Percutaneous mitral repair as treatment in HFrEF (MitraClip/TEER) overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nehal Eid, M.D.[2]

Definition and principle

Mitral transcatheter edge-to-edge repair (M-TEER) is a transseptal, catheter-based therapy that approximates the anterior and posterior mitral valve leaflets, restores leaflet coaptation, and creates a double-orifice valve to reduce mitral regurgitation. M-TEER is the procedural term; MitraClip and PASCAL are device platforms.[1][2]

Target population

The principal evidence-based population comprises patients with heart failure with reduced ejection fraction and chronic severe ventricular secondary mitral regurgitation (vSMR) who remain symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT), including cardiac resynchronization therapy when indicated. ACC/AHA guideline-based COAPT selection generally includes left ventricular ejection fraction (LVEF) 20%–50%, left ventricular end-systolic diameter (LVESD) ≤70 mm, pulmonary artery systolic pressure ≤70 mm Hg, and suitable anatomy on transesophageal echocardiography—principally leaflet coaptation depth and length, inter-leaflet grasping-zone distance, and the presence, extent, and distribution of leaflet calcification.[3][4][1]

Atrial secondary mitral regurgitation (aSMR) is a separate phenotype, usually associated with annular and left atrial dilation, atrial fibrillation, and preserved LV systolic function. Its M-TEER evidence is observational rather than randomized; a core-laboratory analysis from the EXPANDed studies reported high procedural success, durable MR reduction, improved health status, and fewer HF hospitalizations.[5] American guidance includes a Class IIb-B recommendation for mitral surgery in patients with aSMR, preserved LVEF, and persistent symptoms despite GDMT; there is no corresponding European recommendation.[6]

Summary of evidence

  • COAPT enrolled 614 patients with symptomatic secondary MR despite maximally tolerated GDMT. M-TEER reduced all HF hospitalizations within 24 months (35.8% vs 67.9% per patient-year; HR 0.53; 95% CI 0.40–0.70) and all-cause death within 24 months (29.1% vs 46.1%; HR 0.62; 95% CI 0.46–0.82). The HF-hospitalization benefit emerged within 30 days, whereas the mortality benefit emerged predominantly after 1 year.[7][8]
  • Through 5 years in COAPT, the annualized HF-hospitalization rate remained lower with M-TEER (33.1% vs 57.2% per year; HR 0.53; 95% CI 0.41–0.68), as did all-cause mortality (57.3% vs 67.2%; HR 0.72; 95% CI 0.58–0.89). Benefit was consistent across ischemic and nonischemic cardiomyopathy and high and non-high surgical risk; in the echocardiographic substudy, benefit was independent of baseline LVEF, LV volumes, right ventricular systolic pressure, and MR or tricuspid-regurgitation severity, with no significant treatment interactions. However, a post hoc analysis of the small COAPT subgroup resembling MITRA-FR patients—those whose MR was judged proportionate to the degree of LV dilation—did not demonstrate benefit from M-TEER; subgroup consistency therefore should not be interpreted as excluding a phenotype effect. Most mortality benefit accrued during the first 2 years and most hospitalization benefit during the first 3 years; later estimates were attenuated by protocol-permitted crossover in 44.9% of control patients surviving to 2 years. Device-specific safety events occurred in 4 of 293 treated patients (1.4%), all within 30 days.[9][10][1]
  • COAPT-PAS assessed real-world applicability in 5,000 consecutive patients with secondary MR treated at 406 US centers. Despite more comorbidities, more severe HF, and less GDMT than the randomized-trial populations, the implant rate was 97.7%, MR was reduced to ≤2+ at 1 year in 90.7%, KCCQ improved by 29 points, and 1-year HF hospitalization was 18.9%. One-year all-cause mortality or HF hospitalization was 33.7%, comparable to the COAPT randomized device arm (33.5%) and lower than its GDMT arm (46.2%); 1-year all-cause mortality was 22.2%, 19.1%, and 23.1%, respectively.[11]
  • MITRA-FR randomized 304 analyzed patients (307 enrolled) with LVEF 15%–40% and secondary MR defined by effective regurgitant orifice area ≥20 mm² or regurgitant volume ≥30 mL. The composite of all-cause death or unplanned HF hospitalization occurred at 12 months in 54.6% versus 51.3% (HR 1.16; 95% CI 0.73–1.84; P=0.53) and at 24 months in 63.8% versus 67.1% (HR 1.01; 95% CI 0.77–1.34), with no difference in all-cause mortality (34.9% vs 34.2%).[12]
  • Compared with COAPT, MITRA-FR enrolled patients with less severe MR (mean effective regurgitant orifice area 0.31 vs 0.41 cm²) and greater LV dilation (mean indexed LV end-diastolic volume 135 vs 101 mL/m²). The 2-year composite event rates in the medical-therapy groups were nearly identical (67.1% in MITRA-FR vs 67.9% in COAPT), indicating that trial discordance arose primarily from outcomes in the intervention groups rather than differing control-group risk. Other proposed contributors include patient selection, rigor of GDMT optimization, procedural success, operator experience, and durability of MR reduction.[13][14]
  • RESHAPE-HF2 enrolled 505 patients with predominantly moderate-to-severe functional MR. M-TEER reduced first or recurrent HF hospitalization or cardiovascular death (rate ratio 0.64; 95% CI 0.48–0.85), reduced HF hospitalization, and improved health status, but did not demonstrate an all-cause mortality benefit.[15]
  • MATTERHORN randomized 210 patients at high surgical risk with secondary MR to M-TEER or mitral-valve surgery. It enrolled patients across a broad LVEF range (mean LVEF 43.0±11.7%), limiting direct extrapolation to an exclusively HFrEF population. M-TEER was noninferior for the 1-year composite of death, HF hospitalization, mitral reintervention, assist-device implantation, or stroke (16.7% vs 22.5%), with fewer 30-day primary safety events (14.9% vs 54.8%).[16]

