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

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

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

Position Summary

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

• 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. (2) 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) 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.

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 (14) 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. (16) Gjiesdal and colleagues (15) included five randomized, controlled trials in their analysis, including the four trials in the Noheria systematic review, 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. 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 (15) 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.

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.” Theguidelines 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 (17). 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.

In summary, the evidence is sufficient to conclude that catheter ablation is more effective than pharmacologic therapy in maintaining sinus rhythm. For patients with symptomatic atrial fibrillation who have failed antiarrhythmic medications, 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. 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.

References

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 2.02.19
2. Shemin RJ, Cox JL, Gillinov AM et al. Guidelines for reporting data and outcomes for the surgical treatment of atrial fibrillation. Ann Thorac Surg 2007;83(3):1225-30
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;48(4):854-906
4. Wyse DG, Waldo AL, DiMarco JP et al. AFFIRM Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347(23):1825-33
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;347(23):1834-40
6. Falk RH. Management of atrial fibrillation--radical reform or modest modification? N Engl J Med 2002;347(23):1883-4
7. BlueCross and BlueShield Association Technology Evaluation Center Assessments: Catheter Ablation of the Pulmonary Veins as a Treatment for Atrial Fibrillation. 2008
8. Oral H, Pappone C, Chugh A et al. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. N Engl J Med 2006;354(9):934-41
9. Wazni OM, Marrouche NF, Martin DO et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment for symptomatic atrial fibrillation: a randomized trial. JAMA 2005;293(21):2634-40
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; 27(2):216-21
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; 48(11):2340-7
12. Jais P, Cauchemez B, Macle L et al. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation: The A4 study. Circulation, 2008;118(24):2498-505
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;359(17):1778-85
14. Noheria A, Kumar A, Wylie JV et al. Catheter ablation vs. antiarrhythmic drug therapy for atrial fibrillation: a systematic review. Arch Intern Med 2008; 168(6):581-6
15. Gjesdal K, Vist GE, Bugge E et al. Curative ablation for atrial fibrillation: a systematic review. Scand Cardiovasc J 2008: 42(1):3-8
16. Krittayaphong R, Bhuripanyo K, Pooranawattanakul S et al. A randomized clinical trial of the efficacy of radiofrequency ablation and amiodarone in the treatment of symptomatic atrial fibrillation. J Med Assoc Thai 2003;86(suppl 1):S8-S16
17. 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;139(12):1009-17

Cross References

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