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Objectives: The Asian Working Group for Sarcopenia in 2019 (AWGS 2019) emphasized muscle mass measurements. In contrast, the Sarcopenia Definitions and Outcomes Consortium (SDOC) prioritizes functional strength and mobility. Therefore, this study aimed to compare the prognostic utility of the SDOC and AWGS 2019 criteria for all-cause mortality in older patients with heart failure., Design: A post hoc analysis of the Prevalence and Prognostic Value of Physical and Social Frailty in Geriatric Patients Hospitalized for Heart Failure (FRAGILE-HF) study, a prospective, multicenter, observational study., Setting and Participants: Patients aged ≥65 years hospitalized for heart failure across 15 hospitals in Japan., Methods: Sarcopenia was diagnosed according to the AWGS 2019 and SDOC definitions. According to the SDOC criteria and by integrating insights from previous research, patients were categorized into nonsarcopenia, possible sarcopenia, and sarcopenia groups. The primary outcome was 2-year mortality., Results: Of the 1282 study patients, possible sarcopenia and sarcopenia were diagnosed in 357 and 786 individuals, respectively. Kaplan-Meier analysis revealed a significant difference between the groups. Adjusted Cox proportional hazards analysis indicated a significant stepwise association between sarcopenic status and mortality risk (possible sarcopenia: hazard ratio, 1.22; 95% CI, 0.66-2.28; P = .525; sarcopenia: hazard ratio, 1.89; 95% CI, 1.08-3.34; P = .027). When sarcopenia defined by the SDOC and AWGS 2019 criteria was added to the model incorporating conventional risk factors, no significant difference was observed in the prognostic capabilities between the 2 models (net reclassification improvement, -0.009; 95% CI, -0.193 to 0.174; P = .920, with areas under the receiver operating characteristic curve of 0.697 for SDOC and 0.703 for AWGS 2019; P = .675)., Conclusions and Implications: Among older patients with heart failure, the SDOC criteria for sarcopenia diagnosis are useful for risk stratification and provide prognostic capabilities equivalent to those of the AWGS 2019 criteria., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Aims: The 6-min walk test (6MWT) is a widely accepted tool for evaluating exercise tolerance and physical capacity, and the 6-min walk distance (6MWD) is an established prognostic factor in patients with heart failure (HF). However, the prognostic implications of post-6MWT dyspnoea remain unknown. We aimed to investigate the prognostic value of Borg scores after the 6MWT in patients with HF., Methods and Results: Patients hospitalized for HF who underwent the 6MWT before discharge were included. Post-test dyspnoea was assessed using the Borg scale. Patients were stratified into low and high Borg score groups based on the median Borg score. The primary outcome was 2-year mortality. Among 1185 patients analysed, the median Borg score was 12. The 6MWD was significantly shorter in the high Borg score group than in the low Borg score group. The 2-year mortality rate was 20.2%. In the Kaplan-Meier analysis, the high Borg score group demonstrated an association with 2-year mortality, which remained significant even after adjustment for conventional risk factors, including the 6MWD. Furthermore, the Borg scale provided significant net reclassification improvement to the conventional risk model incorporating 6MWD., Conclusion: In hospitalized patients with HF, post-6MWT Borg scores were associated with 2-year mortality independent of the 6MWD, providing incremental prognostic value to the 6MWD. Even if patients are able to walk long distances for 6 min, it is essential to closely observe dyspnoea immediately thereafter., Competing Interests: Conflict of interest: N.K. is affiliated with a department funded by Philips Japan, Inter Reha Co., Ltd, KYOCERA Corporation, AMI Inc., and Fukuda Denshi Co. Ltd based on collaborative research agreements and received honorarium from Novartis Japan, Otsuka Pharmaceutical Co., Ltd, and Eli Lilly Japan K.K. K.K. received funding outside the submitted work from Eiken Chemical Co., Ltd, and SoftBank Corporation, Ltd. T.K. was affiliated with a department sponsored by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. Y.M. received an honorarium from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca and a collaborative research grant from Pfizer Japan Inc., Otsuka Pharmaceutical Co., EN Otsuka Pharmaceutical Co., Ltd, and Nippon Boehringer Ingelheim Co., Ltd. The other authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Sarcopenia is a substantial therapeutic target, yet the validity of risk stratification values per the latest Asian Working Group for Sarcopenia in 2019 (AWGS 2019) remains unconfirmed in patients with heart failure. We hypothesized that using the 6-minute walk test (6MWT) to assess physical performance improves risk stratification., Methods: The study included 832 hospitalized patients with heart failure who could walk at discharge. Sarcopenia was diagnosed using both the original AWGS 2019 criteria (AWGS 2019 model) and an alternative method in which physical performance components were replaced with the 6MWT (modified model). An < 300 m 6MWT indicated low physical performance in the modified model. The primary outcome was 2-year mortality., Results: Sarcopenia and severe sarcopenia were identified in 45 and 150 patients with the AWGS 2019 model and in 75 and 108 patients with the modified model, respectively. Over the 2-year follow-up period, 145 (17.4%) deaths occurred. Adjusted Cox proportional hazard analysis showed both sarcopenia and severe sarcopenia were significantly associated with 2-year mortality in the modified model. In the AWGS 2019 model, only severe sarcopenia was significantly related to 2-year mortality. The modified model demonstrated significant net reclassification improvement (NRI) over the AWGS 2019 model (NRI, 0.396; 95% CI, 0.214-0.578; P < 0.001)., Conclusions: In patients with heart failure who were ambulatory at discharge, sarcopenia assessment with the modified AWGS 2019 model using the 6MWT as a physical performance component improved risk stratification compared with the original AWGS 2019 model. Reconsidering the current criteria to improve risk stratification is necessary to ensure timely, appropriate treatment., Clinical Trial Registration: UMIN000023929., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Aims: In heart failure (HF), inflammation is linked to malnutrition and impaired physical function. In this study, we aimed to assess how novel nutritional-inflammatory markers and lymphocyte-to-C-reactive protein ratio (LCR) and score (LCS) are associated with the nutritional status, physical function, and prognosis of patients with HF., Methods and Results: This study was a secondary analysis of the FRAGILE-HF study, a prospective observational study conducted across 15 hospitals in Japan. We included 1212 patients (mean age, 80.2 ± 7.8 years; 513 women) hospitalized with HF, who were classified into three groups according to their LCS score: 0 (n = 498), 1 (n = 533), and 2 (n = 181). Baseline data on physical examination, echocardiography, blood test results (including lymphocyte counts and CRP levels), and oral medication usage were collected in a clinically compensated state before discharge. Nutritional status and physical function were evaluated using several indices and tests. The primary outcome of this study was all-cause death within 2 years. Univariate and multivariate linear regression analyses were performed to evaluate the associations among the nutritional status, physical function, and LCR/LCS. Patients with an LCS score of 2 were older and had a lower body mass index than those in the other two groups. Multivariate linear regression analysis revealed that lower LCR and higher LCS were independently associated with worse nutritional status, lower handgrip strength, shorter physical performance battery score, and shorter 6-min walk distance. At 2 years, all-cause death occurred in 254 patients: 86 (17.6%), 113 (21.5%), and 55 (30.9%) with LCS scores of 0, 1, and 2, respectively (P = 0.001). Cox proportional hazards analysis revealed that LCR and LCS were significantly associated with 2-year mortality even after adjusting for the conventional risk model (LCS score, 0 vs. 2: hazard ratio, 1.64; 95% confidence interval [CI]; 1.14-2.35; P = 0.007; log-transformed LCR: hazard ratio, 0.88; 95% CI, 0.81-0.95; P = 0.002). LCR yielded additional prognostic predictability compared with the conventional risk model (continuous net reclassification improvement, 0.153; 95% CI, 0.007-0.299; P = 0.041)., Conclusions: LCR and LCS emerge as potential predictors of nutritional status, physical function, and prognosis in older patients with HF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure., Methods and Results: This post hoc analysis was performed using two prospective, multicentre, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. Among the 1243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8 and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF [hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.18-3.78, P = 0.012] and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors., Conclusion: Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality., Competing Interests: Conflict of interest: Y.M. received an honorarium from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca and research grants from Pfizer Japan Inc., Otsuka Pharmaceutical Co., EN Otsuka Pharmaceutical Co., Ltd, and Nippon Boehringer Ingelheim Co., Ltd. T.K. (Takatoshi Kasai) was affiliated with a department sponsored by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. N.K. is affiliated with a department funded by Paramount Bed Ltd., and receives research grants from EchoNous Inc. and AMI Inc. and honorarium from Novartis Pharama, Otsuka Pharma, Boehringer Ingelheim, and Elli Lilly. K.K. received funding outside the submitted work from Eiken Chemical Co., Ltd and SoftBank Corp., Ltd. The other authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Social factors encompass a broad spectrum of nonmedical factors, including objective (social isolation [SI]) and perceived (loneliness) conditions. Although social factors have attracted considerable research attention, information regarding their impact on patients with heart failure is scarce. We aimed to investigate the prognostic impact of objective SI and loneliness in older patients with heart failure., Methods and Results: This study was conducted using the FRAGILE-HF (Prevalence and Prognostic Value of Physical and Social Frailty in Geriatric Patients Hospitalized for Heart Failure; derivation cohort) and Kitasato cohorts (validation cohort), which included hospitalized patients with heart failure aged ≥65 years. Objective SI and loneliness were defined using the Japanese version of Lubben Social Network Scale-6 and diagnosed when the total score for objective and perceived questions on the Lubben Social Network Scale-6 was below the median in the FRAGILE-HF. The primary outcome was 1-year death. Overall, 1232 and 405 patients in the FRAGILE-HF and Kitasato cohorts, respectively, were analyzed. Objective SI and loneliness were observed in 57.8% and 51.4% of patients in the FRAGILE-HF and 55.4% and 46.2% of those in the Kitasato cohort, respectively. During the 1-year follow-up, 149 and 31 patients died in the FRAGILE-HF and Kitasato cohorts, respectively. Cox proportional hazard analysis revealed that objective SI, but not loneliness, was significantly associated with 1-year death after adjustment for conventional risk factors in the FRAGILE-HF. These findings were consistent with the validation cohort., Conclusions: Objective SI assessed using the Lubben Social Network Scale-6 may be a prognostic indicator in older patients with heart failure. Given the lack of established SI assessment methods in this population, further research is required to refine such methods.