Current guideline and regulatory position

The ACC/AHA guideline assigns M-TEER a Class IIa-B recommendation for appropriately selected patients with chronic severe secondary MR who remain symptomatic despite optimal GDMT and meet COAPT-like ventricular, pulmonary-pressure, and anatomic criteria.[3][6]

The structural difference between the American and European frameworks is the surgical-eligibility precondition. European guidelines recommend M-TEER only in patients not eligible for surgery who additionally meet criteria suggesting an increased chance of responding to the procedure (Class IIa-B), whereas American guidance bases candidacy on appropriate anatomy and COAPT-like criteria without requiring surgical ineligibility. European guidance also positions M-TEER or other transcatheter mitral intervention within heart-team evaluation of advanced-HF therapies for high-risk symptomatic patients who are not eligible for surgery and do not meet response criteria, after careful evaluation for left ventricular assist device implantation or heart transplantation (Class IIb-C).[6]

The transatlantic class-of-recommendation divergence for M-TEER concerns primary rather than secondary MR. In patients with favorable anatomy, severe symptoms, high or prohibitive surgical risk, and no evidence of futility, the American recommendation is Class IIa-B and the European recommendation is Class IIb-B.[6][2]

Guideline frameworks differ in quantitative MR-severity thresholds, and the divergence is not fully resolved. European guidance has applied lower cutoffs—effective regurgitant orifice area ≥0.20 cm² and regurgitant volume ≥30 mL—derived from natural-history studies, whereas American recommendations retain the conventional severe-MR threshold of effective regurgitant orifice area ≥0.40 cm²; comparative analyses have also framed the practical difference as approximately 30 versus 40 mm².[1][17]

M-TEER is positioned against weakly recommended surgical alternatives. Mitral surgery for vSMR with persistent symptoms despite GDMT is Class IIb-B in American guidance and Class IIb-C in European guidance when the patient is considered appropriate for surgery. Mitral surgery performed during coronary artery bypass grafting is Class IIa-B in American guidance and Class I-B in European guidance, which extends the recommendation to other indicated cardiac surgery.[6]

Secondary MR may nevertheless be severe at an effective regurgitant orifice area ≥0.30 cm² because two-dimensional proximal isovelocity surface area methods can underestimate a crescentic regurgitant orifice. Quantitative thresholds must also be interpreted relative to LV volume: an effective regurgitant orifice area of 0.30 cm² with a regurgitant volume of 45 mL represents a regurgitant fraction of 75% in a small ventricle but 37.5% in a markedly dilated ventricle. No single echocardiographic parameter defines severity; an integrative assessment is required.[18][1]

Following the 2013 approval of MitraClip for selected patients with primary MR at prohibitive surgical risk, the US FDA extended the indication in March 2019 to symptomatic patients with moderate-to-severe or severe secondary MR (MR grade >III per American Society of Echocardiography criteria), LVEF >20% and <50%, LVESD <70 mm, persistent symptoms despite maximally tolerated GDMT, and mitral anatomy suitable for transcatheter repair as determined by a multidisciplinary heart team.[8][18][1] These strict regulatory inequalities differ slightly from the inclusive 20%–50% and ≤70-mm guideline selection boundaries.

