CRT 2011 Cool New Therapies for Cardiac Arrest: What you need to know to save lives Dr. Michael Mooney Director Interventional Cardiology Minneapolis Heart Institute Associate Professor of Clinical Medicine University of Minnesota

Michael R. Mooney, MD I have no real or apparent conflicts of interest to report. I intend to reference off label or unapproved uses of drugs or devices in my presentation. I intend to discuss therapeutic hypmia which is not FDA approved, it is ILCOR and ACC indicated, however.

Cardiac Arrest Out-of-hospital cardiac arrest (OOHCA) affects 295,000 people annually in the US 7.9% median survival rate Anoxic encephalopathy and neurologic deficits are common and disabling - among survivors Modest gain with CPR advances, many failed clinical trials – BRCT - barbiturates Enormous public health issue - personal, family & societal burdens Growing awareness of needed cardio-cerebral protection Lloyd-Jones D, Adams R, Carnethon M et al. Heart disease and stroke statistics-2009 update. Circulation 2009;119:e21-e181.

Hypothermia Pivotal Studies HACA, 2002 Bernard, 2002

Hypothermia: mechanisms ischemia reperfusion mitochondrial Dysfunction /Ca influx reactive oxygen species (ROS) inflammatory cascades hypothermia vascular dysfunction/hypotension apoptosis – organ dysfunction cerebral edema *Dr. Abella, University of Pennsylvania

Hypothermia Trials: Outcomes (%) P value Normothermia (%) RR (95% CI) Alive at hospital discharge with favourable neurological recovery HACA 0.006 72/136 (53%) 50/137 (36%) 1.51 (1.14-1.89) Bernard 21/43 (49%) 9/34 (26%) 2.65 (1.0-6.88) 0.046 Alive at 6 months with favourable neurological recovery HACA 71/136 (55%) 50/137 (39%) 1.44 (1.11-1.76) 0.009

. Helicopter Locations 2009 In Response to the STEMI Program at MHI Red– Zone II (90-120 mins) Blue– Zone I (< 90 mins) Helicopter Locations 2009 In Response to the STEMI Program at MHI Red– Zone II (90-120 mins) Blue– Zone I (< 9 mins) .

Hypothermia guidelines New Guidelines – more aggressive, 30’ CPR Full recoil. 30:2 Less defib use Hypothermia Level II A recommendation Hypothermia guidelines

Abbott Northwestern Hospital 72/140 51.4% Outcomes Abbott Northwestern Hospital 72/140 51.4% Survival by diagnosis STEMI: 49/76 64.5% Other: 29/64 45.3% Survival by initial rhythm VF/VT: 68/102 66.7% PEA/Asystole: 7/32 21.9% Alive at hospital discharge with favourable neurological recovery

Transfer and Nontransfer Outcomes Transfer = Blue line, ANW = Red line 75% of total patients in the Cool It Program are transfers

Early Cooling is Critical Source Chi Square DF P-value Time ROSC to First Cooling min 5.0785 1 0.0242 Estimate Lower CL Upper CL P-value 1.25 1.06 1.44 0.0081 If the time to first cooling increases by an hour the hazard of death increases 25%.

Hypothermia – The Year in Review New Technology Randomized trials Rapid MI-ICE – Gotberg ,Lund SW Prince – BeneChill

Contribution of Lethal Reperfusion Injury to Final Myocardial Infarct Size Yellon D, Hausenloy D. N Engl J Med 2007;357:1121-1135

Major Mediators of Lethal Reperfusion Injury reactive oxygen species oxygen paradox Ca paradox - sarcolemma cytokines activated complement activated mitocondrial PTP-permeability transition pore accelerated by Ca. neutrophil vascular plugging hypercontractile myocyte uncoupled oxidative-phos all leading to lethal reperfusion injury Yellon D, Hausenloy D. N Engl J Med 2007;357:1121-1135

Anterior Myocardial Infarct Size vs Temp at Reperfusion Source- O’Neill, “Novel Myocardial Preservation Therapies: Past Frustrations and Future Promise”, TCT 2006 15

The Importance of Speed Endovascular Peritoneal * **Bradley et al, American Heart Journal, June 2006 16

Why Use the Peritoneal Cavity? Efficient heat exchange > 50% of total blood flow Large surface area Time to target (10 - 15 minutes to 34°C) Eliminates femoral access interference Eliminates upper chest and neck area interference 17

