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Background: Risk stratification is important in patients with acute heart failure (AHF), and a simple risk score that accurately predicts mortality is needed. The aim of this study is to develop a user-friendly risk-prediction model using a machine-learning method., Methods: A machine-learning-based risk model using least absolute shrinkage and selection operator (LASSO) regression was developed by identifying predictors of in-hospital mortality in the derivation cohort (REALITY-AHF), and its performance was externally validated in the validation cohort (NARA-HF) and compared with two pre-existing risk models: the Get With The Guidelines risk score incorporating brain natriuretic peptide and hypochloremia (GWTG-BNP-Cl-RS) and the acute decompensated heart failure national registry risk (ADHERE)., Results: In-hospital deaths in the derivation and validation cohorts were 76 (5.1 %) and 61 (4.9 %), respectively. The risk score comprised four variables (systolic blood pressure, blood urea nitrogen, serum chloride, and C-reactive protein) and was developed according to the results of the LASSO regression weighting the coefficient for selected variables using a logistic regression model (4 V-RS). Even though 4 V-RS comprised fewer variables, in the validation cohort, it showed a higher area under the receiver operating characteristic curve (AUC) than the ADHERE risk model (AUC, 0.783 vs. 0.740; p = 0.059) and a significant improvement in net reclassification (0.359; 95 % CI, 0.10-0.67; p = 0.006). 4 V-RS performed similarly to GWTG-BNP-Cl-RS in terms of discrimination (AUC, 0.783 vs. 0.759; p = 0.426) and net reclassification (0.176; 95 % CI, -0.08-0.43; p = 0.178)., Conclusions: The 4 V-RS model comprising only four readily available data points at the time of admission performed similarly to the more complex pre-existing risk model in patients with AHF., Competing Interests: Declaration of competing interest Dr. Yuya Matsue is affiliated to a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi and received an honorarium from Otsuka Pharmaceutical Co and Novartis Japan. Dr. Keisuke Kida received honorariums from Daichi Sankyo Co., Ono Pharmaceutical Co., Ltd., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd., and Novartis Pharmaceuticals Co., Ltd. Dr. Takahiro Okumura received research honoraria from Ono Yakuhin, Otsuka, Novartis, and Astrazeneca and research grants from Ono Yakuhin, Amgen Astellas, Pfizer, Alnylam, and Alexion (not in connection with the submitted work). Dr. Yoshihiko Saito received research funds from Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Actelion Pharmaceuticals Japan Ltd., Kyowa Kirin Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nihon Medi-Physics Co., Ltd., Fuji Yakuhin Co., Ltd.; research expences from Roche Diagnostics K.K., Otsuka Pharmaceutical Co., Ltd., Terumo Corporation, Kowa Company, Abbott Medical Japan LLC, Alnylam Japan K.K. Cmic Holdings Co., Ltd.; Speakers' bureau/honorarium from Alnylam Japan K.K., AstraZeneca K.K., Amicus Therapeutics, Inc., Amgen K.K. Edwards Lifesciences Corporation, Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Kowa Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Tsumura & Co., Toa Eiyo Ltd., Nippon Shinyaku Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Bayer Yakuhin Ltd., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K.; Consultation fees from AstraZeneca K.K., Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd.; Other remuneration (supervisor) from Towa Pharmaceutical Co., Ltd. The other authors have nothing to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Hypochloremia is a risk factor for poor outcomes in patients with acute heart failure (AHF). However, the changes in serum chloride levels during decongestion therapy and their impact on prognosis remain unknown., Methods: In total, 2798 patients with AHF were retrospectively studied and divided into four groups according to their admission and discharge serum chloride levels: (1) normochloremia (n=2,192, 78%); (2) treatment-associated hypochloremia, defined as admission normochloremia with a subsequent decrease (<98 mEq/L) during hospitalization (n=335, 12%); (3) resolved hypochloremia, defined as admission hypochloremia that disappeared at discharge (n=128, 5%); (4) persistent hypochloremia, defined as chloride <98 mEq/L at admission and discharge (n = 143, 5%). The primary outcome was all-cause death, and the secondary outcomes were cardiovascular death and a composite of cardiovascular death and rehospitalization for heart failure after discharge., Results: The mean age was 76 ± 12 years and 1584 (57%) patients were men. The mean left ventricular ejection fraction was 46 ± 16%. During a median follow-up period of 365 days, persistent hypochloremia was associated with an increased risk of all-cause death (adjusted hazard ratio [95% confidence interval]: 2.27 [1.53-3.37], p < 0.001), cardiovascular death (2.38 [1.46-3.87], p < 0.001), and a composite of cardiovascular death and heart failure rehospitalization (1.47 [1.06-2.06], p = 0.022). However, the outcomes were comparable between patients with resolved hypochloremia and normochloremia., Conclusions: Persistent hypochloremia was associated with worse clinical outcomes, while resolved hypochloremia and normochloremia showed a comparable prognosis. Changes in serum chloride levels can help identify patients with poor prognoses and can be used to determine subsequent treatment strategies., Competing Interests: Declaration of Competing Interest Dr. Kagiyama is affiliated with and receives a salary from a department funded by Philips Healthcare; Asahi KASEI Corporation; Inter Reha Co., Ltd.; and Toho Holdings Co., Ltd. based on collaborative research agreements. Dr. Kida received honorariums from Daichi Sankyo Co., Ono Pharmaceutical Co., Ltd., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd., and Novartis Pharmaceuticals Co., Ltd. Dr. Matsue received an honorarium from Otsuka Pharmaceutical Co, Novartis Japan, Bayer Inc., and AstraZeneca, and collaborative research grant from Pfizer Japan Inc., Otsuka Pharmaceutical Co and EN Otsuka Pharmaceutical Co., Ltd., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Although an excessive drop in systolic blood pressure (SBP) during acute heart failure (AHF) negatively impacts prognosis, the association between changes in SBP and the diuretic response (DR) is unclear. We aimed to clarify the association between an early drop in SBP and DR/prognosis in patients with AHF., Methods and Results: This was a sub-analysis of the REALITY-AHF study, which registered patients with AHF admitted through emergency departments (EDs). An early SBP drop was defined as the difference between baseline SBP and the lowest value during the first 48 h of hospitalization. DR was defined as the urine output achieved per 40 mg of intravenous furosemide administered. SBP was measured on admission, at 90 min, and 6, 24, and 48 h after admission. Patients were divided into four groups according to their median SBP drop and DR: greater SBP drop/poor DR (n = 322), smaller SBP drop/poor DR (n = 409), greater SBP drop/good DR (n = 419), and smaller SBP drop/good DR (n = 314). The study included 1,464 patients. A greater SBP drop/poor DR was associated with higher baseline SBP and vasodilator use. Multivariable linear regression analysis showed that a greater drop in SBP was associated with poorer DR following adjustment for potential covariates. Cox proportional hazards analysis demonstrated that a greater SBP drop/poor DR was independently associated with 1-year mortality. Both SBP and DR changes were independently associated with prognosis., Conclusion: An early drop in SBP during the first 48 h of hospitalization was associated with poor DR and 1-year mortality in patients with AHF., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/Unique identifier: UMIN000014105., Competing Interests: Conflict of interest: K.K. received an honorarium from Daichi Sankyo Co., Ono Pharmaceutical Co., Ltd., AstraZeneca, Otsuka Pharmaceutical Co., Ltd., and Novartis Pharmaceuticals Co., Ltd. T.O. has received research grants from Ono Pharmaceutical Co., Ltd., Bayer Pharmaceutical Co., Ltd., Daiichi-Sankyo Pharma Inc., and Amgen Astellas BioPharma. T.O. received honorariums from Novartis Pharma, Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., and Medtronic Japan Co., Ltd. N.K. is affiliated with a department funded by Philips Healthcare; Asahi KASEI Corporation; Inter Reha Co., Ltd; and Toho Holdings Co., Ltd based on collaborative research agreements, and receives a research grant from EchoNous Inc. Y.M. is affiliated with a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi, and has received an honorarium from Otsuka Pharmaceutical Co. and Novartis Japan. The other authors have no other conflicts of interest to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We clarified the association between changes in the number of foundational medications for heart failure (FMHF) during hospitalization for worsening heart failure (HF) and post-discharge prognosis. We retrospectively analyzed a combined dataset from three large-scale registries of hospitalized patients with HF in Japan (NARA-HF, WET-HF, and REALITY-AHF) and patients diagnosed with HF with reduced or mildly reduced left ventricular ejection fraction (HFr/mrEF) before admission. Patients were stratified by changes in the number of prescribed FMHF classes from admission to discharge: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor blockers. Primary endpoint was the combined endpoint of HF rehospitalization and all-cause death within 1 year of discharge. The cohort comprised 1113 patients, and 482 combined endpoints were observed. Overall, FMHF prescriptions increased in 413 (37.1%) patients (increased group), remained unchanged in 607 (54.5%) (unchanged group), and decreased in 93 (8.4%) (decreased group) at discharge compared with that during admission. In the multivariable analysis, the increased group had a significantly lower incidence of the primary endpoint than the unchanged group (hazard ratio 0.56, 95% confidence interval 0.45-0.60; P < 0.001). In conclusion, increase in FMHF classes during HF hospitalization is associated with a better prognosis in patients with HFr/mrEF., (© 2022. The Author(s).)

