Sex Differences in Hemodynamics and Outcomes after Transcatheter Aortic Valve Replacement

Clin Res Cardiol (2025). DOI 10.1007/s00392-025-02625-4
H. Guthoff (Köln)¹, M. Abdel-Wahab (Leipzig)², W.-K. Kim (Bad Nauheim)³, H. S. Wienemann (Köln)⁴, J. Shamekhi (Bonn)⁵, C. Eckel (Dortmund)⁶, I. von der Heide (Hamburg)⁷, V. Veulemans (Frankfurt am Main)⁸, M. Landt (Bad Segeberg)⁹, J. Schewel (Hamburg)¹⁰, N. M. Van Mieghem (Rotterdam)¹¹, R. Adrichem (Rotterdam)¹¹, S. Toggweiler (Luzern)¹², T. Rheude (München)¹³, S. Macherey-Meyer (Köln)¹⁴, S. Bleiziffer (Bad Oeynhausen)¹⁵, B. Al-Kassou (Bonn)⁵, S. Nienaber (Köln)⁴, J. Wrobel (Köln)⁴, I. Richter (Leipzig)¹⁶, J. Blumenstein (Dortmund)⁶, M. Renker (Bad Nauheim)³, E. Charitos (Bad Nauheim)³, N. Schofer (Hamburg)¹⁷, T. Zeus (Düsseldorf)¹⁸, T. Schmidt (Hamburg)¹⁹, P. von Stein (Köln)⁴, H. Thiele (Leipzig)², G. Witberg (Petah Tikva)²⁰, M. Adam (Köln)⁴, S. Baldus (Köln)¹⁴, T. K. Rudolph (Bad Oeynhausen)²¹, V. Mauri (Köln)^4
1Universitätsklinikum Köln Klinik III für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; ²Herzzentrum Leipzig - Universität Leipzig Klinik für Innere Medizin/Kardiologie Leipzig, Deutschland; ³Kerckhoff Klinik GmbH Abteilung für Kardiologie Bad Nauheim, Deutschland; ⁴Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; ⁵Universitätsklinikum Bonn Medizinische Klinik und Poliklinik II Bonn, Deutschland; ⁶Kath. St. Paulus Gesellschaft Klinik für Innere Medizin I Dortmund, Deutschland; ⁷Universitätsklinikum Hamburg-Eppendorf Klinik für Kardiologie Hamburg, Deutschland; ⁸Universitätsklinikum Frankfurt Med. Klinik III - Kardiologie, Angiologie Frankfurt am Main, Deutschland; ⁹Segeberger Kliniken GmbH Herzzentrum Bad Segeberg, Deutschland; ¹⁰Katholisches Marienkrankenhaus gGmbH Kardiologie und Angiologie Hamburg, Deutschland; ¹¹Erasmus Medical Center Department of Interventional Cardiology Rotterdam, Niederlande; ¹²Luzerner Kantonsspital Herzzentrum Luzern, Schweiz; ¹³Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland; ¹⁴Herzzentrum der Universität zu Köln Klinik für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; ¹⁵Herz- und Diabeteszentrum NRW Klinik für Thorax- und Kardiovaskularchirurgie Bad Oeynhausen, Deutschland; ¹⁶Helios Park-Klinikum Leipzig Klinik für Innere Medizin I - Kardiologie, Angiologie Leipzig, Deutschland; ¹⁷Universitäres Herz- und Gefäßzentrum Hamburg Allgemeine und Interventionelle Kardiologie Hamburg, Deutschland; ¹⁸Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland; ¹⁹Asklepios Westklinikum Rissen Abteilung für Kardiologie Hamburg, Deutschland; ²⁰Rabin Medical Center Division of Cardiology Petah Tikva, Deutschland; ²¹Herz- und Diabeteszentrum NRW Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland

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.