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Aims: In recent years, there has been remarkable development in machine learning (ML) models, showing a trend towards high prediction performance. ML models with high prediction performance often become structurally complex and are frequently perceived as black boxes, hindering intuitive interpretation of the prediction results. We aimed to develop ML models with high prediction performance, interpretability, and superior risk stratification to predict in-hospital mortality and worsening heart failure (WHF) in patients with acute heart failure (AHF)., Methods and Results: Based on the Kyoto Congestive Heart Failure registry, which enrolled 4056 patients with AHF, we developed prediction models for in-hospital mortality and WHF using information obtained on the first day of admission (demographics, physical examination, blood test results, etc.). After excluding 16 patients who died on the first or second day of admission, the original dataset (n = 4040) was split 4:1 into training (n = 3232) and test datasets (n = 808). Based on the training dataset, we developed three types of prediction models: (i) the classification and regression trees (CART) model; (ii) the random forest (RF) model; and (iii) the extreme gradient boosting (XGBoost) model. The performance of each model was evaluated using the test dataset, based on metrics including sensitivity, specificity, area under the receiver operating characteristic curve (AUC), Brier score, and calibration slope. For the complex structure of the XGBoost model, we performed SHapley Additive exPlanations (SHAP) analysis, classifying patients into interpretable clusters. In the original dataset, the proportion of females was 44.8% (1809/4040), and the average age was 77.9 ± 12.0. The in-hospital mortality rate was 6.3% (255/4040) and the WHF rate was 22.3% (900/4040) in the total study population. In the in-hospital mortality prediction, the AUC for the XGBoost model was 0.816 [95% confidence interval (CI): 0.815-0.818], surpassing the AUC values for the CART model (0.683, 95% CI: 0.680-0.685) and the RF model (0.755, 95% CI: 0.753-0.757). Similarly, in the WHF prediction, the AUC for the XGBoost model was 0.766 (95% CI: 0.765-0.768), outperforming the AUC values for the CART model (0.688, 95% CI: 0.686-0.689) and the RF model (0.713, 95% CI: 0.711-0.714). In the XGBoost model, interpretable clusters were formed, and the rates of in-hospital mortality and WHF were similar among each cluster in both the training and test datasets., Conclusions: The XGBoost models with SHAP analysis provide high prediction performance, interpretability, and reproducible risk stratification for in-hospital mortality and WHF for patients with AHF., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Congestion is a leading cause of hospitalization and a major therapeutic target in patients with heart failure (HF). Clinical practice in Japan is characterized by a long hospital stay, which facilitates more extensive decongestion during hospitalization. We herein examined the time course and prognostic impact of clinical congestion in a large contemporary Japanese cohort of HF., Methods and Results: Peripheral edema, jugular venous pressure, and orthopnea were graded on a standardized 4-point scale (0-3) in 3787 hospitalized patients in a Japanese cohort of HF. Composite Congestion Scores (CCS) on admission and at discharge were calculated by summing individual scores. The primary outcome was a composite of all-cause death or HF hospitalization. The median admission CCS was 4 (interquartile range, 3-6). Overall, 255 patients died during the median hospitalization length of 16 days, and 1395 died or were hospitalized for HF over a median postdischarge follow-up of 396 days. The cumulative 1-year incidence of the primary outcome increased at higher tertiles of congestion on admission (32.5%, 39.3%, and 41.0% in the mild [CCS ≤3], moderate [CCS = 4 or 5], and severe [CCS ≥6] congestion groups, respectively, log-rank P < .001). The adjusted hazard ratios of moderate and severe congestion relative to mild congestion were 1.205 (95% confidence interval [CI], 1.065-1.365; P = .003) and 1.247 (95% CI, 1.103-1.410; P < .001), respectively. Among 3445 patients discharged alive, 85% had CCS of 0 (complete decongestion) and 15% had a CCS of 1 or more (residual congestion) at discharge. Although residual congestion predicted a risk of postdischarge death or HF hospitalization (adjusted hazard ratio, 1.314 [1.145-1.509]; P < .001), the admission CCS correlated with the risk of postdischarge death or HF hospitalization, even in the complete decongestion group. No correlation was observed for postdischarge death or HF hospitalization between residual congestion at discharge and admission CCS (P for the interaction = .316)., Conclusions: In total, 85% of patients were discharged with complete decongestion in Japanese clinical practice. Clinical congestion, on admission and at discharge, was of prognostic value. The severity of congestion on admission was predictive of adverse outcomes, even in the absence of residual congestion., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000017241 (UMIN000015238)., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Backgrounds: The prognostic implication of weight loss after discharge from acute heart failure (AHF) remains unclear. We sought to investigate the association of weight loss between discharge and 6-month visit with subsequent clinical outcomes in patients with AHF., Methods: We analyzed 686 patients with AHF in the prospective longitudinal follow-up study derived from the Kyoto Congestive Heart Failure registry, and divided them into 2 groups based on the weight loss at 6-month index visit. We defined the weight loss as ≥ 5% decrease in body weight from discharge to 6-month index visit., Results: There were 90 patients (13.1%) with a weight loss at 6-month visit. Patients in the weight loss group compared with those in the no weight loss group had higher body weight at discharge and lower body weight at 6-mont visit. Patients in the weight loss group had a lower systolic blood pressure, higher brain-type natriuretic peptide, lower serum albumin, lower hemoglobin, higher prevalence of heart failure with reduced ejection fraction at 6-month visit, and a lower prescription rate of inhibitors of renin-angiotensin system than those in the no weight loss group. The cumulative 6-month incidence of all-cause death was significantly higher in the weight loss group than in the no weight loss group (14.2% and 4.3%, log-rank P<0.001). The excess adjusted risk of the weight loss group relative to the no weight loss group remained significant for all-cause death (HR 2.39, 95%CI 1.01-5.65, P = 0.048)., Conclusion: Body weight loss of ≥5% at 6-month visit after discharge was associated with subsequent all-cause death in patients with AHF., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Seko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Several studies demonstrated that tricuspid regurgitation (TR) is associated with poor clinical outcomes. However, data on patients with TR who experienced acute heart failure (AHF) remains scarce. The purpose of this study is to evaluate the association between TR and clinical outcomes in patients admitted with AHF, using a large-scale Japanese AHF registry., Methods and Results: The current study population consisted of 3735 hospitalized patients due to AHF in the Kyoto Congestive Heart Failure (KCHF) registry. TR grades were assessed according to the routine clinical practice at each participating centre. We compared the baseline characteristics and outcomes according to the severity of TR. The primary outcome was all-cause death. The secondary outcome was hospitalization for heart failure (HF). The median age of the entire study population was 80 (interquartile range: 72-86) years. One thousand two hundred five patients (32.3%) had no TR, while mild, moderate, and severe TR was found in 1537 patients (41.2%), 776 patients (20.8%), and 217 patients (5.8%), respectively. Pulmonary hypertension, significant mitral regurgitation, and atrial fibrillation/flutter were strongly associated with the development of moderate/severe of TR, while left ventricular ejection fraction <50% was inversely associated with it. Among 993 patients with moderate/severe TR, the number of patients who underwent surgical intervention for TR within 1 year was only 13 (1.3%). The median follow-up duration was 475 (interquartile range: 365-653) days with 94.0% follow-up at 1 year. As the TR severity increased, the cumulative 1 year incidence of all-cause death and HF admission proportionally increased ([14.8%, 20.3%, 23.4%, 27.0%] and [18.9%, 23.0%, 28.5%, 28.4%] in no, mild, moderate, and severe TR, respectively). Compared with no TR, the adjusted risks of patients with mild, moderate, and severe TR were significant for all-cause death (hazard ratio [95% confidence interval]: 1.20 [1.00-1.43], P = 0.0498, 1.32 [1.07-1.62], P = 0.009, and 1.35 [1.00-1.83], P = 0.049, respectively), while those were not significant for hospitalization for HF (hazard ratio [95% confidence interval]: 1.16 [0.97-1.38], P = 0.10, 1.19 [0.96-1.46], P = 0.11, and 1.20 [0.87-1.65], P = 0.27, respectively). The higher adjusted HRs of all the TR grades relative to no TR were significant for all-cause death in patients aged <80 years, but not in patients aged ≥80 years with significant interaction., Conclusions: In a large Japanese AHF population, the grades of TR could successfully stratify the risk of all-cause death. However, the association of TR with mortality was only modest and attenuated in patients aged 80 or more. Further research is warranted to evaluate how to follow up and manage TR in this elderly population., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Little is known about the association between the starting of or dose changes in loop diuretics during acute heart failure (AHF) hospitalization and post-discharge outcomes. We investigated the clinical impact of starting loop diuretics and changing the loop diuretics dose during hospitalization on post-discharge outcomes., Methods and Results: From the Kyoto Congestive Heart Failure registry, 3665 consecutive patients hospitalized for HF and discharged alive were included in this study. We analysed 1906 patients without loop diuretics on admission and were discharged alive and 1759 patients who received loop diuretics on admission and were discharged alive. The primary outcome measure was all-cause death. Of the 1906 patients without loop diuretics on admission, 1366 (71.7%) patients started loop diuretics during the index AHF hospitalization. Starting loop diuretics was not associated with lower post-discharge mortality [adjusted hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.68-1.25]. Of the 1759 patients who received loop diuretics on admission, loop diuretic dose was decreased in 23.8%, unchanged in 44.6%, and increased in 31.6% of the patients. Changes in the dose at discharge compared with no change in dose were not associated with lower risk of post-discharge mortality (decrease relative to no change: adjusted HR 0.98, 95% CI 0.76-1.28; increase relative to no change: adjusted HR 1.00, 95% CI 0.78-1.27). Compared with no loop diuretics at discharge, a loop diuretics dose of ≥80 mg at discharge was associated with higher post-discharge mortality risk., Conclusions: In patients with AHF, we found no association between the starting of loop diuretics and post-discharge outcomes and between dose changes and post-discharge outcomes., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: There are no previous studies focusing on collaborative follow-ups between hospitals and clinics for patients discharged after acute heart failure (AHF) in Japan. The purpose of this study was to determine the status of collaboration between hospitals and clinics for patients with AHF in Japan and to compare patient characteristics and clinical outcomes using a large Japanese observational database., Methods and Results: Of 4056 consecutive patients hospitalized for AHF in the Kyoto Congestive Heart Failure registry, we analysed 2862 patients discharged to go home, who were divided into 1674 patients (58.5%) followed up at hospitals with index hospitalization (hospital follow-up group) and 1188 (41.5%) followed up in a collaborative fashion with clinics or other general hospitals (collaborative follow-up group). The primary outcome was a composite of all-cause death or heart failure (HF) hospitalization within 1 year after discharge. Previous hospitalization for HF and length of hospital stay longer than 15 days were associated with hospital follow-up. Conversely, ≥80 years of age, hypertension, and cognitive dysfunction were associated with collaborative follow-up. The cumulative 1-year incidence of the primary outcome, all cause death, and cardiovascular death were similar between the hospital and collaborative follow-up groups (31.6% vs. 29.6%, P = 0.51, 13.1% vs, 13.9%, P = 0.35, 8.4% vs. 8.2%, P = 0.96). Even after adjusting for confounders, the difference in risk for patients in the hospital follow-up group relative to those in the collaborative follow-up group remained insignificant for the primary outcome, all-cause death, and cardiovascular death (HR: 1.11, 95% CI: 0.97-1.27, P = 0.14, HR: 1.10, 95% CI: 0.91-1.33, P = 0.33, HR: 0.96, 95% CI: 0.87-1.05, P = 0.33). The cumulative 1-year incidence of HF hospitalization was higher in the hospital follow-up group than in the collaborative follow-up group (25.5% vs. 21.3%, P = 0.02). The risk of HF hospitalization was higher in the hospital follow-up group than in the collaborative follow-up group (HR: 1.19, 95% CI: 1.01-1.39, P = 0.04)., Conclusions: In patients hospitalized for AHF, 41.5% received collaborative follow-up after discharge. The risk of HF hospitalization was higher in the hospital follow-up group than in the collaborative follow-up, although risk of the primary outcome, all-cause death, and cardiovascular death were similar between groups., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Insomnia is a known risk factor for heart failure (HF) and a predictor of cardiac events in HF patients, but the clinical significance of insomnia in patients with acute HF (AHF) is not adequately evaluated. This study aimed to investigate the association between insomnia and subsequent clinical outcomes in patients with AHF., Methods: From the Kyoto Congestive Heart Failure registry, consecutive 3414 patients hospitalized for HF who were discharged alive were divided into the 2 groups at discharge: insomnia group and non-insomnia group. We compared baseline characteristics and 1 year clinical outcomes according to the presence of insomnia. The primary outcome measure was all-cause death., Results: There were 330 patients (9.7%) and 3084 patients (90.3%) with and without insomnia, respectively. In the multivariable logistic regression analysis, brain-type natriuretic peptide above median value at discharge (OR = 1.50, 95% CI = 1.08-2.10, P = 0.02) and the presence of oedema at discharge (OR = 4.23, 95% CI = 2.95-6.07, P < 0.001) were positively associated with insomnia at discharge, whereas diuretics at discharge (OR = 0.60, 95% CI = 0.39-0.90, P = 0.01) were negatively associated with insomnia at discharge. The cumulative 1 year incidence of all-cause death was significantly higher in the insomnia group than in the non-insomnia group (25.1% vs. 16.2%, P < 0.001). Even after adjusting the confounders, the higher mortality risk of patients with insomnia relative to those without insomnia remained significant (HR = 1.55, 95% CI = 1.24-1.94; P < 0.001)., Conclusions: Patients with insomnia at discharge were associated with a higher risk of mortality than those without insomnia at discharge., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The clinical benefits of neurohormonal antagonists for patients with heart failure (HF) with mid-range and preserved ejection fraction (HFmrEF and HFpEF) are uncertain., Methods and results: This study analyzed 858 consecutive patients with HFmrEF (EF: 40-49%) or HFpEF (EF ≥50%), who were hospitalized for acute HF, and who were discharged alive, and were not taking angiotensin-converting enzyme inhibitors (ACE)-I/ angiotensin II receptor blockers (ARB) or β-blockers at admission. The study population was classified into 4 groups according to the status of prescription of ACE-I/ARB and β-blocker at discharge: no neurohormonal antagonist (n=342, 39.9%), ACE-I/ARB only (n=128, 14.9%), β-blocker only (n=189, 22.0%), and both ACE-I/ARB and β-blocker (n=199, 23.2%) groups. The primary outcome measure was a composite of all-cause death or HF hospitalization. The cumulative 1-year incidence of the primary outcome measure was 41.2% in the no neurohormonal antagonist group, 34.0% in the ACE-I/ARB only group, 28.6% in the β-blocker only group, and 16.4% in the both ACE-I/ARB and β-blocker group (P<0.001). Compared with the no neurohormonal antagonist group, both the ACE-I/ARB and β-blocker groups were associated with a significantly lower risk for a composite of all-cause death or HF hospitalization (HR: 0.46, 95% CI: 0.28-0.76, P=0.002)., Conclusions: In hospitalized patients with HFmrEF and HFpEF, starting both ACE-I/ARB and a β-blocker was associated with a reduced risk of the composite of all-cause death or HF hospitalization compared with patients not starting on an ACE-I/ARB or β-blocker.

