1. 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

2. 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.

3. 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.

4. Hypothermia Pivotal Studies
HACA,
2002
Bernard,
2002

5. 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

6. 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
( )
Bernard
21/43
(49%)
9/34
(26%)
2.65
( )
0.046
Alive at 6 months with favourable neurological recovery
HACA
71/136
(55%)
50/137
(39%)
1.44
( )
0.009

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

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

9. Abbott Northwestern Hospital 72/140 51.4%
Outcomes
Abbott Northwestern Hospital / %
Survival by diagnosis
STEMI: 49/ %
Other: 29/ %
Survival by initial rhythm
VF/VT: 68/ %
PEA/Asystole: 7/ %
Alive at hospital discharge with favourable neurological recovery

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

11. 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%.

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

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

14. 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:

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

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

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

18. 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

19. 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

20. Life Recovery Systems

21. ThermoSuit – LRC Cooling Rates

22. Intravascular Coling Intravascular Cooling
InnerCool - Phillips

23. 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

24. 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

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

26. 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)

27. BeneChill Design Concept

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

29. 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:
Copyright ©2010 American Heart Association

30. 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:
Copyright ©2010 American Heart Association

31. 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:
Copyright ©2010 American Heart Association

33. 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

34. 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