REvascularization and Valve Intervention for Ischemic Valve diseasE: REVIVE Trial

Study Overview
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Brief Summary
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Ischemic mitral regurgitation (MR) and coronary artery disease is common and associated with significant morbidity and mortality. Ischemic MR has been traditionally treated surgically through either valve repair or replacement at the time of concomitant bypass grafting. Although patients with ischemic MR represent a heterogeneous group, outcomes for these patients over the intermediate term is poor owing to left ventricle (LV) dysfunction causing MR and the presence of coronary disease, which portends poor survival. There is an emergence of percutaneous therapies to treat MR which have been shown to be a less invasive, safe, and viable approach to treat comorbid patients. The decision to treat ischemic MR either surgically or percutaneously is influenced by the presence of coronary disease and the ability to provide adequate revascularization. Mitral valve surgery concomitant to surgical revascularization, however, is associated with a several fold increase in mortality. In fact, the incremental risk increase is further magnified in high-risk patients. We therefore propose a novel prospective study to guide intervention for ischemic MR. Patients will be randomized to undergo surgical therapy with either mitral repair/replacement and/or concomitant coronary artery bypass grafting OR percutaneous mitral repair, followed by coronary artery bypass grafting.

Official Title
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A Prospective Randomized Trial Comparing the Surgical Treatment of Ischemic Mitral Regurgitation Versus Percutaneous Mitral Repair Followed by Surgical Revascularization

Conditions
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Mitral Valve Insufficiency, Coronary Artery Disease

Intervention / Treatment
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* Procedure: Percutaneous mitral valve repair
* Procedure: Surgical mitral valve repair/replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with severe ischemic Mitral regurgitation (MR), as defined by the 2017 American Society of Echocardiography (ASE) guidelines for noninvasive evaluation of native valvular regurgitation. Presence of reversible myocardial ischemia confirmed by preoperative myocardial viability study using radionuclide imaging. Exclusion Criteria: Patients with mixed mitral valve pathology, including fibroelastic deficiency, rheumatic valve disease, ruptured mitral valve chordae, mitral valve endocarditis. Patients with acute ischemic MR, defined as MR caused by papillary muscle infarction and rupture. Age < 18 years. Prohibitive surgical risk or contraindications to Cardiopulmonary bypass (CPB) as defined by the Heart Team. Need for a concomitant surgical procedure, excluding Coronary artery bypass grafting (CABG), tricuspid valve repair, Patent foramen ovale (PFO) closure, Atrial septal defect (ASD) closure and Maze procedure. Prior mitral valve repair procedure (percutaneous or surgical). Leaflet anatomy unsuitable for MitraClip implantation, proper MitraClip positioning on the leaflets or sufficient reduction in MR by the MitraClip.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Percutaneous mitral repair<br>Percutaneous mitral repair +/- coronary artery bypass grafting within 14 days of mitral repair. | Procedure: Percutaneous mitral valve repair<br>* Percutaneous mitral repair will be performed using the MitraClip system.<br>|
| Active Comparator: Mitral valve surgery<br>Surgical mitral valve surgery +/- coronary artery bypass grafting | Procedure: Surgical mitral valve repair/replacement<br>* All mitral valve surgeries will be performed either via sternotomy or right thoracotomy, and with cardioplegic arrest and cardiopulmonary bypass. Mitral valve repair may include annuloplasty and adjunctive procedures as determined by the operating surgeon. For mitral valve replacement, the choice of mitral valve prosthesis will be left at the surgeon's discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate | All-cause mortality. Death from cardiovascular and non-cardiovascular causes. | Within 12 months of intervention | 
| Rate of myocardial infarction | These will be defined according to the Fourth Universal Definition of Myocardial Infarction | Within 12 months of intervention | 
| Rate of Stroke | 1) New, acute focal neurological deficit thought to be of vascular origin with signs or symptoms lasting > 24 h and confirmed by a neurologist or 2) new, focal neurological deficit lasting > 24 h with imaging evidence of cerebral infarction or intracerebral hemorrhage. | Within 12 months of intervention | 
| Hospitalization rate for congestive heart failure | Admission to hospital with congestive heart failure exacerbation being the primary reason for admission. Congestive heart failure exacerbation is defined as 1) evidence of fluid overload and elevated filling pressures (for example, a central venous pressure > 8mmHg and/or a pulmonary capillary wedge pressure > 18mmHg) and/or 2) new decrease in cardiac output (for example, cardiac index < 2.2 L/min/m2) and end-organ perfusion (measured by one or more of: urine output < 20mL/hr, lactate >= 2.0, mixed venous oxygen saturation < 70%). | Within 12 months of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in indexed left atrial volume |  | Within 6 and12 months of intervention | 
| Degree of left ventricular remodeling | Quantified by the change in left ventricular end systolic volume index | Within 6 and12 months of intervention | 
| Presence of recurrent MR ≥2+ | Defined as a regurgitant volume of 30-44 ml, a right ventricular ejection fraction of 30-39%, or an effective regurgitant orifice area of 20-29 mm2 | Within 6 and12 months of intervention | 
| Rate of mitral valve re-intervention |  | Within12 months of intervention | 
| Number of Participants with worsening in heart failure symptoms | +1 NYHA Class | Within 6 and12 months of intervention | 
| Cumulative hospital days |  | Within 12-months of intervention |