Is it time for first line ablation in early paroxysmal AF?

Take Home Messages
  • Atrial Fibrillation is associated with mortality, adverse clinical outcomes and has large economic and societal effects.
  • Although rhythm control is not superior to rate control for all patients for mortality, latest evidence suggests the subgroup of early AF does benefit to a greater extent from rhythm control.
  • Time in sinus rhythm is associated with improved mortality and morbidity
  • The most optimal therapy to maintain SR is catheter ablation, and evidence for its use first line is building

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting just under 1.5 million people in the United Kingdom.1 AF is associated with increased risks of death2, stroke3, heart failure4, dementia5, decreased quality of life6,7 and places large financial and societal cost on the NHS8. Consequently, a significant amount of research has been conducted investigating the optimal strategy to treat AF.

These treatment strategies are historically divided into rate and rhythm control. The landmark AFFIRM trial comparing these strategies concluded there was no mortality benefit to pursuing rhythm control9. Consequently, rhythm control has been reserved for treating symptomatic patients refractory to rate control . However, recent research has shown the condition is more complicated, and certain patient groups benefit more from rhythm control. The EAST-AFNET4 trial recently showed patients experiencing ‘early AF,’ that is a history of less than 1 year, to be one of these groups10.

Catheter ablation is an effective strategy to maintain sinus rhythm (SR). It can be performed in two ways: radiofrequency or cryo- ablation (effectively hot or cold therapy). In this article, I shall discuss the argument that it is time catheter ablation should be considered a first line treatment for early AF .

AF Is A Progressive Disease

On a pathophysiological level, AF leads to multi-level changes including intracellular calcium dysregulation, and electrical, structural and autonomic nervous system remodelling11. These pathological changes are progressive, making episodes of AF more frequent and longer. This pre-clinical concept of ‘AF begets AF’ was initially demonstrated in seminal experimental work by Wijffels et al. when the authors showed longer durations of rapid atrial pacing (to assimilate and initiate AF) in goats lead to longer AF maintenance once pacing was discontinued12.

‘AF begets AF’ is a concept seen clinically too. Progression is noted through increasing AF burden in paroxysmal AF (PAF), before eventually changing to persistent AF (PeAF, defined as AF that is continuously sustained beyond 7 days, or perhaps 100% AF burden). This is accompanied by left atrial (LA) structural remodelling, demonstrated in 3D electroanatomical mapping studies where increased low voltage areas (a representation of fibrosis), are seen in patients with PeAF over PAF13,14. A similar finding has been shown by delayed enhancement MRI15. On a more macroscopic level, PAF patients with high AF burdens have larger LA dimensions and reduced contractile properties than those with low burdens16. Collectively, all of this points to a progressive fibrotic atrial cardiomyopathy.

AF Progression Is Associated With Worse Outcomes

These physiological changes translate to poor clinical outcomes. The KP-RHYTHM study17 retrospectively identified 1965 patients with PAF on 14-day ambulatory ECG monitoring. Patients not receiving anticoagulation were divided into tertiles based upon their AF burden. The highest tertile of AF burden (>11.4%) had a 3.2-fold higher incidence of thromboembolism than the lower two tertiles combined, (0.9 vs 2.9 events per person-year) independent of CHA2DS2-VASc score17. This relationship is also seen across studies using implantable cardiac devices to monitor AF burden18.

The correlation with increased adverse events has been extended further from PAF to PeAF. Zhang et al noted the association of AF progression and poor outcomes in their meta-analysis of 70,447 patients receiving anticoagulation. Here the risks of stroke, systemic embolism and mortality were all significantly higher in those with PeAF over PAF19. Indeed, retrospective analysis of direct oral anticoagulant (DOAC) trials, ROCKET AF20, ENGAGE AF21 and ARISTOTLE22 consistently show lower rates of stroke in PAF versus PeAF in anticoagulated patients irrespective of baseline risk factors23. The same finding was shown in non-anticoagulated patients in trials investigating the efficacy of aspirin for AF24.

Other studies have also found significant relationships of increased mortality,25 thromboembolism,25 death from stroke,26 stroke severity,26 decreased brain volume and cognitive ability27 with progression from PAF to PeAF.

Maintaining SR With Antiarrhythmic Drugs (AADs) Is Associated With Reduced Adverse Outcomes

As discussed above, AF is a progressive disease and this progression is related to adverse outcomes. Intervention to stop or slow down this progression can prevent these poor outcomes.