Peritoneal Cooling - Velomedix™, Inc Automated Peritoneal Lavage System (APLS) Efficient heat exchange Tight control for cooling and warming Does not restrict access Fully automated system 18

Rates of Cooling for Available Technologies 7.1 °C/hr 2.7 °C/hr 1.6 °C/hr 1.5 °C/hr 1.3 °C/hr * ** Data sources Thermosuit: Company literature Alsius: Published literature including Wolff paper . Wolff cited an average of 6.8 hrs to target temp with a range of 4-9 hrs. InnerCool: ICE-IT data showed an average of 1.5 hrs. to Target Temp Medivance: Mooney’s paper showed an average time to target temp of 2.7 hrs. with Arctic Sun 2 °C Cooling Time (minutes) * Esophageal Temp (n=2) ** Grines, TCT 2004 19

Life Recovery Systems

ThermoSuit – LRC Cooling Rates

Intravascular Coling Intravascular Cooling InnerCool - Phillips

Rapid MI-ICE study summary 20 pts w/ STEMI randomized iced saline and intravascular cooling v. control (Innercool) Core temp <35 in 40 min D2B 43 min 1500 cc 4 deg. Saline . Demerol , buspirone, Bear Hugger ,intravascular cooling Day 4 - cMRI T2 v. Gadolinium -- Hedstrom E,J AmColl Cardiol Cardiovasc Imaging. 2009;2:569 –576. Troponin T elution curves No difference in clinical outcomes

Rapid MI-ICE Study - Lund,Sweden (Gotberg , Olivecrona ) cMRI Findings A Pilot Study of Rapid Cooling by Cold Saline and Endovascular Cooling Before Reperfusion in Patients With ST-Elevation Myocardial Infarction Circ Cardiovasc Interv published online Aug 24, 2010

Rapid MI-ICE Study - Lund,Sweden (Gotberg , Olivecrona ) Troponin Elution Curves

Intra-Arrest Transnasal Evaporative Cooling: A Randomized, Prehospital, Multicenter Study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness) - Study Outline 200pts witnessed arrest, intra-arrest cooling vs standard care no prehospital iced saline or cold packs 18 adverse device events- 13 nasal discoloration,2 periorbital bleed/emphysema, 3 epistaxis No difference in ROSC 38% vs 42% control Time to Target temp 102 vs 282 (P=.03) Survival 35 vs 41%% (P=.26) Neuro intact 34 vs 21% (P=.21)

BeneChill Design Concept

RhinoChill cooling device Castren, M. et al. Circulation 2010;122:729-736 Copyright ©2010 American Heart Association

Study flow diagram describing the number of patients enrolled and randomized to advanced cardiac life support (ACLS) with or without intranasal cooling Castren, M. et al. Circulation 2010;122:729-736 Copyright ©2010 American Heart Association

Intra-Arrest Transnasal Evaporative Cooling: A Randomized, Prehospital, Multicenter Study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness) Time to target temperature (core) of 34{degrees}C in minutes (median) from the cardiac arrest in the treatment and control groups among those patients admitted to the hospital Castren, M. et al. Circulation 2010;122:729-736 Copyright ©2010 American Heart Association

Rates of neurologically intact survival (defined as having a cerebral performance category [CPC] of 1 or 2) in the treatment and control groups among those patients admitted to the hospital for the entire group, those who received rescuer CPR within 10 minutes, and those with a presenting rhythm of VF Castren, M. et al. Circulation 2010;122:729-736 Copyright ©2010 American Heart Association

Theory meets Practice? – not yet Less than 7% of OOHCA pts get TH - <15,000 of 295,000 Fewer than 300 hospitals have programs or equipment of 6,000 eligible hospitals Awareness and funding limited – FDA approval and perceived complexity are barriers Yet innovation and iteration flourish and successful programs lead the way Research continues – despite challenges b/o enormous persistent unmet need

To maximize benefits, cooling should be initiated as soon as possible. Cardiovascular Emergency Centers To maximize benefits, cooling should be initiated as soon as possible. Survival benefits are dramatic. But, we under-deliver this lifesaving treatment Systems of Care Do Make a Difference TH capable Acute MI PCI centers should offer this lifesaving treatment, it is a public health care imperative. To achieve equivalent access and outcomes in rural and metro patients by providing one Standard of Care for an entire Region for the most complex cardiac emergencies including acute STEMI and cardiac arrest