Prospective Balloon Aortic Valvuloplasty

Study Objectives:

1. To assess the volume of BAV procedures and success of the procedure as a 'bridge' to
AVR/TAVR (percent of BAV patients that go on to receive valve replacement).

2. To establish the demographic profile of the patients having a BAV with clear
determination of the primary indication for the BAV.

3. To collect baseline, 30-day, 3 and 6 month, and 1 year patient data to assess
improvement in primary cardiac condition (AVA, EF & GRAD) and other primary endpoint
conditions and symptomology according to pre-operative BAV rationale (e.g., renal
function, chronic obstructive pulmonary disease, etc - see inclusion criterion).

4. To assess patient Quality Of Life prior to procedure and at all follow-up time points
through to 1-year post-procedure

5. To assess patient's Resilience at baseline and 30 day follow-up using the
Connor-Davidson 10 Resilience Scale.

6. To assess post-operative rate of stroke and other complications (according to VARC2
definitions ).

7. To identify the survival in relation to the treatment indication for BAV.

Background:

BAV is a percutaneous treatment for severe aortic stenosis with a balloon catheter inside
the valve. The balloon stretches the valve open, in an effort to increase the opening size
of the valve and improve blood flow.

While the procedure offers relief from symptoms, the preferred alternative is aortic valve
replacement. The Cardiology/American Heart Association (ACC/AHA) Guidelines on Valvular
Heart Disease assert that BAV should be limited to serving as a bridge to surgery in those
with compromised hemodynamic status or as a method for palliation of symptoms in those who
are not candidates for AVR (Class IIb).

With the commercial release of the Edwards Sapien transcatheter aortic valve system and
increasing availability of TAVR, patients previously bridged to inclusion in TAVR
feasibility trials with BAV might proceed more directly to TAVR. Thus an important challenge
will be to better define the relative role for TAVR and of palliative BAV, especially in
extreme-risk patients for whom the survival benefit of successful TAVR may be limited due to
other life-threatening comorbid conditions.

A retrospective chart review of patients that had undergone BAV from 2006 to May 2013 was
performed. Several indications were identified in relation to this surgical intervention
(palliative therapy from the outset; a means to 'bridge' a patient to operable status /
treatment; therapy for patients under consideration for TAVR but delayed due to trial
constraints; and as ultimate therapy because patients declined further treatment).
Unfortunately, however, patient category determinations were made post-hoc, and proved
problematic to properly validate. The current study proposes to rectify that problem by
collecting definitive diagnostic intention prior to study inclusion.

Methods of Proposed Research:

The study is a prospective collection of patient indication, procedural, and intermediate
outcomes for all patients undergoing BAV. Data from hospital records, 30-day, 3 month, 6
month, and 1-year follow-up clinic visits and all other subsequent clinic and hospital
records through to 1-year post-procedure will be collected.

Study Design:

With a minimum enrollment of 100 total patients, the estimated time period of this study is
6 months + 1 year for all baseline and follow-up data collection (beginning 6/2013 through
10/2014). This estimate is based on an average monthly rate of 7 BAV procedures at Medical
City, and 10 at the Heart Hospital Baylor Plano.

Schedule of Assessments/Data Collection:

Pre-procedure: Kansas City QOL and Connor-Davidson 10 Resilience Scale will be assessed
pre-procedure gained from all consenting patients prior to BAV. Indication for BAV will be
obtained by a case report form for all patients.

Hospitalization period: All other data will be collected from existing medical records for
hospitalization and for BAV procedure through to discharge, as well as all inpatient
hospital visits following BAV through to 1 year follow-up.

30 day, 3 month, 6 month and 1 year clinic follow-up: Clinic follow-up will re-assess
parameters of cardiac function, as well as pulmonary, and/or renal function as deemed
necessary for evaluation of procedural "success" based on pre-BAV indicators. Telephone
follow-up will be performed for any patients that fail to appear for clinic visits. QOL from
all patients who have consented to QOL assessment will be obtained at each time point. The
Connor-Davison 10 Resilience Scale will be collected at the 30 day follow-up visit.

Statistical & Analytical Methods:

The endpoint variables are procedural mortality, survival post intervention and other major
adverse event (the following clinical endpoints will be queried as per VARC2
recommendations: mortality, stroke, myocardial infarction, bleeding complications, acute
kidney injury, vascular complications, conduction disturbances and arrhythmias, and other
relevant complications not previously categorized).

Indication for BAV will be the primary planned comparison, with additional analyses planned
for demographic factors (age, gender, race/ethnicity, height, weight, and BMI, and body
surface area (BSA). Changes in cardiac function (output in l/min, ejection fraction, aortic
peak velocity in m/s, aortic valve area in cm2, aortic valve gradient in mmHg) will be
compared in all patients with echocardiography. Definition of success will also assess
change in renal function (lab creatinine values), and pulmonary (Fev1/DLCO) values, and
pre-post score QOL and resilience scale changes.

Procedural variables will include balloon specifications, number of balloons used for each
patient, number of times each balloon has been dilated, and complications. The latter will
be distinguished in procedural and post procedural adverse events.

The results will be shown as mean and standard deviation, proportion of patients of the
total numbers who had a BAV. The cardiac catheter lab parameters before and after the BAV
procedure will be contrasted using a student's paired both tail T-Tests. A p value of less
than 0.05 will be considered significant. Categorical variables will be compared using a
chi- square test. The association between the risk factors and the outcome of interest will
be tested with a Cox proportional hazards model. In addition Kaplan-Meier survival curves
will be used to determine the time from BAV to procedural death and overall survival
differentiated by each type of BAV indication.

Data Monitoring:

All data will be reviewed by Data Advisory Group for completeness and accuracy.

Inclusion criteria:

Patients will be identified in the valve clinics and from the cath lab schedules. All
patients who are scheduled to have a BAV during the study period in the cath lab at MCD
and THHBP for whom a definitive pre-procedure BAV indication including the following will
be eligible for enrollment:

- BAV as palliation

- BAV offered as a means of assessment for a change to operable status (a 'bridge' to
decision). Patients in this category will be classified by the procedure physician as
to the primary reason of 'bridge' decision - these reasons would include:

- Diagnostic

- Shortness of Breath- Aortic stenosis vs. other etiology such as COPD

- Lack of Energy- Aortic stenosis vs. other etiology

- LV Dysfunction - Aortic stenosis vs. cardiomyopathy

- Therapeutic- determination of improvement to receive treatment

- Frailty - Factors: grip strength, 5 meter walk time, Katz Index of Independence
in Activities of Daily Living (Katz ADL), serum Albumin

- Immobility - Reason for immobility and current assistive device will be
documented

- Stage IV chronic kidney disease - Cockoft- Gault formula (GRF 15-29 mL/min/1.73
m2) or high procedural risk for progression to dialysis dependence

- End stage renal disease currently on dialysis Acute kidney Injury - (Varc 2)

- Severe left ventricular dysfunction - BAV to improve EF (VARC 2) LVEF < 35%
without contractile reserve

- NYHA class IV congestive heart failure

- Active bleeding

- Urgent or emergent clinical status

- Severe liver disease (VARC 2)

- Active Infection

- Other cause:_______________________________

The Kansas City Cardiomyopathy questionnaire (KCCQ), a quality of life (QOL) assessment,
and the Connor-Davidson 10 Resilience Scale will be collected from all patients for whom
informed consent is obtained by the study coordinators to administer the QOL assessment
and resilience scale.

Exclusion Criteria: