Data on the safety and tolerability of sacubitril/valsartan in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) are limited.The REVIEW-HF registry was a nationwide, multicenter, retrospective study that investigated the characteristics and outcomes of patients with heart failure who were newly prescribed sacubitril/valsartan in Japan. We evaluated adverse events (AEs) related to sacubitril/valsartan within 3 months after initiation, defined as hypotension, worsening kidney function, hyperkalemia, and angioedema. The rates of AEs and sacubitril/valsartan discontinuation were compared between patients with and without ATTR-CM.Among the 995 patients enrolled, 17 were diagnosed with ATTR-CM. Patients with ATTR-CM had a significantly higher incidence of AEs (64.7% versus 21.7%, P < 0.001), which were all attributable to hypotension. The discontinuation rate of sacubitril/valsartan was also significantly higher in these patients (76.5% versus 21.7%, P < 0.001), with a median discontinuation time of 8 days (interquartile range, 7-16). In multivariable analysis, ATTR-CM remained significantly associated with a higher risk of AEs (adjusted odds ratio, 7.35; 95% confidence interval, 2.40-22.55; P < 0.001) and sacubitril/valsartan discontinuation (adjusted odds ratio, 8.05; 95% confidence interval, 2.47-26.20; P < 0.001).In conclusion, patients with ATTR-CM had a significantly higher incidence of hypotension and more frequent discontinuation of sacubitril/valsartan compared with those without ATTR-CM. Although the number of patients with ATTR-CM in this study was limited and the findings should be interpreted with caution, careful monitoring may be warranted after the initiation of sacubitril/valsartan in this population.

Background: Frailty, including sarcopenia and osteopenia, is associated with adverse outcomes in patients with heart failure (HF), but its assessment in routine care remains challenging. We evaluated computed tomography (CT)-derived sarcopenia and osteopenia and their associations with 2-year all-cause mortality in older patients hospitalized for HF.Methods: This retrospective cohort study included patients aged ≥65 years who underwent abdominal CT during hospitalization for HF between April 2015 and March 2023. Sarcopenia was defined using the psoas muscle area index, and osteopenia was defined using vertebral trabecular bone attenuation. Patients were classified into four groups: neither condition (Group A, n=157), osteopenia alone (Group B, n=464), sarcopenia alone (Group C, n=68), and both conditions (Group D, n=204). The primary outcome was 2-year all-cause mortality.Results: Among 893 patients, 272 (30.5%) had sarcopenia and 668 (74.8%) had osteopenia. Survival differed significantly among the four groups (log-rank P=0.042), with Group C showing the lowest survival probability. In multivariable Cox analysis, CT-defined sarcopenia was independently associated with all-cause mortality (hazard ratio, 1.77; 95% confidence interval, 1.06–2.95; P=0.029).Conclusions: CT-defined sarcopenia was associated with an increased risk of 2-year all-cause mortality and may provide useful prognostic information in older patients hospitalized for HF.

Objective The perioperative cardiac risk associated with non-cardiac surgery in patients with significant coronary artery stenosis has not been fully determined. This study aimed to assess cardiac events after non-cardiac surgery in patients with or without coronary artery stenosis (CAS) based on pre-operative coronary angiography. Methods This single-center, observational study retrospectively analyzed data from 809 patients without a history of percutaneous coronary intervention or coronary artery bypass grafting who underwent coronary angiography before non-cardiac surgery for risk assessment. After excluding 94 patients who underwent preoperative coronary revascularization, 715 (215 with CAS and 500 without CAS) were assessed. The occurrence of cardiac events, including cardiac death, non-fatal myocardial infarction, the requirement for urgent revascularization, worsening heart failure, worsening angina symptoms, and ventricular tachycardia/fibrillation within 30 days of surgery, was investigated. Results The mean age of the patients was 70.3±9.7 years, and 72.7% were men. Patients with CAS were more likely to be men and had diabetes mellitus and dyslipidemia compared to those without CAS. Regarding perioperative cardiac risk, 401 (56.1%) non-cardiac surgical procedures were categorized as having a high cardiac risk, 248 (34.7%) as intermediate, and 66 (9.2%) as low. Within 30 days of non-cardiac surgery, no significant difference was observed in the occurrence of cardiac events between the patients with and without CAS (1.9% vs. 1.4%, p=0.74). Conclusion The findings suggest that significant CAS is not necessarily associated with an increased perioperative risk of cardiac events.

