Improving Mitral Repair for Functional Mitral Regurgitation

Coronary Artery Disease Clinical Trial

— IMPROVE-FMR  

Official title:

Improving Mitral Repair for Functional Mitral Regurgitation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03366649
• Other study ID #: IRB00097939
• Secondary ID: 1R01HL133667-01A
• Status: Completed
• Phase: N/A
• Start date: March 20, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2024
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Cardiovascular Diseases
• Congestive Heart Failure
• Coronary Artery Disease
• Heart Disease
• Heart Diseases
• Heart Failure
• Heart Valve Diseases
• Mitral Valve Disease
• Mitral Valve Insufficiency
• Valvular Heart Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Emory St. Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Emory University	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in FMR Severity	Severity of mitral regurgitation measured using cardiac echocardiography and/or MRI (per physician's discretion).	Pre-Intervention, Post-Intervention (30 Days), Post-Intervention (6 Months), Post-Intervention (12 Months)
Secondary	Mortality Rate	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)
Secondary	Number of Major Adverse Cardiac Events (MACE)	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
Secondary	Change in Quality-of-Life Scale Score	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)
Secondary	Change in Minnesota Living with Heart Failure (MLHF) Questionnaire Score	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 6), Post-Intervention (Month 12)
Secondary	Change in Functional Status assessed by 6-Minute Walk Test (6MWT)	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)
Secondary	All Cause Readmission Rate	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)
Secondary	Heart Failure Readmission Rate	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)
Secondary	Change in Left Ventricular Volume	Change in left ventricular volume at 6- and 12- months post intervention compared to baseline as measured by echocardiogram	Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
Secondary	Change in Left Ventricular Volume	Change in left ventricular volume at 12 months post intervention compared to baseline as measured by cardiac MRI	Baseline, Post-Intervention (Month 12)
Secondary	Change in Left Ventricular Mass	Change in left ventricular mass at 6- and 12- months post intervention compared to baseline as measured by echocardiogram.	Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
Secondary	Change in Left Ventricular Mass	Change in left ventricular mass at 12 months post intervention compared to baseline as measured by cardiac MRI.	Baseline, Post-Intervention (Month 12)