of life were observed following 3-month astaxanthin supplementation. Methods We investigated the changes in physical activity by the Specific Activity Scale score and healthrelated quality of life by physical and mental component summary scores in Short Form-8 at baseline and after 3-month astaxanthin supplementation. Results Data from 17 patients with heart failure were assessed. Following 3-month astaxanthin supplementation, the Specific Activity Scale score increased from the median of 4.5 (interquartile range, 2.0) to 6.5 (interquartile range, 1.1) metabolic equivalent (P=0.001), and the physical and mental component summary scores increased from 46.1±9.2 to 50.8±6.8 (P=0.015) and from 48.9±9.1 to 53.8±4.8 (P=0.022), respectively. There was a linear relationship of the baseline heart rate, or mental component summary score with the percent change in the Specific Activity Scale score (r=0.523, P=0.031 and r=-0.505, P=0.039, respectively). In addition, there was a direct relationship of ischemic etiology with the percent change in the physical component summary score (r=0.483, P=0.049, respectively). Finally, there was a linear relationship between the percent change in the Specific Activity Scale score and that in the mental component summary score (r=0.595, P=0.012). Conclusions Following 3-month astaxanthin supplementation, improvements of the self-reported physical activity level and health-related quality of life in both mental and physical components were observed. In patients with heart failure, those with higher baseline heart rate, ischemic etiology, and poorer baseline health-related quality of life have potentials to have greater improvement of physical activity and/or health-related quality of life.

Aims Although both hypercapnia and hypocapnia are common in acute heart failure (AHF) patients, routine assessment of arterial blood gas is not recommended. Additionally, no association between hypercapnia and increased mortality has been found, and the prognostic value of hypocapnia in AHF patients remains to be elucidated. In this observational study, we aimed to investigate the relationship between partial pressure of arterial carbon dioxide (PaCO2), especially low PaCO2, and long-term mortality in AHF patients. Methods and results Acute heart failure patients hospitalized in the cardiac intensive care unit of our institution between 2007 and 2011 were screened. All eligible patients were divided into two groups based on the inflection point (i.e. 31.0 mmHg) of the 3-knot cubic spline curve of the hazard ratio (HR), with a PaCO2 of 40 mmHg as a reference. The association between PaCO2 levels and all-cause mortality was assessed using Cox proportional hazards regression models. Among 435 patients with a median follow-up of 1.8 years, 115 (26.4%) died. Adjusted analysis with relevant variables as confounders indicated that PaCO2 Conclusions In AHF patients, lower PaCO2 at admission was associated with increased long-term mortality risk.

Obstructive sleep apnea (OSA) is induced by a sleep-related collapse of the upper airway in association with multiple factors. The severity of OSA is determined by the apnea-hypopnea index (AHI). Although obesity and sex differences are common factors in OSA, the level of the AHI varies to the same degree according to the age and sex and degree of obesity. However, only a few studies have evaluated AHI over 100/h, those reports did not describe why they set the AHI cutoff at 100/h. The purpose of this study was to elucidate the pathogenesis of “very” severe OSA, defined as having an AHI > 100/h. AHI > 100/h was set as very severe OSA (VS-OSA) in this study. As controls, moderate to severe OSA patients, matched with VS-OSA for age, sex, and body mass index (BMI), were enrolled. The findings of polysomnography and cephalography between VS-OSA and controls were compared. Eleven patients in the VS-OSA group (mean AHI 110.2/h) and 22 patients in the control group (mean AHI 41.6/h) were compared (mean age 50.2 vs 50.6, male:female 5:6 vs 10:12, mean BMI 35.4 kg/m2 vs 34.5 kg/m2). There were no significant differences in the clinical characteristics. In the polysomnographic parameters, the VS-OSA group showed apnea predominance, the mean percutaneous oxygen saturation (SO2) was significantly lower in all sleep stages, and the minimum SO2 was significantly lower (49.0% vs 77.5%, p = 0.002). A similar apnea duration and rather shorter hypopnea duration were shown. The time of apnea-to-arousal was significantly earlier (− 0.1 s vs 0.9 s, p = 0.003). Lung-to-finger circulation time showed no differences. The cephalometric findings showed no significant differences. VS-OSA patients were more likely to have apnea predominance, desaturation when sleeping despite a similar apnea duration, and rather shorter hypopnea duration, and arousals were evoked significantly earlier.

Inflammation activation is associated with adverse outcomes in patients with heart failure (HF). Sleep-disordered breathing (SDB) observed in 50% of patients with HF worsens the clinical outcome of HF, possibly through the exacerbation of inflammation. However, data on inflammation activation related to SDB are limited in patients with HF. We investigated the relationship between SDB severity and serum levels of C-reactive protein (CRP) and tumor necrotic factor (TNF)-α in HF patients with systolic dysfunction. Nineteen patients with HF were enrolled (mean age, 67.3 years; 16 men; mean ejection fraction, 33.6%). No significant correlation was observed between log-transformed CRP level and apnea–hypopnea index (AHI). In univariable analysis for serum CRP level, the percentage of rapid eye movement (REM) sleep per total sleep time was the only significant factor. The lower the percentage of REM sleep, the higher was the CRP level (coefficient, − 0.474; P = 0.047). In contrast, the serum TNF-α level was significantly correlated with age, ischemic etiology, diabetes mellitus, estimated glomerular filtration rate (eGFR), and AHI. In multivariable analysis, eGFR (coefficient, − 0.486; P = 0.017) and AHI (coefficient, 0.399; P = 0.044) significantly and independently correlated with TNF-α level. The severity of SDB expressed as AHI was directly related to the circulating level of TNF-α, but not circulating CRP level, in HF patients with systolic dysfunction.