BACKGROUND:Worsening renal function (WRF) in acute heart failure (AHF) has been associated with poor outcomes; however, when accompanied by hemoconcentration, WRF is not necessarily associated with adverse outcomes. The associations of WRF and hemoconcentration with renal outcomes and longitudinal changes in renal function remain unclear. METHODS:In this multicenter retrospective study, 2556 hospitalized patients with AHF (median 80 years; 60% male) were categorized into four groups according to WRF and hemoconcentration status. WRF was defined as a ≥20% decrease in estimated glomerular filtration rate (eGFR) from admission to discharge. Hemoconcentration was defined as concurrent increases in hemoglobin and hematocrit levels from admission to discharge. The primary outcome was a composite of initiation of maintenance dialysis, decline in eGFR to <10 mL/min/1.73 m2, or ≥40% reduction in eGFR within one year after discharge. RESULTS:The WRF/hemoconcentration group had less frequent inotrope use and lower N-terminal pro-B-type natriuretic peptide levels at discharge. The cumulative incidence of the primary outcome was 18.4%, 15.9%, and 20.0% in the No WRF/No hemoconcentration, No WRF/hemoconcentration, and WRF/No hemoconcentration groups, respectively, and was lowest at 9.5% in the WRF/Hemoconcentration group. In multivariable analysis, this group was significantly associated with a lower risk of the primary outcome, compared with the No WRF/No hemoconcentration group (subdistribution hazard ratio 0.58, 95% confidence interval 0.36 to 0.93, p = 0.025). The longitudinal changes in renal function differed significantly across the groups; the WRF/Hemoconcentration group showed an attenuated decline or even improvement in eGFR (+3.6 mL/min/1.73 m2/year), whereas the No WRF/No hemoconcentration group exhibited the steepest decline (-6.2 mL/min/1.73 m2/year). CONCLUSIONS:Renal function changes after AHF hospitalization were heterogeneous, and WRF accompanied by hemoconcentration was associated with favorable renal outcomes within one year after discharge.

We aimed to evaluate the usefulness of the Fibrosis-5 index (FIB-5) for predicting prognosis in patients with chronic heart failure and examine whether combining the Fibrosis-4 (FIB-4) and FIB-5 indices could enhance risk stratification in heart failure. This single-center retrospective cohort study analyzed data from an inpatient database. A total of 1,100 patients (mean age, 78 years; 58.2

Objectives:To characterise the myocardial transcriptomic landscape of patients with systemic sclerosis (SSc) with primary heart involvement (pHI) and identify molecular pathways underlying its pathogenesis. Design:A single-centre study exploring the molecular pathogenesis of SSc-pHI through transcriptomic analysis of endomyocardial biopsy specimens. Setting:Basic research. Participant:This study enrolled seven patients with SSc-pHI and eight patients with dilated cardiomyopathy (DCM) who had undergone endomyocardial biopsy for clinical practice purposes. Interventions:No intervention. Main outcome measures:Not applicable. Methods:Endomyocardial biopsy specimens from patients with SSc-pHI and those with DCM underwent whole RNA sequencing. To enable indirect comparison with non-failing (NF) myocardium, public RNA sequencing data of NF and DCM samples were integrated using DCM as a shared reference. Differential gene expression, pathway enrichment (Ingenuity Pathway Analysis and Gene Set Enrichment Analysis) and immune and stromal cell deconvolution were performed. Histopathological evaluation included LC3 immunostaining and transmission electron microscopy (TEM). Results:A total of 700 genes were differentially expressed between SSc and DCM myocardium. Mitochondrial energy metabolism pathways, including oxidative phosphorylation, fatty acid β-oxidation and the tricarboxylic acid cycle, were markedly suppressed in SSc. Indirect comparison with NF myocardium confirmed reciprocal regulation of mitochondrial metabolism and suggested enhanced autophagy. Cell deconvolution revealed enrichment of M1-like macrophages in SSc myocardium. LC3 immunostaining and TEM revealed increased autophagic vacuoles, lipid droplet accumulation and ischaemia-like ultrastructural alterations. Conclusions:SSc myocardium exhibits metabolic reprogramming characterised by mitochondrial dysfunction and enhanced autophagy, accompanied by macrophage activation.

