A Prospective, Multicenter, Single-Arm Study to Support the Clinical Evidence Base for MRace as a Treatment Option for FMR Patients With Complex M-TEER Anatomies (AU)

Percutaneous approaches to treat MR promise to provide a sufficient reduction in MR without the risks typically associated with open heart surgery. Furthermore there is an unmet clinical need for patients with severe MR who are refused or denied surgery due to high risk. Percutaneous therapy provides a novel alternative treatment option for these patients with the aim of reducing morbidity and mortality over and above current medical therapy. The Polares Medical MRace System is a catheter-based technology designed to permanently implant a prosthesis using a transvenous / transseptal approach to augment the posterior mitral valve leaflet and improve coaptation with the anterior leaflet. Approved edge-to-edge repair has already been shown to be a viable alternative for high risk MR patients. However treatment with these devices is limited to specific anatomies and often requires multiple devices which increases clinical risk, adds to procedural time, and can result in residual MR. The MRace System has been designed to overcome and mitigate some of these shortfalls.

Inclusion criteria

• Patient has symptomatic moderate-to-severe to severe functional mitral regurgitation despite stable doses of optimized guideline-directed medical therapy (GDMT) per the Local Heart Team.

a. Note: In the 30 days prior to performing screening assessments, no new GDMT medications should be introduced, and current doses should be stable (i.e. no decrease of > 50% or increase of > 100%) excluding diuretics. Any changes beyond this range would not be considered stable GDMT.

• Functional MR graded 3+ or higher by transthoracic echocardiography (TTE) within 60 days prior to study procedure as evaluated by the sponsor's Echo Core Lab.
• New York Heart Association (NYHA) Functional Class II, III or ambulatory IV heart failure
• Patient must present with an STS Score less than 10% and deemed by the Local Heart Team to be at high risk but operable for mitral valve surgery.
• The Local Heart Team deems the patient's anatomy to be unsuitable for M-TEER.
• 21 years of age or older.
• Native mitral valve geometry and size is compatible with the Polares MRace system.
• Anatomy is suitable for transfemoral transseptal access with the Polares MRace system.
• Patient is willing to participate in study and provides signed EC-approved informed consent.
• Treating physician and patient agree that patient is able to return for all required post-procedure follow-up visits.
• Patient is approved by an independent Patient Eligibility Committee (PEC) which will confirm the presence of at least of the following one complex anatomical feature:

• Atrial Functional MR with coaptation depth <5-mm
• PLM length < 10 mml
• Gap-Width > 10-18 mm
• Coaptation reserve < 3 mm where the jet is present
• LAI (Leaflet to Annulus-Index) < 1.2
• MVA < 2.5-4.0 cm2
• Leaflet calcium in the M-TEER grasping zone
• Coaptation depth > 10 mm

Exclusion criteria

• Echocardiographic parameters (any of the following, assessed by the Echo Core Lab)

• Left ventricular ejection fraction (LVEF) < 30%
• Pulmonary artery systolic pressure (PASP) > 70mmHg or > 2/3 SBP (Systolic Blood Pressure)
• Left Ventricle End Diastolic Volume (LV EDV) > 200mL for males; >130mL for females
• Left Ventricle End Systolic Volume (LV ESV) > 70 mL
• Left Ventricle End Diastolic Diameter (LV EDD) > 70 mm
• Left Ventricle End Systolic Diameter (LV ESD) > 55 mm
• Anatomical features as per assessment by Local Heart Team and confirmed by the Patient Eligibility Committee

• IC > 4 5mm
• PML > 14 mm
• MR width > 18 mm
• Severe MAC
• PM height < 20 mm
• AML or PML prolapse
• Mean gradient > 5 mmHg
• Barlow's disease
• Severe Right Ventricle (RV) dysfunction as per assessment by Local Heart Team or Patient Eligibility Committee.
• Severe tricuspid regurgitation.
• Severe aortic stenosis or insufficiency.
• Severe mitral annulus calcification.
• Diseased mitral anterior and/or posterior leaflet, such as flail, / prolapse, or/ heavy moderate to severe calcification.
• Presence of an implanted vena cava filter or any other device (e.g. ASD closure device) that may interfere with femoral vein access or delivery system access to the mitral valve.
• Contraindication for transesophageal echocardiography (TEE) or MDCT scan.
• Active infection or endocarditis or infection requiring antibiotic therapy within 2 weeks of scheduled procedure.
• Previous mitral valve surgery or transcatheter mitral valve procedure.
• Prior orthotopic heart transplantation.
• Evidence of intra-cardiac, inferior vena cava (IVC) or femoral venous thrombus. History of deep vein thrombosis (DVT) or pulmonary embolism within 6 months of the index procedure.
• Untreated Class I indication for pacing (CRT). Implant or revision of any pacing device < 30 days prior to intervention.
• Any untreated clinically significant coronary artery disease requiring revascularization. Coronary, carotid, or endovascular artery disease treated percutaneously < 30 days prior to study procedure. Cardiac surgery < 90 days prior to study procedure.
• Myocardial infarction requiring intervention < 30 days prior to study procedure.
• Infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, sarcoidosis), hypertrophic or restrictive cardiomyopathies, and constrictive pericarditis).
• Active peptic ulcer or upper gastrointestinal bleeding < 90 days prior to study procedure.
• Stroke < 180 days prior to study procedure.
• Severe COPD requiring oral steroid therapy or oxygen therapy.
• Severe renal insufficiency (creatinine > 3.0 mg/dL) or patient requiring dialysis
• Cardiogenic shock at time of enrolment. Hemodynamic instability requiring inotropic support or mechanical heart assistance.
• Concurrent medical condition with a life expectancy of less than 2 years.
• Pregnancy or breastfeeding at time of enrolment with a positive pregnancy test within 72 hours before any study-related radiation exposure.
• History of bleeding diathesis or coagulopathy or leukopenia (WBC < 3,000 mcL) or acute anemia (Hb < 9 g/dL) or thrombocytopenia (platelets < 50,000 cells mcL).
• Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine or clopidogrel, nitinol, tantalum or allergy to contrast agents that cannot be pre-medicated.

NOTE: Patient must be able to tolerate at least one antiplatelet medication AND one anticoagulant medication.

• Severe dementia or lack of capacity due to conditions that result in either inability to provide informed consent for the trial/procedure, prevent independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up assessments.
• Patient is in need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months.
• Company employees or their immediate family members.
• Patient is considered to be part of a vulnerable population, is under guardianship, or subject to any other medical, social or psychological conditions that preclude appropriate consent and follow-up.
• Patient is participating in another clinical study for which follow-up is currently ongoing.