Adverse effect of left ventricular hypertrophy in women with heart failure

Background Left ventricular hypertrophy is a hallmark of adverse remodeling in heart failure (HF), yet commonly used echocardiographic measures provide limited insight into sex-specific risk. Interventricular septal (IVS) thickness is routinely measured, but its independent prognostic value and potential sex-related differences in HF outcomes remain poorly defined. Purpose To determine whether IVS thickness independently predicts mortality in HF and to assess whether its prognostic impact differs between women and men. Methods We conducted a retrospective cohort study of HF patients evaluated at our medical center between 2009 and 2025 within the SHEBAHEART registry. IVS thickness measured by transthoracic echocardiography was categorized as normal (<1.1 cm), mildly increased (1.1-1.3 cm), or severely increased (>1.3 cm). Associations with all-cause mortality were evaluated using Kaplan-Meier analysis and multivariable Cox regression, including sex interaction testing and adjustment for anthropometric variables, comorbidities, and echocardiographic parameters. Results The cohort included 20,836 patients (median age 74 years; 39% women). Mild and severe septal hypertrophy were present in 41% and 18% of patients, respectively. Increasing IVS thickness was associated with older age, higher blood pressure, and greater comorbidity burden. During follow-up (median 4-years), 11,930 patients (57%) died, with mortality rising progressively across IVS categories (50%, 62%, and 63%; log-rank p<0.001) (Figure 1). Each 1-mm increase in IVS thickness was associated with a 5.5% increase in the risk of mortality. A significant interaction between sex and septal thickness was observed (p-interaction <0.05). In women, severe septal hypertrophy remained independently associated with increased mortality (adjusted HR 1.23; 95% CI 1.01-1.50; p<0.01). In contrast, the association in men was attenuated after age adjustment and was not significant in fully adjusted models (Figure 2). Conclusion In a large contemporary HF cohort, interventricular septal thickness emerged as a readily available, sex-specific prognostic marker, identifying excess mortality risk in women but not in men. These findings reveal an underrecognized dimension of cardiac remodeling and support the incorporation of septal thickness into sex-specific risk-stratification frameworks, potentially improving precision phenotyping and personalized management in heart failure.