Clinical UM Guideline

This document addresses transcatheter ablation of arrhythmogenic foci in the pulmonary veins for the treatment of atrial fibrillation or atrial flutter.

Note: Please see the following related documents for additional information:

• CG-SURG-05 Maze Procedure
• CG-SURG-55 Cardiac Electrophysiological Studies (EPS) and Catheter Ablation
• SURG.00126 Irreversible Electroporation

Medically Necessary:

Transcatheter ablation of arrhythmogenic foci in the pulmonary veins is considered medically necessary as a treatment of symptomatic individuals with one of the following:

1. Paroxysmal atrial fibrillation (terminates spontaneously or with intervention within 7 days of onset) that is recurrent (2 or more episodes) as an alternative to medical therapy; or
2. Persistent atrial fibrillation (sustained greater than 7 days) when refractory or intolerant to one or more antiarrhythmic drugs (or has a contraindication to all appropriate antiarrhythmic drug therapy).

*See discussion.

Not Medically Necessary:

Transcatheter ablation of arrhythmogenic foci in the pulmonary veins is considered not medically necessary when the medically necessary criteria are not met and for all other indications.

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed, or when the code describes a procedure or situation designated in the Clinical Indications section as not medically necessary.

Atrial fibrillation (AF) is the most common type of heart arrhythmia. According to the Centers for Disease Control and Prevention an estimated 12.1 million people in the United States will have AF by 2030, AF was the underlying cause of 26,535 deaths in 2019. The prevalence of AF in Americans younger than 65 years of age is 2%, while approximately 9% of adults 65 years and older (CDC, 2021) have AF. 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.

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

Atrial fibrillation can be subdivided into paroxysmal (self-terminating), persistent (non-self-terminating), or permanent. Treatment strategies can be broadly subdivided into rate control (the ventricular rate is controlled, and the atria are allowed to fibrillate) or rhythm control (there is an attempt to reestablish and maintain normal sinus rhythm). Rhythm control has long been considered an important treatment goal for AF management, although this has been recently challenged by the results of two randomized trials, both of which reported that pharmacologically maintained rhythm control offers no improvement in mortality compared to rate control. This finding cannot necessarily be extrapolated to rhythm control using ablative techniques however, since antiarrhythmic drug therapy may be associated with increased mortality. For individuals with persistent AF, rhythm control typically involves initial pharmacologic or electronic cardioversion, followed by pharmacologic maintenance of normal sinus rhythm. However, episodes of recurrent AF are typical, and individuals may require multiple episodes of cardioversion. Implantable defibrillators, which among the other potential utility, can detect an episode of AF, but cannot terminate the episode. Individuals with paroxysmal AF, by definition, do not require cardioversion but may be treated pharmacologically to prevent further episodes of AF. Treatment of permanent AF focuses on rate control, using either pharmacologic therapy or ablation of the AV node, followed by ventricular pacing. Although AV nodal ablation produces symptomatic improvement, it does require lifelong anticoagulation (due to the ongoing fibrillation of the atria), loss of AV synchrony and lifelong pacemaker dependency. Implantable atrial defibrillators are contraindicated for individuals with permanent AF.

The above treatment options are not considered curative. A variety of ablative procedures have been researched in an attempt to modify the arrhythmia so that drug therapy becomes more effective or to potentially cure the condition. Ablative approaches focus on interruption of the electrical pathways that contribute to atrial fibrillation. The Maze procedure, an open surgical procedure often combined with other cardiac surgeries, is an ablative procedure involving sequential atriotomy incisions designed to create electrical barriers that prevent the maintenance of AF. Since the inception of this technique in the early 1990’s, there has been a progressive understanding of the underlying electrical pathways in the heart, such that catheter-based radiofrequency procedures have become feasible. Radiofrequency ablation is a widely used technique for a variety of supraventricular arrhythmias, when intracardiac mapping identifies a discrete arrhythmogenic focus that can be the target of ablation. The situation is more complex for AF, since there is not a single arrhythmogenic focus. However, the recent recognition that the triggering foci are commonly located within the myocytes extending into the pulmonary veins creates a potential target for ablation. Three basic strategies have emerged: focal ablation within the pulmonary veins, as identified by electrophysiologic mapping; segmental ostial ablation guided by pulmonary vein potential (electrical approach); or circumferential pulmonary vein ablation (anatomic approach). Circumferential pulmonary vein ablation appears to be the preferred approach at this time.

