mp-283
print Print Back Back

Transcatheter Ablation as a Treatment of Atrial Fibrillation

Policy Number: MP-283

Latest Review Date: July 2019

Category:  Medical                                                                

Policy Grade:  A

Description of Procedure or Service:

Atrial fibrillation (AF) frequently arises from an abnormal focus at or near the junction of the pulmonary veins and the left atrium, thus leading to the feasibility of more focused ablation techniques directed at these structures. Catheter-based ablation, using radiofrequency ablation (RFA) or cryoablation, is being studied as a treatment option for various types of AF.

Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated prevalence of 0.4% of the population, increasing with age. The underlying mechanism of AF involves interplay between electrical triggering events and the myocardial substrate that permits propagation and maintenance of the aberrant electrical circuit. The most common focal trigger of AF appears to be located within the cardiac muscle that extends into the pulmonary veins.

AF accounts for approximately one-third of hospitalizations for cardiac rhythm disturbances. Symptoms of AF (e.g., palpitations, decreased exercise tolerance, dyspnea) are primarily related to poorly controlled or irregular heart rate. The loss of atrioventricular (AV) synchrony results in a decreased cardiac output, which can be significant in patients with compromised cardiac function. In addition, patients with AF are at higher risk for stroke, with anticoagulation is typically recommended. AF is also associated with other cardiac conditions, such as valvular heart disease, heart failure, hypertension, and diabetes. Although episodes of AF can be converted to normal sinus rhythm using pharmacologic or electroshock conversion, the natural history of AF is that of recurrence, thought to be related to fibrillation-induced anatomic and electrical remodeling of the atria.

AF can be subdivided into three types:

  • paroxysmal (episodes that last fewer than 7 days and are self-terminating),

  • persistent (episodes that last for more than 7 days and can be terminated pharmacologically or by electrical cardioversion), or

  • Permanent.

Treatment strategies can be broadly subdivided into rate control, in which only the ventricular rate is controlled and the atria are allowed to fibrillate, or rhythm control, in which there is an attempt to reestablish and maintain normal sinus rhythm. Rhythm control has long been considered an important treatment goal for management of AF, although its primacy has recently been challenged by the results of several randomized trials reporting that pharmacologically maintained rhythm control offered no improvement in mortality or cardiovascular morbidity compared with rate control.

However, rhythm control is not curative. A variety of ablative procedures have been investigated as potentially curative approaches, or as modifiers of the arrhythmia such that drug therapy becomes more effective. Ablative approaches focus on interruption of the electrical pathways that contribute to AF through modifying the arrhythmia triggers and/or the myocardial substrate that maintains the aberrant rhythm. The maze procedure, an open surgical procedure often combined with other cardiac surgeries (e.g., valve repair), is an ablative treatment that involves sequential atriotomy incisions designed to create electrical barriers that prevent the maintenance of AF. Because of the highly invasive nature of this procedure, it is currently mainly reserved for patients undergoing open heart surgery for other reasons (e.g., valve repair, coronary artery bypass grafting).

Catheter Ablation for Atrial Fibrillation

Radiofrequency ablation (RFA) using a percutaneous catheter-based approach is widely used to treat a variety of supraventricular arrhythmias, in which intracardiac mapping identifies a discrete arrhythmogenic focus that is the target of ablation. The situation is more complex for AF, because there may be no single arrhythmogenic focus. AF most frequently arises from an abnormal focus at or near the junction of the pulmonary veins and the left atrium, thus leading to the feasibility of more focused, percutaneous ablation techniques. Strategies that have emerged for focal ablation within the pulmonary veins originally involved segmental ostial ablation guided by pulmonary vein potential (electrical approach) but currently more typically involve circumferential pulmonary vein ablation (anatomic approach). Circumferential pulmonary vein ablation using radiofrequency energy is the most common approach at present. Research into specific ablation and pulmonary vein isolation techniques is ongoing.

Use of current radiofrequency catheters for AF has a steep learning curve because they require extensive guiding to multiple ablation points. The procedure also can be done using cryoablation technology. One of the potential advantages of cryoablation is that cryoablation catheters have a circular or shaped end point, permitting a “one-shot” ablation.

Repeat Procedures

Repeat procedures following initial RFA are commonly performed if AF recurs or if atrial flutter develops postprocedure. The need for repeat procedures may, in part, depend on the clinical characteristics of the patient (e.g., age, persistent vs paroxysmal AF, atrial dilatation), and the type of ablation initially performed. Repeat procedures are generally more limited in scope than the initial procedure. Additional clinical factors are associated with the need for a second procedure, including age, length of AF, permanent AF, left atrial size, and left ventricular ejection fraction.

Policy:

Transcatheter radiofrequency ablation or cryoablation to treat atrial fibrillation may be considered medically necessary as a treatment for either of the following indications which have failed to respond to adequate trials of antiarrhythmic medications:

  • Symptomatic paroxysmal or symptomatic persistent atrial fibrillation; or

  • As an alternative to atrioventricular nodal ablation and pacemaker insertion in patients with class II or III congestive heart failure and symptomatic atrial fibrillation.

Transcatheter radiofrequency ablation or cryoablation to treat atrial fibrillation may be considered medically necessary as an initial treatment for patients with recurrent symptomatic paroxysmal atrial fibrillation (>1 episode, with 4 or fewer episodes in the previous 6 months) in whom a rhythm control strategy is desired.

Repeat radiofrequency ablation or cryoablation may be considered medically necessary in patients with recurrence of atrial fibrillation and/or development of atrial flutter following the initial procedure.

Transcatheter radiofrequency ablation or cryoablation to treat atrial fibrillation is considered not medically necessary and investigational as a treatment for all other indications including, but not limited to cases of atrial fibrillation that do not meet the criteria outlined above.

Key Points:

The most recent literature search was performed through April 6, 2019.

Broadly defined, health outcomes are length of life, quality of life (QOL), and ability to function¾including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

In patients with paroxysmal or persistent atrial fibrillation (AF), catheter ablation may be considered an alternative to drug therapy. In patients with permanent AF, catheter ablation may be considered an alternative to drug therapy or to atrioventricular (AV) nodal ablation and pacing. For all types of AF, it is possible that catheter ablation may not be curative as a sole treatment but might alter the underlying myocardial triggers or substrate in such a way that subsequent pharmacologic therapy may become more effective.

There is ongoing controversy about the relative benefits of rhythm versus rate control in AF, which underlies the evaluation of evidence on catheter ablation. Randomized trials of pharmacologic therapies have not demonstrated the superiority of rhythm control versus rate control.  However, the apparent equivalency of these 2 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, which can be lethal. Therefore, nonpharmacologic strategies for rhythm control have the potential to achieve outcomes superior to those seen with pharmacologic strategies.

Evidence on ablation procedures for AF was reviewed, with a focus on RCTs reporting on the AF-related outcomes of interest (see below). Also, nonrandomized studies and noncomparative studies reporting on longer term outcomes were included to evaluate for durability.

Catheter Ablation for Symptomatic Paroxysmal or Persistent Atrial Fibrillation who have Failed Medical Management

Systematic Reviews

The literature review for this evidence review was informed by a TEC Assessment (2008). Six RCTs met Assessment inclusion criteria. The trials differed in patient populations, specific catheter ablation techniques used, and comparisons made. The trials addressed 3 distinct indications for catheter ablation: (1) patients with paroxysmal AF, as a first-line treatment option (1 trial); (2) patients with symptomatic paroxysmal or persistent AF who had failed treatment with antiarrhythmic drugs (4 trials); and (3) patients with symptomatic AF and heart failure who had failed treatment with standard medications for rate control and who would otherwise be considered for atrioventricular (AV) nodal ablation and pacemaker insertion (1 trial).

All 6 trials reported that maintenance of sinus rhythm was improved for the catheter ablation group. Recurrence rates of AF at 1 year ranged from 11% to 44% for the catheter ablation groups compared with 63% to 96% for the medication groups. Four of the 6 trials reported on QOL outcomes. One of these only reported within-group comparisons, as opposed to between-group comparisons. The other 3 trials reported improvements in QOL associated with catheter ablation. None of the available trials reported meaningful data on cardiovascular morbidity and mortality associated with AF. The Assessment concluded that catheter radiofrequency ablation (RFA) is more effective than medications in maintaining sinus rhythm across a wide spectrum of patients with AF and different variations of catheter ablation. The evidence on QOL is suggestive, but not definitive, of a benefit for patients undergoing catheter ablation. For other outcomes, the evidence did not permit conclusions. Based on these findings, TEC criteria were met for 2 indications: patients with symptomatic paroxysmal or persistent AF who have failed treatment with antiarrhythmic drugs and patients with symptomatic AF and 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 AF for this population will reduce or eliminate the symptoms associated with episodes of AF. For the other indication, the single multicenter RCT available was judged sufficient to conclude that catheter ablation improved outcomes compared with 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 (LVEF), and maintenance of sinus rhythm.

Since the publication of the TEC Assessment, additional systematic reviews and meta-analyses of catheter ablation for AF have been reported.

Nyong et al (2016) reported on a Cochrane review of ablation for individuals with nonparoxysmal AF, which included RCTs comparing radiofrequency catheter or surgical ablation with antiarrhythmic drugs for persistent or long-standing persistent AF. Reviewers selected 3 RCTs (total n=261 subjects; Forleo et al [2009], Stabile et al [2006], and Mont et al [2014] not discussed in detail herein), all comparing catheter RFA (n=159) to antiarrhythmic drugs (n=102) at 12 months. The trials were assessed to have a low or unclear risk of bias. Reviewers’ primary outcomes are summarized in Table 1.

Table 1. Efficacy of Catheter Ablation for Nonparoxysmal Atrial Fibrillation

Outcome (Catheter vs Drug Therapy)

No. of Participants (Studies)

Evidence Qualitya

RR

95% CI

Freedom from atrial arrhythmias or recurrence of any atrial arrhythmias

261 (3 studies)

Low

1.84

1.17 to 2.88

Need for cardioversion

261 (3 studies)

Moderate

0.62

0.47 to 0.82

Cardiac hospitalization

216 (2 studies)

Low

0.28

0.1 to 0.72

Adapted from Nyong et al (2016).
CI: confidence interval; RR: relative risk.
a Assessed using the GRADE assessment tool.

