Skip to main content
SpringerLink
Log in

Irreversible electroporation for catheter-based cardiac ablation: a systematic review of the preclinical experience

  • MULTIMEDIA REPORT
  • Published:
Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Introduction

Irreversible electroporation (IRE) utilizing high voltage pulses is an emerging strategy for catheter-based cardiac ablation with considerable growth in the preclinical arena.

Methods

A systematic search for articles was performed from three sources (PubMed, EMBASE, and Google Scholar). The primary outcome was the efficacy of tissue ablation with characteristics of lesion formation evaluated by histologic analysis. The secondary outcome was focused on safety and damage to collateral structures.

Results

Sixteen studies met inclusion criteria. IRE was most commonly applied to the ventricular myocardium (n = 7/16, 44%) by a LifePak 9 Defibrillator (n = 9/16, 56%), NanoKnife Generator (n = 2/16, 13%), or other custom generators (n = 5/16, 31%). There was significant heterogeneity regarding electroporation protocols. On histological analysis, IRE was successful in creating ablation lesions with variable transmurality depending on the electric pulse parameters and catheter used.

Conclusion

Preclinical studies suggest that cardiac tissue ablation using IRE shows promise in delivering efficacious, safe lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CA:

Coronary arteries

DC:

Direct current

ECG:

Electrocardiogram

IRE:

Irreversible electroporation

PV:

Pulmonary vein

RF:

Radiofrequency

SVC:

Superior vena cava

VF:

Ventricular fibrillation

References

  1. Edmonds JH, Ellison RG, Crews TL. Surgically induced atrioventricular block as treatment for recurrent atrial tachycardia in Wolff-Parkinson-White syndrome. Circulation. 1969;39(5S1):I-105–I-11.

    Article  Google Scholar 

  2. Calkins H, Leon AR, Deam AG, Kalbfleisch SJ, Langberg JJ, Morady F. Catheter ablation of atrial flutter using radiofrequency energy. Am J Cardiol. 1994;73(5):353–6.

    Article  CAS  PubMed  Google Scholar 

  3. Swartz J. A catheter-based curative approach to atrial fibrillation in humans. Circulation. 1994;90:I-335.

    Google Scholar 

  4. Jai P, Hai M, Shah DC, Chouairi S, Gencel L, Cle J. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation. 1997;95(3):572–6.

    Article  Google Scholar 

  5. Haissaguerre M, Gencel L, Fischer B, Le Metayer P, Poquet F, Marcus FI, et al. Successful catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 1994;5(12):1045–52.

    Article  CAS  PubMed  Google Scholar 

  6. Hindricks G, Haverkamp W, Rissel U, Richter K, Gülker H. Experimental observations on the use of radiofrequency energy for ablation of ventricular tissue. New Trends Arrhyt. 1988;4(1–2):337–42.

    Google Scholar 

  7. Gonska B, Brune S, Bethge K, Kreuzer H. Radiofrequency catheter ablation in recurrent ventricular tachycardia. Eur Heart J. 1991;12(12):1257–65.

    Article  CAS  PubMed  Google Scholar 

  8. Nathan AW, Bennett DH, Ward DE, Bexton RS, Camm AJ. Catheter ablation of atrioventricular conduction. Lancet (London, England). 1984;1(8389):1280–4.

    Article  CAS  Google Scholar 

  9. Gallagher JJ, Svenson RH, Kasell JH, German LD, Bardy GH, Broughton A, et al. Catheter technique for closed-chest ablation of the atrioventricular conduction system: a therapeutic alternative for the treatment of refractory supraventricular tachycardia. N Engl J Med. 1982;306(4):194–200.

    Article  CAS  PubMed  Google Scholar 

  10. Ward DE, Davies M. Transvenous high energy shock for ablating atrioventricular conduction in man. Observations on the histological effects. Heart. 1984;51(2):175–8.

    Article  CAS  Google Scholar 

  11. Huang SKS. Advances in applications of radiofrequency current to catheter ablation therapy. Pacing Clin Electrophysiol. 1991;14(1):28–42.