The STOP-AF trial (Packer, 2013) assessed the safety and effectiveness of a cryoballoon ablation technology. Participants with documented symptomatic paroxysmal AF and previously failed therapy with greater than or equal to one membrane active antiarrhythmic drug underwent 2:1 randomization to either cryoballoon ablation (n=163) or drug therapy (n=82). A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and re-ablation if necessary. Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months. Participants had highly symptomatic AF (78% paroxysmal, 22% early persistent) and experienced failure of at least one antiarrhythmic drug. Cryoablation produced acute isolation of three or more pulmonary veins (PVs) in 98.2% and all four PVs in 97.6% of participants. PV isolation (PVI) was achieved with the balloon catheter alone in 83%. At 12 months, treatment success was 69.9% (114 of 163) of cryoablation participants compared with 7.3% of antiarrhythmic drug participants (absolute difference, 62.6% [p<0.001]). Sixty-five (79%) drug-treated participants crossed over to cryoablation during 12 months of study follow-up due to recurrent, symptomatic AF, constituting drug treatment failure. There were 7 of the resulting 228 cryoablated participants (3.1%) with a greater than 75% reduction in PV area during 12 months of follow-up. Twenty-nine of 259 procedures (11.2%) were associated with phrenic nerve palsy (PNP) as determined by radiographic screening; 25 of these had resolved by 12 months. Cryoablation participants had significantly improved symptoms at 12 months. A limitation of the study is the lack of a radiofrequency (RF) ablation arm.

In a single center observational study, Vogt and colleagues (2013), reported follow-up results for 605 participants who underwent cryoablation for symptomatic, paroxysmal or persistent AF. Follow-up results were reported in 451 participants beyond 12 months (mean 30 months), 61% (n=278) of whom 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. The most common acute adverse event reported included PNP, occurring in 12 participants (2%), all of which resolved within 3 to 9 months. The study reported one case of pericardial tamponade, one pericardial effusion, and two strokes.

The second generation version cryoballoon devices for pulmonary vein isolation in treatment of paroxysmal atrial fibrillation have been developed with modifications designed to improve procedural outcomes with respect to the first generation device. A case series by Chierchia and colleagues (2014) reported 1-year follow up on 42 participants who underwent PVI with 28 mm cryoballoon advance (CB-A) (Artic Front Advance, Medtronic Inc., Minneapolis, MN) for paroxysmal AF, with 100% of the PVs isolated with the cryoballoon. After a single procedure, 78% of participants reported freedom of AF off-antiarrhythmic drug treatment at 1 year follow-up (mean 11.6 11.6 ± 2.0 months). Including blanking period of 3 months, participant success rate was reported at 83%. The most common acute adverse event was PNP, occurring in 19% of the population, of which PNP reverted during follow-up period. Metzner and colleagues report results from 50 participants with paroxysmal (n=36) or short-standing persistent AF (n=14) who underwent cryoballoon-based pulmonary vein isolation. Participants were assessed in an outpatient clinic at 3, 6 and 12 months including Holter echocardiograms and telephonic interviews. Recurrence was defined as a symptomatic or documented arrhythmic episode of greater than 30 seconds excluding 3-month blanking period. Follow-up results were reported in 49 of 50 participants (98%) with a mean follow-up duration of 440 ± 39 days. A total of 39 (80%) participants remained in sinus rhythm. Of the remaining 10 participants, 8 required a second procedure using RF ablation. One out of 50 participants (2%) developed PNP.

According to the 2014 American Heart Association (AHA)/ American College of Cardiology (ACC)/ Heart Rhythm Society (HRS) guideline for the management of individuals with atrial fibrillation, the Society includes the following recommendations:

• For individuals with paroxysmal AF, transcatheter radiofrequency pulmonary vein ablation (PVA) may be considered as an alternative for individuals who are symptomatic and resistant to or unable to tolerate antiarrhythmic drug therapy.
• For symptomatic individuals with persistent AF, transcatheter PVA might be considered an alternative to individuals who are intolerant or refractory to antiarrhythmic drug therapy.

*Recommendations for selecting drug therapy for ventricular rate control include the following:

Beta blockers should be instituted following stabilization of patients with decompensated heart failure (HF). The choice of beta blocker depends on the patient’s clinical condition. Digoxin is not usually first-line therapy, it may be combined with a beta blocker and/or a nondihydropyridine calcium channel blocker when ventricular rate control is insufficient and may be useful in patients with HF. In part because of concern over its side-effect profile, use of amiodarone for chronic control of ventricular rate should be reserved for patients who do not respond to or are intolerant of beta blockers or nondihydropyridine calcium antagonists. (2014 AHA/ACC/HRS).

The 2019 AHA/ACC/HRS focused update of the 2014 guideline for the management of AF, provides recommendations for AF catheter ablation in the restoration of sinus rhythm not as a sole intent of obviating the need for anticoagulation. The authors further concluded that cryoballoon ablation can be used as an alternative to point-by-point RF ablation to achieve PVI.