Regarding mortality, the AFFIRM trial showed no mortality benefit between its rhythm and rate control arms. However, post-publication on-treatment analysis discovered that increased time in SR itself was associated with a 47% lower risk of mortality28. Yet, this was offset by a 49% increase with the use of AADs used to try to maintain SR. Consequently, achieving SR with AADs decreased mortality rates, but this was cancelled out by the increased mortality associated with the use of AADs themselves. The mortality improvement with the maintenance of SR was also seen in the DIAMOND study29.

Maintaining SR also reduces risk of stroke. The ATHENA trial showed rhythm control with dronedarone maintained SR greater than placebo in patients with PAF. Specific analysis of stroke in the trial found a relative risk reduction of 34%, (1.2% vs 1.8%, p = 0.027), in the dronedarone arm regardless of anticoagulation30.

Quality of life improves with SR, even when compared to rate controlled AF when examined by validated questionnaires in double blinded31 and open label trials31,32.

Finally, time in SR is associated with greater improvements in NYHA class, quality of life and mortality for patients with heart failure, as evidenced by the double blinded CHF-STAT trial which compared use of amiodarone vs placebo33.

Consequently, although rate vs rhythm trials did not show mortality benefit, the specific achievement of SR maintenance is associated with improvements in mortality, stroke, heart failure and quality of life. On average, these benefits are however diminished by the increase mortality associated with the use of AADs themselves.

In summary, AF progression is associated with LA pathophysiological changes and adverse patient outcomes. Maintenance of SR is associated with improved patient outcomes. Therefore, it stands to reason that establishing SR as swiftly as possible should be a priority to maximise this.

Mortality Benefit For Treating Early AF With Rhythm Control

The recent EAST-AFNET4 trial showed a rhythm control strategy for early AF delivered prognostic benefit over usual care, (rate control followed by rhythm control if intolerable symptoms).10 Here, the rhythm control arm had an incidence of the primary outcome (a composite of cardiovascular death, stroke, or hospitalisation with heart failure or acute coronary syndrome) of 3.9 per 100 person-years compared to 5.0 per 100 person years (p=0.005). There was no significant difference in nights spent in hospital between the groups, nor in all cause mortality

Thus, treating early AF with rhythm control has significant physiological, morbidity and now cardiovascular mortality benefit. This leads one on to discuss what the most effective method of maintaining SR would be.

AADs Have Limited Efficacy

As was shown in the post hoc AFFIRM analysis, the benefit of SR maintenance was offset by the adverse effects of AADs. These adverse effects are a key limiting factor in their use. Furthermore, the efficacy of AADs in achieving SR is limited, the most effective but most toxic being amiodarone, (odds ratio 0.22 for AF recurrence)34. Indeed the authors of AFFIRM say, “Inability to maintain SR and drug intolerance were chief reasons for abandonment of a rhythm control strategy.”

Therefore, having a treatment option that can achieve SR, but could eliminate the use of AADs could provide significantly beneficial outcomes. Pulmonary vein isolation (PVI) via catheter ablation seeks to provide this treatmentAFFIRM was published in 2002, a time when catheter ablation was in its infancy. Indeed only 14 of 2033 patients in the rhythm control arm underwent catheter ablation for atrial arrhythmias in that study9.

Catheter Ablation Decreases AF Recurrence and Burden Over Medical Therapy

When compared to medical therapy, catheter ablation is superior at maintaining SR when comparing time to first arrhythmic recurrence when followed up by Holter monitoring or implantable cardiac devices35,36. However the intermittent nature of Holter monitoring and selection bias of using patients with devices made confirming the superiority of catheter ablation difficult to generalise. However, the recent Canadian trial EARLY-AF37 provided a new gold standard of monitoring patients by using implantable loop recorders (ILR) to eliminate these issues. Using ILRs at the time ofrandomisation to cryoablation or antiarrhythmics, Andrade et al were able to confirm with confidence that atrial arrhythmia recurrence at 1 year was significantly lower in the ablation versus anti-arrhythmic arm (42.9% vs 67.8%). Interestingly, the AF burden was reduced to minimal levels in both arms. Here, catheter ablation was able to decrease AF burden to a median of 0% with an interquartile range (IQR) of 0-0.08%, and AADs 0.13% with IQR of 0.00-1.60%. The ability of ablation to decrease AF burden to this level was also seen in the CIRCA DOSE trial conducted by the same centre (both cryo- and radiofrequency ablation)38 and the CLOSE TO CURE trial (radiofrequency ablation)39. The CIRCA DOSE trial in particular was able to demonstrate a reduction in AF burden pre- and post-procedure by implanting an ILR 30 days prior to ablation, although this was not compared to AADs. Radiofrequency ablation lowered burden from 1.57% to 0.00% (IQR 0.00-0.11%) cryoablation for 4 minutes 3.71% - 0.00% (IQR 0.00-0.24%) and cryoablation for 2 minutes 1.46% to 0.01% (IQR 0.00-0.34%).

