Atrial Fibrillation (AF), Atrial Functional Mitral Regurgitation
Conditions
Keywords
Transcatheter edge to edge repair, Catheter ablation
Brief summary
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
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.
PROCEDURECatheter 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.
Sponsors
Mao Chen
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The experimental group will undergo transcatheter edge-to-edge repair plus catheter ablation, while the controlled group will undergo only catheter ablation.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hierarchical Composite Clinical Endpoint (Win Ratio) | 12 months | The primary endpoint is a single hierarchical composite clinical endpoint analyzed by pairwise comparison. Each participant in the transcatheter edge-to-edge repair (TEER) plus catheter ablation group is compared with each participant in the catheter ablation alone group, in order of clinical priority: all-cause mortality, cumulative cardiovascular-related hospitalization, atrial fibrillation recurrence, and change in quality of life measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Each pairwise comparison is resolved at the highest-priority component that differs between the two participants, and results in a single "win," "loss," or "tie." The treatment effect is summarized as one win ratio, defined as the total number of wins divided by the total number of losses across all pairs, comparing the TEER plus catheter ablation group with the catheter ablation alone group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of 30-day composite safety events | 30 days | The composite safety endpoint includes cardiovascular mortality, stroke, myocardial infarction, acute kidney injury, major bleeding, and non-elective cardiovascular surgery for device-related complications within 30 days after the procedure. |
| Change in mitral regurgitation grade from baseline | 12 months | Mitral regurgitation severity will be assessed by transthoracic echocardiography according to an integrated approach recommended by current guidelines. The outcome will be the proportion of patients achieving mild or less mitral regurgitation (grade ≤2) at 12 months. |
| Composite of all-cause mortality and cardiovascular-related hospitalization | 12 months | The composite endpoint includes all-cause mortality and cardiovascular-related hospitalization within 12 months. Death events will be identified through follow-up records, and cardiovascular-related hospitalizations will be confirmed by medical record review according to predefined criteria. |
| Cardiovascular mortality | 12 months | Cardiovascular mortality is defined as death caused by cardiovascular causes and will be determined through review of medical records and clinical documentation. |
| Heart failure hospitalizations | 12 months | Heart failure hospitalization is defined as an unplanned admission lasting ≥24 hours due to acute decompensated heart failure, with symptoms, signs, and/or laboratory evidence of heart failure and requiring intravenous or mechanical heart failure therapies. Events will be identified through medical records and adjudicated according to predefined criteria. |
| Incidence of stroke or transient ischemic attack | 12 months | Stroke and transient ischemic attack events will be identified through clinical assessment, medical records, and neuroimaging findings. Stroke will be classified as ischemic or hemorrhagic according to clinical diagnosis and imaging evaluation. |
| Change in left atrial volume index | 12 months | Left atrial volume index is assessed by the biplane method of disks and indexed to body surface area. |
| Change in left atrial reservoir function from baseline | 12 months | Left atrial reservoir function will be assessed using speckle-tracking echocardiography, and the change from baseline to 12 months will be evaluated. |
| Change in severity of tricuspid regurgitation from baseline | 12 months | Tricuspid regurgitation severity will be assessed by transthoracic echocardiography using an integrated approach according to current guidelines. The change in tricuspid regurgitation severity from baseline to 12 months will be evaluated. |
| Change in NYHA functional classification from baseline | 12 months | The New York Heart Association (NYHA) functional class will be assessed by clinical evaluation based on patients' symptoms and limitations during physical activity. The change from baseline to 12 months will be evaluated. |
| Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level from baseline | 12 months | Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels will be measured using standard laboratory assays. The change from baseline to 12 months will be evaluated. |
Contacts
CONTACTZhengang Zhao
CONTACTLijun Zeng
PRINCIPAL_INVESTIGATORMao Chen
West China Hospital
Outcome results
None listed