Background: Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between multidomain frailty and the causes of death in elderly patients hospitalized with HF., Methods: We analyzed data from the FRAGILE-HF cohort, where patients aged 65 years and older, hospitalized with HF, were prospectively registered between 2016 and 2018 in 15 Japanese hospitals before discharge and followed up for 2 years. All patients were assessed for physical, social, and cognitive dysfunction, and categorized into 3 groups based on their number of frailty domains (FDs, 0-1, 2, and 3). Kaplan-Meier survival analysis was used to evaluate the association between the number of FDs and all-cause mortality, whereas Fine-Gray competing risk regression analysis was used for assessing the impact on cause-specific mortality., Results: We analyzed 1181 patients with HF (81 years old in median, 57.4% were male), 530 (44.9%), 437 (37.0%), and 214 (18.1%) of whom were categorized into the FD 0 to 1, FD 2, and FD 3 groups, respectively. During the 2-year follow-up, 240 deaths were observed (99 HF deaths, 34 cardiovascular deaths, and 107 noncardiovascular deaths), and an increase in the number of FD was significantly associated with mortality (Log-rank: P <0.001). The Fine-Gray competing risk analysis adjusted for age and sex showed that FDs 2 (subdistribution hazard ratio, 1.77 [95% CI, 1.11-2.81]) and 3 (2.78, [95% CI, 1.69-4.59]) groups were associated with higher incidence of noncardiovascular death but not with HF and other cardiovascular deaths., Conclusions: Although multidomain frailty is strongly associated with mortality in older patients with HF, it is mostly attributable to noncardiovascular death and not cardiovascular death, including HF death., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023929., Competing Interests: Disclosures Dr Matsue received an honorarium from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca and research grants from Pfizer Japan, Inc, Otsuka Pharmaceutical Co, EN Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. Nobuyuki Kagiyama received grants from Philips, Asahi KASEI Corporation, Toho Holdings Co. Ltd, Inter Reha Co. Ltd, EchoNous, Inc., and AMI, Inc. Outside of the submitted work. Dr Kamiya received grants and honorarium from Eiken Chemical Co., Ltd. and a research grant from SoftBnk Corp. Dr Kasai is affiliated with a department sponsored by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. The other authors declare no conflicts.

