Primary Mitral Regurgitation Repair

• Conditions: Mitral Valve Insufficiency; Chronic Mitral Disease; Mitral Valve Disease; Mitral Regurgitation; Myxomatous Mitral Valve Degeneration; Ventricular Remodeling; Mitral Valve Prolapse; Degenerative Mitral Valve Disease

• Registration Number: NCT04067635
• Lead Sponsor: Eric Y. Yang, MD PhD

Brief Summary

This longitudinal cohort study evaluates the relationship of myocardial tissue markers characteristics assessed by cardiac MRI, with clinical measures of symptoms and functions in adults with primary mitral regurgitation. Participants are followed conservatively or may choose to undergo surgical repair at the discretion of their clinical team.

Detailed Description

The transition from compensated to decompensated chronic primary mitral regurgitation remains poorly understood in the clinical setting. Changes at the myocardial tissue level, such as scar formation and decreased contractility, have been implicated in the end stage, decompensated phase of this disease entity.

Advances in cardiac MRI (CMR) have enabled non-invasive characterization of the myocardial tissue components, such as cardiomyocyte volume and extracellular matrix, and tissue contractility. These measures have been well validated in various cardiac pathologies with biopsy studies but only at single time points.

In this study, adults with isolated chronic primary regurgitation will be followed conservatively over at least a year to determine the natural progression of these CMR-derived markers over time and to investigate the prognostic potential of these markers for clinically assessed functional capacity and symptoms. These participants may elect to undergo any valvular intervention at the discretion of their treating clinical team.

Alongside this arm, similar adults with isolated chronic primary regurgitation will be recruited, who have elected upfront to undergo surgical repair. These patients will be similarly studied to determine reverse remodeling of these CMR-derived markers over time and to investigate the prognostic potential of these markers for the same clinical outcomes.

Study Timeline

• Study Start: 2018-05-25
• Status Verified: 2019-08
• Study First Submitted: 2019-08-21
• Study First Submitted QC: 2019-08-22
• Last Update Submitted: 2019-08-22
• Study First Posted: 2019-08-26
• Last Update Posted: 2019-08-28
• Primary Completion: 2021-06
• Study Completion: 2021-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 116

Inclusion Criteria

1. Age ≥18 years

2. Isolated mitral regurgitation

   1. of any primary mechanism and
   2. of moderate-to-severe (Sellers 3+) or greater severity, assessed by any imaging modality (echocardiography, angiography, cardiac MRI)

3. Able to receive gadolinium-based contrast agent (estimated glomerular filtration rate >30 mL/min/1.73 m2, no prior allergy to gadolinium contrast agents)

Exclusion Criteria

1. Refusal to consent
2. Pregnancy during the study
3. Hemodynamically or clinically unstable
4. Inability to undergo a CMR scan, which can include the following reasons: severe claustrophobia, ferromagnetic implants, implanted defibrillator, pacemaker, or abandoned pacemaker leads, cochlear implants, unable to lie flat
5. Other diseases known to influence myocardial fibrosis development (coronary artery disease, diabetes mellitus, uncontrolled hypertension, infiltrative cardiomyopathy, myocarditis, hypertrophic cardiomyopathy, any cardiac tumors, moderate or more valvular heart disease other than primary mitral valve regurgitation)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Changes in cardiomyopathy symptom score	Baseline, 6 (+/-3) months, >12 months	Heart failure symptom scores will be tracked to monitor for changes in symptom burden at 2 subsequent timepoints. Scores are derived from a validated cardiomyopathy symptom patient-reported outcome measure instrument. The full name of the instrument is the Kansas City Cardiomyopathy Questionnaire Short Form (aka KCCQ-12) licensed by CV Outcomes, Inc. Only a complete score is recorded. The full range of scores scale from 0 to 100, with higher scores indicating lower symptom burden.
Changes in distance measured on 6-Minute Walk Test	Baseline, 6 (+/-3) months, >12 months	Distance (meters) walked using a standardized 6-minute walk protocol will be tracked to monitor for changes in functional capacity at 2 subsequent timepoints.

Secondary Outcome Measures

Name	Time	Method
Myocardial extracellular volume fraction	Baseline, 6 (+/-3) months, >12 months	Extracellular volume fraction measure derived using T1 mapping from cardiac MRI techniques. The quantity measured is the proportion of extracellular matrix volume to cardiomyocyte volume.
Cardiovascular Flow Volumes	Baseline, 6 (+/-3) months, >12 months	Cardiovascular MRI measures from phase contrast cine images of flow (mL/s) through major vessels. The flow quantity is integrated over a cardiac cycle to produce a volume (mL) per beat.
Ventricular Mass	Baseline, 6 (+/-3) months, >12 months	Cardiac MRI measures of left ventricular myocardial mass (grams)
Late gadolinium myocardial enhancement	Baseline, 6 (+/-3) months, >12 months	Semi-quantitative measure of left ventricular replacement fibrosis burden using cardiac MRI techniques with gadolinium-based contrast agents. The quantity measured is the percentage of left ventricular myocardial volume found to have late gadolinium enhancement.
Cardiac Morphology	Baseline, 6 (+/-3) months, >12 months	Cardiac MRI measures from cine images of cardiac chamber dimensions (milliliters) at end-diastolic and end-systolic cardiac phases.

Trial Locations

Locations (1)

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States