Reduction of Elimination of Mitral Regurgitation With the SATURN TMVR System (CASSINI-US)

Inclusion Criteria:

• Age 18 years or older.

• Symptomatic, moderate to severe or severe, functional or mixed, mitral regurgitation (≥ Grade 3+).

• NYHA functional Class ≥ II. If Class IV, patient must be ambulatory.

• Ability to tolerate oral anticoagulation.

• Ability to qualify for bailout surgery (which may include open heart surgery).

• High risk for open-heart mitral valve surgery due to age, co-morbidities or frailty,as determined by the Heart Team.

• Willing and able to complete study-related assessments and questionnaires.

Exclusion Criteria:

• Purely degenerative (organic/primary) (i.e. intrinsic valve lesions) mitralregurgitation.

• Excessive frailty or comorbid conditions that preclude the anticipated benefit ofthe mitral valve replacement.

• Life expectancy <1 yr. due to noncardiac conditions.

• Endocarditis in the 3 months prior to procedure date.

• Current admission with acute heart failure exacerbation.

• Dependency on inotropic agents or mechanical circulatory support.

• Untreated clinically significant CAD.

• Active systemic infection.

• Modified Rankin Scale ≥4 disability.

• Chronic renal failure defined as eGFR < 30 mL/min/m2 or on renal replacementtherapy.

• Severe pulmonary arterial hypertension (PAH), defined as PASP > 70mmHg.

• Platelets < 90,000.

• COPD on home oxygen therapy deemed too high risk for intubation.

• Refuses blood transfusions.

• Documented bleeding or coagulation disorders (hypo- or hyper-coagulable states).

• Severe connective tissue disease under chronic immunosuppressive or cortisonetherapy.

• Participating in other investigational studies likely to confound the results oraffect the study.

• Unable or does not sign the study informed consent form.

• Patients classified as "vulnerable patients"

Cardiovascular Exclusion Criteria

• Myocardial infarction during prior 30 days.

• Stroke or TIA during prior 90 days.

• Severe extracardiac arteriopathy (safety measure for extra-circulatory support ifsurgical conversion is needed).

• Prior mitral valve treatment (e.g., valve repair or replacement, MitraClip, etc.),and/or anticipated mitral valve treatment prior to enrollment.

• Prior surgical mechanical valve AVR.

• Prior TAVI. -Need for any planned cardiovascular surgery or intervention (other thanfor MV disease) within 30 days post-index procedure.

• CRT, CRT-D, IPG or ICD implanted in previous 30 days.

• Cardiogenic shock, hemodynamic instability, Systolic Blood Pressure <90mmHg,Inotropic dependent or IABP/mechanical circulatory support.

CABG or PCI within previous 30 days.

• Inadequately treated for cardiac condition per applicable standards, such as forcoronary artery disease, left ventricular dysfunction, mitral regurgitation, orheart failure, as reviewed by the Patient Screening Committee.

• Prior or planned heart transplantation (UNOS status 1).

• Physical evidence of right-sided CHF:

1. Patients with ascites.

2. Patients with anasarca (generalized edema / hydropsy).

• Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis,or other structural heart disease causing heart failure with the exception ofdilated ischemic or non-ischemic cardiomyopathy.

Procedural Exclusion Criteria

• Known hypersensitivity or contraindication to procedural or post-proceduralmedication (e.g., contrast solution, anticoagulation therapy).

• Documented hypersensitivity to nickel or titanium.

Cardiac Imaging Exclusion Criteria (evaluated by Core Labs)

• Contraindications to TEE imaging

• Left ventricular EF ≤ 30% by echocardiogram.

• Severe mitral annular calcification, severe mitral stenosis, valvular vegetation ormass.

• Extensive mitral flail leaflets

• Evidence of new or untreated intracardiac thrombus, mass, or vegetation.

• Severe right ventricular dysfunction.

• Severe tricuspid regurgitation.

• Hemodynamically significant inter-atrial shunt (ASD).

• Severe aortic regurgitation or aortic stenosis.

• Anatomic ineligibility for SATURN Valve or SATURN TS procedure as determined by theScreening Committee.