Disclosures Department of Cardiac Sciences and Libin Cardiovascular - PowerPoint PPT Presentation

Ischemic Conditioning Todd Anderson Libin Cardiovascular Institute University of Calgary

Disclosures • Department of Cardiac Sciences and Libin Cardiovascular Institute – U of Calgary • Grant support by Alberta Innovates – Merck, Amgen, Abbott

Ischemic Conditioning • Ischemia-reperfusion injury • Ischemic conditioning • Endothelial function • PCI • CABG • Myocardial infarction • Others • Remote ischemic conditioning

Ischemic Conditioning • Ischemia-reperfusion injury – Kloner JCI 1974:54:1496 – No reflow in dogs – Reimer et al. Circulation 1977; 56:786 – wavefront of ischemic death – Braunwald and Kloner. JCI 1985;76:1713 – double edged sword and concept of stunned myocardium Circulation 1982 • Ischemic conditioning – Murry et al. Circulation 1986; 74:1174 – IPC – Series of 3-4 cycles of reperfusion and occlusion (minimum of 30 s in duration) – Longer cycles have been used for remote conditioning

Ischemia-reperfusion injury Endothelial Dysfunction No reflow Myocardial stunning Mozaffari et al. Am J CV Disease 2013;3:180

Ischemic Conditioning Mozaffari et al. Am J CV Disease 2013;3:180

Ischemic Conditioning Significant parallelism between pre and post- conditioning End effector is closing of the mitochondrial permeability transfer pore Vinten-Johansen JAP 2007;103:1441

Ischemic Conditioning Canine studies with either 40 minutes or 3 hours of ischemia 4x5min cycles prior Murry et al. Circ 1986;74:1124

Ischemic Conditioning Hausenloy Nature Reviews Cardiology 2011;8:619

Ischemic Conditioning Kharbanda Circ 2001; 103:1624

Flow-Mediated Vasodilation BASELINE REACTIVE HYPEREMIA (3.65 mm) (4.08 mm) FMD = 10.5 %

Ischemic Conditioning Attenuation of NO dependent increases in FBF post IR injury with activation of neutrophils as well Attenuation of FMD with pre-conditioning attenuating this abnormality Kharbanda Circ 2001; 103:1624

Remote Ischemic Conditioning 20 minutes of ischemia with and without 3 cycles of 5 minutes of IPC on the contra-lateral arm Kharbanda Circ 2002; 106:2881

Ischemic Conditioning in PCI 242 elective PCI patients Normal TnI pre Remote IPC with 3 5 min cycles upper arm Primary EP was TnI at 24 h as was lower in IPC group (p=0.04) Crisp et al. Circ 2009;188:820

Remote Ischemic Conditioning in PCI Meta-analysis 4 PCI (2 STEMI) 13 CABG Remote IPC Biomarkers EP Yetgin Circ J 2012;76:2392

Ischemic Post-Conditioning in STEMI No reflow, microvascular dysfunction and hemorrhage, stunning, arrhythmias Frohlich EHJ 2013;34:1714

Ischemic Post-Conditioning 30 patients with primary PCI Randomized to 4 cycles of 1 min inflation/deflation prior to PCI AUC CK rise post MI Staat et al. Circ 2005;112:2143

Ischemic Conditioning in STEMI Schevchuck Circ CV Interventions 2013, 6:484

Ischemic Conditioning in STEMI Biomarker reduction Schevchuck Circ CV Interventions 2013, 6:484

Ischemic Conditioning in STEMI Infarct size by CMR Schevchuck Circ CV Interventions 2013, 6:484

Ischemic Conditioning in STEMI – time effect? Schevchuck Circ CV Interventions 2013, 6:484

Ischemic Post-Conditioning 102 patients with primary PCI Randomized to 4 cycles of 1 min inflation/deflation prior to PCI CMR EP of Area at Risk No change in EF or microvascular obstruction Dwyer et al. J Interventional Cardiol; 2013;26:482.

Remote Ischemic Conditioning in STEMI • 1st STEMI n=242 pts , Upper limb RIPC • 4 x 5 min cycles • Primary – LV function by echo and perfusion • Overall no change in EF but there was improvement in large MI Munk et al. Circ CV Imaging 2010;3:656

Remote Ischemic Conditioning in STEMI • Anterior STEMI • Lower limb RIPC • 3 x 5 min cycles • 100 pts P=0.043 • Primary – CK-MB • Secondary – CMR no difference in infarct size at 3-5 days or 4 months Crimi et al. JACC CV Inter 2013; 6:1055

Ischemic Conditioning and renal function • 225 pts with NSTEMI and PCI • 3 cycles of coronary IPC • AKI endpoint • Baseline creat 88 µM • Trend for decrease in 30 day outcomes as well • Previous trial by Er Circ 2012 Defteros JACC 2013;61:1949

Ischemic Conditioning • Other possible indications • Blood pressure reduction • Exercise capacity improvement • Neurosurgery • Bowel surgery

Ischemic Conditioning - Summary • Attractive, safe and inexpensive approach with rich basic science rationale • Significant heterogeneity in the result so far for IPC in PCI, CABG and STEMI • Similar ambiguity exists for remote IPC • Several large randomized trials are underway • Large definitive trial needed with clinical end- points to determine utility of the approach