ACC 2014

Pooled Analysis of Percutaneous Ventricular Restoration (PVR) therapy using the Parachute Device in Patients with Ischemic Dilated Heart Failure Phil Adamson, Oklahoma Heart Hospital

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Heart Failure at the Center of Healthcare Cost & Reform

1.1M hospitalizations annually 3M physician visits annually 250,000 deaths annually 5 year mortality rate of ~ 50%

HF Costs $31B now.$70B by 2030 HF Hospitalization ~2/3 of HF costs HF included in Quality Metrics Hospital Readmission Reduction Program

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Parachute System

Anchor (Laser Cut)

Engages LV Wall (2mm)

3 shapes (14 or 16Fr)

Suture (Polypropylene)
Collapses Device. Supports ePTFE at the Edge

Membrane (ePTFE)
Dual layer occlusive membrane. Allows tissue growth.

Frame (Nitinol)
16 Arms Laser Cut from a Single Tube

20cc balloon is inflated to anchor device

Foot (Urethane)
Radiopaque. Shock Absorber
65mm Standard (+3mm) Short X X 75mm X X 85mm X X 95mm X X

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LV Remodeling Sequence Post MI

The cause of LV remodeling is the eccentric wall motion caused by the myocardial infarct.

The initial LV dilatation stretches the muscle fibers causing them to contract more forcefully in order to maintain stroke volume.

As the LV enlarges the increased wall tension is detrimental to the surviving myocardiums ability to contract.

To relieve symptoms we must cause the LV to contract more effectively and require less pressure to fill for the next contraction.

The filling pressure increases due to the resistance caused by the less compliant LV. As a result, this backs up blood into the lungs, impeding oxygen exchange causing shortness of breath and decreased exercise ability. Thus the cascade of events from the scar as a result of an MI impairs both systolic and diastolic function of the heart.

The LVs ability to stretch and accommodate filling from the left atrium through the mitral valve is compromised by the presence of the scar.

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Parachute Reduces LV Volume, Reshapes LV, and Restores Cardiac Function

Reduces wall stress in the upper chamber by changing LV geometry and reducing volume

Replaces the stiff/rigid scar with a more compliant Parachute that provides outward force by the anchors to aid in diastolic filling Improves diastolic compliance that reduces end diastolic filling pressures

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Analysis Population 111 Consecutive Intent-to-Treat patients included in this presentation. All enrolled on or before December 31, 2012 in the following trials: Europe Cohort A (16), US Feasibility (18), Europe Cohort B (54), and Parachute III (23)

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Patient Baseline Characteristics, N=111

Demographics Age, years Male BMI Underlying Heart Disease Ischemic NYHA Class NYHA I* NYHA II* NYHA III Medical History Smoking History, % History of Hypertension, % History of Diabetes, % Prior ICD, % Prior CRT, % Prior PCI, % Prior CABG, % HF Hosp. 12M Before Enrlmt, %
*NYHA

Cardiac Medications 60.7 10.6 93/111 (83.8%) 28.5 5.1 111/111 (100%) 1/111 (0.9%) 45/111 (40.6%) 65/111 (58.5%) Aspirin, % Anticoagulant, % ACE Inhibitor, % ARB, % Beta Blocker, % Diuretic, % Optimal Medical Therapy1, %
1defined

86/98 (87.8%) 39/100 (39.0%) 82/111 (73.9%) 21/111 (18.9%) 108/111 (97.3%) 94/111 (84.7%) 87/111 (78.4%)

as beta blocker + diuretic + (ACE or ARB)

78/105 (74.3%) 76/111 (68.5%) 39/111 (35.1%) 42/111 (37.8%) 20/111 (18.0%) 84/111 (75.7%) 19/111 (17.1%) 30/95 (31.6%)
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III or IV in the last 3 months

Left Ventricle Baseline Characteristics, N = 111

Cardiac Output 4.6 2.2 L/min Left Atrial Volume 84.4 28.2 ml

AR 33% MR 79%

LVIDD 6.0 0.9 cm

EDV 240.4 61.0 ml EF 27.9 7.8 % EDP 21.3 19.6 mmHG

EDVi 122.4 27.4, COi 2.3 1.1, LAVi 43.3 14.5
Sample size may differ for each variable due to echo quality and availability
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Long Axis 9.6 1.0 cm

Procedure Data, N=111

Treatment Success, % Device Size 65mm, % 75mm, % 85mm, % 95mm, % Duration, minutes Fluoroscopy Time, minutes Days in Hosp. Prior to Discharge US EU 2.9 1.9 5.9 3.0 3/111 (2.7%) 49/111 (44.1%) 42/111 (37.8%) 17/111 (15.3%) 86.0 41.4 20.7 25.8
Screening Process

106/111 (95.5%)

Procedure Complications by VARC Major, % Minor, %

16/111 (14.4%) 8/111(7.2%) 9/111 (8.2%)

Angiographic sequence of a Parachute implantation in the left ventricle (LV). Pigtail in the LV cavity to perform LV angiography (A), Device placement with foot exposed and in contact with the antero-apical wall (B), Balloon inflation to facilitate self-expansion of the device (C), Device fully expanded but still attached to the delivery system (D) Final positioning after release of the device (E).

