Surgery Section - Transcatheter Radiofrequency Ablation of Arrhythmogenic Foci in the Pulmonary Veins as a Treatment for Atrial Fibrillation

IMPORTANT REMINDER

Regence Medical Policies are developed to provide guidance for members and providers regarding coverage in accordance with contract terms. Benefit determinations are based in all cases on the applicable contract language. To the extent there may be any conflict between the Medical Policy and contract language, the contract language takes precedence.

PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that are considered investigational or cosmetic. Providers may bill members for services or procedures that are considered investigational or cosmetic. Providers are encouraged to inform members before rendering such services that the members are likely to be financially responsible for the cost of these services.

Description

Transcatheter ablation in the atrium of the heart and the pulmonary veins is performed to interrupt the pathways along which abnormal electrical impulses travel. Many of the arrhythmogenic foci, triggers of abnormal electrical impulses, come from the tissues within the pulmonary veins. The impulses spread across the atrium, interfering with normal heart rhythm.

In atrial fibrillation (AF) the contractions of the atrium are rapid, chaotic and ineffective and may cause dizziness, fatigue and the development of blood clots that may lead to stroke.  AF can be subdivided into paroxysmal (episodes that last fewer than seven days and are self-terminating), persistent (episodes that last for more than seven days and can be terminated pharmacologically or by electrical cardioversion), or permanent.  The goals of treatment of AF are to relieve symptoms and to decrease the risk of formation of blood clots.

Unlike conservative treatments for AF such as medications and cardioversion, ablation is intended to be curative. Three basic ablation strategies that target the arrhythmogenic foci in the pulmonary veins have emerged:

1. Focal ablation inside the pulmonary veins
2. Segmental ablation of the ostia of the pulmonary veins
3. Circumferential ablation of the atrial wall outside the ostia of the pulmonary veins

Note: This policy is not intended to address intracardiac atrial ablation for supraventricular tachycardia caused by arrhythmogenic foci other than those within pulmonary veins or ablation techniques other than radiofrequency.

Policy/Criteria

1. Transcatheter radiofrequency ablation of the pulmonary veins as a treatment for atrial fibrillation may be considered medically necessary when at least one of the following criteria are met:
   
   
   1. As an alternative to continued medical management for patients with symptomatic paroxysmal or persistent atrial fibrillation who have failed or could not tolerate antiarrhythmic medications
      
      Symptomatic is defined as impaired ability to complete activities of daily living or essential job related activities due to atrial fibrillation despite treatment to control rate.  Symptoms (e.g., intermittent mild dizziness) that do not significantly impact the patient’s functional level do not meet this definition.
      
      
   2. As an alternative to AV nodal ablation and pacemaker insertion for patients with class II or III congestive heart failure and symptomatic atrial fibrillation in whom heart rate is poorly controlled by standard medications
      
      
2. Up to two repeat ablations may be considered medically necessary in patients with recurrence of atrial fibrillation and/or development of atrial flutter following the initial ablation procedure.
   
   
3. Transcatheter radiofrequency ablation for arrhythmogenic foci in the pulmonary veins is considered investigational for all other indications, including but not limited to ablation as first-line treatment of atrial fibrillation.

Scientific Background

The most important clinical outcome measures in clinical trials for the treatment of atrial fibrillation (AF) are ^[1]:

• Mortality and morbidity (e.g., cardiovascular mortality, stroke, and congestive heart failure); however, these are uncommon events, and currently available trials are not powered to detect differences in these outcomes.
• Quality of life (e.g., symptoms such as reduced exercise tolerance or hypotension that significantly reduce the patient’s daily functional levels)
• Recurrence of AF

Recurrence of AF is a more problematic outcome measure, since the intermittent and often transient nature of recurrences makes accurate measurement difficult. ^[2] This outcome measure has been reported in different ways. For example, the proportion of patients in sinus rhythm at the end of the study, the time to first recurrence, and the number of recurrences within a time period have been reported. A recent publication by Shemin and colleagues highlighted the difficulties in measuring AF recurrence and recommended a measure of AF “burden”, defined as the percentage of time an individual is in AF, as the optimal measure of treatment efficacy. However, this parameter requires continuous monitoring over a relatively long period of time, which is inconvenient for patients, resource intensive and usually not pragmatic in patients who do not already have an implanted pacemaker.

