Inclusion Criteria:

• Eighteen (18) years of age or older as of date on informed consent.

• Patient is able and willing to give informed consent and follow protocol procedures, and comply with follow‐up visit requirements.

• Patient is determined to be at prohibitive risk for mitral valve surgery by the heart team.

• Patient is determined to be a candidate for transcatheter mitral valve repair by the heart team for both PASCAL and MitraClip OR patient is determined to be a candidate for the PASCAL System but not the MitraClip System due to valve anatomy (these patients may qualify to participate in the single-arm PASCAL IID registry and will not be part of the randomized cohort).

• Patient must be deemed a candidate for transseptal catheterization by the site interventional operator.

• Mitral regurgitation (3+ to 4+) by echo (TTE or TEE) as measured by the core lab

  • 180 days for TEE and 60 days for TTE from submission

• Suitable valve and regurgitant jet morphology by TEE

  • 180 days for TEE from submission

• Left ventricular ejection fraction (LVEF) ≥ 20%

  • Measured by TTE; assessed by core lab

• LVEDD ≤ 80mm by TTE

  • 60 days from TTE submission

Exclusion Criteria: 

Potential patients will be excluded if ANY of the following criteria apply:*

• Patient in whom a TEE is contraindicated or screening TEE is unsuccessful.

• Mitral valve anatomy which may preclude proper PASCAL System or MitraClip System access, use and/or deployment or sufficient reduction in mitral regurgitation for the randomized cohort such as:

  • Evidence of moderate to severe calcification in the grasping area;

  • Evidence of severe bi-leaflet/multi scallop prolapse involvement;

  • Presence of significant cleft or perforation in the grasping area;

  • Leaflet mobility length < 8mm;

  • Presence of two or more independent significant jets;

  • Presence of one significant jet in the commissural area.

    • Assessed by core lab.

• Mitral valve orifice area < 4.0 cm²

  • Within 180 days prior to submission of TEE or 60 days of submission of TTE; assessed by core lab.

• Echocardiographic evidence of intracardiac mass, thrombus, or vegetation

  • Assessed by core lab.

• Echocardiographic evidence of severe right ventricular dysfunction per core lab assessment

  • Assessed by core lab per baseline TTE.

• Patient with refractory heart failure requiring advanced intervention (i.e., biventricular pacemakers, left ventricular assist device, transplantation) (ACC/AHA Stage D heart failure).

  • Within 30 days prior to signing informed consent.

• Clinically significant, untreated coronary artery disease requiring revascularization, unstable angina, evidence of acute coronary syndrome, recent myocardial infarction (per WHO definition)

  • MI within 30 days prior to procedure date.

• Recent stroke

  • Within 90 days prior to procedure date.

• Other severe valve disorders requiring intervention or left ventricular outflow obstruction.

• Infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, sarcoidosis), hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or any other structural heart disease causing heart failure other than dilated cardiomyopathy of either ischemic or non-ischemic etiology.

• Bradycardia with heart rate < 45 bpm (unless treated with a permanent pacemaker) or uncontrolled tachyarrhythmias.

• Any recent percutaneous coronary, carotid, endovascular intervention, carotid surgery, or cardiac surgery

  • Within 30 days prior to procedure date.

• Recent implant or revision of any rhythm management device (i.e., pacemaker, cardiac resynchronization therapy [CRT] with or without cardioverter-defibrillator [CRT-D])

  • Within 90 days prior to signing informed consent.

• Tricuspid valve disease requiring surgery or severe tricuspid regurgitation.

• Any planned interventional cardiac procedure

  • Within 90 days prior after the procedure date.

• Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months.

• From date of signature of informed consent.

• Any prior mitral valve surgery (excluding surgical annuloplasty repair) or transcatheter mitral valve procedure.

• Active systemic infection, including active endocarditis

  • Within 30 days prior to procedure date.

• Active rheumatic heart disease or rheumatic etiology for MR.

• Severe aortic stenosis (aortic valve area <1.0 cm²) or severe aortic regurgitation.

• Absence of CRT with a Class I indication criteria for biventricular pacing.

• Resting systolic blood pressure < 90 or > 160 mmHg after repeated measurements

  • Repeated = 3 consecutive measurements.

• Estimated pulmonary artery systolic pressure (PASP) > 70 mmHg assessed by site based on echocardiography or right heart catheterization, unless active vasodilator therapy in the catheterization lab is able to reduce the pulmonary vascular resistance (PVR) to < 3 Wood units or between 3 and 4.5 Wood units with V wave less than twice the mean of the pulmonary capillary wedge pressure

  • Assessed by site.

• Known history of severe symptomatic carotid stenosis (> 50% by ultrasound) or asymptomatic carotid stenosis (>70% by ultrasound).

• History of deep vein thrombosis (DVT) or pulmonary embolism (PE) or DVT/PE in the past 6 months

  • Within six months prior to signing informed consent.

• Presence of an occluded or thrombosed IVC filter that would interfere with the delivery catheter, or presence of an ipsilateral deep vein thrombosis

  • Within 30 days prior to procedure date.

• Severe COPD in which the primary mechanism of dyspnea is pulmonary disease rather than heart failure.

• Severe renal insufficiency with eGFR ≤ 25 ml/min or requiring chronic renal replacement therapy.

• Untreatable hypersensitivity or contraindication to any of the following:

  • Aspirin or Clopidogrel or Ticlopidine; OR

  • Heparin or Bivalirudin, or Warfarin;

  • Nitinol Alloys (nickel and titanium);

  • Contrast media

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

• Known bleeding or clotting disorders or patient refuses blood transfusion.    

• Pregnant or planning pregnancy within next 12 months.

  • Note: Female patients of childbearing potential need to have a negative pregnancy test performed within 14 days prior to intervention and be adherent to an accepted method of contraception.

• Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the Investigator.

• Patient is currently participating in another investigational biologic drug or device clinical study where the primary study endpoint was not reached at time of enrollment.

• Other medical, social, or psychological conditions that preclude appropriate consent and follow-up, including patients under guardianship.

 * Patients who are deemed ineligible for the roll-in or randomized arms of the study by meeting exclusion criteria 2 or 3 may be considered for the PASCAL IID Registry by the Central Screening Committee on a case-by-case basis.