Aims: MitraScore is a novel, simple, and manually calculatable risk score developed as a prognostic model for patients undergoing transcatheter edge-to-edge repair (TEER) for mitral regurgitation. As its components are considered prognostic in heart failure (HF), we aimed to investigate the usefulness of the MitraScore in HF patients., Methods and Results: We calculated MitraScore for 1100 elderly patients (>65 years old) hospitalized for HF in the prospective multicentre FRAGILE-HF study and compared its prognostic ability with other simple risk scores. The primary endpoint was all-cause deaths, and the secondary endpoints were the composite of all-cause deaths and HF rehospitalization and cardiovascular deaths. Overall, the mean age of 1100 patients was 80 ± 8 years, and 58% were men. The mean MitraScore was 3.2 ± 1.4, with a median of 3 (interquartile range: 2-4). A total of 326 (29.6%), 571 (51.9%), and 203 (18.5%) patients were classified into low-, moderate-, and high-risk groups based on the MitraScore, respectively. During a follow-up of 2 years, 226 all-cause deaths, 478 composite endpoints, and 183 cardiovascular deaths were observed. MitraScore successfully stratified patients for all endpoints in the Kaplan-Meier analysis (P < 0.001 for all). In multivariate analyses, MitraScore was significantly associated with all endpoints after covariate adjustments [adjusted hazard ratio (HR) (95% confidence interval): 1.22 (1.10-1.36), P < 0.001 for all-cause deaths; adjusted HR 1.17 (1.09-1.26), P < 0.001 for combined endpoints; and adjusted HR 1.24 (1.10-1.39), P < 0.001 for cardiovascular deaths]. The Hosmer-Lemeshow plot showed good calibration for all endpoints. The net reclassification improvement (NRI) analyses revealed that the MitraScore performed significantly better than other manually calculatable risk scores of HF: the GWTG-HF risk score, the BIOSTAT compact model, the AHEAD score, the AHEAD-U score, and the HANBAH score for all-cause and cardiovascular deaths, with respective continuous NRIs of 0.20, 0.22, 0.39, 0.39, and 0.29 for all-cause mortality (all P-values < 0.01) and 0.20, 0.22, 0.42, 0.40, and 0.29 for cardiovascular mortality (all P-values < 0.02)., Conclusions: MitraScore developed for patients undergoing TEER also showed strong discriminative power in HF patients. MitraScore was superior to other manually calculable simple risk scores and might be a good choice for risk assessment in clinical practice for patients receiving TEER and those with HF., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Frailty is associated with a poor prognosis in older patients with heart failure (HF). However, multidomain frailty assessment tools have not been established in patients with HF, and the association between the frailty phenotype and the deficit-accumulation frailty index in these patients is unclear. We aimed to understand this relationship and evaluate the prognostic value of the deficit-accumulation frailty index in older patients with HF., Methods: We retrospectively analyzed FRAGILE-HF cohort, which consisted of prospectively registered hospitalized patients with HF aged ≥ 65 years. The frailty index was calculated using 34 health-related items. The physical, social, and cognitive domains of frailty were evaluated using a phenotypic approach. The primary endpoint was all-cause mortality., Results: Among 1027 patients with HF (median age, 81 years; male, 58.1%; median frailty index, 0.44), a higher frailty index was associated with a higher prevalence in all domains of cognitive, physical, and social frailty defined by the phenotype model. During the 2-year follow-up period, a higher frailty index was independently associated with all-cause death even after adjustment for Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score plus log B-type natriuretic peptide (per 0.1 increase: hazard ratio, 1.21; 95% confidence interval, 1.07-1.37; P = 0.002). The addition of the frailty index to the baseline model yielded statistically significant incremental prognostic value (net reclassification improvement, 0.165; 95% confidence interval, 0.012-0.318; P = 0.034)., Conclusions: A higher frailty index was associated with a higher prevalence of all domains of frailty defined by the phenotype model and provided incremental prognostic information with pre-existing risk factors in older patients with HF., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Although nutritional assessment and education are important for hospitalized patients with heart failure, the extent of their implementation in real-world clinical practice is unknown. Therefore, this study aimed to investigate the evaluation and management of nutrition during hospitalization for heart failure using a questionnaire survey for cardiologists.In this cross-sectional multicenter survey, 147 cardiologists from 32 institutions completed a web-based questionnaire (response rate, 95%).The survey showed that 78.2% of the respondents performed a nutritional assessment for hospitalized patients, whereas 38.3% used objective tools. In contrast, only 9.5% of the respondents evaluated the presence or absence of cardiac cachexia. Most respondents (89.8%) reported providing nutritional education to their patients before hospital discharge. However, compared with the number of respondents who provided information on sodium (97.0%) and water (63.6%) restrictions, a limited number of respondents provided guidance on optimal protein (20.5%) and micronutrient (9.1%) intake as part of the nutritional education. Less than 50% of the respondents provided guidance on optimal calorie intake (43.2%) and ideal body weight (34.8%) as a part of the nutritional education for patients identified as malnourished.Although nutritional assessment is widely performed for hospitalized patients with heart failure, most assessments are subjective rather than objective. Nutritional education, frequently provided before hospital discharge, is limited to information on water or salt intake restrictions. Therefore, more comprehensive and individualized nutritional assessments and counselling with a scientific basis are required.

Aim: Data on the clinical features and prognosis of patients with isolated cardiac sarcoidosis (iCS) are limited. This study evaluated the clinical characteristics and prognostic impact of iCS., Methods and Results: This was a secondary analysis of the ILLUMINATE-CS study, a multicentre, retrospective registry investigating the clinical characteristics and prognosis of cardiac sarcoidosis. iCS was diagnosed according to the 2016 Japanese Circulation Society (JCS) guidelines. Clinical characteristics and prognosis were compared between patients with iCS and systemic cardiac sarcoidosis (sCS). The primary outcome was a combined endpoint of all-cause death, hospitalization for heart failure, or fatal ventricular arrhythmia events. Among 475 patients with CS (mean age, 62.0 ± 10.9 years; female ratio, 59%) diagnosed by the JCS guidelines, 119 (25.1%) were diagnosed with iCS. Patients with iCS had a higher prevalence of a history of atrial fibrillation or hospitalization for heart failure, or lower left ventricular ejection fraction than those with sCS. During a median follow-up of 42.3 (interquartile range, 22.8-72.5) months, 141 primary outcomes (29.7%) occurred. Cox proportional hazard analysis revealed that iCS was a significant risk factor for the primary outcome in the unadjusted model (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.12-2.34; p = 0.011). However, this association was not retained after adjustment for other covariates (adjusted HR 1.27; 95% CI 0.86-1.88; p = 0.226)., Conclusions: Patients with iCS had more impaired cardiovascular function at the time of diagnosis than those with sCS. However, iCS was not independently associated with poor prognosis after adjustment for prognostic factors., (© 2023 European Society of Cardiology.)