Overall, reviewers concluded that catheter RFA was superior to antiarrhythmic drugs for patients who had not responded to antiarrhythmic drug therapy, but there was uncertainty related to their findings.

Shi et al (2015) reported on the results of a meta-analysis of RCTs comparing catheter ablation with antiarrhythmic drug therapy for AF. The meta-analysis included 11 trials (total n=1763 patients), of which 4 included only patients with paroxysmal AF, 2 included only patients with persistent AF, and 5 included patients with paroxysmal or persistent AF. Eight RCTs included only patients who were drug-refractory or drug-intolerant, and the remaining three included patients treated with catheter ablation as first-line therapy. Catheter ablation-treated patients had lower rates of AF recurrence than antiarrhythmic drug therapy-treated patients (relative risk [RR], 0.47; 95% CI, 0.38 to 0.58; p<0.001; I2=62%, p=0.003).

A Cochrane review by Chen et al (2012) evaluated catheter ablation for paroxysmal and persistent AF. It included 7 RCTs comparing catheter ablation with medical therapy. Reviewers’ main conclusions were that catheter ablation was superior at reducing the recurrence of AF (RR=0.27; 95% CI, 0.18 to 0.41), but that there were no differences in mortality rates (RR=0.50; 95% CI, 0.04 to 5.65), embolic complications (RR=1.01; 95% CI, 0.18 to 5.68), or death from thromboembolism (RR=3.04; 95% CI, 0.13 to 73.4).

Ganesan et al (2013) published results of a systematic review and meta-analysis of studies reporting long-term outcomes after percutaneous catheter ablation for paroxysmal and nonparoxysmal AF. Reviewers included 19 studies (RCTs, case-control and cohort studies, case series) that reported catheter ablation outcomes at 3 years or more after the index ablation procedures. Sample sizes in these studies ranged from 39 to 1404 patients (total n=6167 patients). For a single procedure, the pooled overall success rate at 12 months postprocedure was 64.2% (95% CI, 57.5% to 70.3%). At late follow-up, the overall single-procedure success, defined as freedom from atrial arrhythmia at latest follow-up, was 53.1% (95% CI, 46.2% to 60.0%). The pooled overall multiple-procedure long-term success rate was 79.8% (95% CI, 75.0% to 83.8%). The analysis did not identify any predictors of short- or long-term recurrence. Reporting of periprocedural complications was heterogeneous across studies, but complication rates were generally low.

Earlier systematic reviews and meta-analyses (2008, 2009) comparing RFA with antiarrhythmic drug therapy for AF have reported improved rates of freedom from arrhythmias with catheter ablation.

Other systematic reviews have assessed the effect of RFA on specific AF-related outcomes. Zhuang et al (2014) conducted a meta-analysis that evaluated the effect of RFA on left atrial volume and function in patients with AF. In a summary of data from 26 studies enrolling 1821 patients, RFA was associated in improvements in left atrial volume measurements compared with preablation (e.g., for left atrial diameter); the weighted mean difference (WMD) was -1.52 mm (95% CI, -2.57 to -0.47 mm). There were no significant improvements in left atrial function.

Randomized Controlled Trials

Since the TEC Assessment, additional RCTs comparing RFA with pharmacologic treatment have been identified. Wilber et al (2010) enrolled 167 patients who had failed at least 1 antiarrhythmic medication and had at least 3 AF episodes in the prior 6 months. Patients were randomized to catheter ablation or continued drug therapy and followed for 9 months. At the end of follow-up, 66% of patients in the ablation group were free of recurrent AF compared with 16% of patients in the medication group. Adverse events related to treatment occurred in 4.9% (5/103) of patients treated with ablation and in 8.8% (5/57) of patients treated with medications.

Forleo et al (2009) randomized 70 patients with type 2 diabetes and paroxysmal or persistent AF to RFA or an antiarrhythmic medication. Follow-up was for 1 year, with the primary outcome of recurrence of AF. At the end of the trial, 42.9% (15/35) of patients in the medication group were free of AF compared with 80% (28/35) of patients in the ablation group. QOL also improved significantly for patients in the ablation group. Adverse events from medications occurred more frequently (17.2% [6/35]) than complications from ablation (2.9% [1/35]).

Mont et al (2014) conducted an RCT comparing catheter RFA with antiarrhythmic drug therapy among 146 patients with symptomatic persistent AF. Patients were randomized in a 2:1 fashion to catheter RFA (n=98) or antiarrhythmic drug therapy (n=48). Although the trial was terminated before the planned sample size of 208 was enrolled (due to low enrollment), at 12 months of follow-up, the proportion of patients who were free of sustained AF episodes was higher in the catheter ablation group (70.4%) than in the antiarrhythmic drug therapy group (43.7%; p=0.002). QOL scores did not differ significantly between groups. Longer term outcomes were not reported.

Marrouche et al (2018) conducted an RCT comparing catheter ablation with medical therapy in 363 patients with systematic paroxysmal or persistent AF who had no response to, were unwilling to take, or had unacceptable side effects to antiarrhythmic drugs. Patients were randomized to catheter ablation (n=179) or medical therapy (n=184), with a median follow-up of 38 months. For patients treated with catheter ablation, there was a significantly lower rate of death from cardiac causes (20 [11.2%] vs 41 [22.3%]; hazard ratio [HR], 0.49; 95% CI, 0.29 to 0.84; p=0.009) or hospitalization for worsening heart failure (37 [20.7%] vs 66 [35.9%]; HR=0.56; 95% CI, 0.37 to 0.83; p=0.004) than found in patients treated with medical therapy alone.

Longer Term Outcomes

The available RCTs have mainly reported on short-term outcomes (>1 year) and, therefore, do not provide data on the rate recurrences after 1 year. Longer term outcomes have been reported and have generally found rates of early recurrence in the range of 20% to 30%, requiring repeat ablations. Rates of longer term recurrence are lower if early recurrence does not occur, in the range of 1% to 2% per year.

Hussein et al (2011) reported on 831 patients treated in 2005 (median follow-up, 55 months).

During the first year after ablation, 23.8% had a recurrence of AF. During the remaining follow-up, recurrences occurred in 8.9% additional patients. The overall rate free of arrhythmia and medications was 79.4% at 55 months. An additional 10.5% of patients were arrhythmia-free on medication, for a total clinical improvement rate of 89.9%. In a smaller study (n=509) with a follow-up to 5 years after initial ablation, Teunissen et al (2016) reported that, after a single procedure, 41.3% of patients had long-term maintenance of sinus rhythm.

Bunch et al (2013) reported on results from a prospective cohort study comparing the risk of stroke among patients with AF who had undergone catheter ablation, patients with AF who had not had ablation, and patients without a history of AF.  A total of 4212 patients with AF who had had catheter ablation were age- and sex-matched at a 1:4 ratio with 16,848 subjects in each of the other groups. Mean follow-up time was 3.9 years. At 1 year postprocedure, significantly more patients with AF who had not undergone ablation had a stroke (3.5%) than those with AF who had had ablation (1.4%) or had no history of AF (1.4%; p<0.001 for trend). During the follow-up period, for all ages and CHADS2 profiles, patients with AF who had ablation had a lower stroke risk than those with AF who had not.

Several smaller studies have also reported longer term follow-up after catheter RFA. Weerasooriya et al (2011) reported on 5-year follow-up in 100 patients treated with catheter ablation. Recurrences were most common within the first 6 months, with repeat procedures being common during that period. At 1, 2, and 5 years after ablation, arrhythmia-free survival rates were 87%, 81%, and 63%, respectively. Tzou et al (2010) reported on long-term follow-up for 123 patients who had a previous successful ablation, defined as free of AF at 1 year. At 3-year follow-up, 85% of patients were still free of AF and off all medications; at 5 years, 71% remained free of AF. The authors estimated a late recurrence rate of 7% per year for patients with an initially successful procedure. In a similar study, Bertaglia et al (2010) reported on outcomes after 6 years of follow-up for 229 patients who had had a single, successful ablation. At 1-year follow-up, 77% (177/229) of patients were free of AF and off all medications. After a mean additional follow-up of 49.7 months for these 177 patients, 58% remained free of AF. Sawhney et al (2009) reported on 5-year success rates for 71 patients who underwent ablation in 2002 or 2003. Freedom from symptomatic AF while off medications was achieved in 86% of patients at 1 year, in 79% at 2 years, and in 56% at 5 years. A substantial minority of patients (22.5%) had a recurrence at points more than 2 years after ablation. A study by Anselmino et al (2013) followed 196 patients who underwent catheter RFA for paroxysmal or persistent AF and had an LVEF of 50% or less for a mean of 46.2 months. During follow-up, 29.6% of patients required repeat ablation procedures. At the end of follow-up, 37.8% had had at least 1 episode of AF, atrial flutter, or ectopic atrial tachycardia. Takigawa et al (2014) reported on long-term follow-up for 1220 patients who underwent RFA for symptomatic paroxysmal AF. AF recurrence-free survival probabilities at 5 years were 59.4% after the initial procedure and 81.1% after the final ablation procedure (average procedures per patient, 1.3).

Repeat Procedures

Repeated procedures for recurrent AF or atrial flutter were commonly performed in most clinical trials included in this evidence review. Of the 10 RCTs reviewed comparing RFA with medical management, only 2 did not include repeated procedures. In the other 5 studies, 1 or more repeated procedures were allowed, and success rates reported generally incorporated the results of up to 3 procedures. In 4 studies reporting these data, repeated procedures were performed in 8.2%, 9%, 20%, and 32%of patients randomized to ablation. In their RCT of catheter ablation of AF in patients with heart failure, Hunter et al (2014) reported that repeat procedures were required in 65.4% of the catheter ablation group. Stabile et al (2006) did not report specifics on how many patients actually underwent repeat procedures, but limited data in the publication suggested that up to 30% of treated patients were eligible for repeat procedures. In the Jais et al (2008) study, patients underwent a mean of 1.8 procedures per patient and a median of 2 procedures per patient, indicating that approximately 50% of patients in the ablation group underwent at least 1 repeated procedure.

