device based approaches for heart failure ventricular reshaping
DESCRIPTION
In this presentation titled "Device Based Approaches For Heart Failure: Ventricular Reshaping" Alexandra Lansky, MD explains some of the device-based approaches for heart-failure being used by companies such as Cardio Kinetix (http://www.cardiokinetix.com/)TRANSCRIPT
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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0 30 60 90 120 150 180
KM In
cide
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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