Aims: Acute heart failure (AHF) is a clinical syndrome with a poor prognosis and a major public health concern worldwide. The aim of this study was to investigate whether carperitide administration improves the 1 year prognosis of patients with AHF and to check whether there is an optimal dose of the drug., Methods and Results: We analysed the data of COOPERATE-HF-J (the Consortium for Pooled Data Analysis regarding Hospitalized Patients with Heart Failure in Japan), combining two cohorts (NARA-HF and REALITY-AHF), which included 2435 patients with acute decompensated heart failure. The patients were divided into no carperitide (NO-ANP, n = 1098); very low-dose carperitide (VLD-ANP, <0.02 μg/kg/min, n = 593); and low-dose carperitide groups (LD-ANP, ≥0.02 μg/kg/min, n = 744). The primary endpoint was cardiovascular mortality within 1 year after admission. The secondary endpoints were all-cause mortality and rehospitalization due to worsening heart failure within 1 year after admission. The median carperitide doses in the VLD-ANP and LD-ANP groups were 0.013 and 0.025 μg/kg/min, respectively. Kaplan-Meier analysis showed that cardiovascular mortality and all-cause mortality were significantly lower in the LD-ANP group than in the NO-ANP and VLD-ANP groups (P < 0.001 and P = 0.002, respectively). Multivariable Cox regression analysis for cardiovascular and all-cause mortality revealed that LD-ANP was significantly associated with lower cardiovascular and all-cause mortality within 1 year after admission, even after adjusting other covariates (hazard ratio: 0.696 and 0.791, 95% confidence interval: 0.513-0.944 and 0.628-0.997, P = 0.020 and 0.047, respectively)., Conclusions: Low-dose carperitide was significantly associated with lower cardiovascular and all-cause mortality within 1 year after admission. Our results suggest the necessity for well-designed randomized controlled trials to determine the doses of carperitide that could improve clinical outcomes in patients with AHF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Although intravenous diuretics is a cornerstone of acute heart failure treatment (AHF), its optimal initial dose is unclear. This is a post-hoc analysis of the REALITY-AHF, a prospective multicentre observational registry of AHF. The initial intravenous diuretic dose used in each patient was categorised into below, standard, or above the recommended dose groups according to guideline-recommended initial intravenous diuretic dose. The recommended dose was individualised based on the oral diuretic dose taken at admission. We compared the study endpoints, including 60-day mortality, diuretics response within six hours, and length of hospital stay (HS). Of 1093 patients, 429, 558, and 106 were assigned to the Below, Standard, and Above groups, respectively. The diuretics response and HS were significantly greater in the Below group than in the Standard group after adjusting for covariates. Kaplan-Meier analysis indicated a significantly higher incidence of 60-day mortality in the Above group than the Standard group. This difference was retained after adjusting for other prognostic factors. Treatment with a lower than guideline-recommended intravenous diuretic dose was associated with longer HS, whereas above the guideline-recommended dose was associated with a higher 60-day mortality rate. Our results reconfirm that the guideline-recommended initial intravenous diuretic dose is feasible for AHF., (© 2022. The Author(s).)

Although hypochloremia is strongly associated with adverse prognosis in acute heart failure (AHF), it is unknown whether incorporating hypochloremia into the preexisting risk model improves the model performance. We calculated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score in 1,428 patients with AHF (derivation cohort) and developed 2 risk scores incorporating brain natriuretic peptide (BNP) into the GWTG-HF risk score (GWTG-BNP risk score) and incorporating both BNP and hypochloremia (GWTG-BNP-Cl risk score). Hypochloremia was defined as <98 mmol/L. The external validation and comparison of model performance were performed in an independent group of 1,256 patients with AHF (validation cohort). All models were tested for in-hospital mortality. Hypochloremia was observed in 9.4% and 12.2% of the derivation and validation cohorts, respectively. Hypochloremia was an independent predictor of in-hospital mortality in the derivation cohort (odds ratio 2.02; p = 0.028). In the validation cohort, the GWTG-HF, GWTG-BNP, and GWTG-BNP-Cl risk scores demonstrated good discrimination (area under the curve: 0.742, 0.749, and 0.763, respectively). However, the GWTG-BNP-Cl risk score was more reliable than the GWTG-HF and GWTG-BNP risk scores in risk reclassification (net reclassification improvement: 0.491 and 0.408, respectively; p <0.01 for both). Moreover, this score demonstrated a good calibration of the GWTG-BNP-Cl model (Hosmer-Lemeshow test: p = 0.479). In conclusion, incorporating hypochloremia into the preexisting risk model improves the model performance., Competing Interests: Disclosures Dr. Yuya Matsue is affiliated to a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi and received an honorarium from Otsuka Pharmaceutical Co and Novartis Japan. Dr. Takahiro Okumura received research grants from Ono Pharmaceutical Co., Ltd., Bayer Pharmaceutical Co., Ltd., Daiichi-Sankyo Pharma Inc., and Amgen Astellas BioPharma K.K. outside the submitted work, and received honorariums from Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., and Medtronic Japan Co., Ltd. The other authors have no conlicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Heart failure (HF) is a common and highly morbid cardiovascular disorder. Oxidative stress worsens HF, and uric acid (UA) is a useful oxidative stress marker. The novel anti-hyperuricemic drug febuxostat is a potent non-purine selective xanthine oxidase inhibitor. The present study examined the UA-lowering and prognostic effects of febuxostat in patients with HF compared with conventional allopurinol., Methods: This multicenter, randomized trial included 263 patients with chronic HF who were randomly assigned to two groups and received allopurinol or febuxostat (UA >7.0 mg/dL). All patients were followed up for 3 years after enrollment., Results: There were no significant differences in baseline clinical characteristics between the two groups. The UA level was significantly decreased after 3 years of drug administration compared with the baseline in both groups. Urine levels of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine were lower in the febuxostat group than in the allopurinol group (11.0 ± 9.6 vs. 22.9 ± 15.9 ng/mL), and the rate of patients free from hospitalization due to worsening HF tended to be higher in the febuxostat group than in the allopurinol group (89.0% vs. 83.0%)., Conclusions: Febuxostat is potentially more effective than allopurinol for treating patients with chronic HF and hyperuricemia.This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (https://www.umin.ac.jp/ctr/; ID: 000009817).

Background: Atrial fibrillation (AF) is a common arrhythmia in patients with acute heart failure (AHF). Heart rate (HR) also changes significantly over time. However, the association between changes in HR in AF patients and prognosis is uncertain., Methods and results: We investigated the association between HR reduction in AF achieved within 48 h of admission and 60-day mortality in patients with AHF from the REALITY-AHF study. The percentage HR (%HR) reduction was calculated as (baseline HR-HR at 48 h) / baseline HR × 100. The primary endpoint was 60-day all-cause mortality. In 468 patients with confirmed AF at both admission and 48 h after admission, the median HR at these time points was 105±31 and 84±18 beats/min, respectively. The median %HR reduction was 15.4% (interquartile range 2.2-31.4%). During the 60 days of admission, 39 deaths (8.3%) were recorded, and the %HR reduction within 48 h was significantly associated with 60-day mortality in the unadjusted model (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.77-0.95; P=0.005) and after adjusting for other covariates (HR 0.81; 95% CI 0.68-0.96; P=0.016).Furthermore, the %HR reduction was associated with a significant reduction in 60-day mortality in patients with higher baseline HR., Conclusions: %HR reduction is associated with a better short-term prognosis in patients with AHF presenting with AF, particularly in those with a rapid ventricular response.