Malnutrition frequently coexists with heart failure (HF), leading to series of negative consequences. Cheyne–Stokes respiration (CSR) is predominantly detected in patients with HF. However, the effect of CSR and malnutrition on the long-term prognosis of patients with acute decompensated HF (ADHF) remains unclear. We enrolled 162 patients with ADHF (median age, 62 years; 78.4% men). The presence of CSR was assessed using polysomnography and the controlling nutritional status score was assessed to evaluate the nutritional status. Patients were divided into four groups based on CSR and malnutrition. The primary outcome was all-cause mortality. In total, 44% of patients had CSR and 67% of patients had malnutrition. The all-cause mortality rate was 26 (16%) during the 35.9 months median follow-up period. CSR with malnutrition was associated with lower survival rates (log-rank p < 0.001). Age, hemoglobin, albumin, lymphocyte count, total cholesterol, triglyceride, low-density lipoprotein cholesterol, creatinine, estimated glomerular filtration rate, B-type natriuretic peptide, administration of loop diuretics, apnea-hypopnea index and central apnea-hypopnea index were significantly different among all groups (p < 0.05). CSR with malnutrition was independently associated with all-cause mortality. In conclusion, CSR with malnutrition is associated with a high risk of all-cause mortality in patients with ADHF.

Background: Sleep disordered breathing (SDB) is known as a common comorbidity in patients with atrial fibrillation (AF). Indeed, patients undergoing pulmonary vein isolation (PVI) for AF had a high prevalence of SDB in particular, Cheyne-Stokes respiration (CSR). The aim of the present study is to assess the correlates of SDB severity and CSR in AF patients undergoing PVI. Methods and Results: The study was conducted under a single-center, observational design. We enrolled 140 consecutive patients undergoing PVI. All participants underwent home sleep apnea test (ApneaLink Air, ResMed, Australia) which could determine the severity of SDB as assessed by apnea-hypopnea index (AHI) and the percent of CSR (%CSR) pattern. Overall, 33 (27.9%) patients was no SDB (AHI Conclusion: Increased SDB severity correlated with male sex, high age, obesity, hypertension and chronicity of AF in patients with PVI. Correlates the percent of %CSR were male sex, high age, the chronicity of AF, high value of HbA1c, and greater NT-proBNP. Treatment for SDB should be consider for these AF patients, because SDB increases the recurrence ratio of AF after PVI.

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.

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 (β=0.211; P = .014) and lower PCS score (β=−0.177; P = .045). Conclusion In the patients with HF, RLS was prevalent, and sleep quality and QoL may be disrupted by RLS.

The C-reactive protein (CRP) levels obtained at hospital admission are associated with the prognosis of several cardiovascular diseases, including acute coronary syndrome. Although the admission CRP level is associated with in-hospital mortality in patients with acute decompensated heart failure (ADHF), there are limited data on the association between the admission CRP level and long-term mortality in patients with ADHF. This study included consecutive ADHF patients admitted to our institution from 2007 to 2011. Eligible patients were divided into four groups based on quartiles of admission CRP levels. The association between the admission CRP level and long-term mortality was assessed by multivariable Cox proportional analysis, including other independent variables with p values

Objective Although several studies have reported the relationship between hypoalbuminemia and the clinical outcome, it remains disputable in patients with acute decompensated heart failure (ADHF). We therefore investigated the relationship between hypoalbuminemia on admission and long-term mortality in hospitalized patients following ADHF. Methods We examined a cohort of 751 consecutive patients who were admitted to the cardiac intensive-care unit between 2007 and 2011 with a diagnosis of ADHF. These patients were divided into 2 groups according to the presence or absence of hypoalbuminemia on admission, which was defined as a serum albumin ≤3.4 g/dL. A propensity score (PS) was calculated to evaluate the effects of variables related to the presence or absence of hypoalbuminemia. The association between hypoalbuminemia and mortality was assessed using two Cox regression models-namely, conventional adjustment and matching patients with and without hypoalbuminemia using the PS. Results Among the pre-match patients (n=551), 311 (56%) were classified as exhibiting hypoalbuminemia on admission. There were 152 deaths (27.5%), and the median follow-up was 1.9 years. The presence of hypoalbuminemia on admission tended to be associated with increased mortality in the unadjusted model [hazard ratio (HR) 1.32, 95% confidence interval (95% CI) 0.95-1.84; p=0.098] but not in the conventional adjusted model (HR 0.98, 95% CI 0.64-1.52; p=0.938). Even in post-match patients, no association between hypoalbuminemia and mortality was observed (HR 1.09, 95% CI 0.68-1.76; p=0.722). Conclusion Hypoalbuminemia on admission was not associated with long-term mortality in patients with ADHF, even if PS matching was used.

