Functional Mitral Regurgitation
Conditions
Keywords
Ventricular Dysfunction, Functional Mitral Regurgitation, Heart Failure, Mitral Implant, Secondary Mitral Regurgitation
Brief summary
This research protocol tests a new technique and devices that we have developed to treat functional mitral valve regurgitation, called transcatheter mitral valve cerclage annuloplasty, otherwise known as "cerclage". Functional mitral valve regurgitation is a condition caused by damaged heart muscle involving the left ventricle which results in mitral valve leakage. This leakage causes heart failure (breathlessness and lack of energy especially when walking or exercising, and hospital admissions for fluid buildup). This is an early feasibility study (EFS) evaluation of special devices, permanently implanted in the heart, to perform mitral cerclage annuloplasty. Mitral cerclage annuloplasty is a catheter procedure performed under X-ray and ultrasound guidance without surgery. The cerclage devices compress the mitral valve like a purse-string. The cerclage device has a special feature that prevents a coronary artery from getting squeezed as part of this purse-string. The protocol has been changed to allow patients who have mitral valve regurgitation despite prior Mitra-Clip treatment, and to allow patients who have symptomatic heart failure with mild mitral regurgitation.
Detailed description
Functional mitral regurgitation (also known as secondary mitral regurgitation) is a common complication of left ventricular dysfunction. Ventricular dysfunction leads to dilation, which in turn leads to mitral annular dilation and leaflet traction. This causes a failure of coaptation of the otherwise intact leaflets of the mitral valve, leading to regurgitation through a central orifice between the mal-coapting leaflet tips. Functional mitral regurgitation contributes to heart failure symptoms. Transcatheter Mitral Cerclage Annuloplasty (TMCA) is a new catheter technique that reduces the septal-lateral dimension of the dilated annulus through circumferential compression, prevents extrinsic compression and entrapment of coronary arteries by incorporating a protection element, and exhibits planar discordance that achieves annular reduction even when the coronary sinus is anatomically located along the posterior left atrial wall. This is an entirely right-sided procedure and device.
Interventions
DEVICETransmural Systems Transcatheter Mitral Cerclage Annuloplasty (TMCA)
The Transcatheter Mitral Cerclage Annuloplasty implant has two components, with or without a coronary artery protection element, and the wishbone lock with coronary sinus and right ventricular outflow track limbs. Procedure is performed from a trans-jugular venous approach. Coronary guidewires and microcatheters are used to navigate into a coronary vein to the target capture catheter. The implant is then attached to the back end of the guidewire and pulled out of the internal jugular sheath. The position of the implant is adjusted so the coronary protection element lies directly over any underlying branch of the left coronary artery. The wishbone lock is advanced over the two limbs of the implant and the desired tension is titrated to the degree of mitral regurgitation. Coronary angiography is performed to confirm there is no coronary compression. After desired tension has been achieved, the wishbone lock is locked and the two limbs of the implant are cut with a cutter catheter.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: 1. Adults age \>=21 years 2. Symptomatic functional mitral valve regurgitation 1. Mild or greater mitral valve regurgitation, LVEF \<= 0.50, and NYHA class III - IV heart failure 2. Moderate or greater mitral valve regurgitation and NYHA II - IV heart failure, irrespective of LV systolic function 3. On optimal medical therapy for at least one month 4. Left ventricular ejection fraction \>=0.20 assessed by echocardiography, CT, or CMR 5. Suitable coronary venous anatomy for Transcatheter Mitral Cerclage Annuloplasty based on pre-procedural cardiac CT or coronary venogram 6. Concordance of the Study Eligibility Committee 7. If present, a MitraClip was implanted at least 30 days previously
Exclusion criteria
1. Subjects unable to consent to participate 2. Subjects unwilling to participate or unwilling to return for study follow-up activities. 3. Prior cardiac implanted electronic devices (CIED) likely to be entrapped by cerclage. \-- Candidates with coronary sinus or left ventricular pacing or defibrillation leads that are not likely to be entrapped by cerclage, evident on baseline CT or angiogram, are eligible to participate. 4. TAVR within 6 weeks 5. Intended concurrent structural heart procedure, such as aortic or tricuspid valve intervention 6. Aortic stenosis more than mild in severity 7. Single-leaflet MitraClip detachment, if present 8. Pregnancy or intent to become pregnant prior to completion of all protocol follow-up procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Endpoint is Technical Success | 1 minute following procedure discharge (Exit from the catheterization laboratory) | The primary endpoint is Technical success. This endpoint is measured at exit from the catheterization laboratory. All of the following must be present: 1. Alive 2. Successful deployment and correct positioning of a single intended Transcatheter Mitral Cerclage Annuloplasty (TMCA). Repositioning and recapture of the device, if needed, is not classified as failure. 3. Retrieval of the TMCA delivery system 4. Absence of TMCA-related coronary artery compression and absence of additional procedure such as percutaneous coronary intervention (PCI) to relieve coronary artery compression. 5. No additional unplanned or emergency surgery or re-intervention related to the TMCA or delivery system. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Secondary Endpoint is Procedural Success | Day 30 post procedure | The secondary endpoint is Procedural success This endpoint is measured at 30 days. All of the following must be present: 1. Technical success 2. No Transcatheter Mitral Cerclage Annuloplasty (TMCA) device-related Serious Adverse Events, defined as VARC-2 life-threatening bleeding, major vascular or cardiac complications related to the TMCA requiring unplanned reintervention or surgery. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRobert J Lederman, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Participant flow
Recruitment details
Nineteen subjects consented and underwent cerclage procedures between May 2019 and February 2021, despite COVID-19-related delays.
Participants by arm
| Arm | Count |
|---|---|
| Transcatheter Mitral Valve Cerclage Annuloplasty To evaluate the feasibility and safety of Transcatheter Mitral Cerclage Annuloplasty (TMCA) to treat symptomatic heart failure accompanied by mitral valve regurgitation despite optimal medical therapy.
The TMCA implant is attached to a guidewire and pulled through the internal jugular sheath, along the coronary sinus, through the basal septum, through the tricuspid valve, and back out of the internal jugular sheath. The position of the TMCA implant is adjusted so that the coronary protection element lies directly over any underlying branch of the left coronary artery. | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Transcatheter Mitral Valve Cerclage Annuloplasty |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Heart failure with preserved ejection fraction (HFpEF) | 7 Participants |
| Heart failure with reduced ejection fraction (HFrEF) | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 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 | 12 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 19 |
| other Total, other adverse events | 19 / 19 |
| serious Total, serious adverse events | 12 / 19 |
Outcome results
Primary
The Primary Endpoint is Technical Success
The primary endpoint is Technical success. This endpoint is measured at exit from the catheterization laboratory. All of the following must be present: 1. Alive 2. Successful deployment and correct positioning of a single intended Transcatheter Mitral Cerclage Annuloplasty (TMCA). Repositioning and recapture of the device, if needed, is not classified as failure. 3. Retrieval of the TMCA delivery system 4. Absence of TMCA-related coronary artery compression and absence of additional procedure such as percutaneous coronary intervention (PCI) to relieve coronary artery compression. 5. No additional unplanned or emergency surgery or re-intervention related to the TMCA or delivery system.
Time frame: 1 minute following procedure discharge (Exit from the catheterization laboratory)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Transcatheter Mitral Valve Cerclage Annuloplasty | The Primary Endpoint is Technical Success | 17 Participants |
Secondary
The Secondary Endpoint is Procedural Success
The secondary endpoint is Procedural success This endpoint is measured at 30 days. All of the following must be present: 1. Technical success 2. No Transcatheter Mitral Cerclage Annuloplasty (TMCA) device-related Serious Adverse Events, defined as VARC-2 life-threatening bleeding, major vascular or cardiac complications related to the TMCA requiring unplanned reintervention or surgery.
Time frame: Day 30 post procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Transcatheter Mitral Valve Cerclage Annuloplasty | The Secondary Endpoint is Procedural Success | 16 Participants |