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Radiofrequency Ablation as Initial Therapy in Paroxysmal Atrial Fibrillation
Open accessAbstract
BACKGROUND: There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. METHODS: We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. RESULTS: There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. CONCLUSIONS: In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).
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“Catheter ablation or combination therapy is often effective when antiarrhythmic drugs fail.226,[585][586][587]”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [585]
In the citing paper
“AF ablation, when performed in experienced centres by adequately trained teams, is more effective than antiarrhythmic drug therapy in maintaining sinus rhythm, and the complication rate, though not negligible, is similar to the complication rate for antiarrhythmic drugs.585,717,1042”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [585]
In the citing paper
“AF ablation, when performed in experienced centres by adequately trained teams, is more effective than antiarrhythmic drug therapy in maintaining sinus rhythm, and the complication rate, though not negligible, is similar to the complication rate for antiarrhythmic drugs.585,717,1042”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [585]
In the citing paper
“Complication rates were similar, but ablation was performed in expert centres, justifying catheter ablation as first-line therapy in selected patients with paroxysmal AF who ask for interventional therapy.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [585]
In the citing paper
“As first-line treatment for paroxysmal AF, randomized trials showed only modestly improved rhythm outcome with catheter ablation compared to antiarrhythmic drug therapy.585,[721][722][723]”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [585]
In the citing paper
“Isthmus ablation is comparably safe and more effective than antiarrhythmic drug therapy, and is recommended for recurrent atrial flutter.[585][586][587]713”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [585]
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“In two RF studies, additional ablation lesion was also allowed at the physician’s discretion [MANTRA-PAF (11) and RAAFT-2 (12)], while in Cryo-FIRST study, additional freeze applications were allowed in case of incomplete PVI isolation or focal trigger identification (16).”
BackgroundMethodResultInfluentialWatanabe, R., Nagashima, K., Wakamatsu, Y., Otsuka, N., Yokoyama, K., Matsumoto, N., Otsuka, T., Suzuki, S. S., Hirata, A., Murakami, M., et al. (2021) · Circulation Journal · doi:10.1253/circj.cj-21-0326 · Cited by 33
Kupó, P., Riesz, T., Sághy, L., Vámos, M., Bencsik, G., Makai, A., Kohári, M., Benak, A., Miklós, M., & Pap, R. (2023) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.15893 · Cited by 33
Is pulmonary vein isolation still the cornerstone in atrial fibrillation ablation?
Bunch, T. J., & Cutler, M. J. (2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2072-1439.2014.12.46 · Cited by 33
Pedrote, A. A., Arana‐Rueda, E., García‐Riesco, L., Sánchez-Brotons, J. A., DURÁN‐GUERRERO, M., Gómez‐Pulido, F., Arce‐León, Á., & Frutos‐López, M. (2013) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.12190 · Cited by 32
Avoiding permanent atrial fibrillation: treatment approaches to prevent disease progression
Curtis, A. B., & Shukla (2013) · Vascular Health and Risk Management · doi:10.2147/vhrm.s49334 · Cited by 34
Kraft, M., Büscher, A., Wiedmann, F., L’hoste, Y., Haefeli, W. E., Frey, N., Katus, H. A., & Schmidt, C. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.638445 · Cited by 31
Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation
Andrade, J. G., Turgeon, R. D., Macle, L., & Deyell, M. W. (2022) · European Cardiology Review · doi:10.15420/ecr.2021.38 · Cited by 33
Srivatsa, U. N., Danielsen, B. H., Anderson, I., Amsterdam, E. A., Pezeshkian, N. G., Yang, Y., & White, R. H. R. (2014) · Heart Rhythm · doi:10.1016/j.hrthm.2014.07.017 · Cited by 32
Kim, H. J., Kim, J. S., & Kim, T. S. (2016) · Interactive Cardiovascular and Thoracic Surgery · doi:10.1093/icvts/ivw027 · Cited by 32
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Novel Perspectives on Arrhythmia-Induced Cardiomyopathy
Rocca, D. G. D., Santini, L., Forleo, G. B., Sanniti, A., Prete, A. D., Lavalle, C., Biase, L. D., Natale, A., & Romeo, F. (2014) · Cardiology in Review · doi:10.1097/crd.0000000000000040 · Cited by 31
Lupercio, F. A., Lin, A., Aldaas, O. M., Romero, J. E., Briceno, D. F., Hoffmayer, K. S., Han, F. T., Biase, L. D., Feld, G. K., & Hsu, J. C. (2019) · Journal of Interventional Cardiac Electrophysiology · doi:10.1007/s10840-019-00634-8 · Cited by 30
Exposure-Based Therapy for Symptom Preoccupation in Atrial Fibrillation: An Uncontrolled Pilot Study
Särnholm, J., Skúladóttir, H., Rück, C., Pedersen, S. S., Braunschweig, F., & Ljótsson, B. (2017) · Behavior Therapy · doi:10.1016/j.beth.2017.06.001 · Cited by 30
“…(antiarrhythmics and ablation) that aim to restore normal cardiac rhythm fail to eliminate AF in a substantial proportion of patients, do not affect patients’ prognosis, and are associated with potentially serious complications and side effects (Cosedis Nielsen et al., 2012; Morillo et al., 2014).”
