Sex-Dependent Discrepancies of Left Ventricular Reverse Remodeling after Surgical Aortic Valve Replacement

Background: Aortic stenosis leads to restricted blood outflow from the left ventricle (LV), causing chronic pressure overload, ventricular remodeling, and eventually heart failure. Surgical aortic valve replacement (SAVR) is known to promote reverse remodeling, which involves physiological and structural adaptation of the heart following the cessation of pressure overload. This study investigates the impact of SAVR in 112 in reverse remodeling.

Methods: We analyzed patients’ characteristics and performed measurements before surgery, at 4 to 6 days, 6 months, and 12 months post-SAVR. These included: Heart failure evaluation via New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) scoring. Quality of life assessments were performed using the Kansas City Cardiomyopathy and SF-12. Echocardiographic parameters: aortic flow velocity, regurgitation, aortic valve area, LV ejection fraction (LVEF), LV and atrial volumes, interventricular septum and posterior wall thickness, mitral inflow, mitral annulus movement, and TAPSE for right ventricular function. Biomarkers for myocardial stretch and cardiac damage, kidney function, liver function, lipid profile, and proteomics of EDTA plasma. Histological analysis of perioperative LV biopsies for structural and fibrosis characterization.

Results: All patients survived SAVR, with significant reductions in maximal aortic blood flow velocity observed in both sexes at 4 to 6 days post-surgery. Although female patients had greater initial LV hypertrophy, they demonstrated faster reverse remodeling than males. LVEF increased in both sexes. Sex-dependent differences in NT-proBNP levels were observed during remodeling. SAVR improved NYHA and CCS scores for both sexes, with women showing higher initial NYHA scores. Analysis of differentially expressed circulating mRNAs identified pathways related to matrisome, fibroblast activation, cell–cell contact, and immune response. A principal component analysis revealed distinct sex-based transcriptomic profiles during reverse remodeling.

Conclusion: SAVR effectively restored normal LV-to-aortic blood flow, reversed cardiac remodeling, and improved NYHA and CCS scores in both sexes. However, women presented for surgery at a more advanced age, with greater hypertrophy and were more prone to kidney dysfunction. This study highlights sex-based differences in the dynamics of reverse remodeling, suggesting that detailed analysis of echocardiographic parameters and fluid biopsies may help identify non-responders earlier, allowing for optimized interventions.

Publication History

Article published online:
11 February 2025