TEC Assessment Index
Pulmonary Vein Isolation for Treatment of Atrial Fibrillation
Assessment Program
Volume 21, No. 1
May 2006
Executive Summary
Background
Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with decreased survival, numerous cardiovascular morbidities, and a decrease in quality of life. The current treatment approach for AF is primarily pharmacologic. Pulmonary vein isolation (PVI) is a nonpharmacologic alternative treatment for patients with AF. PVI offers potential benefits compared to current pharmacologic treatments, including the potential to cure AF and to avoid the need for long-term medication management.
Objective
The objective of this Assessment is to determine whether PVI improves health outcomes when used as an alternative to pharmacologic treatment for patients with atrial fibrillation.
Search Strategy
MEDLINE was searched from 1990 to March 2006, using the terms "pulmonary vein isolation," "PVI," and "catheter ablation." These terms were cross-referenced with the terms "atrial fibrillation," and "a fib." Search was limited to English-language articles on human subjects.
Selection Criteria
Controlled trials that were published in the peer-reviewed, English-language literature and compared PVI to alternative treatment(s) were selected for inclusion in this Assessment.*
Main Results
Numerous clinical series of PVI treatment have been published that report primarily on success in maintaining sinus rhythm following PVI. However, these reports provide little evidence on the true efficacy of PVI in maintaining sinus rhythm apart from the natural history of the disorder and/or the impact of ancillary treatment measures. These uncontrolled series also do not provide relevant data on the comparative efficacy of PVI vs. pharmacologic treatment.
Three controlled trials met the inclusion criteria and were reviewed in-depth for this Assessment. One trial was a randomized, controlled trial (RCT) (n=146) that compared PVI plus ancillary treatments (i.e., short-term amiodarone, cardioversion) with ancillary treatments alone for patients with chronic AF. The second trial was a smaller RCT (n=70) that randomized patients with new-onset, paroxysmal AF to PVI or antiarrhythmic drug therapy. The final study was a nonrandomized comparative study (n=1,171) that included patients with symptomatic AF refractory to prior antiarrhythmic drug treatment, and compared outcomes of PVI vs. continued antiarrhythmic drug treatment.
All 3 trials reported improvements in outcomes that favored the PVI group. In the RCT of PVI plus ancillary treatment vs. ancillary treatment alone, maintenance of sinus rhythm was higher in the PVI group, with 74% of patients in the PVI group in sinus rhythm at 1 year, compared to only 4% of patients in the control group who maintained sinus rhythm following ancillary treatment alone.
Two of the 3 trials compared PVI to pharmacologic treatment. The smaller RCT reported a lower incidence of AF recurrence in the PVI group compared to the antiarrhythmic drug group (13% vs. 63%, p<0.001). This study also included quality of life outcomes, with a greater improvement on 5 of 8 subscales of the SF-36 reported for the PVI group. The larger nonrandomized trial corroborated the findings of the smaller RCT of lower recurrence of AF following PVI, with an incidence at 1 year of 20% in the PVI group vs. 58% in the medical treatment group (p<0.001). This nonrandomized study also reported on mortality and AF-related morbidities. The PVI group had improved survival at 3 years (92% vs. 86%, p<0.001) and a reduced likelihood of cardiovascular morbidities (hazard ratio [HR] 0.45; 95% CI: 0.31–0.64).
Adverse events from the procedure can occur, including pulmonary vein stenosis, tamponade, thromboembolism, and perforation of the esophageal wall. The rates of these complications cannot be determined accurately from the available data. The rates of complications in the available studies reflect the specific procedures performed and may not be generalizable to variations on the procedure. There have been numerous modifications to the original PVI technique, mainly with the intention of reducing pulmonary vein stenosis and other complications, and currently there is no standardization of the procedure across medical centers.
Author's Conclusions and Comments
The available controlled trials on PVI are few and the evidence is not currently sufficient to permit conclusions on this treatment. There is only a single, small RCT that compares PVI to pharmacologic management, and this trial does not report on the full range of clinical outcomes. This study is also too small to allow estimation of the complication rates of the procedure. The larger RCT comparing PVI plus ancillary treatment to ancillary treatment alone establishes that PVI is efficacious in maintaining sinus rhythm apart from the effect of natural history and/or ancillary treatment measures. However, this trial does not provide information on the comparative efficacy of PVI vs. alternative treatment modalities. The larger, nonrandomized study is prone to selection bias, since treatment assignment was chosen by the treating physician and/or patient preference. This study does not report systematic evaluation for complications. In addition, these 3 studies treat different patient populations and use different techniques for PVI. Also, the 2 trials with a pharmacologic comparison group compared PVI to a rhythm-control strategy. There are no trials comparing PVI to a rate-control strategy, which is currently the preferred treatment strategy for most patients with AF.