Recommendations for outcome assessment in trials of atrial fibrillation treatment were included in the 2006 American College of Cardiology/American Heart Association practice guidelines for the treatment of atrial fibrillation. ^[3] These guidelines pointed out that the appropriate end points for evaluation of treatment efficacy in patients with paroxysmal and persistent AF have little in common. For example, in studies of persistent AF, the proportion of patients in sinus rhythm at the end of follow-up is a useful end point, but this is a less useful measure in studies of paroxysmal AF. Given all these variables, ideally, controlled clinical trials would report a range of outcomes (including quality of life) and complications in homogeneous patient groups and compared to treatment alternatives, such as pharmacologic therapy, defibrillator therapy, and AV nodal ablation, depending on the classification of AF (paroxysmal, persistent, or permanent).

Underlying these issues in outcome measurement is the ongoing controversy regarding the relative benefits of rhythm versus rate control. Randomized trials of pharmacologic therapies have not demonstrated the superiority of rhythm versus rate control. ^[4-6] However, the apparent equivalency of these two strategies with pharmacologic therapy cannot be extrapolated to the rhythm control achieved with ablation. Antiarrhythmic medications used for rhythm control are only partially effective, and have serious complications, including proarrhythmic properties that can be lethal. Therefore, nonpharmacologic strategies for rhythm control have the potential to achieve superior outcomes than have been seen with pharmacologic strategies.

This policy is currently based on a 2008 TEC Assessment. ^[7] Six randomized, controlled trials met the inclusion criteria for this TEC Assessment. ^[8-13] The trials differed in their patient populations, the specific catheter ablation techniques used, and the comparisons made. The trials addressed three distinct indications for catheter ablation: 1) patients with paroxysmal atrial fibrillation, as a first-line treatment option (n=1 trial ^[9]); 2) patients with symptomatic paroxysmal or persistent atrial fibrillation who have failed treatment with antiarrhythmic drugs (n=4 trials ^[8,10-12]); and 3) patients with symptomatic atrial fibrillation and congestive heart failure who have failed treatment with standard medications for rate control and who would otherwise be considered for AV nodal ablation and pacemaker insertion (n=1 trial ^[13]).

All six trials reported that maintenance of sinus rhythm was improved for the catheter ablation group. Recurrence rates of atrial fibrillation at one year ranged from 11–44% for the catheter ablation groups in these trials, compared with 63–96% for the medication groups. Four of the six trials reported quality of life (QOL) outcomes. One of these ^[8] only reported within-group comparisons, as opposed to between-group comparisons. The other three trials ^[9,12,13] reported improvements in QOL associated with catheter ablation. These QOL measures were self-reported, and since both trials were unblinded, there is the possibility of reporting bias due to placebo effect.

None of the available trials reported meaningful data on cardiovascular morbidity and mortality associated with atrial fibrillation. Larger randomized, controlled trials, such as the ongoing CABANA trial (ClinicalTrials.gov identifier NCT00578617^[14]) with expected completion in 2011, are necessary in order to determine whether catheter ablation leads to improvements in these important clinical outcomes. At present, any conclusions made must be based primarily on the outcome of atrial fibrillation recurrence, supplemented by a smaller amount of evidence on quality of life and physiologic parameters.

