VELOCITY A Prospective, Randomized Trial of Peritoneal Hypothermia in Patients with Acute STEMI Undergoing PCI Gregg W. Stone, MD Columbia University Medical Center The Cardiovascular Research Foundation On behalf of Graham Nichol, Warren Strickland, David Shavelle, Akiko Maehara, Ori Ben-Yehuda, Philippe Genereux, Ovidiu Dressler, Rupa Parvataneni, Melissa Nichols, John McPherson, Gérald Barbeau, Abhay Laddu, Jo Ann Elrod, Griffeth W. Tully, and Russell Ivanhoe

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Consultant Velomedix All faculty disclosures are available on the CRF Events App and online at www.crf.org/tct

Background Systemic hypothermia (≤34.9°C) may reduce infarct size if established before reperfusion Peritoneal lavage has a well-established safety profile for diagnosis of blunt abdominal injury in patients with trauma, and for treatment of accidental hypothermia, end-stage renal disease, and cancer The large surface area of the bowel may facilitate rapid hypothermia, safely reducing infarct size

Velomedix Automated Peritoneal Lavage System Refrigerator (disposable fluid bags inside) Solid state cooling, warming Touchscreen interface Esophageal core temperature probe Peritoneal catheter Lavage fluid line Controller console Hypothermia to 34.9°C is induced before PCI by lavaging the peritoneal cavity with temperature-controlled 2.5 - 4.5 liters of lactated Ringer’s solution Further cooling occurs to a target temperature of 32.5°C, which is maintained for 3 hours post-PCI, after which the system initiates active re- warming and then fluid drainage Shivering prophylaxis and treatment Pre-PCI: Buspirone; meperidine, forced-air warming blanket If needed: Fentanyl, magnesium, dexmedetomidine

MRI Results at Day 3-5 Control (n=20) Hypothermia (n=26) P value Time from PCI (days) 4 (3, 4) 4 (3, 5) 0.53 LV myocardial mass (grams) 125.5 (109.5, 135,5) 123 (107, 142) 0.80 Area at risk (grams) 35.1 (20.4, 50.5) 34.2 (26, 51.6) 0.56 Area at risk (% LV mass) 26.8 (16.7, 40.6) 26.1 (22.7, 34.4) 0.69 Infarct mass (grams) 20.8 (10.9, 27.6) 22.2 (15.6, 30.1) 0.44 Infarct mass/area at risk (%) 55.8 (43.8, 67.2) 67.3 (48.9, 73.3) 0.36 Myocardial salvage (%) 44.2 (32.8, 56.2) 32.7 (26.7, 51.1) Primary efficacy endpoint: Infarct size (% total LV mass) 16.1 (10.0, 22.2) 17.2 (15.1, 20.6) 0.54 MVO (grams) 0 (0, 0.2) 0 (0, 0.7) 0.57 MVO (% total LV mass) 0 (0, 0.5) 0.64 LV end-diastolic volume (mL) 161 (137.5, 172) 159 (125, 191) LV end-systolic volume (mL) 83.3 (66.8, 102) 81.9 (71, 119) 0.63 LV stroke volume (mL) 75.2 (61.4, 81.5) 75.4 (61.1, 84) 0.78 LV ejection fraction (%) 46.3 (42.6, 50.6) 43.3 (37.4, 52) 0.37 Abnormal wall motion score 8 (4, 11.5) 8 (6, 10) 0.52

Major Adverse Cardiac Events 30-day events Control (n=26) Hypothermia (n=28) P value Composite MACE 3 (10.7%) 0.24 Cardiac death 1 (3.6%)* >0.99 Reinfarction 1 (3.6%)** Ischemia-driven TVR 3 (10.7%)** Stent thrombosis Acute (≤24 hrs) 2 (7.1%) 0.49 Subacute (1-30d) 1 (3.6%) Definite Probable - *Pt with aortic dissection mimicking STEMI died after surgery (no PCI or hypothermia); **Due to stent thrombosis

Conclusions Controlled systemic hypothermia through automated peritoneal lavage may be rapidly established in pts with evolving STEMI undergoing primary PCI at the expense of a modest increase in door-to-balloon time In the present randomized trial, peritoneal hypothermia was associated with an increased rate of adverse events (including stent thrombosis) without reducing infarct size