Introduction: Heart failure (HF) with mildly reduced ejection fraction (HFmrEF) is a heterogeneous phenotype, and whether the prognostic weight of ischemic versus non-ischemic etiology differs across left ventricular ejection fraction (LVEF) categories remains uncertain. We examined whether the association between etiology and long-term all-cause mortality is modified by HF phenotype. Material and methods: Within the prospective multicenter HEROES registry, 1,410 patients with HF were classified as having ischemic or non-ischemic etiology and categorized by LVEF. All-cause mortality was obtained through national administrative linkage with complete follow-up. Entropy balancing (13 covariates) and weighted Cox models were applied within each phenotype, with formal testing for etiology-by-phenotype interaction. Robustness was evaluated using restricted mean survival time (RMST), the E-value, and sensitivity analyses. Results: Over a median follow-up of 14.8 months, 219 (15.5%) deaths occurred. Crude mortality was identical between etiologies (15.5% vs. 15.5%; p = 0.93). After balancing, no difference was observed in HFrEF (adjusted hazard ratio [aHR] 1.03, 95% CI: 0.68–1.58) or HFpEF (aHR = 0.84, 95% CI: 0.37–1.90), whereas non-ischemic etiology was associated with higher mortality in HFmrEF (aHR = 3.99, 95% CI: 1.51–10.51; p = 0.005). The etiology-by-phenotype interaction was significant (p = 0.032). In HFmrEF, the RMST difference at 23 months was −2.38 months (95% CI: −3.69 to −1.00), with an E-value of 4.55 (lower confidence limit 1.99); findings were consistent across sensitivity analyses. Conclusions: The prognostic impact of HF etiology appears phenotype-dependent, concentrated within HFmrEF, where non-ischemic etiology substantially worse survival. Given the limited number of events, this phenotype-specific signal is hypothesis-generating and warrants confirmation.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver diseases across all age groups. Methods: This review synthesizes the current evidence from landmark studies on the risk factors, diagnosis, and management of MASLD in pediatric, adult, and particularly elderly patients. Results: Based on the current data, we demonstrated that the prevalence of MASLD increases with age from childhood to middle adulthood, whereas, in elderly individuals, there is no further age-related increase observed. In the pathogenesis of the disease, familial and prenatal factors predominate in the youngest patients, while metabolic factors are the main contributors in adults. However, obesity remains the most significant risk factor for MASLD across all age groups. Therefore, systematic screening for MASLD should be strongly recommended in individuals with obesity. Laboratory parameters indicating an increased risk of MASLD are primarily recommended in screening regimens for children and adults; however, in elderly patients, these parameters may remain within normal ranges due to the long-standing disease course and progression toward fibrosis. On the basis of current studies and guidelines, we showed that lifestyle modification, including dietary changes and increased physical activity, is the cornerstone of treatment across all age groups. Nevertheless, non-pharmacological interventions have limitations in pediatric and elderly populations and are implemented less effectively in these groups than in middle-aged patients. Conclusions: The early identification of high-risk patients and implementation of multidisciplinary, age-targeted metabolic prevention strategies are essential to prevent MASLD progression and its non-liver complications.

Introduction: not needed Material and methods: not needed Results: not needed Conclusions: not needed

Background: Heart failure (HF) is a complex clinical syndrome, and its prognosis depends on many factors, including its etiology and the patient’s sex. We aimed to perform gendered evaluations on ischemic etiology’s impact on HF prognosis. Methods: Hospitalized patients and outpatients were enrolled in the Heart Failure Observational Study (HEROES), which is a prospective, multicenter cohort study, between April 2022 and January 2024. The primary endpoint was all-cause mortality. Results: Among 1410 patients included in the analysis (28.4% females and 71.6% males), 41.1% had ischemic HF etiology, and 58.9% had non-ischemic HF etiology. Ischemic etiology was identified in 28.5% of females and 46.0% of males; p < 0.001. The adjusted hazard ratio (aHR) was 1.16 (95% CI 0.85–1.58; p = 0.363) for all-cause mortality in the non-ischemic group relative to the ischemic reference category. The aHR for all-cause mortality in women relative to men was 1.14 (95% CI: 0.67–1.94; p = 0.633) for ischemic HF and 0.85 (95% CI: 0.56–1.27; p = 0.420) for non-ischemic HF. Conclusions: We found that ischemic and non-ischemic etiologies are associated with comparable all-cause mortality risk in patients with HF. Sex-stratified analyses revealed no significant mortality differentials between women and men within either etiologic category.