Prognostic Utility of Mitral Regurgitation Proportionality in Patients Undergoing Transcatheter Edge-to-Edge Repair: REPAIR Study Insights

P. Jahn (Köln)¹, F. Schindhelm (Essen)², F. Rudolph (Bad Oeynhausen)³, P. Sagemeister (Leipzig)⁴, J. Haurand (Düsseldorf)⁵, J. Jobst (Gießen)⁶, M. Gröger (Ulm)⁷, L. Stolz (München)⁸, C. Schulz (Hamburg)⁹, C. Mues (Dortmund)¹⁰, D. Mustafa (Köln)¹, I. Hoerbrand (Heidelberg)¹¹, A. Sugiura (Bonn)¹², C. Wolff (Leipzig)⁴, P. Lurz (Mainz)¹³, J. von Stein (Köln)¹⁴, G. Ascione (New York)¹⁵, H. Guthoff (Köln)¹⁶, S. Baldus (Köln)¹⁴, W. Rottbauer (Ulm)⁷, M. Gercek (Bad Oeynhausen)³, R. Pfister (Köln)¹, T. Rassaf (Essen)², M. Weber (Bonn)¹², M. Konstandin (Heidelberg)¹¹, H. Möllmann (Dortmund)¹⁰, N. Schofer (Hamburg)¹⁷, J. Hausleiter (München)⁸, M. Keßler (Ulm)⁷, B. Unsöld (Gießen)¹⁸, P. Horn (Mönchengladbach)¹⁹, T. Kister (Leipzig)⁴, V. Rudolph (Bad Oeynhausen)³, A.-A. Mahabadi (Essen)², J. Granada (New York)¹⁵, V. Mauri (Köln)¹, P. von Stein (Köln)^1
1Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; ²Universitätsklinikum Essen Klinik für Kardiologie und Angiologie Essen, Deutschland; ³Herz- und Diabeteszentrum NRW Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland; ⁴Herzzentrum Leipzig - Universität Leipzig Klinik für Innere Medizin/Kardiologie Leipzig, Deutschland; ⁵Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland; ⁶Justus-Liebig-Universität Giessen Kardiologie und Angiologie Gießen, Deutschland; ⁷Universitätsklinikum Ulm Klinik für Innere Medizin II Ulm, Deutschland; ⁸LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland; ⁹Universitäres Herz- und Gefäßzentrum Klinik für Kardiologie mit Schwerpunkt Elektrophysiologie Hamburg, Deutschland; ¹⁰Kath. St. Paulus Gesellschaft Klinik für Innere Medizin I Dortmund, Deutschland; ¹¹Universitätsklinikum Heidelberg Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie Heidelberg, Deutschland; ¹²Universitätsklinikum Bonn Medizinische Klinik und Poliklinik II Bonn, Deutschland; ¹³Universitätsmedizin der Johannes Gutenberg-Universität Mainz Kardiologie 1, Zentrum für Kardiologie Mainz, Deutschland; ¹⁴Herzzentrum der Universität zu Köln Klinik für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; ¹⁵Cardiovascular Research Foundation New York, USA; ¹⁶Universitätsklinikum Köln Klinik III für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; ¹⁷Universitäres Herz- und Gefäßzentrum Allgemeine und Interventionelle Kardiologie Hamburg, Deutschland; ¹⁸Universitätsklinikum Gießen und Marburg GmbH Medizinische Klinik I - Kardiologie und Angiologie Gießen, Deutschland; ¹⁹Städtische Kliniken Mönchengladbach GmbH Kardiologie & Angiologie Mönchengladbach, Deutschland

Background
Mitral valve transcatheter edge-to-edge repair (M‑TEER) is an established treatment option for patients with heart failure and secondary mitral regurgitation (SMR). The proportionality concept proposed considering the ratio of effective regurgitation orifice area (EROA) and left ventricular end-diastolic volume (LVEDV) to facilitate patient selection. Large, contemporary real‑world data testing this concept is limited.

Objective
We therefore aimed to investigate whether baseline EROA/LVEDV ratio stratifies procedural and clinical outcomes in patients undergoing M-TEER.

Methods
Data was drawn from the investigator initiated, industry-independent, German REPAIR registry (REgistry of PAscal for mItral Regurgitation; DRKS00033959). The REPAIR registry includes patients treated with the PASCAL M-TEER system (Edwards Lifesciences) at 14 centers between 2019 and 2024. For this study, patients treated for SMR with available baseline EROA and LVEDV were dichotomized by median EROA/LVEDV. The primary endpoint was a 1-year composite of all-cause mortality or heart failure hospitalization. Secondary endpoints included MR reduction to ≤1+ at discharge, and NYHA class improvement. Sensitivity analyses were performed by tertile- and literature‑based (EROA/LVEDV ≥0.165 mm²/mL, <0.165 and >0.115 mm²/mL and ≤0.115 mm²/mL) grouping. Subgroup analyses were performed according to baseline left ventricular ejection fraction (LVEF) <50% versus ≥50%. Additionally, the associations of continuous EROA, LVEDV, and their ratio with the primary endpoint were assessed using multivariable Cox mixed-effects models adjusted for center effects, age, sex, LVEF, MR grade and NYHA functional class at baseline as well as baseline estimated glomerular filtration rate and records of coronary artery disease, atrial fibrillation or cardiac surgery in medical history.

Results
A total of 786 patients (mean age 76±10 years, 43% female, mean EROA 34±19 mm², mean LVEDV 158±78 mL, median EROA/LVEDV 0.21 mm²/mL, 87% NYHA class III/IV) were included. Technical success rate was 97% in both proportionality groups (p>0.999). MR ≤1+ at discharge was achieved in 75.2% vs. 73.0% (p=0.247) of ≥median EROA/LVEDV and <median EROA/LVEDV patients, respectively. No differences were observed in NYHA improvement. Kaplan-Meier estimates for the composite 1-year endpoint were 23.3% (95% CI: 18.5-27.8%) and 21.9% (95% CI: 17.0‑26.5%, log rank p=0.779). Findings were consistent in tertile and literature-based sensitivity analyses. In subgroup analyses stratified by baseline LVEF, no significant interaction was observed (interaction p=0.671). Neither EROA (HR per 10 mm² increase: 1.02, 95% CI: 0.92–1.14; p=0.695), LVEDV (HR per 10 mL increase: 1.01, 95% CI; 0.99–1.04; p=0.317), nor their ratio (HR: 1.67, 95% CI: 0.66–4.22; p=0.279) were independently associated with the primary endpoint.

Conclusions
In a large contemporary real-world cohort undergoing PASCAL M-TEER, the EROA/LVEDV proportionality framework did not stratify 1‑year all-cause mortality or heart failure hospitalization. MR reduction to ≤1+, and symptomatic response were similar as well. These findings highlight the need for multidimensional approaches exceeding EROA/LVEDV ratio for patient selection for M‑TEER.