The TEC Assessment concluded that catheter ablation catheter ablation is more effective than medications in maintaining sinus rhythm across a wide spectrum of patients with atrial fibrillation, and across different variations of catheter ablation. The evidence on QOL was suggestive of a benefit for patients undergoing catheter ablation, but not definitive. For other outcomes, the evidence did not permit conclusions. It was not possible to estimate the rate of serious complications, such as pulmonary vein stenosis, cardiac tamponade, or atrio-esophageal fistula with precision given the limited number of patients in the trials and the continued evolution of the technique. However, the rate of serious complications is expected to be low, likely in the 1-3% range.

Based on these findings, TEC criteria were met for two indications: 1) patients with symptomatic paroxysmal or persistent atrial fibrillation, who have failed treatment with antiarrhythmic drugs; and 2) patients with symptomatic atrial fibrillation and congestive heart failure, who have failed treatment with standard medications for rate control and who would otherwise be considered for AV nodal ablation and pacemaker insertion. For the first indication, the conclusion followed from the premise that reducing episodes of recurrent atrial fibrillation for this population will reduce or eliminate the symptoms associated with episodes of atrial fibrillation. For the latter indication, the single multicenter randomized, controlled trial available was judged sufficient to conclude that catheter ablation improved outcomes compared to the alternative, AV nodal ablation and pacemaker insertion. While this trial was relatively small, it was judged to be otherwise of high quality and reported improvements of a relatively large magnitude across a range of clinically important outcome measures, including QOL, exercise tolerance, left ventricular ejection fraction, and maintenance of sinus rhythm.

Since the 2008 TEC Assessment, Forleo and colleagues enrolled 70 patients with type II diabetes mellitus and paroxysmal or persistent atrial fibrillation for at least six months duration resistant to one or more trials of antiarrhythmic drugs. ^[15] Patients were randomized to radiofrequency pulmonary vein isolation (PVI) or a new antiarrhythmic drug regimen and followed up for one year. The primary outcome was recurrence of atrial fibrillation, and secondary outcomes were the SF-36 health status questionnaire, thromboembolic events, bleeding, and hospitalizations. Holter monitoring was performed at 3-month intervals to assess recurrence of atrial fibrillation. At one year, 20% of patients in the ablation group had atrial fibrillation recurrence, compared with 57% in the antiarrhythmic drug group (p<0.001). Hospitalizations were more frequent in the drug group (34.3% vs. 8.6%, p<0.01). The ablation group had greater mean improvements on 5 of 8 subscales on the SF-36 questionnaire (p<0.05). The mean improvements on these subscales (0–100 scale) were 8.9 points for general health, 8.4 for physical functioning, 7.7 for social functioning, 6.8 for role emotional, and 5.5 for bodily pain. An improvement of 5–10 points is considered a clinically significant change for the SF-36 measures. This study corroborates previous evidence demonstrating the superiority of catheter ablation in reducing atrial fibrillation recurrence in patients who have failed antiarrhythmic drugs. It also adds to accumulating evidence that catheter ablation is associated with improvements in quality of life compared to continued antiarrhythmic drug treatment.

Numerous other randomized, controlled trials compared variations of the technique for performing radiofrequency ablation such as the location and extent of ablations performed, the use of navigation aids and novel catheters, and the use of computed tomographic image integration. ^[16-21] These randomized, controlled trials do not provide clear evidence of the superiority of one type of technique over others.

Two systematic reviews published in 2008 summarized and synthesized the randomized, controlled trial evidence on catheter ablation versus alternate therapy. These reviews included four of the six trials reviewed for the TEC Assessment.  Noheria and colleagues ^[22] included three of these four randomized, controlled trials ^[9-11] as well as an additional small randomized, controlled trial of 30 patients not included in the TEC Assessment. ^[23] Gjiesdal and colleagues ^[24] included five randomized, controlled trials in their analysis, including the four trials in the Noheria systematic review summarized below, and one additional trial (included in TEC Assessment) that compared catheter ablation plus antiarrhythmic drugs with antiarrhythmic drugs alone. ^[8] Both of these systematic reviews concluded that catheter ablation was more effective than pharmacologic treatment in maintaining normal sinus rhythm.

