The combined use of HGF gene therapy and ventricular assist device improves left ventricular function and enables bridge to recovery in goat model of severe heart failure

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Patients with end-stage heart failure require several months and even years under ventricular assist device (VAD) until receiving heart transplantation. Therefore, additional therapy such as regeneration therapy that promotes recovery of cardiac function is desired.In this study, we performed gene therapy with Hepatocyte Growth Factor (HGF) in the goat heat failure model requiring VAD support and examined the possibility of "bridge to recovery".Six adult goats (56-65kg) underwent ligation of the left anterior descending coronary artery, developed severe congestive heart failure and received the implantation of biventricular VAD (BiVAD). The HGF group was administered HGF c-DNA-plasmid of 2.0mg directly in myocardium, and the control group was administered empty plasmid.Under the BiVAD support, all goats maintained good systemic circulation and LV unloading for four weeks and after that periods we tried weaning from VAD. The HGF group showed good hemodynamics after the removal of VAD, while the control group showed the significant deterioration of hemodynamic condition. The %FS was significantly improved and LV dilatation was markedly suppressed in the HGF group than the control group (HGF vs. control, %FS;36±0.8vs24±0.6%, LVDd;34±2vs46±2mm, p<0.05). Histologically, vascular density around the infarcted area was markedly increased, and fibrous change was suppressed in the HGF group.In conclusion, these results suggest that gene therapy using HGF may increase the chance of "bridge to recovery" in the impaired heart requiring VAD support.