Mitral Valve Insufficiency, Heart Failure
Conditions
Keywords
Advanced Heart Failure, Non-Ischemic Heart Failure, Mitral Regurgitation, Mitral Valve Replacement, Congestive Heart Failure, Surgical Mitral Valvuloplasty, Dilated Cardiomyopathy, Annular Ring
Brief summary
Mitral regurgitation (MR), also known as mitral insufficiency, is a condition in which the heart's mitral valve, located between two of the heart's main chambers, does not firmly shut, allowing blood to leak backwards within the heart. Improper functioning of the mitral valve disrupts the proper flow of blood through the body, resulting in shortness of breath and fatigue. When mild, MR may not pose a significant danger to a person's health, but severe MR may be associated with serious complications, such as heart failure, irregular heart rhythm, and high blood pressure. Although there are treatments for MR, including medication and surgery, more information is needed on the effectiveness of these treatments in people with significant MR. This study will compare the safety and effectiveness of corrective surgery added to optimal medical treatment (OMT) versus OMT alone in treating people with significant MR caused by an enlarged heart.
Detailed description
It is estimated that approximately 4 out of 10 people with an enlarged heart due to heart failure develop MR, referred to as secondary MR. This type of MR is caused by enlargement of the left ventricle (LV), one of the heart's main chambers. In turn, the enlargement leads to stretching of certain heart muscles around the mitral valve and of the valve itself. Symptoms of secondary MR may include shortness of breath, fatigue, dizziness, swollen feet, cough, and heart palpitations. Mitral valve repair or replacement surgery is sometimes considered as a treatment option to restore proper heart function in people with secondary MR. Surgical repair with placement of an artificial ring around the mitral valve can help to tighten the valve and add benefit to non-surgical treatments for MR. However, although surgical placement of the ring improves mitral valve function in most people, it is not known whether this surgery helps people live longer and healthier lives. This study will compare the safety and effectiveness of surgical mitral valvuloplasty with placement of an annular ring (SMVR) added to optimal medical treatment (OMT) versus OMT alone in non-ischemic heart failure patients with significant secondary MR. Participation from baseline through follow-up in this study will last 18 months. All potential participants will initially undergo a transesophageal echocardiogram to confirm the presence of an abnormal mitral valve. Eligible participants will then undergo a number of baseline tests, which will include cardiopulmonary exercise stress testing, a chest wall echocardiogram, blood draw, 6-minute walk test, medical questionnaires, and a physical exam. Next, participants will be randomly assigned to receive immediate open heart surgery with the placement of a mitral valve ring, delayed surgery at least 18 months later, or OMT. Participants assigned to receive immediate surgery will undergo the surgery 2 weeks after baseline testing. Participants assigned to receive OMT will receive treatment with any of the following medication regimens: combination of vasodilator therapy and diuretics, nitrates and nifedipine, and beta-adrenergic blocker therapy. Follow-up visits for all participants will occur at Months 1, 3, 6, 12, and 18 and will include repeat baseline testing. Long-term survival status data may be collected beyond 18 months for some participants.
Interventions
PROCEDURESurgical mitral valvuloplasty with placement of annular ring (SMVR)
Participants will undergo open heart surgery to mechanically reduce mitral regurgitation (MR). A complete rigid or semi-rigid annular ring will be placed unless specifically contraindicated by intraoperative findings. The ring size will be between 24 mm and 27 mm in the anteroposterior diameter. Annular ring sutures will be placed circumferentially approximately 1 mm off the hinge point between the leaflet and the atrial tissue. The total number of sutures will vary between 4 and 7 sutures anteriorly, while 8 to 12 sutures will be utilized for the posterior segment of the annulus. Additional repair of the mitral apparatus itself will be based on intraoperative findings. Leaflet repair will be performed for significant prolapse. Submitral apparatus repair will be performed for ruptured or significantly elongated chordae as well as significant chordal tethering.
