Optimal serum 25-hydroxyvitamin D level to prevent sarcopenia in patients with heart failure: Insights from a dose-response relationship.

BACKGROUND AND AIMS: Low serum 25-hydroxyvitamin D (25 [OH]D) levels have been associated with sarcopenia, frailty, and risk of cardiovascular disease, whereas high levels negatively impact clinical outcomes. We determined optimal serum 25(OH)D concentrations to minimise the probability of sarcopenia in patients with heart failure (HF) by examining the dose-dependent relationship between serum 25(OH)D levels and sarcopenia. METHODS AND RESULTS: We enrolled 461 consecutive patients with HF (mean age, 72 ± 15 years; 39% female) who underwent dual-energy X-ray absorptiometry. Serum 25(OH)D levels were measured using a chemiluminescence immunoassay. Sarcopenia was diagnosed according to the 2019 Asian Working Group for Sarcopenia criteria. Overall, 49% of enrolled patients were diagnosed with sarcopenia. Adjusted logistic regression with restricted cubic spline function revealed that the odds ratio (OR) of sarcopenia increased in patients with HF presenting serum 25(OH)D levels <14.6 ng/ml or > 31.4 ng/ml, reaching the lowest OR at ∼20 ng/ml. Multivariate logistic regression revealed that a serum 25(OH)D level below 14.6 ng/mL was independently associated with the presence of sarcopenia (adjusted OR: 2.16, 95% confidence interval [CI]: 1.24-3.78). Incorporating serum 25(OH)D levels <14.6 ng/ml, but not <20.0 ng/ml, in the baseline model improved continuous net reclassification (0.334, 95% CI: 0.122-0.546) in patients with HF. CONCLUSION: A U-shaped relationship exists between serum 25(OH)D levels and sarcopenia probability in patients with HF. Maintaining serum 25(OH)D levels between 14.6 and 31.4 ng/ml may help prevent sarcopenia in patients with HF.

Circulating level of ß-aminoisobutyric acid (BAIBA), a novel myokine-like molecule, is inversely associated with fat mass in patients with heart failure.

Results of experimental studies have shown that ß-aminoisobutyric acid (BAIBA), an exercise-induced myokine-like molecule, is an endogenous negative regulator of fat mass in mice, but it remains unclear whether that is the case in humans, though an enhanced BAIBA concentration in patients receiving sodium-glucose cotransporter 2 inhibitors was found in our recent study. The objective of this study was to analyze the determinants of circulating BAIBA concentration in humans, with focus on the possible link between circulating BAIBA and body composition including fat mass. Data for 188 consecutive patients with heart failure (HF, 64 ± 13 years; 70% male) who received a dual energy X ray absorptiometry (DEXA) scan for assessment of body composition including fat mass index (FMI) and appendicular skeletal muscle mass index (ASMI) were used in this study. Plasma BAIBA concentration in a fasting state after stabilization of HF was determined using ultraperformance liquid chromatography. Plasma BAIBA was detected in 66% of the patients. In simple linear regression analyses of data from patients in whom plasma BAIBA was detected, plasma BAIBA concentration was positively correlated with uric acid and was negatively correlated with body mass index (BMI), estimated glomerular filtration rate (eGFR), FMI, and % body fat. There were no correlations between plasma BAIBA concentration and indexes of muscle mass and bone mass. The results of multiple linear regression analyses showed that FMI and % body fat in addition to BMI, but not ASMI, were independent explanatory factors for plasma BAIBA concentration. In conclusion, plasma BAIBA concentration is inversely correlated with indexes of fat mass, indicating that BAIBA may be a therapeutic target for excessive fat accumulation.

Independent Link Between Use of Mineralocorticoid Receptor Antagonists and Muscle Wasting in Heart Failure Patients Not Receiving Renin-Angiotensin System Inhibitors.

BACKGROUND: The renin-angiotensin system (RAS) activation is a proposed mechanism of muscle wasting (MW i.e., reduction in muscle mass). Although we reported that RAS inhibitors (RASIs) were associated with lower prevalence of MW in heart failure (HF) patients, the relationship between mineralocorticoid receptor (MR) signaling and MW has not been analyzed.Methods and Results: We analyzed data from 320 consecutive Japanese HF patients who underwent dual-energy X-ray absorptiometry scanning for assessment of appendicular skeletal muscle mass index (ASMI). In multiple linear regression analyses, plasma renin activity (PRA) was negatively correlated with ASMI in patients not receiving RASIs, indicating an untoward role of the RAS in MW. Results of analysis of covariance in which risk factors of MW served as covariates showed that use of MR antagonists (MRAs) was associated with lower ASMI and higher PRA in the non-RASIs group. The close relationship between use of MRAs and lower ASMI or higher PRA in the non-RASIs group was confirmed in analyses in which the differences in baseline characteristics between users and non-users of MRAs were minimized by using an inverse probability of treatment weighting. CONCLUSIONS: Increased PRA by MR inhibition without concurrent RAS inhibition, possibly contributing to upregulation of angiotensin II signaling, may be associated with reduction in muscle mass.

Elevated circulating level of ß-aminoisobutyric acid (BAIBA) in heart failure patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitors.

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 ß-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.

Barthel Index Score Predicts Mortality in Elderly Heart Failure　- A Goal of Comprehensive Cardiac Rehabilitation.

BACKGROUND: A strategy to predict mortality in elderly heart failure (HF) patients has not been established.Methods and Results:We retrospectively enrolled 413 HF patients aged ≥65 years (mean age 78 years) who had received comprehensive cardiac rehabilitation (CR) during hospitalization. Basic activities of daily life were assessed before discharge using the Barthel index (BI). Of 413 HF patients, 116 (28%) died during a median follow-up period of 1.90 years (interquartile range 1.20-3.23 years). An adjusted dose-dependent association analysis showed that the hazard ratio (HR) of mortality increased in an almost linear manner as the BI score decreased, and that a BI score of 85 corresponded to an HR of 1.0. Kaplan-Meier survival curves showed that the survival rate was lower for patients with a low BI (<85) than for those with a high BI (≥85; 65% vs. 74%, respectively; P=0.007). In multivariate Cox regression analyses, low BI was independently associated with higher mortality after adjusting for predictors, including B-type natriuretic peptide. Inclusion of the BI into the adjusted model improved the accuracy of the prediction of mortality. CONCLUSIONS: A BI score <85 at the time of discharge is associated with increased mortality independent of known prognostic markers, and achieving functional status with a BI score ≥85 by comprehensive CR during hospitalization may contribute to favorable outcomes in elderly HF patients.

High percent body fat mass predicts lower risk of cardiac events in patients with heart failure: an explanation of the obesity paradox.

BACKGROUND: Although high body mass index (BMI) is a risk factor of heart failure (HF), HF patients with a higher BMI had a lower mortality rate than that in HF patients with normal or lower BMI, a phenomenon that has been termed the "obesity paradox". However, the relationship between body composition, i.e., fat or muscle mass, and clinical outcome in HF remains unclear. METHODS: We retrospectively analyzed data for 198 consecutive HF patients (76 years of age; males, 49%). Patients who were admitted to our institute for diagnosis and management of HF and received a dual-energy X-ray absorptiometry scan were included regardless of left ventricular ejection fraction (LVEF) categories. Muscle wasting was defined as appendicular skeletal muscle mass index < 7.0 kg/m2 in males and < 5.4 kg/m2 in females. Increased percent body fat mass (increased FM) was defined as percent body fat > 25% in males and > 30% in females. RESULTS: The median age of the patients was 76 years (interquartile range [IQR], 67-82 years) and 49% of them were male. The median LVEF was 47% (IQR, 33-63%) and 33% of the patients had heart failure with reduced ejection fraction. Increased FM and muscle wasting were observed in 58 and 67% of the enrolled patients, respectively. During a 180-day follow-up period, 32 patients (16%) had cardiac events defined as cardiac death or readmission by worsening HF or arrhythmia. Kaplan-Meier survival curves showed that patients with increased FM had a lower cardiac event rate than did patients without increased FM (11.4% vs. 22.6%, p = 0.03). Kaplan-Meier curves of cardiac event rates did not differ between patients with and those without muscle wasting (16.5% vs. 15.4%, p = 0.93). In multivariate Cox regression analyses, increased FM was independently associated with lower cardiac event rates (hazard ratio: 0.45, 95% confidence interval: 0.22-0.93) after adjustment for age, sex, diabetes, muscle wasting, and renal function. CONCLUSIONS: High percent body fat mass is associated with lower risk of short-term cardiac events in HF patients.