Aims: Although sarcopenia is common and associated with poor outcomes in patients with heart failure, its simple screening methods remain unclear. We aimed to investigate the predictive value of the Ishii score, which includes age, grip strength, and calf circumference, for sarcopenia and its prognostic predictability in patients with heart failure., Methods: This was a subanalysis of the FRAGILE-HF study. Receiver operating characteristic curves were used to evaluate the predictive value for sarcopenia. Patients were stratified into the high and low Ishii score groups based on the cutoff values of the Ishii score determined by the Youden index for sarcopenia, and the 1-year mortality rates were compared., Results: Of the 1262 study participants, 936 were evaluated with sarcopenia, and 184 (55 women, 129 men) were diagnosed with sarcopenia. The areas under the receiver operating characteristic curves for sarcopenia were 0.73 and 0.87 for women and men, respectively. The optimal cutoff values for predicting sarcopenia were 165 and 141 for women and men, respectively. Using these cutoff values, the sensitivity and specificity for sarcopenia were 70.9% and 68.5% for women and 88.4% and 69.7% for men, respectively. At 1 year, 151 (low Ishii score group, 98; high Ishii score group, 53) deaths were observed. Adjusted Cox proportional hazards analysis showed that the high Ishii score group was significantly associated with 1-year mortality., Conclusion: Among older patients hospitalized for heart failure, the Ishii score is useful for predicting sarcopenia and 1-year mortality. Geriatr Gerontol Int 2024; 24: 147-153., (© 2023 Japan Geriatrics Society.)

The HANBAH score is a novel simple risk score consisting of hemoglobin level, age, sodium (N) level, blood urea nitrogen level, atrial fibrillation, and high-density lipoprotein. We aimed to validate this score in an external population. This retrospective study included 744 patients hospitalized for acute heart failure between 2015 and 2019. Each of the following criteria was scored as 1 point: hemoglobin level (<13.0 g/L for men and <12.0 g/L for women), atrial fibrillation, age (>70 years), serum blood urea nitrogen level (>26 mg/100 ml for men and >28 mg/100 ml for women), serum high-density lipoprotein level (<25 mg/100 ml), and serum sodium level (<135 mg/100 ml). HANBAH scores were available for 736 patients (age, 75 ± 13 years; 60% male; reduced [<40%] and preserved ejection fraction [≥50%]: 35% and 49%, respectively). All-cause death during follow-up, a composite of death and heart failure rehospitalization, and in-hospital death were observed in 173, 274, and 51 patients, respectively. The HANBAH score was significantly associated with these end points after adjustment for covariates (adjusted hazard ratio 1.38 [95% confidence interval 1.16 to 1.64], p <0.001; 1.27 [1.11 to 1.45], p <0.001; and 1.66 [1.18 to 2.33], p <0.001, respectively). Receiver operating characteristic and net reclassification improvement analyses showed that the HANBAH score performed significantly better than AHEAD (atrial fibrillation, hemoglobin [anemia], elderly, abnormal renal parameters, diabetes mellitus) and AHEAD-U (AHEAD with uric acid) scores and similar to the multi-domain ACUTE HF score for all end points. In conclusion, the HANBAH score showed powerful risk stratification in this external Japanese cohort. Despite its simplicity, it performed better than other simple risk scores and similar to a multidomain risk score., Competing Interests: Declaration of Competing Interest Dr. Kagiyama received a research grant from EchoNous Inc. and AMI Inc. Dr. Kagiyama and Dr. Kasai are affiliated with a department funded by Philips Healthcare, Asahi KASEI Corporation, Inter Reha Co., Ltd., and Toho Holdings Co., Ltd. based on collaborative research agreements. Dr. Matsue received an honorarium from Otsuka Pharmaceutical Co., Novartis Japan, AstraZeneca Japan, and Bayer Japan And a collaborative research grant from Pfizer Inc. and Nippon Boehringer Ingelheim Co., Ltd. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: Heart failure with concomitant sarcopenia has a poor prognosis; therefore, simple methods for evaluating the appendicular skeletal muscle mass index (ASMI) are required. Recently, a model incorporating anthropometric data and the sarcopenia index (i.e., serum creatinine-to-cystatin C ratio [Cre/CysC]), was developed to estimate the ASMI. We hypothesized that this model was superior to the traditional model, which uses only anthropometric data to predict prognosis. This retrospective cohort study compared the prognostic value of low ASMI as defined by the biomarker and anthropometric models in patients with heart failure., Methods and Results: Among 847 patients, we estimated ASMI using an anthropometric model (incorporating age, body weight, and height) in 791 patients and a biomarker model (incorporating age, body weight, hemoglobin, and Cre/CysC) in 562 patients. The primary outcome was all-cause mortality. Overall, 53.4% and 39.1% of patients were diagnosed with low ASMI (using the Asian Working Group for Sarcopenia cut-off) by the anthropometric and biomarker models, respectively. The two models showed a poor agreement in the diagnosis of low ASMI (kappa: 0.57, 95% confidence interval: 0.50-0.63). Kaplan-Meier curves showed that a low ASMI was significantly associated with all-cause death in both models. However, this association was retained after adjustment for other covariates in the biomarker model (hazard ratio: 2.32, p = 0.001) but not in the anthropometric model (hazard ratio: 0.79, p = 0.360)., Conclusion: Among patients hospitalized with heart failure, a low ASMI estimated using the biomarker model, and not the anthropometric model, was significantly associated with all-cause mortality., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