Beyond AF burden and recurrence, radiofrequency ablation has also been shown to slow progression of AF from paroxysmal to persistent forms compared to AADs (2.4% vs 17.5% at 3 years)40. Consequently, ablation is able to slow disease progression , decrease burden and retard recurrence over medical therapy.

Catheter Ablation has Beneficial Clinical and Physiological Effects over Medical Therapy

Perhaps the most significant catheter ablation trial to date is CABANA which compared catheter ablation to medical therapy (rate or rhythm control)41. Although CABANA did not show a mortality benefit for catheter ablation in its intention to treat analysis (5.2% vs 6.1%, p = 0.38), it did for the composite of mortality and cardiovascular hospitalisation (51.7% vs 58.1%, p=0.001). CABANA also showed sustained improvements in quality of life in its catheter ablation arm42. This effect was repeated in the CAPTAF and EARLY AF trials37,43.

For patients with heart failure, CABANA suggested a benefit for catheter ablation with a relative risk reduction of 39% for mortality, stroke, major bleeding or cardiac arrest. Although this did not quite pass the point of statistical significance CASTLE-AF was able to statistically demonstrate this beneficial effect in a highly selected heart failure population44.

A recent nationwide cohort study of 27,097 patients in Korea also confirmed catheter ablation was associated with a decreased risk of dementia independent of stroke and other co-morbidities45.

Despite clinical improvements elsewhere, reduction in stroke rates following catheter ablation have been more difficult to establish, perhaps due to the increased emphasis on compliance with anticoagulation46. This has driven stroke rates to levels <1% and equivalent to patients without AF47. Regardless of this, EAST-AFNET4, whilst not exclusively a catheter ablation trial, did note a significant reduction in stroke rates in its rhythm control arm (0.6 vs 0.9%)10.

Catheter ablation is also associated with improved physiological markers, including NT-proBNP and left ventricular ejection fraction48.

In terms of safety, the most common complications from catheter ablation seen in the CABANA trial were vascular access issues such as haematoma, pseudoaneurysm, and arteriovenous fistulae, (3.9%). Pericardial effusion requiring drainage had an incidence of < 1%. No atrio-oesophageal fistulae or procedure related deaths occurred41.

So although catheter ablation is not associated with decreased mortality for all patients , It is associated with improved quality of life, decreased hospitalisation, decreased risk of dementia, improved physiological markers and for select groups decreased adverse cardiovascular outcomes, all compared to the use of medical therapy and maintaining an acceptable safety profile.

Catheter Ablation as a First Line Therapy

The 2020 ESC guidelines on the management of AF state catheter ablation should be considered before a trial of AADs in patients with paroxysmal AF episodes49 (Class IIa). These recommendations are based upon 3 prospective trials, RAAFT50, RAAFT II51 and MANTRA-PAF52 which examined outcomes between AADs and radiofrequency ablation as a first line therapy. Both RAAFT and RAAFT II showed superiority of radiofrequency ablation for AF recurrence at 12 and 24 months follow up respectively. The larger MANTRA-PAF trial, although not showing a statistically significant difference in AF burden up to 18 months, did at 24 months. A follow up study showed this effect persisted to 5 years53. Furthermore, more patients were arrhythmia free at this time and had improved physical quality of life.

So, there was the suggestion from these trials that early radiofrequency ablation could decrease AF recurrence and burden in the long term . Interestingly, since the publication of these guidelines in August 2020, two further trials investigating the effect  on AF recurrence of first line cryoablation vs AADs for treating PAF have been published, STOP-AF54 and EARLY-AF37. EARLY-AF  as discussed above used ILRs to confirm AF recurrence following intervention. The ablation arm showed a significantly lower recurrence rate and burden with an improvement in quality of life. STOPAF used 24-hour ambulatory ECGs and produced a similar result with a recurrence rate 74.6% vs 45.0%. Although STOP-AF and EARLY-AF provide strong evidence for the efficacy of ablation on suppression of atrial arrhythmias, the effect on quality of life is more difficult to definitively conclude bearing in mind that no sham trial on AF ablation has been conducted.

