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Hypothermia in Acute MI: Rationale and Results of the RAPID MI-ICE StudyPresented by Goran Olivecrona, MD, PhD.On behalf of of the RAPID MI-ICE Investigators Matthias Götberg, MD, Göran Olivecrona, MD,PhD, Sasha Koul, MD, Marcus Carlsson, MD, PhD, Henrik Engblom, MD, PhD, Martin Ugander, MD, PhD, Jesper van der Pals, MD, Lars Algotsson, MD, PhDHåkan Arheden, MD, PhD, David Erlinge, MD, PhDLund University Skane University Hospital, Lund, Sweden
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Hypothermia in Acute MI: Rationale and Results of the
RAPID MI-ICE StudyPresented by Goran Olivecrona, MD, PhD.
On behalf of of the RAPID MI-ICE Investigators
Matthias Götberg, MD, Göran Olivecrona, MD,PhD, Sasha Koul, MD, Marcus Carlsson, MD, PhD, Henrik Engblom, MD, PhD, Martin Ugander, MD, PhD, Jesper van der Pals, MD, Lars
Algotsson, MD, PhDHåkan Arheden, MD, PhD, David Erlinge, MD, PhD
Lund University
Skane University Hospital,
Lund, Sweden
Disclosure Statement of Financial Interest
• Grant/Research Support
• Consulting Fees/Honoraria
• Innercool, San Diego, CA
• Jolife AB, Sweden• Physio Control, Redmond WA• Cordis, Europe• Abbott Vascular, Europe• Edwards Lifesciences, Europe• Medtronic Vascular, Scandinavia• B Braun, Germany
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship Company
The RAPID MI-ICE Study was partly sponsored by an unrestricted research grant from Innercool Therapies, a fully owned subsidiary of Philips Healthcare.
Practical experience from patients surviving drowning in cold water
Basic research in which hypothermia reduces ischemia induced necrosis of a large number of cell types. Prominent effect’s on neurological tissues.
Therapy to prevent brain damage after cardiac arrest (VF) with ROSC.
Hypothermia is used successfully during Cardiovascular Surgery.
Hypothermia Background
Final Infarct size (% of area at risk):
35 C 0% ! 36 C 20% 37 C 40% 38 C 60% 39 C 80%
Results:Greater myocardial salvage
with lower temperature
Hypothermia to Reduce Myocardial Infarct Size Animal studies (ligated LAD)
Hypothermia prior to ischemia1
Hypothermia after onset ischemia3
Results:80% relative reduction in
Infarct size1 Duncker et al. 1996 (Am J Physiol 270, H1189),2 Maeng et al. 2006 (Basic Res Cardio 101: 61-68)3Dae MW, et al. 2002 (Am J Physiol Heart Circ Physiol 282:H1584-91).
Reperfusion 3 h Start at Reperfusion
Ischemia 45 min
Hypothermia 3h
Reperfusion 4 h
Start before Ischemia
Ischemia 45
minHypothermia 5h
Reperfusion 3 h
Start after 20 min End 15 minof ischemia after reperfusion Slow warm up
Ischemia 60 minHypothermia 55 min
Hypothermia after reperfusion2
Results:No myocardial salvage
with hypothermia
• Two large randomized trials using hypothermia as adjunct
treatment to primary PCI in patients with acute MI (ICE-IT1 and COOL
MI2), failed to reach primary endpoint. However, only 1/3 of the
patients randomized to hypothermia reached a core body temperature
< 35°C at the time of reperfusion.
• The subgroups of patients randomized to hypothermia and who reached < 35°C at the time of reperfusion seemed to benefit
(RRR 49% and 43% respectively)
1 Grines CL et al. TCT 2004, 2O'Neill WW et al. TCT 2004
Hypothermia to Reduce Myocardial Infarct Size: Human Studies
Hypothermia to Reduce Myocardial Infarct Size: New Animal studies (LAD occluded with balloon)
Rapid induction of hypothermia with 1. Rapid infusion cold saline 2. Intravascular cooling catheter
Area at risk Final infarct size
39% 17%
39%P <0.05
35% 28%
42% 31%
Götberg M et al . BMC Cardiovasc Disord. 2008, 8:7,
Hypothermia in Acute MI
We hypotesized that a combination of cold saline and endovascular cooling would cool all patients to target
temp < 35°C before primary PCI reperfusion.
