Sex differences in hemodynamics and outcomes after transcatheter aortic valve replacement

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Abstract Background Women remain underrepresented in transcatheter aortic valve replacement (TAVR) trials, despite well-recognized anatomical differences that necessitate tailored procedural strategies. This study assessed sex-specific differences in baseline characteristics, procedural approaches, hemodynamic outcomes, and their impact on 5-year all-cause mortality. Methods We analyzed data from 20,094 patients in the IMPPACT TAVR registry. Hemodynamic outcomes, including prosthesis-patient mismatch (PPM), were defined according to Valve Academic Research Consortium-3 criteria. Kaplan–Meier and Cox models assessed 5-year all-cause mortality, and logistic regression identified predictors of PPM. Results Women comprised 49.1% of the cohort. They were older (81.4 vs. 80.2 years, p < 0.001), more symptomatic (NYHA ≥ III: 74.4% vs. 67.6%, p < 0.001), and more frequently received self-expanding valves (66.5% vs. 45.7%, p < 0.001). Post-TAVR indexed effective orifice areas were slightly larger in women (1.01 ± 0.28 vs. 0.99 ± 0.27cm 2 /m 2 , p < 0.001). Five-year mortality was lower in women (HR 0.81, 95% CI 0.76–0.86, p < 0.001). Severe PPM occurred less frequently in women (4.0% vs. 4.5%, p < 0.001) and was associated with increased mortality only in men (HR 1.32, 95% CI 1.10–1.59, p = 0.002). Adjustment for comorbidities nullified the association between PPM and mortality in both sexes. Conclusions In this international TAVR cohort, women, despite being older, demonstrated better survival than men, with comparable postprocedural hemodynamic outcomes. Severe PPM was associated with increased mortality only in men, likely reflecting underlying comorbidities and low-flow states. After adjustment for confounders, PPM was no longer associated with survival in either sex. These findings underscore the need for strategies accounting for both procedural and patient-specific risks, beyond prosthesis hemodynamics. Graphical Abstract Sex-Specific Differences in TAVR, ( A ) Kaplan-Meier curves with 95% CI for all-cause mortality stratified by sex. ( B ) TTE-derived non-indexed and BSA-indexed pre-TAVR AVA and post-TAVR EOA stratified by sex. ( C ) Distribution of PPM severity stratified by device type and sex. ( D ) Forest plot showing results of the multivariable Cox proportional hazards model for 5-year all-cause mortality including a comparison of severe PPM against non-severe PPM (no and moderate) in men and women. HR with 95% CI are shown. Study center was included as a random effect in the model. Abbreviations: AVA: aortic valve area; BE: balloon-expandable; CI: confidence interval; EOA: effective orifice area; GFR: glomerular filtration rate; HR: hazard ratio; KM: Kaplan-Meier; LVEF: left ventricular ejection fraction; PPM: prosthesis-patient mismatch; PVL: paravalvular leak; SE: self-expanding

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