Clinical Risk Factors and Prognostic Impact of Osteoporosis in Patients With Chronic Heart Failure.

BACKGROUND: The clinical significance of osteoporosis in chronic heart failure (CHF) remains unclear.Methods and Results:A total of 303 CHF patients (75 years, [interquartile range (IQR) 66-82 years]; 41% female) were retrospectively examined. Bone mineral densities (BMDs) at the lumbar spine, femoral neck, and total femur were measured by using dual-energy X-ray absorptiometry (DEXA), and osteoporosis was diagnosed when the BMD at any of the 3 sites was <70% of the Young Adult Mean percentage (%YAM). The prevalence of osteoporosis in CHF patients was 40%. Patients with osteoporosis were older (79 [IQR, 74-86] vs. 72 [IQR, 62-80] years), included a large percentage of females, had slower gait speed and had a lower body mass index. Multivariate logistic regression analysis indicated that sex, BMI, gait speed, loop diuretics use and no use of direct oral anticoagulants (DOACs) were independently associated with osteoporosis. Kaplan-Meier survival curves showed that the rate of death and heart failure hospitalization was higher in patients with osteoporotic BMD at 2 or 3 sites than in patients without osteoporosis (hazard ratio 3.45, P<0.01). In multivariate Cox regression analyses, osteoporotic BMD at 2 or 3 sites was an independent predictor of adverse events after adjustment for prognostic markers. CONCLUSIONS: Loop diuretics use and no DOACs use are independently associated with osteoporosis in CHF patients. Osteoporosis is a novel predictor of worse outcome in patients with CHF.

Nutritional Status and Energy Intake as Predictors of Functional Status After Cardiac Rehabilitation in Elderly Inpatients With Heart Failure　- A Retrospective Cohort Study.

BACKGROUND: Whether the short-term effect of cardiac rehabilitation (CR) in elderly patients with heart failure (HF) is influenced by nutritional status is uncertain, so the present study investigated the effect of nutritional status on functional recovery after CR in elderly HF inpatients.Methods and Results:We enrolled 145 patients admitted for treatment of HF who were aged ≥65 years and had a low functional status defined as a Barthel index (BI) score ≤85 points at the commencement of CR. Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF) and total energy intake per day. The primary endpoint was functional status determined by the BI score at discharge. The median CR period was 20 days (interquartile range: 14-34 days), and 87 patients (60%) were functionally dependent (BI score ≤85) at discharge. Multivariate logistic regression analysis showed that MNA-SF score (odds ratio [OR]: 0.76, P=0.02) and total energy intake at the commencement of CR (OR: 0.91, P=0.02) were independent predictors of functional dependence after CR. MNA-SF score ≤7 and total energy intake ≤24.5 kcal/kg/day predicted functional dependence at discharge with moderate sensitivity and specificity. CONCLUSIONS: MNA-SF score and total energy intake at the commencement of CR are novel predictors of the extent of functional recovery of elderly HF inpatients after in-hospital CR.

Localized electronic structures of graphene oxide studied using scanning tunneling microscopy and spectroscopy.

We have used scanning tunneling microscopy (STM) to elucidate the nanoscale electronic structures of graphene oxide (GO). The unreduced GO layer was imaged using STM without reduction processes when deposited on a Au(111) surface covered with an octanethiolate self-assembled monolayer (C8S-SAM). The STM image of the GO sheet exhibits a grainy structure having a thickness of about 1 nm, which is in good agreement with the previous results obtained using atomic force microscopy (AFM). We found that the C8S-SAM suppresses the adsorption of water remaining on the substrate, which would be important to accomplish the nanoscale imaging of the unreduced GO by STM. Furthermore, we successfully detected the π and π* states localized in the GO sheet using scanning tunneling spectroscopy (STS). The π-π* gap energy and the gap center are not uniform within the GO sheet, indicating the existence of various sizes of the sp2 domain and evidence for the local electronic doping by the substituents.

Surface hydrogenation reactions at the single-molecule level.

Hydrogenation and dehydrogenation reactions on metal surfaces are among the most important in heterogeneous catalysis. Such reactions can be observed and characterized at the single-molecule level with low temperature scanning tunnelling microscopy (LT-STM). A brief review of such studies is presented. A specific example, the hydrogenation of methyl isocyanide to methyl aminocarbyne on the Pt(111) surface, is described in detail. This reaction was first identified in a study with reflection absorption infrared spectroscopy, a technique that averages over monolayer quantities of molecules. The example illustrates the importance of characterization of surface reactions with complementary techniques in order to properly interpret the single-molecule LT-STM images. A second example of the complementary nature of LT-STM and other surface characterization methods is the tip-induced dehydrogenation on Pt(111) of acetonitrile, the more stable isomer of methyl isocyanide.

Relationship Between Participation of In-Hospital Cardiac Rehabilitation and Regional Characteristics in Japan　- Insight From the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination.

Background: The influence of various regional backgrounds on participation in cardiac rehabilitation (CR) remains underexplored. We investigated the regional characteristics that potentially promote CR participation. Methods and Results: This was a nationwide cross-sectional cohort study using the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination. This study included a cohort of 2.7 million inpatients hospitalized between April 2012 and March 2021. The CR participation rate for each hospital was calculated as the percentage of eligible patients who underwent CR during their admission. Among all hospitals, those that do not perform CR were defined as No-CR hospitals. The remaining hospitals were categorized into High- and Low-CR hospitals based on the median level of the CR participation rate (41.5%). High-CR hospitals had significantly smaller medical service areas (P<0.0001), a higher number of physicians per population (P<0.0001), higher air temperature (P=0.02), and fewer primary industry workers (P=0.005) than the other 2 groups. Logistic regression analyses revealed that a lower consumer price index was a significant regional factor that characterized High-CR hospitals, and a lower population aged ≥65 years was a factor approaching significance that characterized the region where High-CR hospitals are located. Conclusions: High-CR hospitals were found in regions with a lower consumer price index and a trend towards a lower population aged ≥65 years.

Relationship between serum iron level and physical function in heart failure patients is lost by presence of diabetes.

