Ablation With Transcatheter Edge-to-edge Repair for Atrial Functional Mitral Regurgitation and Atrial Fibrillation

Official title

Ablation wiTh TRAnsCatheter Edge-to-edge Repair Versus ablaTION Alone for Atrial Functional Mitral Regurgitation and Atrial Fibrillation (ATTRACTION Study)

Overview

This trial is a randomized study for patients with significant atrial functional mitral regurgitation (AFMR) and atrial fibrillation (AF). The composite endpoint of all-cause mortality, cardiovascular-related hospitalizations, AF recurrence, and quality of life improvement is hypothesized to be superior with the combination of transcatheter edge-to-edge repair (TEER) and catheter ablation, compared with catheter ablation alone.

Detailed description

Rationale:

The introduction of transcatheter edge-to-edge repair (TEER) for the treatment of functional mitral regurgitation (FMR) has led to a significant reduction in mortality and heart failure hospitalizations. However, the optimal timing and intervention for patients with atrial functional mitral regurgitation (AFMR) have not been evaluated in clinical trials. Published clinical trials, including COAPT, MITRA-FR, and RESHAPE-HF, did not classify functional mitral regurgitation according to ventricular or atrial origin. Concerns regarding the role of atrial fibrillation (AF) as a potential trigger of atrial dilatation and a consequence of atrial remodeling have led to recommendations for rhythm control in selected patients. Given the high incidence of AFMR among patients with persistent AF, successful ablation and maintenance of sinus rhythm may remain challenging. Therefore, concomitant TEER and catheter ablation are hypothesized to provide greater clinical benefit compared with catheter ablation alone.

Aim:

The purpose of this study is to evaluate the efficacy of TEER combined with catheter ablation in patients with significant AFMR and AF, focusing on clinical outcomes and atrial reverse remodeling.

Study design:

Patients with moderate-to-severe or severe AFMR and AF will be enrolled in a randomized, open-label, controlled study. Patients will be randomized in a 1:1 ratio to receive TEER combined with catheter ablation or catheter ablation alone. The study duration is anticipated to include 24 months of enrollment and 12 months of follow-up.

Interventions

• Device Transcatheter edge to edge repair
  Participants will undergo catheter ablation for persistent atrial fibrillation followed by transcatheter edge-to-edge repair (TEER) for the treatment of functional mitral regurgitation during the same hospitalization. TEER will be performed using an approved transcatheter mitral valve repair system to reduce mitral regurgitation severity and improve cardiac function.
• Procedure Catheter ablation
  Participants will undergo catheter ablation for persistent atrial fibrillation during the study period. The procedure will include pulmonary vein isolation with additional ablation strategies as clinically indicated.

Primary outcome measures

• Hierarchical Composite Clinical Endpoint (Win Ratio) [Time frame: 12 months]

Secondary outcome measures (11)

• Incidence of 30-day composite safety events [Time frame: 30 days]
• Change in mitral regurgitation grade from baseline [Time frame: 12 months]
• Composite of all-cause mortality and cardiovascular-related hospitalization [Time frame: 12 months]
• Cardiovascular mortality [Time frame: 12 months]
• Heart failure hospitalizations [Time frame: 12 months]
• Incidence of stroke or transient ischemic attack [Time frame: 12 months]
• Change in left atrial volume index [Time frame: 12 months]
• Change in left atrial reservoir function from baseline [Time frame: 12 months]
• Change in severity of tricuspid regurgitation from baseline [Time frame: 12 months]
• Change in NYHA functional classification from baseline [Time frame: 12 months]
• Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level from baseline [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Left ventricular ejection fraction ≥ 50%
• Grading of MR: 3+ or 4+ (effective regurgitant orifice area≥30mm2, regurgitant volume ≥45ml)
• Valve morphology: MR originating from the mid portion of the valve; mitral valve area> 4 cm2; Length of posterior leaflet ≥10 mm; Sufficient leaflet tissue for mechanical coaptation: coaptation depth< 11 mm, coaptation length> 2 mm
• Rate control in suspected AF-induced cardiomyopathy (heart rate <80 bpm at rest and <110 bpm during exercise)
• Patients must be willing to comply with all follow-up requirements

Exclusion criteria

• Life expectancy< 1 year due to non-cardiac conditions
• Primary mitral regurgitation: valve abnormalities including leaflet tethering from LV dysfunction, intrinsic leaflet pathology (prolapse, flail, calcification, severe thickening), mitral annular calcification (either severe or <severe but extending into the leaflets), and/or any mixed pathology
• Active endocarditis of the mitral valve or rheumatic mitral valve disease
• Hypotension (systolic pressure < 90 mmHg) or requirement for inotropic support or mechanical hemodynamic support
• Severe tricuspid regurgitation; Physical evidence of right-sided congestive heart failure with echocardiographic evidence of severe right ventricular dysfunction; Fixed pulmonary artery systolic pressure> 70 mmHg
• Stroke/TIA, TAVR, CRT/ CRT-D/ ICD, cardiac intervention or surgery within 30 days before randomization
• Any prior MV surgery or transcatheter procedure
• Need for any cardiac surgery (other than for MV disease)
• Untreated clinically significant coronary artery disease
• Echocardiographic evidence of intracardiac thrombus
• Active infections requiring current antibiotic therapy
• Patients who cannot tolerate anti-platelet/anticoagulation agents/contrast media
• Pregnancy
• Any condition making it unlikely the patient will be able to complete all protocol procedures (including compliance with medical therapy) and follow-up visits
• Patient (or legal guardian) unable or unwilling to provide written informed consent before study enrollment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Stone GW, Vahanian AS, Adams DH, Abraham WT, Borer JS, Bax JJ, Schofer J, Cutlip DE, Krucoff MW, Blackstone EH, Genereux P, Mack MJ, Siegel RJ, Grayburn PA, Enriquez-Sarano M, Lancellotti P, Filippatos G, Kappetein AP; Mitral Valve Academic Research Consortium (MVARC). Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 1: clinical PMID 26170467
• Wunderlich NC, Siegel RJ. Peri-interventional echo assessment for the MitraClip procedure. Eur Heart J Cardiovasc Imaging. 2013 Oct;14(10):935-49. doi: 10.1093/ehjci/jet060. PMID 24062377
• Farhan S, Silbiger JJ, Halperin JL, Zhang L, Dukkipati SR, Vogel B, Kini A, Sharma S, Lerakis S. Pathophysiology, Echocardiographic Diagnosis, and Treatment of Atrial Functional Mitral Regurgitation: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022 Dec 13;80(24):2314-2330. doi: 10.1016/j.jacc.2022.09.046. PMID 36480974
• Obadia JF, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, Lefevre T, Piot C, Rouleau F, Carrie D, Nejjari M, Ohlmann P, Leclercq F, Saint Etienne C, Teiger E, Leroux L, Karam N, Michel N, Gilard M, Donal E, Trochu JN, Cormier B, Armoiry X, Boutitie F, Maucort-Boulch D, Barnel C, Samson G, Guerin P, Vahanian A, Mewton N; MITRA-FR Investigators. Percutaneous Repair or Medical Treatment fo PMID 30145927
• Stone GW, Abraham WT, Lindenfeld J, Kar S, Grayburn PA, Lim DS, Mishell JM, Whisenant B, Rinaldi M, Kapadia SR, Rajagopal V, Sarembock IJ, Brieke A, Marx SO, Cohen DJ, Asch FM, Mack MJ; COAPT Investigators. Five-Year Follow-up after Transcatheter Repair of Secondary Mitral Regurgitation. N Engl J Med. 2023 Jun 1;388(22):2037-2048. doi: 10.1056/NEJMoa2300213. Epub 2023 Mar 5. PMID 36876756

Identifiers

NCT: NCT07744035 · 2026-286

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