Aims: There is a scarcity of data on the post-discharge prognosis in acute heart failure (AHF) patients with a low-income but receiving public assistance. The study sought to evaluate the differences in the clinical characteristics and outcomes between AHF patients receiving public assistance and those not receiving public assistance., Methods and Results: The Kyoto Congestive Heart Failure registry was a physician-initiated, prospective, observational, multicentre cohort study enrolling 4056 consecutive patients who were hospitalized due to AHF for the first time between October 2014 and March 2016. The present study population consisted of 3728 patients who were discharged alive from the index AHF hospitalization. We divided the patients into two groups, those receiving public assistance and those not receiving public assistance. After assessing the proportional hazard assumption of public assistance as a variable, we constructed multivariable Cox proportional hazard models to estimate the risk of the public assistance group relative to the no public assistance group. There were 218 patients (5.8%) receiving public assistance and 3510 (94%) not receiving public assistance. Patients in the public assistance group were younger, more frequently had chronic coronary artery disease, previous heart failure hospitalizations, current smoking, poor medical adherence, living alone, no occupation, and a lower left ventricular ejection fraction than those in the no public assistance group. During a median follow-up of 470 days, the cumulative 1 year incidences of all-cause death and heart failure hospitalizations after discharge did not differ between the public assistance group and no public assistance group (13.3% vs. 17.4%, P = 0.10, and 28.3% vs. 23.8%, P = 0.25, respectively). After adjusting for the confounders, the risk of the public assistance group relative to the no public assistance group remained insignificant for all-cause death [hazard ratio (HR), 0.97; 95% confidence interval (CI), 0.69-1.32; P = 0.84]. Even after taking into account the competing risk of all-cause death, the adjusted risk within 180 days in the public assistance group relative to the no public assistance group remained insignificant for heart failure hospitalizations (HR, 0.93; 95% CI, 0.64-1.34; P = 0.69), while the adjusted risk beyond 180 days was significant (HR, 1.56; 95% CI, 1.07-2.29; P = 0.02)., Conclusions: The AHF patients receiving public assistance as compared with those not receiving public assistance had no significant excess risk for all-cause death at 1 year after discharge or a heart failure hospitalization within 180 days after discharge, while they did have a significant excess risk for heart failure hospitalizations beyond 180 days after discharge., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) and https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000017241 (UMIN000015238)., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: The complex link between nutritional status, protein and lipid synthesis, and immunity plays an important prognostic role in patients with heart failure. However, the association between appetite loss at discharge and long-term outcome remains unclear., Methods: The Kyoto Congestive Heart Failure registry is a prospective cohort study that enrolled consecutive patients hospitalized for acute decompensated heart failure (ADHF) in Japan. We assessed 3528 patients alive at discharge, and for whom appetite and follow-up data were available. We compared one-year clinical outcomes in patients with and without appetite loss at discharge., Results: In the multivariable logistic regression analysis using 19 clinical and laboratory factors with P value < 0.1 by univariate analysis, BMI < 22 kg/m2 (odds ratio (OR): 1.57, 95% confidence interval (CI): 1.11-2.24, P = 0.01), CRP >1.0mg/dL (OR: 1.49, 95%CI: 1.04-2.14, P = 0.03), and presence of edema at discharge (OR: 4.30, 95%CI: 2.99-6.22, P<0.001) were associated with an increased risk of appetite loss at discharge, whereas ambulatory status (OR: 0.57, 95%CI: 0.39-0.83, P = 0.004) and the use of ACE-I/ARB (OR: 0.70, 95% CI: 0.50-0.98, P = 0.04) were related to a decreased risk in the presence of appetite loss. The cumulative 1-year incidence of all-cause death (primary outcome measure) was significantly higher in patients with appetite loss than in those without appetite loss (31.0% vs. 15.0%, P<0.001). The excess adjusted risk of appetite loss relative to no appetite loss remained significant for all-cause death (hazard ratio (HR): 1.63, 95%CI: 1.29-2.07, P<0.001)., Conclusions: Loss of appetite at discharge was associated with worse 1-year mortality in patients with ADHF. Appetite is a simple, reliable, and useful subjective marker for risk stratification of patients with ADHF., Competing Interests: The authors have declared that no competing interests exist.