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

Pokushalov et al (2013) reported on results of an RCT comparing repeat catheter ablation with antiarrhythmic drug therapy for patients with paroxysmal AF who had failed an initial pulmonary vein isolation procedure. After an initial postablation blanking period, 154 patients with symptomatic AF recurrence were randomized to drug therapy (n=77) or repeat ablation (n=77). Patients were followed for 3 years with an implanted cardiac monitor. At the 3-year follow-up, 58% (45/77) of the repeat ablation group was free from AF or atrial tachycardia and antiarrhythmic drugs compared with 12% (9/77) of the antiarrhythmic therapy group (p<0.01). In the antiarrhythmic drug group, 43 (56%) patients crossed over to receive repeat ablation; in the repeat ablation group, 21 (27%) patients required antiarrhythmic drug therapy. By ITT analysis, 65% (50/77) of the repeat ablation group and 45% (35/77) of the drug therapy group were free from AF or atrial tachycardia (p=0.02).

Cryoablation for AF

Randomized Controlled Trials

Packer et al (2013) reported on results of the Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP) AF trial, an RCT comparing cryoablation with antiarrhythmic medications. This trial enrolled 245 patients with paroxysmal AF who had failed at least 1 (median, 1.2) membrane-active antiarrhythmic medications. Patients were randomized in a 2:1 fashion to cryoablation (n=163) or drug therapy (n=82). At 1-year follow-up, 69.9% of patients in the ablation group were free of AF vs 7.3% in the medication group. The single-procedure success rate was 57.7%. There was also a significantly greater reduction in symptoms for the ablation group. Seventy-nine percent of the drug treatment group crossed over to cryoablation during the 12-month follow-up because of recurrent, persistent AF. Cryoablation procedure-related adverse events occurred in 5 (3.1%) patients; major AF events occurred in 3.1% of the cryoablation group compared with 8.5% of the drug treatment group (p<0.001 for noninferiority). Phrenic nerve injury occurred at a rate of 13.5%, of which 86% resolved at 12 months.

Nonrandomized Studies

Su et al (2018) performed a multicenter, retrospective study of patients with drug-refractory paroxysmal AF who underwent cryoballoon ablation. The patients (N=452) were successfully treated with pulmonary vein isolation (99%); with transient phrenic nerve injury found to be the most common complication (1.5%). After 12 months, 87% (n=393) of patients had freedom from atrial arrhythmia.

Longer Term Follow-Up

Similar to RFA, the available RCTs for cryoablation have reported primarily on short-term outcomes. Examples of longer term outcomes include Vogt et al (2013), who reported on 605 patients who underwent cryoablation for symptomatic, paroxysmal, or persistent AF. Follow-up data beyond 12 months were available for 451 patients (median follow-up, 30 months). Of those with follow-up available, 278 (61.6%) were free of AF recurrence with no need for repeat procedures after a 3-month blanking period. After 1, 2, and 3 repeat procedures, rates of freedom from AF were 74.9%, 76.2%, and 76.9%, respectively. Phrenic nerve palsy was the most common adverse event, occurring in 2% of patients, all of which resolved within 3 to 9 months. There were 2 periprocedural strokes (1 periprocedural pericardial tamponade, 1pericardial effusion).

Smaller studies include Neumann et al (2013), who reported on 5-year outcomes after a single cryoablation procedure among 163 patients with symptomatic, drug-refractory paroxysmal AF. Fifty-three percent of subjects were free from recurrent AF, atrial tachycardia, or atrial flutter at 5 years with no additional procedures (after a 3-month blanking period). Boho et al (2015) reported on the follow-up to a median of 3 years after cryoablation for 205 patients with symptomatic paroxysmal or early persistent AF treated at a single institution. At the 6-, 12-, 24-, and 36-month follow-ups, 88%, 71%, 49%, and 31% had no documented recurrence of AF. Davies et al (2016) reported on AF recurrence rates (median follow-up, 56 months) for 200 patients with paroxysmal or persistent AF after cryoablation. During follow-up, 46.7% and 35.6% of those with paroxysmal and persistent AF, respectively, had a recurrence of symptomatic AF after a single procedure.

Andrade et al (2014) published a follow-up analysis of the STOP AF trial to evaluate the incidence and significance of early recurrence of AF after ablation. Of the 163 subjects randomized to cryoablation, 84 (51.5%) patients experienced early recurrence of AF, defined as any recurrence of AF lasting more than 30 seconds between 3 and 12 months postablation. The presence of early AF recurrence was associated with late AF recurrence: late AF recurrence occurred in 41 (25.1%) patients and was more likely in those with early recurrence (55.6% in those with early recurrence vs 12.7% in those without early recurrence; p<0.001).

Complications

Complications of catheter ablation were also reported by Dagres et al (2009) in a large cohort of 1000 patients undergoing ablation at a high-volume center in Europe. No deaths were definitively attributed to the procedure, but there were 2 deaths of uncertain cause within the first 30 days following ablation. Overall, 3.9% of patients had a major complication resulting from the procedure. Tamponade was the most serious life-threatening complication (1.3%). Major vascular complications occurred in 1.1%. Thromboembolism, cerebrovascular accident or TIA, atrioesophageal fistula, and endocarditis were all reported complications that occurred at a rate of less than 1%.

Individual clinical trials and case series have reported relatively low rates of complications but may be limited in their ability to detect uncommon outcomes due to small sample sizes. Gupta et al (2013) conducted a systematic review evaluating periprocedural complications following catheter ablation for AF. Reviewers selected 192 studies that included at least 100 participants undergoing catheter ablation for symptomatic AF and that reported complications. The total sample size was 83,236 patients. The overall acute complication rate was 2.9% (95% CI, 2.6% to 3.2%), with significant heterogeneity across studies. The most common complications were vascular complications (1.4%), cardiac tamponade (1.0%), pericardial effusion (0.7%), stroke/TIA (0.6%), and pulmonary vein stenosis (0.5%).

Cappato et al (2009) performed a multicenter, retrospective case series to estimate the overall mortality rate following ablation. Data were collected on 32569 patients from 162 clinical centers worldwide. Thirty-two deaths were reported, for a mortality rate of 0.98 per 1000 patients. The most common causes of death were tamponade (n=8), stroke (n=5), atrioesophageal fistula (n=5), and pneumonia (n=2).

One goal of the Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation (MACPAF) study was to identify adverse events, particularly cerebral thromboembolism, through the use of serial magnetic resonance imaging (MRI) and neuropsychologic testing. While there is some evidence that RFA for patients with AF reduces stroke risk, a clinically significant stroke or TIA attack occurs in 0.1% to 0.8% of patients undergoing catheter ablation, and several case series have demonstrated peridural brain lesions on diffusion-weighted MRI in up to 18% of patients undergoing catheter ablation of the left atrium. Thus, the MACPAF investigators evaluated patients pre- and postcatheter ablation with brain MRI at 3 Tesla and neurologic and neuropsychological testing. Short-term outcomes from these evaluations were reported by Haeusler et al (2013) and demonstrated that new ischemic lesions occurred in 41% of all patients. However, these brain lesions were not associated with cognitive dysfunction immediately postprocedure. Longer term follow-up was reported by Herm et al (2013). At follow-up MRI 6 months postprocedure, 31.3% of the acute brain lesions had formed a persistent glial scar. Similar to the short-term findings, there was no significant effect of either the ablation procedure or the presence of persistent brain lesions on attention or executive functions, short-term memory, or learning after 6 months.

Waldo et al (2012) reported on the results of a U.S. Food and Drug Administration‒directed postmarketing safety study involving 1275 patients from 6 prospective, multicenter studies of RFA using an open-irrigated catheter. A total of 4.9% (63/1275) of patients experienced serious, acute complications within 7 days of the procedure. Vascular access complications were most common, ranging from 0.5% to 4.7% across the 6 studies. Exacerbations of heart failure occurred in 1.5% of patients, and 2 patients experienced cardiac tamponade. There were no strokes or TIAs reported after the procedure.

Shah et al (2012) used data from a California hospital database to evaluate complications in 4156 patients who underwent catheter ablation for AF. Major complications occurred in 5.1% (211/4156) patients, with approximately half (2.6% [110/4156]) consisting of hemorrhage or hematoma at the vascular entry site. The most common cardiac complication was cardiac perforation and/or tamponade, which occurred in 2.5% (104/4156) of patients. Less common rates of serious adverse events included death (0.02%), stroke/TIA (0.31%), and pneumothorax/hemothorax (0.1%). Factors predictive of complications were female sex, older age, prior hospitalizations for AF, and less hospital expertise with ablation.

In a study of Medicare beneficiaries, Ellis et al (2009) identified 6065 admissions from 168 hospitals in which RFA for AF was performed. The total rate of in-hospital complications was 9.1%, with vascular complications accounting for over half the complications (5.7%). The mortality rate was 0.4%, and 0.6% of patients suffered a stroke or TIA, respectively. Perforation or tamponade occurred in 3.1% of patients and pneumothorax in 0.4%. The presence of chronic obstructive pulmonary disease or unstable angina was associated with a higher risk of complications, while obesity and hyperlipidemia were associated with a lower risk. Age and hospital volume were not significant predictors of risk, but low hospital RFA procedure volume was a significant predictor of in-hospital death.

Comparisons of RFA Techniques

Techniques for RFA for pulmonary vein isolation or substrate ablation have evolved. Specifying RFA techniques is not the focus of the present review, but recent large studies are described briefly.

Reddy et al (2015) reported on the results of a noninferiority RCT comparing a contact force-sensing RFA catheter with a standard (noncontact force-sensing) catheter in 300 patients with treatment-refractory paroxysmal AF. The trial’s primary effectiveness end point was a composite of acute ablation success and long-term ablation success (freedom from symptomatic AF, atrial tachycardia, or atrial flutter at 12 months off antiarrhythmic drugs, after a 3-month blanking period). In the modified ITT population, patients in the contact force-sensing catheter group (n=149) were noninferior to the control catheter group (n=141; 67.8% vs 69.4%, respectively; absolute difference, -1.6%; lower limit of 1-sided 95% CI; -10.7; p=0.007 for noninferiority).

A second, smaller RCT, published by Nakamura et al (2015), compared a contact force-sensing RFA catheter with a standard catheter (N=120), and reported lower rates of pulmonary vein reconnections in those treated with a contact force-sensing catheter.