M-TEER is an adjunct to, and not a substitute for, optimized GDMT. HF therapy should be initiated and titrated first, followed by reassessment of MR severity and symptoms. Candidate selection should occur through a multidisciplinary heart/valve team with HF and electrophysiology input when appropriate. Optimization affects eligibility as well as outcome: GDMT reduces LV volumes and secondary MR severity, and initiation of sacubitril/valsartan reduced potential eligibility for mitral repair by 44% in an analysis cited by the 2024 ACC HFrEF expert consensus decision pathway.[19][4]

Complete GDMT is frequently limited in practice: in the STS/ACC TVT Registry, 19.2% of patients undergoing M-TEER for functional MR were receiving triple HF therapy and 6.5% were receiving none, while only 2.2% of COAPT participants tolerated target doses of all three evaluated GDMT classes.[20][2] Successful M-TEER facilitated subsequent medical-therapy uptitration in approximately 38% of patients in an observational cohort, and uptitration was associated with further reductions in mortality and HF hospitalization.[21]

Key controversies at a glance

  • The mortality benefit demonstrated in COAPT has not been established across all secondary-MR phenotypes or in patients outside COAPT-like selection criteria.[9][15]
  • The proportionate-versus-disproportionate MR framework may help explain trial discordance, but it is not a prospectively validated stand-alone selection criterion.[14]
  • The lower MR-severity boundary at which M-TEER provides clinically meaningful benefit remains uncertain despite differing quantitative thresholds and the RESHAPE-HF2 results.[15][1]
  • Published commentary has noted that RESHAPE-HF2 was neutral for all-cause hospitalization as well as all-cause mortality, leaving uncertainty regarding whether it fully resolves the COAPT–MITRA-FR discordance.[22]
  • Absolute residual risk remains high despite successful M-TEER: at 5 years in COAPT, 73.6% of device-group patients and 91.5% of control-group patients had died or been hospitalized for HF.[9]
  • Residual MR is a major modifiable determinant of outcome. MITRA-PRO found an approximately linear relationship between increasing residual-MR burden and mortality that persisted at 3 years, while EuroSMR data suggest residual MR ≤1+ should be the procedural target in secondary MR. However, a COAPT analysis found benefit with reduction to ≤2+ without demonstrating additional 2-year mortality or HF-hospitalization benefit from further reduction.[23][24][25][26]
  • Concomitant significant tricuspid regurgitation and right ventricular dysfunction are adverse prognostic modifiers. In EuroSMR, 5-year survival after M-TEER differed significantly by residual MR, LVEF, baseline tricuspid-regurgitation severity, and right ventricular dysfunction; these parameters should be weighed when estimating expected benefit and assessing procedural futility.[27]
  • The European framework provides no formal grading of procedural risk or futility but directs assessment of LVEF, myocardial viability, coronary anatomy and revascularization targets, concomitant procedures, M-TEER eligibility, expected durability of surgical repair, predicted surgical risk, and institutional expertise. An LVEF below 15% is regarded as a setting in which valve intervention is futile. American guidance defines procedural risk and futility more explicitly.[6]
  • Elevated postprocedural transmitral gradient did not offset the benefit of MR reduction in COAPT-like patients: discharge mitral-valve gradient was not associated with all-cause mortality, cardiovascular death, or HF hospitalization through 24 months.[28]
  • Echocardiographic misclassification is a practical constraint on patient selection: approximately one-third of patients considered eligible by experienced COAPT enrolling sites did not qualify after core-laboratory review, supporting expert multimodality imaging assessment before intervention. Core-laboratory qualification used a three-tier hierarchy: tier 1 required effective regurgitant orifice area ≥0.30 cm² or pulmonary-vein systolic flow reversal; tier 2, with effective regurgitant orifice area 0.20–0.30 cm², required one additional supporting criterion; and tier 3 required at least two alternative markers of severe MR.[10]
  • Advanced-HF evaluation should proceed in parallel when severe ventricular remodeling, right-sided failure, pulmonary vascular disease, or progressive end-stage HF raises concern for procedural futility.[13]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 O'Gara PT, Mack MJ (2020). "Secondary Mitral Regurgitation". The New England Journal of Medicine. 383 (15): 1458–1467. doi:10.1056/NEJMcp1903331.
  2. ↑ 2.0 2.1 2.2 Hahn RT, Lindenfeld J, Lim SD, Mack MJ, Burkhoff D (2024). "Structural Cardiac Interventions in Patients With Heart Failure: JACC Scientific Statement". Journal of the American College of Cardiology. 84 (9): 832–847. doi:10.1016/j.jacc.2024.05.061.
  3. ↑ 3.0 3.1 Otto CM, Nishimura RA, Bonow RO; et al. (2021). "2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Journal of the American College of Cardiology. 77 (4): e25–e197. doi:10.1016/j.jacc.2020.11.018.
  4. ↑ 4.0 4.1 Heidenreich PA, Bozkurt B, Aguilar D; et al. (2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Journal of the American College of Cardiology. 79 (17): e263–e421. doi:10.1016/j.jacc.2021.12.012.
  5. ↑ Ricciardi MJ, Singh G, Rogers JH; et al. (2026). "Atrial Secondary Mitral Regurgitation Outcomes Following Mitral Transcatheter Edge-to-Edge Repair: Results From the EXPANDed Studies". Circulation: Cardiovascular Interventions: e015883. doi:10.1161/CIRCINTERVENTIONS.125.015883. PMID 41562136 Check |pmid= value (help).
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Coisne A, Lancellotti P, Habib G; et al. (2023). "ACC/AHA and ESC/EACTS Guidelines for the Management of Valvular Heart Diseases: JACC Guideline Comparison". Journal of the American College of Cardiology. 82 (8): 721–734. doi:10.1016/j.jacc.2023.05.061.
  7. ↑ Stone GW, Lindenfeld J, Abraham WT; et al. (2018). "Transcatheter Mitral-Valve Repair in Patients with Heart Failure". The New England Journal of Medicine. 379 (24): 2307–2318. doi:10.1056/NEJMoa1806640.
  8. ↑ 8.0 8.1 Bonow RO, O'Gara PT, Adams DH; et al. (2020). "2019 AATS/ACC/SCAI/STS Expert Consensus Systems of Care Document: Operator and Institutional Recommendations and Requirements for Transcatheter Mitral Valve Intervention". Journal of the American College of Cardiology. 76 (1): 96–117. doi:10.1016/j.jacc.2019.12.002.
  9. ↑ 9.0 9.1 9.2 Stone GW, Abraham WT, Lindenfeld J; et al. (2023). "Five-Year Follow-up after Transcatheter Repair of Secondary Mitral Regurgitation". The New England Journal of Medicine. 388 (22): 2037–2048. doi:10.1056/NEJMoa2300213.
  10. ↑ 10.0 10.1 Asch FM, Grayburn PA, Siegel RJ; et al. (2019). "Echocardiographic Outcomes After Transcatheter Leaflet Approximation in Patients With Secondary Mitral Regurgitation: The COAPT Trial". Journal of the American College of Cardiology. 74 (24): 2969–2979. doi:10.1016/j.jacc.2019.09.017.
  11. ↑ Goel K, Lindenfeld J, Makkar R; et al. (2023). "Transcatheter Edge-to-Edge Repair in 5,000 Patients With Secondary Mitral Regurgitation: COAPT Post-Approval Study". Journal of the American College of Cardiology. 82 (13): 1281–1297. doi:10.1016/j.jacc.2023.07.015. PMID 37730284 Check |pmid= value (help).
  12. ↑ Iung B, Armoiry X, Vahanian A; et al. (2019). "Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation: Outcomes at 2 Years". European Journal of Heart Failure. 21 (12): 1619–1627. doi:10.1002/ejhf.1616. PMID 31476260.
  13. ↑ 13.0 13.1 Lander MM, Brener MI, Goel K; et al. (2023). "Mitral Interventions in Heart Failure". JACC: Heart Failure. 11 (8 Pt 2): 1055–1069. doi:10.1016/j.jchf.2023.07.016.