Aims: Not all worsening renal function (WRF) during heart failure treatment is associated with a poor prognosis. However, a metric capable providing a prognosis of relevant WRF has not been developed. Our aim was to evaluate if a change in tricuspid regurgitation pressure gradient (TRPG) could discriminate prognostically relevant and not relevant WRF in patients with acute heart failure (AHF)., Methods and Results: We examined 809 consecutive hospitalized patients with heart failure (78 ± 12 years, 54% male). WRF was defined as an increase in creatinine >0.3 mg and ≥25% from admission to discharge. TRPG was measured at admission and before discharge using echocardiography. The primary outcome was all-cause death within 1-year after discharge. Patients were classified as follows for analysis: no WRF and no TRPG increase (n = 523); no WRF and TRPG increase (no WRF with iTRPG, n = 170); WRF and no TRPG increase (WRF without iTRPG, n = 90); and WRF and TRPG increase (WRF with iTRPG, n = 26). A change in TRPG weakly but significantly correlated to a change in haemoglobin and haematocrit, a percent decrease in brain natriuretic peptide, and body weight reduction during the index period of hospitalization. All-cause mortality within 1 year was higher in patients with WRF and iTRPG, compared to the other three groups (P = 0.026). On Cox regression analysis, only WRF with iTRPG was associated with higher mortality (hazard ratio 4.24, P = 0.001), even after adjustment for other confounders., Conclusion: An increase in TRPG may provide a marker to identify prognostically relevant WRF in patients with AHF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Although liver dysfunction is one of the common complications in patients with acute heart failure (AHF), no integrated marker has been defined. The albumin-bilirubin (ALBI) score has recently been proposed as a novel, clinically-applicable scoring system for liver dysfunction. We investigated the utility of the ALBI score in patients with AHF compared to that for a preexisting liver dysfunction score, the Model of End-Stage Liver Disease Excluding prothrombin time (MELD XI) score., Methods: We evaluated ALBI and MELD XI scores in 1,190 AHF patients enrolled in the prospective, multicentre Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure study. The associations between the two scores and the clinical profile and prognostic predictive ability for 1-year mortality were evaluated., Results: The mean MELD XI and ALBI scores were 13.4±4.8 and -2.25±0.48, respectively. A higher ALBI score, but not higher MELD XI score, was associated with findings of fluid overload. After adjusting for pre-existing prognostic factors, the ALBI score (HR 2.11, 95% CI: 1.60-2.79, p<0.001), but not the MELD XI score (HR 1.02, 95% CI: 0.99-1.06, p=0.242), was associated with 1-year mortality. Likewise, area under the receiver-operator-characteristic curves for 1-year mortality significantly increased when the ALBI score (0.71 vs. 0.74, p=0.020), but not the MELD XI score (0.71 vs. 0.72, p=0.448), was added to the pre-existing risk factors., Conclusions: The ALBI score is potentially a suitable liver dysfunction marker that incorporates information on fluid overload and prognosis in patients with AHF. These results provide new insights into heart-liver interactions in AHF patients., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Aims: The prognostic impact of worsening renal function (WRF) in patients with acute heart failure (AHF) remains under debate. Successful decongestion might offset the negative impact of WRF, but little is known about indicators of successful decongestion in the very acute phase of AHF. We hypothesized that decongestion as evaluated by the percent reduction in brain natriuretic peptide (BNP) could identify relevant prognostic implications of WRF in the very acute phase of AHF., Methods and Results: Data on 907 consecutive hospitalized patients with AHF in the REALITY-AHF study (age: 78±12 years; 55.1% male) were analyzed. Creatinine and BNP were measured at baseline and 48 hours from admission. WRF was defined as an increase in creatinine >0.3 mg at 48 hours from admission. The primary endpoint was 1-year all-cause mortality. Patients were divided into four groups according to the presence/absence of WRF and a BNP reduction higher/lower than the median: no-WRF/higher-BNP-reduction (n = 390), no-WRF/lower-BNP-reduction (n = 397), WRF/higher-BNP-reduction (n = 63), and WRF/lower-BNP-reduction groups (n = 57). Kaplan-Meier curve analysis showed that the WRF/lower-BNP-reduction group had a worse prognosis than the other groups. In a Cox regression analysis, only the WRF/lower-BNP-reduction group had higher mortality compared to the no-WRF/higher-BNP-reduction group (hazard ratio: 3.34, p<0.001)., Conclusion: In the very acute phase of AHF, BNP reduction may aid in identifying relevant prognostic significance of WRF., Competing Interests: Dr. Yuya Matsue is affiliated with a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi; received an honorarium from Otsuka Pharmaceutical Co.; and received consulting fees from Edwards Lifesciences and Bristol-Myers Squibb. Other authors have nothing to declare. These conflicts of interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The LHFRS is a simple score derived from three factors (history of hypertension, history of coronary artery disease/myocardial infarction, and red blood cell distribution width) deployed for the risk stratification of AHF in Greek population. This study aimed to validate the Larissa Heart Failure Risk Score (LHFRS) in patients with acute heart failure (AHF) in a Japanese population., Methods: We performed post-hoc analysis of 1670 consecutive patients enrolled in the REALITY-AHF. In all, 964 patients were finally enrolled. Exclusion criteria included patients with anemia, malignancies and sepsis. The primary outcome was defined as a composite of all-cause mortality and/or heart failure readmission, and the secondary outcome was defined as all-cause mortality., Results: The median admission LHFRS value was 1 (interquartile range [IQR]: 0-2). During a median follow-up of 365 (IQR: 161-365) days, the primary and secondary outcomes were observed in 321 and 157 patients, respectively. LHFRS was an independent predictor of both the primary (adjusted hazard ratio per 1-point increase, 95% confidence interval: 1.17 [1.04-1.32], p = 0.011), and the secondary outcomes (1.31 [1.12-1.55], p = 0.001). Patients with higher LHFRS scores (≥2) exhibited significantly worse outcomes than those with lower scores (<2) both for the primary outcome (1.40 [1.07-1.83], p = 0.014) and the secondary outcome (1.60 [1.09-2.34], p = 0.015). Additionally, LHFRS revealed an excellent goodness of fit (observed versus predicted outcomes) for predicting both the primary and the secondary outcomes (p > 0.99 and p = 0.99, respectively)., Conclusion: The simple LHFRS was proved as a reliable predictor of outcomes in patients with AHF., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Although angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been recommended for patients with heart failure, their clinical and prognostic impact in the very acute phase of acute heart failure (AHF) is unclear, mainly because data on their safety and efficacy are lacking., Methods: This study was a post hoc analysis of the REALITY-AHF trial. Patients with AHF who did not take an ACEI or ARB at admission were enrolled. Patients who received these medications within 48 h of admission were categorized as the ACEI/ARB group, and all other patients were categorized as the no ACEI/ARB group. The primary endpoint was a composite of all-cause death and heart failure readmission within 1 year of admission., Results: Of the 1682 patients in the REALITY-AHF cohort, 900 were enrolled in this study, and 288 (32%) were included in the ACEI/ARB group. After propensity score matching, 152 pairs were evaluated, and no significant difference was found for in-hospital mortality, worsening renal function, or length of hospital stay. The ACEI/ARB group had significantly higher event-free survival (hazard ratio 0.51; 95% confidence interval 0.32-0.82; p = 0.006)., Conclusions: Early initiation of ACEIs/ARBs within 48 h of admission for hospitalized patients with AHF was not associated with adverse events and correlated with improved outcomes at 1 year from admission.

Background: Prognostication of patients discharged after acute heart failure (AHF) hospitalization remains challenging. Body weight (BW) reduction is often used as a surrogate marker of decongestion despite the paucity of evidence. We thought to test the hypothesis that B-type natriuretic peptide (BNP) reduction during hospitalization has independent prognostic value in AHF., Methods and Results: We studied the prognostic predictability of percentage BNP reduction achieved during hospitalization in patients from the REALITY-AHF study. Percentage BNP reduction was defined as (BNP on admission - BNP at discharge) / BNP on admission × 100. The primary endpoint was 1-year all-cause death. In 1028 patients (age, 77 ± 13 years; 57% male; left ventricular ejection fraction, 47 ± 16%) with AHF, median BNP level at admission was 747 ng/L (interquartile range, 439-1367 ng/L) and median percentage BNP reduction was 62.5% (interquartile range, 36.5-78.5%). The smallest percentage BNP reduction quartile had more than 2-fold higher risk of all-cause death than the greatest quartile (23.0% vs 9.7%, P< .001). After adjusting for covariates including BNP at discharge, the percentage BNP reduction was significantly associated with all-cause death (hazard ratio 0.96, 95% confidence interval 0.93-0.99, P= .032), whereas percentage BW reduction was not. Percentage BNP reduction was more predictive in patients with heart failure with reduced ejection fraction than in those with preserved ejection fraction., Conclusions: The prognostic value of percentage BNP reduction during hospitalization was superior to that of percentage BW reduction and was independent of other risk markers, including BNP at discharge., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In hospitalized heart failure patients, a poor diuretic response (DR) during the first days of hospital admission is associated with worse outcomes. However, it remains unknown whether DR in the first hours has similar prognostic value. Moreover, data on the sequential change in DR during hospital admission are lacking., Methods and Results: DR (urine output per 40-mg furosemide-equivalent diuretics dose) was measured from 0 to 6 hours (DR6), 6 to 48 hours (DR6-48), and 0 to 48 hours (DR48) of the patient's emergency department (ED) arrival in 1551 patients with acute heart failure (AHF; mean age 78 years, 56% male, and 48% de novo patients with heart failure). Patients with a poor DR within the first 6 hours were older age, had worse renal function, and were already on diuretic treatment before admission. DR6 was only weakly correlated with DR6-48 (Spearman's rho = 0.273; P < .001). DR6, DR6-48, and DR48 were all significantly associated with 60-day mortality independent of other prognostic factors. DR6 and DR48 showed comparable prognostic ability. However, the model combining DR6 with DR6-48 significantly exceeded both DR6 (net reclassification improvement 0.249; P = .032) and DR48 (net reclassification improvement 0.287; P = 0.025) with regard to 60-day mortality prediction., Conclusions: DR measured within the first 6 hours of ED arrival and DR measured during the first 48 hours in patients with AHF have similar prognostic value, although they were moderately correlated. Changes in DR over time provide additional prognostic information., (Copyright © 2018. Published by Elsevier Inc.)

