Munehisa Sakamoto

Background: SGLT2 (sodium–glucose cotransporter‐2) inhibitors (SGLT2is) improve outcomes in heart failure (HF), but evidence in patients with frailty and acute HF (AHF) is limited. This study investigated the association between SGLT2i use at discharge and outcomes in patients with AHF, with a focus on frailty. Methods: We analyzed 5579 patients hospitalized for AHF enrolled between 2018 and 2024 in the prospective WET‐HF2 (West Tokyo Heart Failure 2) registry in Japan (age 79 years, 43% women, body mass index 23.1, 23% ischemic cause, left ventricular ejection fraction 45%, 24% SGLT2is at discharge). Frailty was assessed using the Clinical Frailty Scale (≥4; 63%), and complementary analyses were performed using frailty‐related factors (low body mass index, reduced activities of daily living, malnutrition, and dementia). The primary outcome was a composite of cardiac death or HF rehospitalization within 1 year, which occurred in 766 patients (18%). A propensity score was calculated using variables associated with SGLT2i prescription. Results: After propensity score–based inverse probability of treatment weighting adjustment, SGLT2i use was associated with a lower risk of the primary outcome (hazard ratio [HR], 0.76, P =0.045). This association was more pronounced in patients with frailty (HR, 0.59, P =0.005), but not in patients without frailty (HR, 1.18; P _interaction =0.010). Analyses using frailty‐related factors yielded similar patterns. At 1 year, SGLT2i use at discharge was not associated with deterioration in body mass index or nutritional status. Conclusions: In this observational registry, SGLT2i use at discharge was associated with improved outcomes in patients with AHF, particularly those with frailty, without evidence of nutritional harm. These findings support the potential safety of SGLT2is in patients with frailty and AHF.

Background: Although the “I NEED HELP” criteria facilitate timely consideration of advanced heart failure (HF) therapies, patient classification based on the variables included in the criteria are scarcely investigated. This study aimed to identify phenotypically distinct subgroups of patients with advanced HF using unsupervised cluster analysis based on the variables included in these criteria. Methods: A multicenter registry was used to identify patients hospitalized with HF who met at least 1 I NEED HELP criterion. Latent class analysis was performed on 9 variables from the criteria. Results: A total of 2520 patients (mean age, 74±13 years; 40% women) were included in this study. Latent class analysis identified 3 phenotypes: more de novo HF with the lowest number of applicable criteria (phenotype 1, 31%); younger age with the lowest left ventricular ejection fraction and highest number of applicable criteria (phenotype 2, 19%); and older age with more comorbidities and poorer renal function (phenotype 3, 49%). After multivariable adjustment, phenotypes 2 and 3 were associated with a higher incidence of composite all‐cause death or rehospitalization for HF (phenotype 2: hazard ratio [HR], 1.96 [95% CI, 1.58–2.42]; phenotype 3: HR, 1.54 [95% CI, 1.28–1.84]; phenotype 1: reference) during the follow‐up period (median, 461 [interquartile range, 130–730] days). Conclusions: This study describes a novel phenotypical classification based on the I NEED HELP criteria, with significantly different prognoses identified for patients with advanced HF. These classifications may facilitate risk stratification in this population with a complicated clinical profile.