RAPID MI-ICEThe Rapid Intravascular Cooling in Myocardial Infarction as Adjunctive to Percutaneous Coronary
Intervention study
(Safety & Feasibility study in man)
• 20 Patients prospectively randomized
• Anterior or large Inferior STEMI
• <6 hrs from onset of symtoms
• Rapid infusion 1-2 liters 4°C Saline solution.
• Endovascular cooling with Philips InnerCool endovascular system with
Accutrol catheter starting before angiogram and continuing 3 h after PCI
• Cardiac MRI day 4±2, infarct size/ myocardium at risk (T2 stir)
Primary outcome: Safety and feasibilitySecondary outcome: Reduction in infarct size
The study is e-published ahead of print in Circulation: Cardiovasc Interv
Timeline STEMI
Ambulance ReperfusionCathlab
30 min → several h 15 min 15 min
Angio-graphy
15 min
PCI
BuspironeMeperidine ivCold saline 1-2 l
Endovascular catheter placement
Temp
Arrival at cath lab
0 10 20 30 40 50 60 7033
34
35
36
37
HypothermiaControl
Time (min)
Tem
per
atu
re (
C)
ECG Patient Info
Randomization
Time ofreperfusion
Initiation of cold saline
infusion
Initiation ofendovascular
cooling
Patient prep, catheterization Angiography, PCI
End of PCI
14 ± 5 min 14 ± 6 min 15 ± 3 min
40 ± 6 min
HypothermiaControl
3 min prolonged procedure before reperfusion
Temp: 34.7 ± 0.3°C at reperfusion
Feasibility- RAPID MI-ICE
All patients reached target temp
RAPID MI-ICE Clinical and Angiographic Data Variable Hypothermia (n=9) Control (n=9)
Age 62 ± 10 58 ± 7 NS
Women 2 2 NS
Hypertension 3 2 NS
Diabetes 1 2 NS
Infarct related artery LAD 6 7 NS
RCA 3 2 NSInitial TIMI flow 0/1 7 8 NS
2/3 2 1 NS
Onset of symptoms 174 ± 51 174 ± 62 NSto reperfusion (min)
Door-to-balloon time (min) 43 ± 7 40 ± 6 NS
Successful revascularization 9 9 NS
TIMI 3 flow post PCI 9 9 NS
Thrombectomy 8 7 NS
Abciximab 6 6 NS
Bivalirudin 3 3 NS2/20 patients, One from each group was excluded for technical reasons
Variable Hypothermia Control
(n=9) (n=9)
30 day mortality 0 0
Re-infarction 0 0
CABG 0 0
30 day MACE 0 0
Heart failure 0 3
VT/VF 0 2
Stroke 0 0
Infection 3 0
Major bleeding 0 0
Bradycardia 0 0
NT-proBNP day 1
Hypothermia Control0
500
1000
1500
2000
NT-
pro
BN
P (
ng
/l)
Safety- RAPID MI-ICE
Salvaged areas within the area at risk
T2 STIR MRI Evaluation- RAPID MI-ICE
Reduction of infarct size Final Infarct Size/ Myocardium at Risk
Reduction in Troponin (Peak value)
p = 0·04
Hypothermia Control0
10
20
30
40
50
60
70
80
Δ = 38%
Infa
rct
size
/ M
yoca
rdiu
m a
t ri
sk
Hypothermia Control0
1
2
3
4
5
6
7
8
Tro
po
nin
T (
ug
/l)
p = 0·01
Δ = 43%
Efficacy- RAPID MI-ICE
• Troponin T release was significantly reduced.
• Rapid induction of hypothermia with 1-2 l cold saline in combination with an endovascular cooling catheter is safe and feasible in awake patients with acute MI.
Conclusions
• Myocardial infarct size was significantly reduced.
• A Randomized multicenter trial with hypothermia to reduce infarct size is planned (CHILL-MI).
• All patients reached target temperature, <35°C, at the time of reperfusion.
The study is e-published ahead of print in Circulation: Cardiovascular Interventions