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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.)

Aims: The use of tolvaptan is increasing in clinical practice in Japan. However, the characteristics of patients who used tolvaptan and the timing of its use in patients with acute heart failure (AHF) are not fully elucidated., Methods and Results: Among consecutive 4056 patients in the Kyoto Congestive Heart Failure registry, we analysed 3802 patients after excluding patients on dialysis, prior or unknown tolvaptan use at admission, and unknown timing of tolvaptan use, and we divided them into two groups: tolvaptan use (N = 773) and no tolvaptan use (N = 3029). The prevalence of tolvaptan use varied widely from 48.7% to 0% across the participating centres. Factors independently associated with tolvaptan use were diabetes, poor medical adherence, oedema, pleural effusion, hyponatraemia, estimated glomerular filtration rate < 30 mL/min/1.73 m 2 , moderate/severe tricuspid regurgitation, dobutamine infusion within 24 h, and additional inotropes infusion beyond 24 h after admission. The mortality rate at 90 days after admission was significantly higher in the tolvaptan use group than in the no tolvaptan use group (14.3% vs. 8.6%, P = 0.049). However, after adjustment, the excess mortality risk of tolvaptan use relative to no tolvaptan use was no longer significant (hazard ratio = 1.53, 95% confidence interval = 0.77-3.02, P = 0.22). Patients with tolvaptan use had a longer hospital stay [median (interquartile range): 22 (15-34) days vs. 15 (11-21) days, P < 0.0001] and a higher prevalence of worsening renal failure (47.0% vs. 31.8%, P < 0.0001) and worsening heart failure (24.8% vs. 14.4%, P < 0.0001) than those without., Conclusions: AHF patients with tolvaptan use had more congestive status with poorer in-hospital outcomes and higher short-term mortality than those without tolvaptan use., 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)., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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.)

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.)

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.)

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.)

Aims: There is currently no gold standard in evaluating frailty in patients with heart failure (HF), and the prognostic value of frailty according to the Canadian Study of Health and Aging Clinical Frailty Scale (CFS) on mortality in patients with HF is still unknown., Methods and Results: Among consecutive 596 patients after their discharge from HF in Kokura Memorial Hospital (Kitakyushu, Japan) during 2015, their frailty at discharge was assessed according to CFS. Patients were classified into three groups: low (N = 232, 38.9%), intermediate (N = 230, 38.6%), and high (N = 134, 22.5%). The primary endpoint was defined as 2 year all-cause death. The mean age was 76.6 ± 10.1 years, and 55.3% were men in entire cohort. There were significant differences in age, living environment, and dementia among low, intermediate, and high CFS groups. Left ventricular ejection fraction (LVEF) and co-morbidities such as severe renal failure and severe anaemia tended to increase with frailty severity, while body mass index (BMI) and albumin level tended to decrease with frailty severity. Two year cumulative incidences of all-cause death for the three groups were 12.8%, 25.4%, and 52.7% (P < 0.001), respectively. This significant difference in the risk for all-cause death among the CFS groups was driven by the risk for cardiac (8.6%, 14.2%, and 31.0%, respectively, P < 0.001) and non-cardiac death (4.6%, 13.0%, and 31.4%, respectively, P < 0.001). The multivariate analysis showed that high frailty was independently associated with all-cause death (intermediate CFS group: adjusted hazard ratio, 1.43, 95% confidence interval, 0.86-2.36, P = 0.16; high CFS group: adjusted hazard ratio, 3.90, 95% confidence interval, 2.32-6.55, P < 0.001), and this result was consistent, irrespective of stratification based on age, sex, BMI, and LVEF without significant interaction., Conclusions: The simple CFS tool was successful in predicting the risk for all-cause death in patients with HF, and frailty according to CFS was independently associated with all-cause death irrespective of stratification based on age, sex, BMI, and LVEF without significant interaction. The CFS is a valuable prognostic tool in clinical settings., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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.)

Aims: Over the last decade, major developments in medicine have led to significant changes in the clinical management of heart failure patients. This study was designed to evaluate the recent trends in clinical characteristics, management, and short-term and long-term prognosis of patients with acute decompensated heart failure (ADHF) in Japan., Methods and Results: The Kyoto Congestive Heart Failure study is a prospective, observational, multicentre cohort study, enrolling consecutive ADHF patients from 19 participating hospitals in Japan from November 2014 to March 2016. A total of 4000 patients will be enrolled into the study and patients' anthropometric, socio-economic, and clinical data from hospital admission to discharge will be collected. In addition, in a pre-determined subgroup of patients (n=1500), a longitudinal follow-up for 2 years is scheduled., Conclusions: The Kyoto Congestive Heart Failure study will provide valuable information regarding patients with ADHF in the real-world clinical practice of Japan and will be indispensable for future clinical and policy decision-making with respect to heart failure., (© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)