Treatment gradients across the left ventricular ejection fraction spectrum in ambulatory and acute heart failure: a multinational registry analysis

Background The implementation of guideline-directed medical therapy (GDMT) across the spectrum of left ventricular ejection fraction (LVEF) remains suboptimal in real-world settings, particularly in mildly reduced and preserved LVEF phenotypes. Purpose To assess clinical profile, treatment patterns and outcomes across LVEF strata (≤40%, 41–50%, ≥50%) in ambulatory and acute decompensated heart failure (ADHF) within a large multinational registry. Methods We analyzed 6,729 patients from a large multinational prospective registry across 21 countries in the Americas, including both ambulatory HF and ADHF hospitalisations. Patients were categorized into three LVEF strata. Demographics, comorbidities, biomarkers, GDMT use and in-hospital mortality were compared across groups using appropriate statistical tests and trend analyses. Results In the overall cohort increasing LVEF was associated with older age (66-67 years in LVEF ≤40%, 68-69 years in LVEF 41-50% and 71-74 years in LVEF ≥50%; p-trend<0.001) and a lower proportion of men (62-67%, 56% and 47-48%, respectively; p-trend<0.001). Patients with LVEF ≥50% showed a lower prevalence of ischaemic aetiology compared with LVEF ≤40% and LVEF 41-50% (p-trend<0.001). A marked treatment gradient was observed across LVEF strata. In the ambulatory cohort, foundational therapy use declined progressively from 30% in LVEF ≤40% to 15% in LVEF 41–50% and 10% in LVEF ≥50% (p-trend<0.001) with similar reductions for sacubitril/valsartan, SGLT2 inhibitors and mineralocorticoid receptor antagonists (all p-trend<0.001). In ADHF, the prevalence of ischaemic aetiology was comparable in patients with LVEF ≤40% (46%) and LVEF 41–50% (47%) with a lower proportion in patients with LVEF ≥ 50% (36%), (p-trend <0.001). At discharge after ADHF, foundational therapy decreased progressively across increasing LVEF strata (30%, 15% and 10%, respectively; p-trend <0.001). Despite these therapeutic differences, in-hospital mortality did not significantly differ across LVEF categories (p-trend=0.08). Conclusions In this large real-world multinational registry across 21 countries in the Americas, including ambulatory and ADHF populations, significant treatment gradients exist across the LVEF spectrum, particularly in the mildly reduced range. These findings reveal a major population-level implementation gap and support targeted optimisation strategies across the full LVEF continuum in contemporary heart failure care.