Afzal et al (2015) performed a systematic review and meta-analysis, which included 9 studies (1 RCT [but not the Reddy RCT]), comparing RFA with contact force-sensing or noncontact force-sensing catheters. At 12-month follow-up, contact force-sensing catheter-treated patients had lower AF recurrence compared with standard catheter-treated patients (RR=0.63; 95% CI, 0.44 to 0.91; p=0.01).

Section Summary: Individuals with Symptomatic Paroxysmal or Persistent AF who have Failed Antiarrhythmic Drugs

Radiofrequency Ablation for AF

Numerous RCTs of RFA for isolation of the pulmonary veins vs medical management have reported that freedom from AF at 1 year is higher with RFA than with medical management. The trials mainly included patients who failed antiarrhythmic medications. These trials have reported that most patients undergoing RFA were free of AF at 1 year. QOL was also improved in these trials for patients undergoing catheter ablation. A smaller number of studies have evaluated outcomes longer than 1 year and reported that late recurrences occur up to 5 years, but were uncommon after the first year. Complications from RFA were reported at low rates in the RCTs, but the numbers of patients in these trials are too small to accurately estimate rates of uncommon events. Two RCTs have evaluated the use of catheter ablation as an initial strategy for paroxysmal AF; 1 RCT demonstrated reduced rates of AF recurrence, while the other reported reduced cumulative overall AF burden.

Cryoablation

Numerous RCTs and non RCTs have reported the use of cryoablation in patients with symptomatic paroxysmal or persistent AF who have failed antiarrhythmic drugs. Longer term follow-up in these patients has also been reported.

Complications and Adverse Events

Several large, database studies have estimated the adverse event rate from catheter ablation in the clinical care setting. The range of major adverse events in these studies is from 4% to 9%. Deaths have been reported and have occurred at rates less than 1%. Vascular complications at the groin site are the most common adverse events, occurring at rates of up to 5%. Serious cardiovascular adverse events such as tamponade and stroke occur uncommonly, at rates of approximately 1% or lower. There is some evidence that new ischemic lesions are commonly found using MRI after the procedure, but the clinical significance of these defects is unclear.

Individuals with Symptomatic Atrial Fibrillation and Congestive Heart Failure who have Failed Rate Control and Antiarrhythmic Drugs

Radiofrequency Ablation

Systematic Reviews

Zhu et al (2016) reported on a systematic review and meta-analysis of RCTs comparing catheter ablation with medical rate control in patients who had persistent AF and heart failure. Three trials (total n=143 subjects; range, 41-52 subjects) met reviewers’ inclusion criteria, all of which used blinded outcome assessment and were considered to have low risk of bias. For the meta-analysis’s primary end point, compared with medical rate control, catheter ablation was associated with larger improvements in left ventricular end-diastolic fraction (mean difference, 6.22%; 95% CI, 0.7% to 11.74%; I2=63%). Measures of peak oxygen capacity, New York Heart Association functional class, and QOL scores were also significantly improved in the catheter RFA-treated groups.

In that same year, Anselmino et al (2016) reported on a systematic review of available observational studies and RCTs evaluating catheter ablation for AF in patients with chronic heart failure or structural cardiomyopathies. For the population of patients with chronic heart failure, reviewers identified 17 observational studies, 4 RCTs, and 4 meta-analyses. Among the 4 RCTs, one compared catheter ablation with AV node ablation plus biventricular pacemaker insertion and the others compared catheter ablation with optimal medical therapy plus rate control. In the pooled analysis, the mean efficacy of catheter ablation in maintaining sinus rhythm was 59% after a single procedure, increasing to 77% after a repeat procedure.

Vaidya et al (2015) reported on results of a systematic review and meta-analysis of RCTs comparing pulmonary vein isolation, pharmacologic rate control, and AV junction ablation plus pacemaker insertion for AF. Subgroup analyses focused on patients with congestive heart failure. Reviewers identified 7 RCTs, 2 comparing AV junction ablation plus pacemaker insertion with pharmacologic rate control, 1 comparing AV junction ablation plus pacemaker insertion with pharmacologic rate control and pacemaker insertion, 1 comparing pulmonary vein isolation with AV junction ablation plus biventricular pacing, and 3 comparing pulmonary vein isolation with pharmacologic rate control. Sample sizes ranged from 36 to 99 patients, with 425 patients across the 7 studies. When pulmonary vein isolation was compared with pharmacologic rate control, based on 3 RCTs, pulmonary vein isolation-treated patients had higher increases in LVEF (weighted mean difference [WMD], +6.5; 95% confidence interval [CI], 0.6 to 12.5; p=0.03). When pulmonary vein isolation was compared with AV junction ablation plus pacemaker insertion, based on 1 RCT, pulmonary vein isolation-treated patients had higher increases in LVEF (WMD = +9.0; 95% CI, 6.3 to 11.7; p<0.01). Patients treated with pulmonary vein isolation had greater reductions in heart failure symptoms, measured by the Minnesota Living with Heart Failure Questionnaire compared with pharmacologic rate control, in 3 RCTs that included only patients with congestive heart failure (WMD = -11.0; 95% CI, -19.4 to -2.6; p=0.01). Minnesota Living with Heart Failure Questionnaire scores also improved when pulmonary vein isolation was compared with AV junction ablation plus pacemaker insertion.

Randomized Controlled Trials

Hunter et al (2014) conducted an RCT comparing catheter RFA with medical rate control for patients who had persistent AF and symptomatic heart failure, with adequate rate control at the time of enrollment. There was no requirement for patients to have failed antiarrhythmic drug therapy. The trial’s primary end point was the difference between groups in LVEF at 6 months postprocedure. Fifty patients were randomized, 26 to catheter ablation and 24 to medical management. At 6 months, 81% of the catheter ablation group was free from recurrent AF and antiarrhythmic drugs. LVEF at 6 months postprocedure was 40% in the catheter ablation group compared with 31% (p=0.015) in the medical management group. Catheter ablation was also associated with improvements in health-related QOL.

Jones et al (2013) reported on results from an RCT comparing catheter ablation with medical rate control for patients who had symptomatic heart failure, an LVEF of 35% or less, and persistent AF. Fifty-two patients were randomized, 26 each to catheter ablation or medical rate control. At 12 months postprocedure, sinus rhythm was maintained in 88% of the catheter ablation group, with a single-procedure success rate of 68%. For the trial’s primary outcome (peak oxygen consumption at 12 months postprocedure), there was a significant increase in peak consumption in the catheter ablation group (2.13 mL/kg/min) compared with a decrease in the medical management group (-0.94 mL/kg/min; mean difference, +3.07 mL/kg/min; 95% CI, 0.56 to 5.59 mL/kg/min; p=0.018).

Cryoablation

A search of the existing literature revealed no published evidence on the use of cryoablation to treat individuals with AF with heart failure.

Section Summary: Individuals with Symptomatic AF and CHF who have Failed Rate Control and Antiarrhythmic Drugs

Evidence from systematic reviews, RCTs, and an observational study are consistent in demonstrating that catheter ablation improves heart failure outcomes for patients with heart failure and coexisting AF. No literature on cryoablation was identified.

Individuals with Recurrent Symptomatic Paroxysmal Atrial Fibrillation

Randomized Controlled Trials (Multiple Modalities)

Packer et al (2019) published results from the Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial, an international multicenter RCT designed to determine whether catheter ablation is more effective than conventional medical therapy to prevent major cardiovascular events in AF. A total of 2204 patients were enrolled and randomized 1:1 from November 2009-April 2016. Follow-up was conducted through December 2017. Catheter ablation devices used energy sources available in the clinical trial site and with which investigators had the requisite expertise. In the catheter ablation treatment group (n=1108), the primary endpoint (a composite of death, disabling stroke, serious bleeding, and/or cardiac arrest) occurred in 8.0% of patients and in 9.2% of patients in the drug therapy group (HR: 0.86 (95% CI: 0.65-1.15) p=030) and was not superior to medical therapy. There were 13 prespecified secondary outcomes; 3 of which were reported. All-cause mortality did not differ between groups. Death or cardiovascular hospitalization and AF recurrence were statistically significantly reduced in the catheter ablation group.

Mark et al (2019) published the results of 12-month QOL outcomes (median follow-up of 48.5 months) for participants in the CABANA trial. The Atrial Fibrillation Effect on QualiTty-of-Life (AFEQT) mean summary score in the catheter ablation group was 86.4 points vs 80.9 points in the drug therapy group (adjusted difference 5.3 points [95%CI, 3.7-6.9]: P 5 is considered a clinically meaningful difference (adjusted difference, -1.5 points [95% CI, -2.0 to 1.1]; P<0.001). The trial used a modified MAFSI questionnaire combining frequency scores range from 0 to 4 (never to always) and severity scores ranging from 0 (no AF symptoms) to 40 (most severe AF symptoms). The investigators developed a trial specific clinically meaningful change of 1.6 points for the frequency score and 1.3 points for the severity score.

Blomstrom-Lundqvist et al (2019) published the results for the Catheter Ablation compared with Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial, an RCT designed to assess the QOL after catheter ablation compared to medical therapy. The primary outcome at 12 months was the difference in the General Health subscale score. The QOL score increases in the catheter ablation group from 61.8 to 73.9 points vs 62.7 to 65.4 points in the medication group (95% CI: 3.1-14.7; p=0.003).

Radiofrequency Ablation

Systematic Reviews

Hakalathi et al (2015) reported on a systematic review and meta-analysis of RCTs comparing RFA with antiarrhythmic drug therapy as first-line therapy for symptomatic AF. They selected 3 trials (total N=491 patients), including the RAAFT-2 (2014) and MANTRA-PAF (2012) trials (described below) and the earlier RAAFT-1 trial. RAAFT-2 and MANTRA-PAF were considered to be at low risk of bias. RFA was associated with lower risk of recurrence of AF (RR=0.63; 95% CI, 0.44 to 0.92; p=0.02; I2=38%).