The reported benefits associated with PVI in these trials are of large magnitude, and these preliminary studies suggest that PVI may improve outcomes for patients with AF. However, several questions remain before this treatment can be considered part of standard care. First, the PVI technique needs to be standardized so that results across studies can be compared and so that complication rates can be better estimated. The patient population to be treated needs to be better defined. Many experts suggest that younger patients with no paroxysmal AF and other heart disease should be targeted, but this population is represented only in the smaller RCT. This small trial reported the outcomes of maintenance of sinus rhythm and quality of life, but did not include important morbidity and mortality outcomes related to AF. PVI trials should ideally include both a rhythm-control and a rate-control group for comparison. The available trials use a rhythm-control group only.
Numerous RCTs are currently ongoing or in the planning stages, in both the U.S. and Europe. The results of these trials should become available in the next several years and will substantially expand the evidence available to judge the safety and effectiveness of PVI.
Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether PVI as a treatment for atrial fibrillation meets the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria:
1. The technology must have final approval from the appropriate governmental regulatory bodies.
PVI is a percutaneous procedure, and as such is not itself subject to U.S. Food and Drug Administration (FDA) approval. However, the devices used for PVI are subject to FDA approval. The FDA has granted approval to numerous catheter ablation systems under the premarket approval process. Indications for use of these catheters include ablation therapy for arrhythmias such as supraventricular tachycardia, atrial flutter, and ventricular tachycardia. Some of the catheter systems also have approval for treatment of refractory atrial fibrillation.
2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.
The evidence is not sufficient to permit conclusions on the effect of PVI on outcomes of atrial fibrillation. The available evidence includes 3 controlled trials that met the inclusion criteria for this Assessment: 2 RCTs and 1 larger nonrandomized controlled study. One RCT does not compare PVI to pharmacologic management. The second RCT is small and does not report on the full range of clinical outcomes. The third study is a larger, nonrandomized study that is prone to selection bias.
While the results of the available trials are suggestive that PVI may lead to health outcome benefits, larger RCTs are needed that enroll the appropriate population(s) and that include the most relevant comparison groups before conclusions can be made on the efficacy of this treatment.
3. The technology must improve the net health outcome; and
4. The technology must be as beneficial as any established alternatives
The evidence does not permit conclusions as to whether PVI improves health outcomes or is as beneficial as established alternatives.
5. The improvement must be attainable outside the investigational settings.
Whether PVI improves the net health outcome has not been established in the investigational settings.
Based on the above, PVI as a treatment for atrial fibrillation does not meet the TEC criteria.
* In addition, 1 trial comparing PVI plus ancillary treatments with ancillary treatments alone was published after this report was presented at the Medical Advisory Panel (Oral et al. 2006); data from this trial are included in this Assessment. The results of this trial did not change the Assessment conclusions.
TEC Assessment Index
NOTICE OF PURPOSE:TEC Assessments are scientific opinions, provided solely for informational purposes. TEC Assessments should not be construed to suggest that the Blue Cross Blue Shield Association, Kaiser Permanente Medical Care Program or the TEC Program recommends, advocates, requires, encourages, or discourages any particular treatment, procedure, or service; any particular course of treatment, procedure, or service; or the payment or non-payment of the technology or technologies evaluated.
KEYWORDS: CardiovascularMedicine (category); Surgery Surgical Alternatives Interventional Radiology (category); a fib; ablation; ACC; AF; AFFIRM; AHA; American College of Cardiology; American Heart Association; amiodarone; arrhythmia; arrhythmic; atrial; cardiac; cardiology; cardioversion; catheter; chronic; circumferential; control; DCC; electrophysiologic mapping; EPS; fibrillation; guideline; heart; isolation; isthmus; MAZE; mitral; paroxysmal; percutaneous; persistent; pharmacologic; pulmonary vein; PVI; radiofrequency; rate; recurrent; rhythm; sinus rhythm; stenosis; stricture; survival;