In 2023 the ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation Recommendations for AF Catheter Ablation were updated to include:

1. In patients with symptomatic AF in whom antiarrhythmic drugs have been ineffective, contraindicated, not tolerated or not preferred, and continued rhythm control is desired, catheter ablation is useful to improve symptoms. Level of evidence: A
2. In selected patients (generally younger with few comorbidities) with symptomatic paroxysmal AF in whom rhythm control is desired, catheter ablation is useful as first-line therapy to improve symptoms and reduce progression to persistent AF. Level of evidence: A
3. In patients with symptomatic or clinically significant AFL, catheter ablation is useful for improving symptoms. Level of evidence: A

The recommendations further state:

Catheter ablation has become an established therapy for AF because of multiple RCTs and evidence from large registries and continues to evolve as new technologies are developed. Previous professional society documents have provided different recommendations for catheter ablation dependent on whether AF was persistent or paroxysmal. More recent information has shown that ablation for AF is more effective than antiarrhythmic drugs for both persistent and paroxysmal AF and that earlier implementation of rhythm control strategies is an important factor for improving AF ablation success rates. As with all strategies for rhythm control of AF, impact on a patient’s goals of care and QOL should be the focus. For example, significantly reducing the frequency and duration of AF episodes but not eliminating all future episodes of AF may represent a clinically important improvement.

In 2015, the Agency for Healthcare Research and Quality (AHRQ) issued an evidence-based review for catheter ablation for treatment of atrial fibrillation which concludes:

Catheter ablation for the treatment of AF is increasingly being performed on symptomatic patients as an alternative to medical management, or when medical management has been ineffective or not tolerated. AF ablation is typically recommended only for symptomatic patients; asymptomatic patients are usually managed with anticoagulation and/or rate control as needed. The outcomes of this procedure may depend on patient characteristics such as age, AF type, and presence of structural heart disease, as well as on experience of the operator and methods and technologies used during the procedure. Relief of symptoms is a primary reason for considering catheter ablation as a treatment strategy.

A 2016 Cochrane review evaluated the efficacy and safety of ablation for people with non‐paroxysmal AF. When compared to participants receiving heart rhythm drugs, the participants receiving catheter ablation were more likely to be free from AF, had a decreased risk of being hospitalized due to cardiac causes, and a decreased risk of needing cardioversion after 12 months.

In 2016, Kuck and colleagues reported results from a randomized controlled trial (RCT) comparing cryoablation (n=378) to RFA (n=384) in individuals with symptomatic drug-refractory paroxysmal AF (FIRE AND ICE trial). The authors concluded that:

The primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 in the radiofrequency group (1-year Kaplan–Meier event rate estimates, 34.6% and 35.9%, respectively; hazard ratio (HR), 0.96; 95% confidence interval [CI], 0.76 to 1.22; p<0.001 for noninferiority). The primary safety end point occurred in 40 patients in the cryoballoon group and in 51 patients in the radiofrequency group (1-year Kaplan–Meier event rate estimates, 10.2% and 12.8%, respectively; HR, 0.78; 95% CI, 0.52 to 1.18; p=0.24). Cryoballoon ablation was noninferior to RFA with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation, there was no significant difference between the two methods with regard to overall safety.

In 2017 the HRS in conjunction with other organizations published a consensus statement addressing the use of catheter and surgical ablation of atrial fibrillation (Calkins, 2017). The consensus statement notes:

As demonstrated in a large number of published studies, the primary clinical benefit from catheter ablation of AF is an improvement in quality of life resulting from elimination of arrhythmia-related symptoms such as palpitations, fatigue, or effort intolerance. Thus, the primary selection criterion for catheter ablation should be the presence of symptomatic AF.

Kirchhof and colleagues (2020), completed an open, blinded, randomized, parallel-group trial at 135 centers in Europe including 2789 participants. The trial compared outcomes for individuals with early AF (defined as diagnosed ≤ 1 year before enrollment) and cardiovascular conditions to receive either early rhythm control or usual care. Early rhythm control consisted of treatment with antiarrhythmic drugs or AF ablation. Usual care limited rhythm control to management of AF symptoms. The first primary outcome measured was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of HF or acute coronary syndrome; the secondary outcome was the number of nights spent in the hospital per year. The primary safetfy outcome was a composite of death, stroke, or serious adverse events related to rhythm-control therapy. First primary outcome events occurred in 249 of the participants in the early rhythm control group (3.9 per 100 person-years) and in 316 participants in the usual care group (5.0 per 100 person-years) (HR, 0.79; 96%, CI, 0.66 to 0.94; p=0.005). The mean number of nights spent in the hospital did not differ significantly between the groups (5.8 and 5.1 days per year, respectively; p=0.23). The percentage of participants with a primary safety outcome event did not differ significantly between the groups. Serious adverse events related to rhythm control therapy occurred in 4.9% of the participants in the early rhythm control group and 1.4% of the participants in the usual care group. More adverse events were related to rhythm control therapy than usual care. Symptoms and left ventricular function at 2 years did not differ significantly between the groups. The authors concluded that early rhythm control was associated with a decreased risk of adverse cardiovascular outcomes than usual care in individuals with early AF and cardiovascular conditions. Limitations of the study were that only participants with early AF were enrolled and therefore the results may not be generalizable to individuals in whom rhythm control therapy is initiated later. Participants were deemed eligible for either rate control or rhythm control therapy, which may have excluded the most symptomatic population, and therefore the data on recurrent AF in both groups are not comparable with other rhythm-control trials.

