Impact of Moderate-to-Severe Versus Severe Primary Mitral Regurgitation on Procedural Success and Clinical Outcomes After M-TEER: Data From the REPAIR Study

A. M. V. Stilkenböhmer (Bad Oeynhausen)¹, F. Rudolph (Bad Oeynhausen)², M. Gercek (Bad Oeynhausen)², M. Kassar (Basel)³, P. von Stein (Köln)⁴, V. Rudolph (Bad Oeynhausen)², L. Stolz (München)⁵, F. Schindhelm (Essen)⁶, T. Rassaf (Essen)⁶, A.-A. Mahabadi (Essen)⁶, H. Guthoff (Köln)⁷, S. Baldus (Köln)⁸, R. Pfister (Köln)⁴, P. Horn (Mönchengladbach)⁹, J. Haurand (Düsseldorf)¹⁰, M. Kelm (Düsseldorf)¹⁰, C. Schulz (Hamburg)¹¹, N. Schofer (Hamburg)¹², M. Keßler (Ulm)¹³, M. Gröger (Ulm)¹³, W. Rottbauer (Ulm)¹³, J. Hausleiter (München)⁵, C. Ennin (München)¹⁴, C. Mues (Dortmund)¹⁵, C. Grothusen (Dortmund)¹⁵, H. Möllmann (Dortmund)¹⁵, B. Unsöld (Gießen)¹⁶, K. D. Piayda (Gießen)¹⁶, M. Konstandin (Heidelberg)¹⁷, I. Hörbrand (Heidelberg)¹⁷, T. Kister (Leipzig)¹⁸, P. Sagmeister (Leipzig)¹⁸, H. Thiele (Leipzig)¹⁸, C. Wolff (Leipzig)¹⁸, M. Weber (Bonn)¹⁹, A. Sugiura (Bonn)¹⁹, G. Nickenig (Bonn)¹⁹, R. S. von Bardeleben (Mainz)²⁰, P. Lurz (Mainz)²¹, T. Ruf (Mainz)²¹, J. Granada (New York)²², L. Schneider (Ulm)¹³, K. Friedrichs (Bad Oeynhausen)²³, L. Widmann (Gießen)¹⁶, D. Mustafa (Köln)⁴, J. von Stein (Köln)⁸, P. Jahn (Köln)⁴, V. Mauri (Köln)⁴, J. Jobst (Gießen)^16
1Herz- und Diabeteszentrum NRW Klinik für Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland; ²Herz- und Diabeteszentrum NRW Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland; ³Universitätsspital Basel Abt. für Kardiologie Basel, Schweiz; ⁴Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; ⁵LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland; ⁶Universitätsklinikum Essen Klinik für Kardiologie und Angiologie Essen, Deutschland; ⁷Universitätsklinikum Köln Klinik III für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; ⁸Herzzentrum der Universität zu Köln Klinik für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; ⁹Städtische Kliniken Mönchengladbach GmbH Kardiologie & Angiologie Mönchengladbach, Deutschland; ¹⁰Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland; ¹¹Universitäres Herz- und Gefäßzentrum Klinik für Kardiologie mit Schwerpunkt Elektrophysiologie Hamburg, Deutschland; ¹²Universitäres Herz- und Gefäßzentrum Allgemeine und Interventionelle Kardiologie Hamburg, Deutschland; ¹³Universitätsklinikum Ulm Klinik für Innere Medizin II Ulm, Deutschland; ¹⁴LMU Klinikum Medizinische Klinik und Poliklinik I München, Deutschland; ¹⁵Kath. St. Paulus Gesellschaft Klinik für Innere Medizin I Dortmund, Deutschland; ¹⁶Universitätsklinikum Gießen und Marburg GmbH Medizinische Klinik I - Kardiologie und Angiologie Gießen, Deutschland; ¹⁷Universitätsklinikum Heidelberg Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie Heidelberg, Deutschland; ¹⁸Herzzentrum Leipzig - Universität Leipzig Klinik für Innere Medizin/Kardiologie Leipzig, Deutschland; ¹⁹Universitätsklinikum Bonn Medizinische Klinik und Poliklinik II Bonn, Deutschland; ²⁰Universitätsmedizin der Johannes Gutenberg-Universität Mainz Zentrum für Kardiologie im Herz- und Gefäßzentrum Mainz, Deutschland; ²¹Universitätsmedizin der Johannes Gutenberg-Universität Mainz Kardiologie 1, Zentrum für Kardiologie Mainz, Deutschland; ²²Cardiovascular Research Foundation (CRF) New York, USA; ²³Herz- und Diabeteszentrum NRW Klinik für Kardiologie Bad Oeynhausen, Deutschland