Randomized Controlled Trials

RAAFT-2

Morillo et al (2014) published results of the RAAFT-2 trial, an RCT comparing RFA with antiarrhythmic drug therapy as first-line therapy for paroxysmal AF. Eligible patients had symptomatic recurrent paroxysmal AF lasting more than 30 seconds, with 4 or fewer episodes in the prior 6 months, and had had no previous antiarrhythmic drug treatment. The trial enrolled 127 patients at 16 centers; 66 were randomized to RFA and 61 to antiarrhythmic drug therapy, at the discretion of the treating physician. In the RFA group, 63 underwent ablation; during follow-up, 9 underwent reablation and 6 crossed over to receive antiarrhythmic drug therapy. In the drug therapy group, 26 crossed over to undergo ablation and 24 discontinued antiarrhythmic drug therapy but continued in the trial. Analysis was intention-to-treat (ITT). Patients were followed with biweekly scheduled transtelephonic monitor recordings and symptomatic recordings through the 24-month follow-up period. The trial’s primary outcome (recurrence of any atrial tachyarrhythmia lasting >30 seconds) occurred in 72.1% (n=44) in the antiarrhythmic drug group compared with 54.5% (n=36) in the ablation group (HR=0.56; 95% CI, 0.35 to 0.90; p=0.02). Fewer patients in the RFA group had recurrence of symptomatic AF, atrial flutter, or atrial tachycardia (47% vs 59%; HR=0.56; 95% CI, 0.33 to 0.95; p=0.03) or recurrence of symptomatic AF (41% vs 57%; HR=0.52; 95% CI, 0.3 to 0.89; p=0.02). QOL measures did not differ significantly between groups.

MANTRA-PAF

An earlier RCT (MANTRA-PAF) evaluated RFA as the initial therapy for paroxysmal AF was reported by Cosedis Nielsen et al (2012). A total of 294 patients were randomized to initial treatment with catheter ablation or to pharmacologic therapy. Patients were followed to 24 months for the primary outcomes of burden of AF (percentage of time in AF on a Holter monitor) at each time point and cumulative burden of AF over all time points. For individual time points, the burden of AF was lower in the catheter RFA group only at 24 months (9% vs 18%, p=0.007). The 90th percentile cumulative burden did not differ significantly between groups (13% vs 19%; p=0.10). The secondary outcome of a percentage of patients free from AF at 24 months was greater for the catheter ablation group (85% vs 71%, p=0.004), as was the secondary outcome of freedom from symptomatic AF (93% vs 84%, p=0.01). There was 1 death in the ablation group (due to a procedural-related stroke), and 3 patients in that group developed cardiac tamponade following the procedure.

Five-year follow-up from MANTRA-PAF was reported by Nielsen et al (2017). Follow-up was available for 245 (83%) of 294 patients, of whom 227 had Holter recordings. The randomized groups did not differ significantly in terms of their availability for follow-up. On ITT analysis, significantly more patients in the RFA group were free from any AF (126/146 [86%]) than those in the pharmacologic therapy group (105/148 [71%]; RR=0.82; 95% CI, 0.73 to 0.93; p=0.001). Symptomatic AF burden was also significantly lower in the RFA group, although QOL was not.

Section Summary: Individuals with Recurrent Symptomatic Paroxysmal AF

Numerous RCTs, including those that evaluate long-term outcomes, have evaluated RFA and cryoablation in patients with recurrent symptomatic paroxysmal AF. Most recently, the CABANA trial noted that the use of RFA did not show significant improvement over medications.

Summary of Evidence

For individuals who have symptomatic paroxysmal or persistent AF who have failed antiarrhythmic drugs who receive RFA or cryoablation, the evidence includes multiple RCTs and systematic reviews. Relevant outcomes are overall survival, symptoms, morbid events, and quality of life. RCTs comparing RFA with antiarrhythmic medications have reported that freedom from AF is more likely after ablation than after medications. Results of long-term follow-up (5-6 years) after ablation have demonstrated that late recurrences continue in patients who are free of AF at 1 year. However, most patients who are AF-free at 1 year remain AF-free at 5 to 6 years. Multiple RCTs comparing cryoablation with RFA have found that cryoablation is noninferior to RFA for AF control. RFA and cryoablation differ in their adverse event profiles. For example, cryoablation is associated with higher rates of phrenic nerve paralysis but may permit a shorter procedure time. Given current data, it would be reasonable to consider both RFA and cryoablation effective for catheter ablation of AF foci or pulmonary vein isolation, provided there is a discussion about the risks and benefits of each. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have symptomatic AF and congestive heart failure who have failed rate control and antiarrhythmic drugs who receive RFA or cryoablation, the evidence includes a TEC Assessment, supported by RCTs. Relevant outcomes are overall survival, symptoms, morbid events, and quality of life. Based on a multicenter RCT, the TEC Assessment found the evidence sufficient to conclude that catheter ablation improves outcomes more than the alternative, atrioventricular nodal ablation and pacemaker insertion. Findings from this RCT have been supported by other comparative studies, which have reported improvements in AF. It is reasonable to consider both RFA and cryoablation effective for catheter ablation of AF foci or pulmonary vein isolation, provided that there is a discussion about the risks and benefits of each. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have recurrent symptomatic paroxysmal AF who receive RFA or cryoablation as an initial rhythm-control strategy, the evidence includes RCTs, nonrandomized studies, and systematic reviews. Relevant outcomes are overall survival, symptoms, morbid events, and quality of life. The most current RCT with adequate follow-up compared pulmonary vein isolation by catheter ablation (using either cryoablation or RFA to medical therapy. Catheter ablation was not superior to medical therapy for major cardiovascular outcomes but secondary outcomes including AF recurrence favored catheter ablation. QOL measures reported in this RCT favored catheter ablation. Two other RCTs with low risk of bias compared catheter ablation for pulmonary vein isolation with antiarrhythmic medications. One RCT demonstrated reduced rates of AF recurrence, while the other reported reduced cumulative overall AF burden. Together, these results suggest that, when a rhythm-control strategy is desired, catheter ablation is a reasonable alternative to antiarrhythmic drug therapy. While the RCTs comparing ablation with medical therapy were conducted using RFA, it is reasonable to consider both RFA and cryoablation effective for catheter ablation of AF foci or pulmonary vein isolation, provided that there is a discussion about the risks and benefits of each. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Practice Guidelines and Position Statements

Heart Rhythm Society et al

An expert consensus document on catheter and surgical catheter ablation for atrial fibrillation (AF) was developed jointly by 7 cardiac specialty societies (Heart Rhythm Society [HRS], European Heart Rhythm Association, European Cardiac Arrhythmia Society, American College of Cardiology, American Heart Association, Asia Pacific Heart Rhythm Society, Society of Thoracic Surgeons) in 2012. A related group of cardiac specialty societies (HRS, European Heart Rhythm Association, European Cardiac Arrhythmia Society, Asia Pacific Heart Rhythm Society, Latin American Society of Cardiac Stimulation and Electrophysiology) updated these guidelines in 2017, suggesting the following recommendations for catheter ablation (see Table 2).

Table 2. Guidelines for Management of Catheter Ablation for AF

Recommendation

COR

LOE

Symptomatic AF refractory or intolerant to at least 1 class 1 or 3 antiarrhythmic medication

Paroxysmal: Catheter ablation is recommended

I

A

Persistent: Catheter ablation is reasonable

IIa

B-NR

Long-standing persistent: Catheter ablation may be considered

IIb

C-LD

Symptomatic AF prior to initiation of antiarrhythmic drug therapy with a class 1 or 3 antiarrhythmic agent

Paroxysmal: Catheter ablation is reasonable

IIa

B-R

Persistent: Catheter ablation may be considered

IIa

C-EO

Longstanding Persistent: Catheter ablation may be considered

IIb

C-EO

AF: atrial fibrillation; COR: class of recommendation: LOE: level of evidence.

American College of Cardiology et al

In 2014, American College of Cardiology, American Heart Association, and HRS issued guidelines for management of patients with AF. The guidelines included the following recommendations for rate control and rhythm control (see Table 3).

Table 3. Guidelines for Rate and Rhythm in Management of AF

Recommendation

COR

LOE

Rate control

“AV nodal ablation with permanent ventricular pacing is reasonable to control heart rate when pharmacological therapy is inadequate and rhythm control is not achievable.”

I

B

“AV nodal ablation with permanent ventricular pacing should not be performed to improve rate control without prior attempts to achieve rate control with medications.”

IIIa

C

Rhythm control

“AF catheter ablation is useful for symptomatic paroxysmal AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication when a rhythm-control strategy is desired.”

I

A

“Before consideration of AF catheter ablation, assessment of the procedural risks and outcomes relevant to the individual patient is recommended.”

I

C

“AF catheter ablation is reasonable for some patients with symptomatic persistent AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication.”

IIa

A

“In patients with recurrent symptomatic paroxysmal AF, catheter ablation is a reasonable initial rhythm-control strategy before therapeutic trials of antiarrhythmic drug therapy, after weighing the risks and outcomes of drug and ablation therapy.”

IIa

B

“AF catheter ablation may be considered for symptomatic long-standing (>12 months) persistent AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication when a rhythm-control strategy is desired).”

IIb

B

“AF catheter ablation may be considered before initiation of antiarrhythmic drug therapy with a class I or III antiarrhythmic medication for symptomatic persistent AF when a rhythm-control strategy is desired.”

IIb

C

“AF catheter ablation should not be performed in patients who cannot be treated with anticoagulant therapy during and after the procedure.”

IIIa

C

“AF catheter ablation to restore sinus rhythm should not be performed with the sole intent of obviating the need for anticoagulation.”

IIIa

C

AF: atrial fibrillation; AV: arteriovenous; COR: class of recommendation: LOE: level of evidence.
a Not recommended

Although the guidelines did not make a specific recommendation on the use of cryoablation, they did state that “Cryoballoon ablation is an alternative to point-by-point radiofrequency ablation to achieve pulmonary vein isolation.”

U.S. Preventive Services Task Force Recommendations

Not applicable

Key Words:

Atrial fibrillation, circumferential pulmonary vein ablation (PVA), pulmonary vein isolation, arrhythmogenic, cryoablation, cryoballoon therapy, cryoballoon intervention, cryoballoon technique, cryoballoon isolation, cryoballoon ablation

Approved by Governing Bodies:

In February 2009, the NaviStar® ThermoCool® Irrigated Deflectable Diagnostic/Ablation Catheter and EZ Steer ThermoCool NAV Catheter (Biosense Webster) received expanded approval by the U.S. Food and Drug Administration (FDA) through the premarket approval process for RFA to treat drug-refractory recurrent symptomatic paroxysmal AF. FDA product code: OAD.