    Article  CAS  PubMed  Google Scholar 

  12. Olgin JE, Scheinman MM. Comparison of high energy direct current and radiofrequency catheter ablation of the atrioventricular junction. J Am Coll Cardiol. 1993;21(3):557–64.

    Article  CAS  PubMed  Google Scholar 

  13. Pappone C, Oral H, Santinelli V, Vicedomini G, Lang CC, Manguso F, et al. Atrio-esophageal fistula as a complication of percutaneous transcatheter ablation of atrial fibrillation. Circulation. 2004;109(22):2724–6.

    Article  PubMed  Google Scholar 

  14. Black-Maier E, Pokorney SD, Barnett AS, Zeitler EP, Sun AY, Jackson KP, et al. Risk of atrioesophageal fistula formation with contact force-sensing catheters. Heart Rhythm. 2017;14(9):1328–33.

    Article  PubMed  Google Scholar 

  15. Sacher F, Monahan KH, Thomas SP, Davidson N, Adragao P, Sanders P, et al. Phrenic nerve injury after atrial fibrillation catheter ablation: characterization and outcome in a multicenter study. J Am Coll Cardiol. 2006;47(12):2498–503.

    Article  PubMed  Google Scholar 

  16. Calkins H, Reynolds MR, Spector P, Sondhi M, Xu Y, Martin A, Williams CJ, Sledge I. Treatment of atrial fibrillation with anti–arrhythmic drugs or radio frequency ablation: two systematic literature reviews and meta–analyses. Circ Arrhythm Electrophysiol. 2009:CIRCEP. 108.824789.

  17. Schrickel JW, Lickfett L, Lewalter T, Mittman-Braun E, Selbach S, Strach K, et al. Incidence and predictors of silent cerebral embolism during pulmonary vein catheter ablation for atrial fibrillation. Europace. 2010;12(1):52–7.

    Article  PubMed  Google Scholar 

  18. Medi C, Evered L, Silbert B, Teh A, Halloran K, Morton J, et al. Subtle post-procedural cognitive dysfunction after atrial fibrillation ablation. J Am Coll Cardiol. 2013;62(6):531–9.

    Article  PubMed  Google Scholar 

  19. Andrade JG, Dubuc M, Guerra PG, Macle L, Mondésert B, Rivard L, et al. The biophysics and biomechanics of cryoballoon ablation. Pacing Clin Electrophysiol. 2012;35(9):1162–8.

    Article  PubMed  Google Scholar 

  20. Furnkranz A, Bordignon S, Bohmig M, Konstantinou A, Dugo D, Perrotta L, et al. Reduced incidence of esophageal lesions by luminal esophageal temperature-guided second-generation cryoballoon ablation. Heart Rhythm. 2015;12(2):268–74.

    Article  PubMed  Google Scholar 

  21. Narui R, Tokuda M, Matsushima M, Isogai R, Tokutake K, Yokoyama K, et al. Incidence and factors associated with the occurrence of pulmonary vein narrowing after cryoballoon ablation. Circ Arrhythm Electrophysiol. 2017;10(6).

  22. Ichihara N, Miyazaki S, Iwasawa J, Matsuda J, Taniguchi H, Nakamura H, et al. Prevalence and pre-procedural predictors associated with right phrenic nerve injury in electromyography-guided, second-generation cryoballoon ablation. JACC Clin Electrophysiol. 2016;2(4):508–14.

    Article  PubMed  Google Scholar 

  23. Aksu T, Ebru Golcuk S, Yalin K. Haemoptysis and pulmonary haemorrhage associated with cryoballoon ablation. Europace. 2015;17(8):1240.

    Article  PubMed  Google Scholar 

  24. Rems L, Miklavčič D. Tutorial: electroporation of cells in complex materials and tissue. J Appl Phys. 2016;119(20):201101.

    Article  Google Scholar 

  25. Martin RC, McFarland K, Ellis S, Velanovich V. Irreversible electroporation in locally advanced pancreatic cancer: potential improved overall survival. Ann Surg Oncol. 2013;20(3):443–9.

