Device Based Approaches for Heart Failure: Ventricular Reshaping

CardioKinetix

Alexandra Lansky, MD

Associate Professor Yale University School of Medicine

Honorary Reader University College London

Conflicts

Institutional Research Support: CardioKinetix

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

Current Parachute® Technology

Size Matrix

65 65s

75 75s

85 85s

95 95s

• 14Fr and 16Fr Guides (multiple shapes)

Parachute Optimal Implant

Device partions off non-contractile myocardium

Reduces LV volume

Contributes to contractile performance by:

Maintaining compliance

Maintains torsional contraction

Restores conical/longitudinal geometry

Optimizes LV outflow ejection

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

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

Good Image Quality

Apical Akinesis and preserved basal contractility

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

Results • Primary Endpoint: 90% (82/91) of patients

were successfully implanted and free of device-related MACE (death, MI, rehospitalization)

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

• Procedure Complications by VARC – Major – 6.6% – Minor – 8.8%

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Days from Procedure

Efficacy at 6 months 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

6 Minute Walk Test

p<0.05*

*paired data Distance (meter) Change from Baseline

Variable N* Baseline 12M p-value

Heart Rate 73 69.8 ± 9.4 68.4 ± 9.0 NS

Blood Pressure

Systolic, mmHg 73 115.9 ± 16.5 118.1 ± 14.8 NS

Diastolic, mmHg 73 70.7 ± 10.0 72.1 ± 10.5 NS

LV Volume

ESVi, ml/m2 61 86.6 ± 23.2 71.0 ± 21.5 <0.0001

EDVi, ml/m2 61 119.9 ± 24.4 101.3 ± 23.8 <0.0001

LV Contraction

Ejection Fraction, % 61 28.6 ± 7.7 30.8 ± 8.6 0.05

Fractional Shortening, % 56 18.0 ± 10.2 22.2 ± 12.2 <0.05

Contractility Index (Ees), mmHg-m2/ml 61 1.3 ± 0.4 1.7 ± 0.6 <0.0001

Stroke Work / EDVi, mmHg 61 26.9 ± 7.5 29.4 ± 8.9 <0.05

Filling Pressure Subset

End Diastolic Filling Pressure, mmHg 10 18.2 ± 8.2 12.9 ± 4.5** <0.05

LAVi, ml/m2 28 48.0 ± 15.3 36.4 ± 10.8 <0.0001

Hemodynamic Summary: Stable Heart Rate and BP

*paired analysis on available data **data collected with Swan-Ganz catheter at 6M

Variable N* Baseline 12M p-value

Heart Rate 73 69.8 ± 9.4 68.4 ± 9.0 NS

Blood Pressure

Systolic, mmHg 73 115.9 ± 16.5 118.1 ± 14.8 NS

Diastolic, mmHg 73 70.7 ± 10.0 72.1 ± 10.5 NS

LV Volume

ESVi, ml/m2 61 86.6 ± 23.2 71.0 ± 21.5 <0.0001

EDVi, ml/m2 61 119.9 ± 24.4 101.3 ± 23.8 <0.0001

LV Contraction

Ejection Fraction, % 61 28.6 ± 7.7 30.8 ± 8.6 0.05

Fractional Shortening, % 56 18.0 ± 10.2 22.2 ± 12.2 <0.05

Contractility Index (Ees), mmHg-m2/ml 61 1.3 ± 0.4 1.7 ± 0.6 <0.0001

Stroke Work / EDVi, mmHg 61 26.9 ± 7.5 29.4 ± 8.9 <0.05

Filling Pressure Subset

End Diastolic Filling Pressure, mmHg 10 18.2 ± 8.2 12.9 ± 4.5** <0.05

LAVi, ml/m2 28 48.0 ± 15.3 36.4 ± 10.8 <0.0001

Significant LV Volume Reduction

*paired analysis on available data **data collected with Swan-Ganz catheter at 6M

