Improving Mitral Repair for Functional Mitral Regurgitation (IMPROVE-FMR)

December 21, 2024 updated by: Robert Allan Guyton, Emory University

The investigators are interested in determining the best surgical technique to correct functional mitral regurgitation, as there is currently not one technique that is established to work better than the other.

The technique used in current clinical practice is undersizing mitral annuloplasty (UMA), in which a prosthetic ring is implanted onto the mitral valve to correct the leakage. Though widely adopted, durability of the repair is less, as 58% of the patients present with recurrent FMR within 2 years. There are no specific algorithms to predict who might have UMA failure, but research indicates that some geometric indices might be strong predictors. The investigators are interested in testing the hypothesis that, elevated lateral inter-papillary muscle separation (IPMS) is a predictor of post-UMA recurrence of FMR at 12 months. In the first part of this study, the study team will measure lateral IPMS before surgery and relate to post-surgery FMR severity at discharge/30 days, 6 months and 12 months.

A relatively newer technique is papillary muscle approximation (PMA), in which a suture draws together the two muscles that connect the mitral valve to the heart muscle prior to performing UMA. This reduces the lateral inter-papillary muscle separation (IPMS) and is expected to improve the durability of UMA. In the second part of this study, the investigators will perform PMA and UMA together and determine if FMR severity is reduced at discharge/30 days, 6 months and 12 months.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Functional mitral regurgitation (FMR) is a common heart valve lesion that is observed in patients suffering for cardiomyopathies. Timely surgical repair of FMR can reduce volume overload and potentially improve cardiac function. Durable surgical techniques for FMR repair are lacking. Undersizing mitral annuloplasty (UMA) is the current technique of choice, but its durability is quite poor. Thirty five percent of the repairs fail within one year and 58% fail within 2 years.

One of the probable mechanisms causing UMA failure is elevated lateral inter-papillary muscle separation (IPMS). The study investigators are interested in understanding if the extent of lateral IPMS has a direct impact on the failure rates of UMA at 1 year post surgery. Secondly, the investigators are interested in determining if patients with elevated lateral IPMS benefit from papillary muscle approximation (PMA) along with UMA.

The investigators are interested in determining the best way to correct functional mitral regurgitation, as there is currently not one technique that is established to better than the other. The most common repair technique is called undersizing mitral annuloplasty (UMA), in which a prosthetic ring is implanted onto the mitral valve to correct the leakage. Another more recent technique is papillary muscle approximation (PMA), in which a suture draws together the two muscles that connect the mitral valve to the heart muscle prior to performing UMA. In this research study, the study team is investigating whether they can identify those patients who will benefit from one repair over another.

The primary objective of this protocol is to investigate if pre-operative IPMS is predictive of FMR severity at 12 months after UMA to repair FMR. Furthermore, whether a cut-off value of pre-operative inter-papillary muscle separation can be established to predict patients who might have failure of UMA.

The secondary objective of this protocol is to investigate if adding PMA to UMA is an effective technique in reducing recurrence of FMR at 12 months post-procedure.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30342
        • Emory St. Joseph's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Mitral regurgitation of moderate or greater severity, as defined by the guidelines of the American Society of Echocardiography (via a transthoracic echo)
  • Cardiomyopathy of ischemic or non-ischemic origins, with or without the need for coronary revascularization
  • Concomitant right-sided valve repair or replacement (i.e. patients requiring concomitant tricuspid procedures)
  • Able to sign informed consent and release of medical information forms

Exclusion Criteria:

  • Any evidence of structural (chordal or leaflet) mitral lesions
  • Prior mitral valve repair
  • Contraindication for cardiopulmonary bypass
  • Clinical signs of cardiogenic shock at the time of randomization
  • ST-segment elevation myocardial infarction within 14 days before inclusion in this study
  • Congenital heart disease, except patent foramen ovale (PFO) or atrial septal defect (ASD)
  • Chronic renal insufficiency defined by creatinine ≥ 3.0 or chronic renal replacement therapy, who are contraindicated for cardiac surgery
  • Recent history of psychiatric disease that is likely to impair compliance with the study protocol, in the judgement of the investigator
  • Pregnancy at the time of randomization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: UMA (Group 1)
Participants in the UMA group will receive an undersizing mitral annuloplasty (UMA).
Procedure: Undersizing Mitral Annuloplasty
Participants will receive a commercially available annuloplasty ring of the surgeon's choice. Sutures are placed around the mitral annulus, and the metallic ring is then implanted onto the mitral annulus to reduce it in size.
Other: UMA + PMA (Group 2)
Participants in the UMA + PMA group will receive an undersizing mitral annuloplasty (UMA) with papillary muscle approximation (PMA).
Procedure: Undersizing Mitral Annuloplasty
Participants will receive a commercially available annuloplasty ring of the surgeon's choice. Sutures are placed around the mitral annulus, and the metallic ring is then implanted onto the mitral annulus to reduce it in size.
Procedure: Papillary Muscle Approximation
One or two 4-0 pledgeted sutures are used to draw the two papillary muscle tips together to reduce the inter papillary muscle separation (IPMS) before undergoing undersizing mitral annuloplasty.
No Intervention: Retrospectively identified patients
Retrospectively identified patients, who already underwent the standard of care surgery for the lesion of interest at Emory, within 6 months (± 1 month) after the date of their surgery, and are suitable for recruitment to the study for their post-operative research.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in FMR Severity
Time Frame: Pre-Intervention and Post-Intervention (12 Months)

The Severity (grade 0 to 4+) of mitral regurgitation of mitral regurgitation is measured using cardiac echocardiography and/or MRI (per physician's discretion).

