Real World Expanded Multicenter Study of the MitraClip® System (REALISM)

A Continued Access Registry of the Evalve® MitraClip® System: EVEREST II Real World Expanded Multicenter Study of the MitraClip System (REALISM)

Prospective, multicenter, continued access registry of the MitraClip® Cardiovascular Valve Repair System in the treatment of mitral valve regurgitation. Patients will undergo 30-day, 6-month, 12-month, 36-month and 60-month clinical follow-up. The study consists of two arms: a High Risk group (NCT01940120) and a Non-High Risk group (NCT00209274) . Patients that did not meet REALISM High Risk or Non-High Risk eligibility criteria were evaluated for consideration for either Emergency Use (EU) or Compassionate Use (CU).

The EVEREST II REALISM study (REALISM study) is a continued access registry designed for continued data collection on the use of Abbott Vascular's MitraClip System (MitraClip® Device) under more "real world" conditions. After the completion of enrollment in the pivotal EVEREST II Randomized Controlled Trial (RCT) NCT00209274 and EVEREST II High Risk Registry Study NCT01940120, continued access to the technology was warranted to collect additional safety and effectiveness data on the MitraClip® Device. This continued access study was approved by FDA on November 21, 2008 (G030064). There are two arms (High Risk and Non-High Risk) in the REALISM study. Patients that did not meet REALISM High Risk or Non-High Risk eligibility criteria were evaluated for consideration for either Emergency Use (EU) or Compassionate Use (CU). Enrollment in the Non-High Risk arm of the study concluded on April 14, 2011 and enrollment in the High Risk arm concluded on December 19, 2013.

REALISM is a prospective, multi-center, study of the safety and effectiveness of an endovascular approach to the treatment of mitral valve regurgitation using the Evalve Cardiovascular Valve Repair System (MitraClip® implant). Patients with moderate-to-severe (3+) or severe (4+) mitral regurgitation (MR), as determined by the site from a transthoracic echocardiogram (TTE), were considered for enrollment in this study. The TTE and a transesophageal echocardiogram (TEE) are used to assess eligibility criteria for MR severity, valve anatomy and left ventricular parameters.

Patients screened in EVEREST II REALISM Study will first be screened for high risk (HR) status and enrolled into the HR arm if they meet eligibility for this arm of the study. If they do not meet eligibility for the HR arm, patients will be further screened for eligibility for enrollment into the non-high risk (NHR) arm.

Key Inclusion Criteria:

• The primary regurgitant jet originates from malcoaptation of the A2 and P2 scallops of the mitral valve (MV)
• Male or non-pregnant female
• Trans-septal catheterization is determined to be feasible by the treating physician

High Risk Arm:

• Predicted procedural mortality risk calculated using the STS surgical risk calculator of ≥12% or, in the judgment of a cardiac surgeon, the patient is considered a HR surgical candidate due to the presence of one of the following indications:

  1. Porcelain aorta or mobile ascending aortic atheroma
  2. Post-radiation mediastinum
  3. Previous mediastinitis
  4. Functional MR with EF <40
  5. Over 75 years old with EF<40
  6. Re-operation with patent grafts
  7. Two or more prior chest surgeries
  8. Hepatic cirrhosis
  9. Three or more of the following STS high risk factors 9.1 Creatinine >2.5 mg/dL 9.2 Prior chest surgery 9.3 Age over 75 9.4 EF<35

• Symptomatic moderate to severe (3+) or severe (4+) chronic MR and in the judgment of the investigator intervention to reduce MR is likely to provide symptomatic relief for the patient

• American Society of Anesthesiologists (ASA) physical status classification of ASA IV or lower

Non-High Risk Arm:

• Moderate to severe (3+) or severe (4+) chronic MV regurgitation and:

  1. Symptomatic with >25% LVEF and LVESD ≤55mm or, 2. Asymptomatic with one or more of the following: i. Left Ventricular Ejection Fraction (LVEF) 25% to 60% ii. Left Ventricular End-Systolic Diameter (LVESD) ≥40 mm iii. New onset of Atrial fibrillation (AFib) iv. Pulmonary arterial systolic pressure (PASP) >50 mmHg at rest or >60 mmHg with exercise

• Candidate for MV repair or replacement surgery, including cardiopulmonary bypass

Key Exclusion Criteria:

• Evidence of an Acute Myocardial Infarction (AMI) in the prior 12 weeks of the intended treatment

• In the judgment of the Investigator, the femoral vein cannot accommodate a 24 French scale (F) catheter or the presence of an inferior vena cava (IVC) filter would interfere with advancement of the catheter or ipsilateral Deep Venous Thrombus (DVT) is present

• MV orifice area <4.0 cm2

• If leaflet flail is present:

  1. Flail Width ≥15 mm, or
  2. Flail Gap ≥10 mm.

• If leaflet tethering is present:

  1. Vertical coaptation length <2 mm

• Leaflet anatomy which may preclude clip implantation, proper clip positioning on the leaflets or sufficient reduction in MR. This may include:

  1. Evidence of calcification in the grasping area of the A2 and/or P2 scallops
  2. Presence of a significant cleft of A2 or P2 scallops
  3. More than one anatomic criteria dimensionally near the exclusion limits
  4. Bileaflet flail or severe bileaflet prolapse
  5. Lack of both primary and secondary chordal support

• Hemodynamic instability (systolic pressure <90 mmHg without afterload reduction or cardiogenic shock or the need for inotropic support or intra-aortic balloon pump).

• Need for emergency surgery for any reason

• Prior MV surgery or valvuloplasty or any currently implanted mechanical prosthetic valve or currently implanted Ventricular assist device (VAD)

• Echocardiographic evidence of intracardiac mass, thrombus or vegetation

• Active endocarditis or active rheumatic heart disease or leaflets degenerated from either endocarditis or rheumatic disease (i.e. noncompliant, perforated)

• History of bleeding diathesis or coagulopathy or subject will refuse blood transfusions

• Life expectancy <12 months

• Active infections requiring current antibiotic therapy

• Patients in whom transesophageal echocardiography (TEE) is contraindicated

High Risk Arm:

• EF <20%, and/or LVESD >60 mm

Non-High Risk Arm:

• The need for any other cardiac surgery
• Any endovascular therapeutic interventional or surgical procedure performed within 30 days prior to the index procedure
• Severe Left Ventricular (LV) dysfunction (EF <25% and/or LVESD >55mm)
• Severe mitral annular calcification
• Systolic anterior motion of the MV leaflet
• Hypertrophic cardiomyopathy
• History of a stroke or documented Transient Ischemic Attack (TIA) within the prior 6 months
• Upper GI bleeding within the prior 6 months
• Platelet count <75,000 cells/mm³
• Creatinine >2.5mg/dL