Primary Mitral Regurgitation Repair

Primary Mitral Regurgitation Reverse Remodeling

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.

Study Overview

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

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 Type: Observational
• Enrollment (Anticipated): 116

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

cardiac MRI referral base, valve specialty clinic

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cardiomyopathy symptom score	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.	Baseline, 6 (+/-3) months, >12 months
Changes in distance measured on 6-Minute Walk Test	Distance (meters) walked using a standardized 6-minute walk protocol will be tracked to monitor for changes in functional capacity at 2 subsequent timepoints.	Baseline, 6 (+/-3) months, >12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late gadolinium myocardial enhancement	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.	Baseline, 6 (+/-3) months, >12 months
Myocardial extracellular volume fraction	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.	Baseline, 6 (+/-3) months, >12 months
Cardiac Morphology	Cardiac MRI measures from cine images of cardiac chamber dimensions (milliliters) at end-diastolic and end-systolic cardiac phases.	Baseline, 6 (+/-3) months, >12 months
Cardiovascular Flow Volumes	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.	Baseline, 6 (+/-3) months, >12 months
Ventricular Mass	Cardiac MRI measures of left ventricular myocardial mass (grams)	Baseline, 6 (+/-3) months, >12 months

Collaborators and Investigators

• Sponsor: Eric Y. Yang, MD PhD

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2018
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: August 21, 2019
• First Submitted That Met QC Criteria: August 22, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 22, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Mitral Regurgitation; Primary Mitral Regurgitation; Mitral Valve Annuloplasty; Chronic Mitral Regurgitation; Ventricular Reverse Remodeling; Ventricular Recovery
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Valve Prolapse; Mitral Valve Insufficiency; Prolapse; Heart Valve Diseases; Mitral Valve Prolapse; Ventricular Remodeling
• Other Study ID Numbers: Pro00018490

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No