Alongside first line ablation providing arrhythmic freedom greater than AADs, delaying ablation from time of diagnosis decreases ablation success rates and risks adverse outcomes55. By investigating the time from diagnosis to ablation in 4535 patients, Bunch et al noted increased AF recurrence, mortality and heart failure hospitalisation in patients with delayed ablation greater than 180 days when followed up at one year. This suggests time is of the essence in PAF, and delays may push patients beyond physiological points of no return.

The combination of RAAFT I, RAAFT II, MANTRA-PAF, EARLY AF and STOP AF provide increasing evidence that ablation is a more effective, long lasting first line therapy for suppressing atrial arrhythmias in symptomatic PAF than AADs. Furthermore, it provides improved quality of life, and has a more sustained response. It is the most effective rhythm control strategy available. Lastly when considering the results of the EAST-AFNET4 trial, there is now evidence for mortality improvements in early AF. Although there is not a prospective trial that examines mortality after catheter ablation specifically in early PAF, with catheter ablation as the most effective rhythm control therapy, it is not a stretch to hypothesise mortality benefit will be seen in years to come .


Evidence for the use of catheter ablation first line is accumulating.

Early AF is a subgroup of patients likely to benefit from swift initiation of rhythm control.Early AF is purely based on patient history. A more granular approach such as AF burden may benefit future studies to assess benefits of intervention.

Catheter ablation provides the most effective method for maintaining SR without disproportionate increases in adverse effects.

The rate vs rhythm control debate is alive and well, and it will continue to be discussed for years to come.




