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Raman Mitra, MD- PhD, Director Electrophysiology, North Shore University Hospital, Northwell Health, New Hyde Park, NY

Pulsed Field Ablation Technology for Atrial Fibrillation: The Best Thing Since Sliced Bread?

By Raman Mitra, MD- PhD, Director Electrophysiology, North Shore University Hospital, Northwell Health, New Hyde Park, NY

An effective procedure to correct atrial fibrillation and obviate the need for antiarrhythmic medications has been the “Holy Grail” for cardiac electrophysiologists and arrhythmia surgeons over the past four decades.

In 1987, James Cox working with John Boineau, described the Cox-Maze procedure, a technique in which the right and left atria were “cut and sewn” back together to effectively decrease the contiguous surface area of the atria, rendering it difficult for multiple electrical atrial wavelets to perpetuate, a necessary condition for persistent atrial fibrillation1-2. As part of their lesions sets, the pulmonary vein insertions in the posterior left atrium were also fortuitously isolated. It was not until 1998 that Haisaguerre and colleagues identified that rapid electrical firing from the pulmonary veins was a key trigger initiating, and at times, perpetuating atrial fibrillation3.  Atrial fibrillation, however, is a phenotypic description of a very heterogeneous disease process. While in some patients, the root cause may be pulmonary vein triggers, in others, atrial enlargement and scarring allow multiple electrical wavelets to coexist. Any procedure that eliminates pulmonary vein triggers will be effective to correct atrial fibrillation; however, the greater success of the Cox-Maze procedure is the result of also reducing the contiguous surface area of the atria4.

Over the last three decades cardiac electrophysiologists have tried to emulate the surgical approach using transvenous catheters to create transmural atrial lesions. The initial catheters had distal electrode tips of 3-4 mm (about 0.16 in) through which 500kHz of radiofrequency (RF) energy (effectively heating the tip to 50-60 degree Centigrade) was delivered to cauterize the atria from the endocardium (inside). Due to the limitations of sufficient energy delivery and catheter contact, these lesions were often not permanent or transmural (full thickness), leading to frequent recurrence of atrial fibrillation, even for pulmonary vein isolation alone. Even lower success occurred when trying to emulate the full Cox Maze lesion. Additionally, safety hazards due to thermal injury could lead to narrowing of the pulmonary veins or collateral damage to the esophagus, pericardium, thoracic or gastric nerves, as well as clot formation causing strokes, all of which could rarely lead to fatal or catastrophic consequences5.

The current PFA systems, however, have significantly improved efficiency and appear to be safer with respect to certain complications.

Advances in catheter technology, intracardiac imaging, and awareness of potential complications have led to a significant improvement in success rates and decreases in complication rates. Alternative energy sources such as cryoablation and laser balloon ablation were also introduced, despite which 1 year success rates for paroxysmal (intermittent and self-converting) atrial fibrillation was at best near 70%; and for persistent atrial fibrillation, in the 50-60% range, with a gradual increase of atrial fibrillation recurrence of 5-10% /year from the time of ablation, necessitating many repeat procedures6. This fueled the impetus to find novel energy types to create controlled, prescribed, transmural scars without collateral damage7.

Electroporation is technique that has been known for decades, in which a very brief, but high voltage pulse (Pulsed field or PF) is applied to tissue through a catheter, hyper-permeabilizing the cell membrane to ions and molecules, leading to the rapid entry of calcium, loss of ATP (cell’s energy molecule) and ionic gradients, all of which, lead to cell death. One advantage of PF is that the energy frequency can be “tuned” to the tissue, thus being specific for atrial myocardium and not esophageal tissue, and thus, deriving a significant safety advantage over the non-specificity of thermal ablation such as RF (heat) or cryocatheter (cold) approaches8.

While initially PF was thought to be less dependent on catheter contact than thermal ablation, this was found to be incorrect, so like thermal catheters, tissue contact is important. PF carries some unique risks of its own including hemolysis, rarely causing kidney failure if too many applications are delivered, as well as spasm of coronary arteries if PF is applied near the vessel. Despite these concerns, PF ablation has been demonstrated to be as effective and safe as thermal ablation and far less likely to cause collateral damage. The cost per case is higher, but this loss of margin is offset by the cases taking less time, such that 1-2 more cases may be performed in the same time as previous thermal ablations8.

In the fervor of performing more effective ablation, and a one size fits all approach (the antithesis of personalized medicine), physicians and industry may lose sight of a key question:

For a given patient, exactly where and how much do we need to ablate to prevent atrial fibrillation?

To answer that question, electrical mapping of the atrial substrate is needed. Until recently, the catheters needed to map could not be used for ablation, requiring frequent exchanges between the two types of catheters. Exchanges may lead to lengthening case time and increase the risks of stroke. The newest generation of PFA catheters, however, can both map and ablate with the same catheter, as well as deliver both pulsed field and radiofrequency energy, allowing for a more “plug and play” approach to ablation. The ability to deliver dual energy allows delivery of the safest and most effective lesion depending on anatomic location. For example, PF can be applied to the posterior wall to avoid esophageal injury, while RF can be applied near the valve to avoid coronary spasm. Currently, Medtronic’s Affera system is the only system capable of both mapping and delivering dual energy with a single spherical shaped catheter; however, over the next few years, other vendors will follow suit.

Improved ability to ablate larger amounts of atrial tissue without complications may be a double-edged sword as well. Excessive ablation can lead to loss of atrial mechanical function, and delays in the normal sequence of atrial conduction, all of which can have deleterious mechanical consequences that may lead to symptoms of shortness of breath despite achieving normal rhythm. The current PFA systems, however, have significantly improved efficiency and appear to be safer with respect to certain complications. Whether PFA is superior with respect to preventing recurrences of atrial fibrillation in the long term, and thereby justifying the higher cost, is yet to be determined.

References:

  1. Cox JL, Schuessler RB, Boineau JP. The development of Maze procedure for the treatment of atrial fibrillation. Semin Thorac Cardiovasc Surg. 2000 Jan;12(1):2-14.
    doi: 10.1016/s1043-0679(00)70010-4. PMID: 10746916.
  2. Cox JL. A brief overview of surgery for atrial fibrillation. Ann Cardiothorac Surg. 2014 Jan;3(1):80-8.
    doi: 10.3978/j.issn.2225-319X.2014.01.05. PMID: 24516803; PMCID: PMC3904338.
  3. Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Métayer P, Clémenty J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998 Sep 3;339(10):659-66.
    doi: 10.1056/NEJM199809033391003. PMID: 9725923.
  4. Hartley, A, Shalhoub, J, Ng FS, et al. Size matters in atrial fibrillation: the underestimated importance of reduction of contiguous electrical mass underlying the effectiveness of catheter ablation, EP Europace, Volume 23, Issue 11, November 2021, Pages 1698–1707,
    https://doi.org/10.1093/europace/euab078
  5. Benali, K, Khairy, P, Hammache, N. et al. Procedure-Related Complications of Catheter Ablation for Atrial Fibrillation. JACC. 2023 May, 81 (21) 2089–2099.
    https://doi.org/10.1016/j.jacc.2023.03.418
  6. Winkle RA, Mead RH, Engel G et al. Very long-term outcomes of atrial fibrillation ablation. Heart Rhythm. 2023 May;20(5):680-688. doi: 10.1016/j.hrthm.2023.02.002. Epub 2023 Feb 9. PMID: 36764350.
    10.1016/j.hrthm.2023.02.002
  7. Verma MS, Terricabras M, Verma A, The Cutting Edge of Atrial Fibrillation Ablation, Arrhythmia & Electrophysiology Review 2021;10(2):101-107
    https://doi.org/10.15420/aer.2020.40
  8. Tabaja C, Younis A, Hussein A et al. Catheter-Based Electroporation: A Novel Technique for Catheter Ablation of Cardiac Arrhythmias, JACC: Clinical Electrophysiology, Volume 9, Issue 9, 2023, Pages 2008-2023, https://doi.org/10.1016/j.jacep.2023.03.014
  9. Calvert P, Mills MT, Xydis P et al. Cost, efficiency, and outcomes of pulsed field ablation vs thermal ablation for atrial fibrillation: A real-world study. Heart Rhythm, Volume 21, Issue 9, 1537 – 1544
  10. Ekanem, E., Neuzil, P., Reichlin, T. et al. Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study. Nat Med 30, 2020–2029 (2024).
    https://doi.org/10.1038/s41591-024-03114-3