BACKGROUND:The EMPA-ICD (Empagliflozin in Patients with Type 2 Diabetes Treated with an Implantable Cardioverter-Defibrillator; jRCTs031180120) trial is a prospective, multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of empagliflozin on ventricular arrhythmias (VAs) in patients with type 2 diabetes (T2DM) treated with implantable cardioverter-defibrillators (ICDs). The trial showed that empagliflozin reduces VAs, but whether this effect differs by sex remains unclear. OBJECTIVES:This EMPA-ICD trial subanalysis aimed to assess sex-specific differences in the antiarrhythmic effects of empagliflozin in ICD-treated patients with T2DM. METHODS:The primary endpoint was the change in the number of VAs, including nonsustained ventricular tachycardia, sustained ventricular tachycardia, and ventricular fibrillation, detected by the ICDs over 24 weeks. RESULTS:Between April 2019 and April 2021, a total of 150 patients were randomized to receive either empagliflozin or placebo at 31 centers in Japan. In men, the rate of ventricular arrhythmia events was significantly lower in the empagliflozin group than in the placebo group, with a rate ratio of 0.33 (95% CI: 0.27-0.39; P < 0.001). In women, the rate ratio was 1.78 (95% CI: 0.54-5.90; P = 0.35), with no statistically significant difference observed. Notably, a significant interaction between sex and treatment was observed, suggesting a sex-specific treatment response (P = 0.006) CONCLUSIONS: The arrhythmic effect of empagliflozin in patients with T2DM treated with ICDs appears to be more pronounced in men than in women. These findings underscore the need for investigating sex-specific responses to sodium-glucose cotransporter 2 inhibitors, advancing personalized strategies for arrhythmia management.

BACKGROUND:Postoperative decline in activities of daily living (ADL) is common among older patients undergoing cardiac surgery and is associated with poor quality of life and adverse clinical outcomes. Frailty and lower swallowing function have each been linked to postoperative functional decline; however, their combined association with postoperative ADL recovery remains unclear. OBJECTIVES:This retrospective cohort study examined the association between the coexistence of frailty and lower swallowing function and postoperative functional outcomes in older adults undergoing cardiac surgery. METHODS:A total of 123 patients (median age, 73 years; 71.5% male) who underwent elective cardiac surgery between July 2020 and August 2024 were included. The primary outcome was the change in Barthel Index (BI) score from preoperative assessment to hospital discharge. Frailty was assessed using the Japanese version of the Cardiovascular Health Study (J‑CHS) criteria, and swallowing function was evaluated with the Repetitive Saliva Swallowing Test (RSST). Participants were classified into four groups according to the presence or absence of frailty and lower swallowing function (RSST ≤ 4). RESULTS:The mean change in BI score was -2.03 ± 6.68, and those with both frailty and lower swallowing function exhibited a greater BI decline than the other groups (p < 0.001). After adjustment for demographic and clinical variables, the coexistence of frailty and lower swallowing function remained independently associated with BI change (β = -0.371, p < 0.001). CONCLUSIONS:These findings indicate that frailty and lower swallowing function may be meaningful factors associated with postoperative functional decline in older adults undergoing cardiac surgery, emphasizing the potential value of comprehensive preoperative assessment and multidisciplinary management strategies.

Introduction:In this study, we aimed to evaluate the impact of sarcopenia and its severity on postoperative functional decline in patients undergoing cardiac surgery. Methods:This retrospective cohort study included 161 patients (median age, 71 years; 75.8% male) who underwent elective cardiac surgery at a tertiary care hospital between April 2021 and November 2024. Functional decline was assessed by subtracting the preoperative Barthel Index (BI) score from the score at discharge. Sarcopenia severity was assessed based on the Asian Working Group for Sarcopenia 2019 criteria. Multiple linear regression models adjusted for relevant clinical and demographic factors were used to examine the associations among sarcopenia, severe sarcopenia, and functional decline. Results:The mean (standard deviation) change in BI score was -1.4 (5.7). The overall prevalence of sarcopenia was 21.1%, comprising 7.5% (non-severe) sarcopenia and 13.7% severe sarcopenia cases. In the multivariate analysis, the presence of sarcopenia was significantly associated with postoperative functional decline (β = -0.185, p = 0.001), whereas severe sarcopenia exhibited a stronger association with postoperative functional decline (β = -0.268, p < 0.001). Conclusions:These findings indicate that patients with severe sarcopenia require careful attention because of their higher risk of postoperative functional decline.

