title: Therapeutic hypothermia for the treatment of acute myocardial infarction-combined analysis of the RAPID MI-ICE and the CHILL-MI trials.
abstract: In the randomized rapid intravascular cooling in myocardial infarction as adjunctive to percutaneous coronary intervention (RAPID MI-ICE) and rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction CHILL-MI studies, hypothermia was rapidly induced in conscious patients with ST-elevation myocardial infarction (STEMI) by a combination of cold saline and endovascular cooling. Twenty patients in RAPID MI-ICE and 120 in CHILL-MI with large STEMIs, scheduled for primary percutaneous coronary intervention (PCI) within <6 hours after symptom onset were randomized to hypothermia induced by rapid infusion of 600-2000 mL cold saline combined with endovascular cooling or standard of care. Hypothermia was initiated before PCI and continued for 1-3 hours after reperfusion aiming at a target temperature of 33°C. The primary endpoint was myocardial infarct size (IS) as a percentage of myocardium at risk (IS/MaR) assessed by cardiac magnetic resonance imaging at 4±2 days. Patients randomized to hypothermia treatment achieved a mean core body temperature of 34.7°C before reperfusion. Although significance was not achieved in CHILL-MI, in the pooled analysis IS/MaR was reduced in the hypothermia group, relative reduction (RR) 15% (40.5, 28.0-57.6 vs. 46.6, 36.8-63.8, p=0.046, median, interquartile range [IQR]). IS/MaR was predominantly reduced in early anterior STEMI (0-4h) in the hypothermia group, RR=31% (40.5, 28.8-51.9 vs. 59.0, 45.0-67.8, p=0.01, median, IQR). There was no mortality in either group. The incidence of heart failure was reduced in the hypothermia group (2 vs. 11, p=0.009). Patients with large MaR (>30% of the left ventricle) exhibited significantly reduced IS/MaR in the hypothermia group (40.5, 27.0-57.6 vs. 55.1, 41.1-64.4, median, IQR; hypothermia n=42 vs. control n=37, p=0.03), while patients with MaR<30% did not show effect of hypothermia (35.8, 28.3-57.5 vs. 38.4, 27.4-59.7, median, IQR; hypothermia n=15 vs. control n=19, p=0.50). The prespecified pooled analysis of RAPID MI-ICE and CHILL-MI indicates a reduction of myocardial IS and reduction in heart failure by 1-3 hours with endovascular cooling in association with primary PCI of acute STEMI predominantly in patients with large area of myocardium at risk. (ClinicalTrials.gov id NCT00417638 and NCT01379261).
authors.affiliation: 1 Department of Cardiology, Clinical Sciences, Lund University , Lund, Sweden .
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.affiliation: 1 Department of Cardiology, Clinical Sciences, Lund University , Lund, Sweden .
authors.forename: Matthias
authors.initials: M
authors.lastname: Götberg
authors.affiliation: 2 Center for Intensive Internal Medicine , Ljubljana, Slovenia .
authors.forename: Marko
authors.initials: M
authors.lastname: Noc
authors.affiliation: 3 Department of Cardiology, Medical University of Vienna , Vienna, Austria .|4 Department of Emergency Medicine, Medical University of Vienna , Vienna, Austria .
authors.forename: Irene
authors.initials: I
authors.lastname: Lang
authors.affiliation: 3 Department of Cardiology, Medical University of Vienna , Vienna, Austria .|4 Department of Emergency Medicine, Medical University of Vienna , Vienna, Austria .
authors.forename: Michael
authors.initials: M
authors.lastname: Holzer
authors.affiliation: 5 Department of Cardiology, Nykoebing F Hospital , Nykoebing F, Denmark .
authors.forename: Peter
authors.initials: P
authors.lastname: Clemmensen
authors.affiliation: 6 Cardiology Unit, Department of Medicine, Karolinska University Hospital , Stockholm, Sweden .
authors.forename: Ulf
authors.initials: U
authors.lastname: Jensen
authors.affiliation: 7 Department of Cardiology, University Hospital for Internal Medicine, Innsbruck , Austria .
authors.forename: Bernhard
authors.initials: B
authors.lastname: Metzler
authors.affiliation: 8 Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University , Uppsala, Sweden .
authors.forename: Stefan
authors.initials: S
authors.lastname: James
authors.affiliation: 9 Department of Cardiology, Aarhus University Hospital Skejby , Aarhus, Denmark .
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.affiliation: 10 Department of Cardiology, Sahlgrenska University , Gothenburg, Sweden .
authors.forename: Elmir
authors.initials: E
authors.lastname: Omerovic
authors.affiliation: 1 Department of Cardiology, Clinical Sciences, Lund University , Lund, Sweden .
authors.forename: Sasha
authors.initials: S
authors.lastname: Koul
authors.affiliation: 11 Department of Clinical Physiology, Lund University , Lund, Sweden .
authors.forename: Henrik
authors.initials: H
authors.lastname: Engblom
authors.affiliation: 11 Department of Clinical Physiology, Lund University , Lund, Sweden .
authors.forename: Marcus
authors.initials: M
authors.lastname: Carlsson
authors.affiliation: 11 Department of Clinical Physiology, Lund University , Lund, Sweden .
authors.forename: Håkan
authors.initials: H
authors.lastname: Arheden
authors.affiliation: 12 Uppsala Clinical Research Center, Uppsala University , Uppsala, Sweden .
authors.forename: Ollie
authors.initials: O
authors.lastname: Östlund
authors.affiliation: 8 Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University , Uppsala, Sweden .
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: 13 Philips Healthcare , San Diego, California.
authors.forename: Bradley
authors.initials: B
authors.lastname: Klos
authors.affiliation: 1 Department of Cardiology, Clinical Sciences, Lund University , Lund, Sweden .
authors.forename: Jan
authors.initials: J
authors.lastname: Harnek
authors.affiliation: 5 Department of Cardiology, Nykoebing F Hospital , Nykoebing F, Denmark .
authors.forename: Göran K
authors.initials: GK
authors.lastname: Olivecrona
mesh_terms: D001833:Body Temperature Regulation; D006328:Cardiac Catheterization; D003080:Cold Temperature; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D062645:Percutaneous Coronary Intervention; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012965:Sodium Chloride / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D012965:Sodium Chloride