Background Although urinary alpha-1-microglobulin has been used as a marker of tubular dysfunction, its clinical and prognostic values in patients with acute heart failure have not been validated. Methods We analyzed 623 patients (74 ± 13 years old, 60.0% male) with acute heart failure in whom urinary alpha-1-microglobulin (A1MG) levels were measured as tubular markers at the time of admission. The primary endpoint was all-cause mortality. Results The median levels of urinary alpha-1-microglobulin with and without correction for urinary creatinine concentration were 8.80 (interquartile range: 4.20–17.7) mg/dL and 12.9 (5.92–30.7) mg/gCr, respectively. Urinary A1MG levels were significantly correlated with all of beta-2-microglobulin (r = 0.77), N-acetyl-β-D-glucosaminidase (r = 0.51), and estimated glomerular filtration rate (r = −0.42); however, alpha-1-microglobulin was most often predicted using beta-2-microglobulin or N-acetyl-β-D-glucosaminidase. During the 488-day (interquartile range: 185–938 days) follow-up, 141 deaths occurred. Higher A1MG levels were associated with higher mortality even after adjustment for other covariates. Only A1MG, but not beta-2-microglobulin or N-acetyl-β-D-glucosaminidase, yielded incremental prognostic information in addition to the preexisting prognostic factors (net-reclassification improvement: 0.254, P = 0.023; integrated discrimination improvement: 0.015, P = 0.028). Conclusions In patients hospitalized due to acute heart failure, urinary alpha-1-microglobulin was a marker of tubular dysfunction. High alpha-1-microglobulin was associated with all-cause mortality independent of glomerular function and was a better predictor of mortality than urinary beta-2-microglobulin.

Aims Relationships between cardiac acoustic biomarkers (CABs) measured by acoustic cardiography and clinical outcomes have been reported in heart failure (HF) patients. However, no studies have investigated the temporal change of CABs and the corresponding changes in HF status. The purpose of this study was to assess whether the temporal changes of CABs in patients with acute decompensated heart failure (ADHF) reflect changes in cardiac function and status. Methods and results Sixty ADHF patients were enrolled prospectively. CABs and echocardiography data were collected at admission, before discharge, and at the first clinic visit. CABs included electromechanical activation time (EMAT); the time interval from Q wave onset on electrocardiography to the first heart sound (S1), QoS2; the time interval from Q wave onset on electrocardiography to the second heart sound (S2); and third heart sound (S3) and fourth heart sound (S4) intensities, defined as the peak‐to‐peak amplitudes of S3 and S4. EMATc (EMAT/RR) (P = 0.001), S3 intensity (P

Identifying patients at risk for poor clinical outcomes following acute heart failure (AHF) is essential. However, data regarding the prognostic effect of sleep-disordered breathing (SDB) and treatment with positive airway pressure (PAP) on clinical outcomes of hospitalized patients following AHF is lacking.This study investigated the prognostic effect of SDB, PAP treatment, and compliance with PAP treatment on patient clinical outcomes. Polysomnography was performed in hospitalized patients whose left ventricular ejection fraction was 50%. Patients were divided into groups based on whether SDB was defined as an apnea-hypopnea index ≥ 15 and if they had received PAP treatment. Furthermore, patients with SDB and PAP were subdivided into more and less compliant groups. We assessed the incidences of deaths and rehospitalizations due to heart failure.Overall, 241 patients were enrolled; 73% had SDB and 29% were initiated on PAP treatment. At a median follow-up of 1.7 years, 74 clinical events (32 deaths, 42 rehospitalizations) occurred. In the multivariable analysis, compared with the non-SDB group, SDB without PAP treatment was associated with an increased risk of clinical outcomes (hazard ratio [HR] 1.79, P = 0.049), whereas SDB with PAP treatment was not (HR 0.78, P = 0.582). Among patients with PAP treatment, a more compliant group was also inversely associated with clinical events (HR 0.11, P = 0.012).In hospitalized patients with AHF, untreated SDB was associated with worse clinical outcomes that might be reversible by PAP treatment. However, this potential may be suppressed in less compliant patients.

Lung to finger circulation time (LFCT) has been used to estimate cardiac function. We developed a new LFCT measurement device using a laser sensor at fingertip. We measured LFCT by measuring time from re-breathing after 20 seconds of breath hold to the nadir of the difference of transmitted red light and infrared light, which corresponds to percutaneous oxygen saturation. Fifty patients with heart failure were enrolled. The intrasubject stability of the measurement was assessed by the intraclass correlation coefficient (ICC). The ICC calculated from 44 cases was 0.85 (95% confidence interval:0.77-0.91), which means to have “Excellent reliability.” By measuring twice, at least one clear LFCT value was obtained in 89.1% of patients and the overall measurability was 95.7%. We conducted all LFCT measurements safely. High ICCs were obtained even after dividing patients according to age, cardiac index (CI), and New York Heart Association (NYHA) classification; 0.85 and 0.84 (≥ 75 or < 75 years group, respectively), 0.81 and 0.84 (N=28, ≥ or < 2.2 L/min/M2), 0.82 and 0.94 (NYHA Class I-II or Class III). These results show that our new method to measure LFCT is highly stable and feasible for any type of heart failure patients.