Variable N* Baseline 12M p-value

Heart Rate 73 69.8 ± 9.4 68.4 ± 9.0 NS

Blood Pressure

Systolic, mmHg 73 115.9 ± 16.5 118.1 ± 14.8 NS

Diastolic, mmHg 73 70.7 ± 10.0 72.1 ± 10.5 NS

LV Volume

ESVi, ml/m2 61 86.6 ± 23.2 71.0 ± 21.5 <0.0001

EDVi, ml/m2 61 119.9 ± 24.4 101.3 ± 23.8 <0.0001

LV Contraction

Ejection Fraction, % 61 28.6 ± 7.7 30.8 ± 8.6 0.05

Fractional Shortening, % 56 18.0 ± 10.2 22.2 ± 12.2 <0.05

Contractility Index (Ees), mmHg-m2/ml 61 1.3 ± 0.4 1.7 ± 0.6 <0.0001

Stroke Work / EDVi, mmHg 61 26.9 ± 7.5 29.4 ± 8.9 <0.05

Filling Pressure Subset

End Diastolic Filling Pressure, mmHg 10 18.2 ± 8.2 12.9 ± 4.5** <0.05

LAVi, ml/m2 28 48.0 ± 15.3 36.4 ± 10.8 <0.0001

Significant Contractility Improvement

*paired analysis on available data **data collected with Swan-Ganz catheter at 6M

Variable N* Baseline 12M p-value

Heart Rate 73 69.8 ± 9.4 68.4 ± 9.0 NS

Blood Pressure

Systolic, mmHg 73 115.9 ± 16.5 118.1 ± 14.8 NS

Diastolic, mmHg 73 70.7 ± 10.0 72.1 ± 10.5 NS

LV Volume

ESVi, ml/m2 61 86.6 ± 23.2 71.0 ± 21.5 <0.0001

EDVi, ml/m2 61 119.9 ± 24.4 101.3 ± 23.8 <0.0001

LV Contraction

Ejection Fraction, % 61 28.6 ± 7.7 30.8 ± 8.6 0.05

Fractional Shortening, % 56 18.0 ± 10.2 22.2 ± 12.2 <0.05

Contractility Index (Ees), mmHg-m2/ml 61 1.3 ± 0.4 1.7 ± 0.6 <0.0001

Stroke Work / EDVi, mmHg 61 26.9 ± 7.5 29.4 ± 8.9 <0.05

Filling Pressure Subset

End Diastolic Filling Pressure, mmHg 10 18.2 ± 8.2 12.9 ± 4.5** <0.05

LAVi, ml/m2 28 48.0 ± 15.3 36.4 ± 10.8 <0.0001

Significant Filling Pressure Reduction

*paired analysis on available data **data collected with Swan-Ganz catheter at 6M

Parachute Mechanism of Action

• Reduces LV Volume • Reduces wall stress • Preserved LV geometry and • Torsional contraction

Substitutes rigid scar • Improved LV compliance • Better Diastolic filling • Better LV Apical ejection • Reduces end diastolic filling

pressures and LA size reduction

The primary effect of the Parachute is that it improves diastolic compliance, which yields reduced end diastolic filling

pressures and positive clinical results.

• Un-blinded

• Up to 80 sites

• Key Inclusion Criteria:

• NYHA Class III-IV

• EF >15% and < 35%

• Post LAD MI, apical akinesis

• CT imaging at baseline for sizing and anatomy

• Echo at Baseline, 6mo, and annually

• Treated patients on Warfarin and ASA 1yr

PARACHUTE IV N=560

Treated N=280

Control N=280

6M, 1-5Y FU

1:1

PARACHUTE IV Trial Design

Primary efficacy endpoint

• Death or re-hospitalization for worsening HF (WHF)

• Sample size calculation assumes constant hazards and a follow-up of at least 12 months

• This event-driven trial will be concluded when a total of 276 death or reshospitalizations for WHF have occurred and all patients have had at least 12 months of follow-up.

Safety composite at 12 Months

• Defined as all cause death, myocardial infarction, need for elective, emergent, or urgent cardiac or thoracic aortic surgery, renal failure requiring dialysis, peripheral thromboembolism (including retinal), and clinically important stroke (change from baseline of Modified Rankin score > 1).

In addition, there are a number of pre-specified secondary and labeling safety and efficacy end points.

PARACHUTE IV Endpoints