NHLBI DIR Transcatheter Mitral Cerclage Annuloplasty Early Feasibility Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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NHLBI DIR Transcatheter Mitral Cerclage Annuloplasty Early Feasibility Study

Conditions
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Functional Mitral Regurgitation

Intervention / Treatment
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* Device: Transmural Systems Transcatheter Mitral Cerclage Annuloplasty (TMCA)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Adults age >=21 years Symptomatic functional mitral valve regurgitation Mild or greater mitral valve regurgitation, LVEF <= 0.50, and NYHA class III - IV heart failure Moderate or greater mitral valve regurgitation and NYHA II - IV heart failure, irrespective of LV systolic function On optimal medical therapy for at least one month Left ventricular ejection fraction >=0.20 assessed by echocardiography, CT, or CMR Suitable coronary venous anatomy for Transcatheter Mitral Cerclage Annuloplasty based on pre-procedural cardiac CT or coronary venogram Concordance of the Study Eligibility Committee If present, a MitraClip was implanted at least 30 days previously EXCLUSION CRITERIA: Subjects unable to consent to participate Subjects unwilling to participate or unwilling to return for study follow-up activities. 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. TAVR within 6 weeks Intended concurrent structural heart procedure, such as aortic or tricuspid valve intervention Aortic stenosis more than mild in severity Single-leaflet MitraClip detachment, if present Pregnancy or intent to become pregnant prior to completion of all protocol follow-up procedures

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcatheter Mitral Valve Cerclage Annuloplasty<br>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. | Device: Transmural Systems Transcatheter Mitral Cerclage Annuloplasty (TMCA)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: Alive 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. Retrieval of the TMCA delivery system Absence of TMCA-related coronary artery compression and absence of additional procedure such as percutaneous coronary intervention (PCI) to relieve coronary artery compression. No additional unplanned or emergency surgery or re-intervention related to the TMCA or delivery system. | 1 minute following procedure discharge (Exit from the catheterization laboratory) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: Technical success 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. | Day 30 post procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ventricular Dysfunction, Functional Mitral Regurgitation, Heart Failure, Mitral Implant, Secondary Mitral Regurgitation