In combined analysis, Noheria and colleagues reported atrial-fibrillation-free survival at one year to be 75.7% in the catheter-ablation group compared to 18.8% in the comparison group. ^[22] The relative risk for maintaining sinus rhythm was 3.73 (95% CI: 2.47-5.63) for the catheter-ablation group compared to alternative treatment. Gjiesdal and colleagues ^[24] concluded that the available evidence was of moderate quality, and consistent in reporting the atrial-fibrillation-free survival was superior for the catheter ablation group; however, due to unexplained heterogeneity, these authors did not perform a combined analysis.

Piccini and colleagues conducted a meta-analysis of randomized, controlled trials to compare the efficacy and safety of pulmonary vein isolation (PVI) with medical therapy at 12-months follow-up. ^[25] Six trials with a combined total of 693 patients met inclusion criteria. The authors reported freedom from atrial fibrillation of 77% of patient receiving PVI and 29% of patients on medical treatment. PVI was also associated with decreased hospitalization for cardiovascular causes (14% vs. 93%). Repeat PVI was required in 17% of PVI patients.

Society Guidelines and Consensus Statements

In 2006, the American College of Cardiology published an update to their practice guidelines for the treatment of atrial fibrillation. ^[3] These guidelines reflect the results of the rate versus rhythm controlled randomized studies. Explicit recommendations were classed as I, IIa, IIb, or III. Class IIa is defined as: “the weight of evidence or opinion is in favor of the procedure or treatment.” The recommendations were further classified according to the type of data available. Class C data were defined as “expert consensus.” The guidelines described the use of ablation of the pulmonary vein and noted that the “…technique of ablation has continued to evolve from early attempts to target individual ectopic foci within the PV to circumferential electrical isolation of the entire PV musculature.” The following two specific recommendations regarding the use of catheter ablation were judged class IIa:

1. It is reasonable to use ablation of the AV node or accessory pathway to control heart rate when pharmacological therapy is insufficient or associated with side effects (Level of Evidence: B)
   
   
2. Catheter ablation is a reasonable alternative to pharmacological therapy to prevent recurrent AF in symptomatic patients with little or no left atrial enlargement. (Level of Evidence: )

The guidelines also encouraged further research in this area given uncertainties in patient populations, technique, and outcome assessment. The authors stated that “despite these advances, the long-term efficacy of catheter ablation to prevent recurrent AF requires further study.”

The American College of Physicians and American Academy of Family Physicians issued clinical practice guidelines in 2003 for patients with new onset AF ^[26]. These guidelines stated that the majority of patients with new onset AF should be treated with a pharmacologic rate control strategy and long-term anticoagulation. Similar to the ACC/AHA guidelines, this document did not include specific recommendations for catheter-based ablation techniques in their treatment algorithms.

Repeated procedures

Repeated procedures for recurrent atrial fibrillation or atrial flutter were commonly performed in most of the clinical trials included in this policy statement. Of the seven randomized, controlled trials reviewed, only two ^[9,15] did not include repeated procedures. In the other five studies, one or more repeated procedures were allowed, and success rates reported generally incorporated the results of up to three procedures. In three studies that reported these data, repeated procedures were performed in 9% ^[11], 20% ^[13], and 32% ^[8] of patients randomized to ablation. Stabile and colleagues did not report specifics on how many patients actually underwent repeated procedures, but limited data in the publication indicated that up to 30% of treated patients were eligible for repeated procedures. ^[10] In the Jais et al study, patients underwent a mean of 1.8 procedures per patient and a median of two procedures per patient, indicating that approximately 50% of patients in the ablation group underwent at least one repeated procedure. ^[12]

Because of this high rate of repeated procedures, the results reported in these studies do not reflect the success of a single procedure. Rather, they more accurately estimate the success of an ablation strategy that includes repeated procedures for recurrences that occur within the first year of treatment. Nonrandomized evidence suggests that early reablation increases the success of the procedure, when defined as maintenance of sinus rhythm at 1 year. ^[27] There is variability in the protocol for when repeated procedures should be performed. There is also uncertainty concerning other details on repeated procedure, such as how soon after the initial procedure it should be done, the threshold of atrial fibrillation recurrence that should prompt a repeat, and whether medications should be tried prior to a repeated procedure.

Summary

• The evidence is sufficient to conclude that catheter ablation may be appropriate or patients with symptomatic atrial fibrillation who have failed antiarrhythmic medications. For these patients, maintenance of sinus rhythm will lead to an improvement in symptoms and therefore will improve outcomes.
  
  
• For the larger population of patients with atrial fibrillation whose symptoms are adequately controlled by rate control, the evidence is not sufficient to conclude that outcomes are improved. Therefore, there is insufficient evidence to support the use of catheter ablation as first-line treatment.
  
  
• For the small subset of patients with atrial fibrillation and congestive heart failure, in whom standard medications for atrial fibrillation have failed to adequately control ventricular rate, the evidence is sufficient to conclude that catheter ablation improves outcomes compared to the alternative, AV nodal ablation and pacemaker insertion.
  
  
• Up to two repeat procedures may be needed following initial ablation in order to achieve complete control of atrial fibrillation or flutter.
  
  
• The randomized, controlled trials comparing variations of catheter ablation underscore the continued evolution of the procedure, and the uncertainty that exists regarding the optimal approach for catheter ablation to treat atrial fibrillation.

References

1. BlueCross BlueShield Association Medical Policy Reference Manual "Radiofrequency Catheter Ablation of the Pulmonary Veins as Treatment for Atrial Fibrillation " Policy No. 2.02.19
2. Shemin, RJ, Cox, JL, Gillinov, AM, Blackstone, EH, Bridges, CR. Guidelines for reporting data and outcomes for the surgical treatment of atrial fibrillation. Ann Thorac Surg. 2007 Mar;83(3):1225-30.  PMID: 17307507
3. Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006 Aug 15;48(4):854-906.  PMID: 16904574
4. Wyse, DG, Waldo, AL, DiMarco, JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002 Dec 5;347(23):1825-33.  PMID: 12466506
5. Van Gelder, IC, Hagens, VE, Bosker, HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002 Dec 5;347(23):1834-40.  PMID: 12466507
6. Falk, RH. Management of atrial fibrillation--radical reform or modest modification? N Engl J Med. 2002 Dec 5;347(23):1883-4.  PMID: 12466514
7. TEC Assessment "Radiofrequency Catheter Ablation of the Pulmonary Veins for Treatment of Atrial Fibrillation." BlueCross BlueShield Association Technology Evaluation Center, Vol. 23 Tab. 11.
8. Oral, H, Pappone, C, Chugh, A, et al. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. N Engl J Med. 2006 Mar 2;354(9):934-41.  PMID: 16510747
9. Wazni, OM, Marrouche, NF, Martin, DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005 Jun 1;293(21):2634-40.  PMID: 15928285
10. Stabile, G, Bertaglia, E, Senatore, G, et al. Catheter ablation treatment in patients with drug-refractory atrial fibrillation: a prospective, multi-centre, randomized, controlled study (Catheter Ablation For The Cure Of Atrial Fibrillation Study). Eur Heart J. 2006 Jan;27(2):216-21.  PMID: 16214831
11. Pappone, C, Augello, G, Sala, S, et al. A randomized trial of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the APAF Study. J Am Coll Cardiol. 2006 Dec 5;48(11):2340-7.  PMID: 17161267
12. Jais, P, Cauchemez, B, Macle, L, et al. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation: the A4 study. Circulation. 2008 Dec 9;118(24):2498-505.  PMID: 19029470