We aimed to investigate the relationship between left atrial (LA) reverse remodeling and prognosis of heart failure (HF) with recovered ejection fraction (EF) (HFrecEF). Among 1,246 patients with acute heart failure enrolled in the prospective longitudinal follow-up study, 397 patients with HF with mildly-reduced EF and with reduced EF at discharge were analyzed. Echocardiography was performed during the index hospitalization and at the 6-month follow-up after discharge. They were divided into non-HFrecEF (n = 227) and HFrecEF (n = 170) groups. The primary outcome measure was a composite of all-cause death or hospitalization for HF. The cumulative 180-day incidence of the primary outcome measure after follow-up echocardiography was significantly lower in the HFrecEF group than in the non-HFrecEF group (8.9% versus 23.4%, log-rank P = 0.0002). LA reverse remodeling was associated with a lower cumulative 6-month incidence of the primary outcome measure in the HFrecEF group (4.7% versus 18.0%; HR: 0.27, 95%CI: 0.09-0.79, P = 0.01), but not in the non-HFrecEF group (24.4% versus 22.6%; HR: 1.13, 95%CI: 0.65-1.96, P = 0.28) with a significant LA reverse remodeling-by-HFrecEF interaction (P for interaction = 0.02). Combination of left ventricular and atrial reverse remodeling may help in improving HF risk stratification., (© 2022. The Author(s).)

