Abstract 14699: Epicardial Infarct Repair with a Novel Biologic Extracellular Matrix Improves Infarct Healing: Preclinical Validation
BACKGROUND: Despite successful revascularization after MI, the extracellular matrix (ECM) continues to remodel resulting in cardiac fibrosis, LV dilatation and heart failure. We hypothesized that a biologic ECM patch applied surgically to the epicardial surface of infarcted myocardium will limit post-MI remodeling and promote infarct healing. In this study we examined the safety and efficacy of epicardial infarct repair using a novel biologic ECM in a preclinical model.
METHOD/RESULTS: An FDA-approved biologic ECM construct (CorMatrix Cardiovascular Inc. CA, USA) was applied to the epicardium after 75 minutes of coronary ischemia in a porcine model. Animals were randomized following ischemia-reperfusion injury to ECM therapy (n=10) or sham (n=6). Serial cardiac MRI was performed on normal (n=4) and study animals at baseline (1-week) and 6-weeks post-treatment. Regional myocardial recovery was increased at 6-weeks in ECM treated animals compared to shams (change in regional myocardial contraction: +14.90±9.07% vs. -0.85±0.90%; p<0.05) confirming efficacy of therapy. Infarct volumes were comparable between ECM treated animals and shams at baseline and 6-weeks post-treatment (13.44±4.43% vs.10.58±1.31%; p=0.34 and 10.39±3.62% vs. 7.77±4.06% of the LV respectively; p=0.34). MRI revealed an increase in the overall fibrotic burden of infarcted vs. normal animals (0.31±0.02 vs. 0.24±0.01g/mL; p<0.01). A trend toward decreased fibrosis in the remote myocardium was noted in ECM treated animals compared to shams (0.25±0.01 vs. 0.27±0.02g/mL; p=0.28), which was confirmed by histology. Intrathoracic adhesions were assessed as a safety endpoint using a 4-point semi-quantitative scale. ECM treated animals had reduced adhesions compared to shams (1.44±0.51 vs. 3.08±0.89; p<0.05). ECM therapy did not cause myocardial constriction, as LV compliance by passive pressure distension was similar between groups. ECM treated animals showed enhanced vascularity by histology suggesting angiogenesis.
CONCLUSION: A novel biologic ECM therapy applied early after myocardial infarction was both safe and effective in limiting adverse remodeling, stimulating angiogenesis, and restoring regional cardiac recovery. A pilot clinical trial is in progress.
Author Disclosures: H.E. Mewhort: None. J.D. Turnbull: None. J.A. Flewitt: None. H.C. Meijndert: None. D.G. Guzzardi: None. D.A. Svystonyuk: None. C.Y. Yang: None. B.D. Lipon: None. D.S. Park: None. P.W. Fedak: None.
- © 2014 by American Heart Association, Inc.