Wazni and colleagues (2021) reported results from a multicenter, randomized trial the STOP-AF First (Cryoballoon Catheter Ablation in Antiarrhythmic Drug Native Paroxysmal Atrial Fibrillation; NCT03118518) study that performed cryoballoon ablation as initial therapy for individuals with paroxysmal AF for which they had not received rhythm-control therapy. A total of 203 participants (18 to 80 years of age) were randomly assigned (1:1) to receive pulmonary vein isolation with cryoballoon (n=104, ablation group) versus treatment with antiarrhythmic drugs (n=99, drug therapy group). Participants received arrhythmia monitoring with 12-lead electrocardiography conducted at baseline and at 1, 3, 6 and 12 months; participant activated telephone monitoring conducted weekly and when symptoms were present. At 12 months the estimated treatment success was 74.6% (95% CI, 65.0 to 82.0) in the ablation group and 45% (95% CI, 34.6 to 54.7) in the drug-therapy group (P<0.001 by log-rank test). Within the 12 months there were two (1.9%) primary safety end-point events (pericardial effusion and myocardial infarction) in the ablation group. The number of individuals with serious adverse events was similar between the ablation group and the drug-therapy group. Among individuals randomly assigned to the drug-therapy group, 13% of participants discontinued treatment within 12 months and 34% underwent ablation within a year after randomization. The authors concluded that “cryoballoon ablation as initial therapy was superior to drug therapy for the prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation. Serious procedure-related adverse events were uncommon”

Another study, the Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial (NCT00911508) is the largest randomized, open label trial of ablation with the overall goal of establishing the appropriate roles for medical and ablative intervention for AF. The study enrolled 2204 participants at 126 sites worldwide from 2009 to 2016. Packer and colleagues (2019) presented the primary results from the CABANA trial on cardiovascular outcomes and mortality. The trial did not meet its primary end point in the intention-to-treat (ITT) analysis. Mark and colleagues (2019) reported results for the prespecified secondary end point, with increased quality of life (QOL) at 12 months using several scales validated in individuals with AF.

Lo and colleagues (2021) reported results of a manufacturer sponsored, multi-center, single-arm trial, which evaluated the use of the TactiCath Contact Force Ablation Catheter, Sensor Enabled^™ (TactiCath SE, Abbott Inc., Abbott Park, Illinois) for the treatment of drug-refractory, symptomatic paroxysmal AF in 156 individuals at 19 sites in the United States, Europe, and Australia. The primary safety outcome was the rate of device or procedure-related adverse events within 7 days. The primary efficacy outcome was success, defined as PVI at 30 minutes post-ablation. Two outcomes were prospectively captured:1-year freedom from recurrence of symptomatic AF, atrial flutter (AFL), and atrial tachycardia (AT) lasting > 30 seconds without a new or increased dose of Class I/III antiarrhythmic drugs; and 1-year drug-free success defined as the absence of any recurrent AF/AFL/AT lasting > 30 seconds without using Class I/III antiarrhythmic drugs. Exclusion criteria were persistent AF, implanted cardiac defibrillator, left atrial (LA) diameter > 5.0 cm, left ventricular ejection fraction < 35%, New York Heart Association (NYHA) functional class III or IV, body mass index > 40 kg/m2, and previous ablation therapy in the left atrium. There were 8 primary safety events in 7 out of 149 subjects (n=149). The analysis population included all individuals that had the device inserted except for 2 (1 withdrew from the trial before the 30-day visit without experiencing an event, and 1 missed the 30-day visit and did not experience an event). No primary safety events occurred beyond 30 days. The rate of significant device related events was 4.7% which was lower than the performance goal of 16.2% (p<0.0001). No strokes or transient ischemic attacks were reported. One incidence of deep venous thrombosis was related to the surgical removal of a circular mapping catheter, the investigated device was not involved in that event. The most common complication was cardiac tamponade, which occurred in 3 individuals. There was 1 case of atrio-esophageal fistula which was successfully treated with surgical intervention. No deaths were reported. The clinically relevant 1-year success rate was 82.2%, and 1-year drug-free success was 68.2%. The authors concluded that TactiCath SE device achieved performance goals set for safety and effectiveness.

