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Left atrial posterior wall isolation in conjunction with pulmonary vein isolation using cryoballoon for treatment of persistent atrial fibrillation (PIVoTAL): study rationale and design

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Abstract

Background

There is growing evidence in support of pulmonary vein isolation (PVI) with concomitant posterior wall isolation (PWI) for the treatment of patients with symptomatic persistent atrial fibrillation (persAF). However, there is limited data on the safety and efficacy of this approach using the cryoballoon.

Objective

The aim of this multicenter, investigational device exemption trial (G190171) is to prospectively evaluate the acute and long-term outcomes of PVI versus PVI+PWI using the cryoballoon in patients with symptomatic persAF.

Methods

The PIVoTAL is a prospective, randomized controlled study (ClinicalTrials.gov: NCT04505163) in which patients with symptomatic persAF refractory/intolerant to ≥ 1 class I–IV antiarrhythmic drug, undergoing first-time catheter ablation, will be randomized to PVI (n = 183) versus PVI+PWI (n = 183) using the cryoballoon in a 1:1 fashion. The design will be double-blind until randomization immediately after PVI, beyond which the design will transform into a single-blind. PVI using cryoballoon will be standardized using a pre-specified dosing algorithm. Other empiric ablations aside from documented arrhythmias/arrhythmias spontaneously induced during the procedure will not be permitted. The primary efficacy endpoint is defined as AF recurrence at 12 months, after a single procedure and a 90-day blanking period. Arrhythmia outcomes will be assessed by routine electrocardiograms and 7–14 day ambulatory electrocardiographic monitoring at 3, 6, and 12 months post-ablation.

Conclusion

The PIVoTAL is a prospective, randomized controlled trial designed to evaluate the outcomes of PVI alone versus PVI+PWI using the cryoballoon, in patients with symptomatic persAF. We hypothesize that PVI+PWI will prove to be superior to PVI alone for prevention of AF recurrence.

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References

  1. Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339:659–66.

    Article  PubMed  Google Scholar 

  2. Brooks AG, Stiles MK, Laborderie J, Lau DH, Kuklik P, Shipp NJ, et al. Outcomes of long-standing persistent atrial fibrillation ablation: a systematic review. Heart Rhythm. 2010;7:835–46.

    Article  PubMed  Google Scholar 

  3. Lappe JM, Cutler MJ, Day JD, Bunch TJ. Ablation for persistent atrial fibrillation-is there a role for more than PVI? Curr Treat Options Cardiovasc Med. 2016;18:15.

    Article  PubMed  Google Scholar 

  4. Cox JL, Canavan TE, Schuessler RB, Cain ME, Lindsay BD, Stone C, et al. The surgical treatment of atrial fibrillation. II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. J Thorac Cardiovasc Surg. 1991;101:406–26.

    Article  CAS  PubMed  Google Scholar 

  5. Cox JL, Ad N, Palazzo T, Fitzpatrick S, Suyderhoud JP, DeGroot KW, et al. Current status of the maze procedure for the treatment of atrial fibrillation. Semin Thorac Cardiovasc Surg. 2000;12:15–9.

    Article  CAS  PubMed  Google Scholar 

  6. Segerson NM, Daccarett M, Badger TJ, et al. Magnetic resonance imaging-confirmed ablative debulking of the left atrial posterior wall and septum for treatment of persistent atrial fibrillation: rationale and initial experience. J Cardiovasc Electrophysiol. 2010;21:126–32.

    Article  PubMed  Google Scholar 

  7. He X, Zhou Y, Chen Y, Wu L, Huang Y, He J. Left atrial posterior wall isolation reduces the recurrence of atrial fibrillation: a meta-analysis. J Interv Card Electrophysiol. 2016;46:267–74.

    Article  PubMed  Google Scholar 

  8. Proietti R, Santangeli P, Di Biase L, et al. Comparative effectiveness of wide antral versus ostial pulmonary vein isolation: a systematic review and meta-analysis. Circ Arrhythm Electrophysiol. 2014;7:39–45.

    Article  PubMed  Google Scholar 

  9. Bai R, Di Biase L, Mohanty P, et al. Proven isolation of the pulmonary vein antrum with or without left atrial posterior wall isolation in patients with persistent atrial fibrillation. Heart Rhythm. 2016;13:132–40.

    Article  PubMed  Google Scholar 

  10. McLellan AJA, Prabhu S, Voskoboinik A, et al. Isolation of the posterior left atrium for patients with persistent atrial fibrillation: routine adenosine challenge for dormant posterior left atrial conduction improves long-term outcome. Europace. 2017;19:1958–66.

