IMPROVE-FMR: Improving Mitral Repair for Functional Mitral Regurgitation

Sponsor

Emory University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03366649

Collaborator

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

140

Enrollment

Locations

Arms

69.4

Anticipated Duration (Months)

46.7

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiomyopathy Cardiovascular Diseases Congestive Heart Failure Coronary Artery Disease Heart Disease Valvular Heart Disease Mitral Valve Disease	Procedure: Undersizing Mitral Annuloplasty Procedure: Papillary Muscle Approximation	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Improving Mitral Repair for Functional Mitral Regurgitation

Actual Study Start Date :

Mar 20, 2018

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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.

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

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.

Outcome Measures

Primary Outcome Measures

Change in FMR Severity [Pre-Intervention, Post-Intervention (30 Days), Post-Intervention (6 Months), Post-Intervention (12 Months)]
Severity of mitral regurgitation measured using cardiac echocardiography and/or MRI (per physician's discretion).

Secondary Outcome Measures

Mortality Rate [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.
Number of Major Adverse Cardiac Events (MACE) [Duration of Study (6 Years)]
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
Change in Quality of Life Scale Score [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".
Change in Minnesota Living with Heart Failure (MLHF) Questionnaire Score [Baseline, Post-Intervention (Month 6), 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.
Change in Functional Status assessed by 6-Minute Walk Test (6MWT) [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.
All Cause Readmission Rate [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.
Heart Failure Readmission Rate [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
Change in Left Ventricular Volume [Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)]
Change in left ventricular volume at 6 and 12 months post intervention compared to baseline as measured by echocardiogram
Change in Left Ventricular Volume [Baseline, Post-Intervention (Month 12)]
Change in left ventricular volume at 12 months post intervention compared to baseline as measured by cardiac MRI
Change in Left Ventricular Mass [Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)]
Change in left ventricular mass at 6 and 12 months post intervention compared to baseline as measured by echocardiogram.
Change in Left Ventricular Mass [Baseline, Post-Intervention (Month 12)]
Change in left ventricular mass at 12 months post intervention compared to baseline as measured by cardiac MRI.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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 prior to 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Hospital Midtown	Atlanta	Georgia	United States	30308
2	Emory University Hospital	Atlanta	Georgia	United States	30322
3	Emory St. Joseph's Hospital	Atlanta	Georgia	United States	30342