Comparison of catheter ablation for paroxysmal atrial fibrillation between cryoballoon and radiofrequency: a meta-analysis

  • Chao-feng Chen
  • Xiao-fei Gao
  • Xu Duan
  • Bin Chen
  • Xiao-hua Liu
  • Yi-zhou XuEmail author



The present systematic review and meta-analysis aimed to assess and compare the safety and efficacy of radiofrequency (RF) and cryoballoon (CB) ablation for paroxysmal atrial fibrillation (PAF). RF and CB ablation are two frequently used methods for pulmonary vein isolation in PAF, but which is a better choice for PAF remains uncertain.


A systematic review was conducted in Medline, PubMed, Embase, and Cochrane Library. All trials comparing RF and CB ablation were screened and included if the inclusion criteria were met.


A total of 38 eligible studies, 9 prospective randomized or randomized controlled trials (RCTs), and 29 non- RCTs were identified, adding up to 15,496 patients. Pool analyses indicated that CB ablation was more beneficial in terms of procedural time [standard mean difference = −0.58; 95% confidence interval (CI), −0.85 to −0.30], complications without phrenic nerve injury (PNI) [odds ratio (OR) = 0.79; 95% CI, 0.67–0.93; I 2 = 16%], and recrudescence (OR = 0.83; 95% CI, 0.70–0.97; I 2 = 63%) for PAF; however, the total complications of CB was higher than RF. The subgroup analysis found that, compared with non-contact force radiofrequency (non-CF-RF), both first-generation cryoballoon (CB1) and second-generation cryoballoon (CB2) ablation could reduce complications with PNI, procedural time, and recrudescence. However, the safety and efficacy of CB2 was similar to those of CF-RF.


Available overall and subgroup data suggested that both CB1 and CB2 were more beneficial than RF ablation, and the main advantages were reflected in comparing them with non-CF-RF. However, CF-RF and CB2 showed similar clinical benefits.


Clinical benefit Cryoballoon ablation Meta-analysis Paroxysmal atrial fibrillation Radiofrequency ablation 



Dr Chao-feng Chen: contributed to design of this work, statistical analysis and write the manuscript, Bin Chen: contributed to evalute quality and retrieved the required data, Xiao-fei Gao and Xiao-hua Liu: contributed to reviewed the literature, performed the selection of the studies and helped gather references for the manuscript. Dr Yi-zhou Xu: contributed to design of this work, revised and approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have reported to JICE that there was not potential conflicts of interest exist in this article.


This study was supported by authors themselves without any other funding.


There were not any ethics problems in our paper.