  1. Public Health England. Atrial Fibrillation Prevelance Estimates 2019 [cited 2021. Available from:
  2. Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946-52.
  3. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998;82(8A):2N-9N.
  4. Dries DL, Exner DV, Gersh BJ, Domanski MJ, Waclawiw MA, Stevenson LW. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction. J Am Coll Cardiol. 1998;32(3):695-703.
  5. Saglietto A, Matta M, Gaita F, Jacobs V, Bunch TJ, Anselmino M. Stroke-independent contribution of atrial fibrillation to dementia: a meta-analysis. Open Heart. 2019;6(1):e000984.
  6. Peinado R, Arribas F, Ormaetxe JM, Badia X. Variation in quality of life with type of atrial fibrillation. Rev Esp Cardiol. 2010;63(12):1402-9.
  7. Steg PG, Alam S, Chiang CE, Gamra H, Goethals M, Inoue H, et al. Symptoms, functional status and quality of life in patients with controlled and uncontrolled atrial fibrillation: data from the RealiseAF cross-sectional international registry. Heart. 2012;98(3):195-201.
  8. Stewart S, Murphy NF, Walker A, McGuire A, McMurray JJ. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart. 2004;90(3):286-92.
  9. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825-33.
  10. Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020;383(14):1305-16.
  11. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: Executive summary. Heart Rhythm. 2017;14(10):e445-e94.
  12. Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92(7):1954-68.
  13. Kawai S, Mukai Y, Inoue S, Yakabe D, Nagaoka K, Sakamoto K, et al. Non-Pulmonary Vein Triggers of Atrial Fibrillation Are Likely to Arise from Low-Voltage Areas in the Left Atrium. Sci Rep. 2019;9(1):12271.
  14. Rolf S, Kircher S, Arya A, Eitel C, Sommer P, Richter S, et al. Tailored atrial substrate modification based on low-voltage areas in catheter ablation of atrial fibrillation. Circ Arrhythm Electrophysiol. 2014;7(5):825-33.
  15. Kuppahally SS, Akoum N, Burgon NS, Badger TJ, Kholmovski EG, Vijayakumar S, et al. Left atrial strain and strain rate in patients with paroxysmal and persistent atrial fibrillation: relationship to left atrial structural remodeling detected by delayed-enhancement MRI. Circ Cardiovasc Imaging. 2010;3(3):231-9.
  16. Strisciuglio T, El Haddad M, Debonnaire P, De Pooter J, Demolder A, Wolf M, et al. Paroxysmal atrial fibrillation with high vs. low arrhythmia burden: atrial remodelling and ablation outcome. EP Europace. 2020;22(8):1189-96.
  17. Go AS, Reynolds K, Yang J, Gupta N, Lenane J, Sung SH, et al. Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study. JAMA Cardiology. 2018;3(7):601-8.
  18. Steinberg BA, Piccini JP. When Low-Risk Atrial Fibrillation Is Not So Low Risk: Beast of Burden. JAMA Cardiol. 2018;3(7):558-60.
  19. Zhang W, Xiong Y, Yu L, Xiong A, Bao H, Cheng X. Meta-Analysis of stroke and bleeding risk in patients with various atrial fibrillation patterns receiving oral anticoagulants. The American Journal of Cardiology. 2019;123(6):922-8.
  20. Steinberg BA, Hellkamp AS, Lokhnygina Y, Patel MR, Breithardt G, Hankey GJ, et al. Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial. Eur Heart J. 2015;36(5):288-96.
  21. Link MS, Giugliano RP, Ruff CT, Scirica BM, Huikuri H, Oto A, et al. Stroke and Mortality Risk in Patients With Various Patterns of Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48). Circ Arrhythm Electrophysiol. 2017;10(1).
  22. Al-Khatib SM, Thomas L, Wallentin L, Lopes RD, Gersh B, Garcia D, et al. Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial. Eur Heart J. 2013;34(31):2464-71.
  23. Chen LY, Chung MK, Allen LA, Ezekowitz M, Furie KL, McCabe P, et al. Atrial Fibrillation Burden: Moving Beyond Atrial Fibrillation as a Binary Entity: A Scientific Statement From the American Heart Association. Circulation. 2018;137(20):e623-e44.
  24. Vanassche T, Lauw MN, Eikelboom JW, Healey JS, Hart RG, Alings M, et al. Risk of ischaemic stroke according to pattern of atrial fibrillation: analysis of 6563 aspirin-treated patients in ACTIVE-A and AVERROES. Eur Heart J. 2015;36(5):281-7a.
  25. Ganesan AN, Chew DP, Hartshorne T, Selvanayagam JB, Aylward PE, Sanders P, et al. The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. Eur Heart J. 2016;37(20):1591-602.
  26. Naess H, Waje-Andreassen U, Thomassen L. Persistent atrial fibrillation is associated with worse prognosis than paroxysmal atrial fibrillation in acute cerebral infarction. ISRN Cardiol. 2012;2012:650915.
  27. Stefansdottir H, Arnar DO, Aspelund T, Sigurdsson S, Jonsdottir MK, Hjaltason H, et al. Atrial fibrillation is associated with reduced brain volume and cognitive function independent of cerebral infarcts. Stroke. 2013;44(4):1020-5.
  28. Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation. 2004;109(12):1509-13.
  29. Pedersen OD, Brendorp B, Elming H, Pehrson S, Kober L, Torp-Pedersen C. Does conversion and prevention of atrial fibrillation enhance survival in patients with left ventricular dysfunction? Evidence from the Danish Investigations of Arrhythmia and Mortality ON Dofetilide/(DIAMOND) study. Card Electrophysiol Rev. 2003;7(3):220-4.
  30. Connolly SJ, Crijns HJ, Torp-Pedersen C, van Eickels M, Gaudin C, Page RL, et al. Analysis of stroke in ATHENA: a placebo-controlled, double-blind, parallel-arm trial to assess the efficacy of dronedarone 400 mg BID for the prevention of cardiovascular hospitalization or death from any cause in patients with atrial fibrillation/atrial flutter. Circulation. 2009;120(13):1174-80.
  31. Singh BN, Singh SN, Reda DJ, Tang XC, Lopez B, Harris CL, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med. 2005;352(18):1861-72.
  32. Dorian P, Mangat I. Quality of life variables in the selection of rate versus rhythm control in patients with atrial fibrillation: observations from the Canadian Trial of Atrial Fibrillation. Card Electrophysiol Rev. 2003;7(3):276-9.
  33. Deedwania PC, Singh BN, Ellenbogen K, Fisher S, Fletcher R, Singh SN. Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients with heart failure and atrial fibrillation: observations from the veterans affairs congestive heart failure survival trial of antiarrhythmic therapy (CHF-STAT). The Department of Veterans Affairs CHF-STAT Investigators. Circulation. 1998;98(23):2574-9.
  34. Freemantle N, Lafuente-Lafuente C, Mitchell S, Eckert L, Reynolds M. Mixed treatment comparison of dronedarone, amiodarone, sotalol, flecainide, and propafenone, for the management of atrial fibrillation. Europace. 2011;13(3):329-45.
  35. Di Biase L, Mohanty P, Mohanty S, Santangeli P, Trivedi C, Lakkireddy D, et al. Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Multicenter Randomized Trial. Circulation. 2016;133(17):1637-44.
  36. Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. Jama. 2010;303(4):333-40.
  37. Andrade JG, Wells GA, Deyell MW, Bennett M, Essebag V, Champagne J, et al. Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation. New England Journal of Medicine. 2020.
  38. Andrade JG, Champagne J, Dubuc M, Deyell MW, Verma A, Macle L, et al. Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation Assessed by Continuous Monitoring. Circulation. 2019;140(22):1779-88.
  39. Duytschaever M, De Pooter J, Demolder A, El Haddad M, Phlips T, Strisciuglio T, et al. Long-term impact of catheter ablation on arrhythmia burden in low-risk patients with paroxysmal atrial fibrillation: The CLOSE to CURE study. Heart Rhythm. 2020;17(4):535-43.
  40. Kuck K-H, Lebedev DS, Mikhaylov EN, Romanov A, Gellér L, Kalējs O, et al. Catheter ablation or medical therapy to delay progression of atrial fibrillation: the randomized controlled atrial fibrillation progression trial (ATTEST). EP Europace. 2020.
  41. Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, Poole JE, et al. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019;321(13):1261-74.
  42. Mark DB, Anstrom KJ, Sheng S, Piccini JP, Baloch KN, Monahan KH, et al. Effect of Catheter Ablation vs Medical Therapy on Quality of Life Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. Jama. 2019;321(13):1275-85.
  43. Blomstrom-Lundqvist C, Gizurarson S, Schwieler J, Jensen SM, Bergfeldt L, Kenneback G, et al. Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation: The CAPTAF Randomized Clinical Trial. JAMA. 2019;321(11):1059-68.
  44. Marrouche NF, Brachmann J, Andresen D, Siebels J, Boersma L, Jordaens L, et al. Catheter Ablation for Atrial Fibrillation with Heart Failure. N Engl J Med. 2018;378(5):417-27.
  45. Kim D, Yang P-S, Sung J-H, Jang E, Yu HT, Kim T-H, et al. Less dementia after catheter ablation for atrial fibrillation: a nationwide cohort study. European Heart Journal. 2020;41(47):4483-93.
  46. Barra S, Narayanan K, Boveda S, Primo J, Gonçalves H, Baran J, et al. Atrial Fibrillation Ablation and Reduction of Stroke Events. Stroke. 2019;50(10):2970-6.
  47. Freedman B, Martinez C, Katholing A, Rietbrock S. Residual Risk of Stroke and Death in Anticoagulant-Treated Patients With Atrial Fibrillation. JAMA Cardiol. 2016;1(3):366-8.
  48. Fiala M, Wichterle D, Bulková V, Sknouril L, Nevralová R, Toman O, et al. A prospective evaluation of haemodynamics, functional status, and quality of life after radiofrequency catheter ablation of long-standing persistent atrial fibrillation. Europace. 2014;16(1):15-25.
  49. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020.
  50. Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. Jama. 2005;293(21):2634-40.
  51. Morillo CA, Verma A, Connolly SJ, Kuck KH, Nair GM, Champagne J, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. Jama. 2014;311(7):692-700.
  52. Cosedis Nielsen J, Johannessen A, Raatikainen P, Hindricks G, Walfridsson H, Kongstad O, et al. Radiofrequency Ablation as Initial Therapy in Paroxysmal Atrial Fibrillation. New England Journal of Medicine. 2012;367(17):1587-95.
  53. Nielsen JC, Johannessen A, Raatikainen P, Hindricks G, Walfridsson H, Pehrson SM, et al. Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation: 5-year outcome in a randomised clinical trial. Heart. 2017;103(5):368-76.
  54. Wazni OM, Dandamudi G, Sood N, Hoyt R, Tyler J, Durrani S, et al. Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation. New England Journal of Medicine. 2020.
  55. Bunch TJ, May HT, Bair TL, Johnson DL, Weiss JP, Crandall BG, et al. Increasing time between first diagnosis of atrial fibrillation and catheter ablation adversely affects long-term outcomes. Heart Rhythm. 2013;10(9):1257-62.