BackgroundHypnotics are frequently prescribed to hospitalized older adults, but comparative evidence on fall risk across hypnotic classes remains inconsistent, partly due to confounding by indication and inadequate consideration of time at risk during hospitalization.MethodsWe conducted a retrospective multicenter landmark analysis using administrative claims and electronic medical records from two acute-care hospitals in Japan (2018-2024). A day-7 landmark was defined, including patients aged ≥65 years who remained hospitalized and fall-free through hospital day 7. Sustained hypnotic exposure during hospital days 4-7 (≥2 days) was categorized as no sustained use, benzodiazepines/Z-drugs (BZ/Zs) alone, orexin receptor antagonists or ramelteon (ORA/Ram) alone, or combination therapy. The primary outcome was time to first in-hospital fall during hospital days 8-37. Cox proportional hazards models with multiple imputation were used. Competing-risk analyses and propensity score-matched comparisons between single-class users were conducted as sensitivity analyses.ResultsAmong 61,663 patients, 3,884 (6.3%) experienced an in-hospital fall after the landmark. Compared with no sustained hypnotic use, adjusted hazard ratios (HRs) for falls were 1.42 (95% CI, 1.24-1.64) for BZ/Zs, 1.46 (95% CI, 1.25-1.70) for ORA/Ram, and 1.42 (95% CI, 1.05-1.91) for combination therapy. Results were consistent in competing-risk analyses. In propensity score-matched analyses restricted to single-class users, fall risk did not differ significantly between BZ/Zs and ORA/Ram (adjusted HR, 0.98; 95% CI, 0.75-1.28).ConclusionsSustained hypnotic use during hospitalization was associated with a higher incidence of in-hospital falls among older adults. After adjustment for measured clinical factors and treatment selection, no significant difference in fall risk was observed between BZ/Zs and ORA/Ram.

Objectives Sex-specific differences in sarcopenia-related prognosis following cardiac surgery are unclear. We aimed to investigate the association between preoperative computed tomography (CT)-defined sarcopenia and postoperative complications in older patients undergoing elective cardiac surgeries, focusing on sex-specific differences. Methods This retrospective observational study included 133 patients aged ≥65 years who underwent elective open-heart surgeries. Sarcopenia was assessed using the psoas muscle area index derived from preoperative CT scans and defined using sex-specific cut-off values. The primary outcome was postoperative complication. Results Forty-nine (36.8%) patients had sarcopenia. Although the incidence of complications was higher in this group, the difference was not statistically significant between the groups. Multivariate logistic regression analysis excluding patients with pre-existing atrial fibrillation revealed that sarcopenia was independently associated with a higher risk of postoperative complications (odds ratio 3.73, 95% confidence interval 1.49–9.84, P=0.006). The male patients with sarcopenia showed a higher incidence of complications versus those without (56.8% vs. 33.9%, P=0.046), whereas no association was observed in the female patients. Sex-stratified analyses confirmed the independent prognostic value of sarcopenia in male patients only (odds ratio 2.52, 95% confidence interval 1.08–6.01, P=0.033). Conclusion Preoperative CT-defined sarcopenia was independently associated with postoperative complications in older male patients undergoing elective cardiac surgeries, but not in female patients. These findings suggest that the prognostic significance of sarcopenia is sex-specific, and highlight the importance of sex-specific risk stratification strategies in older patient populations undergoing cardiac surgeries.

Background:Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and an independent determinant of prognosis. Increases in pulmonary vascular resistance often precede overt elevation of pulmonary arterial pressure, but early pulmonary vascular involvement remains difficult to detect noninvasively. Conventional echocardiographic assessment in COPD focuses mainly on right ventricular systolic indices, which may remain preserved despite increased pulmonary vascular load. Methods:We conducted a single-center retrospective observational study of 58 patients with stable COPD who underwent right heart catheterization and comprehensive transthoracic echocardiography during the same hospitalization. Right ventricular isovolumetric relaxation time (IRT), a Doppler-derived index of diastolic timing, was evaluated in relation to invasively measured pulmonary vascular resistance, dyspnea severity, exercise capacity, and pulmonary function. Results:A total of 58 patients were included. Patients meeting hemodynamic criteria for pulmonary hypertension exhibited lower diffusing capacity, more severe dyspnea, and reduced exercise capacity despite similar airflow limitation. Pulmonary vascular resistance was significantly higher, while cardiac index remained preserved. IRT was significantly prolonged in patients with pulmonary hypertension and showed a moderate correlation with pulmonary vascular resistance (ρ = 0.56, p < 0.001), six-minute walk distance (ρ = -0.46, p < 0.001), and dyspnea severity (ρ = 0.36, p = 0.006). In contrast, conventional right ventricular systolic indices showed no significant associations with pulmonary vascular resistance. Conclusion:Echocardiographic assessment of IRT may provide a physiologically grounded, noninvasive parameter associated with early right ventricular diastolic response to pulmonary vascular load.

