Abstract 15261: Substrate Modification by Focal Exosome Injection as a Novel Strategy to Prevent Ventricular Tachyarrhythmias: Proof of Concept in a Porcine Model of Chronic Myocardial Infarction
Introduction: Myocardial infarction (MI) survivors are at increased risk of ventricular arrhythmias (VA) and sudden death. Current therapies for VA include ablation to “destroy” re-entry circuits. Isolated late potentials (ILP), which arise from viable myocardial bundles within scar, are targets for ablation in patients with recurrent VA. Cardiosphere-derived cell exosomes (CDCEXO) have been shown to reduce scar and improve ventricular function, due to their regenerative, anti-fibrotic and anti-inflammatory properties. Here we sought to determine if substrate modification with CDCEXO could reduce ILP and the incidence of scar-related VA in a pre-clinical model.
Methods: A balloon catheter was inflated in the LAD for 90 minutes, then reperfused for 8 weeks in 10 minipigs. MRI, programmed electrical stimulation (PES), and electroanatomic mapping (EAM; Rhythmia, Boston Scientific) were performed to evaluate arrhythmia inducibility and define sites of ILP. At 6-9 such sites, human CDCEXO (7.5mg/2ml, n=5) or vehicle only (2ml, n=5) was injected using a NOGA MYOSTAR catheter (Biosense Webster). Two weeks later, EAM and PES were repeated with continuous 12 lead ECG recordings. Final infarct size (scar mass divided by total LV mass) was quantified by MRI.
Results: In CDCEXO-injected pigs vs. controls, infarct size was reduced (-3.4±1.2% vs. 0.6±0.9%, p=0.025) and ejection fraction improved (2.6±2.2% vs. -5.8±2.1% p=0.02). The CDCEXO group exhibited fewer ILP (CDCEXO baseline 18.6±5.9; 2 weeks 3.6±2.9 p<0.05), but ILP did not decrease in the vehicle group (baseline 11.8±3.7 vs. 2 weeks 13.8±5.5 p=NS). The timing of the late component of ILP was decreased in CDCEXO-injected pigs (-23.4±5.8 ms vs. 9.4±6.2 ms P=0.007). VA was induced in 5 of 5 CDCEXO animals at baseline, but only 1 of 5 remained inducible 2 weeks later. All control animals had inducible VA during the 2 week follow up (p=0.04 vs CDCEXO).
Conclusions: CDCEXO delivered by endocardial catheter injection can diminish ILP associated with slow conduction, and decrease the inducibility of VA. Substrate modification was evidenced by decreased infarct size and reduced ILP in CDCEXO but not in control animals. Exosome injection may represent a viable nondestructive alternative to conventional VA ablation.
- Cardiac mapping
- Ventricular arrhythmia
- Cellular Electrophysiology
- Cardiac regeneration
Author Disclosures: J.F. Dawkins: None. J. Valle: None. A. Ehdaie: None. E. Marban: Ownership Interest; Significant; Capricor Therapeutics. E. Cingolani: None.
- © 2016 by American Heart Association, Inc.