A Clinical Evaluation of the Safety and Effectiveness of the MitraClip System in the Treatment of Clinically Significant Functional Mitral Regurgitation

Key Inclusion Criteria:

- Clinically significant functional mitral regurgitation (moderate-to-severe or severe
MR) as defined by European Association of Echocardiography, within 90 days prior to
randomization and confirmed by the Echocardiography Core Laboratory Note: The TTE
must be obtained after the subject has been stabilized on optimal therapy and has
undergone revascularization and/or CRT, as appropriate

- Assessed by the investigator to be on optimal standard of care therapy for heart
failure, according to current ESC/HFA guidelines with no dose changes of heart
failure drugs (with the exception of diuretics) during the last 2 weeks immediately
prior to randomization.

- Symptomatic with documented New York Heart Association Class II, III or IV heart
failure, despite optimal standard of care therapy, within 30 days preceding
randomization

- Minimum of one documented hospitalization (acute care admission or emergency room
visit) for heart failure within 12 months preceding randomization OR values of 300
pg/mL for BNP or 1000 pg/mL for NT-proBNP after optimal medical and/or device
management within 90 days preceding randomization Note: BNP or NT-proBNP must be
obtained after the subject has been stabilized on optimal therapy and has undergone
revascularization and/or CRT, as appropriate

- Ambulatory patient with symptomatic congestive heart failure (CHF) in NYHA
functional class II to IV (despite optimal standard of care therapy as assessed
within 30 days preceding randomization) and with LVEF 20% to 50%. Note: LVEF needs
to be determined by one of the following methods: transthoracic echocardiography
(TTE), contrast ventriculography, gated blood pool scan, cardiac magnetic resonance)
within 90 days prior to randomization

- Patient is ambulatory and able to perform a 6MWT with the only limiting factor(s)
being due to cardiovascular fitness

Key Exclusion Criteria:

- Mitral regurgitation is primarily due to degenerative disease of the mitral valve
apparatus (Degenerative MR) as determined by transesophageal echocardiography (TEE).

- Status 1 heart transplant or prior orthotropic heart transplantation.

- Introduction of a new heart failure drug class within the last 2 weeks prior to
randomization.

- Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90
days prior to randomization. Note:Acute coronary syndrome (ACS) is defined as an ACS
that requires an intervention. Increased troponin without acute symptoms and chest
pain is not defined as ACS.

- Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular
surgery, or atrial fibrillation ablation within 90 days prior to randomization.

- Therapy with or without cardioverter-defibrillator (CRT or CRT-D), or Implantable
Cardioverter Defibrillator (ICD)) within 90 day prior to randomization, or revision
of any implanted rhythm management device within 90 days prior to randomization.

- Need for any cardiovascular surgery.

- Mitral valve surgery is considered the preferred therapeutic option for the subject

- Renal replacement therapy

- 6-Minute Walk Test (6MWT) distance > 475 meters

- Mitral Valve Area (MVA) by planimetry < 4.0 cm2; if MVA by planimetry is not
measurable, pressure half-time measurement is acceptable; MVA must be confirmed by
the Echocardiography Core Laboratory