Clinical trial NCT03366649: Improving Mitral Repair for Functional Mitral Regurgitation
Official title: Improving Mitral Repair for Functional Mitral Regurgitation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
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
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-12-08
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in FMR Severity
timeFrame: Pre-Intervention and Post-Intervention (12 Months)
Secondary outcomes:
measure: Mortality Rate
timeFrame: Post-Intervention (Up to 20 Days), Post-Intervention (Month 6), Post-Intervention (Month 12)
measure: Number of Major Adverse Cardiac Events (MACE)
timeFrame: Up to 12 months post -intervention
measure: Change in Quality-of-Life Scale Score
timeFrame: Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
measure: Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score
timeFrame: Baseline, Post-Intervention (Month 12)
measure: Change in Functional Status Assessed by 6-Minute Walk Test (6MWT)
timeFrame: Baseline, Post-intervention (Month 6), Post-Intervention (Month 12)
measure: All Cause Readmission Rate
timeFrame: Post Surgery (Up to 30 Days)
measure: Heart Failure Readmission Rate
timeFrame: Post Surgery (Up to 30 Days)
measure: Change in Left Ventricular Volume
timeFrame: Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
measure: Change in Ejection Fraction
timeFrame: Baseline, Post-Intervention (Month 12)
measure: Change in Left Ventricular Mass
timeFrame: Baseline, Post-Intervention (Month 12)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory St. Joseph's Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Robert Guyton, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
citation: 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.