    Article  Google Scholar 

  26. Paiella S, Butturini G, Frigerio I, Salvia R, Armatura G, Bacchion M, et al. Safety and feasibility of irreversible electroporation (IRE) in patients with locally advanced pancreatic cancer: results of a prospective study. Dig Surg. 2015;32(2):90–7.

    Article  PubMed  Google Scholar 

  27. Valerio M, Stricker PD, Ahmed HU, Dickinson L, Ponsky L, Shnier R, et al. Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer. Prostate Cancer Prostatic Dis. 2014;17(4):343–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Scheffer HJ, Nielsen K, de Jong MC, van Tilborg AA, Vieveen JM, Bouwman AR, et al. Irreversible electroporation for nonthermal tumor ablation in the clinical setting: a systematic review of safety and efficacy. J Vasc Interv Radiol. 2014;25(7):997–1011.

    Article  PubMed  Google Scholar 

  29. Welden CV, Christein JD, Wilcox CM, Ahmed AM. Initial experience of irreversible electroporation in the treatment of locally advanced pancreatic adenocarcinoma. Gastroenterology. 2017;152(5):S277.

    Article  Google Scholar 

  30. Wojtaszczyk A, Caluori G, Pesl M, Melajova K, Starek Z. Irreversible electroporation ablation for atrial fibrillation. J Cardiovasc Electrophysiol. 2018;29(4):643–51.

    Article  PubMed  Google Scholar 

  31. Sugrue A, Maor E, Ivorra A, Vaidya V, Witt C, Kapa S, et al. Irreversible electroporation for the treatment of cardiac arrhythmias. Expert Rev Cardiovasc Ther. 2018;16(5):349–60.

    Article  CAS  PubMed  Google Scholar 

  32. Reddy VY, Koruth J, Jais P, Petru J, Timko F, Skalsky I, et al. Ablation of atrial fibrillation with pulsed electric fields: an ultra-rapid, tissue-selective modality for cardiac ablation. JACC Clin Electrophysiol. 2018:674.

  33. Vries R, Hooijmans CR, Langendam MW, Luijk J, Leenaars M, Ritskes-Hoitinga M, et al. A protocol format for the preparation, registration and publication of systematic reviews of animal intervention studies. Evid Based Preclin Med. 2015;2(1):1–9.

    Article  Google Scholar 

  34. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. DeSimone CV, Ebrille E, Syed FF, Mikell SB, Suddendorf SH, Wahnschaffe D, et al. Novel balloon catheter device with pacing, ablating, electroporation, and drug-eluting capabilities for atrial fibrillation treatment--preliminary efficacy and safety studies in a canine model. Transl Res. 2014;164(6):508–14.

    Article  PubMed  PubMed Central  Google Scholar 

  37. du Pre BC, van Driel VJ, van Wessel H, Loh P, Doevendans PA, Goldschmeding R, et al. Minimal coronary artery damage by myocardial electroporation ablation. Europace. 2013;15(1):144–9.

    Article  PubMed  Google Scholar 

  38. Hong J, Stewart MT, Cheek DS, Francischelli DE, Kirchhof N. Cardiac ablation via electroporation. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:3381–4.

    Google Scholar 

  39. Lavee J, Onik G, Mikus P, Rubinsky B, editors. A novel nonthermal energy source for surgical epicardial atrial ablation: irreversible electroporation. Heart Surgery Forum; 2007: FORUM MULTIMEDIA PUBLISHING.

  40. Madhavan M, Venkatachalam K, Swale MJ, Desimone CV, Gard JJ, Johnson SB, et al. Novel percutaneous epicardial autonomic modulation in the canine for atrial fibrillation: results of an efficacy and safety study. Pacing Clin Electrophysiol. 2016;39(5):407–17.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Neven K, van Driel V, van Wessel H, van Es R, Doevendans PA, Wittkampf F. Epicardial linear electroporation ablation and lesion size. Heart Rhythm. 2014;11(8):1465–70.