Background: The aim of this study was to assess specialty-related differences in the treatment for patients with acute heart failure (AHF) in the acute phase and subsequent prognostic differences. Methods and Results: We analyzed hospitalizations for AHF in REALITY-AHF, a multicenter prospective registry focused on very early presentation and treatment in patients with AHF. All patients were classified according to the medical specialty of the physicians responsible for contributed most to decisions regarding the initial diagnosis and treatment after the emergency department (ED) arrival. Patients initially managed by emergency physicians (n=614) or cardiologists (n=911) were analyzed. After propensity-score matching, vasodilators were used less often by emergency physicians than by cardiologists at 90 min after ED arrival (29.8% vs. 46.1%, P<0.001); this difference was also observed at 6, 24, and 48 h. Cardiologists administered furosemide earlier than emergency physicians (67 vs. 102 min, P<0.001). However, the use of inotropes, noninvasive ventilation, and endotracheal intubation were similar between groups. In-hospital mortality did not differ between patients managed by emergency physicians and those managed by cardiologists (4.1% vs. 3.8%, odds ratio 1.12; 95% confidence interval 0.58-2.14)., Conclusions: Despite differences in initial management, no prognostic difference was observed between emergency physicians and cardiologists who performed the initial management of patients with AHF.

Heart failure (HF) is a common disease with high prevalence, mortality in hospitalization and after discharge, readmission rates, and burden on healthcare system. Activation of the inflammatory systems is an important role for HF progression, and pentraxin 3 (PTX3) is one of the inflammatory markers. The plasma PTX3 levels increased with advancing the HF severity, and high levels of plasma PTX3 indicated poor prognosis in HF patients. Moreover, we demonstrated that PTX3 had the crucial role for cardiac remodeling under pressure overload using two different genotypes of mice: PTX3 systemic knockout mice and transgenic mice with cardiac-specific overexpression of PTX3.Diuretics are the essential drug for HF treatment, and we designed multicenter, randomized study for evaluating the efficacy and safety of tolvaptan compared to carperitide. Daily urine volume and serum sodium levels were significantly higher, and cardiovascular events were significantly lower in the tolvaptan group than in the carperitide group. Moreover, we investigated the influence of great earthquake in HF patients, and found out that moving into temporary housing by earthquake might affect the incidence of re-hospitalization due to worsening HF.In this review article, we would introduce our research on HF which has various aspects as described above.

Background The Get With the Guidelines-Heart Failure ( GWTG - HF ) risk score was developed using American Heart Association GWTG - HF program data and predicts in-hospital mortality in patients with acute heart failure (HF). We aimed to clarify the prognostic impacts of the GWTG - HF risk score in patients with HF after discharge. Methods and Results We examined the GWTG - HF score in 1452 patients with HF, who were admitted to our hospital and discharged after treatment, by calculating 7 predetermined variables. We divided all subjects into 3 groups according to the GWTG - HF risk score (low, moderate, and high score groups). The plasma B-type natriuretic peptide level significantly increased with increasing GWTG - HF risk score severity (median values of B-type natriuretic peptide: 167.0 in low, 260.7 in moderate, and 418.2 pg/mL in high score groups). We followed up all subjects after discharge, and there were 347 (23.9%) all-cause deaths and 407 (28.0%) cardiac events in follow-up periods. A Kaplan-Meier survival curve demonstrated that event rates of all-cause death and cardiovascular events, including worsening HF and cardiac death, significantly increased with increasing GWTG - HF risk score severity in all subjects, and also in 749 patients with HF with preserved ejection fraction (ejection fraction ≥50%) and 703 patients with HF with reduced ejection fraction (ejection fraction <50%) patients. The multivariable Cox proportional hazard regression analysis demonstrated that the GWTG - HF risk score was one of the significant predictors of all-cause mortality and cardiac events (all-cause mortality: hazard ratio, 1.537, 95% confidence interval, 1.172-2.023; cardiac events: hazard ratio, 1.584, 95% confidence interval, 1.344-1.860, per 10-point increase of GWTG - HF score). Conclusions The GWTG - HF risk score is a useful multivariable score model for several years after hospitalization in patients with HF in a Japanese population.

Exhaled acetone concentration is one of the expected compounds to be a breath biomarker in heart failure. However, it has not been clarified how exhaled acetone concentration changes in clinical course of heart failure.To investigate whether exhaled acetone concentration changes after treatment in acute decompensated heart failure (ADHF).This study included 19 patients with ADHF (ADHF group) and eight patients with stable heart failure (control group). Exhaled acetone was collected from these patients, and the concentration was measured with gas chromatography.The ADHF group had higher heart rates (P = 0.046), higher New York Heart Association class (P < 0.001), higher levels of brain natriuretic peptide (P = 0.026), blood total ketone bodies (P = 0.015), and exhaled acetone concentration (P < 0.001), compared with the control group. In ADHF group, exhaled acetone concentration significantly decreased after treatment (median: 2.40 versus 0.92 ppm, P < 0.001). However, in the control group, exhaled acetone concentration did not significantly change (median: 0.73 versus 0.49 ppm, P = 0.141).In these preliminary findings, exhaled acetone concentration in patients with ADHF drastically decreased by treatment. Serial exhaled acetone measurement might be useful to evaluate the course of ADHF.

Background: The intravascular compartment is known as the plasma volume, and the extravascular compartment represents fluid within the interstitial space. Plasma volume expansion is a major symptom of heart failure. The aim of the current study was to investigate the impact of plasma volume status on the prognosis of acute heart failure syndromes., Methods and Results: We analyzed 1115 patients with acute heart failure syndromes who were admitted to our hospital. These patients were divided into three groups based on their plasma volume status at admission: first tertile (plasma volume status <41.9%, n = 371), second tertile (41.9%⩽ plasma volume status <49.0%, n = 372), and third tertile (49.0%⩽ plasma volume status, n = 372). Plasma volume status was defined as follows: actual plasma volume = (1 - hematocrit) × [ a + ( b × body weight)] ( a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal plasma volume = c × body weight ( c=39 in males and c=40 in females); and plasma volume status = [(actual plasma volume - ideal plasma volume)/ideal plasma volume] × 100 (%). In the Kaplan-Meier analysis, all-cause mortality, cardiac mortality and cardiac events increased progressively from the first to third tertile ( p <0.001, respectively). In the Cox proportional hazard analysis, after adjusting for potential confounding factors, plasma volume status was an independent predictor of all-cause mortality (hazard ratio 1.429, p < 0.001), cardiac mortality (hazard ratio 1.416, p = 0.001) and cardiac events (hazard ratio 1.207, p = 0.004)., Conclusion: Increased congestion is associated with increased morbidity and mortality in heart failure patients. Plasma volume status, which represents intravascular compartment and congestion, can identify poor prognosis in patients with acute heart failure syndromes.

Background: Zinc is an essential cofactor for energy transfer and physiological heart function, has antioxidant properties, and is involved in multiple signaling pathways. We aimed to investigate the associations between serum zinc levels with prognosis, as well as underlying cardiac function and exercise capacity, in patients with heart failure (HF)., Methods and Results: We measured serum zinc levels in 968 consecutive hospitalized patients with decompensated HF, who were divided into 3 groups based on serum zinc levels (µg/dL): first (zinc ≥75, n = 323), second (62≤ zinc <75, n = 322), and third (zinc <62, n = 323) tertiles. We examined cardiac function and exercise capacity and followed up on all patients. Although cardiac function did not differ among the 3 groups, peak oxygen consumption was significantly lower in the third tertile than in the first and second tertiles (peak oxygen consumption, 14.2 vs 15.9 and 15.2 mL/kg/min, P = .010). In the Kaplan-Meier analysis (mean duration of follow-up 1103 days), cardiac and all-cause mortality was highest in the third tertile compared with the first and second tertiles. In the Cox proportional hazard analysis, serum zinc level was a predictor of cardiac and all-cause mortality. In the subgroup analysis, there were no interactions concerning associations between serum zinc levels with prognosis and other important variables, including age, gender, comorbidities, medications, other micronutrient levels, B-type natriuretic peptide, and left ventricular ejection fraction. The associations between zinc levels with mortality were consistent in all subgroups., Conclusion: Decreased serum zinc levels are associated with high mortality, accompanied by impaired exercise capacity., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