Wu and colleagues (2021) reported a meta-analysis that assessed the efficacy and safety between second-generation cryoballoon (CB2) and contact force radiofrequency (CF-RF) using evidence from RCT’s. The primary outcome measured was absence of AT during the follow-up period. Secondary outcomes were procedure-related complications, procedure time and fluoroscopy time. Six RCTs with a total of 987 individuals were reviewed. No differences were found between CB2 and CF-RF in the absence of AT (relative risk [RR] = 1.03, p=0.616), or total procedural-related complications (RR = 1.25, p=0.457). CB2 treatment was associated with a higher risk of PNP than CF-RF (RR = 4.93, p=0.035). The occurrences of pericardial effusion/tamponade and vascular complications were comparable between the CB2 and CF-RF treatments (RR = 0.41, p=0.398; RR = 0.82, p=0.632), respectively. In addition, CB2 treatment had a shorter procedure time than CF-RF (weighted mean difference [WMD] = -20.75 min, p<0.001), whereas no difference was found in terms of fluoroscopy time (WMD = 4.63 min, p=0.179). The authors concluded that additional large-scale studies are needed to compare the clinical efficacy of the two techniques.

Razzack and colleagues (2022) reported a meta-analysis that included six RCTs, with 1212 individuals (ablation n=609; antiarrhythmic n=603), that examined whether early catheter ablation, as first-line therapy for AF is associated with improved clinical outcomes. The primary outcome measured was the first documented recurrence of any AT (symptomatic or asymptomatic; AF, AFL, and AT). Secondary outcomes included symptomatic AT and serious adverse events. The results demonstrated that individuals who underwent ablation were less likely to have recurrent AT compared to individuals that received antiarrhythmic drugs (p<0.00001). Symptomatic AT was lower in the ablation group (p=0.01). No statistically significant differences were noted overall for any type of adverse events (p=0.64) and cardiovascular adverse events (p=0.65). The authors concluded that the efficacy and safety of catheter ablation (RFA and CBA) aimed at electrical PVI resulted in a lower recurrence rate of AT and maintenance of sinus rhythm, and that catheter ablation for AF rhythm control is superior to anti-arrhythmic drugs (AAD) in drug naïve individuals. Limitations of the meta-analysis included studies that differed in the use of Class I or III AADs, types of AF, and method of surveillance used to monitor recurrence, and a varied follow-up period (1–2 years). Five studies included individuals with paroxysmal AF only, therefore the data cannot be extrapolated to individuals with persistent AF. This meta-analysis also combined different ablation techniques, both RFA and CBA, to evaluate the primary efficacy. Additionally, the ablation targets beyond the pulmonary veins were at the treating providers discretion. Further large-scale studies with well controlled methodology are needed to compare the clinical efficacy of the techniques.

Kanagaratnam and colleagues (2023) reported a randomized, multi-center, open label trial (n=321) that compared whether a streamlined approach to AF using the AVATAR protocol of cryoballoon ablation without electrical mapping, and same day discharge achieved improved symptom control in individuals with paroxysmal AF, compared to AAD therapy over a 12-week period. One hundred ten individuals were assigned to the AVATAR protocol group, 103 individuals to the anti-arrhythmic group, and 108 individuals to the conventional ablation group. In the AVATAR-protocol ablation group, the Arctic Front Advance^™ cryoballoon was used to occlude PVs. No intra-cardiac electrical recording catheters were deployed, and PVI was not formally assessed. A bedside transthoracic echocardiogram, hemoglobin check, and femoral puncture site assessment were completed 6 hours post-procedure. If stable, the individual was discharged on the day of intervention. In the AF ablation group, cryo-ablation efficacy was monitored with a circular mapping catheter. PVI was completed with either repeat CBA, deflectable cryotherapy catheter, or RF catheter. Post-procedural tests were the same as the AVATAR group, but individuals were discharged the next day. During the 12-week period, all pre-ablation anti-arrhythmic agents were continued for 4 weeks post-ablation and then reduced with the goal of cessation. Repeat ablations were required for individuals with symptoms due to recurrent AF from PV reconnection. A second ablation was performed at 10 weeks for recurrent AF symptoms, as part of the initial ablative treatment. In the drug therapy arm, individuals were assessed every 4 weeks to optimize anti-arrhythmics. Symptomatically improving individuals were discharged from hospital-based specialist arrhythmia care at 12 weeks. Individuals who had ongoing symptoms or problems related to their assigned therapy “failed 12-week discharge’ and counted as a primary endpoint. The results demonstrated that in the AVATAR group, 108 of 110 individuals (98%) underwent the planned ablation. Of these, 92 (84% of individuals randomized) were discharged the same day. Seventeen individuals (16%) were referred for a redo procedure at the 8-week review of whom 13 (12%) completed the procedure. Ninety-four individuals (85%) achieved symptom control and were discharged from specialist care at 12 weeks. In the anti-arrhythmic group, at 12 weeks, 47 individuals (46%) had achieved symptom control and were discharged from specialist hospital care, and 2 individuals had crossed over and completed ablation. In the conventional ablation group, 103 of 108 underwent the planned ablation (95%). Ninety-nine individuals had confirmed PVI (92%). Ten individuals (10%) were referred for a redo procedure at 8-week review. Ninety-seven individuals (90%) were discharged from specialist hospital care following review at 12 weeks. The HR for a primary endpoint event occurring when comparing AVATAR protocol group to drug therapy was 0.156, p<0.000. Twenty-three individuals (21%) recorded an endpoint event in the AVATAR group compared to 76 individuals (74%) within the drug therapy group. Comparing AVATAR and conventional ablation groups resulted in a non-significant HR of 1.173, p=0.61 with 23 individuals (21%) and 19 individuals (18%), respectively, recording primary endpoint events (p=0.61). The authors concluded that the AVATAR protocol was superior to drug therapy for avoiding hospital episodes related to AF treatment, but that conventional cryoablation was not superior to the AVATAR protocol.

