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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.)

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.)

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.)

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.)

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 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.)

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.)

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.)

A carbohydrate antigen, sialyl Lewis X (SLEX), is an inflammation-associated liver cell antigen, which is increasingly expressed as histological diagnosis progresses. A solid phase radioimmunoassay was developed to determine the plasma levels of this substance which were found to be elevated in about 70% of patients with liver disease, with no significant differences among disease groups. Although the plasma levels of SLEX were not directly correlated with the degree of hepatic SLEX expression, the abnormal values were only found in cases with hepatic SLEX expression. Cirrhotic patients with and without hepatocellular carcinoma had comparable values. Plasma levels of SLEX decreased significantly in chronic hepatitis patients successfully treated with IFN, but not in those without a favourable clinical response. Plasma SLEX was carried by some macromolecules with chromatographic and buoyant properties of mucin-type glycoproteins, and others of non-mucin type. These observations suggested that (i) the plasma levels of SLEX increase significantly but non-specifically in liver diseases, (ii) liver cells in the inflammatory lesion are probably the origin of the SLEX-active glycoproteins in the peripheral circulation, (iii) both the increased hepatic synthesis and impaired secretion of the SLEX-positive glycoproteins might be related to the tissue expression and plasma levels of SLEX, and (iv) plasma SLEX might be a useful marker to evaluate the activity of inflammatory liver disease in individual patients and to monitor their treatment.

The hepatocellular expression of the carbohydrate antigen sialyl monomeric Lewis X (SMLex) and sialyl oligomeric Lewis X(SOLex) in chronic hepatitis was examined using specific monoclonal antibodies. Both of these sialyl Lewis X (SLex) antigens were membranously expressed in chronic hepatitis in spite of their absence in normal liver. Although SMLex was detected in mild hepatic inflammation, the expression of SOLex was associated only with moderate to severe necroinflammation. Hepatocellular expression of these antigens increased significantly as histological diagnosis advanced. Chronological observation also showed the change of SLex expression according to the histological change. The present observations suggest that hepatocellular SLex is a novel histological marker with a close correlation to the severity of necroinflammation in chronic hepatitis.