We investigated the clinical and prognostic implications of hyaluronic acid, a liver fibrosis marker, in patients with heart failure. We measured hyaluronic acid levels on admission in 655 hospitalized patients with heart failure between January 2015 and December 2019. Patients were stratified into three groups according to hyaluronic acid level: low (< 84.3 ng/mL, n = 219), middle (84.3-188.2 ng/mL, n = 218), and high (≥ 188.2 ng/mL, n = 218). The primary endpoint was all-cause death. The high hyaluronic acid group had higher N-terminal pro-brain-type natriuretic peptide levels, larger inferior vena cava, and shorter tricuspid annular plane systolic excursion than the other two groups. During the follow-up period (median 485 days), 132 all-cause deaths were observed: 27 (12.3%) in the low, 37 (17.0%) in the middle, and 68 (31.2%) in the high hyaluronic acid (P < 0.001) groups. Cox proportional hazards analysis revealed that higher log-transformed hyaluronic acid levels were significantly associated with all-cause death (hazard ratio, 1.38; 95% confidence interval, 1.15-1.66; P < 0.001). No significant interaction was observed between hyaluronic acid level and reduced/preserved left ventricular ejection fraction on all-cause death (P = 0.409). Hyaluronic acid provided additional prognostic predictability to pre-existing prognostic factors, including the fibrosis-4 index (continuous net reclassification improvement, 0.232; 95% confidence interval, 0.022-0.441; P = 0.030). In hospitalized patients with heart failure, hyaluronic acid was associated with right ventricular dysfunction and congestion and was independently associated with prognosis regardless of left ventricular ejection fraction., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Background: No study with an adequate patients' number has examined the relationship/overlap between sarcopenia and cachexia. We examined the prevalence of the overlap and prognostic implications of sarcopenia and cachexia in older patients with heart failure using well-accepted definitions., Methods: This was a post-hoc sub-analysis of the FRAGILE-HF study, a prospective, multicenter, observational study conducted at 15 hospitals in Japan. In total, 905 hospitalized older patients were classified into four groups based on the presence or absence of cachexia and/or sarcopenia, which were defined according to the Evans and Asian Working Group for Sarcopenia criteria revised in 2019, respectively. The primary endpoint was 2-year all-cause mortality., Results: Cachexia and sarcopenia prevalence rates were 32.7% and 22.7%, respectively. Patients were classified into the non-cachexia/non-sarcopenia (55.7%), cachexia/non-sarcopenia (21.7%), non-cachexia/sarcopenia (11.6%), and cachexia/sarcopenia (11.0%) groups. During the 2-year follow-up period after discharge, 158 (17.5%) all-cause deaths (124 cardiovascular deaths [CVD] and 34 non-CVD) were observed. The cachexia/sarcopenia group had the lowest body fat mass and exhibited significantly higher mortality rates (log-rank P < 0.001). Cox proportional hazard analysis revealed that cachexia/sarcopenia was an independent prognostic factor after adjusting for known prognostic factors (versus non-cachexia/non-sarcopenia: hazard ratio, 2.78; 95% confidence interval, 1.80-4.29; P < 0.001). Neither cachexia/non-sarcopenia nor non-cachexia/sarcopenia were significantly associated with all-cause mortality compared with non-cachexia/non-sarcopenia., Conclusions: Cachexia and sarcopenia are prevalent among older hospitalized patients with heart failure; nonetheless, the overlap is not as prominent as previously expected. The presence of cachexia and sarcopenia is a risk factor for all-cause mortality., Competing Interests: Declaration of Competing Interest Yuya Matsue and Takatoshi Kasai are affiliated with a department-sponsored by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. Yuya Matsue received an honorarium from Otsuka Pharmaceutical Co. and Novartis Japan. Nobuyuki Kagiyama received grants from Philips, Asahi KASEI Corporation, Toho Holdings Co. Ltd., Inter Reha Co. Ltd., and EchoNous. Inc., as well as research grants from AMI Inc. outside of the submitted work. Kentaro Kamiya received research funding from Eiken Chemical Co. Ltd. The other authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The incremental prognostic value of the six-minute walking test over conventional risk factors has not been evaluated in an adequate number of patients with heart failure with preserved ejection fraction (HFpEF). Therefore, we aimed to examine its prognostic significance using data from the FRAGILE-HF study., Methods and Results: A total of 513 older patients who were hospitalized for worsening heart failure were examined. Patients were classified according to the tertiles of six-minute walking distance (6MWD): T1 (<166 m), T2 (166-285 m), and T3 (≥285 m). During the 2-year follow-up period after discharge, 90 all-cause deaths occurred. Kaplan-Meier curves showed that the T1 group had significantly higher event rates than the other groups (log-rank p = 0.007). Cox proportional hazard analysis revealed that the T1 group was independently associated with lower survival, even after adjusting for conventional risk factors (T3: hazard ratio 1.79, 95% confidence interval 1.02-3.14, p = 0.042). The addition of the 6MWD to the conventional prognostic model showed a statistically significant incremental prognostic value (net reclassification improvement 0.27, 95% confidence interval 0.04-0.49; p = 0.019)., Conclusions: The 6MWD is associated with survival in patients with HFpEF and has an incremental prognostic value over conventional well-validated risk factors., Competing Interests: Declaration of Competing Interest Y. M. and T. K. are affiliated with a department sponsored by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. Y. M. received an honorarium from Otsuka Pharmaceutical Co. and Novartis Japan. N. K. was affiliated with a department endowed by grants from Philips, Asahi KASEI Corporation, Toho Holdings Co., Ltd., and Inter Reha Co., Ltd., received research grants from EchoNous. Inc. and AMI Inc., and received an honorarium from Novartis Japan outside the submitted work. K. K. received funding outside the submitted work from Eiken Chemical Co., Ltd. and SoftBank Cor. Ltd. The other authors have no conflicts of interest to declare. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hypertension is a leading cause of heart failure and other cardiovascular diseases. Its role in the pathogenesis of heart failure with reduced ejection fraction (HFrEF) differs from that in heart failure with preserved ejection fraction (HFpEF). Moreover, rigorous blood pressure control may reduce the incidence of heart failure. However, once heart failure develops, prognosis is affected by blood pressure, which may differ between patients with and without heart failure. Therefore, the association between guideline-directed medical therapy (GDMT) for heart failure and its uptitration must be considered for blood pressure management and should not be overlooked. Heart failure medications affect the blood pressure and efficacy per baseline blood pressure value. This review discusses the potential mechanisms by which hypertension leads to HFrEF or HFpEF, the impact of hypertension on incident heart failure, and the recommended approaches for blood pressure management in patients with heart failure. Comparison between patients with and without heart failure regarding blood pressure The association between CV events and SBP is linear in patients without heart failure; however, it becomes J-shaped or inverse linear in those with heart failure. The management of BP, including optimal BP or pharmacotherapy, differs between the two populations. ACEi angiotensin-converting enzyme inhibitors, ARB angiotensin II receptor blockers; ARNi angiotensin receptor-neprilysin inhibitors, BB beta-blockers, BP blood pressure, CV cardiovascular, DASH Dietary Approaches to Stop Hypertension, GDMT guideline-directed medical therapy, HF heart failure, HFrEF heart failure with reduced ejection fraction, MRA mineralocorticoid receptor antagonists, SBP systolic blood pressure, SGLT2i sodium-glucose cotransporter 2 inhibitors., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: The ACUTE HF score is a simple risk score that predicts the prognosis of patients with acute heart failure (HF) using clinical and echocardiographic parameters. As this score was developed for a small European population, we aimed to validate this score in an external population., Methods and Results: This retrospective observational cohort analysis included patients hospitalized with acute HF during 2015-2019. Of 744 patients, 703 patients with available ACUTE HF scores were analyzed (75 ± 13 years; 61% male; left ventricular ejection fraction [LVEF] 49 ± 17%). Approximately one-third (34.4%) of the patients had reduced LVEF (<40%), and 51.4% exhibited preserved LVEF (≥50%). During a median follow-up of 452 days, primary and secondary outcomes were observed in 110 and 204 patients, respectively. The ACUTE HF score successfully stratified patients for primary (all-cause mortality) and secondary endpoints (a composite of all-cause mortality and heart failure rehospitalization) in Kaplan-Meier analyses (log-rank test, P < 0.001). Multivariable Cox proportional hazards models showed that the score was significantly independently associated with both primary and secondary endpoints after adjusted by covariates (P < 0.001)., Conclusion: We validated the risk prediction ability of ACUTE HF score in an Asian population. This score may be applicable in clinical practice., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background The prognostic role of BNP (B-type natriuretic peptide) in patients with cardiac sarcoidosis without evident heart failure is unknown. Methods and Results This is a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients With Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of cardiac sarcoidosis. We analyzed patients with cardiac sarcoidosis without evident heart failure at the time of diagnosis. The association between baseline BNP levels and prognosis was investigated. The primary end point was the combined end point of all-cause death, heart failure hospitalization, and fatal ventricular arrhythmia. In total, 238 patients (61.0±11.1 years, 37% men) were analyzed, and 61 primary end points were observed during a median follow-up period of 3.0 (interquartile range, 1.7-5.8) years. Patients with high BNP (BNP above the median value of BNP) were older and had a lower renal function and left ventricular ejection fraction than those with low BNP values. Kaplan-Meier curve analysis indicated that high BNP levels were significantly associated with a high incidence of primary end points (log-rank P =0.004), and this association was retained even in multivariable Cox regression (hazard ratio, 2.06 [95% CI, 1.19-3.55]; P =0.010). Log-transformed BNP as a continuous variable was associated with the primary end point (hazard ratio, 2.12 [95% CI, 1.31-3.43]; P =0.002). Conclusions High baseline BNP level was an independent predictor of future adverse events in patients with cardiac sarcoidosis without heart failure at the time of diagnosis. Registration URL: https://www.umin.ac.jp/english/; Unique Identifier: UMIN-CTR: UMIN000034974.