Aims: Little is known about the characteristics and outcomes of patients who undergo coronary angiography during heart failure (HF) hospitalization, as well as those with coronary stenosis, and those who underwent coronary revascularization., Methods and Results: We analysed 2163 patients who were hospitalized for HF without acute coronary syndrome or prior HF hospitalization. We compared patient characteristics and 1 year clinical outcomes according to (i) patients with versus without coronary angiography, (ii) patients with versus without coronary stenosis, and (iii) patients with versus without coronary revascularization. The primary outcome measure was the composite of all-cause death or HF hospitalization. Coronary angiography was performed in 37.0% of patients. In the multivariable logistic regression analysis, factors independently associated with coronary angiography were age < 80 years [adjusted odds ratio (OR) = 1.76, 95% confidence interval (CI) = 1.41-2.20, P < 0.001], men (adjusted OR = 1.28, 95% CI = 1.03-1.59, P = 0.02), diabetes (adjusted OR = 1.27, 95% CI = 1.02-1.60, P = 0.04), no atrial fibrillation or flutter (adjusted OR = 1.45, 95% CI = 1.17-1.82, P < 0.001), no prior device implantation (adjusted OR = 1.81, 95% CI = 1.13-2.91, P = 0.01), current smoking (adjusted OR = 1.40, 95% CI = 1.05-1.87, P = 0.02), no cognitive dysfunction (adjusted OR = 1.90, 95% CI = 1.34-2.69, P < 0.001), ambulatory status (adjusted OR = 2.89, 95% CI = 2.03-4.10, P < 0.001), HF with reduced ejection fraction (adjusted OR = 1.55, 95% CI = 1.24-1.93, P < 0.001), estimated glomerular filtration rate ≥ 30 mL/min/1.73 m 2 (adjusted OR = 1.93, 95% CI = 1.45-2.58, P < 0.001), no anaemia (adjusted OR = 1.27, 95% CI = 1.02-1.59, P = 0.04), and no prescription of β-blockers prior to admission (adjusted OR = 1.32, 95% CI = 1.03-1.68, P = 0.03). Patients who underwent coronary angiography had a lower risk of the primary outcome [adjusted hazard ratio (HR) = 0.70, 95% CI = 0.58-0.85, P < 0.001]. Among the patients who underwent coronary angiography, those with coronary stenosis (38.9%) did not have lower risk of the primary outcome measure than those without coronary stenosis (adjusted HR = 0.93, 95% CI = 0.65-1.32, P = 0.68). Among the patients with coronary stenosis, those with coronary revascularization (54.3%) did not have higher risk of the primary outcome measure than those without coronary revascularization (adjusted HR = 1.36, 95% CI = 0.84-2.21, P = 0.22)., Conclusions: In patients with acute HF, patients who underwent coronary angiography had a lower risk of clinical outcomes and were significantly different from those who did not undergo coronary angiography., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: This study aimed to investigate the association between changes in brain natriuretic peptide (BNP) from discharge to 6-month visit and subsequent clinical outcomes in patients with acute heart failure (AHF)., Methods: Among 1246 patients enrolled in the prospective longitudinal follow-up study nested from the Kyoto Congestive Heart Failure registry, this study population included 446 patients with available paired BNP data at discharge and 6-month index visit. This study population was classified into 3 groups by percent change in BNP from discharge to 6-month visit; the low tertile (≤-44%, N = 149), the middle tertile (>-44% and ≤22%, N = 149) and the high tertile (>22%, N = 148)., Findings: The cumulative 180-day incidence after the index visit of the primary outcome measure (a composite endpoint of all-cause death or hospitalization for HF) was significantly higher in the high and middle tertiles than in the low tertile (26.8% and 14.4% versus 6.9%, log-rank P<0.0001). The adjusted excess risk of the high tertile relative to the low tertile remained significant for the primary outcome measure (hazard ratio: 3.43, 95% confidence interval: 1.51-8.46, P = 0.003)., Conclusions: Percent change in BNP was associated with a subsequent risk for a composite of all-cause death and hospitalization for HF after adjustment of the absolute BNP values, suggesting that observing the change in BNP levels, in addition to absolute BNP levels themselves, helps us to manage patient with HF., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Current guidelines restrict the use of inotropes for the treatment for heart failure (HF) unless the patients are hypotensive or hypoperfused because of safety concerns. This study sought to characterise the contemporary real-world use of inotropes and associated long-term outcomes according to systolic blood pressure (sBP) and perfusion status., Design: A multicentre prospective cohort study., Setting: This study was nested from the Kyoto Congestive Heart Failure registry, which included consecutive Japanese patients admitted for HF., Participants: We categorised 3995 patients into two groups: sBP ≥90 mm Hg and warm profile group, and sBP <90 mm Hg or cold profile group. In each group, patients were stratified across the use of inotropes within 24 hours of hospital presentation., Primary and Secondary Outcomes: The primary outcome was all-cause death throughout follow-up. Secondary outcomes included cardiovascular death throughout follow-up, all-cause death during index hospitalisation and after discharge, and HF hospitalisation., Results: A total of 793 patients (20%) presented with sBP <90 mm Hg or cold profile, whereas 3202 patients had sBP ≥90 mm Hg and warm profile; 276 patients (35%) in the sBP <90 mm Hg/cold group and 312 patients (10%) in the sBP ≥90 mm Hg/warm group received initial inotropic treatment. Adjusted excess risk of inotrope use relative to no inotrope for the primary outcome measure was significant in the sBP ≥90 mm Hg/warm group (adjusted HR), 1.36; 95% CI 1.09 to 1.72, p=0.006) but not in the sBP <90 mm Hg/cold group (adjusted HR, 1.28, 95% CI 0.96 to 1.69, p=0.09). Risk for postdischarge all-cause death and HF hospitalisation was not significantly different between the patients with inotropes and no inotropes in both groups., Conclusion: Inotrope use in the absence of hypotension and hypoperfusion is still common, but associated with a worse long-term prognosis., Trial Registration Number: UMIN000015238., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background No studies have explored the association between newly diagnosed infections after admission and clinical outcomes in patients with acute heart failure. We aimed to explore the factors associated with newly diagnosed infection after admission for acute heart failure, and its association with in-hospital and post-discharge clinical outcomes. Methods and Results Among 4056 patients enrolled in the Kyoto Congestive Heart Failure registry, 2399 patients without any obvious infectious disease upon admission were analyzed. The major in-hospital and post-discharge outcome measures were all-cause deaths. There were 215 patients (9.0%) with newly diagnosed infections during hospitalization, and 2184 patients (91.0%) without infection during hospitalization. The factors independently associated with a newly diagnosed infection were age ≥80 years, acute coronary syndrome, non-ambulatory status, hyponatremia, anemia, intubation, and patients who were not on loop diuretics as outpatients. The newly diagnosed infection group was associated with a higher incidence of in-hospital mortality (16.3% and 3.2%, P <0.001) and excess adjusted risk of in-hospital mortality (odds ratio, 6.07 [95% CI, 3.61-10.19], P <0.001) compared with the non-infection group. The newly diagnosed infection group was also associated with a higher 1-year incidence of post-discharge mortality (19.3% in the newly diagnosed infection group and 13.6% in the non-infection group, P <0.001) and excess adjusted risk of post-discharge mortality (hazard ratio, 1.49 [95% CI, 1.08-2.07], P =0.02) compared with the non-infection group. Conclusions Elderly patients with multiple comorbidities were associated with the development of newly diagnosed infections after admission for acute heart failure. Newly diagnosed infections after admission were associated with higher in-hospital and post-discharge mortality in patients with acute heart failure. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT02334891.

Background Heart failure (HF) is a known risk factor for ischemic stroke, but data regarding ischemic stroke during hospitalization for acute decompensated HF (ADHF) are limited. Methods and Results We analyzed the data from a multicenter registry (Kyoto Congestive Heart Failure [KCHF] Registry) that enrolled 4056 consecutive patients with ADHF in Japan (mean age, 78 years; men, 2238 patients [55%]; acute coronary syndrome [ACS], 239 patients [5.9%]). We investigated the incidence and predictors of ischemic stroke during hospitalization for ADHF. During the hospitalization, 63 patients (1.6%) developed ischemic stroke. The median interval from admission to the onset of ischemic stroke was 7 [interquartile range: 2-14] days, and the most common underlying cause was cardioembolism (64%). Men (OR, 1.87; 95%CI, 1.11-3.24), ACS (OR, 2.31; 95%CI, 1.01-4.93), absence of prior HF hospitalization (OR, 2.21; 95%CI, 1.24-4.21), and high B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) levels (above the median) at admission (OR, 3.15; 95%CI, 1.84-5.60) were independently associated with ischemic stroke. In patients without ACS, the independent risk factors for ischemic stroke were fully consistent with those in the main analysis. Higher quartiles of BNP/NT-proBNP levels were significantly associated with higher incidence of ischemic stroke ( P for trend, <0.001). Patients with ischemic stroke showed higher in-hospital mortality, longer length of hospital stay, and poorer functional status at discharge. Conclusions During hospitalization for ADHF, 1.6% of the patients developed ischemic stroke. Men, ACS, absence of prior HF hospitalization, and high BNP/NT-proBNP levels at admission were independently associated with ischemic stroke.

