Irreversible electroporation near the heart: ventricular arrhythmias can be prevented with ECG synchronization

Ajita Deodhar, Timm Dickfeld, Gordon W Single, William C Hamilton Jr, Raymond H Thornton, Constantinos T Sofocleous, Majid Maybody, Mithat Gónen, Boris Rubinsky, Stephen B Solomon, Ajita Deodhar, Timm Dickfeld, Gordon W Single, William C Hamilton Jr, Raymond H Thornton, Constantinos T Sofocleous, Majid Maybody, Mithat Gónen, Boris Rubinsky, Stephen B Solomon

Abstract

Objective: Irreversible electroporation is a nonthermal ablative tool that uses direct electrical pulses to create irreversible membrane pores and cell death. The ablation zone is surrounded by a zone of reversibly increased permeability; either zone can cause cardiac arrhythmias. Our purpose was to establish a safety profile for the use of irreversible electroporation close to the heart.

Materials and methods: The effect of unsynchronized and synchronized (with the R wave on ECG) irreversible electroporation in swine lung and myocardium was studied in 11 pigs. Twelve lead ECG recordings were analyzed by an electrophysiologist for the presence of arrhythmia. Ventricular arrhythmias were categorized as major events. Minor events included all other dysrhythmias or ECG changes. Cardiac and lung tissue was submitted for histopathologic analysis. Electrical field modeling was performed to predict the distance from the applicators over which cells show electroporation-induced increased permeability.

Results: At less than or equal to 1.7 cm from the heart, fatal (major) events occurred with all unsynchronized irreversible electroporation. No major and three minor events were seen with synchronized irreversible electroporation. At more than 1.7 cm from the heart, two minor events occurred with only unsynchronized irreversible electroporation. Electrical field modeling correlates well with the clinical results, revealing increased cell membrane permeability up to 1.7 cm away from the applicators. Complete lung ablation without intervening live cells was seen. No myocardial injury was seen.

Conclusion: Unsynchronized irreversible electroporation close to the heart can cause fatal ventricular arrhythmias. Synchronizing irreversible electroporation pulse delivery with absolute refractory period avoids significant cardiac arrhythmias.

Figures

Fig. 1
Fig. 1
Action potential, contractile response, and ECG. At 50 milliseconds after R wave, cardiac muscle is absolutely refractory. Synchronized irreversible electroporation pulse, which lasts for 70 microseconds, is denoted by continuous vertical line. Adapted from Ganong [13].
Fig. 2
Fig. 2
Electrical field modeling shows extent of zone of reversibly increased permeability (arrows). Ablation zone size with two applicators (B1 and B2) 15 mm apart and 2-cm active applicator is superimposed.
Fig. 3
Fig. 3
Field model zones superimposed on intraprocedure CT scans. A, Zone of increased permeability (darker gray zone) overlaps myocardium. Lighter gray zone represents ablation zone. Synchronization would be necessary to avoid cardiac arrhythmia. B, Zone of increased permeability (darker gray zone) is away from myocardium. Lighter gray zone represents ablation zone. Synchronization is not essential.

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