Sex-Specific Prognostic Significance of Interventricular Septal Thickness in Heart Failure

Abstract Background Interventricular septal (IVS) thickness is routinely measured by echocardiography, yet its prognostic significance in heart failure (HF), and whether it differs by sex, remains uncertain. Methods This retrospective study included patients with HF from the SHEBAHEART registry (2009-2025). IVS thickness was classified as normal (<1.1 cm), mildly thickened (≥1.1 to ≤1.3 cm), or severely thickened (>1.3 cm), using identical thresholds by sex. Associations with all-cause mortality were evaluated using Kaplan-Meier analysis and multivariable Cox models adjusted for age, body mass index, systolic blood pressure, comorbidities, and left ventricular ejection fraction, with formal testing for sex-by-IVS interaction. Results Among 20,836 patients (median age, 74 years; 39% women), 41% had mild and 18% had severe IVS thickening. During a median follow-up of 4 years, 11,930 patients (57%) died; 4-year Kaplan-Meier cumulative mortality increased across IVS categories (35%, 39%, and 42%; P < 0.001). In primary complete-case analysis (n = 13,902), the sex-by-IVS interaction was significant (P = 0.030). Adjusted hazard ratios (95% confidence intervals) for mild and severe thickening were 1.16 (1.07-1.26) and 1.19 (1.08-1.32) in women, compared with 1.02 (0.96-1.09) and 1.07 (0.99-1.16) in men. The sex-by-IVS interaction remained significant in multiple-imputation and time-varying Cox analyses, but not with sex-specific IVS reference partitions. Conclusions With common absolute IVS thresholds, increased septal thickness was more strongly associated with all-cause mortality in women than in men with HF. These findings support evaluation of IVS thickness as a potential component of sex-specific risk stratification in HF.