Tiara* Transcatheter Mitral Valve Replacement Study

• Safety: Freedom from all-cause mortality and major adverse events defined

as disabling stroke, myocardial infarction (peri-procedural or spontaneous),

renal failure requiring dialysis, life-threatening bleeding, and cardiac

surgical

or transcatheter reintervention at 30 days from the implant procedure.

• Device performance: The reduction of MR to optimal or acceptable at 30

days. MR reduction is considered optimal when post-procedure MR is

reduced to trace or absent. MR reduction is considered acceptable when

post-procedure MR is reduced by at least 1 class or grade from baseline and

to no more than moderate (2+) in severity.

• Freedom from all-cause mortality and major adverse events defined as

disabling stroke, myocardial infarction (peri-procedural or spontaneous), renal

failure requiring dialysis, life-threatening bleeding, and cardiac surgical or

transcatheter reintervention at 90 days, 180 days, one (1) year and annually

to five (5) years from the implant procedure.

• Individual components of the primary safety endpoint (major adverse events

of all-cause mortality, disabling stroke, myocardial infarction [peri-procedural

or spontaneous], renal failure requiring dialysis, life-threatening bleeding,

and

cardiac surgical or transcatheter reintervention) at 30 days from the implant

procedure, 90 days, 180 days, 1 year, and annually to 5 years from the

implant procedure.

• Technical success (measured at exit from the procedure room). All of the

following must be present:

o Absence of procedural mortality; and

o Successful access, delivery, and retrieval of the device delivery

system; and

o Successful deployment and correct positioning of the first intended

device; and

o Freedom from emergency surgery or reintervention related to the

device or access procedure.

• Procedural success (measured at 30 days). All of the following must be

present:

o Device success (either optimal or acceptable); and

o Absence of major device or procedure related serious adverse

events (SAEs), including:

* Death

* Stroke

* Life-threatening bleeding (MVARC scale)

* Major vascular complications

* Major cardiac structural complications

* Stage 2 or 3 acute kidney injury (includes new dialysis)

* Myocardial infarction or coronary ischemia requiring PCI or

CABG

* Any valve-related dysfunction, migration, thrombosis, or

other complication requiring surgery or repeat intervention

• Incidence of mitral valvular insufficiency of >= moderate at post-procedure,

discharge, 30 days, 90 days, 180 days, 1 year, and annually to 5 years as

compared to baseline.

• Device migration defined as any movement of any valve structure(s)

compared with the final implant location, resulting in hemodynamic or

pathoanatomic

consequences (e.g., mitral paravalvular leak or left ventricular

outflow tract obstruction).

• Device fracture (adjudicated as affecting valve performance or not affecting

valve performance).

• Device success defined as (measured at each assessment interval).

All of the following must be present:

o Absence of procedural mortality or stroke; and

o Proper placement and positioning of the device; and

o Freedom from unplanned surgical or interventional procedures

related to the device or access procedure; and

o Continued intended safety and performance of the device,

including:

* No evidence of structural or functional failure

* No specific device-related technical failure issues and

complications

* Reduction of MR to either optimal or acceptable levels*

without significant mitral stenosis (i.e., post-procedure

EROA is >=1.5 cm2 with a transmitral gradient <5 mm Hg),and with no greater than

mild (1+) paravalvular MR (and

without associated hemolysis)

• Performance (as assessed at 30 days, 90 days, 180 days, and once annually

for 5 years as compared to baseline):

o Clinical performance as measured by NYHA Functional Class,

6 Minute Walk Test (6MWT), and the Kansas City Cardiomyopathy

Questionnaire (KCCQ).

o Hemodynamic performance as assessed by echocardiography:

mean MV gradient, mitral regurgitation, effective orifice area (EOA)

of the MV, LV systolic and diastolic dimensions as well as volume.

• Patient success (measured at 1 year). All of the following must be present:

o Device success (either optimal or acceptable), and

o Patient returned to the pre-procedural setting; and

o No rehospitalizations or reinterventions for mitral regurgitation; and

o Improvement from baseline in symptoms (e.g., NYHA improvement

by >=1 functional class); and

o Improvement from baseline in functional status (e.g., 6MWT

improvement by >=50 meters); and

o Improvement from baseline in quality-of-life (e.g., Kansas City

Cardiomyopathy Questionnaire improvement by >=10)