Devices using laser or cryoablation techniques for substrate ablation have been approved by FDA through the premarket approval process for AF (FDA product code: OAE). They include:

  • Arctic Front™ Cardiac CryoAblation Catheter and CryoConsole (Medtronic) in 2010.

  • TactiCath™ Quartz Catheter and TactiSysQuartz® Equipment (St. Jude Medical) in 2014.

  • HeartLight® Endoscopic Ablation System (Cardiofocus) in 2016.

  • The FreezorXtra Catheter (Medtronic) in 2016.

Also, numerous catheter ablation systems have been approved by FDA for other ablation therapy for arrhythmias such as supraventricular tachycardia, atrial flutter, and ventricular tachycardia. FDA product code: LPB.

Benefit Application:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply.  FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.

Current Coding:

CPT Codes:

93656

Comprehensive electrophysiologic evaluation including transseptal catheterizations, insertion and repositioning of multiple electrode catheters with induction or attempted induction of an arrhythmia including left or right atrial pacing/recording when necessary, right ventricle pacing/recording when necessary, and HIS bundle recording when necessary with intracardiac catheter ablation of atrial fibrillation by pulmonary vein isolation

93657

; additional linear or focal intracardiac catheter ablation of the left or right atrium for treatment of atrial fibrillation remaining after completion of pulmonary vein isolation

93799

Unlisted cardiovascular service or procedure

References:

  1. Abugattas JP, Iacopino S, Moran D, et al. Efficacy and safety of the second generation cryoballoon ablation for the treatment of paroxysmal atrial fibrillation in patients over 75 years: a comparison with a younger cohort. Europace. Nov 1 2017;19(11):1798-1803.

  2. AFFIRM Investigators.  A comparison of rate control and rhythm control in patients with atrial fibrillation.  NEJM, December 2002, Vol. 347, No. 23, pp. 1825-1833.

  3. Afzal MR, Chatta J, Samanta A, et al. Use of contact force sensing technology during radiofrequency ablation reduces recurrence of atrial fibrillation: A systematic review and meta-analysis. Heart Rhythm. Sep 2015; 12(9):1990-1996.

  4. American College of Cardiology AHA, the Heart Rhythm Society. 2014 ACC/AHA/HRS Guideline on the Management of Patients with Atrial Fibrillation. 2014; //content.onlinejacc.org/article.aspx?articleid=1854230. Accessed April 2015.

  5. American College of Physicians AAoFP. Clinical Practice Guidelines: Atrial Fibrillation. 2008; www.aafp.org/patient-care/clinical-recommendations/all/atrial-fibrillation.html. Accessed April 201

  6. Andrade JG, Khairy P, Guerra PG, et al.  Efficacy and safety of cryoballoon ablation for atrial fibrillation: a systematic review of published studies.  Heart Rhythm 2011; 8(9):1444-51.

  7. Andrade JG, Khairy P, Macle L, et al. Incidence and significance of early recurrences of atrial fibrillation after cryoballoon ablation: insights from the multicenter Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) Trial. Circ Arrhythm Electrophysiol. Feb 2014; 7(1):69-75.

  8. Anselmino M, Grossi S, Scaglione M et al. Long-term results of transcatheter atrial fibrillation ablation in patients with impaired left ventricular systolic function. J. Cardiovasc. Electrophysiol. 2013; 24(1):24-32.

  9. Anselmino M, Matta M, Castagno D, et al. Catheter ablation of atrial fibrillation in chronic heart failure: state-of-the-art and future perspectives. Europace. Feb 8 2016.

  10. Arentz T, et al.  Feasibility and safety of pulmonary vein isolation using a new mapping and navigation system in patients with refractory atrial fibrillation.  Circulation 2003; 108: 2484-2490.

  11. Aryana A, Singh SM, Kowalski M, 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. Aug 2015; 26(8):832-839.

  12. Bertaglia E, Tondo C, De Simone A et al. Does catheter ablation cure atrial fibrillation? Single-procedure outcome of drug-refractory atrial fibrillation ablation: a 6-year multicentre experience. Europace 2010; 12(2):181-7.

  13. Blomström-Lundqvist C, Gizurarson S, Schwieler J, 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;Epub ahead of print.

  14. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Catheter ablation of the pulmonary veins as a treatment for atrial fibrillation. TEC Assessments. 2008; Volume 23 Tab 11.

  15. Boho A, Misikova S, Spurny P, et al. A long-term evaluation of cryoballoon ablation in 205 atrial fibrillation patients: a single center experience. Wien Klin Wochenschr. Oct 2015; 127(19-20):779-785.

  16. Buiatti A, von Olshausen G, Barthel P, et al. Cryoballoon vs. radiofrequency ablation for paroxysmal atrial fibrillation: an updated meta-analysis of randomized and observational studies. Europace. Mar 01 2017; 19(3):378-384.

  17. Bunch TJ, May HT, Bair TL et al. Atrial fibrillation ablation patients have long-term stroke rates similar to patients without atrial fibrillation regardless of CHADS2 score. Heart Rhythm 2013; 10(9):1272-7.

  18. Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace. Jan 1 2018;20(1):e1-e160.

  19. Calkins H, Kuck KH, Cappato R et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm 2012; 9(4):632-96 e21.

  20. Calkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm. Apr 2012; 9(4):632-696 e621.

  21. Cappato R, Calkins H, Chen SA et al. Prevalence and causes of fatal outcome in catheter ablation of atrial fibrillation. J Am Coll Cardiol 2009; 53(19):1798-803.

  22. Cappato R, et al.  Prospective assessment of late conduction recurrence across radiofrequency lesions producing electrical disconnection at the pulmonary vein ostium in patients with atrial fibrillation.  Circulation 2003; 108: 1599-1604.

  23. Cardoso R, Mendirichaga R, Fernandes G, et al. Cryoballoon versus radiofrequency catheter ablation in atrial fibrillation: a meta-analysis. J Cardiovasc Electrophysiol. Oct 2016; 27(10):1151-1159.

  24. Chen CF, Gao XF, Duan X, et al. Comparison of catheter ablation for paroxysmal atrial fibrillation between cryoballoon and radiofrequency: a meta-analysis. J Interv Card Electrophysiol. Jan 07 2017.

  25. Chen HS, Wen JM, Wu SN et al. Catheter ablation for paroxysmal and persistent atrial fibrillation. Cochrane Database Syst Rev 2012; 4:CD007101.

  26. Cheng X, Hu Q, Zhou C, et al. The long-term efficacy of cryoballoon vs irrigated radiofrequency ablation for the treatment of atrial fibrillation: A meta-analysis. Int J Cardiol. Feb 15 2015; 181:297-302. 

  27. Chun KR, Schmidt B, Metzner A, et al. The 'single big cryoballoon' technique for acute pulmonary vein isolation in patients with paroxysmal atrial fibrillation: a prospective observational single centre study. Eur Heart J. Mar 2009; 30(6):699-709.

  28. Cosedis Nielsen J, Johannessen A, Raatikainen P, et al. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med. Oct 25 2012; 367(17):1587-1595.

  29. Cummings JE, et al.  Brief communication: Atrial-esophageal fistulas after radiofrequency ablation. Annals of Internal Medicine 2006; 144: 572-574.

  30. Dagres N, Hindricks G, Kottkamp H et al. Complications of atrial fibrillation ablation in a high-volume center in 1,000 procedures: still cause for concern? J Cardiovasc Electrophysiol 2009; 20(9):1014-9.

  31. Davies AJ, Jackson N, Barlow M, et al. Long Term Follow-up of pulmonary vein isolation using cryoballoon ablation. Heart Lung Circ. Mar 2016; 25(3):290-295.

  32. Di Biase L, Mohanty P, Mohanty S, et al. 408-08 - Ablation vs. amiodarone for treatment of persistent atrial fibrillation in patients with congestive heart failure and an implanted device: Results from the AATAC Multicenter Randomized Trial. American College of Cardiology Scientific Sessions; March 16, 2015, 2015; San Diego, CA.

  33. Dill T, et al. Pulmonary vein diameter reduction after radiofrequency catheter ablation for paroxysmal atrial fibrillation evaluated by contrast-enhanced three-dimensional magnetic resonance imaging. Circulation 2003; 107: 845-850.

  34. Dukkipati SR, Cuoco F, Kutinsky I, et al. Pulmonary vein isolation using the visually guided laser balloon: a prospective, multicenter, and randomized comparison to standard radiofrequency ablation. J Am Coll Cardiol. Sep 22 2015; 66(12):1350-1360.

  35. Ellis ER, Culler SD, Simon AW et al. Trends in utilization and complications of catheter ablation for atrial fibrillation in Medicare beneficiaries. Heart Rhythm 2009; 6(9):1267-73.

  36. Fadahunsi O, Talabi T, Olowoyeye A, et al. Ablation of complex fractionated atrial electrograms for atrial fibrillation rhythm control: a systematic review and meta-analysis. Can J Cardiol. Jul 16 2015.

  37. Falk RH.  Management of atrial fibrillation—Radical reform or modest modification?  NEJM, December 2002, Vol. 347, No. 23, pp. 1883-1884.

  38. 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; 20(1):22-8.

  39. Fuster V, et al.  ACC/AHA/ESC Guidelines for the management of patient’s atrial fibrillation: Executive summary.  JACC, October 2001, Vol. 38, No. 4, pp. 1231-1265.

  40. 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.

  41. Ganesan AN, Shipp NJ, Brooks AG et al. Long-term outcomes of catheter ablation of atrial fibrillation: a systematic review and meta-analysis. J Am Heart Assoc 2013; 2(2):e004549.

  42. Geng J, Zhang Y, Wang Y, et al. Catheter ablation versus rate control in patients with atrial fibrillation and heart failure: A multicenter study. Medicine (Baltimore). Dec 2017;96(49):e9179.

  43. Gjesdal K, Vist GE, Bugge E et al. Curative ablation for atrial fibrillation: a systematic review. Scand Cardiovasc J 2008; 42(1):3-8.

  44. Gupta A, Perera T, Ganesan A et al. Complications of catheter ablation of atrial fibrillation: a systematic review. Circ Arrhythm Electrophysiol 2013; 6(6):1082-8.

  45. Haeusler KG, Koch L, Herm J et al. 3 Tesla MRI-detected brain lesions after pulmonary vein isolation for atrial fibrillation: results of the MACPAF study. J. Cardiovasc. Electrophysiol. 2013; 24(1):14-21.

  46. Haeusler KG, Koch L, Ueberreiter J et al. Stroke risk associated with balloon based catheter ablation for atrial fibrillation: Rationale and design of the MACPAF Study. BMC Neurol 2010; 10:63.

  47. Hakalahti A, Biancari F, Nielsen JC, et al. Radiofrequency ablation vs. antiarrhythmic drug therapy as first line treatment of symptomatic atrial fibrillation: systematic review and meta-analysis. Europace. Mar 2015; 17(3):370-378.

  48. Herm J, Fiebach JB, Koch L 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 Arrhythm Electrophysiol 2013; 6(5):843-50

  49. Hu X, Jiang J, Ma Y, et al. Is there still a role for additional linear ablation in addition to pulmonary vein isolation in patients with paroxysmal atrial fibrillation? An Updated Meta-analysis of randomized controlled trials. Int J Cardiol. Apr 15 2016; 209:266-274.

  50. Hunter RJ, Baker V, Finlay MC, 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. Dec 2015; 26(12):1307-1314.

  51. Hunter RJ, Berriman TJ, Diab I et al. A Randomised Controlled Trial of Catheter Ablation versus Medical Treatment of Atrial Fibrillation in Heart Failure (THE CAMTAF TRIAL). Circ Arrhythm Electrophysiol 2014.

  52. Hunter RJ. Point by Point RF Ablation Versus the Cryoballoon or a Novel Combined Approach: a RTC Comparing Three Methods of PVI for Paroxysmal AF (The Cryo versus RF Trial). Paper presented at: Heart Rhythm Society2014; San Francisco, CA.

  53. Hussein AA, Saliba WI, Martin DO et al. Natural history and long-term outcomes of ablated atrial fibrillation. Circ Arrhythm Electrophysiol 2011; 4(3):271-8.

  54. 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.

  55. January CT, Wann LS, Alpert JS, 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. J Am Coll Cardiol. Dec 02 2014; 64(21):e1-76.

  56. Jones DG, Haldar SK, Hussain W et al. A randomized trial to assess catheter ablation versus rate control in the management of persistent atrial fibrillation in heart failure. J. Am. Coll. Cardiol. 2013; 61(18):1894-903.

  57. Jourda F, Providencia R, Marijon E, 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. Feb 2015; 17(2):225-231. 

  58. Joy PS, Gopinathannair R, Olshansky B. Effect of ablation for atrial fibrillation on heart failure readmission rates. Am J Cardiol. Nov 1 2017;120(9):1572-1577.

  59. Julia J, Chierchia GB, de Asmundis C, 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. Mar 2015; 42(2):161-169.

  60. Katritsis DG, et al.  Ablation of superior pulmonary veins compared to ablation of all four pulmonary veins:  A randomized clinical trial.  Journal of Cardiovascular Electrophysiology, June 2004, Vol. 15, No. 6, pp. 641-645.

  61. Kay GN, Ellenbogen KA, Giudici M et al. The Ablate and Pace Trial: a prospective study of catheter ablation of the AV conduction system and permanent pacemaker implantation for treatment of atrial fibrillation. APT Investigators. J. Interv. Card. Electrophysiol. 1998; 2(2):121-35.

  62. 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.

  63. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. Nov 2016; 18(11):1609-1678.

  64. Koch L, Haeusler KG, Herm J et al. Mesh ablator vs. cryoballoon pulmonary vein ablation of symptomatic paroxysmal atrial fibrillation: results of the MACPAF study. Europace 2012; 14(10):1441-9.

  65. Kojodjojo P, O’Neill MD, Lim PB, Malcolm-Lawes L, et al.  Pulmonary venous isolation by antral ablation with a large cryoballoon for treatment of paroxysmal and persistent atrial fibrillation:  medium-term outcomes and non-randomized comparison with pulmonary venous isolation by radiofrequency ablation.  Heart 2010; 96:1379-84.

  66. 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; 86 Suppl 1:S8-16.

  67. Kuck KH, Brugada J, Furnkranz A, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med. Jun 09 2016; 374(23):2235-2245.

  68. Kuck KH, Furnkranz A, Chun KR, et al. Cryoballoon or radiofrequency ablation for symptomatic paroxysmal atrial fibrillation: reintervention, rehospitalization, and quality-of-life outcomes in the FIRE AND ICE trial. Eur Heart J. Oct 07 2016; 37(38):2858-2865.

  69. Lakhani M, Saiful F, Parikh V, et al. Recordings of diaphragmatic electromyograms during cryoballoon ablation for atrial fibrillation accurately predict phrenic nerve injury. Heart Rhythm. Mar 2014; 11(3):369-374.

  70. Lee MA, et al.  The effect of atrial pacing therapies on atrial tachyarrhythmia burden and frequency.  JACC, June 2003, Vol. 41, No. 11, pp. 1926-1932.

  71. 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; 19(6):599-605.

  72. Linhart M, Bellmann B, Mittmann-Braun E 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(12):1343-8.

  73. Linhart M, Nielson A, Andrie RP, et al. Fluoroscopy of spontaneous breathing is more sensitive than phrenic nerve stimulation for detection of right phrenic nerve injury during cryoballoon ablation of atrial fibrillation. J Cardiovasc Electrophysiol. Aug 2014; 25(8):859-865.

  74. Liu XH, Chen CF, Gao XF, et al. Safety and efficacy of different catheter ablations for atrial fibrillation: a systematic review and meta-analysis. Pacing Clin Electrophysiol. Aug 2016; 39(8):883-899.

  75. Luik A, Merkel M, Hoeren D et al. Rationale and design of the FreezeAF trial: a randomized controlled noninferiority trial comparing isolation of the pulmonary veins with the cryoballoon catheter versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation. Am. Heart J. 2010; 159(4):555-60 e1.

  76. Luik A, Radzewitz A, Kieser M, et al. Cryoballoon versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation: the prospective, randomized, controlled, noninferiority FreezeAF study. Circulation. Oct 6 2015; 132(14):1311-1319.

  77. Malmborg H, Lonnerholm S, Blomstrom P et al. Ablation of atrial fibrillation with cryoballoon or duty-cycled radiofrequency pulmonary vein ablation catheter: a randomized controlled study comparing the clinical outcome and safety; the AF-COR study. Europace 2013; 15(11):1567-73.

  78. Mansour M, et al.  Efficacy and safety of segmental ostial versus circumferential extra—Ostial pulmonary vein isolation for atrial fibrillation.  Journal of Cardiovascular Electrophysiology, May 2004, Vol. 15, No. 5, pp. 532-537.

  79. Mark DB, Anstrom KJ, Sheng S, 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;Epub ahead of print.

  80. Marrouche NF, Brachmann J, Andresen D, et al. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med. Feb 1 2018;378(5):417-427

  81. Mont L, Bisbal F, Hernandez-Madrid A et al. Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study). Eur. Heart J. 2013.

  82. Mont L, Bisbal F, Hernandez-Madrid A, et al. Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study). Eur Heart J. Feb 2014; 35(8):501-507.

  83. Morillo CA, Verma A, Connolly SJ, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. JAMA. Feb 19 2014; 311(7):692-700.

  84. Morillo CA, Verma A, Connolly SJ, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. JAMA. Feb 19 2014; 311(7):692-700. 

  85. Nair GM, Nery PB, Diwakaramenon S et al. A Systematic Review of Randomized Trials Comparing Radiofrequency Ablation with Antiarrhythmic Medications in Patients with Atrial Fibrillation. J. Cardiovasc. Electrophysiol. 2009; 20(2):138-44.

  86. Nakamura K, Naito S, Sasaki T, et al. Randomized comparison of contact force-guided versus conventional circumferential pulmonary vein isolation of atrial fibrillation: prevalence, characteristics, and predictors of electrical reconnections and clinical outcomes. J Interv Card Electrophysiol. Dec 2015; 44(3):235-245.

  87. Neumann T, Vogt J, Schumacher B, et al. Circumferential pulmonary vein isolation with the cryoballoon technique results from a prospective 3-center study. J Am Coll Cardiol. Jul 22 2008; 52(4):273-278.

  88. Neumann T, Wojcik M, Berkowitsch A et al. Cryoballoon ablation of paroxysmal atrial fibrillation: 5-year outcome after single procedure and predictors of success. Europace 2013; 15(8):1143-9.

  89. Nielsen JC, Johannessen A, Raatikainen P, 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. Mar 2017; 103(5):368-376.

  90. Noheria A, Kumar A, Wylie JV, Jr. et al. Catheter ablation vs antiarrhythmic drug therapy for atrial fibrillation: a systematic review. Arch Intern Med 2008; 168(6):581-6.

  91. Nyong J, Amit G, Adler AJ, et al. Efficacy and safety of ablation for people with non-paroxysmal atrial fibrillation. Cochrane Database Syst Rev. Nov 22 2016; 11:CD012088.

  92. Oral H, et al.  Catheter ablation for paroxysmal atrial fibrillation:  Segmental pulmonary vein ostial ablation versus left atrial ablation.  Circulation 2003; 108: 2355-2360.

  93. Oral H, et al.  Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation, March 2002; 105: 1077-1081.

  94. Oral H, et al. A tailored approach to catheter ablation of paroxysmal atrial fibrillation.  Circulation 2006; 113: 1824-1831.

  95. 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.

  96. Packer DL, Kowal RC, Wheelan KR et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial. J. Am. Coll. Cardiol. 2013; 61(16):1713-23.

  97. Packer DL, Mark DB, Robb RA, 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;Epub ahead of print.

  98. 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.

  99. Pappone C, et al.  Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation.  Circulation, January 2004; 109: 327-334.

  100. Pappone G, et al.  Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation.  JACC, July 2003, Vol. 42, No. 2, pp. 185-197.

  101. Paylos JM, Hoyt RH, Ferrero C et al. Complete pulmonary vein isolation using balloon cryoablation in patients with paroxysmal atrial fibrillation. Rev. Esp. Cardiol. 2009; 62(11):1326-31.