AIMS: Iron deficiency (ID) is common in patients with heart failure (HF) and is reportedly associated with exercise intolerance and impaired quality of life. Iron supplementation therapy in HF patients with ID improves exercise capacity. Conversely, protective roles of iron depletion in the development of diabetes mellitus (DM) and its complications have been proposed. This study aimed to determine the impact of ID on physical function in HF patients with and without DM. METHODS AND RESULTS: We enrolled consecutive patients who were admitted to our institute for HF diagnosis and management. The short physical performance battery (SPPB) was used to evaluate physical function, and low physical function was defined as an SPPB score of <10 points as individuals with SPPB scores of <10 points are most likely to be classified as frail and are at high risk for disability and future adverse events, including death. ID was defined as serum ferritin < 100 or 100-299 ng/mL when transferrin saturation (TSAT) was <20% according to the HF guidelines. Among the 562 HF patients (72 ± 14 years old; 56% male), 329 patients (58%) and 191 patients (34%) had ID and low physical function, respectively. Multivariate logistic regression analysis showed that TSAT as a continuous variable, but not ID, was a predictor of low physical function (odds ratio: 0.980, P = 0.024). Subgroup analysis showed that a significant association between low TSAT and low physical function was lost in HF patients with DM (P for interaction < 0.001). A spline dose-response curve for the relationship between TSAT and risk of low physical function with adjustments for covariates associated with low physical function in non-DM patients was almost linear with an increase in the risk of low physical function as the TSAT increased, but such a relationship was not found in the analyses of DM patients. A lack of close TSAT-SPPB relationship in HF patients with DM was confirmed also in a propensity-score-matched cohort. CONCLUSIONS: TSAT as a continuous variable, but not ID, was independently associated with physical function in HF patients, and a significant association was lost in patients with HF and DM, suggesting a limited impact of iron supplementation therapy in HF patients with DM.

Coexistence of sarcopenia and self-reported weight loss is a powerful predictor of mortality in older patients with heart failure.

AIM: We examined whether the addition of self-reported weight loss improves the accuracy of prediction of mortality caused by sarcopenia in heart failure (HF) patients. METHODS: We enrolled 477 HF patients (mean age 77 years) who received combined assessment of sarcopenia and self-reported weight loss. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia. If the patients answered "yes" to the question "have you lost 2 kg or more in the past 6 months?", they were diagnosed as having self-reported weight loss. RESULTS: Sarcopenia and self-reported weight loss coexisted in 32% of patients. During a median follow-up period of 763 days, 65 patients (15%) died. Kaplan-Meier curves showed a significantly higher rate of mortality in HF patients with both sarcopenia and self-reported weight loss than in HF patients with sarcopenia alone. Multivariate Cox proportional hazards analysis showed that the coexistence of sarcopenia and self-reported weight loss is an independent predictor of mortality in HF patients. Inclusion of the coexistence of sarcopenia and self-reported weight loss in the baseline model consisting of established prognostic markers significantly improved both the net reclassification index and the integrated discrimination index. CONCLUSIONS: The coexistence of sarcopenia and self-reported weight loss is a powerful predictor of mortality in HF patients. Geriatr Gerontol Int 2024; 24: 95-101.

Associations between in-hospital daily protein intake and adverse clinical outcomes in older patients with heart failure.

AIMS: The adverse effects of low daily protein intake (DPI) on clinical outcomes in patients with heart failure (HF) are known; however, an optimal DPI to predict event adverse outcomes remains undetermined. Moreover, whether protein restriction therapy for chronic kidney disease is applicable in patients with HF and renal dysfunction remains unclear. METHODS AND RESULTS: In this single-centre, ambispective cohort study, we included 405 patients with HF aged ≥65 years (mean age, 78.6 ± 7.5 years; 50% women). DPI was estimated from consumption over three consecutive days before discharge and normalized relative to the ideal body weight [IBW, 22 kg/m2 × height (m)2]. The primary outcome was a composite of all-cause mortality and HF-related readmission within the 2 year post-discharge period. RESULTS: During an average follow-up period of 1.49 ± 0.74 years, 100 patients experienced composite events. Kaplan-Meier survival curves revealed a significantly lower composite event-free rate in patients within the lowest quartile of DPI than in the upper quartiles (log-rank test, P = 0.02). A multivariate Cox proportional hazards analysis after adjusting for established prognostic markers and non-proteogenic energy intake revealed that patients in the lowest DPI quartile faced a two-fold higher risk of composite events than those in the highest quartile [hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.08-3.82; P = 0.03]. The composite event risk linearly increased as DPI decreased (P for nonlinearity = 0.90), with each standard deviation (0.26 g/kg IBW/day) decrease in DPI associated with a 32% increase in composite event risk (HR, 1.32; 95% CI, 1.10-1.71; P = 0.04). There was significant heterogeneity in the effect of DPI, with the possible disadvantage of lower DPI in patients with HF with cystatin C-based estimated glomerular filtration rate <30 mL/min/1.73 m2. The cutoff value of DPI for predicting the occurrence of composite events calculated from the Youden index was 1.12 g/kg IBW/day. Incorporating a DPI < 1.12 g/kg IBW/day into the baseline model significantly improved the prediction of post-discharge composite events (continuous net reclassification improvement, 0.294; 95% CI, 0.072-0.516; P = 0.01). CONCLUSIONS: Lower DPI during hospitalization is associated with an increased risk of mortality and HF readmission independent of non-proteogenic energy intake, and the possible optimal DPI for predicting adverse clinical outcomes is >1.12 g/kg IBW/day in older patients with HF. Caution is warranted when protein restriction therapy is administered to older patients with HF and renal dysfunction.

