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

DISCLOUSRES NO relevant conflicts to disclose

Shah et al JACCI 2015

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

Cardiogenic Shock Complicating Acute Myocardial Infarction

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

SHOCK Trial 1-Year Survival In Press

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; 41:1087-1095

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)

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

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

2010 STEMI study (333 patients) CONFIDENTIAL

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

Infarct Size All Patients Anterior MI < 6 hours AMIHOT 60 60 p=0.30 50 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)

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