Sex differences and gender-related disparities in transcatheter tricuspid edge-to-edge repair for secondary tricuspid regurgitation: toward a personalized approach in cardiac care
Background Tricuspid regurgitation (TR) is a frequently underdiagnosed and undertreated condition that is linked to a poor prognosis. Tricuspid regurgitation (TR) may occur as atrial secondary TR (A-STR), which is associated with right atrial dilation and is more common in women, or as ventricular secondary TR (V-STR), which is associated with right ventricular dilation and is more frequently observed in men. Transcatheter edge-to-edge repair (TEER) of tricuspid regurgitation using the TriClip system (Abbott Cardiovascular) has demonstrated a favorable procedural safety profile and consistent improvements in TR severity, symptoms, and quality of life in selected patients at high or prohibitive surgical risk. Randomized 1-year trials did not show significant reductions in mortality or heart failure hospitalization; however, the subsequent 2-year TRILUMINATE follow-up reported fewer recurrent heart failure hospitalizations without a mortality benefit. Objective To review evidence on sex differences in tricuspid regurgitation across epidemiology, pathophysiology, guideline-directed management, and outcomes after T-TEER, together with gender-related disparities in access to care, in order to inform more personalized therapeutic strategies. Methods A structured narrative review of PubMed/MEDLINE was conducted from database inception through 31 January 2026. The electronic search was supplemented by backward citation searching and by the examination of relevant guidelines and consensus documents from official scientific society websites. Study identification and selection were documented using a PRISMA-informed flow diagram. Because of substantial clinical and methodological heterogeneity among the available studies, the evidence was synthesized narratively without quantitative meta-analysis. Evidence Randomized trials and registries demonstrate high rates of successful device implantation and tricuspid regurgitation reduction after tricuspid transcatheter edge-to-edge repair, although procedural endpoints, definitions, denominators, and assessment time points differ across studies and are therefore not directly comparable. At 1 year, the mean change in Kansas City Cardiomyopathy Questionnaire score from baseline was +12.3 points with T-TEER versus +0.6 points with medical therapy in the TRILUMINATE primary randomized cohort, and +15.9 versus +0.4 points in Tri.Fr, corresponding to reported between-group differences of +11.7 and +14.5 points, respectively. In the single-arm bRIGHT registry, the paired within-group mean KCCQ improvement from baseline was +19 points. Exploratory observational data suggest that sex may modify the prognostic association between right ventricular–pulmonary arterial coupling and mortality after TTVI; however, the proposed sex-specific TAPSE/mPAP thresholds were internally derived in a single retrospective cohort and require external validation before any clinical application. Conclusion TEER with the TriClip system appears to be a viable treatment option in women, who often present with A-STR and preserved right ventricular function. Available evidence suggests broadly comparable procedural success and symptomatic improvement in women and men, although most sex-specific findings derive from exploratory analyses. Integrating sex-specific considerations into diagnosis, treatment, and follow-up may help optimize intervention timing and improve the overall management of TR.
Authors
- Anna Vittoria Mattioli (ORCID: https://orcid.org/0000-0003-1487-9530)
- Pierluca Macripò
- Daniela Aschieri (ORCID: https://orcid.org/0000-0002-1577-5402)
- Francesca Coppi (ORCID: https://orcid.org/0000-0001-7715-6941)
- Gabriele Melegari (ORCID: https://orcid.org/0000-0003-4512-4835)
- Alberto Barbieri (ORCID: https://orcid.org/0000-0002-3904-1323)
- Carlo Mario Lombardi (ORCID: https://orcid.org/0000-0002-7120-5877)
- Moretti Martina
- Susan Darroudi (ORCID: https://orcid.org/0000-0002-5377-729X)
- Fabio Alfredo Sgura
- Marco Loffi (ORCID: https://orcid.org/0000-0002-1682-1386)
- Dalia Caleffi (ORCID: https://orcid.org/0009-0009-8696-5447)
- Giulia Ghizzoni (ORCID: https://orcid.org/0000-0002-7495-2093)
- Francesco Fedele (ORCID: https://orcid.org/0000-0003-2567-7918)
- Marianna Adamo (ORCID: https://orcid.org/0000-0002-3855-1815)
- Alessio Baccarani
- Gianluca Pagnoni (ORCID: https://orcid.org/0009-0008-7067-279X)
- Federica Arturi
- Arianna Maini (ORCID: https://orcid.org/0009-0007-4929-4678)
- Francesco Sbarra (ORCID: https://orcid.org/0009-0009-5244-0802)
- Francesco Marangi (ORCID: https://orcid.org/0009-0002-5161-5358)
- Damiano De Cesare
- Ashraf Nassar
- Simona Castellino
Institutions
- University of Modena and Reggio Emilia (IT)
- Surgical Specialties (Canada) (CA)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- Azienda Ospedaliero-Universitaria di Modena (IT)
- Guglielmo da Saliceto Hospital (IT)
- Surgical Specialties (United States) (US)
- Istituto Nazionale per le Ricerche Cardiovascolari (IT)
- Istituti Ospitalieri di Cremona (IT)
- Azienda Socio Sanitaria Territoriale di Cremona (IT)
- University of Brescia (IT)
- Sapienza University of Rome (IT)
- University of Bologna (IT)
Publication Details
- Journal
- Frontiers in Cardiovascular Medicine
- Published
- 2026-10-30
- DOI
- https://doi.org/10.3389/fcvm.2026.1831980
- Primary Topic
- Cardiac Valve Diseases and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Iowa Nutrient Research Center, College of Agriculture and Life Sciences, Iowa State University
- NextGenerationEU