Abstract 14056: Reducing to Practice the Concept of a Biological Pacemaker: Efficacy of Percutaneous, Right-Sided Gene Delivery in the Bundle of His versus Open-Chest Ventricular Wall Injection in a Porcine Model of Complete Heart Block
Introduction: Present therapy for symptomatic bradycardia relies on electronic pacemakers. Complications may arise from device implantation, malfunction or infection. Biological pacemakers may, in principle, circumvent these problems, but practical delivery methods have not been developed. We developed and compared two delivery strategies: a percutaneous right-sided approach, versus open chest ventricular wall injection.
Methods: Complete AV nodal block was induced in pigs by radiofrequency ablation after implantation of a single-chamber pacemaker (PM) to maintain a ventricular backup rate of 50 bpm. Biological pacemaker activity was created with intramyocardial delivery of gene constructs to suppress IK1 (Kir2.1AAA) and co-expression of the If current gene (HCN2) by adenoviral vectors. Adenovirus expressing GFP served as a control with either delivery route. Transgenes were injected either directly into the ventricular wall (open chest) or the Bundle of His via a NOGA Myostar catheter after electro-anatomical mapping using catheters advanced through the right femoral vein. Animals were followed for 2 weeks with serial ECGs, Holters, and PM interrogations.
Results: Active transgene-injected animals in the percutaneous group displayed biological pacemaker activity, with a physiologically-relevant rate of 87±2 bpm. The control animals remained largely dependent on the electronic pacemaker with rates of 53±3 bpm (days 3-14 post-injection; p<0.05 vs active transgene); electronic PM utilization was 20±6% in the active transgene-injected animals compared to 76±17% in controls. In contrast, open-chest animals, injected in the ventricular wall presented no differences in HR at day 7 (64.4±5.4 active transgene vs. 66.4±3.5 bpm GFP).
Conclusions: Our data provide proof-of-principle demonstration of a biological pacemaker by gene transfer using a percutaneous (right sided) delivery approach. The delivery of the genes by endomyocardial injection catheter in the Bundle of His resulted in superior efficacy when compared to free wall injection. This minimally-invasive approach could be used as a bridge-to-device to create a hardware-free interval sufficient to treat pacemaker device infections before re-implanting a permanent device.
- © 2011 by American Heart Association, Inc.