We aimed to investigate the impact of testosterone on the prognosis of heart failure (HF), as well as the underlying cardiac function, cardiac damage, and exercise capacity. We analyzed consecutive 618 men with HF (age 65.9 years). These patients were divided into quartiles based on their serum levels of total testosterone (TT): first (TT > 631 ng/dl, n = 154), second (462 < TT ≤ 631 ng/dl, n = 155), third (300 < TT ≤ 462 ng/dl, n = 156), and fourth (TT ≤ 300 ng/dl, n = 153) quartiles. In the Kaplan-Meier analysis (mean 1,281 days), all-cause mortality progressively increased throughout from the first to the fourth groups. In the multivariable Cox proportional hazard analysis, TT was found to be an independent predictor of all-cause mortality (hazard ratio 0.929, p = 0.042). In addition, we compared the parameters of echocardiography and cardiopulmonary exercise testing, as well as levels of B-type natriuretic peptide and cardiac troponin I, among the 4 groups. Left ventricular ejection fraction and B-type natriuretic peptide did not differ among the groups. In contrast, the fourth quartile, compared with the first, second, and third groups, had higher levels of troponin I and lower peak VO 2 (p <0.05, respectively). Decreased serum testosterone is associated with myocardial damage, lower exercise capacity, and higher mortality in men with HF., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Sleep-disordered breathing (SDB) is associated with arterial stiffness, which may be one of the factors that lead to heart failure (HF). We examined the relationship between pulse wave velocity (PWV) and SDB in patients who have HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)., Methods and Results: We measured the apnoea-hypopnoea index (AHI) by polysomnography, echocardiographic parameters, and PWV in 221 HF patients. Age, blood pressure, and PWV were higher in HFpEF (ejection fraction > 50%, n = 70) patients than in HFrEF (ejection fraction < 50%, n = 151) patients. All HF patients were divided into three groups according to AHI: none-to-mild SDB group (AHI < 15 times/h, n = 77), moderate SDB group (15 < AHI < 30 times/h, n = 59), and severe SDB group (AHI > 30 times/h, n = 85). Although blood pressure and echocardiographic parameters did not differ among the three groups, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups (P = 0.002). When the HFrEF and HFpEF patients were analysed separately, PWV was significantly higher in the severe SDB group than in the none-to-mild and moderate SDB groups in patients with HFpEF (P = 0.002), but not in those with HFrEF (P = 0.068). In the multiple regression analysis to determine PWV, the presence of severe SDB was found to be an independent predictor of high PWV in HFpEF (β = 0.234, P = 0.005), but not in HFrEF patients., Conclusions: Severe SDB is associated with elevated arterial stiffness and may be related to the pathophysiology of HF, especially in HFpEF patients., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Guideline-directed medical therapy (GDMT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF). However, the prognostic impact of medication optimization at the time of discharge in patients hospitalized with heart failure (HF) is unclear. We analyzed 534 patients (73 ± 13 years old) with HFrEF. The status of GDMT at the time of discharge (prescription of angiotensin converting enzyme inhibitor [ACE-I]/angiotensin receptor blocker [ARB] and β blocker [BB]) and its association with 1-year all-cause mortality and HF readmission were investigated. Patients were divided into 3 groups: those treated with both ACE-I/ARB and BB (Both group: n = 332, 62%), either ACE-I/ARB or BB (Either group: n = 169, 32%), and neither ACE-I/ARB nor BB (None group: n = 33, 6%), respectively. One-year mortality, but not 1-year HF readmission rate, was significantly different in the 3 groups, in favor of the Either and Both groups. A favorable impact of being on GDMT at the time of discharge on 1-year mortality was retained even after adjustment for covariates (Either group: hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.21 to 0.90, p = 0.025 and Both group: HR 0.29, 95% CI 0.13-0.65, p = 0.002, vs None group). For 1-year HF readmission, no such association was found. In conclusion, optimization of GDMT before the time of discharge was associated with a lower 1-year mortality, but not with HF readmission rate, in patients hospitalized with HFrEF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: Heart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects, including stiffness and/or congestion of multiple organs. Poor prognosis is expected in heart failure patients with liver stiffness, which has recently been assessed by non-alcoholic fatty liver disease fibrosis score (NFS; based on aspartate aminotransferase to alanine aminotransferase ratio, platelet counts, and albumin). We aimed to investigate the impact of NFS on prognosis of HFpEF patients, with consideration for the peripheral collagen markers such as procollagen type III peptide (PIIIP), type IV collagen 7S, and hyaluronic acid., Methods and Results: We performed a prospective observational study. Consecutive 492 hospitalized HFpEF patients were divided into four groups based on their NFS: first-fourth quartiles (n = 123). The fourth quartile group had the highest levels of PIIIP, type IV collagen 7S, hyaluronic acid, and B-type natriuretic peptide (P<0.001 each). In addition, there were significant positive correlations between PIIIP, type IV collagen 7S, hyaluronic acid, B-type natriuretic peptide, and NFS (P < 0.001 each). In the follow-up period (mean 1107 days), 93 deaths occurred. All-cause mortality increased in all four quartiles (8.1%, 12.2%, 23.6%, and 31.7%, P < 0.001). In the multivariable Cox proportional hazard analysis, NFS was an independent predictor of all-cause mortality in the HFpEF patients., Conclusions: NFS, a novel indicator of liver fibrosis, correlates with circulating systemic markers of fibrosis and congestion and is associated with higher all-cause mortality in HFpEF patients. NFS can be calculated simply and may be a useful tool to assess liver stiffness and prognosis in HFpEF patients., (© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Atrial fibrillation (AF) is common in patients with heart failure and is associated with higher mortality. Although previous studies have reported that direct oral anticoagulants (DOACs) reduce the risk of cardiovascular events in out-patients with AF, it remains unclear whether DOACs reduce mortality in hospitalized heart failure (HHF) patients with AF. Therefore, we examined the impact of DOACs on mortality in this group of patients., Methods: Consecutive 497 HHF patients with AF were retrospectively registered and divided into three groups on the basis of the presence of anticoagulant therapy: non-anticoagulant group (Non, n = 90), Vit K antagonists (VKAs) group (n = 257) and DOACs group (n = 150). We followed up all the patients for mortality., Results: In the Kaplan-Meier analysis (mean follow-up of 1093 days), all-cause mortality was significantly lower in the VKAs and DOACs groups than in the Non group (31.1% and 15.3% vs. 43.3%, log-rank P < 0.001). In the multivariable Cox proportional hazard analysis after adjusting for other potential confounding factors, usage of DOACs and VKAs were independently associated with lower mortality in HHF patients AF (DOACs, HR 0.356, P = 0.001; VKAs, HR 0.472, P = 0.002). Furthermore, the propensity-matched 1:1 cohort was assessed based on the propensity score (DOACs, n = 114 and VKAs, n = 114). All-cause mortality was significantly lower in the DOACs group than in the VKAs group in the post-matched cohort (12.3% vs. 35.1%, log-rank P = 0.038). In the Cox proportional hazard analysis, the use of DOACs was associated with lower mortality in the post-matched cohort (HR 0.526, P = 0.041)., Conclusion: Appropriate use of anticoagulants in HHF patients with AF is important, and DOACs potentially improve all-cause mortality in such patients.

Background: Several echocardiographic parameters are currently used to evaluate left ventricular (LV) filling pressure. However, these parameters are not always consistent in the clinical setting. We aimed to determine a novel parameter by multiplying log B-type natriuretic peptide (lnBNP) and the ratio of mitral inflow early and late diastolic filling velocities (E/A) for the prediction of pulmonary capillary wedge pressure (PCWP)., Methods and Results: One hundred ninety-eight patients suspected of chronic heart failure were analyzed. The product of lnBNP and E/A (BNP × E/A) showed the highest correlation coefficient with mean PCWP (R = 0.7326) compared with E/A (R = 0.7010) and E/e' (R = 0.3922). Multivariate logistic regression analysis revealed that BNP × E/A was associated with elevated PCWP (odds ratio 1.640, 95% confidence interval 1.312-2.197; P <.01). In the receiver operating characteristic curve analysis for detecting elevated PCWP, BNP × E/A showed the largest area under the curve (AUC) compared with E/A and E/e' (0.880 vs 0.827 and 0.788, respectively; P <.05). BNP × E/A still showed large AUC (0.842) for detection of elevated PCWP in patients with normal LV ejection fraction., Conclusion: BNP × E/A is a useful parameter for detecting elevated PCWP regardless of the LV ejection fraction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: It is widely recognized that overt hyper- as well as hypothyroidism are potential causes of heart failure (HF). Additionally it has been recently reported that subclinical hypothyroidism (sub-hypo) is associated with atherosclerosis, development of HF, and cardiovascular death. We aimed to clarify the effect of sub-hypo on prognosis of HF, and underlying hemodynamics and exercise capacity., Methods: We measured the serum levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4) in 1100 consecutive HF patients. We divided these patients into 5 groups on the basis of plasma levels of TSH and FT4, and focused on euthyroidism (0.4 ≤ TSH ≤ 4 μIU/mL and 0.7 ≤ FT4 ≤ 1.9 ng/dL; n = 911; 82.8%) and sub-hypo groups (TSH > 4 μIU/mL and 0.7 ≤ FT4 ≤ 1.9 ng/dL; n = 132; 12.0%). We compared parameters of echocardiography, cardiopulmonary exercise testing, and cardiac catheterization, and followed up for cardiac event rate and all-cause mortality between the 2 groups., Results: Although left ventricular ejection fraction did not differ between the 2 groups, the sub-hypo group had lower peak breath-by-breath oxygen consumption and higher mean pulmonary arterial pressure than the euthyroidism group (peak breath-by-breath oxygen consumption, 14.0 vs 15.9 mL/min/kg; P = 0.012; mean pulmonary arterial pressure, 26.8 vs 23.5 mm Hg, P = 0.020). In Kaplan-Meier analysis (mean 1098 days), the cardiac event rate and all-cause mortality were significantly higher in the sub-hypo group than those in the euthyroidism group (log rank, P < 0.01, respectively). In Cox proportional hazard analysis, sub-hypo was a predictor of cardiac event rate and all-cause mortality in HF patients (P < 0.05, respectively)., Conclusions: Sub-hypo might be associated with adverse prognosis, accompanied by impaired exercise capacity and higher pulmonary arterial pressure, in HF patients., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims We aimed to determine the differences of impact of cardiopulmonary exercise testing (CPX) parameters on prognosis of heart failure with reduced left ventricular ejection fraction (HFrEF), preserved ejection fraction (HFpEF) and mid-range ejection fraction (HFmrEF). Methods We compared clinical characteristics and CPX parameters among the three groups, and the value of each CPX parameter to predict adverse cardiac events (cardiac deaths and re-hospitalizations for heart failure), cardiac deaths and all-cause deaths. Results Of 1190 patients, 41.9% had HFrEF, 36.8% had HFpEF and 21.3% had HFmrEF. The patients in HFrEF group had higher rates of adverse cardiac events, cardiac death and all-cause death than those of HFpEF and HFmrEF groups. In HFrEF, the independent predictors of adverse cardiac events were peak oxygen consumption and oxygen uptake efficiency slope, predictors of cardiac death were peak oxygen consumption and oxygen uptake efficiency slope, and the predictor of all-cause death was peak oxygen consumption. In HFpEF, the predictor of adverse cardiac events was peak oxygen consumption, predictors of cardiac deaths and all-cause deaths were peak oxygen consumption and exertional oscillatory ventilation. In HFmrEF, predictors of adverse cardiac events were peak oxygen consumption and oxygen uptake efficiency slope, and the predictor of cardiac deaths and all-cause deaths was peak oxygen consumption. Conclusion Peak oxygen consumption is the strong predictor for adverse events in all groups. Oxygen uptake efficiency slope predicts adverse prognosis in HFrEF, but not in HFpEF. In contrast, exertional oscillatory ventilation is the predictor only in HFpEF. Thus, different CPX parameters may be able to differentially predict prognosis in HFrEF and HFpEF. Those for predicting prognosis in HFmrEF may be intermediate between HFrEF and HFpEF.