Lung to finger circulation time (LFCT) has been used to estimate cardiac function. We developed a new LFCT measurement device using a laser sensor at fingertip. We measured LFCT by measuring time from re-breathing after 20 s of breath hold to the nadir of the difference of transmitted red light and infrared light, which corresponds to percutaneous oxygen saturation. Fifty patients with heart failure were enrolled. The intrasubject stability of the measurement was assessed by the intraclass correlation coefficient (ICC). The ICC calculated from 44 cases was 0.85 (95% confidence interval: 0.77–0.91), which means to have “Excellent reliability.” By measuring twice, at least one clear LFCT value was obtained in 89.1% of patients and the overall measurability was 95.7%. We conducted all LFCT measurements safely. High ICCs were obtained even after dividing patients according to age, cardiac index (CI); 0.85 and 0.84 (≥ 75 or 2). These results show that our new method to measure LFCT is highly stable and feasible for any type of heart failure patients.

Introduction: Identifying hospitalized patients at a high risk for worse long-term clinical outcomes following acute heart failure (AHF) is important. However, limited data regarding influence of sleep-disordered breathing (SDB) and its treatment by positive airway pressure (PAP) on post-discharge clinical outcomes in hospitalized patients following AHF are available. Hypothesis: Presence of SDB may be associated with worse long-term clinical outcomes, which may be reversible by PAP therapy in patients with AHF. The aim of this study is to investigate relationship between SDB, its treatment by PAP and long-term clinical outcomes. Methods: After the initial improvement of AHF, overnight polysomnography was performed on consecutive hospitalized patients whose left ventricular (LV) ejection fraction ≤45% between May 2012 and April 2018. In the present study, SDB was defined as an apnea-hypopnea index ≥15. Patients with SDB were subdivided as those with or without PAP treatment. The incidence of deaths and re-hospitalizations due to exacerbation of heart failure until April 2019 were assessed by stepwise multivariable Cox proportional model. Results: Overall, 241 patients were enrolled. Among them, 73% had SDB and 29% were initiated into PAP. At a median follow-up of 1.7 years, 89 patients had clinical events (36.9%). In the stepwise multivariable analysis, SDB was associated with increased risk of clinical events (hazard ratio [HR], 2.20; P=0.007). Among SDB patients, stepwise multivariable analysis showed that PAP treatment was associated with reduced risk of clinical events (HR 0.45; P=0.022). Conclusions: In hospitalized patients following AHF, presence of SDB was associated with worse long-term clinical outcomes, which may be reversible by PAP therapy. Thus, following AHF, hospitalized patients with LV systolic dysfunction should be evaluated whether they have SDB and considered for SDB treatment before discharge.

Background/Introduction Acute heart failure (AHF) is one of the major causes of mortality, and identifying the patients at high risk of mortality at the time of admission is crucial to improve clinical outcomes. Although some risk prediction models for patients with AHF have been proposed mainly from randomized clinical trials, the patients in such studies tend not to be similar to those in the real world. Recently, BIOSTAT risk score and AHEAD score derived from two large-scale registry dataset are proposed as useful risk stratification tools for patients with AHF. However, these scores have not been well externally validated and their prognostic prediction performance has not been directly compared. Purpose To validate and compare prognostication of BIOSTAT risk score and AHEAD score in AHF patients. Methods Patients who consecutively admitted to the cardiac intensive-care unit in our institution with a diagnosis of AHF from 2007 to 2011 were analyzed. Among them, patients with acute coronary syndrome, dialysis, malignancy were excluded. BIOSTAT risk score was calculated using 5 factors (age, blood urea nitrogen, BNP, hemoglobin, prescription of beta blockers), and AHEAD score was also calculated with 5 factors (atrial fibrillation, hemoglobin, age, creatinine, and diabetes mellitus). We also developed AHEAD + BNP model incorporating BNP into AHEAD score. Endpoint was 1-year all-cause death. Results Overall, 591 eligible patients were enrolled (mean age was 70±14 years old, 64.8% were male) and 96 patients (16.2%) died during the follow-up of 1-year. The median [interquartile range] of AHEAD score and BIOSTAT risk score were 2 [1–3] and 3 [2–4], respectively. The areas under the curves of receiver operating characteristic curve (AUC) were 0.66 for AHEAD, 0.68 for AHEAD + BNP, and 0.72 for BIOSTAT, respectively. The calibration plots for AHEAD, AHEAD + BNP, and BIOSTAT models showed good calibration (Hosmer-Lemeshow test: p=0.89, 0.74, and 0.74, respectively). The BIOSTAT model's AUC was significantly higher compared to AHEAD (p=0.018) and marginally statistically higher compared to AHEAD + BNP (p=0.054). However, BIOSTAT model showed statistically significant net reclassification improvement compared to both AHEAD (NRI: 0.43, p Conclusion The BIOSTAT score comprised of five readily available clinical variables predict 1-year mortality of patients with AHF with good discrimination and calibration. ROC curves Funding Acknowledgement Type of funding source: None

In patients with heart failure (HF), the impact of the Geriatric Nutritional Risk Index (GNRI) on in-hospital mortality and length of hospital stay remains unclear. We aimed to identify the factors associated with increased in-hospital mortality and longer length of hospital stay considering the GNRI in acute decompensated HF with reduced and preserved ejection fraction (HFrEF and HFpEF, respectively). Patients with acute decompensated HF who were admitted to our institution between 2007 and 2011 were investigated. A total of 451 (201, HFrEF, 250, HFpEF) patients were divided into the following: patients with GNRI &lt, 92 and &ge, 92. In HFrEF, there were no significant differences in in-hospital mortality and length of hospital stay between patients with GNRI &lt, 92 (median (interquartile range), 24.0 (23.8) days and 20.0 (15.0) days, respectively, p = 0.32). In HFpEF, despite no differences in in-hospital mortality, patients with GNRI &lt, 92 had significantly longer length of hospital stay than those with GNRI &ge, 92 (median (interquartile range), 20.0 (22.3) days and 17.0 (16.0) days, respectively, p = 0.04). In HFpEF, GNRI &lt, 92, along with lower hemoglobin, higher B-type natriuretic peptide, and elevated C-reactive protein levels, were the independent factors for longer length of hospital stay. Among patients with acute decompensated HF, assessment of nutritional status with GNRI is useful for stratifying patients at high risk for longer length of hospital stay in HFpEF but not in HFrEF. These observations are particularly important when considering the increasing elderly population and prevalence of HFpEF.

Although hyponatremia during hospitalization for acute decompensated heart failure (ADHF) is reportedly related with poor prognosis, the available data regarding the impact of serum sodium level within the low-normal range at admission on clinical events in patients with ADHF is limited.We studied eligible patients admitted to our institution in 2007-2011. All the patients were categorized into 3 groups according to the admission serum sodium levels of < 135 mmol/L (hyponatremia), ≥ 135 and < 140 mmol/L (low-normal range), or ≥ 140 mmol/L (normal range). The association between admission serum sodium levels and long-term clinical events, a composite of all-cause deaths and re-hospitalizations for ADHF, was assessed by multivariable Cox proportional analysis.Of the 584 eligible patients, 208 (35.6%) were in the low-normal range and 99 (16.9%) had hyponatremia on admission. On multivariable analysis, compared with those with a sodium level ≥ 140 mmol/L, patients with hyponatremia were at increased risk for clinical events (hazard ratio [HR], 1.53; P = 0.041), whereas the HR of those in the low-normal range was attenuated and insignificant (HR, 1.08; P = 0.625). However, the HR of each category increased significantly as sodium level decreased (P value for HR trend, 0.024). In addition, when serum sodium level was treated as a continuous variable, the lower the serum sodium level, the greater the risk of clinical events (P = 0.012). The cut-off value of serum sodium level to predict mortality was < 138 mmol/L.In conclusion, a low serum sodium level on admission for ADHF, even if low-normal, can increase the risk of long-term mortality and/or re-hospitalization for ADHF.

In patients with heart failure (HF), sleep‐disordered breathing (SDB) is a common comorbidity and a risk factor for poor clinical outcomes. SDB can be ameliorated by continuous positive airway pressure; however, inadequate adherence remains a major cause of treatment failure. On the other hand, the efficacy of oral appliance (OA) has been proved in orthodontics and otolaryngology, although the efficacy of OA in patients with HF remains to be elucidated. This trial aims to determine the efficacy of OA for SDB in patients with HF. Patients with HF undergoing optimal medical therapy who were diagnosed as having SDB (apnea‐hypopnea index [AHI] ≥ 10 and percentage of central AHI per total AHI ≤ 70%) by using polysomnography (PSG) will be enrolled in the present study. Either patients with HF with reduced ejection fraction (left ventricular ejection fraction [LVEF] ≤ 50%) or HF with preserved ejection fraction (history of hospitalization because of acute decompensated HF) or plasma B‐type natriuretic peptide (BNP) level ≥ 100 pg/mL will be included. Each patient will be randomly assigned into active OA or sham OA. PSG, laboratory, and echocardiographic data will be obtained after 3 months of intervention. The main outcome measures are AHI, plasma BNP, and E/e’ determined with echocardiography. Furthermore, overnight urinary catecholamine, 6‐min walk distance, Epworth sleepiness scale, and health‐related quality of life will be assessed simultaneously. This trial started on April 1, 2017, and the projected end date is March 31, 2019. This study was registered in the University Hospital Medical Information Network (UMIN000025731).

Sleep-disordered breathing (SDB) has been recognized as an important risk factor for coronary artery disease (CAD). However, SDB was not fully examined, because sleep studies are limited. Nocturnal pulse oximetry has been suggested to be a useful tool for evaluating SDB. Therefore, the aim of this study was to investigate the influence of SDB assessed by nocturnal pulse oximetry on clinical outcomes in patients who underwent percutaneous coronary intervention (PCI). We conducted a prospective, multicenter, observational cohort study, wherein SDB was assessed by finger pulse oximetry in patients who underwent PCI from January 2014 to December 2016. SDB was defined as 4% oxygen desaturation index of 5 and higher. The primary endpoint was major adverse cardiac or cerebrovascular event (MACCE), defined as a composite of all-cause mortality, acute coronary syndrome, and/or stroke. Of 539 patients, 296 (54.9%) had SDB. MACCE occurred in 32 patients (5.8%) during a median follow-up of 1.9 years. The cumulative incidence of MACCE was significantly higher in patients with SDB (P = 0.0134). In the stepwise multivariable Cox proportional model, the presence of SDB was a significant predictor of MACCE (hazard ratio 2.26; 95% confidence interval 1.05–5.4, P = 0.036). SDB determined by nocturnal pulse oximetry was associated with worse clinical outcomes in patients who underwent PCI. Screening for SDB with nocturnal pulse oximetry was considered to be important for risk stratification in patients with CAD.

