Investigating Treatment with Therapeutic Hypothermia for Ischaemia of the Heart Mechanical Left Ventricular Unloading and Therapeutic Hypothermia

1. Basir MB, Schreiber T, Dixon S, et al. Feasibility of early mechanical circulatory support in acute myocardial infarction complicated by cardiogenic shock: the Detroit cardiogenic shock initiative. Catheter Cardiovasc Interv 2018;91:454–461. https://doi.org/10.1002/ccd.27427;

PMID: 29266676. 2. Basir MB, Kapur NK, Patel K, et al. Improved outcomes associated with the use of shock protocols: updates from the National Cardiogenic Shock Initiative. Catheter Cardiovasc Interv 2019;93:1173–83. https://doi.org/10.1002/ccd.28307; PMID: 31025538. 3. Scholz KH, Maier SKG, Maier LS, et al. Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial. Eur Heart J 2018;39:1065–1074. https://doi.org/10.1093/eurheartj/ehy004; PMID: 29452351. 4. Basir MB, Schreiber TL, Grines CL, et al. Effect of early initiation of mechanical circulatory support on survival in cardiogenic shock. Am J Cardiol 2017;119:845–51. https://doi. org/10.1016/j.amjcard.2016.11.037; PMID: 28040188. 5. Thiele H, Zeymer U, Neumann FJ, et al. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial. Lancet 2013;382:1638–45. https://doi.org/10.1016/

S0140-6736(13)61783-3; PMID: 24011548. 6. Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2019;40:87–165. https://doi.org/10.1093/eurheartj/ehy394;

PMID: 30165437. 7. Ouweneel DM, Eriksen E, Sjauw KD, et al. Percutaneous mechanical circulatory support versus intra-aortic balloon pump in cardiogenic shock after acute myocardial infarction. J Am

Coll Cardiol 2017;69:278–87. https://doi.org/10.1016/j.jacc.2016.10.022; PMID: 27810347. 8. Schäfer A, Werner N, Burkhoff D, et al. Influence of timing and predicted risk on mortality in impella-treated infarct-related cardiogenic shock patients. Front Cardiovasc Med 2020;7:74. https://doi.org/10.3389/fcvm.2020.00074; PMID: 32478095. 9. Helgestad OKL, Josiassen J, Hassager C, et al. Contemporary trends in use of mechanical circulatory support in patients with acute MI and cardiogenic shock. Open Heart 2020;7:e001214. https://doi.org/10.1136/openhrt-2019-001214; PMID: 32201591. 10. Meraj PM, Doshi R, Schreiber T, et al. Impella 2.5 initiated prior to unprotected left main PCI in acute myocardial infarction complicated by cardiogenic shock improves early survival. J

Interv Cardiol 2017;30:256–63. https://doi.org/10.1111/joic.12377; PMID: 28419573. 11. Hemradj VV, Karami M, Sjauw KD, et al. Pre-PCI versus immediate post-PCI Impella initiation in acute myocardial infarction complicated by cardiogenic shock. PLoS One 2020;15:e0235762. https://doi.org/10.1371/journal.pone.0235762; PMID: 32687502. 12. O’Neill WW, Grimes C, Schreiber T, et al. Analysis of outcomes for 15,259 US patients with acute myocardial infarction cardiogenic shock (AMICS) supported with the Impella device. Am

Heart J 2018;202:33–8. https://doi.org/10.1016/j.ahj.2018.03.024; PMID: 29803984. 13. O’Neill WW, Schreiber T, Wohns DHW, et al. The current use of Impella 2.5 in acute myocardial infarction complicated by cardiogenic shock: results from the USpella Registry. J Interv Cardiol 2014;27:1–11. https://doi.org/10.1111/joic.12080; PMID: 24329756. 14. Schroeter MR, Köhler H, Wachter A, et al. Use of the Impella device for acute coronary syndrome complicated by cardiogenic shock – experience from a single heart center with analysis of long-term mortality. J Inv Cardiol 2016;28:467–72. PMID: 27529657. 15. Samuels LE, Kaufman MS, Thomas MP, et al. Pharmacological criteria for ventricular assist device insertion following postcardiotomy shock: experience with the Abiomed BVS system.