    Article  PubMed  Google Scholar 

  11. Aryana A, Baker JH, Espinosa Ginic MA, Pujara DK, Bowers MR, O’Neill PG, et al. Posterior wall isolation using the cryoballoon in conjunction with pulmonary vein ablation is superior to pulmonary vein isolation alone in patients with persistent atrial fibrillation: a multicenter experience. Heart Rhythm. 2018;15:1121–9.

    Article  PubMed  Google Scholar 

  12. Nishimura T, Yamauchi Y, Aoyagi H, Tsuchiya Y, Shigeta T, Nakamura R, et al. The clinical impact of the left atrial posterior wall lesion formation by the cryoballoon application for persistent atrial fibrillation: feasibility and clinical implications. J Cardiovasc Electrophysiol. 2019;30:805–14.

    Article  PubMed  Google Scholar 

  13. Elbatran AI, Anderson RH, Mori S, Saba MM. The rationale for isolation of the left atrial pulmonary venous component to control atrial fibrillation: a review article. Heart Rhythm. 2019;16:1392–8.

    Article  PubMed  Google Scholar 

  14. Bai R. Left atrial posterior wall isolation: the icing on the cake. J Interv Card Electrophysiol. 2016;46:199–201.

    Article  PubMed  Google Scholar 

  15. Anderson RH, Brown NA, Moorman AFM, et al. Development and structures of the venous pole of the heart. Dev Dyn. 2006;235:2–9.

    Article  PubMed  Google Scholar 

  16. Webb S, Kanani M, Anderson RH, Richardson MK, Brown NA. Development of the human pulmonary vein and its incorporation in the morphologically left atrium. Cardiol Young. 2001;11:632–42.

    Article  CAS  PubMed  Google Scholar 

  17. Jones SA, Yamamoto M, Tellez JO, Billeter R, Boyett MR, Honjo H, et al. Distinguishing properties of cells from the myocardial sleeves of the pulmonary veins: a comparison of normal and abnormal pacemakers. Circ Arrhythm Electrophysiol. 2008;1:39–48.

    Article  PubMed  Google Scholar 

  18. Roberts-Thomson KC, Stevenson I, Kistler PM, Haqqani HM, Spence SJ, Goldblatt JC, et al. The role of chronic atrial stretch and atrial fibrillation on posterior left atrial wall conduction. Heart Rhythm. 2009;6:1109–17.

    Article  PubMed  Google Scholar 

  19. Corradi D, Callegari S, Maestri R, et al. Differential structural remodeling of the left-atrial posterior wall in patients affected by mitral regurgitation with or without persistent atrial fibrillation: a morphological and molecular study. J Cardiovasc Electrophysiol. 2012;23:271–9.

    Article  PubMed  Google Scholar 

  20. Markides V, Schilling RJ, Ho SY, Chow AW, Davies DW, Peters NS. Characterization of left atrial activation in the intact human heart. Circulation. 2003;107:733–9.

    Article  PubMed  Google Scholar 

  21. Suenari K, Chen YC, Kao YH, Cheng CC, Lin YK, Chen YJ, et al. Discrepant electrophysiological characteristics and calcium homeostasis of left atrial anterior and posterior myocytes. Basic Res Cardiol. 2011;106:65–74.

    Article  CAS  PubMed  Google Scholar 

  22. Ehrlich JR, Cha T, Zhang L, et al. Cellular electrophysiology of canine pulmonary vein cardiomyocytes: action potential and ionic current properties. J Physiol. 2003;551(Pt 3):801–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Verheule S, Tuyls E, Van Hunnik A, et al. Fibrillatory conduction in the atrial free walls of goats in persistent and permanent atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3:590–9.

    Article  PubMed  Google Scholar 

  24. Tahir KS, Mounsey JP, Hummel JP. Posterior wall isolation in atrial fibrillation ablation. J Innov Card Rhythm Manag. 2018;9:3186–94.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Allessie MA, De Groot NMS, Houben RPM, et al. Electropathological substrate of long-standing persistent atrial fibrillation in patients with structural heart disease: longitudinal dissociation. Circ Arrhythm Electrophysiol. 2010;3:606–15.

    Article  PubMed  Google Scholar 

  26. Mandapati R, Skanes A, Chen J, Berenfeld O, Jalife J. Stable microreentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. Circulation. 2000;101(2):194–9.

    Article  CAS  PubMed  Google Scholar 

  27. Narayan SM, Krummen DE, Clopton P, Shivkumar K, Miller JM. Direct or coincidental elimination of stable rotors or focal sources may explain successful atrial fibrillation ablation: on-treatment analysis of the CONFIRM trial (conventional ablation for AF with or without focal impulse and rotor modulation). J Am Coll Cardiol. 2013;62:138–47.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, Vasavakul T, et al. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol. 2004;43:2044–53.

    Article  PubMed  Google Scholar 

  29. Lin WS, Tai CT, Hsieh MH, et al. Catheter ablation of paroxysmal atrial fibrillation initiated by non-pulmonary vein ectopy. Circulation. 2003;107:3181–3.

    Article  Google Scholar 

  30. Kalifa J, Maixent JM, Chalvidan T, Dalmasso C, Colin D, Cozma D, et al. Energetic metabolism during acute stretch-related atrial fibrillation. Mol Cell Biochem. 2008;317(1–2):69–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hunter RJ, Liu Y, Lu Y, Wang W, Schilling RJ. Left atrial wall stress distribution and its relationship to electrophysiologic remodeling in persistent atrial fibrillation. Circ Arrhythm Electrophysiol. 2012;5:351–60.

    Article  PubMed  Google Scholar 

  32. Pison L, La Meir M, van Opstal J, Blaauw Y, Maessen J, Crijns HJ. Hybrid thoracoscopic surgical and transvenous catheter ablation of atrial fibrillation. J Am Coll Cardiol. 2012;60:54–61.

    Article  PubMed  Google Scholar 

  33. Lim TW, Koay CH, See VA, McCall R, Chik W, Zecchin R, et al. Single-ring posterior left atrial (box) isolation results in a different mode of recurrence compared with wide antral pulmonary vein isolation on long-term follow-up: longer atrial fibrillation-free survival time but similar survival time free of any atrial arrhythmia. Circ Arrhythm Electrophysiol. 2012;5:968–77.

    Article  PubMed  Google Scholar 

  34. Reddy VY, Neuzil P, D'Avila A, Ruskin JN. Isolating the posterior left atrium and pulmonary veins with a "box" lesion set: use of epicardial ablation to complete electrical isolation. J Cardiovasc Electrophysiol. 2008;19:326–9.

    Article  PubMed  Google Scholar 

  35. Higuchi S, Sohara H, Nakamura Y, Ihara M, Yamaguchi Y, Shoda M, et al. Is it necessary to achieve a complete box isolation in the case of frequent esophageal temperature rises? Feasibility of shifting to a partial box isolation strategy for patients with non-paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 2016;27:897–904.

    Article  PubMed  Google Scholar 

  36. Kim J, Shin SY, Na JO, et al. Does isolation of the left atrial posterior wall improve clinical outcomes after radiofrequency catheter ablation for persistent atrial fibrillation? A prospective randomized clinical trial. Int J Cardiol. 2015;181:277–83.

    Article  PubMed  Google Scholar 

  37. Nagashima K, Okumura Y, Watanabe I, et al. Hot balloon versus cryoballoon ablation for atrial fibrillation: lesion characteristics and efficacy. Circ Arrhythm Electrophysiol. 2018;11:e005861.

    Article  PubMed  Google Scholar 

  38. Perrotta L, Konstantinou A, Bordignon S, Fuernkranz A, Dugo D, Chun KJ, et al. What is the acute antral lesion size after pulmonary vein isolation using different balloon ablation technologies? Circ J. 2017;81:172–9.

    Article  PubMed  Google Scholar 

  39. Okumura Y, Watanabe I, Iso K, et al. Mechanistic insights into durable pulmonary vein isolation achieved by second-generation cryoballoon ablation. J Atr Fibrillation. 2017;9:18–24.

    Google Scholar 

  40. Reddy VY, Sediva L, Petru J, Skoda J, Chovanec M, Chitovova Z, et al. Durability of pulmonary vein isolation with cryoballoon ablation: results from the SUstained PV isolation with ARctic front advance (SUPIR) study. J Cardiovasc Electrophysiol. 2015;26:493–500.

    Article  PubMed  Google Scholar 

  41. Piccini JP, Braegelmann KM, Simma S, Koneru JN, Ellenbogen KA. Risk of atrioesophageal fistula with cryoballoon ablation of atrial fibrillation. Heart Rhythm O2. 2020; in press;1:173–9.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Aryana A, Pujara DK, Baker JH, et al. Long-term durability of posterior wall isolation using the cryoballoon in patients with persistent atrial fibrillation: a multicenter analysis of repeat catheter ablations. J Interv Card Electrophysiol. 2020; under review.

  43. Aryana A, Allen SL, Pujara DK, et al. Concomitant pulmonary vein and posterior wall isolation using cryoballoon with adjunct radiofrequency in persistent atrial fibrillation. JACCCEP. 2020;in press.

  44. Osório TG, Iacopino S, Coutiño HE, Ströker E, Sieira J, Salghetti F, et al. Evaluation of the luminal esophageal temperature behavior during left atrium posterior wall ablation by means of second-generation cryoballoon. J Interv Card Electrophysiol. 2019;55:191–6.

    Article  PubMed  Google Scholar 

  45. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019;74:104–32.