Background: Breath acetone is a noninvasive biomarker of heart failure; however, its significance in heart failure patients with diabetes mellitus has yet to be clarified. The objective of this study is to investigate whether exhaled acetone concentration is a noninvasive biomarker in heart failure patients with diabetes mellitus., Methods: This study prospectively included 35 diabetic patients with stage C heart failure and 20 diabetic patients with or at risk of heart failure (stage A or B). Exhaled breath was collected after an overnight fast., Results: The stage C group had significantly higher brain natriuretic peptide levels, larger left ventricular diameter, lower left ventricular ejection fraction, and more frequent use of β-blocker, compared with the stage A or B group. The stage C group had higher exhaled acetone concentrations than the stage A or B group (p = 0.013). Exhaled acetone concentration was correlated with total ketone bodies (r = 0.588, p < 0.001) and brain natriuretic peptide (r = 0.415, p = 0.002)., Conclusion: Stage C heart failure patients with diabetes mellitus have elevated exhaled acetone concentrations. Exhaled acetone concentration could be a noninvasive biomarker in heart failure patients with diabetes mellitus.

Aim: To investigate the clinical features of heart failure in extremely elderly patients., Methods: We analyzed 1163 consecutive hospitalized heart failure patients. The patients were divided into an extremely elderly group (≥85 years-of-age, n = 88) and a non-extremely elderly group (<85 years-of-age, n = 1075)., Results: The extremely elderly group had higher rates of hypertension, chronic kidney disease, anemia, higher systolic blood pressure and lower body mass index, and lower use of β-blockers and anticoagulants compared with the non-extremely elderly group. During the mean follow-up period of 1038 days, the extremely elderly group had higher mortality compared with the non-extremely elderly group (P < 0.001). In multivariate analysis, in the non-extremely elderly group, age (HR 1.027, P < 0.001), body mass index (HR 0.919, P < 0.001), New York Heart Association III or IV (HR 3.626, P < 0.001), preserved ejection fraction (HR 0.553, P < 0.001), anemia (HR 1.941, P < 0.001), β-blockers (HR 0.695, P = 0.028) and renin-angiotensin system inhibitors (HR 0.603, P = 0.001) were independent predictors for all-cause death. In contrast, atrial fibrillation (HR 2.042, P = 0.015) and renin-angiotensin system inhibitors (HR 0.470, P = 0.014) were independent predictors for all-cause death in the extremely elderly group, suggesting that the prognostic factors were different between the two groups., Conclusions: We should be careful of atrial fibrillation and renin-angiotensin system inhibitors in managing extremely elderly patients with heart failure. Geriatr Gerontol Int 2017; 17: 2194-2199., (© 2017 Japan Geriatrics Society.)

Background: Acute heart failure (AHF) is a life-threatening disease requiring urgent treatment, including a recommendation for immediate initiation of loop diuretics., Objectives: The authors prospectively evaluated the association between time-to-diuretic treatment and clinical outcome., Methods: REALITY-AHF (Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure) was a prospective, multicenter, observational cohort study that primarily aimed to assess the association between time to loop diuretic treatment and clinical outcome in patients with AHF admitted through the emergency department (ED). Door-to-furosemide (D2F) time was defined as the time from patient arrival at the ED to the first intravenous furosemide injection. Patients with a D2F time <60 min were pre-defined as the early treatment group. Primary outcome was all-cause in-hospital mortality., Results: Among 1,291 AHF patients treated with intravenous furosemide within 24 h of ED arrival, the median D2F time was 90 min (IQR: 36 to 186 min), and 481 patients (37.3%) were categorized as the early treatment group. These patients were more likely to arrive by ambulance and had more signs of congestion compared with the nonearly treatment group. In-hospital mortality was significantly lower in the early treatment group (2.3% vs. 6.0% in the nonearly treatment group; p = 0.002). In multivariate analysis, earlier treatment remained significantly associated with lower in-hospital mortality (odds ratio: 0.39; 95% confidence interval: 0.20 to 0.76; p = 0.006)., Conclusions: In this prospective multicenter, observational cohort study of patients presenting at the ED for AHF, early treatment with intravenous loop diuretics was associated with lower in-hospital mortality. (Registry focused on very early presentation and treatment in emergency department of acute heart failure syndrome; UMIN000014105)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Effective treatments in heart failure (HF) patients with ischemic etiology have not been fully established. Nicorandil, combination of nitrate component and sarcolemmal adenosine triphosphate-sensitive potassium channel opener, is a potent vasodilator of coronary and peripheral vessels and has been used as an antianginal agent. Therefore, we examined impacts of nicorandil on cardiac mortality in ischemic HF patients., Methods: Consecutive 334 HF patients with ischemic etiology were retrospectively registered and divided into 2 groups based on oral administration of nicorandil: nicorandil group (n = 116) and non-nicorandil group (n = 218). We retrospectively examined cardiac mortality., Results: In the Kaplan-Meier analysis (mean follow-up period 963 days), cardiac mortality was significantly lower in the nicorandil group than in the non-nicorandil group (11.2% vs. 19.7%, P = 0.032). In the Cox proportional hazard analysis, usage of nicorandil was a suppressor of cardiac mortality (hazard ratio 0.512, 95% confidence interval 0.275-0.953, P = 0.035), and this result was consistent in several subgroup analyses, such as left ventricular ejection fraction, percutaneous coronary intervention, coronary artery bypass graft, diabetes, β-blockers, and statins., Conclusion: Nicorandil is potentially effective for reducing mortality in patients with ischemic heart failure., Trial Registration: This was a retrospective study.

