Trial Outcomes & Findings for Improving Mitral Repair for Functional Mitral Regurgitation (NCT NCT03366649)

NCT ID: NCT03366649

Last Updated: 2025-01-16

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 34 participants
• Primary outcome timeframe: Pre-Intervention and Post-Intervention (12 Months)
• Results posted on: 2025-01-16

Participant Flow

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.

Participant milestones

Measure	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.	UMA + PMA (Group 2) Participants in the UMA + PMA group will receive an undersizing mitral annuloplasty (UMA) with papillary muscle approximation (PMA). 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. Papillary 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.	No Intervention: Retrospectively Identified Patients Retrospectively identified patients, who already underwent the standard of care surgery for the lesion of interest at Emory, within 6 months (± 1 month) after their surgery, and suitable for recruitment to the study for their post-operative research.
Overall Study STARTED	34	0	0
Overall Study COMPLETED	26	0	0
Overall Study NOT COMPLETED	8	0	0

Reasons for withdrawal

Measure	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.	UMA + PMA (Group 2) Participants in the UMA + PMA group will receive an undersizing mitral annuloplasty (UMA) with papillary muscle approximation (PMA). 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. Papillary 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.	No Intervention: Retrospectively Identified Patients Retrospectively identified patients, who already underwent the standard of care surgery for the lesion of interest at Emory, within 6 months (± 1 month) after their surgery, and suitable for recruitment to the study for their post-operative research.
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

Improving Mitral Repair for Functional Mitral Regurgitation

Baseline characteristics by cohort

Measure	UMA (Group 1) n=30 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants
Age, Categorical >=65 years	16 Participants n=5 Participants
Age, Continuous	64.6 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	UMA (Group 1) n=26 Participants 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.
Change in FMR Severity Baseline	2.7 score on a scale Standard Deviation 0.8
Change in FMR Severity 12 months post-intervention	0.7 score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	UMA (Group 1) n=26 Participants 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.
Mortality Rate up to 20 days post-Intervention	0 Participants
Mortality Rate 12 months post-intervention	0 Participants

SECONDARY outcome

Timeframe: Up to 12 months post -intervention

Population: Participants with valid data.

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

Outcome measures

Measure	UMA (Group 1) n=26 Participants 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.
Number of Major Adverse Cardiac Events (MACE) Congestive heart failure (CHF) hospitalization	1 Participants
Number of Major Adverse Cardiac Events (MACE) Death	0 Participants
Number of Major Adverse Cardiac Events (MACE) Mitral valve re-intervention	0 Participants
Number of Major Adverse Cardiac Events (MACE) Stroke	0 Participants
Number of Major Adverse Cardiac Events (MACE) Worsening heart failure (+1 New York Heart Association (NYHA) class)	0 Participants

SECONDARY outcome

Timeframe: 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.

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".

Outcome measures

Measure	UMA (Group 1) n=10 Participants 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.
Change in Quality-of-Life Scale Score Baseline	69.0 Score on a scale Standard Deviation 19.0
Change in Quality-of-Life Scale Score Post-Intervention (Month 12)	76.9 Score on a scale Standard Deviation 16.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	UMA (Group 1) n=11 Participants 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.
Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score Baseline	44.2 score on a scale Standard Deviation 31.3
Change in Minnesota Living With Heart Failure (MLHF) Questionnaire Score 12 months Post-Intervention	30.9 score on a scale Standard Deviation 28.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	UMA (Group 1) n=11 Participants 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.
Change in Functional Status Assessed by 6-Minute Walk Test (6MWT) Baseline	1048.4 feet Standard Deviation 293.7
Change in Functional Status Assessed by 6-Minute Walk Test (6MWT) 12 months Post-Intervention	1210.6 feet Standard Deviation 203.6

SECONDARY outcome

Timeframe: Post Surgery (Up to 30 Days)

Population: Participants with valid data.

Readmission rate will be calculated for any cause within the first 30 days following surgery throughout the duration of the study.

Outcome measures

Measure	UMA (Group 1) n=26 Participants 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.
All Cause Readmission Rate Post-Surgery (up to 30 days)	2 Participants
All Cause Readmission Rate Post-Surgery (30 days through 12 Months)	4 Participants

SECONDARY outcome

Timeframe: Post Surgery (Up to 30 Days)

Population: Participants with valid data.