Although elevated blood urea nitrogen (BUN)-to-creatinine (BUN/Cr) ratio at hospital admission has been reported to be associated with poor short-term prognosis, its association to long-term mortality in patients with acute decompensated heart failure (ADHF) remains to be elucidated. Moreover, an additive prognostic value to preexisting renal markers including creatinine and BUN has not been well described. A cohort of 557 consecutive ADHF patients admitted to the cardiac intensive care unit was studied. All cohorts were divided into high and low BUN/Cr ratios according to the median value of BUN/Cr ratio at admission. Association between admission BUN/Cr ratio and long-term all-cause mortality was assessed. There were 145 deaths (27%) observed during the follow-up period of 1.9 years in median. Patients with high BUN/Cr ratio showed with higher mortality compared to low BUN/Cr ratio (log-rank: P = 0.006). In the multivariable analysis, patients with high BUN/Cr ratio at admission were associated with high mortality independently from other covariates including BUN and creatinine (HR 1.81, 95% CI 1.16-2.80, P = 0.009). In patients with ADHF, there is a relationship between admission BUN-to-creatinine ratio and long-term mortality.

Background Diabetes mellitus is considered an important risk factor for cardiovascular diseases. High hemoglobin A1c (HbA1c) levels, which indicate poor glycemic control, have been associated with occurrence of cardiovascular diseases. There are few parameters which can predict cardiovascular risk in patients with well-controlled diabetes. Low 1,5-anhydroglucitol (1,5-AG) levels are considered a clinical marker of postprandial hyperglycemia. We hypothesized that low 1,5-AG levels could predict long-term mortality in acute coronary syndrome (ACS) patients with relatively low HbA1c levels. Methods The present study followed a retrospective observational study design. We enrolled 388 consecutive patients with ACS admitted to the cardiac intensive care unit at the Juntendo University Hospital from January 2011 to December 2013. Levels of 1,5-AG were measured immediately before emergency coronary angiography. Patients with early stent thrombosis, no significant coronary artery stenosis, malignancy, liver cirrhosis, a history of gastrectomy, current steroid treatment, moderately to severely reduced kidney function (estimated glomerular filtration rate

Background The effect of elevated blood glucose (BG) levels on the long-term prognosis of acute decompensated heart failure (ADHF) patients has not been well defined. The purpose of this study is to evaluate the long-term prognosis of ADHF with elevated BG. Methods A cohort of patients consecutively admitted to the cardiac intensive care unit from 2007 to 2011 was studied. Among these, 495 patients who met the criteria were divided into 4 groups based on their BG level and diabetes mellitus (DM) status. The risks for all-cause mortality in each group were assessed using the multivariate Cox proportional hazards model. Results At a median follow-up of 1.8 years, 148 patients had died. There were 168 patients without either BG elevation or DM, 67 without BG elevation but with DM, 105 with BG elevation but not DM, and 155 with both BG elevation and DM. In a multivariate model, those with BG elevation, regardless of DM status, showed a greater risk of increased mortality when compared with patients without either BG elevation or DM [hazard ratio (HR), 1.79; p = 0.042 for BG elevation without DM and HR, 1.73; p = 0.048 for BG elevation with DM]. Conclusion Elevated BG levels, irrespective of the DM status, at the time of admission in patients with ADHF, appear to be a prognostic marker for ADHF.

Medical therapy for severe aortic valve stenosis (AS) is necessary for inoperable patients due to comorbid conditions. Tolvaptan (TLV), unlike other diuretics, resulted in modest changes in filling pressures associated with an increase in urine output, suggesting that TLV improves congestive heart failure (CHF) due to severe AS without hemodynamic instability.We retrospectively investigated 14 consecutive patients ≥ 80 years of age admitted due to decompensated CHF with severe AS at Juntendo University Hospital from April 2014 to November 2015. Seven of the 14 patients were treated with TLV. We examined the safety and efficacy of TLV treatment for severe AS.Mean age was 90.0 ± 6.3 years and mean aortic valve area was 0.57 ± 0.22 cm2. Urine volume at day 1 of TLV treatment was increased and urine osmolality significantly decreased at day 1 of TLV treatment (all P < 0.05). New York Heart Association classification and brain natriuretic peptide levels significantly improved 1 week after treatment and at discharge (all P < 0.05) whereas brain natriuretic peptide levels did not improve in the patients without TLV. Severe adverse events did not occur during TLV treatment. During the first 3 days, blood pressure and heart rate were relatively stable. TLV treatment did not affect serum creatinine, blood urea nitrogen, or the estimated glomerular filtration rate.In elderly patients with severe AS, TLV treatment improved CHF without hemodynamic instability. Further prospective studies are needed to assess the safety and efficacy of TLV in decompensated heart failure due to severe AS.

