Percutaneous mitral repair as treatment in HFrEF (MitraClip/TEER) indications and contraindications

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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]

Indications and Contraindications

Candidacy framework

Candidacy for mitral transcatheter edge-to-edge repair (M-TEER) in heart failure with reduced ejection fraction (HFrEF) should be determined by a multidisciplinary heart/valve team using four sequential filters:[1][2]

  1. Confirm chronic ventricular secondary mitral regurgitation (vSMR) of qualifying post-treatment severity.
  2. Confirm persistent symptoms and MR despite maximally tolerated guideline-directed medical therapy (GDMT), including cardiac resynchronization therapy (CRT) when indicated.
  3. Apply the guideline-specific clinical and ventricular criteria.
  4. Confirm suitable mitral anatomy on transesophageal echocardiography (TEE) and exclude technical contraindications, competing treatment pathways, and futility.


Mandatory optimization before candidacy assessment

American and European guidelines restrict mitral intervention for secondary MR to patients who remain symptomatic despite GDMT, including CRT when indicated. The prerequisite recommendation is Class I-C in the ACC/AHA framework and Class I-B in the ESC/EACTS framework.[2]

Transcatheter intervention for moderate-to-severe or severe secondary MR should not proceed until guideline-recommended HF treatment has been fully optimized, as assessed by the multidisciplinary team with HF and electrophysiology input when required.[3]

Optimization can alter eligibility by reducing LV remodeling and MR severity. The 2024 ACC HFrEF pathway cites an analysis in which initiation of sacubitril/valsartan reduced potential mitral-repair eligibility by 44%; improvement in SMR has been reported in up to 40% of patients receiving optimized therapy.[4]

Maximally tolerated therapy is not synonymous with achieving every target dose. In a post hoc COAPT analysis, only 2.2% of patients tolerated goal doses of all three evaluated GDMT classes, most commonly because of hypotension or kidney dysfunction. The candidacy record should document attempted titration and the reason each treatment could not be advanced.[5]

MR severity used for referral should be reassessed after GDMT optimization and CRT, when indicated, rather than taken from a pre-optimization study. HF clinic–led rapid GDMT and volume optimization should be followed by repeat clinical and imaging assessment after approximately 1 to 6 months to reaffirm or defer the need for M-TEER. The optimal duration is not firmly established. Reassessment may also demonstrate improvement in previous risk factors such as pulmonary hypertension or RV dysfunction.[6]

Qualifying MR severity is not defined by a single EROA value. COAPT used a hierarchical screening approach in which lower EROA cutoffs could qualify when supported by additional markers of severe regurgitation, such as pulmonary-vein systolic flow reversal.[6]

Guideline indications

The principal American and European recommendations for chronic secondary MR are summarized below.[1][2]

Guideline recommendations relevant to M-TEER candidacy
Clinical situation ACC/AHA ESC/EACTS
GDMT and collaborative heart-team management before intervention Class I-C Class I-B
Persistent symptoms despite optimal GDMT; LVEF 20%–50%; LV end-systolic diameter ≤70 mm; pulmonary artery systolic pressure ≤70 mm Hg; appropriate mitral anatomy M-TEER: Class IIa-B —
Persistent symptoms despite optimal GDMT; patient not eligible or appropriate for surgery; criteria suggesting an increased likelihood of response — M-TEER: Class IIa-B
High-risk symptomatic patient not eligible for surgery and without recognized response criteria, after careful evaluation for left ventricular assist device or heart transplantation — M-TEER or another transcatheter therapy: Class IIb-C
Concomitant mitral surgery when coronary artery bypass surgery is being performed Class IIa-B Class I-B; also applies during other cardiac surgery

The principal transatlantic difference is the surgical-eligibility precondition. European guidance conditions M-TEER on surgical ineligibility or inappropriateness, whereas the American secondary-MR recommendation is based on COAPT-like clinical criteria and suitable anatomy without requiring surgical ineligibility.[2]

Published comparisons do not describe the European secondary-MR recommendation uniformly. Some summarize both American and European guidance as providing a Class IIa recommendation for COAPT-like patients, whereas other comparisons describe the two-tier European structure shown above. The primary ESC/EACTS guideline should therefore be consulted when applying the exact European recommendation structure.[5][2]

