Clin Res Cardiol (2022).

Impact of sex on vascular closure device outcomes after transcatheter aortic valve implantation: A subgroup analysis of the randomized CHOICE-CLOSURE trial
I. Richter1, P. Hartung1, O. Dumpies1, D. Obradovic2, J. Wilde1, N. Majunke1, P. Boekstegers3, R. Müller3, M. Seyfarth4, M. M. Vorpahl4, P. Kiefer5, T. Noack5, S. Leontyev5, J. Rotta Detto Loria1, A.-K. Funkat6, S. Hohenstein6, S. Desch1, D. Holzhey7, H. Thiele1, M. Abdel-Wahab1, für die Studiengruppe: CHOICE-CLOSURE
1Klinik für Innere Medizin/Kardiologie, Herzzentrum Leipzig - Universität Leipzig, Leipzig; 2Klinik für Innere Medizin I - Kardiologie, Angiologie, Helios Park-Klinikum Leipzig, Leipzig; 3Herzzentrum Siegburg, Klinik für Kardiologie, Angiologie, HELIOS Klinikum Siegburg, Siegburg; 4Medizinische Klinik 3 - Kardiologie, Helios Klinikum Wuppertal - Herzzentrum, Wuppertal; 5Universitätsklinik für Herzchirurgie, Herzzentrum Leipzig - Universität Leipzig, Leipzig; 6Leipzig Heart Institute, Leipzig; 7Klinik für Herz- und Thoraxchirurgie, Helios Klinikum Wuppertal - Herzzentrum, Wuppertal;
Background: Female sex has been consistently described as a risk factor for bleeding and vascular complications after transcatheter aortic valve implantation (TAVI).  However, and despite the growing awareness about sex-specific disparities in this setting, studies investigating sex-specific treatment strategies of vascular access-site closure after TAVI remain limited. We therefore sought to evaluate sex-specific outcomes of percutaneous access-site closure techniques in the CHOICE-CLOSURE (Randomized Comparison of CatHeter-based Strategies fOr Interventional ACcess SitE CLOSURE during Transfemoral Transcatheter Aortic Valve Implantation) trial. 
Methods: The CHOICE-CLOSURE trial randomized 516 patients undergoing transfemoral TAVI to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) or a primary suture-based technique (ProGlide, Abbott Vascular). The primary endpoint of access-site or access-related major and minor vascular complications defined according to the Valve Academic Research Consortium-2 definition during index hospitalization was significantly less frequent in the suture-based group. This pre-specified subgroup analysis examines study outcome measures stratified by sex.
Results: The study population included 230 (44.6%) females (n=115 in each group) and 286 (55.4%) males (n=143 in each group). Compared to males, female patients were older (81.1 ± 5.52 vs. 80.1 ± 6.49 years, p=0.028) and had a significantly higher Society of Thoracic Surgeons score (4.52 ± 2.92 vs. 3.72, ± 2.77 %, p=0.002). In addition, females had significantly smaller vascular diameters (p<0.001) resulting in the use of significantly smaller sheath sizes (14.71 ± 1.50 vs. 15.46 ± 1.81 French, p<0.001).
The primary end-point was more common in the plug-based group compared to the suture-based group in both females (22.6% vs. 13.9%, relative risk [RR] 1.62, 95% confidence interval [CI] 0.92-2.86, p=0.125) and males (16.8% vs. 10.5%, RR 1.60, 95%CI 0.88-2.92, p=0.168). Females treated with the plug-based technique experienced significantly higher rates of pseudoaneurysms and clinically-significant access-site hematomas compared to those treated with the suture-based technique (6.1% vs. 0%, p=0.021, and 16.5% vs. 7.0%, p=0.041, respectively), with a similar trend in males (7% vs. 4.2%, p=0.440, and 14.7% vs. 7.7%, p=0.091). Median time to hemostasis was significantly shorter with the plug-based technique in both sex groups (females: 67 [34, 148] vs. 226 [152, 280] seconds, p<0.001, males: 88 [30,180] vs. 248 [182-346] seconds, p<0.001).
Conclusion: Despite female-specific vascular access site characteristics, findings of this subgroup analysis of the CHOICE-CLOSURE trial support the overall superiority of the suture-based technique compared to the plug-based technique during transfemoral TAVI, with no sex-specific interaction.