BackgroundPulsed Field Ablation of Atrial Fibrillation: A Comprehensive Review
Matos, C. D., Hoyos, C., Miranda‐Arboleda, A. F., Díaz, J. C., Hincapie, D., Patiño, C., Hernadez, R. H., Zei, P. C., Romero, J. E., & Osorio, J. (2023) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2411337 · Cited by 29
Janosi, K.-F., Debreceni, D., Janosa, B., Bocz, B., Símor, T., & Kupó, P. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1033755 · Cited by 28
Wasmer, K., BREITHARDT, G. E., & Eckardt, L. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu113 · Cited by 29
Dinshaw, L., Schäffer, B., Akbulak, Ö., Jularic, M., Hartmann, J., Klatt, N., Dickow, J., Gunawardene, M., Münkler, P., Hakmi, S., et al. (2019) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.13890 · Cited by 28
“Catheter ablation (CA) is increasingly becoming the therapy of choice of symptomatic atrial fibrillation (AF).(1,2) Frequently, patients with a cardiac implantable electronic device (CIED) including transvenous leads (TVL) undergo CA.”
BackgroundEffects of Inflammatory Cell Death Caused by Catheter Ablation on Atrial Fibrillation
Liu, D., Li, Y., & Zhao, Q. (2023) · Journal of Inflammation Research · doi:10.2147/jir.s422002 · Cited by 27
Multimorbidity in Older Adults with Atrial Fibrillation
Chen, M. A. (2016) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2016.01.001 · Cited by 27
Hindricks, G., Shamloo, A. S., Lenarczyk, R., Kalarus, Z. F., Arya, A., Kircher, S., Darma, A., & Dagres, N. (2018) · Kardiologia Polska · doi:10.5603/kp.a2018.0216 · Cited by 27
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Hindricks, G., Potpara, T., Dagres, N., Arbelo, E., Bax, J. J., Blomström‐Lundqvist, C., Boriani, G., Castellà, M., Dan, G., Dilaveris, P., et al. (2021) · Revista Española de Cardiología · doi:10.1016/j.recesp.2020.10.022 · Cited by 33
JCS / JHRS 2024 Guideline Focused Update on Management of Cardiac Arrhythmias
Iwasaki, Y., Noda, T., Akao, M., Fujino, T., Hirano, T., Inoue, K., Kusano, K., Nagai, T., Satomi, K., Shinohara, T., et al. (2025) · Journal of Arrhythmia · doi:10.1002/joa3.70033 · Cited by 28
Liu, G., Long, M., Hu, X., Hu, C., & Du, Z. (2020) · Heart Lung and Circulation · doi:10.1016/j.hlc.2020.10.010 · Cited by 28
Särnholm, J., Skúladóttir, H., Rück, C., Klavebäck, S., Ólafsdóttir, E., Pedersen, S. S., Braunschweig, F., & Ljótsson, B. (2021) · JMIR Cardio · doi:10.2196/24524 · Cited by 25
Benefits of early rhythm control of atrial fibrillation
Eckardt, L., Wolfes, J., & Frommeyer, G. (2023) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2023.04.001 · Cited by 27
Fekete, M., Liotta, E. M., Molnár, T., Fülöp, G., & Lehoczki, A. (2024) · GeroScience · doi:10.1007/s11357-024-01290-1 · Cited by 27
Electrocardiographic Predictors of Incident Atrial Fibrillation
Nguyen, K. T., Vittinghoff, E., Dewland, T. A., Mandyam, M. C., Stein, P. K., Soliman, E. Z., Heckbert, S. R., & Marcus, G. M. (2016) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2016.06.008 · Cited by 25
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Optimal Rhythm Control Strategy in Patients With Atrial Fibrillation
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Chua, W., Khashaba, A., Canagarajah, H., Nielsen, J. C., Biase, L. D., Hæusler, K. G., Hindricks, G., Mont, L., Piccini, J. P., Schnabel, R. B., et al. (2024) · EP Europace · doi:10.1093/europace/euae028 · Cited by 27
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Flecainide acetate for the treatment of atrial and ventricular arrhythmias
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“ablative techniques, operator experience, clinical parameters, and strategy of follow-up [10].”
Background
Metadata
- Authors
- Cosedis Nielsen, J., Johannessen, A., Raatikainen, P., Hindricks, G., Walfridsson, H., Kongstad, O., Pehrson, S., Englund, A., Hartikainen, J., Mortensen, L. S., & Hansen, P. S.
- Affiliations
- Gentofte Hospital (DK)
- Tampere University Hospital (FI)
- University Hospital Leipzig (DE)
- Linköping University Hospital (SE)
- Skåne University Hospital (SE)
- Rigshospitalet (DK)
- Örebro University Hospital (SE)
- Kuopio University Hospital (FI)
- Aarhus University Hospital (DK)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-10-25
- Volume
- 367
- Issue
- 17
- Pages
- 1587-1595
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2164489173
- Cited by
- 720
- References
- 26
- Citations by year
- 2026: 18 · 2025: 42 · 2024: 60 · 2023: 33 · 2022: 73 · 2021: 79 · 2020: 58 · 2019: 39 · 2018: 38 · 2017: 50 · 2016: 53 · 2015: 44 · 2014: 68 · 2013: 54 · 2012: 8
- FWCI
- 35.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Funders
- Sanofi
- Hjerteforeningen (05-4-B284-A466-22237)
- Foundation for Cardiovascular Research
- Sydäntutkimussäätiö
- St. Jude Medical
- Biosense Webster
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Keywords
- paroxysmal atrial fibrillation, radiofrequency catheter ablation, antiarrhythmic drugs, class Ic antiarrhythmic drugs, class III antiarrhythmic agents, first-line therapy, arrhythmia burden, symptomatic atrial fibrillation, cardiac tamponade
- MeSH terms
- Aged, Anti-Arrhythmia Agents, Atrial Fibrillation, Atrial Flutter, Female, Flecainide, Follow-Up Studies, Humans, Male, Middle Aged, Propafenone, Quality of Life, Electrocardiography, Ambulatory, Treatment Outcome, Catheter Ablation, Cost of Illness, Statistics, Nonparametric, Intention to Treat Analysis
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