Cardiac reparative therapy with adipose graft transposition procedure (AGTP) improves electrophysiological remodeling of chronic myocardial infarction

Abstract

Background: Cardiac regeneration is a promising therapeutic option for patients with prior myocardial infarction (MI). Adipose graft transposition procedure (AGTP) is a cardiac reparative therapy consisting of the transposition of a vascularized adipose flap from the autologous pericardium over the epicardial scar area which has shown to reduce the infarct size and improve the left ventricular function. Purpose(s): To assess the impact of the AGTP on the electrophysiological remodeling of the post-MI scar by means of electrophysiological study (EPS) high density (HD) mapping and 3D contrast-enhanced MRI (ceMRI). Method(s): A lateral MI was induced in 14 Landrace X Large White pigs by coil deployment at the first marginal branch of the circumflex artery. A 3D ceMRI EPS and endocardial HD mapping were performed 2 (baseline) and 6 weeks post-MI (30 day post-treatment). Subjects were randomized to AGTP (n=8) or sham surgery (n=6) following baseline tests. Voltage and activation maps were blindly analyzed off-line with self-customized ParaView-based software. ceMRI was post-processed with ADAS3D. Conventional bipolar and unipolar voltage cut-offs were used (0.5-1.5mV and 6.7mV respectively). Conduction velocity (CV) was determined for every pair of contiguous points. Areas of CV were quantified for every 0.2m/s steps (<0.2 - 4 m/s). Result(s): At follow-up and compared to the sham group the AGTP group showed a significant reduction of the border zone area in both bipolar voltage mapping (-18+/-50% vs +10+/-144% p=0.043) and ceMRI (-2.0+/-1.7 vs +1.1+/-2.8g; p=0.047) as well as a reduction in dense scar mass by ceMRI (-1.1+/-0.7g vs. +0.6+/-0.9 g p=0.001). The AGTP group had a significant reduction of the size of very-slow CV areas (<0.2 m/s) compared to the sham group (-3.5+/-3.4 vs. +1.5+/-3.8 mm2 p=0.022) without differences in other CV ranges. EPS did not induce ventricular tachycardia in any subject at baseline and only in 1 of the sham group at the follow-up. Conclusion(s): Cardiac reparative therapy with AGTP of post-MI scar reduced the size of border zone tissue and very-slow conduction zones and could provide a protective effect against arrhythmic events in ischemic heart disease.