The EMPOWER Trial - The Carillon Mitral Contour System® in Treating Heart Failure With FMR

A total of 300 subjects will be randomized at up to 100 investigational sites in the United States, Canada, and Europe. Subjects will be randomized into one of two study groups using a 1:1 (Intervention : Control) ratio.

Study subjects who are eligible for this clinical study will undergo a transthoracic echocardiographic examination prior to randomization to evaluate the inclusion criteria associated with the severity of mitral regurgitation. A coronary angiogram will be performed to evaluate the coronary artery anatomy and a venogram to assess the suitability of the coronary sinus/great cardiac vein (CS/GCV) for placement of the Carillon implant.

If the subject meets the anatomic requirements for the Carillon implant placement, the subject will be randomized. Subjects who meet all eligibility criteria will be randomized into one of two study groups (Intervention or Control).

Subjects randomized to the Intervention group will undergo the Carillon implant procedure.

Subjects randomized to the Control group will experience an index procedure similar to the Intervention group (without implant placement) to ensure they will not be able to deduce the group assignment based on the type of intervention or time associated with the procedure.

After the study subjects are discharged, the subjects' primary care specialists (cardiologist/heart failure physician) and clinical investigation site staff will coordinate follow-up evaluations. Subjects will be evaluated at one (1), six (6), twelve (12), eighteen (18) and twenty-four (24) months post-randomization, to assess long-term safety, and functional and clinical status.

After the 24-month evaluation, all subjects will be unblinded. All Intervention and Control subjects will be followed with an abbreviated annual contact and echocardiogram for an additional three (3) years, for a total of five (5) years.

Inclusion criteria

• Symptomatic heart failure with functional (secondary) mitral regurgitation of at least 1+ (mild) severity
• NYHA II, III, or IV
• Six Minute Walk distance ≥ 100 meters and ≤ 600 meters
• Left Ventricular Ejection Fraction ≤ 50%
• LVEDD:

• ≥ 55 mm (women)
• ≥ 57 mm (men)
• LVESD ≤ 75 mm
• Corrected NT-proBNP > 1200 pg/ml measured within 60 days of randomization, and/or one or more heart failure hospitalizations within one year prior to consent or one or more outpatient visits for intensification of heart failure therapy within one year prior to consent.
• Optimal Guideline directed heart failure medical therapy assessed by the Central Review Committee
• Age ≥ 18 years old
• Carillon implant can be sized and placed in accordance with the IFU
• The subject has been informed of the nature of the trial and agrees to its provisions, including the possibility of randomization to the Control group and returning for all required post-procedure follow-up visits, and has provided written informed consent

Exclusion criteria

• Presence of a mechanical or bio-prosthetic mitral valve or, mitral valve annuloplasty, or leaflet repair device
• Significant organic mitral valve pathology (e.g., moderate or severe myxomatous degeneration, with or without mitral leaflet prolapse, rheumatic disease, full or partial chordal rupture)
• Severe tricuspid regurgitation associated with right ventricular dysfunction and enlargement
• Severe mitral annular calcification
• Severe aortic stenosis
• Expected to require any cardiac surgery, including surgery for coronary artery disease (CAD) or valve disease within one (1) year
• Chronic, severe, medical conditions or pathology, other than heart failure, that will prevent likely survival beyond twelve (12) months or any other medical condition that, in the judgement of the Investigator or Central Review Committee, makes the patient a poor candidate for this study

• An entire list of eligibility is available in the clinical investigational plan