Biological pacemaker created by percutaneous gene delivery via venous catheters in a porcine model of complete heart block

BackgroundPacemaker-dependent patients with device infection require temporary pacing while the infection is treated. External transthoracic pacing is painful and variably effective, while temporary pacing leads are susceptible to superinfection.ObjectiveTo create a biological pacemaker delivered via venous catheters in a porcine model of complete heart block, providing a temporary alternative/adjunct to external pacing devices without additional indwelling hardware.MethodsComplete atrioventricular (AV) nodal block was induced in pigs by radiofrequency ablation after the implantation of a single-chamber electronic pacemaker to maintain a ventricular backup rate of 50 beats/min. An adenoviral vector cocktail (KAAA + H2), expressing dominant-negative inward rectifier potassium channel (Kir2.1AAA) and hyperpolarization-activated cation channel (HCN2) genes, was injected into the AV junctional region via a NOGA Myostar catheter advanced through the femoral vein.ResultsAnimals injected with KAAA + H2 maintained a physiologically relevant ventricular rate of 93.5 ± 7 beats/min (n = 4) compared with control animals (average rate, 59.4 ± 4 beats/min; n = 6 at day 7 postinjection; P <.05). Backup electronic pacemaker utilization decreased by almost 4-fold in the KAAA + H2 group compared with the control (P <.05), an effect maintained for the entire 14-day window. In contrast to the efficacy of gene delivery into the AV junctional region, open-chest, direct injection of KAAA + H2 (or its individual vectors) into the ventricular myocardium failed to elicit significant pacemaker activity.ConclusionsThe right-sided delivery of KAAA + H2 to the AV junctional region provided physiologically relevant biological pacing over a 14-day period. Our approach may provide temporary, bridge-to-device pacing for the effective clearance of infection prior to the reimplantation of a definitive electronic pacemaker.