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

Abstract

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 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). Methods 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). Results 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. Conclusions 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. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FIS grant - Instituto de Salud Carlos III