Background Sleep is an important recovery period for athletes. In general, women are not satisfied with their sleep quality, which is also true for female soccer players, although the reasons remain to be elucidated. This study aimed to confirm sex difference in sleep quality among athletes from various fields of sport, and to investigate factors related to poor subjective sleep quality in male and female athletes. Methods We collected data concerning subjective sleep quality, measured by Pittsburgh Sleep Quality Index (PSQI), from athletes who were 16 to 40 years of age and played various types of sports. Data concerning their sports, lifestyle, and sleep issues and sleep environments, and also menstrual issues for females, were collected. Results Data from 207 male athletes and 215 female athletes were assessed. Among them, 31.4% of men and 48.8% of women had poor subjective sleep quality (i.e., PSQI≥6). In male athletes, witnessed apnea, episodes of disorientation or confusion during the time of sleep, long time gap between dinner and bedtime, and turning on the heating in the winter, were identified as factors associated with poor sleep quality by multivariate analysis, whereas in female athletes, bathing close to bedtime, habitual drinking, and being annoyed by noises at bedtime were identified. Conclusions In both populations, females had poorer subjective sleep quality than males. Sex differences exist in factors associated with poor subjective sleep quality. Thus, different approaches should be considered to improve their sleep quality.

Background: Sleep disordered breathing (SDB) is an important modifiable risk factor of treatment resistant hypertension (TRH). Overnight rostral fluid shift from lower extremities is associated with the severity of SDB in patients prone to fluid accumulation (e.g. TRH, heart failure, and end-stage renal disease). However, the association between overnight rostral fluid shift and SDB in Japanese patients with TRH remains unclear. Methods: All patients with TRH underwent polysomnography. Neck circumference (NC) and leg fluid volume (LFV) were measured by tape measure and bioelectrical impedance just before sleep and after waking up. Correlation between apnea-hypopnea index (AHI), overnight change of LFV (ΔLFV), and overnight change of NC (ΔNC) were assessed by regression analysis. Results: Total 11 patients were examined (7 men [63%], Age: 62.6±13.4 years, body mass index: 28.1±4.2 kg/m 2 ). Mean AHI, ΔLFV, and ΔNC were 30.5±24.1/h. -267.5±156.1 ml, and 0.4±0.5 cm, respectively. ΔLFV correlated significantly with ΔNC (r=-0.63; P=0.04). Besides, both ΔLFV and ΔNC were significantly associated AHI respectively (ΔLFV, r=-0.92; P Conclusion: In Japanese patients with TRH, overnight rostral fluid shift contributes to the worsening of SDB, in association with the increase in NC.

Sleep is an important recovery phase after exercise that should be taken into account by athletes. Females are likely to be dissatisfied with their sleep quality, report sleepiness and, consequently, experience impaired quality-of-life (QOL). However, limited data are available regarding sex differences in sleep quality, sleepiness, and QOL in athletes. Male and female collegiate soccer players were recruited. The Pittsburgh Sleep Quality Index (PSQI) was used to assess subjective sleep quality and the Japanese Version of the Epworth Sleepiness Scale (JESS) was used to evaluate subjective sleepiness. Health-related QOL was evaluated through the short form (SF)-8. Logistic regression analyses were undertaken to assess associations between poor sleep quality (defined as PSQI ≥ 6), subjective sleepiness (defined as JESS ≥ 11), and poor QOL (defined as

The TCB index (triglycerides &times, total cholesterol &times, body weight), a novel simply calculated nutritional index based on serum triglycerides (TGs), serum total cholesterol (TC), and body weight (BW), was recently reported to be a useful prognostic indicator in patients with coronary artery disease. Thus, this study aimed to investigate the relationship between TCBI and long-term mortality in acute decompensated heart failure (ADHF) patients. Patients with a diagnosis of ADHF who were consecutively admitted to the cardiac intensive care unit in our institution from 2007 to 2011 were targeted. TCBI was calculated using the formula TG (mg/dL) &times, TC (mg/dL) &times, BW (kg)/1000. Patients were divided into two groups according to the median TCBI value. An association between admission TCBI and mortality was assessed using univariable and multivariable Cox proportional hazard analyses. Overall, 417 eligible patients were enrolled, and 94 (22.5%) patients died during a median follow-up period of 2.2 years. The cumulative survival rate with respect to all-cause, cardiovascular, and cancer-related mortalities was worse in patients with low TCBI than in those with high TCBI. In the multivariable analysis, although TCBI was not associated with cardiovascular and cancer mortalities, the association between TCBI and reduced all-cause mortality (hazard ratio: 0.64, 95% confidence interval: 0.44&ndash, 0.94, p = 0.024) was observed. We computed net reclassification improvement (NRI) when TCBI or Geriatric Nutritional Risk Index (GNRI) was added on established predictors such as hemoglobin, serum sodium level, and both. TCBI improved discrimination for all-cause mortality (NRI: 0.42, p &lt, 0.001, when added on hemoglobin and serum sodium level). GNRI can improve discrimination for cancer mortality (NRI: 0.96, p = 0.002, when added on hemoglobin and serum sodium level). TCBI, a novel and simply calculated nutritional index, can be useful to stratify patients with ADHF who were at risk for worse long-term overall mortality.

