NHLBI DIR Transcatheter Mitral Cerclage Annuloplasty Early Feasibility Study

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Functional Mitral Regurgitation
• Intervention / Treatment: Device: Transmural Systems Transcatheter Mitral Cerclage Annuloplasty (TMCA)

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Georgia
    • Atlanta, Georgia, United States, 30322-1102
      • Emory University
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Device: Transmural 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Robert J Lederman, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2019
• Primary Completion (Actual): February 23, 2021
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 26, 2019
• First Submitted That Met QC Criteria: April 26, 2019
• First Posted (Actual): April 29, 2019

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Heart Failure; Functional Mitral Regurgitation; Ventricular Dysfunction; Mitral Implant; Secondary Mitral Regurgitation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: 190088; 19-H-0088

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The authors are willing to share de-identified subject data upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes