Clinical Research in Cardiology

, Volume 107, Issue 7, pp 570–577 | Cite as

Safety and efficacy of persistent atrial fibrillation ablation using the second-generation cryoballoon

  • Kivanc Yalin
  • Amr Abdin
  • Evgeny Lyan
  • Noureddin Sawan
  • Spyridon Liosis
  • Christian Elsner
  • Alexander Jobs
  • Ben Brüggemann
  • Jelena Koester
  • Ingo Eitel
  • Charlotte Eitel
  • Roland Richard Tilz
Original Paper



The second-generation cryoballoon (CB) is increasingly used for treatment of persistent atrial fibrillation (AF). Data regarding the clinical outcome and mechanism of arrhythmia recurrence following persistent AF ablation using CB is sparse. In this study, we aimed to assess the efficacy of CB and mechanisms of atrial tachyarrhythmia (ATA) recurrence in patients with persistent AF.

Methods and results

A total of 133 patients (66 ± 10 years, 60% male) with symptomatic persistent AF, who were scheduled for PVI using the second-generation CB were enrolled. Follow-up included 24 h Holter recording at 3, 6 and 12 months. Any documented episode of ATA lasting more than 30 s was considered as a recurrent arrhythmic event. All targeted veins were isolated (100%). Phrenic nerve palsy with recovery during follow-up occurred in six patients (4.5%), no patient experienced tamponade or a cerebrovascular event. During 12.6 ± 5.4 months of follow-up, 89/133 (67%) patients were free of ATA recurrences. Multivariable analysis revealed recurrence in the blanking period (HR 11.46, 0.95 CI 3.92–33.49, p < 0.001), presence of cardiomyopathy (HR 2.75, 0.95 CI 1.09–6.96, p = 0.032) and PV abnormality (HR 3.56, 0.95 CI 1.21–10.43, p = 0.021) as predictors for late recurrence.


In patients with persistent AF, second-generation cryoballoon use is associated with an excellent safety profile and favorable outcomes. Arrhythmia recurrence during the blanking period, presence of cardiomyopathy and PV abnormality were independent predictors of long-term AF recurrence.


Persistent atrial fibrillation Cryoballoon ablation 



Atrial tachyarrhythmia


Atrial fibrillation






Cavotricuspid isthmus


European Heart Rhythm Association


Implantable cardioverter defibrillator


International normalized ratio


Left atrium


Left common pulmonary vein


Left inferior pulmonary vein


Left superior pulmonary vein


Left ventricular ejection fraction




Phrenic nerve palsy


Pulmonary vein


Pulmonary vein isolation


Right inferior pulmonary vein


Right middle pulmonary vein


Right superior pulmonary vein




Sinus rhythm



K. Yalin recieved research and educational grant from Turkish Society of Cardiology. E. Lyan received travel grants and Speaker’s Bureau Honoraria from Biosense Webster, Medtronic, Boston Scientific. R. Tilz received travel grants from St. Jude Medical, Topera, Biosense Webster, Daiichi Sankyo, Sentrheart and Speaker’s Bureau Honoraria from Biosense Webster, Biotronik, Pfizer, Topera, Bristol-Myers Squibb; Bayer, Sanofi Aventis.


  1. 1.
    Paulus Kirchhof, Authors/Task Force Members; Stefano Benussi, Authors/Task Force Members; Dipak Kotecha, Authors/Task Force Members; Anders Ahlsson, Authors/Task Force Members; Dan Atar, Authors/Task Force Members; Barbara Casadei, Authors/Task Force Members; Manuel Castella, Authors/Task Force Members; Hans-Christoph Diener, Authors/Task Force Members; Hein Heidbuchel, Authors/Task Force Members; Jeroen Hendriks, Authors/Task Force Members; Gerhard Hindricks, Authors/Task Force Members; Antonis S. Manolis, Authors/Task Force Members; Jonas Oldgren, Authors/Task Force Members; Bogdan Alexandru Popescu, Authors/Task Force Members; Ulrich Schotten, Authors/Task Force Members; Bart Van Putte, Authors/Task Force Members; Panagiotis Vardas, Authors/Task Force Members; Stefan Agewall, Document Reviewers; John Camm, Document Reviewers; Gonzalo Baron Esquivias, Document Reviewers; Werner Budts, Document Reviewers; Scipione Carerj, Document Reviewers; Filip Casselman, Document Reviewers; Antonio Coca, Document Reviewers; Raffaele De Caterina, Document Reviewers; Spiridon Deftereos, Document Reviewers; Dobromir Dobrev, Document Reviewers; José M. Ferro, Document Reviewers; Gerasimos Filippatos, Document Reviewers; Donna Fitzsimons, Document Reviewers; Bulent Gorenek, Document Reviewers; Maxine Guenoun, Document Reviewers; Stefan H. Hohnloser, Document Reviewers; Philippe Kolh, Document Reviewers; Gregory Y. H. Lip, Document Reviewers; Athanasios Manolis, Document Reviewers; John McMurray, Document Reviewers; Piotr Ponikowski, Document Reviewers; Raphael Rosenhek, Document Reviewers; Frank Ruschitzka, Document Reviewers; Irina Savelieva, Document Reviewers; Sanjay Sharma, Document Reviewers; Piotr Suwalski, Document Reviewers; Juan Luis Tamargo, Document Reviewers; Clare J. Taylor, Document Reviewers; Isabelle C. Van Gelder, Document Reviewers; Adriaan A. Voors, Document Reviewers; Stephan Windecker, Document Reviewers; Jose Luis Zamorano, Document Reviewers; Katja Zeppenfeld, Document Reviewers; 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37(38):2893–2962Google Scholar
  2. 2.
    Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR et al (2016) Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med 374:2235–2245CrossRefPubMedGoogle Scholar
  3. 3.
    Metzner A, Reissmann B, Rausch P, Mathew S, Wohlmuth P, Tilz R et al (2014) One-year clinical outcome after pulmonary vein isolation using the second-generation 28-mm cryoballoon. Circ Arrhythm Electrophysiol 7:288–292CrossRefPubMedGoogle Scholar
  4. 4.
    Tilz RR, Chun KR, Schmidt B, Fuemkranz A, Wissner E, Koester I et al (2010) Catheter ablation of long-standing persistent atrial fibrillation: a lesson from circumferential pulmonary vein isolation. J Cardiovasc Electrophysiol 21:869–874CrossRefPubMedGoogle Scholar
  5. 5.
    Lin T, Rillig A, Bucur T, Metzner A, Mathew S, Wissner E et al (2016) Focal impulse and rotor modulation using the novel 64-electrode basket catheter: electrogram characteristics of human rotors. Europace 17:1791–1797CrossRefGoogle Scholar
  6. 6.
    Rostock T, Salukhe TV, Steven D, Drewitz I, Hoffmann BA, Bock K et al (2011) Long-term single- and multiple-procedure outcome and predictors of success after catheter ablation for persistent atrial fibrillation. Heart Rhythm 8:1391–1397CrossRefPubMedGoogle Scholar
  7. 7.
    Scherr D, Khairy P, Miyazaki S, Aurillac-Lavignolle V, Pascale P, Wilton SB et al (2015) Five-year outcome of catheter ablation of persistent atrial fibrillation using termination of atrial fibrillation as a procedural endpoint. Circ Arrhythm Electrophysiol 8:18–24CrossRefPubMedGoogle Scholar
  8. 8.
    Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, Macle L, Morillo CA, Haverkamp W, Weerasooriya R, Albenque JP, Nardi S, Menardi E, Novak P, Sanders P (2015) STAR AF II Investigators. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 372:1812–1822CrossRefPubMedGoogle Scholar
  9. 9.
    Fürnkranz A, Bordignon S, Schmidt B, Gunawardene M, Schulte-Hahn B, Urban V et al (2013) Improved procedural efficacy of pulmonary vein isolation using the novel second-generation cryoballoon. J Cardiovasc Electrophysiol 24:492–497CrossRefPubMedGoogle Scholar
  10. 10.
    Di Giovanni G, Wauters K, Chierchia GB, Sieira J, Levinstein M, Conte G et al (2014) One-year follow-up after single procedure cryoballoon ablation: a comparison between the first and second generation balloon. J Cardiovasc Electrophysiol 25:834–839CrossRefPubMedGoogle Scholar
  11. 11.
    Ciconte G, Baltogiannis G, de Asmundis C, Sieira J, Conte G, Di Giovanni G et al (2015) Circumferential pulmonary vein isolation as index procedure for persistent atrial fibrillation: a comparison between radiofrequency catheter ablation and second-generation cryoballoon ablation. Europace 17:559–565CrossRefPubMedGoogle Scholar
  12. 12.
    Koektuerk B, Yorgun H, Hengeoez O, Turan CH, Dahmet A, Yang A et al (2015) Cryoballoon ablation for pulmonary vein isolation in patients with persistent atrial fibrillation: one-year outcome using second generation cryoballoon. Circ Arrhythm Electrophysiol 8(5):1073–1079CrossRefPubMedGoogle Scholar
  13. 13.
    Lemes C, Wissner E, Lin T, Mathew S, Deiss S, Rillig A et al (2016) One-year clinical outcome after pulmonary vein isolation in persistent atrial fibrillation using the second-generation 28 mm cryoballoon: a retrospective analysis. Europace 18:201–205CrossRefPubMedGoogle Scholar
  14. 14.
    Koutalas E, Rolf S, Dinov B, Richter S, Arya A, Bollmann A, Hindricks G, Sommer P (2015) Contemporary mapping techniques of complex cardiac arrhythmias—identifying and modifying the arrhythmogenic substrate. Arrhythm Electrophysiol Rev 4:19–27CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Aytemir K, Oto A, Canpolat U, Sunman H, Yorgun H, Şahiner L, Kaya EB (2013) Immediate and medium-term outcomes of cryoballoon-based pulmonary vein isolation in patients with paroxysmal and persistent atrial fibrillation: single-centre experience. J Interv Card Electrophysiol 38:187–195CrossRefPubMedGoogle Scholar
  16. 16.
    Metzner A, Heeger CH, Wohlmuth P, Reißmann B, Rillig A, Tilz RR, Mathew S, Lemes C, Deiß S, Maurer T, Saguner A, Ouyang F, Kuck KH, Wißner E (2016) Two-year outcome after pulmonary vein isolation using the second-generation 28-mm cryoballoon: lessons from the bonus freeze protocol. Clin Res Cardiol 105(1):72–78CrossRefPubMedGoogle Scholar
  17. 17.
    Guhl EN, Siddoway D, Adelstein E, Voigt A, Saba S, Jain SK (2016) Efficacy of cryoballoon pulmonary vein isolation in patients with persistent atrial fibrillation. J Cardiovasc Electrophysiol 27:423–427CrossRefPubMedGoogle Scholar
  18. 18.
    Omran H, Gutleben KJ, Molatta S, Fischbach T, Wellmann B, Horstkotte D, Körber B, Nölker G (2018) Second generation cryoballoon ablation for persistent atrial fibrillation: an updated meta-analysis. Clin Res Cardiol 107:182–192CrossRefPubMedGoogle Scholar
  19. 19.
    Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG; STOP AF Cryoablation Investigators. 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):1713–1723CrossRefPubMedGoogle Scholar
  20. 20.
    Sohns C, Sohns JM, Bergau L, Sossalla S, Vollmann D, Lüthje L et al (2013) Pulmonary vein anatomy predicts freedom from atrial fibrillation using remote magnetic navigation for circumferential pulmonary vein ablation. Europace 15:1136–1142CrossRefPubMedGoogle Scholar
  21. 21.
    Heeger CH, Tscholl V, Wissner E, Fink T, Rottner L, Wohlmuth P et al (2017) 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 14:1111–1118CrossRefPubMedGoogle Scholar
  22. 22.
    Shigeta T, Okishige K, Yamauchi Y, Aoyagi H, Nakamura T, Yamashita M et al (2017) Clinical assessment of cryoballoon ablation in cases with atrial fibrillation and a left common pulmonary vein. J Cardiovasc Electrophysiol 28(9):1021–1027CrossRefPubMedGoogle Scholar
  23. 23.
    Guler TE, Aksu T, Yalin K, Golcuk SE, Mutluer FO, Bozyel S (2017) Combined cryoballoon and radiofrequency ablation versus alone radiofrequency ablation for long-standing atrial fibrillation. Am J Med Sci (epub of print)Google Scholar
  24. 24.
    Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ, Miller JM (2012) Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (conventional ablation for atrial fibrillation with or without focal impulse and rotor modulation) trial. J Am Coll Cardiol 60:628–636CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Yorgun H, Aytemir K, Canpolat U, Şahiner L, Kaya EB, Oto A (2014) Additional benefit of cryoballoon-based atrial fibrillation ablation beyond pulmonary vein isolation: modification of ganglionated plexi. Europace 16:645–651CrossRefPubMedGoogle Scholar
  26. 26.
    Guhl EN, Siddoway D, Adelstein E, Bazaz R, Mendenhall GS, Nemec J, Saba S, Schwartzman D, Voigt A, Wang NC, Jain SK (2016) Incidence and predictors of complications during cryoballoon pulmonary vein isolation for atrial fibrillation. J Am Heart Assoc 5(7).
  27. 27.
    Metzner A, Rausch P, Lemes C, Reissmann B, Bardyszewski A, Tilz R et al (2014) The incidence of phrenic nerve injury during pulmonary vein isolation using the second-generation 28 mm cryoballoon. J Cardiovasc Electrophysiol 25(5):466–470CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kivanc Yalin
    • 1
    • 2
  • Amr Abdin
    • 1
  • Evgeny Lyan
    • 1
  • Noureddin Sawan
    • 1
  • Spyridon Liosis
    • 1
  • Christian Elsner
    • 1
  • Alexander Jobs
    • 1
  • Ben Brüggemann
    • 1
  • Jelena Koester
    • 1
  • Ingo Eitel
    • 1
  • Charlotte Eitel
    • 1
  • Roland Richard Tilz
    • 1
  1. 1.Department of Cardiology, Angiology and Intensive Care Medicine, University Heart Center Luebeck, Medical Clinic IIUniversity Hospital Schleswig-HolsteinLuebeckGermany
  2. 2.Department of Cardiology, Faculty of MedicineUsak UniversityUsakTurkey

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