  1. 1.
    January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, et al. 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 practice guidelines and the Heart Rhythm Society. Circulation. 2014;130:e199–267.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Haissaguerre M, Jais 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.CrossRefPubMedGoogle Scholar
  3. 3.
    Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015;372:1812–22.CrossRefPubMedGoogle Scholar
  4. 4.
    Hunter RJ, Baker V, Finlay MC, Duncan ER, Lovell MJ, Tayebjee MH, et al. Point-by-point radiofrequency ablation versus the cryoballoon or a novel combined approach: a randomized trial comparing 3 methods of pulmonary vein isolation for paroxysmal atrial fibrillation (the cryo versus RF trial). J Cardiovasc Electrophysiol. 2015;26:1307–14.CrossRefPubMedGoogle Scholar
  5. 5.
    Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med. 2016;374:2235–45.CrossRefPubMedGoogle Scholar
  6. 6.
    Perez-Castellano N, Fernandez-Cavazos R, Moreno J, Canadas V, Conde A, Gonzalez-Ferrer JJ, et al. The COR trial: a randomized study with continuous rhythm monitoring to compare the efficacy of cryoenergy and radiofrequency for pulmonary vein isolation. Heart Rhythm : Off J Heart Rhythm Soc. 2014;11:8–14.CrossRefGoogle Scholar
  7. 7.
    Koch L, Haeusler KG, Herm J, Safak E, Fischer R, Malzahn U, et al. Mesh ablator vs. cryoballoon pulmonary vein ablation of symptomatic paroxysmal atrial fibrillation: results of the MACPAF study. Europace. 2012;14:1441–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Khoueiry Z, Albenque JP, Providencia R, Combes S, Combes N, Jourda F, et al. Outcomes after cryoablation vs. radiofrequency in patients with paroxysmal atrial fibrillation: impact of pulmonary veins anatomy. Europace. 2016;18:1343–51.CrossRefPubMedGoogle Scholar
  9. 9.
    Akerstrom F, Bastani H, Insulander P, Schwieler J, Arias MA, Jensen-Urstad M. Comparison of regular atrial tachycardia incidence after circumferential radiofrequency versus cryoballoon pulmonary vein isolation in real-life practice. J Cardiovasc Electrophysiol. 2014;25:948–52.CrossRefPubMedGoogle Scholar
  10. 10.
    Jourda F, Providencia R, Marijon E, Bouzeman A, Hireche H, Khoueiry Z, et al. Contact-force guided radiofrequency vs. second-generation balloon cryotherapy for pulmonary vein isolation in patients with paroxysmal atrial fibrillation-a prospective evaluation. Europace. 2015;17:225–31.CrossRefPubMedGoogle Scholar
  11. 11.
    Luik A, Radzewitz A, Kieser M, Walter M, Bramlage P, Hormann P, et al. Cryoballoon versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation: the prospective, randomized, controlled, noninferiority freezeAF study. Circulation. 2015;132:1311–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Pokushalov E, Romanov A, Artyomenko S, Baranova V, Losik D, Bairamova S, et al. Cryoballoon versus radiofrequency for pulmonary vein re-isolation after a failed initial ablation procedure in patients with paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 2013;24:274–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Squara F, Zhao A, Marijon E, Latcu DG, Providencia R, Di Giovanni G, et al. Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation. Europace. 2015;17:718–24.CrossRefPubMedGoogle Scholar
  14. 14.
    Wasserlauf J, Pelchovitz DJ, Rhyner J, Verma N, Bohn M, Li Z, et al. Cryoballoon versus radiofrequency catheter ablation for paroxysmal atrial fibrillation. Pacing Clin Electrophysiol: PACE. 2015;38:483–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Straube F, Dorwarth U, Ammar-Busch S, Peter T, Noelker G, Massa T, et al. First-line catheter ablation of paroxysmal atrial fibrillation: outcome of radiofrequency vs. cryoballoon pulmonary vein isolation. Europace. 2016;18:368–75.CrossRefPubMedGoogle Scholar
  16. 16.
    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.CrossRefPubMedGoogle Scholar
  17. 17.
    Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet (London, England). 1999;354:1896–900.CrossRefGoogle Scholar
  18. 18.
    Chierchia GB, Capulzini L, Droogmans S, Sorgente A, Sarkozy A, Muller-Burri A, et al. Pericardial effusion in atrial fibrillation ablation: a comparison between cryoballoon and radiofrequency pulmonary vein isolation. Europace. 2010;12:337–41.CrossRefPubMedGoogle Scholar
  19. 19.
    Defaye P, Kane A, Jacon P, Mondesert B. Cryoballoon for pulmonary vein isolation: is it better tolerated than radiofrequency? Retrospective study comparing the use of analgesia and sedation in both ablation techniques. Arch Cardiovasc Dis. 2010;103:388–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Gaita F, Leclercq JF, Schumacher B, Scaglione M, Toso E, et al. Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electrophysiol. 2011;22:961–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Herm J, Fiebach JB, Koch L, Kopp UA, Kunze C, Wollboldt C, et al. Neuropsychological effects of MRI-detected brain lesions after left atrial catheter ablation for atrial fibrillation: long-term results of the MACPAF study. Circ Arrhythmia Electrophysiol. 2013;6:843–50.CrossRefGoogle Scholar