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

Outcome measures

Measure	UMA (Group 1) n=26 Participants 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.
Heart Failure Readmission Rate	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	UMA (Group 1) n=26 Participants 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.
Change in Left Ventricular Volume Baseline	5.4 centimeters Standard Deviation 0.8
Change in Left Ventricular Volume 12 months Post-Intervention	4.8 centimeters Standard Deviation 0.8

SECONDARY outcome

Timeframe: Baseline, Post-Intervention (Month 12)

Population: Participants who had adequate echocardiograms to complete this evaluation.

Change in left ventricular ejection fraction at 12- months post-intervention compared to baseline as measured by echocardiogram.

Outcome measures

Measure	UMA (Group 1) n=26 Participants 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.
Change in Ejection Fraction Baseline	45 percentage of ejection fraction Standard Deviation 14
Change in Ejection Fraction 12 months post-intervention	46 percentage of ejection fraction Standard Deviation 14

SECONDARY outcome

Timeframe: 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.

Change in left ventricular mass at 12 months post intervention compared to baseline as measured by cardiac MRI.

Outcome measures

Outcome data not reported

Adverse Events

UMA (Group 1)

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	UMA (Group 1) n=26 participants at risk 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.
Cardiac disorders Atrial fibrillation + congestive heart failure (CHF)	3.8% 1/26 • Number of events 1 • Considering the observational nature of this study, and the absence of any experimental procedures, adverse event (AE) reporting was limited only to those events that occurred from the specific non-standard-of-care lab procedures that were performed at 6- and 12-month visits. An adverse event (AE) is any undesirable clinical occurrence related to a non-standard-of-care study intervention. Pre-existing or associated Conditions with standard care are not AEs unless they change in nature, severity, or degree. AEs are typically reported in trials involving experimental interventions. In this observational study, AE reporting was limited to events from non-standard-of-care lab procedures at the 6- and 12-month visits, none of which were related to those procedures.
Cardiac disorders Atrial Flutter	3.8% 1/26 • Number of events 1 • Considering the observational nature of this study, and the absence of any experimental procedures, adverse event (AE) reporting was limited only to those events that occurred from the specific non-standard-of-care lab procedures that were performed at 6- and 12-month visits. An adverse event (AE) is any undesirable clinical occurrence related to a non-standard-of-care study intervention. Pre-existing or associated Conditions with standard care are not AEs unless they change in nature, severity, or degree. AEs are typically reported in trials involving experimental interventions. In this observational study, AE reporting was limited to events from non-standard-of-care lab procedures at the 6- and 12-month visits, none of which were related to those procedures.
Gastrointestinal disorders Acute cholecystitis with perforated gallbladder	3.8% 1/26 • Number of events 1 • Considering the observational nature of this study, and the absence of any experimental procedures, adverse event (AE) reporting was limited only to those events that occurred from the specific non-standard-of-care lab procedures that were performed at 6- and 12-month visits. An adverse event (AE) is any undesirable clinical occurrence related to a non-standard-of-care study intervention. Pre-existing or associated Conditions with standard care are not AEs unless they change in nature, severity, or degree. AEs are typically reported in trials involving experimental interventions. In this observational study, AE reporting was limited to events from non-standard-of-care lab procedures at the 6- and 12-month visits, none of which were related to those procedures.
General disorders Syncope	3.8% 1/26 • Number of events 1 • Considering the observational nature of this study, and the absence of any experimental procedures, adverse event (AE) reporting was limited only to those events that occurred from the specific non-standard-of-care lab procedures that were performed at 6- and 12-month visits. An adverse event (AE) is any undesirable clinical occurrence related to a non-standard-of-care study intervention. Pre-existing or associated Conditions with standard care are not AEs unless they change in nature, severity, or degree. AEs are typically reported in trials involving experimental interventions. In this observational study, AE reporting was limited to events from non-standard-of-care lab procedures at the 6- and 12-month visits, none of which were related to those procedures.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Robert Guyton

Emory University

Phone: 404 686-4499

Email: rguyton@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place