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

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

Background: The purpose of this study was to clarify the prevalence, association with frailty and exercise capacity, and prognostic implication of sarcopenic obesity in patients with heart failure., Methods: The present study included 779 older adults hospitalized with heart failure (median age: 81 years; 57.4% men). Sarcopenia was diagnosed based on the guidelines by the Asian Working Group for Sarcopenia. Obesity was defined as the percentage of body fat mass (FM) obtained by bioelectrical impedance analysis. The FM cut-off points for obesity were 38% for women and 27% for men. The primary endpoint was 1-year all-cause death. We assessed the associations of sarcopenic obesity occurrence with the short physical performance battery (SPPB) score and 6-minute walk distance (6MWD)., Results: The rates of sarcopenia and obesity were 19.3 and 26.2%, respectively. The patients were classified into the following groups: non-sarcopenia/non-obesity (58.5%), non-sarcopenia/obesity (22.2%), sarcopenia/non-obesity (15.3%), and sarcopenia/obesity (4.0%). The sarcopenia/obesity group had a lower SPPB score and shorter 6MWD, which was independent of age and sex (coefficient, - 0.120; t-value, - 3.74; P < 0.001 and coefficient, - 77.42; t-value, - 3.61; P < 0.001; respectively). Ninety-six patients died during the 1-year follow-up period. In a Cox proportional hazard analysis, sarcopenia and obesity together were an independent prognostic factor even after adjusting for a coexisting prognostic factor (non-sarcopenia/non-obesity vs. sarcopenia/obesity: hazard ratio, 2.48; 95% confidence interval, 1.22-5.04; P = 0.012)., Conclusion: Sarcopenic obesity is a risk factor for all-cause death and low physical function in older adults with heart failure., Trial Registration: University Hospital Information Network (UMIN-CTR: UMIN000023929 )., (© 2022. The Author(s).)