Grade 0: None Grade 1 (Mild): Small, restricted jet of regurgitation with minimal impact on the heart's function. Typically, no symptoms and normal or near-normal left ventricular function.

Grade 2 (Moderate): Moderate jet size with some effect on the heart, but symptoms may still be absent or minimal. Mild to moderate left ventricular dilation may be present.

Grade 3 (Moderately Severe): Larger jet, more significant regurgitation, potentially causing mild heart failure symptoms or moderate dilation of the left ventricle.

Grade 4 (Severe): A large, prominent jet of regurgitation that significantly impacts heart function, often resulting in severe symptoms and marked left ventricular dilation.
Pre-Intervention and Post-Intervention (12 Months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality Rate
Time Frame: Post-Intervention (Up to 20 Days), Post-Intervention (Month 6), Post-Intervention (Month 12)
The number of participants who are deceased will be collected throughout the study at discharge and planned follow up visits.
Post-Intervention (Up to 20 Days), Post-Intervention (Month 6), Post-Intervention (Month 12)
All Cause Readmission Rate
Time Frame: Post Surgery (Up to 30 Days)
Readmission rate will be calculated for any cause within the first 30 days following surgery throughout the duration of the study.
Post Surgery (Up to 30 Days)
Heart Failure Readmission Rate
Time Frame: Post Surgery (Up to 30 Days)

Readmission rate will be calculated for heart failure after 30 days following surgery throughout the duration of the study. Classification of readmission as heart failure related requires at least 2 out of the following signs and symptoms of acute decompensated heart failure:

  • Dyspnea felt related to HF
  • Treatment with intravenous diuretic, vasodilator or inotropic therapy
  • X ray evidence of pulmonary edema or pulmonary vascular congestion
  • Rales on physical exam
  • Pulmonary capillary wedge pressure (PCWP) or LVEDP > 18mm Hg
Post Surgery (Up to 30 Days)
Change in Left Ventricular Mass
Time Frame: Baseline, Post-Intervention (Month 12)
Change in left ventricular mass at 12 months post intervention compared to baseline as measured by cardiac MRI.
Baseline, Post-Intervention (Month 12)
Number of Major Adverse Cardiac Events (MACE)
Time Frame: Up to 12 months post -intervention

MACE is defined as a composite of clinical events comprised of the following:

  • Death
  • Stroke
  • Worsening heart failure (+1 New York Heart Association (NYHA) class)
  • Congestive heart failure (CHF) hospitalization
  • Mitral valve re-intervention
Up to 12 months post -intervention
Change in Quality-of-Life Scale Score
Time Frame: Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
Participants will be asked to measure their perceived quality of life on a scale from 0 to 100 where 0 indicates "worst imaginable health state" and 100 indicates "best imaginable health state".
Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score
Time Frame: Baseline, Post-Intervention (Month 12)
The Minnesota Living with Heart Failure Questionnaire is a 21-item questionnaire that asks participants to describe how much their heart failure has affected life during the past month (4 weeks). Participants are asked if their heart failure prevented them from living as they want when completing daily tasks. Responses are rated on a scale from 0 to 5; 0 represents "no", 1 represents "very little" and 5 represents "very much" on a continuum. The MLHF score is obtained by summing the subjects responses. A minimum score is 0 indicating no affect to life and a maximum score is 105 indicating the greatest affect to life.
Baseline, Post-Intervention (Month 12)
Change in Functional Status Assessed by 6-Minute Walk Test (6MWT)
Time Frame: Baseline, Post-intervention (Month 6), Post-Intervention (Month 12)
Functional status will be measured by a 6-minute walk test, which assesses the distance walked (in feet) on a flat, hard surface in a period of 6 minutes (the 6MWD). The test is used for preoperative and postoperative evaluation and for measuring the response to therapeutic interventions for pulmonary and cardiac disease. Optimal reference equations from healthy population-based samples using standardized 6MWT methods are not yet available. A low 6MWD is nonspecific and nondiagnostic. When the 6MWD is reduced, a thorough search for the cause of the impairment is warranted.
Baseline, Post-intervention (Month 6), Post-Intervention (Month 12)
Change in Left Ventricular Volume
Time Frame: Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
Change in left ventricular volume at 6- and 12-month post-intervention compared to baseline as measured by as measured by the left ventricular end-diastolic diameter determined by echocardiogram.
Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
Change in Ejection Fraction
Time Frame: Baseline, Post-Intervention (Month 12)
Change in left ventricular ejection fraction at 12- months post-intervention compared to baseline as measured by echocardiogram.
Baseline, Post-Intervention (Month 12)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Robert Guyton, MD, Emory University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 20, 2018

Primary Completion (Actual)

December 31, 2023

Study Completion (Actual)

December 31, 2023

Study Registration Dates

First Submitted

November 30, 2017

First Submitted That Met QC Criteria

December 6, 2017

First Posted (Actual)

December 8, 2017

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 21, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00097939
  • 1R01HL133667-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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