Adverse plasma branched-chain amino acid profile mirrors fatty muscle degeneration in diabetic heart failure patients.

AIMS: Elevated plasma branched-chain amino acids (BCAAs) are tightly linked to incident diabetes and its complications, while lower BCAAs are associated with adverse outcomes in the elderly and heart failure (HF) patients. The interplay between body compositions and plasma BCAAs, especially under the influence of co-morbid diabetes in HF patients, is not well understood. Here, we examined the impact of diabetes on the prognostic value of plasma BCAA and its association with body compositions in HF patients. METHODS AND RESULTS: We retrospectively examined 301 HF patients (70 ± 15 years old; 59% male), among which 36% had diabetes. Blood samples for plasma BCAA measurements were collected in a fasting state after stabilization of HF and analysed using ultraperformance liquid chromatography. A dual-energy X-ray absorptiometry scan assessed regional body compositions, and muscle wasting was defined as appendicular skeletal muscle mass index (ASMI) < 7.00 and <5.40 kg/m2 for males and females, respectively, according to the criteria of the Asian Working Group for Sarcopenia. Although analyses of covariance revealed that plasma BCAAs were significantly higher in diabetic patients, low valine (<222.1 nmol/mL) similarly predicted adverse events defined by HF hospitalization, lethal arrhythmia, or all-cause death in both diabetic and non-diabetic patients independently of age, sex, and NT-proBNP (adjusted hazard ratio [HR] 3.1, 95% confidence interval [CI] of 1.1-8.6 and adjusted HR 2.67, 95% CI 1.1-6.5, respectively; P for interaction 0.88). In multivariate linear regression analyses comprising age, sex, and regional body compositions as explanatory variables, plasma BCAAs were positively correlated with visceral adipose tissue area in non-diabetic patients (standardized ß coefficients [ß] = 0.44, P < 0.001). In contrast, in diabetic patients, plasma BCAAs were correlated positively with ASMI (ß = 0.49, P = 0.001) and negatively with appendicular fat mass index (AFMI; ß = -0.42, P = 0.004). Co-morbid diabetes was independently associated with muscle wasting (adjusted odds ratio 2.1, 95% CI 1.1-4.0) and significantly higher plasma 3-methylhistidine level, a marker of myofibrillar degradation. In diabetic patients, ASMI uniquely showed a J-shaped relationship with AFMI, and in a subgroup of HF patients with muscle wasting, diabetic patients showed 12% higher AFMI than non-diabetic patients despite comparable ASMI reductions. CONCLUSIONS: Despite higher plasma BCAA levels in HF patients with diabetes, the prognostic value of low valine remained consistent regardless of diabetes status. However, low BCAAs were distinctly associated with fatty muscle degeneration in the extremities in diabetic patients, suggesting the importance of targeted interventions to prevent such tissue remodelling in this population.

Tailoring electronic states of a single molecule using adamantane-based molecular tripods.

