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

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ClinicalTrials.gov Identifier: NCT03366649
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : October 10, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Sai Muralidhar Padala, Emory University

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 Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 20, 2018
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023

Arm Intervention/treatment
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. 10-12 ethicon sutures are placed around the mitral annulus, and the metallic ring is then implanted onto the mitral annulus to reduce it in size. To ensure uniformity between patients, an Edwards Lifesciences Physio II ring will be used in all patients, with a ring size ranging between 26mm-30mm.

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. 10-12 ethicon sutures are placed around the mitral annulus, and the metallic ring is then implanted onto the mitral annulus to reduce it in size. To ensure uniformity between patients, an Edwards Lifesciences Physio II ring will be used in all patients, with a ring size ranging between 26mm-30mm.

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.



Primary Outcome Measures :
  1. Change in FMR Severity [ Time Frame: 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 :
  1. 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.

  2. Number of Major Adverse Cardiac Events (MACE) [ Time Frame: Duration of Study (6 Years) ]

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

    • Death
    • Stroke
    • Worsening heart failure (+1 NYHA class)
    • CHF hospitalization
    • Mitral valve re-intervention

  3. 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".

  4. Change in Minnesota Living with Heart Failure (MLHF) Questionnaire Score [ Time Frame: 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.

  5. 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.

  6. 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.

  7. 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
    • PCWP or LVEDP > 18mm Hg

  8. 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 months post intervention compared to baseline as measured by echocardiogram

  9. Change in Left Ventricular Volume [ Time Frame: Baseline, Post-Intervention (Month 12) ]
    Change in left ventricular volume at 12 months post intervention compared to baseline as measured by cardiac MRI

  10. Change in Left Ventricular Mass [ Time Frame: 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.

  11. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients with functional mitral regurgitation (FMR) from either ischemic or non-ischemic cardiomyopathies, referred for surgical or transcatheter mitral valve annuloplasty. Suitability for mitral annuloplasty is determined by the surgeon, using some or all the criteria described below:

  • Left ventricular end diastolic diameter is less than or equal to 70mm.
  • Systolic tenting height is less than or equal to 12mm
  • Mitral regurgitation of moderate or greater severity, as defined by the guidelines of the American society of echocardiography at the time of the study approval (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, or able to assign a legal representative who can sign on the patient's behalf.

Exclusion Criteria:

  • Any evidence of structural (chordal or leaflet) mitral lesions.
  • Planned concomitant intra-operative procedures (except for closure of patent foramen ovale or atrial septal defect)
  • Planned concomitant intra-operative Maze procedure for symptomatic paroxysmal atrial fibrillation.
  • Persistent atrial fibrillation
  • 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 PFO or 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03366649


Contacts
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Contact: Sai Muralidhar Padala, PhD 404-251-0651 spadala@emory.edu
Contact: Robert A Guyton, MD 4047783836 rguyton@emory.edu

Locations
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United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Sai Padala, PhD    404-251-0651    spadala@emory.edu   
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Sai Padala, PhD    404-251-0651    spadala@emory.edu   
Emory St. Joseph's Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Sai Padala, PhD    404-251-0651    spadala@emory.edu   
Sponsors and Collaborators
Emory University
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Sai Muralidhar Padala, PhD Emory University

Publications:

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Responsible Party: Sai Muralidhar Padala, Assistant Professor of Cardiothoracic Surgery, Emory University
ClinicalTrials.gov Identifier: NCT03366649     History of Changes
Other Study ID Numbers: IRB00097939
1R01HL133667-01A1 ( U.S. NIH Grant/Contract )
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: October 2019

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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
Keywords provided by Sai Muralidhar Padala, Emory University:
Bypass Surgery
Cardiology
Coronary Artery Bypass Surgery
Mitral Valve Repair
Mitral Valve Surgery
Coronary Revascularization
Additional relevant MeSH terms:
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Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Failure
Heart Diseases
Cardiomyopathies
Mitral Valve Insufficiency
Heart Valve Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases