Journal of Interventional Cardiac Electrophysiology

, Volume 55, Issue 3, pp 251–265 | Cite as

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

  • Alan Sugrue
  • Vaibhav Vaidya
  • Chance Witt
  • Christopher V. DeSimone
  • Omar Yasin
  • Elad Maor
  • Ammar M. Killu
  • Suraj Kapa
  • Christopher J. McLeod
  • Damijan Miklavčič
  • Samuel J. AsirvathamEmail author



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


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.


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.


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


Cardiac ablation Irreversible electroporation Pulsed electric field Atrial fibrillation Arrhythmias Catheter ablation Translational studies 



Coronary arteries


Direct current




Irreversible electroporation


Pulmonary vein




Superior vena cava


Ventricular fibrillation



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).


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).

Compliance with ethical standards

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.

Supplementary material

10840_2019_574_MOESM1_ESM.pdf (238 kb)
ESM 1 (PDF 238 kb)


  1. 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.CrossRefGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 3.
    Swartz J. A catheter-based curative approach to atrial fibrillation in humans. Circulation. 1994;90:I-335.Google Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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. 7.
    Gonska B, Brune S, Bethge K, Kreuzer H. Radiofrequency catheter ablation in recurrent ventricular tachycardia. Eur Heart J. 1991;12(12):1257–65.CrossRefPubMedGoogle Scholar
  8. 8.
    Nathan AW, Bennett DH, Ward DE, Bexton RS, Camm AJ. Catheter ablation of atrioventricular conduction. Lancet (London, England). 1984;1(8389):1280–4.CrossRefGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 11.
    Huang SKS. Advances in applications of radiofrequency current to catheter ablation therapy. Pacing Clin Electrophysiol. 1991;14(1):28–42.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.Google Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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).Google Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 23.
    Aksu T, Ebru Golcuk S, Yalin K. Haemoptysis and pulmonary haemorrhage associated with cryoballoon ablation. Europace. 2015;17(8):1240.CrossRefPubMedGoogle Scholar
  24. 24.
    Rems L, Miklavčič D. Tutorial: electroporation of cells in complex materials and tissue. J Appl Phys. 2016;119(20):201101.CrossRefGoogle Scholar
  25. 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.CrossRefGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 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.CrossRefGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar
  31. 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.CrossRefPubMedGoogle Scholar
  32. 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.Google Scholar
  33. 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.CrossRefGoogle Scholar
  34. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.PubMedGoogle Scholar
  39. 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.Google Scholar
  40. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 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.CrossRefPubMedGoogle Scholar
  42. 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.Google Scholar
  43. 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.CrossRefPubMedGoogle Scholar
  44. 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.CrossRefPubMedGoogle Scholar
  45. 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.CrossRefPubMedGoogle Scholar
  46. 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.CrossRefPubMedGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. 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.Google Scholar
  49. 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.CrossRefPubMedGoogle Scholar
  50. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 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.CrossRefPubMedGoogle Scholar
  55. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 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.CrossRefGoogle Scholar
  58. 58.
    Reberšek M. Beyond electroporation pulse parameters: from application to evaluation. Handb Electroporation. 2017:1–21.Google Scholar
  59. 59.
    Schoenbach KH. From the basic science of biological effects of ultrashort electrical pulses to medical therapies. Bioelectromagnetics. 2018;39:257–76.CrossRefPubMedGoogle Scholar
  60. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 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.CrossRefGoogle Scholar
  62. 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.CrossRefPubMedGoogle Scholar
  63. 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.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Alan Sugrue
    • 1
  • Vaibhav Vaidya
    • 1
  • Chance Witt
    • 1
  • Christopher V. DeSimone
    • 1
  • Omar Yasin
    • 1
  • Elad Maor
    • 2
  • Ammar M. Killu
    • 1
  • Suraj Kapa
    • 1
  • Christopher J. McLeod
    • 1
  • Damijan Miklavčič
    • 3
  • Samuel J. Asirvatham
    • 1
    Email author
  1. 1.Department of Cardiovascular Diseases, Department of Internal MedicineMayo ClinicRochesterUSA
  2. 2.Leviev Heart Center, Sheba Medical Center, and Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Faculty of Electrical EngineeringUniversity of LjubljanaLjubljanaSlovenia

Personalised recommendations