Adsorption structures and electronic states of molecular tripods, having a Br atom (BATT) and a ferrocene derivative (Ferrocene-ATT) at the head part of the adamantane-based trithiolate, adsorbed on Au(111) have been investigated using low temperature scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS). We found that BATT and Ferrocene-ATT form self-assembled monolayers (SAMs), and their orderings are identical to one another, which suggests that the adsorption structure of adamantane-based molecular tripods is independent of the type of functional substituent attached to the head part. The electronic states originated from the ferrocene group were confirmed in the STS spectrum of Ferrocene-ATT whereas those are absent in the BATT spectrum. We note that the ferrocene part has few interactions with the Au substrate owing not only to the upright geometry of Ferrocene-ATT but also to the insulative properties of the adamantane base. The STS mapping revealed the spatial distribution of the electronic state of Ferrocene-ATT.

Comparison of the Treatment Persistence Among 4 Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation: A 5-Year Retrospective Cohort Study.

Four direct oral anticoagulants (DOACs) are used in Japan (edoxaban, rivaroxaban, apixaban, and dabigatran); however, few studies have examined the long-term treatment persistence of these DOACs. Furthermore, the factors associated with persistence remain unclear. This single-center, retrospective cohort study enrolled participants who were newly prescribed the 4 DOACs between January 1, 2012, and April 30, 2020. We assessed the treatment persistence rate by calculating the cumulative incidence rate of prescription switch or discontinuation for 5 years from the initial prescription. The factors associated with persistence were examined using multivariate analysis. The edoxaban was used as a reference for comparison with the other DOACs. The persistence rate at 5 years was 52.9% for all DOACs, including 67.0%, 51.6%, 50.2%, and 37.0% for edoxaban, rivaroxaban, apixaban, and dabigatran, respectively. Multivariate analysis revealed that age >65 years (hazard ratio [HR], 0.62 [95%CI, 0.41-0.93]), chronic kidney disease (HR, 1.63 [95%CI, 1.11-2.39]), baseline hemoglobin (HR, 0.85 [95%CI, 0.78-0.93]), diabetes mellitus (HR, 0.51 [95%CI, 0.29-0.93]), and type of DOACs (rivaroxaban: HR, 1.81 [95%CI, 1.03-3.18]; apixaban: HR, 2.00 [95%CI, 1.15-3.48]; and dabigatran: HR, 2.84 [95%CI, 1.66-4.86]) were significantly associated with nonpersistence at 1 year. At 5 years, diabetes mellitus (HR, 0.60 [95%CI, 0.37-0.97]) and type of DOAC were significantly associated with nonpersistence (rivaroxaban: HR, 1.79 [95%CI, 1.09-2.94]; apixaban: HR, 2.04 [95%CI, 1.26-3.31]; and dabigatran: HR, 2.76 [1.73-4.42]). Long-term treatment persistence differed according to the type of DOAC, with edoxaban exhibiting the highest level of persistence. The factors associated with persistence may change over the treatment course, but larger studies are required to generalize our findings.

Independent Association Between Use of Proton Pump Inhibitors and Muscle Wasting in Patients with Heart Failure: A Single-Center, Ambispective, Observational Study.

BACKGROUND: Although proton pump inhibitors (PPIs) play a pivotal role in the prevention and treatment of gastric acid-related diseases and gastrointestinal adverse events caused by antiplatelet therapies, the safety of long-term use of PPIs has been questioned. OBJECTIVE: The aim of this study was to determine the effects of use of PPIs on muscle mass and bone mineral density in heart failure (HF) patients. METHODS: This was a single-center, ambispective (combined retrospective and prospective), observational study. HF patients (n = 747; 72 years of age; males, 54%) who received a dual-energy x-ray absorptiometry scan were enrolled. Muscle wasting was defined as appendicular skeletal muscle mass index (ASMI) < 7.0 kg/m2 in males and <5.4 kg/m2 in females. Propensity scores for the use of PPIs were calculated using a multivariate logistic regression model to minimize selection bias. RESULTS: Before propensity score matching, ASMI was significantly lower in patients receiving PPIs than in patients not receiving PPIs, resulting in a higher prevalence of muscle wasting in the PPI group. Such a relationship between use of PPIs and muscle wasting remained after propensity score matching. In multivariate Cox regression analyses, use of PPIs was independently associated with presence of muscle wasting (hazard ratio 1.68, 95% confidence interval 1.05-2.69) after adjustment for established risk factors of sarcopenia. On the other hand, there were no differences in bone mineral density between the PPI group and the no-PPI group. CONCLUSION: Use of PPIs is associated with a high risk of muscle wasting in HF patients. Caution is warranted when long-term PPI treatment is performed in sarcopenic HF patients and HF patients with several risk factors for muscle wasting.

