Cardiomyopathy, Cardiovascular Diseases, Congestive Heart Failure, Coronary Artery Disease, Heart Disease, Mitral Valve Disease, Valvular Heart Disease
Conditions
Keywords
Bypass Surgery, Cardiology, Coronary Artery Bypass Surgery, Mitral Valve Repair, Mitral Valve Surgery, Coronary Revascularization
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.
Interventions
PROCEDUREUndersizing Mitral Annuloplasty
Participants will receive a commercially available annuloplasty ring of the surgeon's choice. Sutures are placed around the mitral annulus, and the metallic ring is then implanted onto the mitral annulus to reduce it in size.
PROCEDUREPapillary Muscle Approximation
One or two 4-0 pledgeted sutures are used to draw the two papillary muscle tips together to reduce the inter papillary muscle separation (IPMS) before undergoing undersizing mitral annuloplasty.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in FMR Severity | Pre-Intervention and Post-Intervention (12 Months) | The Severity (grade 0 to 4+) of mitral regurgitation of mitral regurgitation is measured using cardiac echocardiography and/or MRI (per physician's discretion). Grade 0: None Grade 1 (Mild): Small, restricted jet of regurgitation with minimal impact on the heart's function. Typically, no symptoms and normal or near-normal left ventricular function. Grade 2 (Moderate): Moderate jet size with some effect on the heart, but symptoms may still be absent or minimal. Mild to moderate left ventricular dilation may be present. Grade 3 (Moderately Severe): Larger jet, more significant regurgitation, potentially causing mild heart failure symptoms or moderate dilation of the left ventricle. Grade 4 (Severe): A large, prominent jet of regurgitation that significantly impacts heart function, often resulting in severe symptoms and marked left ventricular dilation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Major Adverse Cardiac Events (MACE) | Up to 12 months post -intervention | MACE is defined as a composite of clinical events comprised of the following: * Death * Stroke * Worsening heart failure (+1 New York Heart Association (NYHA) class) * Congestive heart failure (CHF) hospitalization * Mitral valve re-intervention |
| Change in Quality-of-Life Scale Score | Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12) | Participants will be asked to measure their perceived quality of life on a scale from 0 to 100 where 0 indicates worst imaginable health state and 100 indicates best imaginable health state. |
| Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score | Baseline, Post-Intervention (Month 12) | The Minnesota Living with Heart Failure Questionnaire is a 21-item questionnaire that asks participants to describe how much their heart failure has affected life during the past month (4 weeks). Participants are asked if their heart failure prevented them from living as they want when completing daily tasks. Responses are rated on a scale from 0 to 5; 0 represents no, 1 represents very little and 5 represents very much on a continuum. The MLHF score is obtained by summing the subjects responses. A minimum score is 0 indicating no affect to life and a maximum score is 105 indicating the greatest affect to life. |
| Change in Functional Status Assessed by 6-Minute Walk Test (6MWT) | Baseline, Post-intervention (Month 6), Post-Intervention (Month 12) | Functional status will be measured by a 6-minute walk test, which assesses the distance walked (in feet) on a flat, hard surface in a period of 6 minutes (the 6MWD). The test is used for preoperative and postoperative evaluation and for measuring the response to therapeutic interventions for pulmonary and cardiac disease. Optimal reference equations from healthy population-based samples using standardized 6MWT methods are not yet available. A low 6MWD is nonspecific and nondiagnostic. When the 6MWD is reduced, a thorough search for the cause of the impairment is warranted. |
| Mortality Rate | Post-Intervention (Up to 20 Days), Post-Intervention (Month 6), Post-Intervention (Month 12) | The number of participants who are deceased will be collected throughout the study at discharge and planned follow up visits. |
| Heart Failure Readmission Rate | Post Surgery (Up to 30 Days) | Readmission rate will be calculated for heart failure after 30 days following surgery throughout the duration of the study. Classification of readmission as heart failure related requires at least 2 out of the following signs and symptoms of acute decompensated heart failure: * Dyspnea felt related to HF * Treatment with intravenous diuretic, vasodilator or inotropic therapy * X ray evidence of pulmonary edema or pulmonary vascular congestion * Rales on physical exam * Pulmonary capillary wedge pressure (PCWP) or LVEDP \> 18mm Hg |
| Change in Left Ventricular Volume | Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12) | Change in left ventricular volume at 6- and 12-month post-intervention compared to baseline as measured by as measured by the left ventricular end-diastolic diameter determined by echocardiogram. |
| Change in Ejection Fraction | Baseline, Post-Intervention (Month 12) | Change in left ventricular ejection fraction at 12- months post-intervention compared to baseline as measured by echocardiogram. |
| Change in Left Ventricular Mass | Baseline, Post-Intervention (Month 12) | Change in left ventricular mass at 12 months post intervention compared to baseline as measured by cardiac MRI. |
| All Cause Readmission Rate | Post Surgery (Up to 30 Days) | Readmission rate will be calculated for any cause within the first 30 days following surgery throughout the duration of the study. |
Countries
United States
Participant flow
Recruitment details
Efforts were made to include post-surgery patients and those from prior years. However, required preoperative imaging was unavailable, preventing preop vs. follow-up comparisons. No participants were enrolled in UMA + PMA (Group 2), and no retrospectively identified patients were included in Group 3.