Background: The number of patients with heart failure (HF) is increasing with aging of the population, resulting in a shift in care from hospitals to community settings. Although predicting medium-term prognosis after discharge could improve community-based management and reduce readmissions, no established model has integrated structured multidimensional assessments into HF prognostic modeling. Methods and Results: This multicenter study developed and validated machine learning (ML) models (i.e., logistic regression, random forest, extreme gradient boosting, and light gradient boosting) to predict 180-day mortality or emergency hospitalization in 4,904 patients with HF. Patients were randomly divided into training and validation sets (8 : 2). Nursing care needs, derived from structured nursing assessments that capture patients' physical status and care dependency, were included as a predictive feature. All models demonstrated acceptable discriminative performance based on the area under the precision-recall curve, favorable calibration assessed by the calibration slope and Brier score, and effective risk stratification. The Shapley additive explanations algorithm identified nursing care needs as an important prognostic factor, alongside established laboratory variables for HF prognosis. Conclusions: ML models incorporating nursing care needs effectively predicted the 180-day prognosis of patients with HF. The prominent contribution of nursing care needs underscores the value of incorporating structured multidimensional care-related information into prognostic modeling and highlights the importance of team-based post-discharge HF management.

Obesity is an independent risk factor for heart failure (HF) onset; however, weight loss is an independent poor prognostic factor in patients with HF. According to the obesity paradox, higher body weight is associated with better prognosis in these patients. This retrospective cohort study investigated the obesity paradox in super-elderly, understudied patients (aged ≥ 85 years) with HF and examined its impact on all-cause mortality. We included patients hospitalized for HF between April 2015 and March 2023. Participants were divided into four age groups: Groups A (< 65 years), B (65–74 years), C (75–84 years, elderly), and D (≥ 85 years, super-elderly). The primary endpoint was the 1-year all-cause mortality rate after discharge. The secondary endpoints included cardiac and non-cardiac death rates and all-cause mortality rates stratified by left ventricular ejection fraction (LVEF). Overall, 3,811 individuals (mean age: 74.3 years, 60.4

Worsening renal function (WRF) frequently occurs in acute heart failure (AHF) and represents a clinical challenge, as it may lead to inappropriate alterations in therapy. Understanding its mechanisms and prognostic implications is essential for optimization of treatment. The prognostic impact of WRF depends on clinical context. WRF is associated with poor outcomes when residual congestion persists; however, it is not harmful if effective decongestion is achieved. Systemic processes such as inflammation and oxidative stress may contribute to WRF with adverse outcomes, as demonstrated by novel biomarkers. Conversely, the initial decline in glomerular filtration rate observed following the initiation of heart failure therapies is typically a benign physiological response. This review outlines the concept, pathophysiology, prognosis, and management of WRF in AHF. Clinicians should carefully interpret the clinical context of WRF and avoid the premature discontinuation of heart failure therapies to ensure optimal therapeutic decision-making.

Introduction:This study aimed to examine the predictive factors and timing of delirium onset in hospitalized patients with heart failure, focusing on the impact of total anticholinergic load and other contributing variables. Methods:The single-site retrospective cohort study included 694 patients hospitalized for heart failure and receiving treatment for hyperpolypharmacy between January 2015 and March 2023. The patients were categorized into delirium and non-delirium groups, with the delirium group further subdivided into early-onset (within 6 days) and late-onset (day 7 or later) subgroups. Logistic regression analyses were performed to identify significant factors associated with delirium onset. Results:Compared with the non-delirium group, the delirium group (n = 54) showed a higher total anticholinergic load, malnutrition prevalence, and elevated N-terminal pro-brain natriuretic peptide levels. Early-onset delirium was associated with a higher total anticholinergic load and C-reactive protein levels, whereas late-onset delirium correlated with malnutrition. Hyperactive delirium was predominant in the early-onset group and the hypoactive or mixed subtypes in the late-onset. Conclusions:Elevated anticholinergic loads and the presence of infection were primary contributors to early-onset delirium; malnutrition and the body mass index were critical for late-onset delirium. These findings emphasize the need for targeted preventive strategies based on delirium onset timing.