Impact of Radar Chart-Based Information Sharing in a Multidisciplinary Team on In-Hospital Outcomes and Prognosis in Older Patients With Heart Failure.

Background: A multidisciplinary team (MDT) approach is crucial for managing older patients with heart failure (HF). We investigated the impact on clinical outcomes of implementation of a conference sheet (CS) with an 8-component radar chart for visualizing and sharing patient information. Methods and Results: We enrolled 395 older inpatients with HF (median age 79 years [interquartile range 72-85 years]; 47% women) and divided them into 2 groups according to CS implementation: a non-CS group (before CS implementation; n=145) and a CS group (after CS implementation; n=250). The clinical characteristics of patients in the CS group were assessed using 8 scales (physical function, functional status, comorbidities, nutritional status, medication adherence, cognitive function, HF knowledge level, and home care level). In-hospital outcomes (Short Physical Performance Battery, Barthel Index score, length of hospital stay, and hospital transfer rate) were significantly better in the CS than non-CS group. During the follow-up period, 112 patients experienced composite events (all-cause death or admission for HF). Inverse probabilities of treatment-weighted Cox proportional hazard analyses demonstrated a 39% reduction in risk of composite events in the CS group (adjusted hazard ratio 0.65; 95% confidence interval 0.43-0.97). Conclusions: Radar chart-based information sharing among MDT members is associated with superior in-hospital clinical outcomes and a favorable prognosis.

Development and validation of osteoporosis risk assessment score, ORAS, in heart failure patients: comparison with the Osteoporosis Self-Assessment Tool for Asians (OSTA).

AIM: Osteoporosis is prevalent and is associated with poor prognosis in heart failure (HF) patients. However, bone mineral density (BMD) measurement by a dual-energy X-ray absorptiometry (DEXA) scan is not always available in a daily clinical setting and large-scale population-based studies. METHODS: A single-center, cross-sectional observational study was conducted with 387 patients (median age: 77 years [interquartile range: 68 to 83 years]; 37% women). BMDs were measured by DEXA scans, and osteoporosis was diagnosed as ≤ -2.5 standard deviation of the BMDs in healthy young adults. Osteoporosis risk assessment score (ORAS) was developed using significant predictors from a logistic regression model for osteoporosis and was subsequently validated. RESULTS: Osteoporosis was found in 103 (27%) of the 387 HF patients. Multivariate logistic regression analyses yielded the ORAS based on sex, BMI, handgrip strength, and anti-coagulant therapy utilization. The C-index of ORAS in the developmental set (0.796, 95% confidence interval: 0.747 to 0.845) was similar to the bootstrap validation of the prediction model (0.784), and tended to be higher than that of the Osteoporosis Self-Assessment Tool for Asians (OSTA). A nomogram of ORAS, established on the basis of the final logistic regression model, demonstrated 100% sensitivity at the lowest score (35 points), with an optimal cutoff point of 127 points, yielding 85% sensitivity and 62% specificity. CONCLUSIONS: ORAS exhibits superior predictive performance to OSTA in predicting osteoporosis in HF patients, establishing itself as a valuable tool for early detection in both daily clinical practice and large-scale population-based studies.