J Card Surg 1999;14:288–93. https://doi.org/10.1111/j.1540-8191.1999.tb00996.x; PMID: 10874615. 16. Fincke R, Hochman JS, Lowe AM, et al. Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry. J Am Coll

Cardiol 2004;44:340–8. https://doi.org/10.1016/j.jacc.2004.03.060; PMID: 15261929. 17. O’Neill WW. Achieving >70% AMI-CS survival: insight from National Cardiogenic Shock

Initiative. Presented at TCT Connect, 18 October 2020. 18. Tehrani BN, Truesdell AG, Sherwood MW, et al. Standardized team-based care for cardiogenic shock. J Am Coll Cardiol 2019;73:1658–9. https://doi.org/10.1016/j.jacc.2018.12.084;

PMID: 30947919. 19. Sawa Y. Efficacy and safety analysis of initial Impella experience in Japan. A novel percutaneous hemodynamic support device: report from J-PVAD registry. Presented at: 84th

Annual Scientific Meeting of the Japanese Circulation Society, 30 July 2020. 20. Hanson ID, Tagami T, Mando R, et al. SCAI shock classification in acute myocardial infarction: insights from the National Cardiogenic Shock Initiative. Catheter Cardiovasc Interv 2020;96:1137–42. https://doi.org/10.1002/ccd.29139; PMID: 32672388. 21. Lemor A, Basir MB, Patel K, et al. Multivessel versus culprit-vessel percutaneous coronary intervention in cardiogenic shock. JACC Cardiovasc Interv 2020;13;1171–8. https://doi. org/10.1016/j.jcin.2020.03.012; PMID: 32360256.

Investigating Treatment with Therapeutic Hypothermia for Ischaemia of the Heart

Presented by Bob Kloner, MD, PhD

Huntington Medical Research Institutes, Pasadena, CA, US

Mechanical Left Ventricular Unloading and Therapeutic Hypothermia

Presented by Kiyo Ishikawa, MD

Icahn School of Medicine at Mount Sinai, New York, NY, US

Dr Bob Kloner is Chief Science Officer and Director of Cardiovascular Research at Huntington Medical Research Institutes and Professor of Medicine at the USC Keck School of Medicine. Dr Kiyo Ishikawa is Assistant Professor of Medicine at the Icahn School of Medicine at Mount Sinai.

Dr Kloner’s two decades of research demonstrate that therapeutic hypothermia (TH) reduces myocardial damage in the setting of acute MI. Topical cooling of the heart to a target a temperature <35°C prior to ischaemia or coronary occlusion, followed by reperfusion, or opening of a coronary artery, significantly decreased infarct size in rabbits and sheep.1,2 Mild regional hypothermia prior to ischaemia also preserved metabolic activity in the ischaemic or occluded area by retention of adenosine triphosphate stores, glycogen stores and creatine phosphate.3

TH after ischaemia onset also reduced infarct size in rabbits and rats if administered immediately prior to reperfusion.4–6 TH induction by intracoronary injection of chilled saline prior to reperfusion limits the noreflow or microvascular obstruction (MVO) area of the infarct.6 TH initiated after reperfusion also substantially reduced the extent of no-reflow, but did not decrease infarct size.7,8 TH using a non-invasive convective-immersion cooling ThermoSuit produced a similar cardioprotective decrease in no reflow, cardiac scar length and infarct size of ischaemic animals.9,10 TH also assisted healing after MI, with increased infarcted wall thickness, decreased inflammatory gene expression and improved left ventricular (LV) fractional shortening and ejection fraction.11 TH also improved long-term survival and blunted inflammation in rats exposed to haemorrhagic shock.12

Dr Kloner concluded his talk with a summary of TH clinical studies. Few have been successful due to difficulties decreasing temperature to a sufficient degree, delaying conventional therapy.

Four clinical studies demonstrated that TH reperfusion with a target temperature of <35°C prior to reperfusion decreases infarct size and MVO in patients with ST-segment elevation MI (STEMI).13–16