  22. 22.
    Schmidt B, Gunawardene M, Krieg D, Bordignon S, Furnkranz A, Kulikoglu M, et al. A prospective randomized single-center study on the risk of asymptomatic cerebral lesions comparing irrigated radiofrequency current ablation with the cryoballoon and the laser balloon. J Cardiovasc Electrophysiol. 2013;24:869–74.CrossRefPubMedGoogle Scholar
  23. 23.
    Tse HF, Kwong YL, Lau CP. Transvenous cryoablation reduces platelet activation during pulmonary vein ablation compared with radiofrequency energy in patients with atrial fibrillation. J Cardiovasc Electrophysiol. 2005;16:1064–70.CrossRefPubMedGoogle Scholar
  24. 24.
    Attanasio P, Huemer M, Shokor Parwani A, Boldt LH, Mügge A, Haverkamp W, et al. Pain reactions during pulmonary vein isolation under deep sedation: cryothermal versus radiofrequency ablation. Pacing Clin Electrophysiol. 2016;39(5):452–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Antolič B, Pernat A, Cvijić M, Žižek D, Jan M, Šinkovec M. Radiofrequency catheter ablation versus balloon cryoablation of atrial fibrillation: markers of myocardial damage, inflammation, and thrombogenesis. Wien Klin Wochenschr. 2016;128(13–14):480–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Hofmann R, Honig S, Leisch F, Steinwender C. Pulmonary vein isolation with Mesh Ablator versus cryoballoon catheters: 6-month outcomes. J Interv Card Electrophysiol. 2010;29:179–85.CrossRefPubMedGoogle Scholar
  27. 27.
    Knecht S, Sticherling C, von Felten S, Conen D, Schaer B, Ammann P, et al. Long-term comparison of cryoballoon and radiofrequency ablation of paroxysmal atrial fibrillation: a propensity score matched analysis. Int J Cardiol. 2014;176:645–50.CrossRefPubMedGoogle Scholar
  28. 28.
    Kuhne M, Suter Y, Altmann D, Ammann P, Schaer B, Osswald S, et al. Cryoballoon versus radiofrequency catheter ablation of paroxysmal atrial fibrillation: biomarkers of myocardial injury, recurrence rates, and pulmonary vein reconnection patterns. Heart Rhythm: Off J Heart Rhythm Soc. 2010;7:1770–6.CrossRefGoogle Scholar
  29. 29.
    Miyazaki S, Kuroi A, Hachiya H, Nakamura H, Taniguchi H, Ichihara N, et al. Early recurrence after pulmonary vein isolation of paroxysmal atrial fibrillation with different ablation technologies—prospective comparison of radiofrequency vs. second-generation cryoballoon ablation. Circ J. 2016;80:346–53.CrossRefPubMedGoogle Scholar
  30. 30.
    Providencia R, Defaye P, Lambiase PD, Pavin D, Cebron JP, Halimi F, et al. Results from a multicentre comparison of cryoballoon vs. radiofrequency ablation for paroxysmal atrial fibrillation: is cryoablation more reproducible? Europace. 2016.Google Scholar
  31. 31.
    Kardos A, Kis Z, Som Z, Nagy Z, Foldesi C. Two-year follow-up after contact force sensing radiofrequency catheter and second-generation cryoballoon ablation for paroxysmal atrial fibrillation: a comparative single centre study. Biomed Res Int. 2016;2016:6495753.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Neumann T, Kuniss M, Conradi G, Janin S, Berkowitsch A, Wojcik M, et al. MEDAFI-Trial (Micro-embolization during ablation of atrial fibrillation): comparison of pulmonary vein isolationusing cryoballoon technique vs. radiofrequency energy. Europace. 2011;13(1):37–44.CrossRefPubMedGoogle Scholar
  33. 33.
    Herrera Siklódy C, Arentz T, Minners J, Jesel L, Stratz C, Valina CM, et al. Cellular damage, platelet activation, and inflammatory response after pulmonary vein isolation: randomized study comparing radiofrequency ablation with cryoablation. Heart Rhythm. 2012;9(2):189–96.CrossRefPubMedGoogle Scholar
  34. 34.
    Julia J, Chierchia GB, de Asmundis C, Mugnai G, Sieira J, Ciconte G, et al. Regular atrial tachycardias following pulmonary vein isolation for paroxysmal atrial fibrillation: a retrospective comparison between the cryoballoon and conventional focal tip radiofrequency techniques. J Interv Card Electrophysiol. 2015;42:161–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Linhart M, Bellmann B, Mittmann-Braun E, Schrickel JW, Bitzen A, Andrie R, et al. Comparison of cryoballoon and radiofrequency ablation of pulmonary veins in 40 patients with paroxysmal atrial fibrillation: a case–control study. J Cardiovasc Electrophysiol. 2009;20:1343–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Mugnai G, Chierchia GB, de Asmundis C, Sieira-Moret J, Conte G, Capulzini L, et al. Comparison of pulmonary vein isolation using cryoballoon versus conventional radiofrequency for paroxysmal atrial fibrillation. Am J Cardiol. 2014;113:1509–13.CrossRefPubMedGoogle Scholar
  37. 37.