  102. Paylos JM, Hoyt RH, Ferrero C, et al. Complete pulmonary vein isolation using balloon cryoablation in patients with paroxysmal atrial fibrillation. Rev Esp Cardiol. Nov 2009; 62(11):1326-1331.

  103. Pokushalov E, Romanov A, De Melis M et al. Progression of atrial fibrillation after a failed initial ablation procedure in patients with paroxysmal atrial fibrillation: a randomized comparison of drug therapy versus reablation. Circ Arrhythm Electrophysiol 2013; 6(4):754-60.

  104. Providencia R, Lambiase PD, Srinivasan N, et al. Is there still a role for complex fractionated atrial electrogram ablation in addition to pulmonary vein isolation in patients with paroxysmal and persistent atrial fibrillation? Meta-analysis of 1415 patients. Circ Arrhythm Electrophysiol. Oct 2015; 8(5):1017-1029.

  105. Reddy VY, Dukkipati SR, Neuzil P, et al. Randomized, controlled trial of the safety and effectiveness of a contact force-sensing irrigated catheter for ablation of paroxysmal atrial fibrillation: results of the TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) study. Circulation. Sep 8 2015; 132(10):907-915.

  106. Saad E, et al.  Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation:  Functional characterization, evolution, and influence of the ablation strategy.  Circulation, December 2003; 108: 3102-3107.

  107. Sawhney N, Anousheh R, Chen WC et al. Five-year outcomes after segmental pulmonary vein isolation for paroxysmal atrial fibrillation. Am J Cardiol 2009; 104(3):366-72.

  108. Schmidt B, Neuzil P, Luik A, et al. Laser balloon or wide-area circumferential irrigated radiofrequency ablation for persistent atrial fibrillation: a multicenter prospective randomized study. Circ Arrhythm Electrophysiol. Dec 2017;10(12).

  109. Schmidt M, Dorwarth U, Andresen D et al. Cryoballoon versus RF Ablation in Paroxysmal Atrial Fibrillation: Results from the German Ablation Registry. J. Cardiovasc. Electrophysiol. 2014; 25(1):1-7.

  110. Schmidt M, Dorwarth U, Andresen D, et al. German ablation registry: Cryoballoon vs radiofrequency ablation in paroxysmal atrial fibrillation-One-year outcome data. Heart Rhythm. Apr 2016; 13(4):836-844.  

  111. Scott PA, Silberbauer J, Murgatroyd FD. The impact of adjunctive complex fractionated atrial electrogram ablation and linear lesions on outcomes in persistent atrial fibrillation: a meta-analysis. Europace. Mar 2016; 18(3):359-367.

  112. Shah RU, Freeman JV, Shilane D et al. Procedural complications, rehospitalizations, and repeat procedures after catheter ablation for atrial fibrillation. J Am Coll Cardiol 2012; 59(2):143-9.

  113. 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.

  114. Shi LZ, Heng R, Liu SM, et al. Effect of catheter ablation versus antiarrhythmic drugs on atrial fibrillation: A meta-analysis of randomized controlled trials. Exp Ther Med. Aug 2015; 10(2):816-822.

  115. 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.

  116. Squara F, Zhao A, Marijon E, et al. Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation. Europace. May 2015; 17(5):718-724. 

  117. 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.

  118. Stabile G, et al.  Is pulmonary vein isolation necessary for curing atrial fibrillation?  Circulation, August 2003; 108: 657-660.

  119. Su W, Orme GJ, Hoyt R, et al. Retrospective review of Arctic Front Advance Cryoballoon Ablation: a multicenter examination of second-generation cryoballoon (RADICOOL trial). J Interv Card Electrophysiol. Apr 2018;51(3):199-204.

  120. Takigawa M, Takahashi A, Kuwahara T, et al. Long-term follow-up after catheter ablation of paroxysmal atrial fibrillation: the incidence of recurrence and progression of atrial fibrillation. Circ Arrhythm Electrophysiol. Apr 2014; 7(2):267-273.

  121. Teunissen C, Kassenberg W, van der Heijden JF, et al. Five-year efficacy of pulmonary vein antrum isolation as a primary ablation strategy for atrial fibrillation: a single-centre cohort study. Europace. Feb 2 2016.

  122. Theis C, Konrad T, Mollnau H, et al. Arrhythmia termination versus elimination of dormant pulmonary vein conduction as a procedural end point of catheter ablation for paroxysmal atrial fibrillation: a prospective randomized trial. Circ Arrhythm Electrophysiol. Oct 2015; 8(5):1080-1087.

  123. Tzou WS, Marchlinski FE, Zado ES et al. Long-term outcome after successful catheter ablation of atrial fibrillation. Circ Arrhythm Electrophysiol 2010; 3(3):237-42.

  124. Vaidya K, Arnott C, Russell A, et al. Pulmonary Vein Isolation Compared to Rate Control in Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis. Heart Lung Circ. Aug 2015; 24(8):744-752. 

  125. Van Belle Y, Janse P, theuns D, et al.  One year follow-up after cryoballoon isolation of the pulmonary veins in patients with paroxysmal atrial fibrillation.  Europase 2008; 10:1270-6.

  126. Van Gelder I, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation.  NEJM, December 2002, Vol. 347, No. 23.

  127. Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. May 7 2015; 372(19):1812-1822.

  128. Vogt J, Heintze J, Gutleben KJ et al. Long-term outcomes after cryoballoon pulmonary vein isolation: results from a prospective study in 605 patients. J. Am. Coll. Cardiol. 2013; 61(16):1707-12.

  129. Waldo AL, Wilber DJ, Marchlinski FE et al. Safety of the open-irrigated ablation catheter for radiofrequency ablation: safety analysis from six clinical studies. Pacing Clin. Electrophysiol. 2012; 35(9):1081-9.

  130. Wasserlauf J, Pelchovitz DJ, Rhyner J, et al. Cryoballoon versus radiofrequency catheter ablation for paroxysmal atrial fibrillation. Pacing Clin Electrophysiol. Apr 2015; 38(4):483-489.

  131. Wazni OM, et al.  Circumferential pulmonary-vein ablation for atrial fibrillation.  NEJM, May 2006, Vol. 354, No. 21, pp. 2289-2291.

  132. Wazni OM, et al.  Radiofrequency ablation vs. antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: A randomized trial. JAMA, June 2005; 293(21): 2634-2640.

  133. 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; 293(21):2634-40.

  134. Weerasooriya R, Khairy P, Litalien J et al. Catheter ablation for atrial fibrillation: are results maintained at 5 years of follow-up? J Am Coll Cardiol 2011; 57(2):160-6.

  135. Wilber DJ, Pappone C, Neuzil P 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.

  136. Wood MA and Ellenbogen KA.  Catheter ablation of chronic atrial fibrillation—the gap between promise and practice.  NEJM, March 2006; 354: 967-969.

  137. 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; 347(23):1825-33.

  138. Xu J, Huang Y, Cai H, et al. Is cryoballoon ablation preferable to radiofrequency ablation for treatment of atrial fibrillation by pulmonary vein isolation? A meta-analysis. PLoS One. 2014; 9(2):e90323.

  139. Zhu M, Zhou X, Cai H, et al. Catheter ablation versus medical rate control for persistent atrial fibrillation in patients with heart failure: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). Jul 2016; 95(30):e4377.

  140. Zhuang Y, Yong YH, Chen ML. Updating the evidence for the effect of radiofrequency catheter ablation on left atrial volume and function in patients with atrial fibrillation: a meta-analysis. JRSM Open. Mar 2014; 5(3):2054270414521185.

Policy History:

Medical Policy Group, May 2006 (2)

Medical Policy Group, August 2006 (2)

Medical Policy Group, January 2007 (2)

Medical Policy Administration Committee, February 2007

Available for comment February 9-March 26, 2007

Medical Policy Group, September 2009 (3)

Medical Policy Administration Committee, September 2009

Available for comment September 18-November 2, 2009

Medical Policy Group, October 2012 (2): Cryoablation of pulmonary veins as a treatment for atrial fibrillation added as a non covered indication. Updates to Description, Policy, Key Points, Approved by Governing Bodies, and References

Medical Policy Administration Committee, November 2012

Medical Policy Group, May 2013 (2):  Added policy statement for coverage of cryoablation of pulmonary veins.  Key Points, Key Words, and References updated to support coverage statement.

Medical Policy Administration Committee, June 2013

Available for comment May 30 through July 13, 2013

Medical Policy Panel March 2014

Medical Policy Group March 2014 (4):  Changed title by removing “in the Pulmonary Veins”;  Removed “in the Pulmonary Veins” from the policy; Updated Description, Key Points, and References.

Medical Policy Administration Committee, May 2014

Available for comment May 5 through June 18, 2014

Medical Policy Group June 2014(4): Updated 2013 CPT Codes. Removed section of the policy related to structural heart disease.

Medical Policy Administration Committee, July 2014

Available for comment June 30 through August 13, 2014

Medical Policy Panel, June 2015

Medical Policy Group, June 2015 (4): Updates to Key Points, Approved Governing Bodies and References.  Removed “of Arrhythmogenic Foci” from the title.  Reworded 1st policy statement for clarification and specified paroxysmal and persistent afib.  New policy statements added; removed arrhythmogenic foci from last policy statement and changed to a fib.

Medical Policy Administration Committee July 2015

Available for comment July 7 through August 20, 2015

Medical Policy Panel, May 2016

Medical Policy Group, May 2016 (4): Updates to Description, Key Points, References. Removed policy statements from June 2013; Added “recurrent” and “>1 episode, with 4 or fewer episodes in the previous 6 months”. Also added “radiofrequency” and “or cryoablation” to investigational statement for clarification.

Medical Policy Panel, May 2017

Medical Policy Group, May 2017 (4): Updates to Key Points and References. No change to Policy Statement.

Medical Policy Panel, May 2018

Medical Policy Group, June 2018 (4):  Removed policy statements that were effective for dates of service on or after June 1, 2013 and prior to May 1, 2014.  Updates to Key Points and References.  No change to Policy Statement

Medical Policy Panel, July 2019

Medical Policy Group, July 2019 (4): Updates to Description, Key Points, and References.  No change to policy statements.


This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.