Sohns and colleagues (2023), conducted a single-center, open-label, randomized, superiority clinical trial that examined individuals with symptomatic AF and end-stage HF who were referred for heart transplantation evaluation. Participants were assigned to receive either catheter ablation and guideline-directed medical therapy or medical therapy alone. The primary outcome measured was a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation. A total of 97 participants were assigned to the ablation group and 97 to the medical therapy group. Participants with symptomatic AF were assigned to the ablation group and had direct current cardioversion after the transseptal puncture. If this was not successful, the catheter-ablation procedure was started with the participant in AF, and direct-current cardioversion was attempted after ablation around the PVs. The goal was to achieve electrical isolation of all PVs and to restore sinus rhythm. Participants in the medical therapy only group were treated within the AHA/ACC/HRS/ ESC guidelines. Catheter ablation was performed in 81 of 97 participants (84%) in the ablation group and in 16 of 97 participants (16%) in the medical-therapy group; the median follow-up was 18 months. Of the 97 participants in the ablation group, 81 underwent ablation. In the ablation group, 51 had PVI alone and 30 underwent PVI as well as ablation of other areas. A total of 16 participants (16%) in the medical-therapy group underwent a catheter-ablation procedure. There were 4 procedure-related complications (3 in the ablation group and 1 in the medical-therapy group), all of which were related to the vascular access site. A primary end point event occurred in 8 participants (8%) in the ablation group and in 29 participants (30%) in the medical-therapy group (HR, 0.24; 95% CI, 0.11 to 0.52; p<0.001). Limitations of this study included the single center nature of the trial and the early termination based upon the recommendation of the data and safety monitoring board. Results may have differed with longer term follow-up. Additionally, 16 participants in the medical-therapy group crossed over to undergo catheter ablation. The analyses were reported on an ITT basis which may have reduced the benefit associated with the ablation group. The authors concluded that in individuals with AF and end-stage HF the combination of catheter ablation and medical therapy was associated with a decreased risk of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation than medical therapy alone.

Other Uses

Transcatheter radiofrequency ablation or cryoablation of arrhythmogenic foci in the pulmonary veins has also been evaluated to treat AFL. The AHA defines AFL as an arrhythmia that spreads through the atria at a regular, very rapid rate causing the upper chambers of the heart to contract quickly. Typical AFL is a less common arrhythmia than AF in clinical practice, although has similar symptoms and complications. AFL can be found concurrently in individuals with AF. The cavotricuspid isthmus between the inferior vena cava and the tricuspid annulus (IVC-TA isthmus) is an obligatory route for typical AFL and is considered the best anatomic target for ablation. However, researchers are assessing the hypothesis that the use of cryoballoon PVI can achieve electrical disconnection between the pulmonary veins and the heart, resulting in higher rates of freedom from abnormal heart rhythms. An ongoing study evaluating cryoballoon pulmonary vein ablation as first-line treatment for typical AFL (CRAFT) (NCT03401099) has an estimated enrollment of 130 participants and an estimated study completion date of December, 2023. However, at the time of this review no results have been posted from the CRAFT trial.

According to January and colleagues (2014) AFL may arise during treatment with an antiarrhythmic administered for treatment of recurrent AF. “Catheter ablation of the cavotricuspid isthmus is effective for prevention of recurrent AFL in these patients while allowing continued antiarrhythmic treatment to prevent recurrent AF.”

Peyrol and colleagues (2015), reported a case series of 12 individuals with a mean age of 62 years that underwent simultaneous delivery of RF at the cavotricuspid isthmus during cryoballoon ablations at the PV ostia for drug resistant AF and typical AFL. PVI was achieved in all PVs as was sustained bidirectional cavotricuspid isthmus conduction block in all participants. The protocol did not result in prolonged procedure duration or radiation exposure when compared to cryoballoon-PVI alone. No interferences between ablation energy systems were observed. The authors concluded that the study demonstrated coexistent paroxysmal AF and typical AFLcan be treated using hybrid energy sources with concomitant cavotricuspid isthmus ablation. Additional larger studies are needed to validate this approach and evaluate potential benefits compared with a sequential approach.