13. Khan, MN, Jais, P, Cummings, J, et al. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med. 2008 Oct 23;359(17):1778-85.  PMID: 18946063
14. The clinicaltrial.gov website.   [cited 3/15/10]; Available from: http://www.clinicaltrials.gov/ct2/search
15. Forleo, GB, Mantica, M, De Luca, L, et al. Catheter ablation of atrial fibrillation in patients with diabetes mellitus type 2: results from a randomized study comparing pulmonary vein isolation versus antiarrhythmic drug therapy. J Cardiovasc Electrophysiol. 2009 Jan;20(1):22-8.  PMID: 18775050
16. Rajappan, K, Baker, V, Richmond, L, et al. A randomized trial to compare atrial fibrillation ablation using a steerable vs. a non-steerable sheath. Europace. 2009 May;11(5):571-5.  PMID: 19351628
17. Della Bella, P, Fassini, G, Cireddu, M, et al. Image integration-guided catheter ablation of atrial fibrillation: a prospective randomized study. J Cardiovasc Electrophysiol. 2009 Mar;20(3):258-65.  PMID: 19261038
18. Oral, H, Chugh, A, Yoshida, K, et al. A randomized assessment of the incremental role of ablation of complex fractionated atrial electrograms after antral pulmonary vein isolation for long-lasting persistent atrial fibrillation. J Am Coll Cardiol. 2009 Mar 3;53(9):782-9.  PMID: 19245970
19. Deisenhofer, I, Estner, H, Reents, T, et al. Does electrogram guided substrate ablation add to the success of pulmonary vein isolation in patients with paroxysmal atrial fibrillation? A prospective, randomized study. J Cardiovasc Electrophysiol. 2009 May;20(5):514-21.  PMID: 19207759
20. Perez-Castellano, N, Villacastin, J, Salinas, J, et al. Cooled ablation reduces pulmonary vein isolation time: results of a prospective randomised trial. Heart. 2009 Mar;95(3):203-9.  PMID: 18070948
21. Khaykin, Y, Skanes, A, Champagne, J, et al. A randomized controlled trial of the efficacy and safety of electroanatomic circumferential pulmonary vein ablation supplemented by ablation of complex fractionated atrial electrograms versus potential-guided pulmonary vein antrum isolation guided by intracardiac ultrasound. Circ Arrhythm Electrophysiol. 2009 Oct;2(5):481-7.  PMID: 19843915
22. Noheria, A, Kumar, A, Wylie, JV, Jr., Josephson, ME. Catheter ablation vs antiarrhythmic drug therapy for atrial fibrillation: a systematic review. Arch Intern Med. 2008 Mar 24;168(6):581-6.  PMID: 18362249
23. Krittayaphong, R, Raungrattanaamporn, O, Bhuripanyo, K, et al. A randomized clinical trial of the efficacy of radiofrequency catheter ablation and amiodarone in the treatment of symptomatic atrial fibrillation. J Med Assoc Thai. 2003 May;86 Suppl 1:S8-16.  PMID: 12866763
24. Gjesdal, K, Vist, GE, Bugge, E, et al. Curative ablation for atrial fibrillation: a systematic review. Scand Cardiovasc J. 2008 Feb;42(1):3-8.  PMID: 18273730
25. Piccini, JP, Lopes, RD, Kong, MH, Hasselblad, V, Jackson, K, Al-Khatib, SM. Pulmonary vein isolation for the maintenance of sinus rhythm in patients with atrial fibrillation: a meta-analysis of randomized, controlled trials. Circ Arrhythm Electrophysiol. 2009 Dec;2(6):626-33.  PMID: 20009077
26. Snow, V, Weiss, KB, LeFevre, M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med. 2003 Dec 16;139(12):1009-17.  PMID: 14678921
27. Lellouche, N, Jais, P, Nault, I, et al. Early recurrences after atrial fibrillation ablation: prognostic value and effect of early reablation. J Cardiovasc Electrophysiol. 2008 Jun;19(6):599-605.  PMID: 18462321

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