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Peer-reviewedCC BY 4.0Frontiers in Cardiovascular Medicine

Sex differences and gender-related disparities in transcatheter tricuspid edge-to-edge repair for secondary tricuspid regurgitation: toward a personalized approach in cardiac care

12 more authors
10 affiliations
  1. 1Cardiologic Unit, Specialistic Medicine Department, Guglielmo da Saliceto Hospital
  2. 2National Institute for Cardiovascular Research (INRC)
  3. 3Cardiology Division, Department of Biomedical Metabolic and Neural Sciences, University of Modena and Reggio Emilia
  4. 4Division of Cardiology, Cremona Hospital, Division of Cardiology, Azienda Socio-Sanitaria Territoriale di Cremona
  5. 5Cardiology Division, Azienda Ospedaliera Universitaria di Modena
  6. 6School of Anaesthesia and Intensive Care, University of Modena and Reggio Emilia
  7. 7Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia
  8. 8Department of Quality of Life, University of Bologna - Alma Mater Studiorum
  9. 9Emeritus Professor of Cardiology, Sapienza University of Rome
  10. 10Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Institute of Cardiology, ASST Spedali Civili, University of Brescia

Abstract

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.

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BibTeX
@article{pagnoni2026differences,
  title = {{Sex differences and gender-related disparities in transcatheter tricuspid edge-to-edge repair for secondary tricuspid regurgitation: toward a personalized approach in cardiac care}},
  author = {Gianluca Pagnoni and Francesco Sbarra and Arianna Maini and Ashraf Nassar and Simona Castellino and Francesco Marangi and Damiano De Cesare and Martina Moretti and Pierluca Macripò and Marco Loffi and Giulia Ghizzoni and Dalia Caleffi and Federica Arturi and Gabriele Melegari and Susan Darroudi and Alessio Baccarani and Fabio Alfredo Sgura and Anna Vittoria Mattioli and Daniela Aschieri and Francesco Fedele and Carlo Mario Lombardi and Marianna Adamo and Alberto Barbieri and Francesca Coppi},
  journal = {Frontiers in Cardiovascular Medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fcvm.2026.1831980},
  url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1831980/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Sex differences and gender-related disparities in transcatheter tricuspid edge-to-edge repair for secondary tricuspid regurgitation: toward a personalized approach in cardiac care
AU  - Gianluca Pagnoni
AU  - Francesco Sbarra
AU  - Arianna Maini
AU  - Ashraf Nassar
AU  - Simona Castellino
AU  - Francesco Marangi
AU  - Damiano De Cesare
AU  - Martina Moretti
AU  - Pierluca Macripò
AU  - Marco Loffi
AU  - Giulia Ghizzoni
AU  - Dalia Caleffi
AU  - Federica Arturi
AU  - Gabriele Melegari
AU  - Susan Darroudi
AU  - Alessio Baccarani
AU  - Fabio Alfredo Sgura
AU  - Anna Vittoria Mattioli
AU  - Daniela Aschieri
AU  - Francesco Fedele
AU  - Carlo Mario Lombardi
AU  - Marianna Adamo
AU  - Alberto Barbieri
AU  - Francesca Coppi
PY  - 2026
DA  - 2026/10/30
JO  - Frontiers in Cardiovascular Medicine
DO  - 10.3389/fcvm.2026.1831980
UR  - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1831980/full
AB  - 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.
SN  - 2297-055X
ER  -