Participants by arm
| Arm | Count |
|---|---|
| UMA (Group 1) Participants in the UMA group will receive an undersizing mitral annuloplasty (UMA).
Undersizing Mitral Annuloplasty: Participants will receive a commercially available annuloplasty ring of the surgeon's choice. Sutures are placed around the mitral annulus, and the metallic ring is then implanted onto the mitral annulus to reduce it in size. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Failed preoperative screening | 4 | 0 | 0 |
| Overall Study | Had concomitant valves replacements, therefore not included in data analysis | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | UMA (Group 1) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 64.6 years STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 30 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 0 / 26 |
| serious Total, serious adverse events | 4 / 26 |
Outcome results
Primary
Change in FMR Severity
The Severity (grade 0 to 4+) of mitral regurgitation of mitral regurgitation is measured using cardiac echocardiography and/or MRI (per physician's discretion). Grade 0: None Grade 1 (Mild): Small, restricted jet of regurgitation with minimal impact on the heart's function. Typically, no symptoms and normal or near-normal left ventricular function. Grade 2 (Moderate): Moderate jet size with some effect on the heart, but symptoms may still be absent or minimal. Mild to moderate left ventricular dilation may be present. Grade 3 (Moderately Severe): Larger jet, more significant regurgitation, potentially causing mild heart failure symptoms or moderate dilation of the left ventricle. Grade 4 (Severe): A large, prominent jet of regurgitation that significantly impacts heart function, often resulting in severe symptoms and marked left ventricular dilation.
Time frame: Pre-Intervention and Post-Intervention (12 Months)
Population: Data is available only for the 12-month follow-up, as other data was unavailable due to many follow-ups occurring during the COVID pandemic.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UMA (Group 1) | Change in FMR Severity | Baseline | 2.7 score on a scale | Standard Deviation 0.8 |
| UMA (Group 1) | Change in FMR Severity | 12 months post-intervention | 0.7 score on a scale | Standard Deviation 0.7 |
Secondary
All Cause Readmission Rate
Readmission rate will be calculated for any cause within the first 30 days following surgery throughout the duration of the study.
Time frame: Post Surgery (Up to 30 Days)
Population: Participants with valid data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UMA (Group 1) | All Cause Readmission Rate | Post-Surgery (up to 30 days) | 2 Participants |
| UMA (Group 1) | All Cause Readmission Rate | Post-Surgery (30 days through 12 Months) | 4 Participants |
Secondary
Change in Ejection Fraction
Change in left ventricular ejection fraction at 12- months post-intervention compared to baseline as measured by echocardiogram.
Time frame: Baseline, Post-Intervention (Month 12)
Population: Participants who had adequate echocardiograms to complete this evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UMA (Group 1) | Change in Ejection Fraction | Baseline | 45 percentage of ejection fraction | Standard Deviation 14 |
| UMA (Group 1) | Change in Ejection Fraction | 12 months post-intervention | 46 percentage of ejection fraction | Standard Deviation 14 |
Secondary
Change in Functional Status Assessed by 6-Minute Walk Test (6MWT)
Functional status will be measured by a 6-minute walk test, which assesses the distance walked (in feet) on a flat, hard surface in a period of 6 minutes (the 6MWD). The test is used for preoperative and postoperative evaluation and for measuring the response to therapeutic interventions for pulmonary and cardiac disease. Optimal reference equations from healthy population-based samples using standardized 6MWT methods are not yet available. A low 6MWD is nonspecific and nondiagnostic. When the 6MWD is reduced, a thorough search for the cause of the impairment is warranted.
Time frame: Baseline, Post-intervention (Month 6), Post-Intervention (Month 12)
Population: Participants who completed the study procedure. Data is available only for the 12-month follow-up, as other data was unavailable due to many follow-ups occurring during the COVID pandemic.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UMA (Group 1) | Change in Functional Status Assessed by 6-Minute Walk Test (6MWT) | Baseline | 1048.4 feet | Standard Deviation 293.7 |
| UMA (Group 1) | Change in Functional Status Assessed by 6-Minute Walk Test (6MWT) | 12 months Post-Intervention | 1210.6 feet | Standard Deviation 203.6 |
Secondary
Change in Left Ventricular Mass
Change in left ventricular mass at 12 months post intervention compared to baseline as measured by cardiac MRI.
