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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.)

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: 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.)