Background
Mitral valve transcatheter edge-to-edge repair (M-TEER) is an established therapy for patients with primary mitral regurgitation (PMR) at high surgical risk. The impact of baseline mitral regurgitation (MR) severity on MR reduction and clinical outcomes following M-TEER in PMR remains insufficiently investigated. The present study aims to address this gap.

Methods
REPAIR (REgistry of PAscal for mItral Regurgitation; DRKS00033959) is an investigator-initiated, multicentre registry including patients undergoing M-TEER with a PASCAL system (Edwards Lifesciences, Irvine, CA, USA) between 2019 and 2024 at 14 centres. Patients with PMR were included and stratified according to baseline MR severity into moderate-to-severe (grades 2+ and 3+) and severe PMR (grade 4+). The primary endpoint was survival free from heart failure hospitalisation (HFH) at one year. Secondary endpoints included the same endpoint stratified by residual MR grade at discharge, MR reduction to <=1+ at discharge, and 30-day functional improvement from NYHA class III/IV to class I/II.

Results
Among 2,601 patients in REPAIR, 846 were classified as PMR. Of these, 343 (40.5%) had moderate-to-severe and 503 (59.5%) had severe PMR. Baseline characteristics and symptom burden were comparable between groups, with median age 82.0 (IQR 78.2–85.1) vs. 81.9 (77.0–85.2) years. NYHA class III/IV was present in 264 (78.6%) vs. 415 (82.5%) patients. Markers of MR severity were higher in the severe vs. moderate-to-severe PMR group, including VC width (7.7 [6.5–9.5] vs. 7.0 [6.0–8.0] mm, p=0.001), EROA (46 [37–63] vs. 35 [30–50] mm², p=0.001), and RegVol (66 [50–89.5] vs. 51 [38.5–63.5] mL, p=0.001).

Kaplan-Meier analysis of the primary endpoint demonstrated comparable outcomes at 1 year, with estimated event-free survival of 83.4% in patients with moderate-to-severe and 82.6% in those with severe PMR (log-rank p=0.469, Figure 1). In contrast, residual MR had a significant impact on outcomes with higher residual MR grades (2-4+) associated with worse outcomes compared with residual MR 0-1+ (log-rank p=0.001, Figure 2).

M-TEER resulted in significant MR reduction in both groups (p<0.001 compared to baseline). Residual MR <=1+ was achieved in a higher proportion of patients with moderate-to-severe PMR (262/343 patients; 78.0%) than in patients with severe PMR (319/503; 66,2%; p<0.001, Figure 3). Functional status improved significantly in both groups after M-TEER without significant differences between groups with NYHA class III/IV symptoms decreasing from 78.4% to 27.7% in moderate-to-severe PMR (p<0.001) and from 82.5% to 29.3% in severe PMR (p < 0.001).

Conclusions
In this large, retrospective real-world registry of patients undergoing M-TEER with the Edwards PASCAL system, moderate-to-severe baseline PMR was associated with higher rates of optimal MR reduction, while survival and heart failure hospitalizations at one year and symptomatic improvement were comparable between groups.

Fig. 1: Kaplan-Meier analysis for the endpoint of survival free from heart failure hospitalisation according to baseline PMR severity

Fig. 2: Kaplan-Meier analysis for the endpoint of survival free from heart failure hospitalisation stratified by residual MR 0-1+ and 2-4+

Fig. 3: MR reduction at discharge according to baseline PMR severity

Fig. 4: NYHA distribution at baseline and at 30-day follow-up