Background: Sodium glucose cotransporter 2 inhibitor (SGLT2i) has recently been suggested to reduce the risk of cardiovascular events. Left ventricular hypertrophy (LVH) is associated with cardiovascular events. Diabetic macroangiopathy is a crucial complication in patients with diabetes mellitus (DM). This study examined the effect of SGLT2i on LVH in patients with type 2 DM (T2DM)., Methods: The retrospective cohort study was conducted in consecutive outpatients with T2DM from 2010 to 2020. Left ventricular mass index (LVMI) was used as an indicator of LVH based on echocardiography. The minimum follow-up period was 1 year. After propensity score-matching for clinical profiles, patients who underwent annual echocardiography twice for a routine checkup and took SGLT2i were defined to the SGLT2i group, whereas patients without SGLT2 inhibitors were defined to the non-SGLT2 group. SGLT2i was administered after baseline echocardiography followed by a second examination., Results: LVMI levels in the SGLT2i group (n = 169) significantly decreased from baseline compared with those in the non-SGLT2i group (n = 169), % changes in LVMI2.7(g/m 2.7 ) in median (interquartile ranges [IQR]) were - 7.7 (-18.7, 2.5) vs -3.6 (-14.3, 5.8), respectively, P = 0.017). In a subgroup analysis, LVMI levels in the patients who had LVH in the SGLT2i group more significantly decreased than those without LVH, % changes in LVMI2.7(g/m 2.7 ) in median (IQR) were -13.5 (-22.1, -2.4) vs -2.8 (-12.6, 9.8), respectively, P < 0.001)., Conclusions: SGLT2i treatment was shown to improve LVH in patients with T2DM and may play a pivotal role in the future treatment of diabetic cardiovascular complications., (© 2021 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Abstract: There was no previous report on the prognostic impact of new-onset or improved anemia after discharge from acute decompensated heart failure (ADHF).We analyzed 771 patients with ADHF and who were followed in multicenters in Japan was divided into 4 groups based on the hemoglobin values at discharge and 6-month index visit: 373 patients (48.4%) with persistent anemia, 87 patients (11.3%) with new-onset anemia, 91 patients (11.8%) with improved anemia, and 220 patients (28.5%) without anemia.The primary outcome measure was a composite of all-cause death or HF hospitalization after index visit. The cumulative 6-month incidences of the primary outcome measure were 25.2% for persistent anemia, 18.5% for new onset anemia, 9.0% for improved anemia, and 9.2% for no anemia (log-rank P < .001). Compared with the no anemia group, the excess risk for the primary outcome measure remained significant in the persistent anemia group [hazard ratio (HR) 2.70, 95% confidence interval (95% CI), 1.45-5.44, P = .001] and in the new-onset anemia group (HR 2.73, 95% CI 1.19-6.25, P = .02), while it was not significant in the improved anemia group (HR 1.69, 95% CI 0.68-4.03, P = .25).Persistent and new-onset anemia at 6-month visit were associated with a subsequent higher risk for all-cause death or HF hospitalization in patients with ADHF, suggesting the importance of detecting anemia during follow-up., Competing Interests: The authors declare that there is no conflict of interest, (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background No clinical studies have focused on the factors associated with discharge destination in patients with acute decompensated heart failure. Methods and Results Of 4056 consecutive patients hospitalized for acute decompensated heart failure in the KCHF (Kyoto Congestive Heart Failure) registry, we analyzed 3460 patients hospitalized from their homes and discharged alive. There were 3009 and 451 patients who were discharged to home and nonhome, respectively. We investigated the factors associated with nonhome discharge and compared the outcomes between home discharge and nonhome discharge. Factors independently and positively associated with nonhome discharge were age ≥80 years (odds ratio [OR],1.76; 95% CI,1.28-2.42), body mass index ≤22 kg/m 2 (OR,1.49; 95% CI,1.12-1.97), poor medication adherence (OR, 2.08; 95% CI,1.49-2.88), worsening heart failure (OR, 2.02; 95% CI, 1.46-2.82), stroke during hospitalization (OR, 3.74; 95% CI, 1.75-8.00), functional decline (OR, 12.24; 95% CI, 8.74-17.14), and length of hospital stay >16 days (OR, 4.14; 95% CI, 3.01-5.69), while those negatively associated were diabetes mellitus (OR, 0.69; 95% CI, 0.51-0.94), cohabitants (OR, 0.62; 95% CI, 0.46-0.85), and ambulatory state before admission (OR, 0.25; 95% CI, 0.18-0.36). The cumulative 1-year incidence of all-cause death was significantly higher in the nonhome discharge group than in the home discharge group. The nonhome discharge group compared with the nonhome discharge group was associated with a higher adjusted risk for all-cause death (hazard ratio, 1.66; P <0.001). Conclusions The discharge destination of patients with acute decompensated heart failure is influenced by factors such as prehospital social background, age, body mass index, low self-care ability, events during hospitalization (worsening heart failure, stroke, etc), functional decline, and length of hospital stay; moreover, the prognosis of nonhome discharge patients is worse than that of home discharge patients. Registration Information clinicaltrials.gov. Identifier: NCT02334891.

Background Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long-term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). Methods and Results Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, we identified the current study population of 3380 patients with three-vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow-up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P =0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28-2.42; P <0.001) and no excess mortality risk in patients without heart failure (HR, 1.04; 95% CI, 0.80-1.34; P =0.77). Conclusions There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure.

Aims: Although the prognostic impact of the high tricuspid regurgitation pressure gradient (TRPG) has been investigated, the association of the decrease in TRPG during follow-up with clinical outcomes in heart failure (HF) has not been previously studied. The aim of this study was to investigate the association of a decrease in TRPG between hospitalization and 6 month visit with subsequent clinical outcomes in patients with acute decompensated HF (ADHF)., Methods and Results: Among 721 patients with available TRPG data both during hospitalization and a subsequent 6 month visit, the study population was divided into two groups: a decrease in TRPG group (>10 mmHg decrease at 6 month visit) (N = 179) and no decrease in TRPG group (N = 542). The primary outcome measure was a composite of all-cause death or HF hospitalization. The cumulative 6 month incidence of primary outcome measure was significantly lower in the decrease in TRPG group than in the no decrease in TRPG group (12.2% vs. 18.7%, P = 0.02). After adjusting for confounders, there was a significantly lower risk in decrease in TRPG group than in the no decrease in TRPG group for the measured primary outcome (hazard ratio: 0.56, 95% confidence interval 0.32-0.93, P = 0.02). The lower risk in decrease in TRPG group was not different among the basal TRPG values., Conclusions: Heart failure patients with a decrease in TRPG at 6 months after discharge from ADHF hospitalization had lower subsequent risk of all-cause death and HF hospitalization than those without a decrease in TRPG, regardless of TRPG values., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background It remains unclear whether beta-blocker use at hospital admission is associated with better in-hospital outcomes in patients with acute decompensated heart failure. Methods and Results We evaluated the factors independently associated with beta-blocker use at admission, and the effect of beta-blocker use at admission on in-hospital mortality in 3817 patients with acute decompensated heart failure enrolled in the Kyoto Congestive Heart Failure registry. There were 1512 patients (39.7%) receiving, and 2305 patients (60.3%) not receiving beta-blockers at admission for the index acute decompensated heart failure hospitalization. Factors independently associated with beta-blocker use at admission were previous heart failure hospitalization, history of myocardial infarction, atrial fibrillation, cardiomyopathy, and estimated glomerular filtration rate <30 mL/min per 1.73 m 2 . Factors independently associated with no beta-blocker use were asthma, chronic obstructive pulmonary disease, lower body mass index, dementia, older age, and left ventricular ejection fraction <40%. Patients on beta-blockers had significantly lower in-hospital mortality rates (4.4% versus 7.6%, P <0.001). Even after adjusting for confounders, beta-blocker use at admission remained significantly associated with lower in-hospital mortality risk (odds ratio, 0.41; 95% CI, 0.27-0.60, P <0.001). Furthermore, beta-blocker use at admission was significantly associated with both lower cardiovascular mortality risk and lower noncardiovascular mortality risk. The association of beta-blocker use with lower in-hospital mortality risk was relatively more prominent in patients receiving high dose beta-blockers. The magnitude of the effect of beta-blocker use was greater in patients with previous heart failure hospitalization than in patients without ( P for interaction 0.04). Conclusions Beta-blocker use at admission was associated with lower in-hospital mortality in patients with acute decompensated heart failure. Registration URL: https://www.upload.umin.ac.jp/; Unique identifier: UMIN000015238.

