Sex differences in cardiovascular complications after allogeneic hematopoietic stem cell transplantation: the prognostic role of pre-therapeutic echocardiography and left ventricular ejection fraction

Abstract Background Allogeneic hematopoietic stem cell transplantation (alloHSCT) represents a major therapeutic challenge in the treatment of hematologic malignancies. However, the conditioning regimens, including chemotherapy and radiotherapy, are associated with both short- and long-term cardiotoxicity, increasing the risk of major adverse cardiovascular events (MACE). While sex-based differences in cardiovascular disease (CVD) have been extensively documented in the general population, their impact on post-alloHSCT outcomes and the prognostic value of echocardiographic parameters remain poorly understood. Purpose To study sex differences in alloHSCT outcomes and identify predictors of MACE by sex, including echocardiographic markers and particularly left ventricular ejection fraction (LVEF), in a large cohort of alloHSCT patients. Methods We conducted a retrospective, single-center cohort study including all patients undergoing alloHSCT between 2011 and 2020. The primary outcome was MACE, including cardiovascular death, heart failure (HF), arrhythmias, acute arterial events, proximal venous thromboembolism (VTE), myocarditis, and pericardial disease. Echocardiographic data, including baseline LVEF, were systematically collected. A propensity score matching was performed to compare males and females. Predictors of early (≤100 days) and late MACE (>100 days) were identified using Fine-and-Gray models. Results In the propensity-score matched population (N=1,100 patients, 50% males and 50% females, mean age 44±16 years), 26% patients experienced MACE after a median (IQR) follow-up of 2 (1-5) years. The cumulative incidence of early MACE (≤100 days) was similar between males and females (12.4% versus 11.3%, p=0.56), with the primary causes being HF and supraventricular arrhythmia in males, and HF and pericardial disease in females. At long term, the cumulative incidence of late MACE remained comparable between males and females (17.1% vs. 16.8%, p=0.96), with HF, VTE, and pericardial disease as the predominant causes. Among echocardiographic parameters, a baseline LVEF