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- ↵∗University of Ljubljana, Faculty of Electrical Engineering, Trzaska 25, 1000 Ljubljana, Slovenia
In a recent State-of-the-Art Review article, Wittkampf et al. (1) offered their view on irreversible electroporation (IRE) as a promising and potentially disruptive technology in cardiac ablation for pulmonary vein isolation. The investigators recognize advantages and disadvantages that electroporation offers over existing thermal ablation modalities. Myocardium has a lower irreversible electroporation threshold than other tissues, thus providing tissue specificity and limiting extracardiac injury. Mentioned challenges include epicardial fat, dependency on tissue-electrode contact, gas bubble formation, nerve and skeletal muscle stimulation, and technological challenge of applying high-voltage pulses.
However, some of generalizations that the investigators make based on long monophasic pulses and unipolar delivery (ground patch serving as the return electrode) should be considered with caution. Unipolar delivery produces a diffuse field gradient that can result in broad neuromuscular recruitment and diffuse lesion margins. Wittkampf et al. (1) do not recognize that bipolar delivery would confine the electric field surrounding the electrode array, minimizing skeletal muscle stimulation and resulting in well-demarcated lesion margins. They refer to a new energy source that may eliminate electrolysis and skeletal muscle contractions that is under development. There was however no insight on the device’s characteristics or pulse parameters provided. Avoiding electrolysis and skeletal muscle stimulation is challenging. However, the electroporation community has already introduced delivery methods utilizing short, biphasic, high-frequency pulses with bipolar delivery methods that limit electrochemistry and extracardiac muscle contractions.
The investigators suggest that total applied current is “the parameter that most directly relates to voltage gradient, which causes electroporation” but fail to report total current throughout their review. Even though they recognize that “the local effect of the application directly depends on the strength of the local electrical field” and that “the relationship between applied voltage and local field is rather complex,” I believe tissue conductivity is crucial to electric field distribution and was only partially addressed in their discussion. The local electric field (current density divided by conductivity tensor) is responsible for electroporation. Current preferentially flows through paths of higher conductivity—more longitudinally than perpendicularly in cardiac tissue due to fiber orientation. Also, electrical conductivity of infarcted myocardium is more conductive than that of a healthy myocardium. Varying conductivity influences the electric field distribution and may create inconsistent lesions. In addition, tissue heating, perfusion, and pulse delivery also change conductivity—all of which occur already during pulse delivery, hence current changes during pulse(s).
I thank Wittkampf et al. (1) for this discussion and introducing crucial questions regarding cardiac electroporation; however, there are some that were not discussed but need attention: How do electroporated cardiac cells die? What impact does intracardiac ablation have on blood cell lysis? How is “damage” inflicted to the ablated tissue resolved by the immune system? Is substantial heat generated by long monophasic pulses that could result in microbubbles and thermally generated particles? The recent clinical study demonstrating the feasibility of cardiac ablation gives extreme importance to additional preclinical cardiac irreversible electroporation work (2). The electroporation research community can support the investigation of these questions and others.
Please note: Prof. Miklavcic has received research funding and consulting fees from Medtronic.
The author attests he is in compliance with human studies committees and animal welfare regulations of the author’s institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- 2018 American College of Cardiology Foundation
- Wittkampf F.H.M.,
- van Es R.,
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