Background: It has been recently reported that histamine H 2 receptor antagonists (H2RAs) are associated with impairment of ventricular remodeling and incident heart failure. In addition, favorable pleiotropic effects and adverse effects of proton pump inhibitors (PPIs) on cardiovascular disease have also been reported. We examined the associations of acid suppressive therapy using H2RAs or PPIs with cardiac mortality in patients with heart failure., Methods and Results: In total, 1191 consecutive heart failure patients were divided into 3 groups: a non-acid suppressive therapy group (n=363), an H2RA group (n=164), and a PPI group (n=664). In the follow-up period (mean 995 days), 169 cardiac deaths occurred. In the Kaplan-Meier analysis, cardiac mortality was significantly lower in the PPI group than in the H2RA and non-acid suppressive therapy groups (11.0% versus 21.3% and 16.8%, respectively; log-rank P =0.004). In the multivariable Cox proportional hazards analysis, use of PPIs, but not H2RAs, was found to be an independent predictor of cardiac mortality (PPIs: hazard ratio 0.488, P =0.002; H2RAs: hazard ratio 0.855, P =0.579). The propensity-matched 1:1 cohort was assessed based on propensity score (H2RAs, n=164; PPIs, n=164). Cardiac mortality was significantly lower in the PPI group than in the H2RA group in the postmatched cohort (log-rank P =0.025). In the Cox proportional hazards analysis, the use of PPIs was a predictor of cardiac mortality in the postmatched cohort (hazard ratio 0.528, P =0.028)., Conclusions: PPIs may be associated with better outcome in patients with heart failure., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) lowers the risk of atherosclerotic cardiovascular events, particularly ischemic heart disease. In addition, the ratio of eicosapentaenoic acid (EPA; n-3 PUFA) to arachidonic acid (AA; n-6 PUFA) has recently been recognized as a risk marker of cardiovascular disease. In contrast, the prognostic impact of the EPA/AA ratio on patients with heart failure (HF) remains unclear., Methods and Results: A total of 577 consecutive patients admitted for HF were divided into 2 groups based on median of the EPA/AA ratio: low EPA/AA (EPA/AA <0.32 mg/dl, n = 291) and high EPA/AA (EPA/AA ≥0.32, n = 286) groups. We compared laboratory data and echocardiographic findings and followed cardiac mortality. Although body mass index, blood pressure, B-type natriuretic peptide, hemoglobin, estimated glomerular filtration rate, total protein, albumin, sodium, C-reactive protein, and left ventricular ejection fraction did not differ between the 2 groups, cardiac mortality was significantly higher in the low EPA/AA group than in the high EPA/AA group (12.7 vs 5.9%, log-rank P = .004). Multivariate Cox proportional hazard analysis revealed that the EPA/AA ratio was an independent predictor of cardiac mortality (hazard ratio 0.677, 95% confidence interval 0.453-0.983, P = .041) in patients with HF., Conclusion: The EPA/AA ratio was an independent predictor of cardiac mortality in patients with HF; therefore, the prognosis of patients with HF may be improved by taking appropriate management to control the EPA/AA balance., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Although pulmonary hypertension due to left heart disease (LHD-PH) accounts for the largest proportion of pulmonary hypertension, few reports on the epidemiological analysis of LHD-PH exist. Recently, pulmonary arterial capacitance (PAC) has attracted attention as a possible factor of right ventricular afterload along with pulmonary vascular resistance. We therefore investigated the clinical significance of PAC in LHD-PH., Methods: The subject consisted of 252 LHD-PH patients (145 men, mean age 63.4 ± 14.7 years) diagnosed by right heart catheterization. PAC was estimated by the ratio between stroke volume and pulmonary arterial pulse pressure. Patients were classified into four groups according to the PAC (1st quartile was 0.74 to 1.76 ml/mmHg, the 2nd quartile 1.77 to 2.53 ml/mmHg, the 3rd quartile 2.54 to 3.59 ml/mmHg, and the 4th quartile 3.61 to 12.14 ml/mmHg). The end-points were defined as rehospitalization due to worsening heart failure and/or cardiac death. The Cox proportional hazard regression model was used to determine what variables were associated with cardiac events., Results: The patients in the 1st quartile had the lowest cardiac index and stroke volume index, and the highest mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, and pulmonary vascular resistance compared with the 2nd, 3rd, and 4th quartiles. Fifty-four patients experienced cardiac events during the follow-up period (median 943 days). The event-free rate of the 1st quartile was significantly lower than that of the 3rd and 4th quartiles (66.7% vs 82.5% [3rd quartile], P = 0.008; and 92.1% [4th quartile], P < 0.001). The Cox hazard analysis revealed that PAC was significantly associated with cardiac events (HR 0.556, 95% CI 0.424-0.730, P < 0.001)., Conclusion: PAC is useful in the prediction of cardiac event risk in LHD-PH patients., Competing Interests: Koichi Sugimoto belongs to endowed department sponsored by Acterion Pharmaceuticals Japan. All other authors declare that no competing interest exists. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Background: Insomnia is associated with incident heart failure (HF), but the clinical significance and impact of insomnia on HF remain unclear., Methods and results: Consecutive 1,011 patients admitted for HF were divided into 2 groups according to the presence of insomnia: HF with insomnia (insomnia group, n=519) and HF without insomnia (non-insomnia group, n=492). We compared (1) cardiac event rates including cardiac death and worsening HF; and (2) underlying clinical background including laboratory data, echocardiographic data, and cardiopulmonary exercise test between the 2 groups. On Kaplan-Meier analysis, cardiac event rate was significantly higher in the insomnia group than in the non-insomnia group (39.1 vs. 23.4%, P<0.001). The insomnia group, as compared with the non-insomnia group, had (1) higher plasma renin activity (P=0.042), renin concentration (P=0.007), and aldosterone (P=0.047); (2) lower peak V̇O2(14.9 vs. 16.3 ml/kg/min, P=0.002) and higher V̇E/V̇CO2slope (36.0 vs. 33.5, P=0.001); and (3) similar B-type natriuretic peptide and left ventricular ejection fraction. Importantly, on multivariate Cox proportional hazard analysis after adjusting for potential confounding factors, insomnia was an independent predictor of cardiac events in HF patients (hazard ratio, 1.899; P<0.001)., Conclusions: Insomnia is an independent predictor of cardiac events in HF patients. HF patients with insomnia have activated renin-angiotensin-aldosterone system and lower exercise capacity. (Circ J 2016; 80: 1571-1577).

Serum uric acid is a predictor of cardiovascular mortality in heart failure with reduced ejection fraction. However, the impact of uric acid on heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we investigated the association between hyperuricemia and mortality in HFpEF patients. Consecutive 424 patients, who were admitted to our hospital for decompensated heart failure and diagnosed as having HFpEF, were divided into two groups based on presence of hyperuricemia (serum uric acid ≥7 mg/dl or taking antihyperuricemic agents). We compared patient characteristics, echocardiographic data, cardio-ankle vascular index, and cardiopulmonary exercise test findings between the two groups and prospectively followed cardiac and all-cause mortality. Compared with the non-hyperuricemia group (n = 170), the hyperuricemia group (n = 254) had a higher prevalence of hypertension (P = 0.013), diabetes mellitus (P = 0.01), dyslipidemia (P = 0.038), atrial fibrillation (P = 0.001), and use of diuretics (P < 0.001). Cardio-ankle vascular index (8.7 vs. 7.5, P < 0.001) and V̇e/V̇co2 slope (34.9 vs. 31.9, P = 0.02) were also higher. In addition, peak V̇o2 (14.9 vs. 17.9 ml·kg(-1)·min(-1), P < 0.001) was lower. In the follow-up period (mean 897 days), cardiac and all-cause mortalities were significantly higher in those with hyperuricemia (P = 0.006 and P = 0.004, respectively). In the multivariable Cox proportional hazard analyses after adjustment for several confounding factors including chronic kidney disease and use of diuretics, hyperuricemia was an independent predictor of all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.036-3.793, P = 0.039). Hyperuricemia is associated with arterial stiffness, impaired exercise capacity, and high mortality in HFpEF., (Copyright © 2015 the American Physiological Society.)

Background: Chronic kidney disease--mineral and bone disorders (CKD-MBD) are associated with vascular calcification and abnormal electrolytes that lead to cardiovascular disease and mortality. CKD-MBD is identified by imbalances in serum calcium (Ca), phosphate, and parathyroid hormone (PTH). Although the relation of phosphate and PTH with the prognosis of HF patients has been reported, the association of Ca with prognosis in patients with heart failure (HF) and CKD remains unclear., Methods and Results: We examined 191 patients admitted for HF and CKD (estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2)), and they were divided into 2 groups based on levels of corrected Ca: low Ca (Ca <8.4 mg/dL; n = 32) and normal-high Ca (8.4 ≤Ca; n = 159). We compared laboratory and echocardiographic findings, as well as followed cardiac and all-cause mortality. The low-Ca group had 1) higher levels of alkaline phosphatase (308.9 vs. 261.0 U/L; P = .026), 2) lower levels of 1,25-dihydroxy vitamin D (26.1 vs. 45.0 pg/mL; P = .011) and hydrogen carbonate (22.4 vs. 24.5 mmol/L; P = .031), and 3) a tendency to have a higher PTH level (87.5 vs. 58.6 pg/mL; P = .084). In contrast, left and right ventricular systolic function, estimated glomerular filtration rate, urine protein, phosphate, sodium, potassium, magnesium, and zinc did not differ between the 2 groups. In the Kaplan-Meier analysis, cardiac and all-cause mortality were significantly higher in the low-Ca group than in the normal-high-Ca group (P < .05). In the multivariable Cox proportional hazard analyses, hypocalcemia was an independent predictor of all-cause mortality in HF and CKD patients (P < .05)., Conclusions: Hypocalcemia was an independent predictor of all-cause mortality in HF and CKD patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Right-heart dysfunction is associated with poor prognosis in heart failure with preserved left ventricular ejection fraction (HFpEF). It remains unclear whether sleep-disordered breathing (SDB) treatment using positive airway pressure (PAP) improves right-heart and pulmonary function and exercise capacity and reduces mortality rates of HFpEF patients., Hypothesis: PAP may improve right-heart and pulmonary function, exercise capacity and prognosis in HFpEF patients with SDB., Methods: One hundred nine consecutive patients with HFpEF (left ventricular ejection fraction >50%) and moderate to severe SDB (apnea-hypopnea index ≥15/h) treated with medications were divided into 2 groups: 31 patients with PAP (PAP group) and 78 patients without PAP (non-PAP group). Right ventricular fractional area change (RV-FAC), tricuspid valve regurgitation pressure gradient (TR-PG), tricuspid valve E/E', forced expiratory volume in 1 second/forced vital capacity (FEV1 /FVC), percentage of vital capacity, and peak VO2 were determined before and 6 months later, and all-cause mortality was followed up for 916 days., Results: All parameters improved in the PAP group (RV-FAC, 36.0% -46.5%; TR-PG, 31.1 mm Hg-22.4 mm Hg; tricuspid valve E/E', 7.8-5.1; FEV1 /FVC, 83.9%-89.8%; percentage of vital capacity, 83.5%-89.9%; and peak VO2 , 16.6 mL/kg/min-19.6 mL/kg/min; P <0.05, respectively) but not in the non-PAP group. Importantly, all-cause mortality was significantly lower in the PAP group than in the non-PAP group (0% vs 12.8%; log-rank P = 0.014)., Conclusions: Positive airway pressure improves right-heart and pulmonary function and exercise capacity and may reduce all-cause mortality in patients with HFpEF and SDB., (© 2015 Wiley Periodicals, Inc.)

