The subgroups of patients randomized to hypothermia and who reached
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Transcript of The subgroups of patients randomized to hypothermia and who reached
Cold saline and endovascular cooling induces rapid hypothermia before reperfusion in STEMI patients
treated with primary PCI, is safe and reduces infarct size with a scattered myocardial salvage
Presented by Prof David Erlinge, MD, PhD,On behalf 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, PhD
Håkan Arheden, MD, PhD, David Erlinge, MD, PhD
Lund University, Skane University HospitalLund, Sweden
Disclosure statement: The study was partly sponsored by an unrestricted research grant from Innercool Therapies, a fully owned subsidiary of Philips Healthcare.
• In a pig model, we have shown that myocardial infarct size is significantly reduced only if the temperature < 35°C before reperfusion3.
1 Duncker et al. 1996 (Am J Physiol 270, H1189),2 Dae MW, et al. 2002 (Am J Physiol Heart Circ Physiol 282:H1584-91).,3 Götberg M et al . BMC Cardiovasc Disord. 2008, 8:7, 4 Grines CL et al. TCT 2004, 5 O'Neill WW et al. TCT 2004
• Two large randomized trials using hypothermia as adjunct treatment to primary PCI in patients with acute MI (ICE-IT4 and COOL MI5), 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)
Hypothermia in Acute MI
• A large number of animal studies have shown that hypothermia reduces myocardial infarct size1-2.
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• 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
Timeline STEMI
Ambulance ReperfusionArrival Cathlab
30 min → several h 15 min 15 min
Angio-graphy
15 min
PCI
BuspironeMeperidine ivCold saline 1-2 l
Endovascular catheter placement
Temp
Feasibility
Arrival at cath lab
0 10 20 30 40 50 60 7033
34
35
36
37
HypothermiaControl
Time (min)
Tem
pera
ture
(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 min40 ± 6 min
HypothermiaControl
3 min prolonged procedure before reperfusion
Temp: 34.7 ± 0.3°C at reperfusion
All patients reached target temp
Clinical and Angiographic Data Variable Hypothermia (n=9) Control (n=9)Age 62 ± 10 58 ± 7 NS Women 2 2 NSHypertension 3 2 NSDiabetes 1 2 NSInfarct related artery LAD 6 7 NS
RCA 3 2 NSInitial TIMI flow 0/1 7 8 NS
2/3 2 1 NSOnset of symptoms 174 ± 51 174 ± 62 NSto reperfusion (min)Door-to-balloon time (min) 43 ± 7 40 ± 6 NS
Successful revascularization 9 9 NSTIMI 3 flow post PCI 9 9 NSThrombectomy 8 7 NSAbciximab 6 6 NSBivalirudin 3 3 NS
2/20 patients, One from each group was excluded for technical reasons
Variable Hypothermia Control (n=9) (n=9)
30 day mortality 0 0Re-infarction 0 0 CABG 0 030 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
Safety
NT-proBNP day 1
Hypothermia Control0
500
1000
1500
2000
NT-
proB
NP
(ng/
l)
Reduction of infarct size Final Infarct Size/ Myocardium at Risk
Reduction in Troponin (Peak value)
Efficacy
p = 0·04
Hypothermia Control0
1020304050607080
Δ = 38%
Infa
rct s
ize
/ Myo
card
ium
at r
isk
Hypothermia Control012345678
Trop
onin
T (u
g/l)
p = 0·01Δ = 43%
Speckled infarction in pigWavefront phenomenon
(Jennings)Hypothermia Normothermia
Hypothermia causes disruption of the wavefront phenomenon.Götberg M et al . BMC Cardiovasc Disord. 2008, 8:7
Also seen in hypothermia treatment by Dae et al., Am J Physiol, 2002, with SPECT
Speckled infarction in man
• Troponin T release was significantly reduced.
• Rapid induction of hypothermia with 1-2 l cold saline and endovascular 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.
• Hypothermia disrupts the wavefront phenomenon into a speckled infarction.
The study is accepted for publication in Circulation: Cardiovascular Interventions