Prognostic value of estimating appendicular muscle mass in heart failure using creatinine/cystatin C.

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.

Clinical and prognostic implications of hyaluronic acid in hospitalized patients with heart failure.

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.

Structural Analysis of a Trimer of ß2-Microgloblin Fragment by Molecular Dynamics Simulations.

A peptide ß2-m21-31, which is a fragment from residue 21 to residue 31 of ß2-microgloblin, is experimentally known to self-assemble and form amyloid fibrils. In order to understand the mechanism of amyloid fibril formations, we applied the replica-exchange molecular dynamics method to the system consisting of three fragments of ß2-m21-31. From the analyses on the temperature dependence, we found that there is a clear phase transition temperature in which the peptides aggregate with each other. Moreover, we found by the free energy analyses that there are two major stable states: One of them is like amyloid fibrils and the other is amorphous aggregates.