Improving Mitral Repair for Functional Mitral Regurgitation

NCT03366649 | Terminated Results DMC

• 2 other identifiers: IRB000979391R01HL133667-01A1
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 3

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.

Conditions

Cardiomyopathy; Cardiovascular Diseases; Congestive Heart Failure; Coronary Artery Disease; Heart Disease; Valvular Heart Disease; Mitral Valve Disease

Keywords

Bypass Surgery; Cardiology; Coronary Artery Bypass Surgery; Mitral Valve Repair; Mitral Valve Surgery; Coronary Revascularization

Outcome Measures

Primary Outcomes (1)

• Change in FMR Severity

  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 Outcomes (10)

• Mortality Rate

  Post-Intervention (Up to 20 Days), Post-Intervention (Month 6), Post-Intervention (Month 12)

• Number of Major Adverse Cardiac Events (MACE)

  Up to 12 months post -intervention

• Change in Quality-of-Life Scale Score

  Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)

• Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score

  Baseline, Post-Intervention (Month 12)

• Change in Functional Status Assessed by 6-Minute Walk Test (6MWT)

  Baseline, Post-intervention (Month 6), Post-Intervention (Month 12)

Study Arms (3)

UMA (Group 1)

OTHER

Participants in the UMA group will receive an undersizing mitral annuloplasty (UMA).

Procedure: Undersizing Mitral Annuloplasty

UMA + PMA (Group 2)

OTHER

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

Retrospectively identified patients

NO INTERVENTION

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.

Interventions

Undersizing Mitral Annuloplasty PROCEDURE

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.

UMA (Group 1); UMA + PMA (Group 2)

Papillary Muscle Approximation PROCEDURE

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.

UMA + PMA (Group 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Emory University: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (3)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Emory St. Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Related Publications (4)

• Kalra K, Wang Q, McIver BV, Shi W, Guyton RA, Sun W, Sarin EL, Thourani VH, Padala M. Temporal changes in interpapillary muscle dynamics as an active indicator of mitral valve and left ventricular interaction in ischemic mitral regurgitation. J Am Coll Cardiol. 2014 Nov 4;64(18):1867-79. doi: 10.1016/j.jacc.2014.07.988. Epub 2014 Oct 27.

  PMID: 25444139 BACKGROUND

• Michler RE, Smith PK, Parides MK, Ailawadi G, Thourani V, Moskowitz AJ, Acker MA, Hung JW, Chang HL, Perrault LP, Gillinov AM, Argenziano M, Bagiella E, Overbey JR, Moquete EG, Gupta LN, Miller MA, Taddei-Peters WC, Jeffries N, Weisel RD, Rose EA, Gammie JS, DeRose JJ Jr, Puskas JD, Dagenais F, Burks SG, El-Hamamsy I, Milano CA, Atluri P, Voisine P, O'Gara PT, Gelijns AC; CTSN. Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation. N Engl J Med. 2016 May 19;374(20):1932-41. doi: 10.1056/NEJMoa1602003. Epub 2016 Apr 3.

  PMID: 27040451 BACKGROUND

• Kron IL, Hung J, Overbey JR, Bouchard D, Gelijns AC, Moskowitz AJ, Voisine P, O'Gara PT, Argenziano M, Michler RE, Gillinov M, Puskas JD, Gammie JS, Mack MJ, Smith PK, Sai-Sudhakar C, Gardner TJ, Ailawadi G, Zeng X, O'Sullivan K, Parides MK, Swayze R, Thourani V, Rose EA, Perrault LP, Acker MA; CTSN Investigators. Predicting recurrent mitral regurgitation after mitral valve repair for severe ischemic mitral regurgitation. J Thorac Cardiovasc Surg. 2015 Mar;149(3):752-61.e1. doi: 10.1016/j.jtcvs.2014.10.120. Epub 2014 Nov 6.

  PMID: 25500293 BACKGROUND

• Acker MA, Parides MK, Perrault LP, Moskowitz AJ, Gelijns AC, Voisine P, Smith PK, Hung JW, Blackstone EH, Puskas JD, Argenziano M, Gammie JS, Mack M, Ascheim DD, Bagiella E, Moquete EG, Ferguson TB, Horvath KA, Geller NL, Miller MA, Woo YJ, D'Alessandro DA, Ailawadi G, Dagenais F, Gardner TJ, O'Gara PT, Michler RE, Kron IL; CTSN. Mitral-valve repair versus replacement for severe ischemic mitral regurgitation. N Engl J Med. 2014 Jan 2;370(1):23-32. doi: 10.1056/NEJMoa1312808. Epub 2013 Nov 18.

  PMID: 24245543 BACKGROUND

MeSH Terms

Conditions

Cardiomyopathies; Cardiovascular Diseases; Heart Failure; Coronary Artery Disease; Heart Diseases; Heart Valve Diseases

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Limitations and Caveats

Funds were granted for a clinical study led by the original PI, but enrollment halted during the pandemic. Follow-up was difficult, preventing study procedures, and preoperative imaging was lacking, preventing comparisons. The PI left in April 2023, leaving no expert MRI analysts for limited data. Dr. Guyton took over 8 months before the study was terminated. The NIH redirected funding to large animal studies and computational analysis.

Results Point of Contact

• Title: Dr. Robert Guyton
• Organization: Emory University

rguyton@emory.edu

404 686-4499

Study Officials

• Robert Guyton, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 8, 2017
• Study Start: March 20, 2018
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: January 16, 2025
• Results First Posted: January 16, 2025

Record last verified: 2024-12

Locations

US (3)