Background and Aims
Women have been largely underrepresented in transcatheter aortic valve replacement (TAVR) trials for severe aortic stenosis (AS). Recently, sex-specific differences have gained interest, particularly regarding procedural strategies and outcomes. Women typically present at an older age with more symptomatic disease and have smaller annular dimensions. These differences may predispose women to complications such as prosthesis-patient mismatch (PPM) and could necessitate different procedural approaches. Recent trials like SMART and RHEIA have begun to explore these sex-specific and inherent anatomical differences, but their significance in large real-world populations remains unclear. This study aimed to assess variations in baseline characteristics, hemodynamic outcomes, PPM incidence, and their impact on three-year all-cause mortality.
Methods
We analyzed data from 20,094 patients in the IMPPACT TAVR registry, receiving TAVR for severe native AS across 26 high-volume centers in Europe and Israel between 2006 and 2022. PPM was classified based on Valve Academic Research Consortium-3 criteria. Kaplan-Meier estimates and Cox proportional hazards models were used to assess mortality, while logistic regression identified predictors of severe PPM.
Results
Women comprised 49.1% of the cohort, were older (81 vs. 80 years, p<0.001) and more symptomatic (NYHA ≥III: 74.4 vs. 67.6%, p<0.001). Aortic annulus area was smaller in women (409±65 vs. 513±82 mm², p<0.001) but pre-TAVR indexed aortic valve area (AVA) was similar (0.39±0.11 in women vs. 0.39±0.10 cm2/m2 in men, p=0.231) (B). Women more often received self-expanding (SE) valves (66.5 vs. 45.7%, p<0.001) and had higher rates of pre- (60.3 vs. 52.1%, p<0.001) and post-dilation (24.4 vs. 21.7%, p<0.001). Post-TAVR mean transvalvular pressure gradients (9.7±4.6 in women vs. 9.9±4.4 mmHg in men, p<0.001) and indexed effective orifice areas (1.01±0.28 in women vs. 0.99±0.27 cm²/m² in men, p<0.001) were comparable between sexes (B). Three-year mortality was lower in women (HR 0.80, 95% CI 0.75-0.86, p<0.001) (A). Severe PPM was less frequent in women (4.0 vs. 4.5%, p<0.001) (C) and was associated with increased mortality only in men (HR 1.35, 95% CI 1.10-1.65, p=0.004). Adjusting for comorbidities nullified the impact of PPM on mortality in both sexes (D).
Conclusions
This study highlights important sex-specific considerations in TAVR. A higher symptom burden in women while having comparable pre-TAVR AVA raises concerns about current guideline thresholds which do not account for inherent anatomical differences. Developing optimal sex-specific criteria could help ensure appropriate treatment in women. Their favorable survival underscores the likely benefits of timely intervention. Severe PPM was linked to increased mortality only in men, likely due to comorbidities causing low-flow states rather than true anatomical mismatch. These findings suggest that clinicians should adopt a comprehensive, patient-specific approach to risk assessment and management, rather than focusing solely on PPM avoidance. Future research should explore flow-independent methods for evaluating valve performance and its impact on outcomes, as well as refine sex-specific criteria to optimize timing of treatment, procedural strategies, and outcomes for both women and men.
