Left Ventricular Fibrosis, Mitral Valve Prolapse, Ventricular Arrhythmias
Conditions
Keywords
Mitral valve repair (MVr), Transcatheter-edge-to-edge-repair (TEER), Cardiac magnetic resonance imaging (CMR), ZioPatch monitoring, Heart biopsy
Brief summary
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.
Detailed 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.
Interventions
PROCEDURECardiac Magnetic Resonance Imaging
Non-invasive imaging test that uses powerful magnets and radio waves to create detailed pictures of the heart without using radiation.
DEVICEZioPatch Monitoring
ZioPatch is a small, wearable heart monitor that sticks to the chest and records the heart's electrical activity continuously for up to 14 days. It helps doctors detect irregular heart rhythms (arrhythmias) without the need for bulky wires or equipment.
PROCEDUREMyocardial Tissue Biopsy
During the MVr procedure, surgeons will biopsy approximately 50 μg of tissue from the endocardial and subendocardial myocardium in the inferobasilar and control areas using a surgical rongeur.
Sponsors
Annetine Gelijns
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
The PRIMARY trial is an open-label trial. As in the parent trial, clinical investigators, and coordinators, however, will be blinded to all overall outcome data in the ancillary study.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of Myocardial Fibrosis | 1 year post index procedure. | Myocardial fibrosis is the buildup of excess fibrous connective tissue in the heart muscle often resulting from chronic injury or stress. It can impair the heart's ability to contract and relax properly leading to reduced cardiac function. |
| Presence of Ventricular Arrythmia | 1 year post index procedure. | A ventricular arrhythmia is an abnormal heart rhythm that starts in the lower chambers of the heart (the ventricles). It can cause the heart to beat too fast, which may reduce blood flow to the body and, in some cases, be life-threatening. |
| Proteomics | 1 year post index procedure. | Proteomics is the large-scale study of proteins, which are essential molecules that carry out most functions in the body. By analyzing proteins in tissues or fluids, scientists can better understand diseases, identify biomarkers, and discover new treatment targets. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Computational and Predictive Models of Treatment Outcome | 1 year post index procedure. | specific treatment. These tools help doctors make more personalized and effective care decisions based on patterns found in large sets of medical information. |
Countries
Germany, United Kingdom, United States
Contacts
STUDY_DIRECTORJoanna Chikwe, MD
Cedars-Sinai
STUDY_DIRECTORMartin Leon, MD
Columbia University
Outcome results
None listed