Aims Reduction in appendicular skeletal muscle mass index (ASMI) assessed by dual‐energy X‐ray absorptiometry (DEXA) has been shown to be independently associated with a higher mortality rate in patients with heart failure (HF). However, DEXA is not suitable for measurement of muscle mass in a daily clinical setting and in large population‐based studies. The aim of this study was to determine whether ASMI predicted from anthropometric indicators (predicted ASMI) serves as an alternative to DEXA‐measured ASMI for predicting all‐cause death in HF patients. Methods and Results Data for 539 HF patients who received a DEXA scan and measurements of calf circumferences (CC) and mid‐arm circumferences (MAC) in our hospital were analysed. Predicted ASMI was calculated as we previously reported: predicted ASMI (kg/m2) = [0.214 × weight (kg) + 0.217 × CC (cm) − 0.189 × MAC (cm) + 1.098 (male = 1, female = −1) + 0.576]/height2 (m2). Low ASMI values were defined as <7.00 kg/m2 and <5.40 kg/m2 for men and women, respectively, according to the criteria of the Asian Working Group for Sarcopenia. The median follow‐up period was 1.75 years (interquartile range, 0.96–2.37 years), and 79 patients (15%) died. Kaplan–Meier survival curves showed that patients with low DEXA‐measured ASMI and patients with low predicted ASMI had significantly lower survival rates than those for patients with high ASMI. In multivariate Cox proportional hazard analyses adjusted for age, sex, logarithmic B‐type natriuretic peptide, cystatin C based‐estimated glomerular filtration rate, and gait speed, DEXA‐measured ASMI [hazard ratio (HR), 0.982; 95% confidence interval (CI), 0.967–0.998; P = 0.026] and predicted ASMI (HR, 0.979; 95% CI, 0.962–0.996; P = 0.018) were independent predictors of all‐cause mortality. Inclusion of predicted ASMI into the adjustment model significantly improved continuous net reclassification improvement (0.338; 95% CI, 0.103–0.572; P < 0.01) and integrated discrimination improvement (0.020; 95% CI, 0.004–0.035; P < 0.05) for predicting mortality after discharge. Conclusions Predicted ASMI, as well as DEXA‐measured ASMI, can predict all‐cause death in HF patients, and calculation of predicted ASMI will be useful for detecting high‐risk patients in a daily clinical setting and in large population‐based studies.

Background Accurate prediction of mortality in heart failure (HF) patients is crucial for decision-making regarding HF therapies, but a strategy for the prediction of mortality in elderly HF patients has not been established. In addition, although favorable effects of comprehensive cardiac rehabilitation (CR) on clinical outcomes and functional status in HF patients have been demonstrated, a goal of comprehensive CR during hospitalization for reducing mortality remains unclear. Aims We examined whether assessment of basic activities of daily living (ADL) by the Barthel Index (BI), the most widely used tool for assessment of basic ADL, is useful for predicting all-cause mortality in elderly HF patients who received comprehensive CR. Methods This study was a single-center, retrospective and observational study. We retrospectively examined 413 HF patients aged ≥65 years (mean age, 78±7 years; 50% female) who were admitted to our institute for management of HF and received comprehensive CR during hospitalization. Functional status for performing basic ADL ability was assessed by the BI within 3 days before discharge. The clinical endpoint was all-cause death during the follow-up period. Results Of 413 HF patients, 116 patients (28%) died during a follow-up period of median 1.90-years (interquartile range, 1.20–3.23 years). Results of an adjusted dose-dependent association analysis showed that the hazard ratio (HR) of mortality increases in an almost linear fashion as the BI score decreases and that the BI score corresponding the hazard ratio of 1.0 is 85 (Figure A). To minimize the differences in potential confounding factors between patient with low BI (&lt;85) and patients with high BI (≥85), inverse probability treatment weighting (IPTW) was calculated using propensity score. Kaplan-Meier survival curves, in which selection bias was minimized by use of IPTW for confounders, showed that patients with low BI (&lt;85) had a higher mortality rate than did patients with high BI (≥85) (Figure B). In multivariate Cox regression analyses, low BI was independently associated with higher mortality after adjustment for predictors including brain natriuretic peptide and prior HF hospitalization (IPTW-adjusted HR, 1.75 [95% confidence interval, 1.03–2.98], p&lt;0.001). Inclusion of the BI into the adjustment model improved the accuracy of prediction of mortality (continuous net reclassification improvement, 0.292, p=0.008; integrated discrimination improvement, 0.017, p=0.022). Conclusion A BI score of &lt;85 at the time of discharge is associated with increased mortality independently of known prognostic markers, and achievement of functional status of a BI score ≥85 by comprehensive CR during hospitalization may contribute to a favorable outcome in elderly HF patients. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the Japan Society for the Promotion of Science

