Clinical Trials

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 compliance.
• Patient is determined to be at prohibitive risk for mitral valve surgery by a heart team.
• Patient is determined to be a candidate for transcatheter mitral valve repair by a heart team for both the PASCAL System and the MitraClip System; 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+ mo to 4+) by echo (TTE or TEE) as measured by the core lab.
• Suitable valve and regurgitant jetrphology by TEE.
• Left ventricular ejection fraction (LVEF) ≥ 20%.
• LVEDD ≤ 80mm by TTE.

Exclusion Criteria:

• Primarily degenerative MR.
• Patient in whom TEE is contraindicated or screening TEE is unsuccessful.
• Mitral valve anatomy which might limit PASCAL System or MitraClip System access, use, and/or deployment or sufficient reduction in mitral regurgitation will be evaluated on a case-by-case basis by the Central Screening Committee. Anatomic considerations including, but not limited to, the following will be taken into consideration for assignment into the roll-in, randomized, or registry cohorts or excluded altogether:
  • Insufficient mobile leaflet available for grasping the PASCAL or MitraClip System;
  • Evidence of moderate or severe calcification in the grasping area;
  • Presence of a significant cleft or perforation in the grasping area;
  • Lack of both primary and secondary chordal support in the grasping area;
  • Leaflet mobility < 8 mm;
  • Mitral valve orifice area < 4.0 cm^2.
• Echocardiographic evidence of intracardiac mass, thrombus, or vegetation. Chronic scarred thrombi may be considered for inclusion by the core lab.
• Echocardiographic evidence of severe right ventricular dysfunction.
• Patient with refractory heart failure requiring advanced intervention (i.e., left ventricular assist device, transplantation) (ACC/AHA Stage D heart failure).
• Recent stroke.
• Bradycardia with heart rate < 45 bpm (unless treated with a permanent pacemaker) or uncontrolled tachyarrhythmia.
• Any recent percutaneous coronary, carotid, endovascular intervention, carotid surgery, or cardiac surgery.
• Recent implant or revision of any rhythm management device (i.e., pacemaker, ICD, cardiac resynchronization therapy [CRT] with or without cardioverterdefibrillator [CRT-D]).
• Tricuspid valve disease requiring surgery or severe tricuspid regurgitation.
• Other severe valve disorders requiring intervention or left ventricular outflow obstruction.
• Clinically significant, untreated coronary artery disease requiring revascularization, unstable angina, evidence of acute coronary syndrome, or recent myocardial infarction (per WHO definition).
• Any planned interventional cardiac procedure
• Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months.
• Recent hemodynamic instability (e.g., need for inotropic support or intra-aortic balloon pump or other hemodynamic support device).
• Known history of untreated severe symptomatic carotid stenosis (> 50% by ultrasound) or asymptomatic carotid stenosis (> 70% by ultrasound).*
• Severe COPD in which the primary mechanism of dyspnea is pulmonary disease rather than heart failure.
• 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 160 mmHg after repeated measurements
• Estimated pulmonary artery systolic pressure (PASP) > 70 mm Hg 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.
• History of deep vein thrombosis (DVT) or pulmonary embolism (PE) or DVT/PE in the past 6 months.
• Presence of an occluded or thrombosed IVC filter that would interfere with the delivery catheter, or presence of an ipsilateral deep vein thrombosis.
• 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.
• Severe renal insufficiency with eGFR ≤ 25 mL/min or requiring chronic renal replacement therapy.
• Concurrent medical condition with life expectancy of less than 12 months in the judgment of the investigator.
• Known bleeding or clotting disorders or patient refuses blood transfusion.
• Modified Rankin Scale ≥ 4 disability.
• Any prior mitral valve surgery or transcatheter mitral valve procedure (excluding chordal replacement or surgical annuloplasty repair).
• Active systemic infection, including active endocarditis.
• 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.
• 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 procedure and be adherent to an accepted method of contraception.
• Patient is currently participating or has participated in another investigational drug or device clinical study where the primary study endpoint was not reached at time of enrollment.
• Any condition, in the opinion of the investigator, making it unlikely the patient will be able to complete all protocol procedures (including compliance with guideline directed medical therapy) and follow-up visits.
• Other medical, social, or psychological conditions that preclude appropriate consent and follow-up, including patients under guardianship.

* Carotid stenosis refers specifically to the internal carotid artery unless significant external carotid artery involvement is also observed.