Primary Mitral Regurgitation Repair

Sponsor

Eric Y. Yang, MD PhD (Other)

Overall Status

Unknown status

CT.gov ID

NCT04067635

Collaborator

(none)

116

Enrollment

Location

36.2

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mitral Valve Insufficiency Mitral Valve Prolapse Chronic Mitral Disease Mitral Regurgitation Mitral Valve Disease Degenerative Mitral Valve Disease Myxomatous Mitral Valve Degeneration Ventricular Remodeling

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 Design

Study Type:

Observational

Anticipated Enrollment :

116 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Primary Mitral Regurgitation Reverse Remodeling

Actual Study Start Date :

May 25, 2018

Anticipated Primary Completion Date :

Jun 1, 2021

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Conservative Arm Participants are followed by the research team conservatively. Participants in this arm may choose to undergo any valvular intervention at the discretion of their treating clinical team.
Surgical Arm Participants have already elected upfront to undergo surgical repair (at least, mitral annuloplasty) with their treating clinical team, just prior to enrollment into this study.

Outcome Measures

Primary Outcome Measures

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

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.
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.
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.
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years
Isolated mitral regurgitation
of any primary mechanism and
of moderate-to-severe (Sellers 3+) or greater severity, assessed by any imaging modality (echocardiography, angiography, cardiac MRI)
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:

Refusal to consent
Pregnancy during the study
Hemodynamically or clinically unstable
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
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)