Coronary Artery Disease, Mitral Valve Insufficiency
Conditions
Keywords
Ischemic Mitral Regurgitation, Mitral Valve Disease, Severe Mitral Regurgitation
Brief summary
People with coronary artery disease (CAD) or people who have had a heart attack may develop a leak in the mitral valve of their heart and may therefore need to undergo surgery to fix the valve. The best way to fix the mitral valve remains undetermined. This study will evaluate whether it is better for people with severe mitral valve leakage to undergo a mitral valve replacement procedure or a mitral valve repair procedure.
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. After a heart attack, some people may develop a leak in the mitral valve of the heart. This condition is known as ischemic mitral regurgitation (IMR), and it can cause blood to flow backward into the heart. If left untreated, severe IMR can lead to heart failure or serious heart rhythm irregularities, known as arrhythmias. People with severe mitral valve leakage routinely undergo one of two surgical procedures to fix the mitral valve: a mitral valve repair procedure, in which a surgical ring is used to repair the valve; or a mitral valve replacement procedure, in which the damaged valve is replaced with a new one. Currently, there is no consensus in the medical community as to which procedure is more beneficial. The purpose of this study is to determine whether people with severe mitral valve regurgitation should undergo a mitral valve repair procedure or a mitral valve replacement procedure. This study will enroll people with CAD who have severe 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 the mitral valve repair procedure or the mitral valve replacement procedure. 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 Day 30 and 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 with Annuloplasty
The annuloplasty ring will be chosen by the surgeon. The ring is sized to the anterior leaflet and intertrigonal distance. A semi-rigid or rigid annuloplasty ring will be used, and if tethering is present, a subvalvar procedure will be performed.
PROCEDUREMitral Valve Replacement
Mitral valve replacement will include complete preservation of the subvalvar apparatus. The technique of preservation, choice of prosthetic valve, and technique of suture placement will be dependent on the surgeon's preference. The prosthetic valve will be tested for paravalvular leaks by using the left ventricular saline infusion test.
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
* Chronic severe ischemic mitral regurgitation (often with tethering as a major mechanism) 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 ≥ 0.4 cmsq. If ERO \< 0.4, 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 * Eligible for surgical repair and replacement of mitral valve * CAD with or without the need for coronary revascularization
Exclusion criteria
* Any evidence of structural (chordal or leaflet) mitral valve disease or ruptured papillary muscle * Prior mitral valve repair * Severe irreversible pulmonary hypertension in the judgment of the investigator * Medically unable to undergo cardiopulmonary bypass (CPB) * Inability to derive ERO and end-systolic volume index (ESVI) by transthoracic echocardiography * Planned concomitant intra-operative procedures (with the exception of tricuspid valve repair, closure of patent foramen ovale \[PFO\] or atrial septal defect \[ASD\] or Maze procedure) * Clinical signs of cardiogenic shock at the time of surgery * Treatment with long-term intravenous inotropic therapy at the time of surgery * 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 * Excessive surgical risk, as judged by the surgical investigator * Recent history of psychiatric disease (including drug or alcohol abuse) that is likely to impair compliance with the study, as judged by 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 this study * Any concurrent disease with a life expectancy of less than 2 years * Pregnant
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 |
|---|---|
| All-cause Mortality | Measured at Month 24 |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mitral Valve Repair With Annuloplasty Participants will undergo mitral valve repair with annuloplasty and a sub-valvular procedure for severe tethering.
Mitral Valve Repair with Annuloplasty: The annuloplasty ring will be chosen by the surgeon. The ring is sized to the anterior leaflet and intertrigonal distance. A semi-rigid or rigid annuloplasty ring will be used, and if tethering is present, a subvalvar procedure will be performed. | 126 |
| Mitral Valve Replacement Participants will undergo mitral valve replacement and complete preservation of the sub-valvular apparatus.
Mitral Valve Replacement: Mitral valve replacement will include complete preservation of the subvalvar apparatus. The technique of preservation, choice of prosthetic valve, and technique of suture placement will be dependent on the surgeon's preference. The prosthetic valve will be tested for paravalvular leaks by using the left ventricular saline infusion test. | 125 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 24 | 29 |
| Overall Study | Lost to Follow-up | 4 | 6 |
| Overall Study | Withdrawal by Subject | 8 | 6 |
Baseline characteristics
| Characteristic | Mitral Valve Repair With Annuloplasty | Total | Mitral Valve Replacement |
|---|---|---|---|
| Age, Continuous | 68.9 years STANDARD_DEVIATION 10.2 | 68.4 years STANDARD_DEVIATION 9.6 | 67.9 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 24 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 113 Participants | 227 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 44 Participants | 24 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 | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 104 Participants | 202 Participants | 98 Participants |
| Region of Enrollment Canada | 25 Participants | 51 Participants | 26 Participants |
| Region of Enrollment United States | 101 Participants | 200 Participants | 99 Participants |
| Sex: Female, Male Female | 49 Participants | 96 Participants | 47 Participants |
| Sex: Female, Male Male | 77 Participants | 155 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 24 / 126 | 29 / 125 |
| other Total, other adverse events | 33 / 126 | 44 / 125 |
| serious Total, serious adverse events | 89 / 126 | 88 / 125 |
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 With Annuloplasty | Degree of Left Ventricular Remodeling, as Assessed by Left Ventricular End Systolic Volume Index (LVESVI) | 54.6 ml per square meter of body-surface area | Standard Deviation 25 |
| Mitral Valve Replacement | Degree of Left Ventricular Remodeling, as Assessed by Left Ventricular End Systolic Volume Index (LVESVI) | 60.7 ml per square meter of body-surface area | Standard Deviation 31.5 |
Comparison: The trial was designed with a power of 90% to detect a between-group difference of 15 ml per square meter in the LVESVI from baseline to 12 months. We assumed a baseline LVESVI of 100 ml per square meter, improvements of 20 ml per square meter in the repair group and 35 ml per square meter in the replacement group, and equal 1-year mortality of 10 to 20% in the two groups. The primary null hypothesis was that there would be no between-group difference in the LVESVI at 12 months.p-value: 0.18Wilcoxon (Mann-Whitney)
Secondary
All-cause Mortality
Time frame: Measured at Month 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mitral Valve Repair With Annuloplasty | All-cause Mortality | 24 Participants |
| Mitral Valve Replacement | All-cause Mortality | 29 Participants |
p-value: 0.3995% CI: [0.46, 1.35]Log Rank