Coronary Artery Disease, Mitral Valve Insufficiency
Conditions
Keywords
Ischemic Mitral Regurgitation, Mitral Valve Regurgitation
Brief summary
Coronary artery bypass grafting (CABG) is a procedure that people with coronary artery disease (CAD) may undergo to increase blood flow to the heart. During a CABG procedure, people who have a leak in one of the valves in the heart-the mitral valve-may at the same time undergo a procedure that repairs the valve. This study will evaluate whether people with moderate mitral valve leakage would be better off undergoing CABG plus the mitral valve repair procedure or undergoing CABG alone.
Detailed description
CAD occurs when the arteries that supply blood to the heart become blocked as a result of plaque buildup. In severe cases, CAD can cause chest pain, shortness of breath, and heart attack. CABG is one treatment option for people with CAD. During a CABG procedure, a healthy artery or vein from another part of the body is connected to the blocked coronary artery. Blood flow is then routed around the blockage to the heart. After a heart attack, some people may have a leak in the mitral valve of the heart. This condition is known as ischemic mitral regurgitation (IMR) and is associated with poor health outcomes, including worsening heart failure. In people with severe mitral valve leakage, the CABG procedure and a mitral valve repair procedure are routinely performed together; however, in people with only moderate valve leakage, there is no consensus in the medical community as to whether the mitral valve repair procedure is beneficial at the time of CABG. The purpose of this study is to determine whether people with moderate mitral valve regurgitation should undergo a mitral valve repair procedure in addition to CABG or undergo CABG alone. This study will enroll people with CAD who require a CABG procedure and have moderate mitral regurgitation. At a baseline study visit, participants will undergo a physical examination; blood collection; neurocognitive tests; and questionnaires regarding medical history, medication history, and quality of life. In the operating room, participants will be randomly assigned to undergo either CABG surgery and the mitral valve repair procedure or only CABG surgery. Blood, urine, and tissue samples may be collected from participants after the surgery; this is optional and will only be done with prior approval from participants. All participants will attend study visits at Months 6, 12, and 24. At each visit, participants will take part in a medication history review, a physical examination, an echocardiogram, a cardiopulmonary exercise test, neurocognitive tests, and quality of life surveys.
Interventions
PROCEDUREMitral Valve Repair
Surgical techniques for mitral valve repair may need to be adjusted at the discretion of the surgeon, as based on intra-operative findings that may not be previously recognized in the pre-operative evaluation. The common elements for mitral annuloplasty planned as part of this study include the following: 1. All procedures will be performed with cardiopulmonary bypass (CPB) and with moderate hypothermia. Cannulation will be central with aortic cannulation for arterial inflow from the cardiopulmonary bypass circuit. Right atrial or bicaval (inferior and superior vena cava) drainage cannulas will be employed. 2. The heart will be arrested with cardioplegia. 3. A complete annular ring shall be placed unless specifically contraindicated by intra-operative findings. Additional repair of the mitral apparatus itself will be based on intra-operative findings.
PROCEDURECABG
CABG will be performed using standard surgical techniques. Conduit selection and harvesting methods will not be prescribed, except that utilization of the left internal mammary artery (LIMA) is recommended when a left anterior descending (LAD) graft is indicated. The technical details of bypass grafting will not be prescribed. Complete revascularization will be performed, within the judgment of the surgical investigator.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Canadian Institutes of Health Research (CIHR)
National Institute of Neurological Disorders and Stroke (NINDS)
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Moderate mitral regurgitation in the judgment of the clinical site echocardiographer, assessed by transthoracic echocardiogram. Assessment of mitral regurgitation will be performed using an integrative method (Zoghbi W. et al. J. American Society of Echocardiography. 2003:16:777-802. see appendix). Quantitative guidelines as proposed would be: ERO between 0.2 cmsq to 0.39 cmsq. If ERO \< 0.2, then the degree of mitral regurgitation will be guided by other color Doppler quantitative methods (jet area/left atrial area ratio, vena contracta, supportive criteria in an integrated fashion * CAD that is amenable to CABG and a clinical indication for revascularization * Age ≥ 18 years
Exclusion criteria
* Any evidence of structural (chordal or leaflet) mitral valve disease * Inability to derive ERO and end-systolic volume index (ESVI) by transthoracic echocardiography * Planned concomitant intra-operative procedures (with the exception of closure of patent foramen ovale \[PFO\] or atrial septal defect \[ASD\]or Maze procedure or left atrial appendage excision) * Prior surgical or percutaneous mitral valve repair * Contraindication to cardiopulmonary bypass (CPB) * Clinical signs of cardiogenic shock at the time of surgery * Treatment with chronic intravenous inotropic therapy at the time of surgery * Severe, irreversible pulmonary hypertension in the judgment of the investigator * ST segment elevation myocardial infarction (MI) requiring intervention in the 7 days before surgery * Congenital heart disease (except PFO or ASD) * Evidence of cirrhosis or liver synthetic failure * Recent history of psychiatric disease (including drug or alcohol abuse) that is likely to impair compliance with the study, in the judgment of the investigator * Therapy with an investigational intervention at the time of screening, or planning to enroll in an additional investigational intervention study during participation in the study * Any concurrent disease with a life expectancy of less than 2 years * Pregnancy at the time of randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Degree of Left Ventricular Remodeling, as Assessed by Left Ventricular End Systolic Volume Index (LVESVI) | Measured at Month 12 |
Secondary
| Measure | Time frame |
|---|---|
| Major Adverse Cardiac Event, Including Death, Stroke, Worsening Heart Failure (+1 New York Heart Association [NYHA] Class), Congestive Heart Failure Hospitalization, or Mitral Valve Re-intervention | Measured at Month 24 |
Countries
Canada, Denmark, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mitral Valve Repair Participants will undergo CABG and a mitral valve repair procedure.