The European category for patients without response criteria is not a routine extension of the principal indication. It requires high procedural risk, surgical ineligibility, and prior consideration of LVAD or transplantation.[2]

Boundaries of the randomized evidence: COAPT exclusions

The COAPT trial-protocol exclusions define the boundaries of the randomized evidence more precisely than the inclusion criteria alone. Important exclusions included:[7][5]

  • Cardiogenic shock or requirement for inotropic support.
  • LVEF outside the COAPT range of 20%–50%.
  • LV end-systolic diameter greater than 70 mm.
  • Pulmonary artery systolic pressure greater than 70 mm Hg and unresponsive to vasodilator therapy.
  • Severe chronic lung disease requiring continuous home oxygen or chronic oral corticosteroids.
  • Severe tricuspid regurgitation.
  • Symptomatic right ventricular HF with moderate or severe RV dysfunction.
  • Tricuspid or aortic valve disease requiring surgery or intervention.

The registry-adapted definition used in the TVT Registry was narrower. It comprised six operational features: cardiogenic shock, inotropic support, LVEF outside the COAPT range, LV end-systolic diameter greater than 70 mm, home oxygen use, or severe tricuspid regurgitation. Registry-derived ineligibility rates should therefore be interpreted against this definition rather than the full trial protocol.[8]

These criteria define the studied population but are not all absolute contraindications. Among 6,675 TVT Registry patients undergoing M-TEER, 44.3% were classified as COAPT-ineligible. They experienced similar improvement in health status at 30 days but had lower technical procedural success (86.9% versus 92.6%) and more in-hospital complications (11.8% versus 5.7%). One-year mortality and HF hospitalization were also higher among COAPT-ineligible patients.[8][5]


Ineligibility is graded rather than binary. In a three-center European series of 305 COAPT-ineligible patients, 2-year death or HF hospitalization occurred in 55% of patients with one exclusion criterion versus 69% of those with multiple criteria. NYHA class II, age below 75 years, creatinine below 2 mg/dL, LV end-diastolic volume below 240 mL, and absence of hemodynamic instability, atrial fibrillation, and chronic obstructive pulmonary disease were independently associated with a favorable outcome.[9]

Symptomatic benefit may be less dependent on strict COAPT eligibility than survival. Significant improvement in six-minute walk distance and Minnesota Living With Heart Failure Questionnaire scores has been observed in both COAPT-eligible and COAPT-ineligible patients. Symptom relief may therefore remain a legitimate treatment goal when survival benefit is uncertain, provided procedural risk and expected durability are acceptable.[10]


FDA-labeled population

In March 2019, the United States indication for transcatheter edge-to-edge clip repair was extended to symptomatic patients with moderate-to-severe or severe secondary MR, as defined by American Society of Echocardiography grading, with an LVEF greater than 20% and less than 50% and an LV end-systolic diameter less than 70 mm.[11]

The 2020 ACC focused update summarizes the approved population using an LVEF of 20%–50% and an LV end-systolic diameter of 70 mm or less. The COAPT-derived criteria underlying the indication also included a pulmonary artery systolic pressure of 70 mm Hg or less.[3][12]

The regulatory label and professional-society recommendations should not be treated as interchangeable documents; their inequality conventions and accompanying selection language differ.

Anatomic suitability

Anatomic screening determines whether the leaflets can be grasped securely while preserving an adequate diastolic mitral-valve area. Relevant features include leaflet length and mobility, coaptation gap, tenting, calcification, leaflet integrity, jet location, chordal support, baseline valve area, and transmitral gradient.[13][14]

Anatomic assessment for M-TEER candidacy
Feature Favorable or required Challenging or unfavorable
Location of dominant pathology Central segment 2 Segment 1 or 3, commissural pathology, or multiple independent significant jets
Leaflet integrity Intact leaflet body with adequate tissue and chordal support Cleft, perforation, deep fold, or insufficient secondary chordal support
Leaflet mobility and coaptation Mobile leaflets with an achievable coaptation zone Marked tethering; Carpentier IIIa restriction; flail gap >10 mm; flail width >15 mm; coaptation depth >11 mm
Calcification None, or mild calcification outside the grasping zone Severe calcification at the grasping zone; above-mild or severe mitral annular calcification modifies expected durability and survival
Mitral-valve area and gradient Mitral-valve area ≥4.0 cm² is desirable Mitral-valve area 3.5–4.0 cm² is marginal; mitral-valve area <3.5 cm² or mean transmitral gradient >5 mm Hg is a relative contraindication, particularly with severe annular calcification
Device-specific leaflet length MitraClip NT/NTW: anterior and posterior leaflet length ≥6.0 mm
MitraClip XT/XTW: minimum 9 mm
PASCAL: anterior and posterior leaflet length ≥8 mm 		Leaflet length below the applicable device-specific minimum

The anatomic thresholds have not been harmonized. The 2017 ACC pathway lists a mitral-valve area below 4.0 cm² and a mean transmitral gradient above 5 mm Hg as relative echocardiographic contraindications, particularly with severe mitral annular calcification. It categorizes a valve area of 3.5–4.0 cm² as challenging in selected anatomic or body-size contexts. The 2026 ASE recommendations use a mitral-valve area below 3.5 cm² as the relative contraindication threshold while identifying an area of at least 4.0 cm² as desirable.[14][13]

The anticipated reduction in diastolic mitral-valve area is approximately 47% with a PASCAL P10 device, 52% with MitraClip NT, and 57% with MitraClip XTW. Leaflet pathology and the location of MR also influence the final valve area.[13]

Mitral-valve area should be measured by three-dimensional multiplanar-reconstruction planimetry at the leaflet tips. Oblique two-dimensional planimetry may overestimate area, and measurement on a three-dimensional rendered en-face image is strongly discouraged because of slice thickness and parallax. The transmitral gradient should be interpreted in the context of heart rate, regurgitant volume, and forward flow.[13]


Contraindications and competing pathways

Absolute or near-absolute technical contraindications

  • Active endocarditis or mitral vegetation.[15]
  • Left atrial thrombus, another intracardiac mass, or thrombus within the inferior vena cava or femoral venous access route.[15][13]
  • Interatrial-septal anatomy that prevents an adequate and safe transseptal puncture.[13]
  • Valve morphology that prevents secure leaflet grasping or an acceptably durable result.[13]

Relative anatomic or imaging contraindications

  • Baseline mean transmitral gradient greater than 5 mm Hg, particularly when accompanied by severe annular calcification. A flow-mediated gradient is not automatically prohibitive because severe MR itself may elevate the gradient and effective MR reduction may lower it.[13]
  • Mitral-valve area below 3.5 cm² under the 2026 ASE criteria; older consensus pathways use a more conservative threshold below 4.0 cm².[13][14]
  • Rheumatic etiology or Carpentier IIIa leaflet restriction.
  • Cleft or perforated leaflet or inadequate secondary chordal support.
  • Leaflet length below the device-specific minimum.
  • Severe calcification within the intended grasping zone.
  • Inability to advance a TEE transducer safely; a smaller probe or three-dimensional intracardiac echocardiography may provide an alternative in selected centers.[13]

These findings require individualized assessment rather than automatic rejection when a safe alternative imaging or device strategy remains feasible.

Mitral annular calcification

Severe mitral annular calcification (MAC) is a modifier of expected benefit rather than an absolute exclusion. The 2025 AATS expert consensus assigns a Class IIb, Level C-LD recommendation for M-TEER in symptomatic patients with MAC and severe MR who have an acceptable mitral-valve area but are at high surgical risk. When severe mitral stenosis is likely to develop after M-TEER, transcatheter mitral valve replacement may be considered instead (Class IIa, Level C-LD), although anatomic constraints—principally the risk of left ventricular outflow tract obstruction—may make replacement infeasible. Assessment should integrate mitral-valve area, baseline mean gradient, leaflet calcification, and leaflet mobility.[16]

Observational data support technical feasibility but suggest attenuated long-term benefit. In a 968-patient cohort, technical success and 1-year MR reduction were not materially affected by MAC extent, but 2-year reintervention was more frequent with above-mild MAC (11.9% versus 6.2%; P=0.033).[17]

A meta-analysis of 2,808 patients found comparable procedural success, reintervention, and HF readmission but higher all-cause mortality in patients with MAC (OR 1.82; 95% CI 1.15–2.86; P=0.01).[18] In a separate 280-patient series, moderate or severe MAC was associated with lower 1-year survival (56.8% versus 80.0%; HR 1.98; 95% CI 1.27–3.10) and less symptomatic improvement at 30 days.[19]

These observational associations should inform consent and futility assessment but should not be interpreted as proof that MAC itself causes excess mortality.

Futility and alternative treatment pathways

  • Severe RV dysfunction by core-laboratory assessment was an exclusion criterion in CLASP IIID, and COAPT excluded symptomatic right ventricular HF accompanied by moderate or severe RV dysfunction. Such findings should prompt explicit futility assessment rather than routine proceeding.[20][7]
  • Refractory or advanced HF requiring consideration of LVAD or heart transplantation should prompt parallel advanced-HF evaluation rather than delayed assessment after unsuccessful M-TEER.[2][5]
  • European guidance regards mitral intervention as futile when LVEF is below 15%.[2]
  • Clinically significant coronary disease requiring revascularization or a requirement for another cardiac operation may favor surgery rather than isolated M-TEER.[2][11]
  • Unstable angina or a recent myocardial infarction or stroke warrants deferral and reassessment rather than routine immediate M-TEER.[11]

Populations outside the principal vSMR indication

Atrial secondary MR. American guidance provides a Class IIb-B recommendation for mitral surgery or intervention in atrial secondary MR with preserved LVEF and persistent symptoms despite GDMT. European guidelines provide no corresponding recommendation. COAPT-derived ventricular criteria should not be transferred directly to this phenotype.[2]

MR below conventional guideline severity. RESHAPE-HF2 enrolled patients with a mean EROA of 0.25 cm²; only 14% had an EROA greater than 0.40 cm² and nearly one-quarter had an EROA below 0.20 cm². The trial broadened the evidence base toward moderate-to-severe MR, but the lower severity boundary at which M-TEER should be routinely recommended remains unresolved.[21][22]

Primary or mixed MR causing HFrEF. Severe primary structural MR should be evaluated for surgery first. For primary MR with favorable anatomy, severe symptoms, high or prohibitive surgical risk, and no evidence of futility, M-TEER carries a Class IIa American recommendation and a Class IIb European recommendation.[5][2]

Areas of uncertainty

  • European guidance invokes “criteria suggesting an increased chance of responding” without a single validated response instrument.
  • The proportionate/disproportionate MR framework remains a physiologic construct and should not be used as a stand-alone eligibility rule. A COAPT echocardiographic substudy found benefit across multiple baseline echocardiographic measures, whereas a post hoc analysis of a small COAPT subgroup resembling MITRA-FR patients, whose MR was considered proportionate to LV dilation, did not demonstrate benefit.[12]
  • Feasibility with a mitral-valve area of 3.5–4.0 cm² is patient-, device-, and operator-dependent.[13][14]
  • The optimal duration of pre-referral GDMT optimization and reassessment is uncertain; the proposed 1-to-6-month interval requires further validation.[6]
  • Published comparisons differ in their summaries of the precise European recommendation tiers; the primary ESC/EACTS guideline should be verified when applying class and level of evidence.[5][2]
  • Observational MAC outcome associations may reflect comorbidity and disease burden rather than a causal effect of calcification.[18][19]