    Schmidt M, Dorwarth U, Andresen D, Brachmann J, Kuck KH, Kuniss M, et al. Cryoballoon versus RF ablation in paroxysmal atrial fibrillation: results from the German Ablation Registry. J Cardiovasc Electrophysiol. 2014;25:1–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Kojodjojo P, O’Neill MD, Lim PB, Malcolm-Lawes L, Whinnett ZI, Salukhe TV, et al. Pulmonary venous isolation by atrial ablation with a large cryoballoon for treatment of paroxysmal and persistent atrial fibrillation: medium-term outcomes and non-randomised comparison with pulmonary venous isolation by radiofrequency ablation. Heart. 2010;96(17):1379–84.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Schmidt M, Dorwarth U, Andresen D, Brachmann J, Kuck K, Kuniss M. German Ablation Registry: cryoballoon versus RF ablation in paroxysmal atrial fibrillation—one year outcome data. Heart Rhythm. 2016;13(4):836–44.CrossRefPubMedGoogle Scholar
  40. 40.
    Nagy Z, Kis Z, Som Z, Földesi C, Kardos A. Catheter ablation for paroxysmal atrial fibrillation: new generation cryoballoon or contact force sensing radiofrequency ablation? Orv Hetil. 2016;157(22):849–54.CrossRefPubMedGoogle Scholar
  41. 41.
    Aryana A, Singh SM, Kowalski M, Pujara DK, Cohen AI, Singh SK, et al. Acute and long-term outcomes of catheter ablation of atrial fibrillation using the second-generation cryoballoon versus open-irrigated radiofrequency: a multicenter experience. J Cardiovasc Electrophysiol. 2015;26(8):832–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Aryana A, Singh SM, Mugnai G, de Asmundis C, Kowalski M, Pujara DK, et al. Pulmonary vein reconnection following catheter ablation of atrial fibrillation using the second-generation cryoballoon versus open-irrigated radiofrequency: results of a multicenter analysis. J Interv Card Electrophysiol. 2016.Google Scholar
  43. 43.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMedGoogle Scholar
  44. 44.
    Bowden J, Tierney JF, Copas AJ, Burdett S. Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics. BMC Med Res Methodol. 2011;11:41.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    DeVille JB, Svinarich JT, Dan D, Wickliffe A, Kantipudi C, Lim HW, et al. Comparison of resource utilization of pulmonary vein isolation: cryoablation versus RF ablation with three-dimensional mapping in the value PVI study. J Invasive Cardiol. 2014;26(6):268–72.PubMedGoogle Scholar
  46. 46.
    Furnkranz A, Brugada J, Albenque JP, Tondo C, Bestehorn K, Wegscheider K, et al. Rationale and design of FIRE AND ICE: a multicenter randomized trial comparing efficacy and safety of pulmonary vein isolation using a cryoballoon versus radiofrequency ablation with 3D-reconstruction. J Cardiovasc Electrophysiol. 2014;25:1314–20.CrossRefPubMedGoogle Scholar
  47. 47.
    Liu XH, Chen CF, Gao XF, Xu YZ. Safety and efficacy of different catheter ablations for atrial fibrillation: a systematic review and meta-analysis. Pacing Clin Electrophysiol. 2016;39(8):883–99.CrossRefPubMedGoogle Scholar
  48. 48.
    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;16.Google Scholar
  49. 49.
    Liu J, Kaufmann J, Kriatselis C, Fleck E, Gerds-Li JH. Second generation of cryoballoons can improve efficiency of cryoablation for atrial fibrillation. Pacing Clin Electrophysiol. 2015;38(1):129–35.CrossRefPubMedGoogle Scholar
  50. 50.
    Aryana A, Morkoch S, Bailey S, Lim HW, Sara R, d’Avila A, et al. Acute procedural and cryoballoon characteristics from cryoablation of atrial fibrillation using the first- and second-generation cryoballoon: a retrospective comparative study with follow-up outcomes. J Interv Card Electrophysiol. 2014;41(2):177–86.CrossRefPubMedGoogle Scholar
  51. 51.
    Kimura M, Sasaki S, Owada S, Horiuchi D, Sasaki K, Itoh T. Comparison of lesion formation between contact force-guided and non-guided circumferential pulmonary vein isolation: a prospective, randomized study. Heart Rhythm. 2014;11:984–91.CrossRefPubMedGoogle Scholar
  52. 52.
    Marijon E, Fazaa S, Narayanan K, Guy-Moyat B, Bouzeman A, Providencia R, et al. Real-time contact force sensing for pulmonary vein isolation in the setting of paroxysmal atrial fibrillation: procedural and 1-year results. J Cardiovasc Electrophysiol. 2014;25:130–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Yokoyama K, Nakagawa H, Shah DC, Lambert H, Leo G, Aeby N, et al. Novel contact force sensor incorporated in irrigated radiofrequency ablation catheter predicts lesion size and incidence of steam pop and thrombus. Circ Arrhythm Electrophysiol. 2008;1:354–62.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Chao-feng Chen
    • 1
  • Xiao-fei Gao
    • 1
  • Xu Duan
    • 1
  • Bin Chen
    • 1
  • Xiao-hua Liu
    • 1
  • Yi-zhou Xu
    • 1
    • 2
    Email author
  1. 1.Hangzhou First People’s HospitalNanjing Medical University, Zhejiang Chinese Medical UniversityHangzhouChina
  2. 2.Department of CardiologyHangzhou Hospital of Nanjing Medical UniversityHangzhouChina

Personalised recommendations