P3671Myocardial regeneration strategy using Wharton's jelly multipotent stem cells as an “unlimited” therapeutic agent: 3-year outcomes in a pilot cohort of circulate-acute myocardial infarction trial

Abstract

Introduction: CIRCULATE‐AMI (NCT03404063) is a cardiac Magnetic Resonance Imaging (cMRI) infarct size‐reduction‐powered double‐blind controlled trial (RCT) that is randomizing consecutive patients with their first, large AMI (cMRILVEF ≤45%) with successful infarct‐related artery (IRA) primary percutaneous coronary intervention reperfusion to transcoronary administration of Wharton Jelly Multipotent Stem Cells (WJMSCs) vs. placebo (2:1), preceded by evaluation of safety, WJMSCs myocardial uptake, and cMRI and SPECT left ventricular remodeling in pilot study cohort (PSC). Aim: To evaluate WJMSCs transplantation safety, WJMSCs myocardial uptake, and evolution of left‐ventricular (LV) remodeling in CIRCULATE‐AMI PSC. Material and methods: 30x106 WJMSCs labeled with 99mTc‐extametazime were administered via IRA in a ten‐patient PSC (age 32‐65 years, peak hs‐ Troponin T 17.3±9.1ng/mL and peak CK‐MB 533±89U/L, cMRI‐LVEF 40.3±2.7% and infarct size 20.1±2.8%) at ≈5‐7 days after AMI using a cell deliverydedicated, coronary‐non‐occlusive method. Other treatments were per current guidelines. Results: WJMSCs showed an unprecedented high myocardial uptake (30.2±5.3%; 95% CI 26.9‐33.5%), corresponding to ≈9×106 cells retention in the infarct zone ‐ in absence of epicardial flow or myocardial perfusion impairment (TIMI‐3 in all; cTFC 45±8 vs. 44±9, p=0.51) or any hs‐Troponin T elevation. By 3 years, one patient died from a new, non‐index territory AMI; there were no other MACCE and no adverse events that might be related to WJMSCs. cMRI infact size was reduced from 33.2±7.6g to 25.5±6.4g at 1 year and 23.1±5.6g at 3 years (p=0.03 vs. baseline). cMRI, SPECT, and echo showed a significant increase in LVEF between WJMSCs administration and 1 year (41.9±2.6% vs. 51.0±3.3%, 36.0±3.9% vs 44.9±5.0%, and 38.4±2.5% vs. 48.0±2.1% respectively, p<0.01 for all) that was sustained at 3 years (cMRI‐LVEF evolution in Figure). (Figure presented) Conclusions: CIRCULATE‐AMI PSC data suggest that WJMSC transcoronary application in a recent large AMI in humans may be associated with a significant LVEF improvement that is sustained at 3 years. While animal work is elucidating underlying mechanism(s), the current RCT cohort will provide placebo‐related insights into WJMSCs inhibition of LV adverse remodeling and clinical outcomes.