Optimal medical therapy can include, but is not limited to, any of the following treatment regimens: combination of vasodilator therapy and diuretics, nitrates and nifedipine, and beta-adrenergic blocker therapy.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Heart Failure Clinical Research Network
Duke University
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
* Symptomatic chronic heart failure, New York Heart Association (NYHA) class II to IIIb * Left ventricular ejection fraction of 0.35 due to non-ischemic etiology * Evidence by transthoracic echocardiography (TTE) of moderate or severe MR without obvious primary mitral valve pathology * Peak VO2 less than or equal to 22 ml/kg/min, as obtained at study entry * Optimal heart failure therapy for at least 6 months prior to study entry
Exclusion criteria
* Significant coronary artery disease (greater than 75% lesion in any vessel) by coronary angiography or by a history of a prior heart attack * Heart failure due to active myocarditis, congenital heart disease, or obstructive hypertrophic cardiomyopathy * Significant ventricular arrhythmias not treated with an implantable defibrillator * Primary MR due to significant chordal or leaflet abnormalities by TTE * Other hemodynamically relevant stenotic or regurgitant valvular diseases * Severe tricuspid regurgitation (TR) (moderate TR is allowed) * Severe pulmonic regurgitation (PR) (moderate PR is allowed) * Moderate to severe aortic regurgitation * Any moderate to severe stenotic lesions using American Heart Association/American College of Cardiology (AHA/ACC) criteria 31 * Dependence on chronic inotropic therapy * Restrictive cardiomyopathy or constrictive pericarditis * Severe right ventricular dysfunction * Baseline creatinine greater than or equal to 3 mg/dL or renal replacement therapy (chronic hemodialysis or peritoneal dialysis) * Poor transthoracic sonographic windows precluding reasonable assessment of LV endocardial borders from apical imaging on TTE * Inability to perform the spirometric exercise testing * Significant chronic lung disease that might interfere with the ability to interpret the spirometric measurements, including home oxygen, forced expiratory volume in 1 second (FEV1) less than 1.0 L/min, or exertional hypoxemia with saturations less than 90% * Any known neoplastic disease other than skin cancer * Other terminal illness with a life expectancy less than 1 year * Plan for percutaneous mitral valve procedure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Effect of Adding SMVR to OMT Alone on LV Remodeling, Specifically LV End-systolic Volume Index (LVESVI) | Measured at Month 18 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6-minute Walk Test | Measured at baseline and Month 18 but n/a | The 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No data were collected for this outcome measure and no analysis was performed. |
| Change in Minnesota Living With Heart Failure (MLHF) Score | Planned to be measured at baseline and Month 18 but n/a | Change in MLHF score. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed. |
| Peak VO2 | Measured at Month 18 | — |
| Total Mortality (All Causes) | Measured at Month 18 | Total all-cause mortality at 18 months. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed. |
| Perioperative Mortality | Measured between Days 0 and 30 postsurgery | — |
| Total Days Alive and Total Days Not Hospitalized | Measured at baseline and Month 18 | Total days alive and not hospitalized by 18 months. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1 Medical Therapy Plus Surgical Repair Participants will receive optimal medical therapy plus surgical mitral valve repair with complete annular ring placement | 1 |
| 2 Medical Therapy Only Participants will receive optimal medical therapy alone | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | 2 Medical Therapy Only | 1 Medical Therapy Plus Surgical Repair | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 63 years | 65.5 years | 64.25 years STANDARD_DEVIATION 1.49 |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 1 / 1 | 1 / 1 |
Outcome results
Primary
Effect of Adding SMVR to OMT Alone on LV Remodeling, Specifically LV End-systolic Volume Index (LVESVI)
Time frame: Measured at Month 18
Population: Data were not analyzed due to study termination
Secondary
Change in 6-minute Walk Test
The 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No data were collected for this outcome measure and no analysis was performed.
Time frame: Measured at baseline and Month 18 but n/a
Population: The 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No data were collected for this outcome measure and no analysis was performed.
Secondary
Change in Minnesota Living With Heart Failure (MLHF) Score
Change in MLHF score. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed.
Time frame: Planned to be measured at baseline and Month 18 but n/a
Population: the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No data were collected for this outcome measure and no analysis was performed.
Secondary
Peak VO2
Time frame: Measured at Month 18
Population: The 2 patients enrolled in the study did not reach their endpoints before the trial was closed. No data were collected for this outcome measure and no analysis was performed.
Secondary
Perioperative Mortality
Time frame: Measured between Days 0 and 30 postsurgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Optimal Medical Therapy Plus Surgical MVR | Perioperative Mortality | 0 participants |
| Optimal Medical Therapy Alone | Perioperative Mortality | 0 participants |
Secondary
Total Days Alive and Total Days Not Hospitalized
Total days alive and not hospitalized by 18 months. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed.
Time frame: Measured at baseline and Month 18
Population: The 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No data were collected for this outcome measure and no analysis was performed.
Secondary
Total Mortality (All Causes)
Total all-cause mortality at 18 months. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed.
Time frame: Measured at Month 18
Population: The 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No data were collected for this outcome measure and no analysis was performed.