    Article  PubMed  Google Scholar 

  42. Neven K, van Driel V, van Wessel H, van Es R, Doevendans PA, Wittkampf F. Myocardial lesion size after epicardial electroporation catheter ablation following subxiphoid puncture. Circ Arrhythm Electrophysiol. 2014:CIRCEP. 114.001659.

  43. Neven K, van Driel V, van Wessel H, van Es R, du Pre B, Doevendans PA, et al. Safety and feasibility of closed chest epicardial catheter ablation using electroporation. Circ Arrhythm Electrophysiol. 2014;7(5):913–9.

    Article  PubMed  Google Scholar 

  44. van Driel VJ, Neven K, van Wessel H, Vink A, Doevendans PA, Wittkampf FH. Low vulnerability of the right phrenic nerve to electroporation ablation. Heart Rhythm. 2015;12(8):1838–44.

    Article  PubMed  Google Scholar 

  45. van Driel VJ, Neven KG, van Wessel H, du Pre BC, Vink A, Doevendans PA, et al. Pulmonary vein stenosis after catheter ablation: electroporation versus radiofrequency. Circ Arrhythm Electrophysiol. 2014;7(4):734–8.

    Article  PubMed  Google Scholar 

  46. Wittkampf FH, van Driel VJ, van Wessel H, Neven KG, Grundeman PF, Vink A, et al. Myocardial lesion depth with circular electroporation ablation. Circ Arrhythm Electrophysiol. 2012;5(3):581–6.

    Article  PubMed  Google Scholar 

  47. Wittkampf FH, van Driel VJ, van Wessel H, Vink A, Hof IE, Grundeman PF, et al. Feasibility of electroporation for the creation of pulmonary vein ostial lesions. J Cardiovasc Electrophysiol. 2011;22(3):302–9.

    Article  PubMed  Google Scholar 

  48. Zager Y, Kain D, Landa N, Leor J, Maor E. Optimization of irreversible electroporation protocols for in-vivo myocardial decellularization. PLoS One. 2016;11(11):e0165475. PMCID: PMC5125564 a patent application entitled “Myocardial Ablation by Irreversible Electroporation” (Application #: US14/894,349). This patent relates in part to the results presented in this study. In addition, Dr. Maor has a granted patent entitled “Extracellular matrix material created using non-thermal irreversible electroporation” (US8835166 B2). There are no additional patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

  49. Neven K, van Es R, van Driel V, van Wessel H, Fidder H, Vink A, et al. Acute and long-term effects of full-power electroporation ablation directly on the porcine esophagus. Circ Arrhythm Electrophysiol. 2017;10(5):e004672.

    Article  PubMed  Google Scholar 

  50. Livia C, Sugrue A, Witt T, Polkinghorne MD, Maor E, Kapa S, et al. Elimination of Purkinje fibers by electroporation reduces ventricular fibrillation vulnerability. J Am Heart Assoc. 2018;7(15):e009070.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Witt CM, Sugrue A, Padmanabhan D, Vaidya V, Gruba S, Rohl J, et al. Intrapulmonary vein ablation without stenosis: a novel balloon-based direct current electroporation approach. J Am Heart Assoc. 2018;7(14):e009575.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Thomson KR, Cheung W, Ellis SJ, Federman D, Kavnoudias H, Loader-Oliver D, et al. Investigation of the safety of irreversible electroporation in humans. J Vasc Interv Radiol. 2011;22(5):611–21.

    Article  PubMed  Google Scholar 

  53. Charpentier KP, Wolf F, Noble L, Winn B, Resnick M, Dupuy DE. Irreversible electroporation of the liver and liver hilum in swine. HPB. 2011;13(3):168–73.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Cannon R, Ellis S, Hayes D, Narayanan G, Martin RC 2nd. Safety and early efficacy of irreversible electroporation for hepatic tumors in proximity to vital structures. J Surg Oncol. 2013;107(5):544–9.