    Article  PubMed  Google Scholar 

  46. Aryana A, Kenigsberg DN, Kowalski M, Koo CH, Lim HW, O'Neill PG, et al. Cryo-DOSING investigators. Verification of a novel atrial fibrillation cryoablation dosing algorithm guided by time-to-pulmonary vein isolation: results from the Cryo-DOSING study (Cryoballoon-ablation DOSING based on the assessment of time-to-effect and pulmonary vein isolation guidance). Heart Rhythm. 2017;14:1319–25.

    Article  PubMed  Google Scholar 

  47. Aufderheide T. Etiology, electrophysiology, and myocardial mechanics of pulseless electrical activity. In: Cardiac arrest, the science and practice of resuscitation medicine. Second ed. New York: Cambridge University Press; 2007. p. 426–46.

    Chapter  Google Scholar 

  48. Gage AA, Baust JM, Baust JG. Experimental cryosurgery investigations in vivo. Cryobiology. 2009;59:229–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Takami M, Misiri J, Lehmann HI, Parker KD, Johnson SB, Sarmiento RI, et al. Spatial and time-course thermodynamics during pulmonary vein isolation using the second-generation cryoballoon in a canine in vivo model. Circ Arrhythm Electrophysiol. 2015;8:186–92.

    Article  PubMed  Google Scholar 

  50. Aryana A, Mugnai G, Singh SM, Pujara DK, de Asmundis C, Singh SK, et al. Procedural and biophysical indicators of durable pulmonary vein isolation during cryoballoon ablation of atrial fibrillation. Heart Rhythm. 2016;13:424–32.

    Article  PubMed  Google Scholar 

  51. Heeger CH, Tscholl V, Wissner E, Fink T, Rottner L, Wohlmuth P, et al. Acute efficacy, safety, and long-term clinical outcomes using the second-generation cryoballoon for pulmonary vein isolation in patients with a left common pulmonary vein: a multicenter study. Heart Rhythm. 2017;14:1111–8.

    Article  PubMed  Google Scholar 

  52. Ströker E, Takarada K, de Asmundis C, Abugattas JP, Mugnai G, Velagić V, et al. Second-generation cryoballoon ablation in the setting of left common pulmonary veins: procedural findings and clinical outcome. Heart Rhythm. 2017;14:1311–8.

    Article  PubMed  Google Scholar 

  53. Handler M, Fischer G, Seger M, Kienast R, Hanser F, Baumgartner C. Simulation and evaluation of freeze-thaw cryoablation scenarios for the treatment of cardiac arrhythmias. Biomed Eng Online. 2015;14:12.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Cardiovascular Services, Mercy General Hospital and Dignity Health Heart and Vascular Institute, 3941 J Street, Suite #350, Sacramento, CA, 95819, USA

    Arash Aryana & Shelley L. Allen

  2. Texas School of Public Health, Houston, TX, USA

    Deep K. Pujara

  3. Saint Thomas Heart, Nashville, TN, USA

    James H. Baker & Martin A. Espinosa

  4. UCLA Cardiac Arrhythmia Center, Los Angeles, CA, USA

    Eric F. Buch

  5. University of California Davis Medical Center, Sacramento, CA, USA

    Uma Srivatsa

  6. UCHealth Medical Center, Fort Collins, CO, USA

    Ethan Ellis

  7. Tampa Cardiac Specialists, Tampa, FL, USA

    Kevin Makati

  8. Staten Island University Hospital, Staten Island, NY, USA

    Marcin Kowalski

  9. MedStar Georgetown University Hospital and Medical Center, Washington, DC, USA

    Sung Lee

  10. Brigham and Women’s Hospital, Boston, MA, USA

    Thomas Tadros

  11. Stanford University Medical Center, Stanford, CA, USA

    Tina Baykaner

  12. Texas Cardiac Arrhythmia Institute, St. David’s Medical Center, Austin, TX, USA

    Amin Al-Ahmad & Andrea Natale

  13. Beth Israel Deaconess Medical Center, Boston, MA, USA

    André d’Avila

  14. Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA

    Luigi Di Biase

  15. Heart Center, Japan Red Cross Yokohama City Bay Hospital, Yokohama, Japan

    Kaoru Okishige

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  1. Arash Aryana
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Correspondence to Arash Aryana.

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Conflict of interest

Drs. Al-Ahmad, Aryana, Baker, Buch, Espinosa, Kowalski, Natale and Okishige have received consulting fees and speaker honoraria and Drs. Aryana has received research grants from Medtronic, Inc.

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Aryana, A., Pujara, D.K., Allen, S.L. et al. Left atrial posterior wall isolation in conjunction with pulmonary vein isolation using cryoballoon for treatment of persistent atrial fibrillation (PIVoTAL): study rationale and design. J Interv Card Electrophysiol 62, 187–198 (2021). https://doi.org/10.1007/s10840-020-00885-w

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