Aims: The association between serum cholinesterase and prognosis in acute heart failure (AHF) remains to be elucidated. We investigated the serum cholinesterase level at discharge from hospitalization for AHF and its association with clinical outcomes in patients with AHF., Methods and Results: Among 4056 patients enrolled in the Kyoto Congestive Heart Failure multicentre registry, we analysed 2228 patients with available serum cholinesterase data. The study population was classified into three groups according to serum cholinesterase level at discharge: low tertile (<180 U/L, N = 733), middle tertile (≥180 U/L and <240 U/L, N = 746), and high tertile (≥240 U/L, N = 749). Patients in the low tertile had higher tricuspid pressure gradient, greater inferior vena cava diameter, and higher brain natriuretic peptide (BNP) levels than those in the high tertile. The cumulative 1-year incidence of the primary outcome measure (a composite endpoint of all-cause death and hospitalization for HF) was higher in the low and middle tertiles than in the high tertile [46.5% (low tertile) and 31.4% (middle tertile) vs. 22.1% (high tertile), P < 0.0001]. After adjustment for 26 variables, the excess risk of the low tertile relative to the high tertile for the primary outcome measure remained significant (hazard ratio 1.37, 95% confidence interval 1.10-1.70, P = 0.006). Restricted cubic spline models below the median of cholinesterase demonstrated incrementally higher hazards at low cholinesterase levels., Conclusions: Low serum cholinesterase levels are associated with congestive findings on echocardiography, higher BNP, and higher risks for a composite of all-cause death and HF hospitalization in patients with AHF., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: The association between sequential changes in left atrial diameter (LAD) and prognosis in heart failure (HF) remains to be elucidated. The present study aimed to investigate the link between reduction in LAD and clinical outcomes in patients with HF., Design: A multicentre prospective cohort study., Setting: This study was nested from the Kyoto Congestive Heart Failure registry including consecutive patients admitted for acute decompensated heart failure (ADHF) in 19 hospitals throughout Japan., Participants: The current study population included 673 patients with HF who underwent both baseline and 6-month follow-up echocardiography with available paired LAD data. We divided them into two groups: the reduction in the LAD group (change <0 mm) (n=398) and the no-reduction in the LAD group (change ≥0 mm) (n=275)., Primary and Secondary Outcomes: The primary outcome measure was a composite of all-cause death or hospitalisation for HF during 180 days after 6-month follow-up echocardiography. The secondary outcome measures were defined as the individual components of the primary composite outcome measure and a composite of cardiovascular death or hospitalisation for HF., Results: The cumulative 180-day incidence of the primary outcome measure was significantly lower in the reduction in the LAD group than in the no-reduction in the LAD group (13.3% vs 22.2%, p=0.002). Even after adjusting 15 confounders, the lower risk of reduction in LAD relative to no-reduction in LAD for the primary outcome measure remained significant (HR 0.59, 95% CI 0.36 to 0.97 p=0.04)., Conclusion: Patients with reduction in LAD during follow-up after ADHF hospitalisation had a lower risk for a composite endpoint of all-cause death or HF hospitalisation, suggesting that the change of LAD might be a simple and useful echocardiographic marker during follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To examine the association of a high C-reactive protein (CRP) level at discharge from an acute decompensated heart failure (ADHF) hospitalisation with the 1-year clinical outcomes., Design: A post-hoc subanalysis of a prospective cohort study of patients hospitalised for ADHF (using the Kyoto Congestive Heart Failure (KCHF) registry) between October 2014 and March 2016 with a 1-year follow-up., Setting: A physician-initiated multicentre registry enrolled consecutive hospitalised patients with ADHF for the first time at 19 secondary and tertiary hospitals in Japan., Participants: Among the 4056 patients enrolled in the KCHF registry, the present study population consisted of 2618 patients with an available CRP value both on admission and at discharge and post-discharge clinical follow-up data. We divided the patients into two groups, those with a high CRP level (>10 mg/L) and those with a low CRP level (≤10 mg/L) at discharge from the index hospitalisation., Primary and Secondary Outcome Measures: The primary outcome measure was all-cause death after discharge from the index hospitalisation. The secondary outcome measures were heart failure hospitalisations, cardiovascular death and non-cardiovascular death., Results: The high CRP group and low CRP group included 622 patients (24%) and 1996 patients (76%), respectively. During a median follow-up period of 468 days, the cumulative 1-year incidence of the primary outcome was significantly higher in the high CRP group than low CRP group (24.1% vs 13.9%, log-rank p<0.001). Even after a multivariable analysis, the excess mortality risk in the high CRP group relative to the low CRP group remained significant (HR, 1.43; 95% CI, 1.19 to 1.71; p<0.001). The excess mortality risk was consistent regardless of the clinically relevant subgroup factors., Conclusions: A high CRP level (>10 mg/L) at discharge from an ADHF hospitalisation was associated with an excess mortality risk at 1 year. TRIAL REGISTRATION DETAILS: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000017241 (UMIN000015238)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the prognostic importance of hypoalbuminemia, the prognostic implication of a change in albumin levels has not been fully investigated during hospitalization in patients with acute decompensated heart failure (ADHF)., Methods: Using the data from the Kyoto Congestive Heart Failure registry on 3160 patients who were discharged alive for acute heart failure hospitalization and in whom the change in albumin levels was calculated at discharge, we evaluated the association with an increase in serum albumin levels from admission to discharge and clinical outcomes by a multivariable Cox hazard model. The primary outcome measure was a composite of all-cause death or hospitalization for heart failure., Findings: Patients with increased albumin levels (N = 1083, 34.3%) were younger and less often had smaller body mass index and renal dysfunction than those with no increase in albumin levels (N = 2077, 65.7%). Median follow-up was 475 days with a 96% 1-year follow-up rate. Relative to the group with no increase in albumin levels, the lower risk of the increased albumin group remained significant for the primary outcome measure (hazard ratio: 0.78, 95% confidence interval: 0.69-0.90: P = 0.0004) after adjusting for confounders including baseline albumin levels. When stratified by the quartiles of baseline albumin levels, the favorable effect of increased albumin was more pronounced in the lower quartiles of albumin levels, but without a significant interaction effect (interaction P = 0.49)., Conclusions: Independent of baseline albumin levels, an increase in albumin during index hospitalization was associated with a lower 1-year risk for a composite of all-cause death and hospitalization in patients with acute heart failure., Competing Interests: The authors have declared that no competing interests exist.

The prognostic implications of very low body mass index (BMI) values remain unclear in patients with acute decompensated heart failure (ADHF). This study aimed to investigate the prognostic impact of BMI classification based on the World Health Organization criteria in patients with ADHF. Among 3509 patients with ADHF and available BMI data at discharge in 19 participating hospitals in Japan between October 2014 and March 2016, the study population was divided into five groups; (1) Severely underweight: BMI < 16 kg/m 2 , (2) Underweight: BMI ≥ 16 kg/m 2 and < 18.5 kg/m 2 , (3) Normal weight: BMI ≥ 18.5 kg/m 2 and < 25 kg/m 2 , (4) Overweight: BMI ≥ 25 kg/m 2 and < 30 kg/m 2 (5) Obese: BMI ≥ 30 kg/m 2 . The primary outcome measure was all-cause death. The median follow-up duration was 471 days, with 96.4% follow up at 1-year. The cumulative 1-year incidence of all-cause death was higher in underweight groups, and lower in overweight groups (Severely underweight: 36.3%, Underweight: 23.9%, Normal weight: 14.4%, Overweight: 7.9%, and Obese: 9.0%, P < 0.001). After adjusting confounders, the excess mortality risk remained significant in the severely underweight group (HR, 2.32; 95%CI, 1.83-2.94; P < 0.001), and in the underweight group (HR, 1.31; 95%CI, 1.08-1.59; P = 0.005) relative to the normal weight group, while the lower mortality risk was no longer significant in the overweight group (HR, 0.82; 95%CI, 0.62-1.10; P = 0.18) and in the obese group (HR, 1.09; 95%CI, 0.65-1.85; P = 0.74). Very low BMI was associated with a higher risk for one-year mortality after discharge in patients with ADHF.