  14. ↑ 14.0 14.1 Grayburn PA, Sannino A, Packer M (2019). "Proportionate and Disproportionate Functional Mitral Regurgitation: A New Conceptual Framework That Reconciles the Results of the MITRA-FR and COAPT Trials". JACC: Cardiovascular Imaging. 12 (2): 353–362. doi:10.1016/j.jcmg.2018.11.006. PMID 30553663.
  15. ↑ 15.0 15.1 15.2 Anker SD, Friede T, von Bardeleben RS; et al. (2024). "Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation". The New England Journal of Medicine. 391 (19): 1799–1809. doi:10.1056/NEJMoa2314328.
  16. ↑ Baldus S, Doenst T, Pfister R; et al. (2024). "Transcatheter Repair versus Mitral-Valve Surgery for Secondary Mitral Regurgitation". The New England Journal of Medicine. 391 (19): 1787–1798. doi:10.1056/NEJMoa2408739. PMID 39216093 Check |pmid= value (help).
  17. ↑ Ostrominski JW, DeFilippis EM, Bansal K; et al. (2024). "Contemporary American and European Guidelines for Heart Failure Management: JACC: Heart Failure Guideline Comparison". JACC: Heart Failure. 12 (5): 810–825. doi:10.1016/j.jchf.2024.02.020.
  18. ↑ 18.0 18.1 Bonow RO, O'Gara PT, Adams DH; et al. (2020). "2020 Focused Update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation". Journal of the American College of Cardiology. 75 (17): 2236–2270. doi:10.1016/j.jacc.2020.02.005.
  19. ↑ Maddox TM, Januzzi JL, Allen LA; et al. (2024). "2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee". Journal of the American College of Cardiology. 83 (15): 1444–1488. doi:10.1016/j.jacc.2023.12.024.
  20. ↑ Varshney AS, Shah M, Vemulapalli S; et al. (2023). "Heart Failure Medical Therapy Prior to Mitral Transcatheter Edge-to-Edge Repair: The STS/ACC Transcatheter Valve Therapy Registry". European Heart Journal. 44 (44): 4650–4661. doi:10.1093/eurheartj/ehad584.
  21. ↑ Adamo M, Tomasoni D, Stolz L; et al. (2023). "Impact of Transcatheter Edge-to-Edge Mitral Valve Repair on Guideline-Directed Medical Therapy Uptitration". JACC: Cardiovascular Interventions. 16 (8): 896–905. doi:10.1016/j.jcin.2023.01.362.
  22. ↑ Obadia JF, Armoiry X, Messika-Zeitoun D, Trochu JN, Iung B (2024). "Plea for an In-Depth Analysis of the RESHAPE-HF2 Results". Journal of the American College of Cardiology. 84 (24): 2369–2371. doi:10.1016/j.jacc.2024.08.030.
  23. ↑ Boekstegers P, Hausleiter J, Schmitz T; et al. (2023). "Intraprocedural Residual Mitral Regurgitation and Survival After Transcatheter Edge-to-Edge Repair: Prospective German Multicenter Registry (MITRA-PRO)". JACC: Cardiovascular Interventions. 16 (5): 574–585. doi:10.1016/j.jcin.2022.12.015.
  24. ↑ Rottländer D, Hausleiter J, Schmitz T; et al. (2025). "Impact of Intraprocedural Residual Mitral Regurgitation on Long-Term Survival: The MITRA-PRO Registry 3-Year Follow-Up". JACC: Cardiovascular Interventions. 18 (3): 403–405. doi:10.1016/j.jcin.2024.10.019.
  25. ↑ Higuchi S, Orban M, Stolz L; et al. (2021). "Impact of Residual Mitral Regurgitation on Survival After Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation". JACC: Cardiovascular Interventions. 14 (11): 1243–1253. doi:10.1016/j.jcin.2021.03.050.
  26. ↑ Kar S, Mack MJ, Lindenfeld J; et al. (2021). "Relationship Between Residual Mitral Regurgitation and Clinical and Quality-of-Life Outcomes After Transcatheter and Medical Treatments in Heart Failure: COAPT Trial". Circulation. 144 (6): 426–437. doi:10.1161/CIRCULATIONAHA.120.053061.
  27. ↑ Stocker TJ, Stolz L, Karam N; et al. (2024). "Long-Term Outcomes After Edge-to-Edge Repair of Secondary Mitral Regurgitation: 5-Year Results From the EuroSMR Registry". JACC: Cardiovascular Interventions. 17 (21): 2543–2554. doi:10.1016/j.jcin.2024.08.016.
  28. ↑ Halaby R, Herrmann HC, Gertz ZM; et al. (2021). "Effect of Mitral Valve Gradient After MitraClip on Outcomes in Secondary Mitral Regurgitation: Results From the COAPT Trial". JACC: Cardiovascular Interventions. 14 (8): 879–889. doi:10.1016/j.jcin.2021.01.049.
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