References

  1. ↑ 1.0 1.1 Otto CM, Nishimura RA, Bonow RO; et al. (2021). "2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease". Journal of the American College of Cardiology. 77 (4): e25–e197. doi:10.1016/j.jacc.2020.11.018.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 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.
  3. ↑ 3.0 3.1 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.
  4. ↑ Maddox TM, Januzzi JL, Allen LA; et al. (2024). "2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction". Journal of the American College of Cardiology. 83 (15): 1444–1488. doi:10.1016/j.jacc.2023.12.024.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 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.
  6. ↑ 6.0 6.1 6.2 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.
  7. ↑ 7.0 7.1 Saxon JT, Cohen DJ, Chhatriwalla AK; et al. (2020). "Impact of COPD on Outcomes After MitraClip for Secondary Mitral Regurgitation: The COAPT Trial". JACC: Cardiovascular Interventions. 13 (23): 2795–2803. doi:10.1016/j.jcin.2020.09.023.
  8. ↑ 8.0 8.1 Chhatriwalla AK, Cohen DJ, Vemulapalli S; et al. (2024). "Transcatheter Edge-to-Edge Repair in COAPT-Ineligible Patients With Functional Mitral Regurgitation". Journal of the American College of Cardiology. 83 (4): 488–499. doi:10.1016/j.jacc.2023.11.012.
  9. ↑ Scotti A, Munafò A, Adamo M; et al. (2022). "Transcatheter Edge-to-Edge Repair in COAPT-Ineligible Patients: Incidence and Predictors of 2-Year Good Outcome". The Canadian Journal of Cardiology. 38 (3): 320–329. doi:10.1016/j.cjca.2021.12.003. PMID 34923063 Check |pmid= value (help).
  10. ↑ Koell B, Orban M, Weimann J; et al. (2021). "Outcomes Stratified by Adapted Inclusion Criteria After Mitral Edge-to-Edge Repair". Journal of the American College of Cardiology. 78 (24): 2408–2421. doi:10.1016/j.jacc.2021.10.011.
  11. ↑ 11.0 11.1 11.2 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.
  12. ↑ 12.0 12.1 O'Gara PT, Mack MJ (2020). "Secondary Mitral Regurgitation". The New England Journal of Medicine. 383 (15): 1458–1467. doi:10.1056/NEJMcp1903331.
  13. ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 Little SH, Quader N, Brady M; et al. (2026). "Guidelines for the Intraprocedural Imaging for Mitral Valve Transcatheter Edge-to-Edge Repair (M-TEER): Recommendations From the American Society of Echocardiography". Journal of the American Society of Echocardiography. 39 (6): 529–550. doi:10.1016/j.echo.2026.03.003.
  14. ↑ 14.0 14.1 14.2 14.3 O'Gara PT, Grayburn PA, Badhwar V; et al. (2017). "2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation". Journal of the American College of Cardiology. 70 (19): 2421–2449. doi:10.1016/j.jacc.2017.09.019.
  15. ↑ 15.0 15.1 Beigel R, Wunderlich NC, Kar S, Siegel RJ (2014). "The Evolution of Percutaneous Mitral Valve Repair Therapy: Lessons Learned and Implications for Patient Selection". Journal of the American College of Cardiology. 64 (24): 2688–2700. doi:10.1016/j.jacc.2014.08.049.
  16. ↑ El-Eshmawi A, Halas M, Bethea BT; et al. (2025). "The American Association for Thoracic Surgery (AATS) 2025 Expert Consensus Document: Surgical Management of Mitral Annular Calcification". The Journal of Thoracic and Cardiovascular Surgery. 170 (2): 502–522. doi:10.1016/j.jtcvs.2025.04.003.
  17. ↑ Shechter A, Lee M, Kaewkes D; et al. (2024). "Implications of Mitral Annular Calcification on Outcomes Following Mitral Transcatheter Edge-to-Edge Repair". Circulation: Cardiovascular Interventions. 17 (2): e013424. doi:10.1161/CIRCINTERVENTIONS.123.013424. PMID 38235546 Check |pmid= value (help).
  18. ↑ 18.0 18.1 Idowu A, Adebolu O, Siraj B; et al. (2025). "Transcatheter Edge-to-Edge Repair in Patients With Mitral Annular Calcification: A Systematic Review and Meta-Analysis". The American Journal of the Medical Sciences: S0002-9629(25)01101-2. doi:10.1016/j.amjms.2025.07.008. PMID 40675369 Check |pmid= value (help).
  19. ↑ 19.0 19.1 Hatab T, Bou Chaaya RG, Zaid S; et al. (2023). "Feasibility and Outcomes of Mitral Transcatheter Edge-to-Edge Repair in Patients With Variable Degrees of Mitral Annular Calcification". Journal of the American Heart Association. 12 (19): e031118. doi:10.1161/JAHA.123.031118. PMID 37753800 Check |pmid= value (help).
  20. ↑ Hausleiter J, Lim DS, Gillam LD; et al. (2023). "Transcatheter Edge-to-Edge Repair in Patients With Anatomically Complex Degenerative Mitral Regurgitation". Journal of the American College of Cardiology. 81 (5): 431–442. doi:10.1016/j.jacc.2022.11.034.
  21. ↑ 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.
  22. ↑ Ponikowski P, Friede T, von Bardeleben RS; et al. (2024). "Hospitalization of Symptomatic Patients With Heart Failure and Moderate to Severe Functional Mitral Regurgitation Treated With MitraClip: Insights From RESHAPE-HF2". Journal of the American College of Cardiology. 84 (24): 2347–2363. doi:10.1016/j.jacc.2024.08.027.
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