The 2019 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) focused update of the 2014 guideline for the management of atrial fibrillation, does not address use of radiofrequency ablation or cryoablation for PVI in the treatment of AFL.

The evidence regarding the use of transcatheter radiofrequency ablation or cryoablation of arrhythmogenic foci in the pulmonary vein for the treatment of AFL is currently insufficient to allow conclusions to be made.

Arrhythmogenic: Producing or promoting arrhythmia.

Atrial fibrillation: A supraventricular (originating in the atria) tachyarrhythmia characterized by uncoordinated atrial activation and ineffective atrial contraction. Characteristics on an ECG include 1) irregular R-R intervals (when atrioventricular [AV] conduction is present), 2) absence of distinct repeating P waves, and 3) irregular atrial activity.

The classifications of AF are defined by the AHA/ACC/HRS Guidelines for the management of AF as follows (January, 2014):

• Paroxysmal AF - AF that terminates spontaneously or with intervention within 7 days of onset. Episodes may recur with variable frequency.
• Persistent AF - Continuous AF that is sustained greater than 7 days.

Atrial flutter: A condition less common than AF, the heart’s electrical signals spread through the atria in a fast and regular rhythm.

Foci: Plural of focus, the origin or center of a disseminated disease.

Myocardial substrate: Myocardial cells that is capable of receiving and responding to electrical impulses.

Symptomatic atrial fibrillation: Atrial fibrillation with one or more of the following symptoms, including but not limited to: palpitations, chest pain, dyspnea, dizziness, fatigue, hypotension, syncope or heart failure (Nabauer, 2009; AHA/ACA/HRS, 2014).

Peer Reviewed Publications:

1. Andrade JG, Wells GA, Deyell MW, et al. Cryoablation or drug therapy for initial treatment of atrial fibrillation. N Engl J Med. 2021; 384(4):305-315.
2. Bourke JP, Dunuwille A, O’Donnell D, et al. Pulmonary vein ablation for idiopathic atrial fibrillation: six month outcome of first procedure in 100 consecutive patients. Heart. 2005; 91(1):51-57.
3. Calo L, Lamberti F, Loricchio ML, et al. Left atrial ablation versus biatrial ablation for persistent and permanent atrial fibrillation: a prospective and randomized study. J Am Coll Cardiol. 2006; 47(12):2504-2512.
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12. Kuck KH, Brugada J, Furnkranz A, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Eng J Med. 2016; 374(23):2235-2245.
13. Kuck KH, Lebedev DS, Mikhaylov EN, et al. Catheter ablation or medical therapy to delay progression of atrial fibrillation: the randomized controlled atrial fibrillation progression trial (ATTEST). Europace. 2021; 23(3):362-369.
14. Lo MY, Sanders P, Sommer P, et al. Safety and effectiveness of a next-generation contact force catheter: results of the TactiSense trial. JACC Clin Electrophysiol. 2021 Aug; 7(8):1013-1021.
15. 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; 321(13):1275-1285.
16. Mack CA, Milla F, Ko W, et al. Surgical treatment of atrial fibrillation using argon-based cryoablation during concomitant cardiac procedures. Circulation. 2005; 112(9 Suppl):I1-6.
17. Metzner A, Reissmann B, Rausch P, et al. One-year clinical outcome after pulmonary vein isolation using the second-generation 28-mm cryoballoon. Circulation. 2014; 7:288-292.
18. Mont L, Bisbal F, Hernández-Madrid A, et al. Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study). Eur Heart J. 2014; 35(8):501-507.
19. 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. 2014; 311(7):692-699.
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21. 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. 2017; 103(5):368-376.
22. Oral H, Chugh A, Good E, et al. a tailored approach to catheter ablation of paroxysmal atrial fibrillation. Circulation. 2006; 113(15):1824-1831.
23. 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):1713-1723.
24. 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; 321(13):1261-1274.
25. Packer DL, Piccini JP, Monahan KH, et al. Ablation versus drug therapy for atrial fibrillation in heart failure: results from the CABANA Trial. Circulation. 2021; 143(14):1377-1390.
26. Pappone C, Augello G, Sala S, et al. A randomized trial of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation. J Am Coll Cardiol. 2006; 48(11):2340-2347.
27. Pappone C, Rosanio S, Augello G, et al. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol. 2003; 42(2):185-197.
28. Pappone C, Santinelli V, Manguso F, et al. Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation. Circulation. 2004; 109(3):327-334.
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Government Agency, Medical Society, and Other Authoritative Publications:

1. Agency for Healthcare Research and Quality. Catheter Ablation for treatment of atrial fibrillation. Evidence-based practice center systematic review protocol. 2015 April. Project ID: CRDT0913. Available at: https://www.ahrq.gov/sites/default/files/wysiwyg/research/findings/ta/topicrefinement/afib_topicref.pdf. Accessed on June 10, 2024.
2. Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLEAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Available at: https://www.hrsonline.org/Policy-Payment/Clinical-Guidelines-Documents/2017-HRS-EHRA-ECAS-APHRS-SOLAECE-Expert-Consensus-Statement-on-Catheter-and-Surgical-Ablation-of-Atrial-Fibrillation. Accessed on June 10, 2024.
3. 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. Available at: https://www.hrsonline.org/Policy-Payment/Clinical-Guidelines-Documents/Expert-Consensus-Statement-on-Catheter-and-Surgical-Ablation-of-Atrial-Fibrillation-AFib/2012-HRS-EHRA-ECAS-Expert-Consensus-Statement-on-Catheter-and-Surgical-Ablation-of-Atrial-Fibrillation. Accessed on June 10, 2024.
4. Fuster V, Ryden LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation : a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011; 123:e269-e367. Available at: http://circ.ahajournals.org/content/123/10/e269.full.pdf+html. Accessed on June 10, 2024.
5. 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. March 2014. Available at: http://circ.ahajournals.org/content/130/23/e199.full.pdf+html?sid=0768d2d4-f9b0-40be-ad01-d9e979cfb142. Accessed on June 10, 2024.
6. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused update of the 2014 AHA/ACC/HRS guideline of the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. 2019. Available at: https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000665. Accessed on June 10, 2024.
7. Joglar, J, Chung, M. et al. 2023 ACC/AHA/ACCP/HRS Guideline for the diagnosis and management of atrial fibrillation: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024 Jan; 83(1)109–279. Available at: https://doi.org/10.1016/j.jacc.2023.08.017. Accessed on June 12, 2024.
8. Liverpool Heart and Chest Hospital NHS Foundation Trust. Cryoballoon Ablation as First Line Treatment of Atrial Flutter (CRAFT). NLM Identifier: NCT03401099. Last updated November 13, 2023. Available at: https://clinicaltrials.gov/ct2/show/NCT03401099. Accessed on June 10, 2024.
9. Mayo Clinic. Catheter ablation vs anti-arrhythmic drug therapy for atrial fibrillation trial (CABANA). NLM Identifier: NCT00911508. Last updated April 21, 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT00911508. Accessed on June 10, 2024.
10. Nyong J, Amit G, Adler AJ, et al. Efficacy and safety of ablation for people with non‐paroxysmal atrial fibrillation. Cochrane Database of Syst. Rev, 2016; (11): CD012088. Available at: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012088.pub2/full.
11. University Hospital, Rousen. Cryoballoon Pulmonary Venous Isolation in Patients Referred for Typical Arial Flutter Ablation (PAF CRIOBLAF). NLM Identifier. NCT01521988. Last updated May 29, 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT01521988. Accessed on June 10, 2024.
12. Wann LS, Curtis AB, January CT, et al. 2011 ACCF/AHA/HRS Focused Update on the Management of Patients with Atrial Fibrillation (Updating the 2006 Guideline) J Am Coll Cardiol 2011; 57(2):223–242. Available at: http://circ.ahajournals.org/content/123/1/104.extract. Accessed on June 10, 2024.

1. American Heart Association. About arrhythmia. September 30, 2016. Available at: https://www.heart.org/en/health-topics/arrhythmia/about-arrhythmia. Accessed on July 13, 2023.
2. American Heart Association. Non-surgical procedures for atrial fibrillation (AFib or AF). Last reviewed July 31, 2016. Available at: https://cpr.heart.org/en/health-topics/atrial-fibrillation/treatment-and-prevention-of-atrial-fibrillation/nonsurgical-procedures-for-atrial-fibrillation-afib-or-af. Accessed on March 29, 2023.
3. American Heart Association. Other rhythm disorders. September 2016. Last reviewed November 16, 2022. Available at: https://www.heart.org/en/health-topics/arrhythmia/about-arrhythmia/other-heart-rhythm-disorders. Accessed on June 10, 2024.
4. Centers for Disease Control and Prevention. Atrial fibrillation. Updated May 15, 2024. Available at: https://www.cdc.gov/heart-disease/about/atrial-fibrillation.html?CDC_AAref_Val=https://www.cdc.gov/heartdisease/atrial_fibrillation.htm.Accessed on June 10, 2024.

Ablation, Soft Tissue
Atrial Fibrillation
Cryoablation
Pulmonary Vein Ablation for Atrial Fibrillation
Pulmonary Vein Ablation for Atrial Flutter
Radiofrequency Ablation

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.