The Official Journal of EuroPCR and the European Association of Percutaneous Coronary Interventions (EAPCI)
A multicentre, prospective, randomised controlled trial to assess the safety and effectiveness of cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction: the COOL AMI EU Pivotal Trial
Marko Noc1, PhD, MD; Peep Laanmets2, MD; Aleksandar N. Neskovic3, MD, PhD; Milovan Petrović4, MD; Bojan Stanetic5, MD, PhD; Daniel Aradi6, MD, PhD; Robert G Kiss7, MD; Imre Ungi8, MD; Béla Merkely9, MD, PhD; Martin Hudec10, MD; Peter Blasko11, MD, PhD; Ivan Horvath12, MD, PhD; John R. Davies13, PhD, MRCP; Vladan Vukcevic14, MD, PhD; Michael Holzer15, MD; Bernhard Metzler16, MD, MSc; Adam Witkowski17, MD, PhD; Andrejs Erglis18, MD, PhD; Misa Fister1, MD, PhD; Gergely Nagy19, MD, PhD; Josko Bulum20, MD, PhD; István Édes21, MD, PhD; Jan Z. Peruga22, MD, PhD; Beata Średniawa23, MD, PhD; David Erlinge24, MD, PhD; Thomas R. Keeble13,25, BSc, MD, MRCP
1. University Medical Centre Ljubljana, Slovenia; 2. North-Estonia Medical Centre Foundation, Tallinn, Estonia; 3. Clinical Hospital Center Zemun, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 4. Institute of Cardiovascular Diseases of Vojvodina, Sremska Kamenica, Faculty of Medicine, Novi Sad, Serbia; 5. University Clinical Center of the Republic of Srpska, Medical Faculty of University of Banja Luka, Banja Luka, Bosnia; 6. Heart Center, Balatonfüred, Hungary; 7. Military Hospital, Budapest, Hungary; 8. University of Szeged, Szeged, Hungary; 9. Heart and Vascular Center, Semmelweis University, Budapest, Hungary; 10. Stredoslovenski Ustav Srdcovych a Cievnych Chorob, Banska Bystrica, Slovakia; 11. Kardiocentrum Nitra s.r.o., Nitra, Slovakia; 12. Department of Cardiology, Health Faculty of Medicine, University of Pecs, Hungary; 13. Essex Cardiothoracic Centre, Basildon and Thurrock University Hospital NHS Foundation Trust, Basildon, UK; 14. Clinical Center of Serbia, Belgrade, Serbia; 15. Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria; 16. University Hospital of Internal Medicine lll/Cardiology and Angiology, Medical University Innsbruck, Innsbruck, Austria; 17. The Cardinal Stefan Wyszynski Institute of Cardiology, Warshaw, Poland; 18. Pauls Stradins Clinical University Hospital, University of Latvia, Riga, Latvia; 19. Borsod-Abauj-Zemplen County Central Hospital and University Teaching Hospital, 1st Department of Internal Medicine and Cardiology, Miskolc, Miskolc, Hungary; 20. University Hospital Center Zagreb, Zagreb, Croatia; 21. Department of Cardiology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrbrecen, Hungary; 22. Medical University in Łódź, Bieganski Hospital, Łódź, Poland; 23. Silesian Center for Heart Diseases, Department of Cardiology, Medical University of Silesia, DMS in Zabrze, Zabrze, Poland; 24. Department of Cardiology, Lund University, Clinical Sciences, Skane University Hospital, Lund, Sweden; 25. Anglia Ruskin School of Medicine, Chelmsford, Essex, UK
Background: Despite primary PCI (PPCI), ST-elevation myocardial infarction (STEMI) can still result in large infarct size (IS). New technology with rapid intravascular cooling showed positive signals for reduction in IS in anterior STEMI.
Aims: We investigated the effectiveness and safety of rapid systemic intravascular hypothermia as an adjunct to PPCI in conscious patients, with anterior STEMI, without cardiac arrest.
Methods: Hypothermia was induced using the ZOLL® Proteus™ intravascular cooling system. After randomisation of 111 patients, 58 to hypothermia and 53 to control groups, the study was prematurely discontinued by the sponsor due to inconsistent patient logistics between the groups resulting in significantly longer total ischaemic delay in the hypothermia group (232 vs 188 minutes; p<0.001).
Results: There were no differences in angiographic features and PPCI result between the groups. Intravascular temperature at wire crossing was 33.3+0.9°C. Infarct size/left ventricular (IS/LV) mass by cardiac magnetic resonance (CMR) at day 4-6 was 21.3% in the hypothermia group and 20.0% in the control group (p=0.540). Major adverse cardiac events at 30 days increased non-significantly in the hypothermia group (8.6% vs 1.9%; p=0.117) while cardiogenic shock (10.3% vs 0%; p=0.028) and paroxysmal atrial fibrillation (43.1% vs 3.8%; p<0.001) were significantly more frequent in the hypothermia group.
Conclusions: The ZOLL Proteus intravascular cooling system reduced temperature to 33.3°C before PPCI in patients with anterior STEMI. Due to inconsistent patient logistics between the groups, this hypothermia protocol resulted in a longer ischaemic delay, did not reduce IS/LV mass and was associated with increased adverse events.