Aims: The association between sex and long-term outcome in patients hospitalized for acute decompensated heart failure (ADHF) has not been fully studied yet in Japanese population. The aim of this study was to determine differences in baseline characteristics and management of patients with ADHF between women and men and to compare 1-year outcomes between the sexes in a large-scale database representing the current real-world clinical practice in Japan., Methods and Results: Kyoto Congestive Heart Failure registry is a prospective cohort study enrolling consecutive patients hospitalized for ADHF in Japan among 19 centres. Baseline characteristics, clinical presentation, management, and 1-year outcomes were compared between men and women. A total of 3728 patients who were alive at discharge constituted the current study population. There were 1671 women (44.8%) and 2057 men. Women were older than men [median (IQR): 83 (76-88) years vs. 77 (68-84) years, P < 0.0001]. Hypertensive and valvular heart diseases were more prevalent in women than in men (28.0% vs. 22.5%, P = 0.0001; and 26.9% vs. 14.0%, P < 0.0001, respectively), whereas ischaemic aetiology was less prevalent in women than in men (20.0% vs. 32.5%, P < 0.0001). Women less often had reduced left ventricular ejection fraction (<40%) than men (27.5% vs. 45.1%, P < 0.0001). The cumulative incidence of all-cause death or hospitalization for heart failure was not significantly different between women and men (33.6% vs. 34.3%, P = 0.71), although women were substantially older than men. After multivariable adjustment, the risk of all-cause death or hospitalization for heart failure was significantly lower among women (adjusted hazard ratio: 0.84, 95% confidence interval: 0.74-0.96, P = 0.01)., Conclusions: Women with heart failure were older and more often presented with preserved EF with a non-ischaemic aetiology and were associated with a reduced adjusted risk of 1-year mortality compared with men in the Japanese population., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

The high controlling nutritional status (CONUT) score that represents poor nutritional status has been acknowledged to have prognostic implications in chronic heart failure. We aimed to investigate its role in acute decompensated heart failure (ADHF). Using the data from an multicenter registry that enrolled 4056 consecutive patients hospitalized for ADHF in Japan between 2014 and 2016, we analyzed 2466 patients in whom data on the components of the CONUT score at hospital presentation were available. The decrease of lymphocyte count and total cholesterol was assigned with 0, 1, 2, and 3 points and the decrease of albumin was assigned with 0, 2, 4, and 6 points according to the severity. We defined low CONUT score as 0-4 (N = 1568) and high CONUT score as 5-9 (N = 898). The patients in the high CONUT score group were older and more likely to have a smaller body mass index than those in the low CONUT score group. The high CONUT score group was associated with higher rate of death and infection during the index hospitalization compared to the low CONUT score group (9.0% versus 4.4%, and 21.9% versus 12.7%, respectively). After adjusting for confounders, the excess risk of high relative to low CONUT score for mortality and infection was significant (OR: 1.61, 95%CI: 1.05-2.44, and OR: 1.66, 95%CI: 1.30-2.12, respectively). The effect was incremental according to the score. High CONUT score was associated with higher risk for in-hospital mortality and infection in an incremental manner in patients hospitalized for ADHF.

Background: Transcatheter aortic valve implantation (TAVI) is criticized by some as an expensive treatment in super-elder patients with limited life expectancy. However, there is a knowledge gap regarding the magnitude of clinical benefit provided by TAVI in comparison with conservative management in patients with severe aortic stenosis (AS) in real clinical practice, which would be important in the decision making for TAVI., Methods: We combined two independent registries, namely CURRENT AS and K-TAVI registries. CURRENT AS was a multicenter registry enrolling 3815 consecutive patients with severe AS irrespective to treatment modalities between January 2003 and December 2011. K-TAVI was a multicenter, prospective registry including 449 consecutive patients with severe AS, who underwent TAVI with SAPIEN XT balloon-expandable valves between October 2013 and June 2016. In these 2 registries, 449 patients received TAVI and 894 patients were managed with conservative strategy. We conducted propensity score matching and finally obtained a cohort of 556 patients (278 patients for each group) for the analysis. The primary outcome measures were all-cause death and heart failure (HF) hospitalization at 2-year., Results: The cumulative 2-year incidences of all-cause death and HF hospitalization were significantly lower in the TAVI group than in the conservative group (16.8% versus 36.6%, P<0.001, and 10.7% versus 37.2%, P<0.001). After adjusting the residual confounders, TAVI reduced the risks of all-cause death (HR, 0.46; 95%CI, 0.32-0.69; P = 0.0001) and HF hospitalizations (HR, 0.25; 95%CI, 0.16-0.40; P<0.0001) compared with conservative strategy. There was no difference in the cumulative incidence of non-cardiovascular death between the 2 groups., Conclusions: TAVI in the early Japanese experience was associated with striking risk reduction for all-cause death as well as HF hospitalization as compared with the historical cohort of patients with severe AS who were managed conservatively just before introduction of TAVI in Japan., Competing Interests: The authors have declared that no competing interests exist.

Importance: Scarce data are available on the association of mineralocorticoid receptor antagonist (MRA) use with outcomes in acute decompensated heart failure (ADHF)., Objective: To investigate the association of MRA use with all-cause mortality and hospital readmission in patients with ADHF., Design, Setting, and Participants: This cohort study examines participants enrolled in the Kyoto Congestive Heart Failure (KCHF) registry, a physician-initiated, prospective, multicenter cohort study of consecutive patients admitted for ADHF, between October 1, 2014, and March 31, 2016, into 1 of 19 secondary and tertiary hospitals throughout Japan. To balance the baseline characteristics associated with the selection of MRA use, a propensity score-matched cohort design was used, yielding 2068 patients. Data analysis was conducted from April to August 2018., Exposures: Prescription of MRA at discharge from the index hospitalization., Main Outcomes and Measures: Composite of all-cause death or heart failure hospitalization after discharge., Results: Among 3717 patients hospitalized for ADHF, 1678 patients (45.1%) had received MRA at discharge and 2039 (54.9%) did not. After propensity score matching, 2068 patients (with a median [interquartile range] age of 80 [72-86] years, and of whom 937 [45.3%] were women) were included. In the matched cohort (n = 1034 in each group), the cumulative 1-year incidence of the primary outcome was statistically significantly lower in the MRA use group than in the no MRA use group (28.4% vs 33.9%; hazard ratio [HR], 0.81; 95% CI, 0.70-0.93; P = .003). Of the components of the primary outcome, the cumulative 1-year incidence of heart failure hospitalization was significantly lower in the MRA use group than in the no MRA use group (18.7% vs 24.8%; HR, 0.70; 95% CI, 0.60-0.86; P < .001), whereas no difference in mortality was found between the 2 groups (15.6% vs 15.8%; HR, 0.98; 95% CI, 0.82-1.18; P = .85). No difference in all-cause hospitalization was observed between the 2 groups (35.3% vs 38.2%; HR, 0.88; 95% CI, 0.77-1.01; P = .07). In additional analyses that stratified by left ventricular ejection fraction, the association of MRA use with the primary outcome was statistically significant in patients with left ventricular ejection fraction of 40% or greater., Conclusions and Relevance: Use of MRA at discharge from ADHF hospitalization did not appear to be associated with lower mortality but was associated with a lower risk of heart failure readmission. This finding suggests that MRA treatment at discharge may have minimal, if any, clinical advantages.

Background: There is a scarcity of reports on the clinical characteristics and management practice in contemporary all-comer patients with acute decompensated heart failure (ADHF)., Methods and results: The Kyoto Congestive Heart Failure (KCHF) registry is a prospective observational cohort study enrolling 4,056 consecutive patients who had hospital admission due to ADHF without any exclusion criteria between October 2014 and March 2016 in the 19 participating hospitals in Japan. Baseline characteristics, clinical presentations, management, and in-hospital outcomes were compared between heart failure (HF) with reduced left ventricular ejection fraction (LVEF; HFrEF, LVEF <40%), HF with mid-range LVEF (HFmrEF, LVEF 40-49%), and HF with preserved LVEF (HFpEF, LVEF ≥50%). Of the 4,041 patients with documented LVEF, 1,744 (43%) had HFpEF; 746 (19%), HFmrEF; and 1,551 (38%), HFrEF. The median age was 80 years (IQR, 72-86 years) in the entire population, and was higher with increasing LVEF (P<0.001). The in-hospital mortality rate was higher in the HFrEF than in the HFmrEF and HFpEF groups (9.2%, 4.8%, and 5.1%, respectively, P<0.001)., Conclusions: This registry elucidated the clinical features and clinically relevant in-hospital outcomes in contemporary consecutive patients with ADHF in real-world clinical practice in Japan. When classified by LVEF, significant differences in characteristics and in-hospital outcomes existed between patients with HFrEF, HFmrEF, and HFpEF.