VARC definition citation: Leon et al: Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium. EU Heart Journal (2011) 32, 205-217.
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Hemodynamic Data, N=95

Variable Heart Rate Blood Pressure Systolic, mmHg Diastolic, mmHg LV Volume ESVi, ml/m2 EDVi, ml/m2 Systolic Improvement Ejection Fraction, % Fractional Shortening, % Contractility Index (Ees), mmHg-m2/ml Stroke Work / EDVi, mmHg Diastolic Improvement LAVi, ml/m2 43 43.6 15.1 37.8 10.9 <0.05 81 72 81 81 28.4 8.0 18.5 9.8 1.3 0.5 26.8 8.7 30.4 8.1 20.3 8.6 1.6 0.6 29.0 8.2 <0.05 0.14 <0.0001 <0.05 81 81 87.6 24.6 120.8 26.2 73.2 22.7 103.8 25.9 <0.0001 <0.0001 95 95 118.6 17.2 71.7 10.0 117.3 14.6 71.6 10.1 NS NS N* 95 Baseline 67.5 13.1 12M 67.9 10.5 p-value NS

*Paired analysis on available data thus the different Ns

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NYHA, N=106
100%

80%
35% Maintain 29% Maintain

No Data Death Transplant/ VAD IV

60%

32% Maintain 54% Improve N=43 N=62

40%
51% +1 NYHA

40% +1 NYHA

III II I

20%
16% +2 NYHA

0%
Baseline, All 12M Baseline, NYHA II* 12M Baseline, NYHA III 12M
N=106 is the number of patients discharged with the Parachute 11 device

*NYHA II at baseline had to be NYHA III or IV in the last 3 months

NYHA, N=106
100%

80%
35% Maintain 29% Maintain

No Data Death Transplant/ VAD IV

60%

32% Maintain 54% Improve N=43 N=62

40%
51% +1 NYHA

40% +1 NYHA

III II I

20%
16% +2 NYHA

0%
Baseline, All 12M Baseline, NYHA II* 12M Baseline, NYHA III 12M
N=106 is the number of patients discharged with the Parachute 12 device

*NYHA II at baseline had to be NYHA III or IV in the last 3 months

NYHA, N=106
100%

80%
35% Maintain 29% Maintain

No Data Death Transplant/ VAD IV

60%

32% Maintain 54% Improve N=43 N=62

40%
51% +1 NYHA

40% +1 NYHA

III II I

20%
16% +2 NYHA

0%
Baseline, All 12M Baseline, NYHA II* 12M Baseline, NYHA III 12M
N=106 is the number of patients discharged with the Parachute 13 device

*NYHA II at baseline had to be NYHA III or IV in the last 3 months

6 Minute Walk Data, N=89

600 75%

500 50% 400 +87.0 53.5 M

p<0.05
300 25% -0.1 11.0 M 200 0% 100 -62.6 43.8 M 365 Baseline 390 12M -25%

Improved (>20 M) Maintain Declined (<20 M)

N=89 is the number of patients completing both a baseline and 14 12M 6MWT

Stroke Rate
50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 0
No. at Risk BL 106
15

2.9%

90

180

270

360

180 days 96

360 days 82

Mortality (all-cause) Rate

50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 0
No. at Risk BL 106
16

5.7%

90

180

270

360

180 days 99

360 days 84

Mortality + HFH Rate

50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 0
No. at Risk BL 106 180 days 86
17

21.7%

90

180

270

360

360 days 73

Conclusions
Device efficacy as measured by hard clinical endpoints of death and repeat hospitalization for worsening HF are favorable when compared to published literature and support the design of the current US randomized trial, PARACHUTE IV (actively enrolling) Hemodynamic improvements are seen in both the systolic and diastolic phases of the cardiac cycle Functional improvement is shown by an increase in the 6MWT and reduction in NYHA class High procedural success rate of 96% with a low Major VARC rate of 7.2%

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