Time frame: Baseline, Post-Intervention (Month 12)
Population: Some MRIs were performed but not analyzed, as these were research trial MRIs. The original PI and a research post-doc who were the expert analysts, left before reading the MRIs. Only eight patients had both pre- and post-MRIs. Outsourcing analysis was too costly, and meaningful comparisons weren't possible with such a small sample, so the MRIs were not read for the study.
Secondary
Change in Left Ventricular Volume
Change in left ventricular volume at 6- and 12-month post-intervention compared to baseline as measured by as measured by the left ventricular end-diastolic diameter determined by echocardiogram.
Time frame: Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
Population: Participants with valid data. Data is available only for the 12-month follow-up, as other data was sparse due to many follow-ups occurring during the COVID pandemic.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UMA (Group 1) | Change in Left Ventricular Volume | Baseline | 5.4 centimeters | Standard Deviation 0.8 |
| UMA (Group 1) | Change in Left Ventricular Volume | 12 months Post-Intervention | 4.8 centimeters | Standard Deviation 0.8 |
Secondary
Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score
The Minnesota Living with Heart Failure Questionnaire is a 21-item questionnaire that asks participants to describe how much their heart failure has affected life during the past month (4 weeks). Participants are asked if their heart failure prevented them from living as they want when completing daily tasks. Responses are rated on a scale from 0 to 5; 0 represents no, 1 represents very little and 5 represents very much on a continuum. The MLHF score is obtained by summing the subjects responses. A minimum score is 0 indicating no affect to life and a maximum score is 105 indicating the greatest affect to life.
Time frame: Baseline, Post-Intervention (Month 12)
Population: Participants who answered the specific questionnaires within the specific study window. Data is available only for the 12-month follow-up, as other data was unavailable due to many follow-ups occurring during the COVID pandemic.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UMA (Group 1) | Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score | Baseline | 44.2 score on a scale | Standard Deviation 31.3 |
| UMA (Group 1) | Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score | 12 months Post-Intervention | 30.9 score on a scale | Standard Deviation 28 |
Secondary
Change in Quality-of-Life Scale Score
Participants will be asked to measure their perceived quality of life on a scale from 0 to 100 where 0 indicates worst imaginable health state and 100 indicates best imaginable health state.
Time frame: Baseline, Post-Intervention (Month 6), Post-Intervention (Month 12)
Population: Participants who completed the questionnaires within the specific study window. Data is available only for the 12-month follow-up, as other data was unavailable due to many follow-ups occurring during the COVID pandemic.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UMA (Group 1) | Change in Quality-of-Life Scale Score | Baseline | 69.0 Score on a scale | Standard Deviation 19 |
| UMA (Group 1) | Change in Quality-of-Life Scale Score | Post-Intervention (Month 12) | 76.9 Score on a scale | Standard Deviation 16.9 |
Secondary
Heart Failure Readmission Rate
Readmission rate will be calculated for heart failure after 30 days following surgery throughout the duration of the study. Classification of readmission as heart failure related requires at least 2 out of the following signs and symptoms of acute decompensated heart failure: * Dyspnea felt related to HF * Treatment with intravenous diuretic, vasodilator or inotropic therapy * X ray evidence of pulmonary edema or pulmonary vascular congestion * Rales on physical exam * Pulmonary capillary wedge pressure (PCWP) or LVEDP \> 18mm Hg
Time frame: Post Surgery (Up to 30 Days)
Population: Participants with valid data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| UMA (Group 1) | Heart Failure Readmission Rate | 0 Participants |
Secondary
Mortality Rate
The number of participants who are deceased will be collected throughout the study at discharge and planned follow up visits.
Time frame: Post-Intervention (Up to 20 Days), Post-Intervention (Month 6), Post-Intervention (Month 12)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UMA (Group 1) | Mortality Rate | up to 20 days post-Intervention | 0 Participants |
| UMA (Group 1) | Mortality Rate | 12 months post-intervention | 0 Participants |
Secondary
Number of Major Adverse Cardiac Events (MACE)
MACE is defined as a composite of clinical events comprised of the following: * Death * Stroke * Worsening heart failure (+1 New York Heart Association (NYHA) class) * Congestive heart failure (CHF) hospitalization * Mitral valve re-intervention
Time frame: Up to 12 months post -intervention
Population: Participants with valid data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UMA (Group 1) | Number of Major Adverse Cardiac Events (MACE) | Congestive heart failure (CHF) hospitalization | 1 Participants |
| UMA (Group 1) | Number of Major Adverse Cardiac Events (MACE) | Death | 0 Participants |
| UMA (Group 1) | Number of Major Adverse Cardiac Events (MACE) | Mitral valve re-intervention | 0 Participants |
| UMA (Group 1) | Number of Major Adverse Cardiac Events (MACE) | Stroke | 0 Participants |
| UMA (Group 1) | Number of Major Adverse Cardiac Events (MACE) | Worsening heart failure (+1 New York Heart Association (NYHA) class) | 0 Participants |