Sex-Dependent molecular Fingerprint of Left Ventricular Reverse Remodeling After Surgical Aortic Valve Replacement

All articles of this category (opens in new window) Background: Aortic stenosis (AS) imposes chronic left ventricular (LV) pressure overload, leading to hypertrophy, remodeling, and, without intervention, ultimately to heart failure. Surgical aortic valve replacement (SAVR) relieves outflow obstruction and induces reverse remodeling, characterized by partial restoration of LV´s prepressure overload state. Methods: We studied 164 patients undergoing SAVR, with comprehensive assessments at four timepoints. Evaluations included heart failure status, quality-of-life scores, echocardiography (aortic flow velocity, regurgitation, valve area, LV ejection fraction [LVEF], LV and atrial volumes, wall thickness), biomarkers of myocardial stretch and injury, renal and hepatic function, lipid profile, circulating mRNAs, and histological analysis of perioperative LV biopsies. Results: Women presented with more pronounced baseline LV hypertrophy but exhibited faster and more pronounced reverse remodeling than men, with greater reductions in LV mass and septal thickness indexed. Despite higher age and worse heart failure scores at baseline, women achieved superior structural recovery after 1 year. However, women had lower glomerular filtration rate, higher creatinine, and greater susceptibility to renal dysfunction. LVEF improved significantly in both sexes. N-terminal pro-B-type natriuretic peptide was higher in women at baseline and postoperatively, consistent with longer hypertension exposure and greater myocardial stretch. Transcriptomic profiling of total blood identified sex-specific molecular patterns. Differentially expressed mRNAs were enriched in pathways regulating extracellular matrix remodeling, fibroblast activation, angiogenesis, immune signaling, and oxidative stress. In women, early post-SAVR enrichment included matrix-degrading enzymes (MMP14, ADAM9) and angiogenic/fibrotic regulators (PDGFC, WNT pathways), while men showed enrichment of oxidative stress- and membrane transport–related transcripts (GLRX5, DNAJ30, FZD5). Conclusion: The timely performed SAVR restores normal flow dynamics, improves LV structure and function, and enhances functional status and quality of life. Gender-specific differences were evident: women demonstrated greater reverse remodeling despite higher age and worse baseline parameters, yet were more vulnerable to renal impairment. Integrating molecular and structural data may enable early identification of nonresponders and guide personalized therapeutic strategies after SAVR. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany