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



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).


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.


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.


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.


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).


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



atrial fibrillation


left atrium


phrenic nerve injury


pulmonary vein


pulmonary vein isolation





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.


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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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