Astaxanthin has strong antioxidant properties. We conducted a prospective pilot study on heart failure (HF) patients with left ventricular (LV) systolic dysfunction to investigate improvements in cardiac function and exercise tolerance in relation to suppression of oxidative stress by 3-month astaxanthin supplementation. Oxidative stress markers&mdash, serum Diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and urinary 8-hydroxy-2&prime, deoxyguanosine (8-OHdG) concentrations, LV ejection fraction (LVEF), and 6-min walk distance (6MWD) were assessed before and after 3-month astaxanthin supplementation. Finally, the data of 16 HF patients were analyzed. Following 3-month astaxanthin supplementation, dROM level decreased from 385.6 &plusmn, 82.6 U.CARR to 346.5 &plusmn, 56.9 U.CARR (p = 0.041) despite no changes in BAP and urinary 8-OHdG levels. LVEF increased from 34.1 &plusmn, 8.6% to 38.0 &plusmn, 10.0% (p = 0.031) and 6MWD increased from 393.4 &plusmn, 95.9 m to 432.8 &plusmn, 93.3 m (p = 0.023). Significant relationships were observed between percent changes in dROM level and those in LVEF. In this study, following 3-month astaxanthin supplementation, suppressed oxidative stress and improved cardiac contractility and exercise tolerance were observed in HF patients with LV systolic dysfunction. Correlation between suppression of oxidative stress and improvement of cardiac contractility suggests that suppression of oxidative stress by astaxanthin supplementation had therapeutic potential to improve cardiac functioning.

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, p0.001; 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 (β = 0.174, p0.001), physical component summary (β = -0.127, p = 0.029), and mental component summary (β = -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.

Background Suvorexant, an orexin receptor antagonist, is known as a safe and effective sleep medication. Many patients with heart failure (HF) have sleep-disordered breathing (SDB) and are short sleepers, and it is unknown whether suvorexant is effective in HF patients and can improve insomnia safely. The aim of this study is to examine the effect of suvorexant on SDB in patients with HF. Methods The Heart Failure with Insomnia and Suvorexant trial of Juntendo University Hospital and Juntendo Shizuoka Hospital (J-FLAVOR trial) is a multicenter trial with a randomized double crossover design. We will enroll a total of 30 HF patients treated in the Juntendo University Hospital and Juntendo Shizuoka Hospital. Eligible patients will undergo portable sleep monitoring twice with or without oral administration of suvorexant in a randomly assigned order. Before the study night, patients in the suvorexant first group will receive suvorexant for 4 consecutive days. There are at least 3 wash-out days between the study nights with and without suvorexant. Primary outcome measures of the non-inferiority trial of suvorexant include the apnea-hypopnea index and the severity of SDB, and the results will be compared between the study nights with and without suvorexant. Conclusion The present study can determine whether suvorexant can be used in HF patients without affecting their SDB. This is a pilot study to primarily assess whether suvorexant affects the severity of SDB in patients with HF. Therefore, further study is warranted to investigate whether suvorexant alters short- and long-term clinical outcomes by providing longer and better sleep in patients with HF.

Background: Hyperuricemia has been known as a risk factor of hypertension, stroke and coronary artery disease (CAD). Uric acid (UA) itself has antioxidative activity, but it is also reported that UA can also stimulate oxidative stress. In healthy subjects, it has been shown that UA has diurnal variation; elevate in the early morning. However, it is unclear whether such diurnal variation is observed and whether corresponding diurnal variation of oxidative stress can also be observed even in patients with CAD. Therefore, we investigated presence of diurnal variation of serum levels of UA, oxidative stress makers in patients with hypertension and CAD. Method: We measured serum levels of UA, NOx, and urinary levels of 8-OHdG, serum at 6 p.m., 6 a.m., 12 p.m. in 26 men with CAD. We excluded patients who was taking drugs which can affect UA levels. Result: Overall 20 patients were enrolled. Serum UA levels were 5.67±0.99 mg/dl at 6 p.m., 5.86±0.99 mg/dl at 6 a.m., and 5.73±0.99 mg/dl at 12 p.m., indicating obvious diurnal variation (P=0.0004). Serum UA levels increased significantly from 6 p.m. to 6 a.m. (P=0.002) and decreased significantly from 6 a.m. to 12 p.m. (P=0.002). Urinary level of 8-OHdG were 13.96±4.95 ng/mlCr at 6 p.m., 19.47±9.20 ng/mlCr at 6 a.m., and 16.19±5.52 ng/mlCr at 12 p.m., indicting corresponding diurnal variation to the serum UA level (P=0.013). Similarly, urinary levels of 8-OHdG increased significantly from 6 p.m. to 6 a.m. (P=0.008) and tend to decrease from 6 a.m. to 12 p.m. (P=0.57). Serum NOx levels were 13.19±6.60μM at 6 p.m., 12.11±6.02μM at 6 a.m. and 15.08±6.61μM at 12 p.m. and showed reciprocal diurnal variation to the serum UA and urinary 8-OHdG levels (p=0.0028). Discussion: Serum UA levels showed diurnal variation even in patients with hypertension and CAD. Considering the fact that oxidative stress makers showed corresponding diurnal variations, diurnal variation of serum UA level may play a role in the pathogenesis of CAD.

Background Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown. Methods We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease. Results Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group (DGLA: 23.2 ± 9.8 vs. 31.5 ± 12.0 μg/ml, AA: 151.1 ± 41.6 vs. 173.3 ± 51.6 μg/ml, and DGLA/AA: 0.16 ± 0.05 vs. 0.19 ± 0.06, all p