It is unknown how much different are the clinical outcomes between asymptomatic and symptomatic patients with severe aortic stenosis (AS). In the CURRENT AS registry enrolling 3,815 consecutive patients with severe AS, we compared the long-term outcomes between 1808 asymptomatic and 1215 symptomatic patients (exertional dyspnea: N = 813, syncope: N = 136, and angina: N = 266) without heart failure (HF) hospitalization. Symptomatic patients had greater AS severity, and more depressed left ventricular function than asymptomatic patients without much difference in other baseline characteristics. During a median follow-up of 3.2 years, aortic valve replacement (AVR) was performed in 62% of symptomatic patients, and 38% of asymptomatic patients. The cumulative 5-year incidences for the primary outcome measure (a composite of aortic valve-related death or HF hospitalization) was higher in symptomatic patients than in asymptomatic patients (32.3% versus 27.6%, P < 0.001). After adjusting for AVR and other variables, the greater risk of symptomatic relative to asymptomatic patients for the primary outcome measure was significant (hazard ratio 1.64, 95% confidence interval 1.41-1.96, P < 0.001). In conclusions, the excess risk of symptomatic relative to asymptomatic patients with severe AS for the aortic valve-related event was significant. However, the prevalence of AVR in symptomatic patients was not optimal.

Background: Clinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear., Methods and results: From a Japanese multicenter registry enrolling consecutive patients with severe AS, 3,813 patients were categorized into the 3 groups according to the symptom of heart failure (HF); No HF (n=2,210), chronic HF (CHF) (n=813) and AHF defined as hospitalized HF at enrolment (n=790). Median follow-up was 1,123 days with 93% follow-up rate at 2 years. Risk factors for developing AHF included age, female sex, lower body mass index, untreated coronary artery stenosis, anemia, history of HF, left ventricular ejection fraction <50%, presence of any combined valvular disease, peak aortic jet velocity ≥5 m/s and tricuspid regurgitation pressure gradient ≥40 mmHg, and negative risk factors included dyslipidemia, history of percutaneous coronary intervention and hemodialysis. Respective cumulative 5-year incidences of all-cause death and HF hospitalization in No HF, CHF and AHF groups were 37.1%, 41.8% and 61.8% (P<0.001) and 20.7%, 33.8% and 52.3% (P<0.001). Even in the initial aortic valve replacement (AVR) stratum, AHF was associated with excess 5-year mortality risk relative to No HF and CHF (adjusted hazard ratio [HR] 1.64; 95% confidence interval [CI]: 1.14-2.36, P=0.008; adjusted HR 1.47; 95% CI: 1.03-2.11, P=0.03, respectively)., Conclusions: AHF complicating severe AS was associated with an extremely dismal prognosis, which could not be fully resolved by AVR. Careful management to avoid the development of AHF is crucial.

Background: The significance of routine measurement of lactate level is unclear in patients with critical acute decompensated heart failure (ADHF)., Methods and Results: Consecutive 754 patients who were admitted to the intensive care unit (ICU) in our hospital from January 2007 to March 2012 and given a diagnosis of ADHF were eligible for retrospective entry into the registry. Lactate level was measured on admission from routine arterial blood sample and we investigated by comparing the lactate level and parameters of conventional in-hospital mortality predictors. Among the patients, 88 (12%) died during hospitalization. The lactate level had great power to predict in-hospital mortality, as suggested by the c-statistics of 0.71. The occurrence of in-hospital death was more pronounced in patients with high levels of lactate (>3.2mmol/l) and the tendency was observed in patients in both the acute coronary syndrome (ACS) group and non-ACS group. In multivariate analysis, elevated lactate levels remained an independent predictor of in-hospital death (odds ratio, 2.14; 95% confidence interval, 1.10-4.21; p=0.03)., Conclusions: Elevated levels of arterial lactate on admission were related to worse in-hospital mortality in patients with ADHF either with or without ACS, suggesting that the presence of high lactate in patients who enter the ICU with ADHF could help stratify the initial risk of early mortality., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Patients with reduced peak oxygen uptake (VO2) due to chronic heart failure (CHF) exhibit abnormal VO2 kinetics even during mild to moderate exercise. This is characterized by a reduced ratio of the VO2 increase to the work rate increment (DeltaVO2/DeltaWR) during ramp exercise, and by a slow increase in VO2 during constant work rate exercise. Because the slow kinetics alone is unlikely to explain the reduced DeltaVO2/DeltaWR on theoretical grounds, we can postulate that the linearity between work rate and VO2 may be impaired when exercise is imposed in a ramp fashion. The present study was designed to address this issue. In 21 CHF patients and 17 normal controls, we performed both symptom-limited exercise testing (15 W. min(-1) ramp) and a constant work rate exercise test (0 W followed by 50-W step). The VO2 step response was used to mathematically derive the hypothetical VO2 ramp response by time integration. Although peak VO2 and work rate were both significantly lower in patients, the attenuation in peak VO2 was more prominent ( p<0.05), which could be explained by a lower DeltaVO2/DeltaWR in patients compared with controls [8.1 (SD 1.0) and 9.8 (0.5) ml. min(-1). W(-1), p<0.01]. The hypothetical DeltaVO2/DeltaWR derived from the VO2 step response was also significantly lower in patients [8.7 (1.0) and 10.0 (0.7) ml. min(-1). W(-1), p<0.01]. The hypothetical and measured DeltaVO2/DeltaWR were highly correlated ( r=0.78, p<0.001). Thus, we can reasonably predict the VO2 ramp response from the VO2 response to a step increase in work rate, indicating that linearity between VO2 and work rate is held constant irrespective of loading patterns. Additional studies, such as those including evaluation of anaerobic bioenergetics, are needed to further elucidate the precise mechanism(s) of this phenomenon.

Background: The detailed causes of death in non–ST-segment–elevation myocardial infarction (NSTEMI) have not been adequately evaluated compared to those in ST-segment elevation myocardial infarction (STEMI). Methods: The study population was 6,228 AMI patients who underwent percutaneous coronary intervention (STEMI: 4,625 patients and NSTEMI: 1,603 patients). The primary outcome was all-cause death. Results: Within 6 months after AMI, the adjusted mortality risk was not significantly different between NSTEMI patients and STEMI patients (HR: 0.83, 95%CI: 0.67–1.03, P = 0.09). Regarding the causes of death within 6 months after AMI, mechanical complications more frequently occurred in STEMI patients than in NSTEMI patients, while proportions of post resuscitation status on arrival and heart failure were higher in in NSTEMI patients than in STEMI patients. Beyond 6 months after AMI, the adjusted mortality risk of NSTEMI relative to STEMI was not significantly different. (HR: 1.04, 95%CI: 0.90–1.20, P = 0.59). Regarding causes of death beyond 6 months after AMI, almost half of deaths were cardiovascular causes in both groups, and breakdown of causes of death was similar between NSTEMI and STEMI. Conclusion: The mortality risk within and beyond 6 months after AMI were not significantly different between STEMI patients and NSTEMI patients after adjusting confounders. Deaths due to post resuscitation status and heart failure were more frequent in NSTEMI within 6 months after AMI. [ABSTRACT FROM AUTHOR]