Mitral Valve Repair: Surgical techniques for mitral valve repair may need to be adjusted at the discretion of the surgeon, as based on intra-operative findings that may not be previously recognized in the pre-operative evaluation. The common elements for mitral annuloplasty planned as part of this study include the following:
1. All procedures will be performed with cardiopulmonary bypass (CPB) and with moderate hypothermia. Cannulation will be central with aortic cannulation for arterial inflow from the cardiopulmonary bypass circuit. Right atrial or bicaval (inferior and superior vena cava) drainage cannulas will be employed.
2. The heart will be arrested with cardioplegia.
3. A complete annular ring shall be placed unless specifically contraindicated by intra-operative findings. Additional repair of the mitral apparatus itself will be based on intra-operative findings.
CABG: CABG will be performed using | 150 |
| CABG Participants will undergo CABG.
CABG: CABG will be performed using standard surgical techniques. Conduit selection and harvesting methods will not be prescribed, except that utilization of the left internal mammary artery (LIMA) is recommended when a left anterior descending (LAD) graft is indicated. The technical details of bypass grafting will not be prescribed. Complete revascularization will be performed, within the judgment of the surgical investigator. | 151 |
| Total | 301 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 15 | 16 |
| Overall Study | Lost to Follow-up | 4 | 19 |
| Overall Study | Withdrawal by Subject | 8 | 8 |
Baseline characteristics
| Characteristic | CABG | Total | Mitral Valve Repair |
|---|---|---|---|
| Age, Continuous | 65.2 years STANDARD_DEVIATION 11.3 | 64.7 years STANDARD_DEVIATION 10.5 | 64.3 years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 26 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 137 Participants | 275 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 9 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 50 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 122 Participants | 237 Participants | 115 Participants |
| Region of Enrollment Canada | 36 participants | 71 participants | 35 participants |
| Region of Enrollment Denmark | 1 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 114 participants | 228 participants | 114 participants |
| Sex: Female, Male Female | 52 Participants | 96 Participants | 44 Participants |
| Sex: Female, Male Male | 99 Participants | 205 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 15 / 150 | 16 / 151 |
| other Total, other adverse events | 44 / 150 | 37 / 151 |
| serious Total, serious adverse events | 88 / 150 | 79 / 151 |
Outcome results
Primary
Degree of Left Ventricular Remodeling, as Assessed by Left Ventricular End Systolic Volume Index (LVESVI)
Time frame: Measured at Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mitral Valve Repair | Degree of Left Ventricular Remodeling, as Assessed by Left Ventricular End Systolic Volume Index (LVESVI) | 49.6 ml per square meter | Standard Deviation 31.5 |
| CABG | Degree of Left Ventricular Remodeling, as Assessed by Left Ventricular End Systolic Volume Index (LVESVI) | 46.1 ml per square meter | Standard Deviation 22.4 |
Comparison: The primary null hypothesis was that there would be no significant between-group difference in the LVESVI at 12 months.p-value: 0.61Wilcoxon (Mann-Whitney)
Secondary
Major Adverse Cardiac Event, Including Death, Stroke, Worsening Heart Failure (+1 New York Heart Association [NYHA] Class), Congestive Heart Failure Hospitalization, or Mitral Valve Re-intervention
Time frame: Measured at Month 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mitral Valve Repair | Major Adverse Cardiac Event, Including Death, Stroke, Worsening Heart Failure (+1 New York Heart Association [NYHA] Class), Congestive Heart Failure Hospitalization, or Mitral Valve Re-intervention | 46 Participants |
| CABG | Major Adverse Cardiac Event, Including Death, Stroke, Worsening Heart Failure (+1 New York Heart Association [NYHA] Class), Congestive Heart Failure Hospitalization, or Mitral Valve Re-intervention | 48 Participants |
p-value: 0.83Chi-squared