Meta-Analysis of Percutaneous Ventricular Restoration (PVR) therapy

using the Parachute® Device in Patients with Ischemic Dilated Heart Failure

Martyn R. Thomas, MD

St. Thomas’ Hospital London, United Kingdom

Potential conflicts of interest

Speaker's name: Dr Martyn Thomas

I have the following potential conflicts of interest to report: Consultant: … Cardiokinetix and Principal Investigator of Parachute III

Anterior Infarct Results in a scarred / thin wall initiating ventricular remodeling and dilation.

24% of MIs Develop HF1

Wall Motion Abnormality Akinetic, Dyskinetic, and/or Aneursym 1Jhund and McMurray. Heart Failure After Acute MI. Circulation. 2008;118:2019-2021

Parachute Patient Target Ischemic Heart Failure

Mechanism of Action

Reduces wall stress in the upper chamber by changing LV geometry

Reduces end diastolic filling pressures due to improved compliance.

Substitutes the stiff/rigid scar with a more compliant Parachute that also provides outward force at the anchors to aid in diastolic filling

The primary effect of the Parachute is improving diastolic compliance, which yields reduced end diastolic filling pressures and positive clinical results.

PARACHUTE Clinical Program Device has developed through programme

2005

2008

2011

2012

PARACHUTE Cohort A (N=19, 14 implants)

PARACHUTE US Feasibility (N=20, 17 implants)

PARACHUTE Cohort B (N=59, 54 implants)

PARACHUTE III (N=54, 43 implants)

CE MARK APPROVAL DATA

EU CONFIRMATORY DATA

EU POST MARKET DATA

New guide catheters and 6 additional implant sizes

All data is pooled as a post hoc meta-analysis. All events have been adjudicated by a CEC. All echo data has been analyzed by a core lab.

Enrollment complete 3 year data available

Enrollment complete

Enrollment complete

Population

• 133 Patients Treated with a Parachute to Date • 91 Intent-to-Treat patients included in this

presentation. – Enrolled on or before September 26, 2012 – Cohort A, US Feasibility, Cohort B, and Parachute III

– Population is made up of 34 patients from Cohort A

and US Feasibility, 48 patients from Cohort B and 9 patients from Parachute III.

Current Parachute® Technology

Size Matrix

65 65s

75 75s

85 85s

95 95s

Clinical Case Details

• 87 yr old female • Anterior STEMI January 2011 with “late”

presentation. No PPCI or thrombolysis. • By December 2011; NYHA 3 despite optimal

medical therapy and CRT device therapy. • Diffuse 3V coronary disease with no

percutaneous revascularisation option. • 6 min walk 194m limited by SOB

16/14F sheath

Trial & Analysis Population • DESIGN: Non-randomized, multi-center • PATIENTS: 91 ITT (86 Treated) • SITES: 25 • Key Inclusion

• NYHA II-IV • EF 15% - 40% • LV Wall Motion Abnormality

• Key Exclusion • Clinically significant untreated CAD • Revasc, CRT / ICD, or AMI within

60 days of enrollment • AR or MR > 2+

• ANALAYSIS PLAN: Meta-analysis of the first 91 Parachute patients to reach 6M follow-up

Intent-to-Treat, N=91

Treated, N=86

6 Month, N=86

Unsuccessful Treatment, N=5 2 percutaneous snares

2 surgical removals, 1 perforation

Demographics N = 91

Age, years 60.7 ± 10.2 Gender, male 88% Weight, kg 86.6 ± 17.7 Height, cm 172.7 ± 7.8 Smoking History 77% History of Stroke 11% History of Hypertension 65% History of Diabetes 34% History of Dyslipidemia 85% Prior ICD Implantation 34% Prior CRT Device 9% Prior PCI 77% Prior CABG Surgery 15% HF Hosp. 12M Before Enrolled 32% Months (median) since MI 40

• Major Procedure / Valve Complications – 6.6% – (2) aortic valve (requiring AVR). – (2) left ventricle injury – (2) bleed

• Minor Procedure Complications – 8.8%

Procedural Complications

Aortic Valve Damage Investigated and Solution Implemented – 6Fr intermediate catheter used to create smooth transition from 0.035” wire to dilator – IFU updated

Before

After

Results

• Primary Endpoint: 90% (82/91) of patients were successfully implanted and free of device-related MACE – (5) Unsuccessful implantations

• (3) acute device removals due to positioning • (1) device removal due to suspected infection • (1) guide catheter perforation

– (1) mitral apparatus damage leading to death – (2) heart failure hospitalization – (1) peripheral embolization (left popliteal)

• Stroke: 1% (1/91) – Non-device / non-procedure related

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0.2

0.3

0.4

0.5

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0 30 60 90 120 150 180

KM In

cide

nce

(%)

Days from Procedure

Efficacy Mortality + HF Hosp. for Treated Population

No. at Risk 86 60 54

17.9%

NYHA Classification, n=86 At 6 Months, 89% of Patients Improved or Maintained Functional

Status.

53% Improved 36% Maintained

NYHA III Subset, n=51

33% Maintained

35% Improved 1 Class

27% Improved 2 Class

LV Volume, n=74

20%

23%

All paired volumes compared to baseline have a p-value of < 0.001

How might volume reduction influence survival: 41 ml (23%) reduction in ESV?

6 Minute Walk Test

p<0.05*

*paired data Distance (meter) Change from Baseline

Discussion Why the Parachute in light of the STICH results?

• Degree of Volume (LVESV) Reduction – Parachute 23% vs. STICH 13%

• More than just volume reduction…. – Method of Addressing the Scar

• Parachute partitions with a flexible device • SVR excises and closes by suturing a non-flexible patch

– Diastolic Filling is directly related to the active process of LV relaxation leading to a “suction” effect (this suction effect is thought to be caused by rapid untwisting of the LV apex in early diastole)

• Parachute is flexible and applies a small amount of outward force during filling • SVR leaves behind a rigid apex

– LV Shape • Parachute leaves a consistent conical shape and allows “torsion”. • SVR post-OP shape is operator dependant and tends to result in a “flat” apex

– Parachute procedure is considerably lower risk than SVR

Parachute IV

• Pivotal randomised US trial. • Approx 500 patients randomised to Medical

Therapy and the Parachute v Medical Therapy alone.

• Primary endpoint is death or rehospitalisation for heart failure (event driven)

Conclusions

(1) The Parachute device has been in development and in Clinical Programmes since 2005. (2) There have been important learnings and developments along the way: - Sizing: Now 8 different sizes of the device CE marked - Guide Catheter development and use including strategies to

avoid aortic valve trauma: (now 3 guide shapes available and new tapered obturator tip and “steerable” guiding catheter in development).

Conclusions

(3) The early clinical data (including a number of FIM patients with early versions of the device) is very encouraging including important improvements in NYHA class and LV volume reduction. (4) Continued post CE mark clinical experience and the pivotal US (Parachute IV) trial will establish where this device sits in the treatment of heart failure.

Endpoints

• Primary – Successful delivery and deployment of the Parachute Implant through

6-month follow-up without the occurrence of Major Adverse Cardiac Events (MACE) related to the investigational device.

• Secondary – Change in Left Ventricular Volume Indexes (End Systolic {LVESVI} and

End Diastolic {LVEDVI}) measured by echocardiography from baseline to 6 months

– Change in exercise tolerance from baseline to 6 and 12 month follow-up as measured by 6-Minute Walk Test

– Combined cardiovascular mortality and morbidity that includes all cause death, hospitalization for heart failure, myocardial infarction and stroke from baseline to 6 and 12 months