Aims: A patient's understanding of his or her own comorbidities is part of the recommended patient education for those with heart failure. The accuracy of patients' understanding of their comorbidities and its prognostic impact have not been reported., Methods and Results: Patients hospitalized for heart failure (n = 1234) aged ≥65 years (mean age: 80.1 ± 7.7 years; 531 females) completed a questionnaire regarding their diagnoses of diabetes, malignancy, stroke, hypertension, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD). The patients were categorized into three groups based on the number of agreements between self-reported comorbidities and provider-reported comorbidities: low (1-2, n = 19); fair (3-4, n = 376); and high (5-6, n = 839) agreement groups. The primary outcome was a composite of all-cause mortality or heart failure rehospitalization at 1 year. The low agreement group had more comorbidities and a higher prevalence of a history of heart failure. The agreement was good for diabetes (κ = 0.73), moderate for malignancy (κ = 0.56) and stroke (κ = 0.50), and poor-to-fair for hypertension (κ = 0.33), COPD (κ = 0.25), and CAD (κ = 0.30). The fair and low agreement groups had poorer outcomes than the good agreement group [fair agreement group: hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.01-1.56; P = 0.041; low agreement group: HR: 2.74: 95% CI: 1.40-5.35; P = 0.003]., Conclusions: The ability to recognize their own comorbidities among older patients with heart failure was low. Patients with less accurate recognition of their comorbidities may be at higher risk for a composite of all-cause mortality or heart failure rehospitalization., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Renal dysfunction includes glomerular dysfunction (GD) and tubular dysfunction (TD); however, there is limited information regarding the prevalence, coexistence, and prognostic relevance of TD and GD among patients with acute heart failure (AHF)., Methods and results: This study reviewed 489 patients with AHF who had undergone testing at the time of their admission to identify GD (estimated glomerular filtration rate <60 mL/min/1.73 m 2 ) and TD (urinary β-2-microglobulin ≥300 µg/gCr). Patients were grouped according to the presence/absence of GD and TD as having neither condition (n=116), isolated TD (n=101), isolated GD (n=83), or coexisting GD plus TD (n=189). During a median follow up of 466 days (interquartile range: 170-871 days), 107 deaths were observed. Kaplan-Meier curve analysis revealed that, relative to the absence of a GD and TD group, higher mortality rates were observed in the groups with isolated TD, isolated GD, and coexisting GD plus TD (log-rank P<0.001). Similarly, the adjusted Cox regression analyses revealed that significantly higher risks of mortality were associated with isolated TD, isolated GD, and coexisting GD plus TD. Moreover, isolated GD and isolated TD were both independently associated with increased risks of all-cause mortality., Conclusions: As a significant proportion of patients with AHF had isolated TD and an increased risk of mortality, patients with AHF should be screened for TD even if they do not have GD.

Although postural hypotension (PH) is reportedly associated with mortality in the general population, the prognostic value for heart failure is unclear. This was a post-hoc analysis of FRAGILE-HF, a prospective multicenter observational study focusing on frailty in elderly patients with heart failure. Overall, 730 patients aged ≥ 65 years who were hospitalized with heart failure were enrolled. PH was defined by evaluating seated PH, and was defined as a fall of ≥ 20 mmHg in systolic and/or ≥ 10 mmHg in diastolic blood pressure within 3 min after transition from a supine to sitting position. The study endpoints were all-cause death and heart failure readmission at 1 year. Predictive variables for the presence of PH were also evaluated. PH was observed in 160 patients (21.9%). Patients with PH were more likely than those without PH to be male with a New York Heart Association classification of III/IV. Logistic regression analysis showed that male sex, severe heart failure symptoms, and lack of administration of angiotensin-converting enzyme inhibitors were independently associated with PH. PH was not associated with 1-year mortality, but was associated with a lower incidence of readmission after discharge after adjustment for other covariates. In conclusion, PH was associated with reduced risk of heart failure readmission but not with 1-year mortality in older patients with heart failure., (© 2022. The Author(s).)

Aims: Urinary liver-type fatty acid-binding protein (L-FABP) is expressed in proximal tubular epithelial cells and excreted into the urine during tubular injury. We hypothesized that high urinary L-FABP is associated with poor prognosis in patients with acute heart failure (AHF)., Methods and Results: We analysed 623 patients (74 ± 13 years old; 60.0% male patients) with AHF. Urinary L-FABP levels were measured at the time of admission and adjusted for the urinary creatinine concentration. The primary endpoint was all-cause mortality. The median value and interquartile range of urinary L-FABP levels were 6.66 and 3.37-21.1 μg/gCr, respectively. Urinary L-FABP levels were significantly correlated with both beta-2 microglobulin and cystatin C levels; the correlation with the former was higher than that with the latter. During the follow-up of 631 (interquartile range: 387-875) days, 142 deaths occurred. A high tertile of urinary L-FABP level was associated with high mortality; this association was retained after adjusting for other covariates (second tertile hazard ratio 1.40, P = 0.152 vs. first tertile; third tertile hazard ratio 1.94, P = 0.005 vs. first tertile)., Conclusions: Urinary L-FABP is more closely associated with tubular dysfunction than with glomerular dysfunction. Tubular dysfunction, which was evaluated based on urinary L-FABP levels, in patients with AHF is associated with all-cause mortality and is independent of pre-existing risk factors. L-FABP should be considered for use in the prognosis of AHF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background and Aims: Frailty and sarcopenia are common and confer poor prognosis in elderly patients with heart failure; however, gender differences in its prevalence or prognostic impact remain unclear., Methods and Results: We included 1332 patients aged ≥65 years, who were hospitalized for heart failure. Frailty and sarcopenia were defined using the Fried phenotype model and Asian Working Group for Sarcopenia criteria, respectively. Gender differences in frailty and sarcopenia, and interactions between sex and prognostic impact of frailty/sarcopenia on 1-year mortality were evaluated. Overall, 53.9% men and 61.0% women and 23.7% men and 14.0% women had frailty and sarcopenia, respectively. Although sarcopenia was more prevalent in men, no gender differences existed in frailty after adjusting for age. On Kaplan-Meier analysis, frailty and sarcopenia were significantly associated with 1-year mortality in both sexes. On Cox proportional hazard analysis, frailty was associated with 1-year mortality only in men, after adjusting for confounding factors (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.19-3.16; P = 0.008 for men; HR, 1.63; 95% CI, 0.84-3.13; P = 0.147 for women); sarcopenia was an independent prognostic factor in both sexes (HR, 1.93; 95% CI, 1.13-3.31; P = 0.017 for men; HR, 3.18; 95% CI, 1.59-5.64; P = 0.001 for women). There were no interactions between sex and prognostic impact of frailty/sarcopenia (P = 0.806 for frailty; P = 0.254 for sarcopenia)., Conclusions: Frailty and sarcopenia negatively affect older patients with heart failure from both sexes., Clinical Trials: This study was registered at the University Hospital Information Network (UMIN-CTR, unique identifier: UMIN000023929) before the first patient was enrolled., Competing Interests: Declaration of competing interest Dr. Yuya Matsue and Takatoshi Kasai are affiliated with a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi; Dr. Yuya Matsue received an honorarium from Otsuka Pharmaceutical Co and Novartis Japan. Dr Kagiyama reports grants from Philips, Asahi KASEI Corporation, Toho Holdings Co. Ltd, and Inter Reha Co. Ltd, that are not related to the content of this article. Dr. Kamiya has received research funding from Eiken Chemical Co., Ltd. The other authors have nothing to declare., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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

