Misperception in Heart Failure Phenotyping: Moving Beyond the Chamber to the Myocardium

Left ventricular ejection fraction (LVEF) remains the cornerstone of heart failure (HF) phenotyping, yet it weakly correlates with outcomes and may overestimate systolic function, especially in elderly women with altered left ventricular geometry. We evaluated the limitations of conventional LVEF-based phenotyping, assessed sex-specific differences in left ventricular geometry, and tested whether geometry-adjusted LVEF or left ventricular global longitudinal strain (LVGLS) improves prognostic performance.

We retrospectively analyzed 3688 patients (53.0% men; median age, 70 years) hospitalized for acute HF from the STRATS-AHF (Strain for Risk Assessment and Therapeutic Strategies in Patients With Acute Heart Failure) multicenter registry (2009-2016). Population distributions of LVEF, LVGLS, and a geometry-adjusted index (iLVEF_RWT: LVEF indexed to relative wall thickness) were compared by sex, and their prognostic value for all-cause mortality was evaluated using Cox regression models.

Women showed a bimodal distribution of LVEF and a steeper age-related increase compared with men, accompanied by higher relative wall thickness. In contrast, both iLVEF_RWT and LVGLS followed unimodal Gaussian distributions across sexes. During a median follow-up of 32.6 months (interquartile range, 12.6-55.0), 1427 patients (38.7%) died. All 3 indices predicted mortality (per 10% decrease in LVEF: hazard ratio (HR) 1.16; per 10-unit decrease in iLVEF_RWT: HR 1.05; per 1% decrease in LVGLS: HR 1.07; all P<0.001). The prognostic value of LVEF was attenuated in patients with concentric remodeling (P for interaction =0.035), whereas iLVEF_RWT and LVGLS remained predictive regardless of geometry.

LVEF may overestimate systolic function in concentric remodeling, particularly in elderly women. Geometry-adjusted iLVEF_RWT and LVGLS can provide consistent physiological interpretation and robust prognostic utility.