PRIMARY Ancillary Substudy

Annetine Gelijns

Status: Enrolling

Conditions: Mitral Valve Prolapse; Left Ventricular Fibrosis; Ventricular Arrhythmias

Treatments: Device: ZioPatch Monitoring; Procedure: Cardiac Magnetic Resonance Imaging; Procedure: Myocardial Tissue Biopsy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07103733

GCO 08-1078 ANC

5U01HL088942-17 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The PRIMARY trial (NCT05051033), which compares mitral valve repair (MVr) to transcatheter-edge-to-edge-repair (TEER), offers a platform for conducting mechanistic studies to develop early insights into the pathophysiological processes by which mitral valve prolapse (MVP) can impact left ventricular (LV) myocardial structure and function, and, thereby, predispose to arrhythmias and sudden death. Such insights are key to identifying interventions to reduce the long-term sequelae of heart failure (HF) and arrhythmias, as well as delineate optimal therapeutic approaches for different patient sub-groups.

Full description

This is an ancillary study of a multicenter randomized clinical trial comparing MVr to TEER for degenerative mitral regurgitation (MR) involving up to 250 patients from the parent trial. All patients will receive rhythm monitoring, up to 200 patients will receive pre/post intervention CMR, all patients in the parent trial will undergo a transthoracic echocardiogram (TTE) (as part of the randomized controlled trial (RCT)), and 60 surgical patients will undergo tissue biopsies. The study is being conducted in highly experienced clinical centers in the U.S., Canada, Germany, the U.K. and Spain. The estimated enrollment period is 12-18 months. Outcomes will be measured from baseline to 12 months after randomization.

This mechanistic ancillary study has the following aims:

1. To compare the impact of MVr and TEER on disordered ventricular biomechanics and myocardial fibrosis that predispose to ventricular arrhythmias, using speckle tracking strain echocardiography, cardiac magnetic resonance imaging (CMR), and rhythm monitoring pre- and post-mitral valve (MV) intervention. The research team hypothesize's that a treatment strategy that more effectively and durably reduces MVP and MR will lead to improved ventricular mechanics, limit progression of myocardial fibrosis and decrease the burden of ventricular arrhythmias and HF.
2. To compare the impact of MVr and TEER on recurrent/residual MR, LV and left atrial (LA) reverse remodeling with baseline and 1-year post-intervention CMR, and to use quantitative CMR myocardial tissue phenotyping as a predictor of response to MVr and TEER.
3. To construct functional pre-operative CMR fingerprints that recapitulate the mechanical state of the heart to develop individualized computational models, which will be altered in silico based on the proposed treatment plan, to predict patients' response to therapy. These results will be validated against post-operative outcome data to test the validity of this approach for predicting treatment response.
4. To explore the relationships among gene products, structural variables, and post-operative clinical outcomes, including reverse remodeling, using tissue obtained at surgery from ventricular myocardium.

Enrollment: 250 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients who meet all eligibility criteria and are randomized in the parent PRIMARY trial.
• For the ancillary biospecimen study, patients who are randomized to MVr in the parent trial.

Exclusion criteria

• Severe claustrophobia not controlled with sedation.
• Prior adverse reaction to gadolinium administration.
• Patients with an implantable subcutaneous cardioverter defibrillator and/or cardiac resynchronization therapy device with defibrillator may be excluded as they typically produce substantial artifacts on cardiac MRI making assessment very challenging.
• Known allergic reaction to adhesives or hydrogels or with family history of adhesive skin allergies (for patients undergoing rhythm monitoring).

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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250 participants in 2 patient groups

Mitral valve repair

Active Comparator group

Description:

Mitral surgery will be conducted using general anesthesia and cardiopulmonary bypass. Mitral surgery may be performed via a sternotomy or a right thoracotomy approach with or without robotic assistance.

Treatment:

Procedure: Myocardial Tissue Biopsy

Procedure: Cardiac Magnetic Resonance Imaging

Device: ZioPatch Monitoring

Transcatheter edge-to-edge repair

Active Comparator group

Description:

Patients will be treated with a commercially-approved edge-to-edge mitral repair device.

Treatment:

Procedure: Cardiac Magnetic Resonance Imaging

Device: ZioPatch Monitoring