Ventricular nanosecond pulsed electric field delivery using active fixation leads: a proof-of-concept preclinical study

Background Mid-myocardial ventricular arrhythmias are challenging to treat. Cardiac electroporation via pulsed electric fields (PEFs) offers significant promise. We therefore tested PEF delivery using screw-in pacemaker leads as proof-of-concept. Methods In 5 canine models, we applied nanosecond PEF (pulse width 300 ns) across the right ventricular (RV) septum using a single lead bipolar configuration ( n = 2) and between two leads ( n = 3). We recorded electrograms (EGMs) prior to, immediately post, and 5 min after PEF. Cardiac magnetic resonance imaging (cMRI) and histopathology were performed at 2 weeks and 1 month. Results Nanosecond PEF induced minimal extracardiac stimulation and frequent ventricular ectopy that terminated post-treatment; no canines died with PEF delivery. With 1 lead, energy delivery ranged from 0.64 to 7.28 J. Transient ST elevations were seen post-PEF. No myocardial delayed enhancement (MDE) was seen on cMRI. No lesions were noted on the RV septum at autopsy. With 2 leads, energy delivery ranged from 56.3 to 144.9 J. Persistent ST elevations and marked EGM amplitude decreases developed post-PEF. MDE was seen along the septum 2 weeks and 1 month post-PEF. There were discrete fibrotic lesions along the septum; pathology revealed dense connective tissue with < 5% residual cardiomyocytes. Conclusions Ventricular electroporation is feasible and safe with an active fixation device. Reversible changes were seen with lower energy PEF delivery, whereas durable lesions were created at higher energies. Graphical abstract Central illustration: pulsed electric field delivery into ventricular myocardium with active fixation leads