Hypothermia in Acute MI:

Rationale and Results of the

RAPID MI-ICE Study
Presented 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

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

• Grant/Research Support • Innercool, San Diego, CA
• •
• Consulting Fees/Honoraria • Jolife AB, Sweden
• Physio Control, Redmond WA
• Cordis, Europe
• Abbott Vascular, Europe
• Edwards Lifesciences, Europe
• Medtronic Vascular, Scandinavia
• B Braun, Germany

The RAPID MI-ICE Study was partly sponsored by an unrestricted research grant from
Innercool Therapies, a fully owned subsidiary of Philips Healthcare.
 Hypothermia Background

 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 to Reduce Myocardial Infarct Size
Animal studies (ligated LAD)

Hypothermia prior Hypothermia Hypothermia after

to ischemia1 after reperfusion2 onset ischemia3

Reperfusion 4 h Ischemia 45 min Reperfusion 3 h Reperfusion 3 h

Ischemia 45 Ischemia 60 min
min
Hypothermia 5h Hypothermia 3h Hypothermia 55 min

Start before Start at Start after 20 min End 15 min

Ischemia Reperfusion of ischemia after reperfusion
Slow warm up

Final Infarct size

(% of area at risk):
35 C 0% ! Results:
36 C 20% No myocardial salvage
37 C 40% with hypothermia
38 C 60%
39 C 80%

Results: Results:
Greater myocardial salvage 80% relative reduction in
with lower temperature Infarct size
1 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).
 Hypothermia to Reduce Myocardial Infarct Size:
Human Studies

•Two large randomized trials using hypothermiaas

adjunct
treatment to primary PCI in patients with acute MI (ICE-
IT 1 and COOL
MI 2 ), failed to reach primary endpoint. However, only
1/3 of the
patients randomizedto hypothermia reached a core body
temperature
•The subgroups of patients randomized to hypothermia
andwho
< 35°C reached < 35°C
at the time at the time of reperfusion
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:
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-ICE
The 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 feasibility

§Secondary outcome: Reduction in infarct
size The study is e-published ahead of print in Circulation: Cardiovasc Interv
 Timeline STEMI

30 min → several h 15 min 15 min 15 min

Ambulance Cathlab Angio- PCI Reperfusion

graphy
Endovascular
catheter placement

Buspirone
Temp
Meperidine iv
Cold saline 1-2 l
 Feasibility- RAPID MI-ICE
ECG
Patient Info Patient prep,
Randomization catheterization Angiography, PCI

14 ± 5 min 14 ± 6 min 15 ± 3 min Hypothermia

40 ± 6 min Control

3 min prolonged
37
procedure before
T e m p e ra tu re (C )

36 Hypothermia
reperfusion
Control
35 Temp: 34.7 ± 0.3°C at
reperfusion
34

33
0 10 20 30 40 50 60 70
All patients reached
Time (min)
target temp
Arrival at Initiation of Initiation of Time of End of PCI
cath lab cold saline endovascular reperfusion
infusion cooling
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 NS
Initial TIMI flow
  0/1 7 8 NS
2/3 2 1 NS
Onset of symptoms 174 ± 51 174 ± 62 NS
to 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
2/20 patients, NS from each group
One
was excluded for technical reasons
 Safety- RAPID MI-ICE

Variable Hypothermia Control NT-proBNP day 1

(n=9) (n=9)
30 day mortality 0 0
Re-infarction 0 0
2000
CABG 0 0
30 day MACE 0 0

NT-proBNP (ng/l)
1500
Heart failure 0 3
VT/VF 0 2
1000
Stroke 0 0
Infection 3 0
500
Major bleeding 0 0
Bradycardia 0 0
0
Hypothermia Control
T2 STIR MRI Evaluation- RAPID MI-ICE

Salvaged areas within the area at risk

 Efficacy- RAPID MI-ICE

Reduction of infarct size Reduction in Troponin

inal Infarct Size/ Myocardium at Risk (Peak value)

Δ = 38% Δ = 43%
p = 0·04 p = 0·01
Infarct size / Myocardium at risk

80 8
70 7

Troponin T (ug/l)
60 6
50 5
40 4
30 3
20 2
10 1
0 0
Hypothermia Control Hypothermia Control
 Conclusions
•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.

•All patients reached target temperature, <35°C, at the time of

reperfusion.

•Myocardial infarct size was significantly reduced.

•Troponin T release was significantly reduced.

• A Randomized multicenter trial with hypothermia to reduce infarct

size is planned (CHILL-MI).

The study is e-published ahead of print in Circulation: Cardiovascular Interventions