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Dosing of the second-generation cryoballoon using acute time-to-pulmonary vein isolation as an indicator of durable ablation in a canine model

  • Wilber Su
  • Nicolas Coulombe
  • Nicole Kirchhof
  • Erin Grassl
  • Dan Wittenberger
Article
  • 117 Downloads

Abstract

Background

Rigid time-based dosing protocol(s) currently used in the clinic for cryoballoon ablation of atrial fibrillation may be inadequate to guide the circumferential and transmural cryothermal energy transfer across the pulmonary vein (PV) and may result in injury to collateral tissues or electrical gaps between the PV and left atrium (LA).

Objective

A physiologic endpoint (e.g., acute time-to-PV isolation a.k.a. time-to-effect; TTE) may be effective in the determination of a transmural lesion formation and may allow for individualized ablation dosing across each PV.

Methods

Thirty PVs from 15 dogs were randomized into five dosing protocols, including (1) TTE + 60 s, (2) TTE + 90 s, (3) TTE + 120 s, (4) TTE + 150 s, and (5) 2 × 180 s. Ablations were conducted with a 23-mm second-generation cryoballoon, and TTE was assessed during a freeze by pacing from an inner balloon-lumen circular diagnostic catheter to a quadripolar diagnostic catheter in the coronary sinus. After ablation, animals were survived for 30 to 34 days, and repeat electrophysiology assessment of PV isolation was conducted after which animals were euthanized for gross anatomy and histological examination.

Results

At study termination, efficacy endpoint evaluations were based on maintenance of PV electrical isolation, gross anatomy assessment of PV lesions, and histological examination of PVs. Five efficacy endpoint failures were noted, including the following: 1 PV in the TTE + 90 sec group; 2 PVs in the TTE + 120 sec group; 1 PV in the TTE + 150 s group; and 1 PV in the 2 × 180 s group. Regarding safety, one phrenic nerve injury was observed in the 2 × 180 s cohort. No other complications were observed.

Conclusions

In a canine model, effective PV isolation could be found even in the shortest duration dosing cohort (TTE + 60 s). One complication (phrenic nerve injury) was observed in the longest duration dosing group (2 × 180 s). Further studies will be required to correlate these results to a 28-mm cryoballoon (more commonly used in the cryoablation of a human LA); however, to date, this is the first reporting of a successful cryoablation using TTE + 60 s dosing (approximately 90 s total duration of freezing).

Keywords

Arrhythmia Atrial fibrillation Catheter ablation Cryoablation Cryoballoon Pulmonary vein isolation Time-to-effect 

Abbreviations

AF

atrial fibrillation

LA

left atrium

PNI

phrenic nerve injury

PV

pulmonary vein

PVI

pulmonary vein isolation

TTE

time-to-effect

Notes

Acknowledgements

The authors would like to thank Hae Lim for helping in the manuscript preparation.

Compliance with ethical standards

Financial support

This study was funded by Medtronic, Inc.

Conflict of interest

Dr. Wilber Su is a consultant for Medtronic Inc. Nicolas Coulombe, Nicole Kirchhof, Erin Grassl, and Dan Wittenberger are employees of Medtronic, Inc.

References

  1. 1.
    Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial. J Am Coll Cardiol. 2013;61(16):1713–23.CrossRefPubMedGoogle Scholar
  2. 2.
    Cardoso R, Mendirichaga R, Fernandes G, Healy C, Lambrakos LK, Viles-Gonzalez JF, et al. Cryoballoon versus radiofrequency catheter ablation in atrial fibrillation: a meta-analysis. J Cardiovasc Electrophysiol. 2016;27(10):1151–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Garg J, Chaudhary R, Palaniswamy C, Shah N, Krishnamoorthy P, Bozorgnia B, et al. Cryoballoon versus radiofrequency ablation for atrial fibrillation: a meta-analysis of 16 clinical trials. J Atr Fibrillation. 2016;9(3):1429–38.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Mugnai G, de Asmundis C, Velagic V, Hünük B, Ströker E, Wauters K, et al. Phrenic nerve injury during ablation with the second-generation cryoballoon: analysis of the temperature drop behaviour in a large cohort of patients. Europace. 2016;18(5):702–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Andrade JG, Dubuc M, Ferreira J, Guerra PG, Landry E, Coulombe N, et al. Histopathology of cryoballoon ablation-induced phrenic nerve injury. J Cardiovasc Electrophysiol. 2014;25(2):187–94.CrossRefPubMedGoogle Scholar
  6. 6.
    Straube F, Dorwarth U, Hartl S, Bunz B, Wankerl M, Ebersberger U, et al. Outcome of paroxysmal atrial fibrillation ablation with the cryoballoon using two different application times: the 4- versus 3-min protocol. J Interv Card Electrophysiol. 2016;45(2):169–77.CrossRefPubMedGoogle Scholar
  7. 7.
    Miyazaki S, Hachiya H, Nakamura H, Taniguchi H, Takagi T, Hirao K, et al. Pulmonary vein isolation using a second-generation cryoballoon in patients with paroxysmal atrial fibrillation: one-year outcome using a single big-balloon 3-minute freeze technique. J Cardiovasc Electrophysiol. 2016;27(12):1375–80.CrossRefPubMedGoogle Scholar
  8. 8.
    Chun KR, Stich M, Fürnkranz A, Bordignon S, Perrotta L, Dugo D, et al. Individualized cryoballoon energy pulmonary vein isolation guided by real-time pulmonary vein recordings, the randomized ICE-T trial. Heart Rhythm. 2017;14(4):495–500.CrossRefPubMedGoogle Scholar
  9. 9.
    Aryana A, Kenigsberg DN, Kowalski M, Koo CH, Lim HW, O'Neill PG, et al. 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(9):1319–25.CrossRefPubMedGoogle Scholar
  10. 10.
    Su W, Kowal R, Kowalski M, Metzner A, Svinarich JT, Wheelan K, et al. Best practice guide for cryoballoon ablation in atrial fibrillation: the compilation experience of more than 3000 procedures. Heart Rhythm. 2015;12(7):1658–66.CrossRefPubMedGoogle Scholar
  11. 11.
    Heeger CH, Wissner E, Mathew S, Hayashi K, Sohns C, Reißmann B, et al. Short tip-big difference? First-in-man experience and procedural efficacy of pulmonary vein isolation using the third-generation cryoballoon. Clin Res Cardiol. 2016;105(6):482–8.CrossRefPubMedGoogle Scholar
  12. 12.
    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(2):424–32.CrossRefPubMedGoogle Scholar
  13. 13.
    Coulombe N, Paulin J, Su W. Improved in vivo performance of second-generation cryoballoon for pulmonary vein isolation. J Cardiovasc Electrophysiol. 2013;24(8):919–25.CrossRefPubMedGoogle Scholar
  14. 14.
    Neumann T, Vogt J, Schumacher B, Dorszewski A, Kuniss M, Neuser H, et al. Circumferential pulmonary vein isolation with the cryoballoon technique results from a prospective 3-center study. J Am Coll Cardiol. 2008;52(4):273–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Ottaviano L, Chierchia GB, Bregasi A, Bruno N, Antonelli A, Alsheraei AT, et al. Cryoballoon ablation for atrial fibrillation guided by real-time three-dimensional transoesophageal echocardiography: a feasibility study. Europace. 2013;15(7):944–50.CrossRefPubMedGoogle Scholar
  16. 16.
    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(1):186–92.CrossRefPubMedGoogle Scholar
  17. 17.
    Ghosh J, Martin A, Keech AC, Chan KH, Gomes S, Singarayar S, et al. Balloon warming time is the strongest predictor of late pulmonary vein electrical reconnection following cryoballoon ablation for atrial fibrillation. Heart Rhythm. 2013;10(9):1311–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Goldberger JJ, Mitrani RD. Cryoballoon ablation for atrial fibrillation: double jeopardy? J Cardiovasc Electrophysiol. 2016;27(12):1381–3.CrossRefPubMedGoogle Scholar
  19. 19.
    John RM, Kapur S, Ellenbogen KA, Koneru JN. Atrioesophageal fistula formation with cryoballoon ablation is most commonly related to the left inferior pulmonary vein. Heart Rhythm. 2017;14(2):184–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Banner University Medical Center- Phoenix and University of ArizonaPhoenixUSA
  2. 2.Medtronic CryoCathPointe-ClaireCanada
  3. 3.Medtronic Physiology Research LaboratoriesMinneapolisUSA

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