Abstract 15869: Antiarrhythmic Effects of Mesenchymal Stromal Cells in a Post-Infarct Swine Model of Ventricular Tachycardia

Abstract

Introduction: Mesenchymal Stromal Cells (MSC) reduce scar burden in models of ischemic cardiomyopathy. It is unknown whether MSCs exert antiarrhythmic effects. Hypothesis: MSCs reduce inducibility of monomorphic VT (mmVT) or prolong VT cycle length by ≥20 msec in a post-infarct swine model of VT. Methods: Two groups of 8 Yorkshire Swine underwent a 180-minute occlusion of the LAD. Group 1 (n=8) pigs underwent initial MRI scan, electrophysiology study (EPS), and 3D electroanatomic mapping (EAM) with injection of open-label MSCs (200M cells) around the borderzone of the infarct, using a NOGA Myostar catheter (J&J) guided by EAM. Group 1 pigs had repeat EAM, and final EPS 8 weeks later. Group 2 pigs (n=8) were randomized between placebo and MSC and underwent sequential MSC injections (100M cells/procedure), 7 weeks apart, followed by final EPS and MRI 7 weeks later. Scar% = total scar/myocardial mass (grams). Results: MmVT was induced in 5 of 8 (62.5%) at initial EPS (i-EPS) in Group 1 pigs and 3 of 8 (37.5%) at final EPS (f-EPS). In Group 2 all 4 MSC-treated swine had inducible mmVT during i-EPS but only 2 had mmVT at f-EPS. Overall, 9 of 12 MSC-treated pigs had mmVT initially and 5 of 12 pigs had mmVT at f-EPS (p=0.12). For MSC-treated pigs with persistently inducible mmVT (Groups 1 & 2), the baseline VT CL increased in all pigs by ≥20msec and increased from 216 ± 17 msec initially to 274 ± 35 msec at f-EPS (p = 0.001). In Group 1, Scar% was unchanged (22.2±1.6% to 20.5±2.1%) after single MSC treatment (p=0.17). In Group 2 MSC-treated pigs, Scar% decreased from 25.8±2.0% to 17.9±0.6% after 2 MSC treatments (p=0.014). In pigs with mmVT at i-EPS, the scar% was 24.4±1.2%, compared with 19.3±2.0% in pigs without i-EPS inducible mmVT (p=0.025). In pigs with mmVT at f-EPS, scar% was 22.5±1.8% compared with 18.1±1.6% in pigs without mmVT at f-EPS (p=0.048). Placebo-treated pigs showed no change in scar% (22.5±2.6% to 22.4±2.9%, p=0.44) and no change in VT inducibility (3 of 4 pigs at i-EPS and f-EPS). Conclusions: This study demonstrates that MSC injection reduced myocardial scar and either suppressed induction of VT or prolonged VT cycle length, consistent with an antiarrhythmic effect. Lower scar burden was associated with non-inducibility of VT, either at baseline or final EPS.