1. CRT 2015 Unmet Needs in STEMI Interventions
William W. O’Neill, MD
Henry Ford Health System
Medical Director
Center for Structural Heart Disease

2. DISCLOUSRES
NO relevant conflicts to disclose

3. Shah et al JACCI 2015

4. Advances in REPERFUSION Therapy
1980’s 1. Timely opening of IRA feasible 2. I.C. Stretokinase saves lives 3. IV TPA saves lives 4. Primary PCI feasible 1990’s Thrombolytic Wars 1. SK to TPA to TnK 2. Lytics vs. PTCA (26 trials) 2000’s 1. Primary PCI preferred strategy 2. Ancillary therapies validated ( Bivalirudin, Clopidogrel etc) 3. Systems of care, process of care established 2010’s UNMET NEEDS

5. Cardiogenic Shock Complicating Acute Myocardial Infarction

6. Worcester Experience Resource Use in Shock (NEJM 1999;340:1162)

7. SHOCK Trial 1-Year Survival
In Press

8. Amount of Direct Unloading Correlates to Infarct Size
Ligation of 1st diagonale in Animal Model.
Area at risk is ~14% of LV
67.24.6
as Proportion of Area at Risk (%)
Infarct Size 20 40 60 80
Control
Impella
Half Flow
65.06.3
54.08.0
41.65.8
IABP
Full Flow
Impella study – Flameng et al 2000.
Meyns et al., J Am Coll Cardiol 2003; 41:

9. Timing of Insertion vs Outcome in AMI Shock
Impella placed BEFORE PCI (N=22)
Median = -0.3 hrs before 1st balloon inflation
p=0.02
for patients undergoing PCI (%)
Survival in AMI Shock
Impella placed AFTER PCI (N=34)
Median = 1.4 hrs after 1st balloon inflation
Follow-up (days)

10. Door-to-Balloon Time & Infarct Size
Pooled Sestamibi Analysis
Door-to-Balloon Time & Infarct Size
Anterior vs. Non-Anterior MI
(9,43)
(6,41)
(1,33)
(0,34)
(0,14)
(0,16)
(0,16)
(0,16)
Door-to-Balloon Time (Minutes)
O’Neill et al. JACC 2005;45[suppl A]:225A

11. Remote Ischemic Preconditioning
New Therapy to Reduce Infarct Size
Preconditioning
Cell Signaling
Systemic Protection
Upper arm intermittently occluded with cuff
4 cycles: 5 min ON, 5 min OFF
40 min total
Survival kinase pathways activated (cGMP/PKG, RISK, SAFE)
Mitochondrion is preserved: potassium –dependent KATP channel activated; permeability transition pore closed
Anti-inflammatory genes activated
Reduced infarct size
Reduced inflammation
Vital organs protected: brain, kidneys, lungs, liver
CONFIDENTIAL

12. 2010 STEMI study (333 patients)
CONFIDENTIAL

13. Present Status
Proof-of-concept and industrial design prototypes are complete
Feasibility of systolic BP detection is demonstrated
Design firms, clinical research organization (CRO) are prequalified, detailed proposals and quotes received
Accepted to Commercialization Acceleration Program at the Wharton Business School
Initial prototype
Industrial Design
CONFIDENTIAL

15. Infarct Size All Patients Anterior MI < 6 hours AMIHOT 60 60 p=0.3050 50 40 40 30 30
% of Left Ventricle 23 20 20 13 11 9 10 10
Control
(n=122) AO
(n=121)
Control
(n=52) AO
(n=49)

16. Future Reperfusion Algorithm
Chest pain onset
PCI
TIMI III flow
Recovery
assessment
Good recovery
Poor recovery
Protective measures
Filters, thrombectomy
Microcirculatory agents
Home
Myocyte regeneration
ST resolution
MRI
MCE