    Article  PubMed  Google Scholar 

  55. Mali B, Gorjup V, Edhemovic I, Brecelj E, Cemazar M, Sersa G, et al. Electrochemotherapy of colorectal liver metastases-an observational study of its effects on the electrocardiogram. Biomed Eng Online. 2015;14(3):S5.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Bertacchini C, Margotti PM, Bergamini E, Lodi A, Ronchetti M, Cadossi R. Design of an irreversible electroporation system for clinical use. Technol Cancer Res Treat. 2007;6(4):313–20.

    Article  PubMed  Google Scholar 

  57. Deodhar A, Dickfeld T, Single GW, Hamilton WC Jr, Thornton RH, Sofocleous CT, et al. Irreversible electroporation near the heart: ventricular arrhythmias can be prevented with ECG synchronization. Am J Roentgenol. 2011;196(3):W330–W5.

    Article  Google Scholar 

  58. Reberšek M. Beyond electroporation pulse parameters: from application to evaluation. Handb Electroporation. 2017:1–21.

  59. Schoenbach KH. From the basic science of biological effects of ultrashort electrical pulses to medical therapies. Bioelectromagnetics. 2018;39:257–76.

    Article  PubMed  Google Scholar 

  60. Mercadal B, Arena CB, Davalos RV, Ivorra A. Avoiding nerve stimulation in irreversible electroporation: a numerical modeling study. Phys Med Biol. 2017;62(20):8060–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Raso J, Frey W, Ferrari G, Pataro G, Knorr D, Teissie J, et al. Recommendations guidelines on the key information to be reported in studies of application of PEF technology in food and biotechnological processes. Innovative Food Sci Emerg Technol. 2016;37:312–21.

    Article  Google Scholar 

  62. Cemazar M, Sersa G, Frey W, Miklavcic D, Teissié J. Recommendations and requirements for reporting on applications of electric pulse delivery for electroporation of biological samples. Bioelectrochemistry. 2018;122:69–76.

    Article  CAS  PubMed  Google Scholar 

  63. Campana LG, Clover AJ, Valpione S, Quaglino P, Gehl J, Kunte C, et al. Recommendations for improving the quality of reporting clinical electrochemotherapy studies based on qualitative systematic review. Radiol Oncol. 2016;50(1):1–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

D.M. would like to acknowledge that this study was conducted within the scope of the LEA EBAM: European Laboratory of Pulsed Electric Fields Applications in Biology and Medicine (2011–2018).

Funding

The study was in part funded by the Slovenian Research Agency (ARRS) through ARRS research programme—Electroporation-based technologies and treatments (P2-0249, 2015–2020).

Author information

Authors and Affiliations

  1. Department of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Alan Sugrue, Vaibhav Vaidya, Chance Witt, Christopher V. DeSimone, Omar Yasin, Ammar M. Killu, Suraj Kapa, Christopher J. McLeod & Samuel J. Asirvatham

  2. Leviev Heart Center, Sheba Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Elad Maor

  3. Faculty of Electrical Engineering, University of Ljubljana, Trzaska 25, 1000, Ljubljana, Slovenia

    Damijan Miklavčič

Authors
  1. Alan Sugrue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vaibhav Vaidya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chance Witt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher V. DeSimone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Omar Yasin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elad Maor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ammar M. Killu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Suraj Kapa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christopher J. McLeod
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Damijan Miklavčič
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Samuel J. Asirvatham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samuel J. Asirvatham.

Ethics declarations

Conflict of interest

Authors SJA/SK/CW/CVD have filed but no issued patents within the realm of tools for electroporation. Author DM receives research funding and consulting fees from Medtronic. All other authors have no disclosures.

Ethical approval

For studies by the authors as include in this review, all applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 238 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sugrue, A., Vaidya, V., Witt, C. et al. Irreversible electroporation for catheter-based cardiac ablation: a systematic review of the preclinical experience. J Interv Card Electrophysiol 55, 251–265 (2019). https://doi.org/10.1007/s10840-019-00574-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10840-019-00574-3

Keywords

Search

Navigation