Heart failure and frailty share aging as a strong risk factor. The prevalence of frailty has been shown to be particularly high in elderly patients with heart failure. Moreover, it is important not to confine frailty to physical aspects. Rather, it should be considered to consist of multiple domains, including physical disability, psychiatric disorders, cognitive impairment, depression, and social disconnection. Development of interventions that can improve frailty domains are not well established, although observational studies have evaluated the association of various frailty domains and their prognostic impact. Some interventions, including resistance exercise, functional exercise, and respiratory muscle training have been demonstrated to hold potential for improving physical frailty. In terms of cognitive dysfunction, previous studies have demonstrated that exercise therapy is also effective for cognitive dysfunction. The social domain of frailty is one of the least investigated domains, particularly in patients with heart failure. However, heart failure is also strongly associated with physical frailty and cognitive impairment and has a poor prognosis in old patients. The prevalence of social frailty in elderly patients who need hospitalization due to heart failure is higher than previously thought. Very few studies have tested interventions targeting social frailty. Frailty and heart failure affect each other, and both are becoming increasingly important in society. In this article, we review the physical, cognitive, and social domains of frailty and the possible interventions to improve them in patients with heart failure.

Background: Although urinary alpha-1-microglobulin has been used as a marker of tubular dysfunction, its clinical and prognostic values in patients with acute heart failure have not been validated., Methods: We analyzed 623 patients (74 ± 13 years old, 60.0% male) with acute heart failure in whom urinary alpha-1-microglobulin (A1MG) levels were measured as tubular markers at the time of admission. The primary endpoint was all-cause mortality., Results: The median levels of urinary alpha-1-microglobulin with and without correction for urinary creatinine concentration were 8.80 (interquartile range: 4.20-17.7) mg/dL and 12.9 (5.92-30.7) mg/gCr, respectively. Urinary A1MG levels were significantly correlated with all of beta-2-microglobulin (r = 0.77), N-acetyl-β-D-glucosaminidase (r = 0.51), and estimated glomerular filtration rate (r = -0.42); however, alpha-1-microglobulin was most often predicted using beta-2-microglobulin or N-acetyl-β-D-glucosaminidase. During the 488-day (interquartile range: 185-938 days) follow-up, 141 deaths occurred. Higher A1MG levels were associated with higher mortality even after adjustment for other covariates. Only A1MG, but not beta-2-microglobulin or N-acetyl-β-D-glucosaminidase, yielded incremental prognostic information in addition to the preexisting prognostic factors (net-reclassification improvement: 0.254, P = 0.023; integrated discrimination improvement: 0.015, P = 0.028)., Conclusions: In patients hospitalized due to acute heart failure, urinary alpha-1-microglobulin was a marker of tubular dysfunction. High alpha-1-microglobulin was associated with all-cause mortality independent of glomerular function and was a better predictor of mortality than urinary beta-2-microglobulin., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Frailty is a common comorbidity associated with adverse events in patients with heart failure, and early recognition is key to improving its management. We hypothesized that the AST to ALT ratio (AAR) could be a marker of frailty in patients with heart failure. Data from the FRAGILE-HF study were analyzed. A total of 1327 patients aged ≥ 65 years hospitalized with heart failure were categorized into three groups based on their AAR at discharge: low AAR (AAR < 1.16, n = 434); middle AAR (1.16 ≤ AAR < 1.70, n = 487); high AAR (AAR ≥ 1.70, n = 406). The primary endpoint was one-year mortality. The association between AAR and physical function was also assessed. High AAR was associated with lower short physical performance battery and shorter 6-min walk distance, and these associations were independent of age and sex. Logistic regression analysis revealed that high AAR was an independent marker of physical frailty after adjustment for age, sex and body mass index. During follow-up, all-cause death occurred in 161 patients. After adjusting for confounding factors, high AAR was associated with all-cause death (low AAR vs. high AAR, hazard ratio: 1.57, 95% confidence interval, 1.02-2.42; P = 0.040). In conclusion, AAR is a marker of frailty and prognostic for all-cause mortality in older patients with heart failure.

Background & Aims: Although the Global Leadership Initiative on Malnutrition (GLIM) proposed a consensus scheme for diagnosing malnutrition in adults in clinical settings globally, the prevalence and prognostic value of malnutrition defined by GLIM criteria have yet to be evaluated in elderly patients with heart failure. This study aimed to determine the prevalence and prognostic implication of malnutrition as defined by GLIM criteria in comparison to those for a pre-existing definition of malnutrition, the geriatric nutritional risk index (GNRI), in elderly patients with heart failure METHODS: We evaluated malnutrition by two metrics, the GLIM criteria and geriatric nutritional risk index (GNRI), in 890 hospitalized patients with decompensation of heart failure aged ≥65 years, able to ambulate at discharge. The primary outcome was all-cause death within 1 year of discharge., Results: According to GLIM criteria and GNRI <92, 42.4% and 46.5% of participants, respectively, had malnutrition, with moderate agreement (Cohen's kappa coefficient: 0.46 [95% confidence interval: 0.40-0.51]). During 1 year of follow-up, 101 (11.4%) deaths were observed, and malnutrition defined by either the GLIM criteria or GNRI was associated with a higher mortality rate, independent of other prognostic factors (GNRI: hazard ratio, 1.45, P = 0.031; GLIM: hazard ratio, 1.57, P = 0.016). Although malnutrition defined by either criterion showed additive prognostic value when added to a model incorporating pre-existing prognostic factors, defining malnutrition by GLIM criteria instead of the GNRI yielded a statistically significant improvement in model prognostic predictive ability (net-reclassification improvement, 0.44, P < 0.001; integrated discrimination index, 0.013, P < 0.001)., Conclusions: In elderly patients with heart failure, 42.4% are malnourished according to the GLIM criteria, which is associated with a poor prognosis, independent of known prognostic factors., Clinical Trial Registration: University Hospital Medical Information Network (UMIN-CTR, https://www.umin.ac.jp/ctr/index.htm, study unique identifier: UMIN000023929)., Competing Interests: Conflict of interest Mr. Susumu Hirose is an employee of Pfizer, Inc. Drs. Yuya Matsue and Takatoshi Kasai are affiliated with a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi, and received an honorarium from Otsuka Pharmaceutical Co. All other authors have nothing to declare. Dr. Kentaro Kamiya has received research fund from Eiken Chemical Co., Ltd., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)