Background: The prognostic impact of worsening renal function (WRF) during the vulnerable phase following discharge after hospitalization for acute decompensated heart failure (HF) remains unclear. This study investigated the determinants of WRF 1 year after discharge (1Y‐WRF) and its association with clinical outcomes in patients with acute decompensated HF. Methods: Data were analyzed for 1753 patients hospitalized with acute decompensated HF from WET‐HF2 (West Tokyo Heart Failure 2), a multicenter registry. 1Y‐WRF was defined as a ≥25% decrease in estimated glomerular filtration rate (eGFR). The primary end point was a composite of all‐cause mortality and HF rehospitalization beyond 1 year after discharge. Exploratory subgroup analyses were conducted based on age, sex, left ventricular ejection fraction, diabetes, eGFR, HF rehospitalization, and loop diuretic intensification within 1 year after discharge, anemia, and renin‐angiotensin‐aldosterone system inhibitors use. Results: Of the 1753 patients (median age 76 years, 39.9% female, median eGFR 50.7 mL/min per 1.73 m ² at discharge), 285 (16.3%) developed 1Y‐WRF. Female sex, anemia, higher New York Heart Association class, and higher eGFR at discharge were associated with 1Y‐WRF. Over a median follow‐up of 1 year, 1Y‐WRF was associated with an increased risk of the composite end point (adjusted hazard ratio, 1.34 [95% CI, 1.02–1.75], P =0.035), primarily driven by HF rehospitalization. The adverse prognostic impact was notable in young patients and those with high eGFR and no HF rehospitalization within 1 year after discharge. Conclusions: In a contemporary cohort of acute decompensated heart failure 1Y‐WRF was relatively common and associated with subsequent worse clinical outcomes.

Background: Ischemic stroke (IS) is a serious complication in heart failure, particularly following hospitalization for acute decompensated heart failure (ADHF). However, its actual incidence during the acute and stable treatment phases remains unclear. Moreover, the association between IS and hemoglobin levels, which fluctuate during these phases, has not been comprehensively investigated. Methods: Patient-level data from 2018 to 2024 were extracted from a prospective multicenter cohort study that consecutively enrolled patients hospitalized with ADHF. Cerebrovascular events were confirmed by local board-certified neurologists using imaging modalities. The incidence of IS and its association with hemoglobin levels, categorized by the universal anemia definition (hemoglobin p for trend =0.002). Cardioembolic stroke (61.7%) was the predominant subtype throughout phases. After covariate adjustments, higher hemoglobin levels (non-anemia) were associated with increased risk of early IS (sHR 2.05,95%CI 1.09– 3.83, p=0.03), but not with late IS (adjusted HR 1.21,95% CI 0.65–2.23, p=0.55), with restricted cubic spline further demonstrating non-linear phase-dependent differences in the impact of hemoglobin levels on IS risk. Conclusion: IS occurred across phases of ADHF management, with higher incidence within 30 days after hospitalization. The relationship between hemoglobin levels and IS risk varies by phase, highlighting non-anemia as a potential marker for high-risk patients in the early phase. Incorporating hemoglobin levels into risk stratification could guide targeted screening and preventive strategies.

Background: Recently, patients with supra-normal left ventricular ejection fraction (snLVEF) are reported to have high risk of adverse outcomes, especially in women. We sought to evaluate sex-related differences in the association between LVEF and long-term outcomes in heart failure (HF) patients. Methods: The multicenter WET-HF Registry enrolled all patients hospitalized for acute decompensated HF (ADHF). We analyzed 3,943 patients (age 77 years; 59.8% male) registered from 2006 to 2017. According to LVEF the patients were divided into the 3 groups: HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) and preserved EF (HFpEF). The primary endpoint was defined as the composite of cardiac death and ADHF rehospitalization after discharge. Results: Implementation of guideline-directed medical therapy (GDMT) such as renin-angiotensin-system inhibitor (RASi), β-blocker and their combination at discharge was significantly lower in women than men in HFmrEF. Lower prescription of RASi + β-blocker combination in female HFmrEF was noted even after adjustment for covariates (p=0.007). There were no such sex-related differences in HFrEF. Female sex was associated with higher incidence of the primary endpoint and ADHF rehospitalization after adjustment for covariates exclusively in HFmrEF. Restricted cubic spline analysis demonstrated a U-shaped relationship between LVEF and the hazard ratio of the primary endpoint in women, but such relationship was not observed in men ( p for interaction=0.037). Conclusions: In women, not only lower LVEF but also snLVEF were associated with worse long-term outcomes. Additionally, sex-related differences in the GDMT implementation for HFmrEF highlight the need for sex-specific guidelines to optimize HF management.