AimsAlthough the impact of physical frailty on prognosis and the effect of cardiac rehabilitation in HF patients has been well established, data for the prognostic impact of social frailty (SF) in HF patients are limited. In addition, the relative importance of each SF domain in clinical outcomes remains unclear. We aimed to get a new insight into the associations of SF with clinical outcomes in elderly hospitalized HF patients.MethodsA single-center, retrospective cohort study was conducted using data from 310 in-hospital HF patients aged ≥ 65 years (mean age of 78 ± 8 years; 49% women). Makizako’s five questions, a self-reported questionnaire, were used to define SF. The primary outcome was composite events defined by all-cause death and cardiovascular events.ResultsOf the 310 elderly HF patients, 188 patients (61%) had SF. Seventy-five patients (24%) had composite events during a mean follow-up period of 1.93 ± 0.91 years. Kaplan-Meier curves showed that patients with SF had a significantly higher composite event rate than patients without SF. In multivariate Cox regression analyses, SF was independently associated with a higher composite event rate after adjusting for prognostic markers [adjusted hazard ratio (HR), 2.01; 95% confidence interval (CI), 1.07–3.78; p = 0.04]. Of the 5 questions for defining SF, an answer of yes to the question about not feeling helpful toward friends or family, which indicates loss of perceived social role, was an independent predictor of composite events (adjusted HR, 2.28; 95% CI, 1.36–3.82; p &lt; 0.01). Inclusion of loss of perceived social role into the baseline prognostic model improved both the continuous net reclassification improvement (0.562; 95% CI, 0.298–0.827; p &lt; 0.01) and integrated discrimination improvement (0.031; 95% CI, 0.006–0.056; p = 0.02).ConclusionLoss of perceived social role is associated with increased adverse event risk and provides additive prognostic information in elderly HF patients.

Aims The mechanism by which a sodium-glucose cotransporter inhibitor (SGLT2i) induces favorable effects on diabetes and cardiovascular diseases including heart failure (HF) remains poorly understood. Metabolomics including amino acid profiling enables detection of alterations in whole body metabolism. The aim of this study was to determine whether plasma amino acid profiles are modulated by SGLT2i use in HF patients with type 2 diabetes mellitus (T2DM). Methods We retrospectively examined 81 HF patients with T2DM (68 ± 11 years old; 78% male). Plasma amino acid concentrations in a fasting state after stabilization of HF were determined using ultraperformance liquid chromatography. To minimize potential selection bias in the retrospective analyses, the differences in baseline characteristics between patients receiving an SGLT2i and patients not receiving an SGLT2i were controlled by using an inverse probability of treatment weighting (IPTW)-adjusted analysis. Results Of amino acids measurable in the present assay, plasma β-aminoisobutyric acid (BAIBA), an exercise-induced myokine-like molecule also known as 3-aminoisobutyric acid or 3-amino-2-methyproponic acid, was detected in 77% of all patients and the proportion of patients in whom plasma BAIBA was detected was significantly higher in patients receiving an SGLT2i than in patients not receiving an SGLT2i (93% vs. 67%, p = 0.01). Analyses in patients in whom plasma BAIBA was detected showed that plasma BAIBA concentration was significantly higher in patients receiving an SGLT2i than in patients not receiving an SGLT2i (6.76 ± 4.72 vs. 4.56 ± 2.93 nmol/ml, p = 0.03). In multivariate logistic regression analyses that were adjusted for age and sex, SGLT2i use was independently associated with BAIBA detection. The independent association between BAIBA and SGLT2i use remained after inclusion of body mass index, HF with reduced ejection fraction, ischemic etiology, renal function, NT-proBNP, albumin, hemoglobin, and HbA1c into the Cox proportional hazards model. When the differences in baseline characteristics between patients receiving an SGLT2i and patients not receiving an SGLT2i were controlled by using an IPTW-adjusted analysis, least squares mean of plasma BAIBA concentration was significantly higher in patients receiving an SGLT2i than in patients not receiving an SGLT2i. Conclusion SGLT2i use is closely associated with increased circulating BAIBA concentration in HF patients with T2DM.

Background Frailty is a complex syndrome characterized by a decline in functional reserve, and associated with aging and chronic diseases including heart failure (HF). The impact of physical frailty on prognosis and the effect of cardiac rehabilitation in HF patients have been well established. However, the data on the prognostic impact of social frailty (SF) in HF patients is limited. Aims We aimed to get new insight into mechanisms of the association of SF with clinical outcomes in older hospitalized HF patients. Methods A single-center, retrospective cohort study was conducted using data from 308 HF patients aged ≥65 years (mean age of 78±8 years; 49% females) who were admitted to our institute for the management of HF. SF was assessed using the validated Makizako's five questions. The following responses were considered positive for SF: (1) going out less frequently compared with last year; (2) not visiting friends; (3) not talking with someone every day; (4) not feeling helpful toward friends or family; and (5) living alone. SF was defined as two or more positive responses. The primary outcome was composite events defined by all-cause death and cardiovascular events. The missing data were imputed using multiple imputation by chained -equations algorithm. Results Of 308 older HF patients, 189 patients (61%) were SF. Patients with SF were significantly older, had lower body mass index, and a higher percentage of patients with physical frailty and cognitive frailty than those without SF. Seventy-five patients (24%) experienced composite events during a median follow-up period of 1.55-years (interquartile range, 0.88–2.20 years). Kaplan-Meier curves showed a significantly higher composite event rate in patients with SF than those without SF. In multivariate Cox regression analyses, SF was independently associated with a higher composite event rate after adjusting for pre-existing risk factors [adjusted hazard ratio (HR), 1.91; 95% confidence interval (CI), 1.09–3.35; p=0.03] (Figure 1A). In addition, further analyses showed that only the positive response on the question corresponding to the social role – not feeling helpful toward friends or family – among the questionnaire was an independent predictor for the incidence of the composite event (adjusted HR, 2.10; 95% CI, 1.29–3.41; p&lt;0.01, Figure 1B). Inclusion of the response to the question regarding the social role into the baseline prognostic model improved the accuracy of prediction of the composite event (continuous net reclassification improvement, 0.46; 95% CI, 0.21–0.71; p&lt;0.01; integrated discrimination improvement, 0.025; 95% CI 0.004–0.047; p=0.02; Figure 2). Conclusion Loss of social role awareness was associated with increased composite event risk and provided additive prognostic information in older HF patients, suggesting the importance of healthcare professionals' decision-making on the prevention and management of SF. Funding Acknowledgement Type of funding sources: None.