Sleep-disordered breathing (SDB) has a critical association with mortality and morbidity of patients with chronic heart failure (CHF). Troponin T is a marker of ongoing myocardial damage and predicts adverse clinical outcomes in patients with CHF. Carnitine plays an important role in the utilization of fatty acids in the myocardium. It has been reported that myocardial carnitine levels decrease in the failing heart. We hypothesized that plasma troponin T and carnitine are increased due to the leakage from damaged cardiomyocytes or the alteration of myocardial metabolism in CHF patients with SDB. We examined the relation of plasma troponin T and carnitine levels with severity of SDB in CHF. We used portable sleep monitor and measured the apnea-hypopnea index (AHI), plasma levels of high-sensitive troponin T and carnitine in 131 CHF patients. These patients were divided into three groups based on AHI: group A (None-mild SDB AHI < 15/h, n = 45), group B (Moderate SDB 15 ≤ AHI < 30/h, n = 32) and group C (Severe SDB AHI ≥ 30/h, n = 54). Levels of high-sensitive troponin T and plasm total carnitine were significantly higher in group C than in groups A and B [high-sensitive troponin T; group A 0.009 (0.005-0.016), group B 0.012 (0.006-0.021), group C 0.021 (0.011-0.039) ng/ml, total carnitine; group A 61.0 ± 15.1, group B 65.0 ± 13.5, group C 73.3 ± 17.5 μmol/l, P < 0.01 vs. group A and P < 0.05 vs. group B, respectively]. Furthermore, in the multiple regression analysis, the independent factors to determine plasma levels of log (high-sensitive troponin T) were high-sensitive C-reactive protein and AHI, and the independent factors to determine plasma levels of carnitine were glomerular filtration rate and AHI. The present study suggests that SDB is associated with latent myocardial damage and alteration of myocardial carnitine metabolism in patients with CHF, presented by higher circulating troponin T and carnitine levels.

Aim: The purpose in the present study was to compare prognostic risk factors between older and younger chronic heart failure (CHF) patients., Methods: We examined 598 consecutive CHF patients (476 men and 122 women, mean age 61.4 ± 14.3 years) who underwent cardiopulmonary exercise testing, echocardiography and blood examination. We divided the 598 patients into two groups: the elderly group (age ≥75 years, n = 123) and the young group (age <75, n = 475). We compared blood testing data, exercise capacity, cardiac function and prognosis between the two groups. Patients were followed up (median 782 days) to register cardiac deaths or rehospitalization as a result of worsening heart failure., Results: Patients in the elderly group were associated with higher frequencies of atrial fibrillation and diuretic use than those in the young group. Patients in the elderly group had lower hemoglobin concentration, more impaired renal function, higher plasma B-type natriuretic peptide (BNP) levels, smaller left ventricular volume, longer deceleration time of early mitral wave and lower exercise capacity than those in the young group. There were 199 cardiac events during follow-up periods. As expected, Kaplan-Meier analysis showed that patients in the elderly group had higher cardiac event rates than those in the young group. In the young group, multivariable Cox hazard analysis showed that hemoglobin concentration, log BNP and peak VO(2) were independent predictors related to cardiac events. In contrast, in the elderly group, estimated glomerular filtration rate, atrial fibrillation and peak VO(2) were independent factors to predict adverse clinical outcomes., Conclusions: Prognostic factors were different between the elderly and young patients in CHF., (© 2014 Japan Geriatrics Society.)

We determine the importance of indicators of nutrition including lymphocyte, total protein, albumin, cholinesterase and body mass index, and compare the prognostic significance in chronic heart failure (CHF). We examined consecutive 465 CHF patients (376 males, age 62 ± 14 years) who underwent cardiopulmonary exercise testing, echocardiography and blood examination including indicators of nutrition at the same time in our hospital. The patients were followed up [median period 766 days (interquartile range 500-1060)] to register cardiac deaths and rehospitalization due to worsening heart failure. There were 180 cardiac events during the follow-up periods. Patients with cardiac events had lower cholinesterase level than those without events (P < 0.001). On the receiver operating characteristic analysis, the best cut-off value for cholinesterase was 240 U/l (area under the curve 0.720). In the Kaplan-Meier analysis, patients with cholinesterase <240 U/l had significantly higher cardiac event rates than those with cholinesterase >240 U/l. Multivariable Cox proportional hazards model demonstrated that NYHA class III [hazard ratio (HR): 1.688, 95 % confidence interval (CI) 1.062-2.684, P = 0.027], eGFR (HR: 0.983, 95 % CI 0.971-0.995, P = 0.006), sodium concentration (HR: 0.947, 95 % CI 0.897-0.999, P < 0.046), log BNP (HR: 1.880, 95 % CI 1.509-2.341, P < 0.001), cholinesterase (HR: 0.996, 95 % CI 0.993-0.998, P = 0.002) and exertional periodic breathing (HR: 1.619, 95 % CI 1.098-2.388, P = 0.015) were independent factors to predict adverse clinical outcomes. Serum cholinesterase level was an important prognostic factor in CHF.

Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. Carperitide has natriuretic and vasodilatory effects, and tolvaptan produces water excretion without electrolyte excretion. We previously reported the usefulness of tolvaptan compared to carperitide in ADHF patients with fluid volume retention. The purpose of this study was to examine whether the efficacy of tolvaptan was altered in ADHF patients with reduced left ventricular systolic function and in those with hypotension. A total of 109 hospitalized ADHF patients were randomly assigned to either a tolvaptan or a carperitide treatment group. Baseline clinical characteristics were not different between the two groups. We divided these patients based on the left ventricular ejection fraction (EF) by echocardiography, and blood pressure (BP) at the time of admission. Daily urine volume between the tolvaptan and carperitide groups in patients with preserved EF (≥ 50%) was not different, however, in those with reduced EF (< 50%), the urine volume was significantly higher in the tolvaptan group than in the carperitide group (day 2, 3, 4, P < 0.05 for all). Daily urine volume did not differ between these two groups in the high blood pressure group (BP ≥ 140 mmHg), but was significantly higher in the tolvaptan group than in the carperitide group (day 1, P = 0.021; day 3, P = 0.017) in the low blood pressure group (BP < 140 mmHg). The present study reveals that tolvaptan is more effective than carperitide, especially in ADHF patients with reduced left ventricular systolic function and without hypertension.

Background: The impact of peripheral artery disease (PAD) on heart failure (HF) prognosis remains unclear., Methods and Results: A total of 388 consecutive decompensated HF patients were divided into 2 groups based on the presence of PAD: HF with PAD (PAD group, n=101, 26.0%) and HF without PAD (non-PAD group, n=287, 74.0%). We compared clinical features, echocardiographic parameters, cardiopulmonary exercise testing results, laboratory findings, as well as cardiac, non-cardiac, and all-cause mortality between the 2 groups. The PAD group, as compared with the non-PAD group, had (1) higher prevalence of coronary artery disease (40.6 vs. 27.5%, P=0.011) and cerebrovascular disease (34.7 vs. 18.2%, P=0.001); (2) higher tumor necrosis factor-α (1.82 vs. 1.49 pg/ml, P=0.023), C-reactive protein (0.32 vs. 0.19 mg/dl, P=0.045), and troponin T (0.039 vs. 0.021 ng/ml, P=0.019); (3) lower LVEF (42.4 vs. 48.5%, P<0.001); (4) lower peak V̇O2(13.4 vs. 15.9 ml·kg(-1)·min(-1), P=0.001); and (5) higher V̇E/V̇CO2slope (38.8 vs. 33.7, P<0.001). On Kaplan-Meier analysis, cardiac, non-cardiac, and all-cause mortality were significantly higher in the PAD group than in the non-PAD group (P<0.05, respectively). On Cox proportional hazard analysis after adjusting for confounding factors, PAD was an independent predictor of cardiac and all-cause mortality (P<0.05, respectively) in HF patients., Conclusions: PAD was common and an independent predictor of cardiac and all-cause mortality in HF patients.

Background: Sleep-disordered breathing (SDB) is critically associated with cardiovascular mortality and morbidity, especially in patients with heart failure (HF). However, the majority of SDB patients remain undiagnosed. In contrast, abnormality in heart rate variability has been reported in patients with SDB. To explore an efficient electrocardiogram (ECG)-based screening tool for SDB, we examined the usefulness of cyclic variation in heart rate score (CVHRS) by Holter ECG in subjects with HF., Methods: In this study, 102 subjects with HF were enrolled. We simultaneously performed Holter ECG with overnight portable sleep monitoring, and we measured the respiratory disturbance index (RDI) and CVHRS. We determined the temporal position of the individual dips comprising the CVHRS using time-domain methods. CVHRS was measured as cyclic and autocorrelated dips in smoothed interbeat interval time series., Results: There were 25 subjects with severe SDB (RDI ≥ 30 events/h) and 77 subjects with none-to-moderate SDB (0 ≤ RDI < 30 events/h). There was a significant positive correlation between CVHRS and RDI (r = 0.60, P < .001). In receiver operating characteristic analysis, CVHRS (cutoff of 30 events/h) identified severe SDB with a sensitivity of 82%, a specificity of 77%, and an area under the curve of 0.83., Conclusions: CVHRS determined by Holter ECG is a useful screening index for severe SDB in subjects with HF., (Copyright © 2015 by Daedalus Enterprises.)