Catheter Ablation of Chronic Atrial Fibrillation — The Gap between Promise and Practice
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《新英格兰医药杂志》
Atrial fibrillation remains the most common heart-rhythm abnormality seen in general clinical practice, and its incidence is increasing. Atrial fibrillation is an enormous health concern because it increases the risk of death, congestive heart failure, and thromboembolism and decreases the quality of life. It places an increasing burden on the health care system because of the associated costs of hospitalization and outpatient care. The pharmacologic approach to the maintenance of sinus rhythm in patients with atrial fibrillation is compromised by its limited efficacy, side effects, and concern about safety. For these reasons, since the initial description of pulmonary-vein ablation in the Journal,1 intense efforts have been directed toward the use of catheter ablation to "cure" paroxysmal atrial fibrillation.
The importance of the pulmonary veins and surrounding left atrium in the initiation of atrial fibrillation is now widely accepted by electrophysiologists. Electrical isolation of the pulmonary veins by radiofrequency catheter ablation has a success rate approaching 75 to 85 percent in patients without clinically significant structural heart disease.2,3 According to the latest guidelines of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology, catheter ablation is considered standard therapy for patients who have symptomatic paroxysmal atrial fibrillation after having had no response to a single antiarrhythmic drug.4
In contrast to its established use for paroxysmal atrial fibrillation, the role of catheter ablation for chronic atrial fibrillation is less well studied. Evidence to date suggests that the mechanisms of chronic atrial fibrillation are more complex than those causing paroxysmal atrial fibrillation.5 The use of more extensive ablation procedures that modify the electrical substrate as well as the initiators of atrial fibrillation is often necessary to prevent chronic atrial fibrillation. Few studies have systematically examined the results of catheter ablation in patients with chronic atrial fibrillation.
The study by Oral et al. in this issue of the Journal evaluates the potential of catheter ablation as a treatment for chronic atrial fibrillation.6 In this report, 146 patients with medically refractory, chronic atrial fibrillation were randomly assigned to undergo circumferential pulmonary-vein ablation or to receive short-term medical therapy with amiodarone. Clinically significant structural heart disease was present in 8 percent of patients. All patients had received at least two ineffective antiarrhythmic drugs and had undergone at least one cardioversion before participating in the trial. At the 12-month follow-up visit, 74 percent of patients who had undergone ablation were in sinus rhythm without antiarrhythmic-drug therapy, as compared with only 4 percent of control patients who did not cross over to ablation therapy.
This study is noteworthy for several reasons. It convincingly demonstrates that catheter ablation alone can lead to sustained sinus rhythm in specific patients with chronic atrial fibrillation. The nonpharmacologic maintenance of sinus rhythm is an important clinical goal with far-reaching implications. Although recent trials have demonstrated no advantage to pharmacologic rhythm control, as compared with rate control, for most clinical outcomes, there is genuine concern that the benefits of sinus rhythm are negated by the deleterious effects of antiarrhythmic drugs.7 For example, the maintenance of sinus rhythm has been associated with a survival advantage that may be offset by the use of antiarrhythmic drugs.8 The ability to maintain sinus rhythm without drugs may shift the current balance between rate- and rhythm-control strategies and require a complete reassessment of their relative benefits.
The study by Oral et al. also establishes a standard for the design and electrocardiographic follow-up of future ablation trials. Such trials have rarely used a prospective, randomized design. The intensity with which Oral et al. assessed the rhythm status of their patients — assessments were made on 85 percent of all patient-days during one year of follow-up — is unprecedented for ablation trials. The importance of this methodologic achievement should not be underestimated. Asymptomatic atrial fibrillation is common after the initiation of any treatment for atrial fibrillation.9 Failure to recognize these episodes leads to an overestimate of treatment efficacy. Such an intensive and rigorous assessment of procedural efficacy is necessary to advance the science of ablation.
This study also calls attention to the difficulty in selecting meaningful end points for atrial-fibrillation trials. The end point used by Oral and colleagues requires interpretation. According to the study design, the end point would be met if a patient had a single brief episode of atrial fibrillation 12 months after ablation. Although a single brief recurrence of atrial fibrillation represents a technical failure and a study end point, it is hard to argue that the procedure is not a clinical success. Readers of articles on future clinical studies will need to distinguish between scientific and clinical outcomes.
Despite the contributions of this study to determining the role of catheter ablation in patients with chronic atrial fibrillation, these results must be kept in perspective. Catheter ablation is not yet a proven therapeutic option for the general population with chronic atrial fibrillation, and the present study leaves some issues unresolved. Most important, the study group is not representative of the greater population of patients with chronic atrial fibrillation — such patients are generally elderly and have structural heart disease and coexisting conditions. The electrical substrate for atrial fibrillation in such patients may be less responsive to ablation.10 Oral et al. do not put their results into the context of other treatment strategies, including pharmacologic rate control or evolving surgical therapy. The relative merits of each strategy are unknown.
Another potential drawback of this and other studies of ablation is that follow-up was brief. It is unclear whether atrial fibrillation may occur later in the course owing to the progression of structural heart disease. Finally, even though these investigators are highly skilled innovators of circumferential pulmonary-vein ablation, one third of the patients required additional ablation procedures. Although Oral et al. reported no complications, stroke and fatal complications are known risks of left atrial ablation, and major complications have been reported to occur in 1 to 5 percent of patients who undergo this procedure. It is not clear whether less experienced operators will be able to duplicate these safety and efficacy results.
Catheter ablation for chronic atrial fibrillation is at that interim stage of clinical development between demonstrating its promise and defining its role in clinical practice. Although it is possible to use catheter ablation to eliminate chronic atrial fibrillation, it is premature to recommend this procedure for all patients. A large, prospective clinical trial comparing the short- and long-term outcomes among patients undergoing catheter ablation with those receiving antiarrhythmic drug therapy or drug therapy to control the heart rate is needed to define the role of catheter ablation in various populations of patients. Until such trials are performed, younger patients who are refractory to medical treatment and who have limited or no structural heart disease may be most likely to benefit from this procedure. Ablation procedures are not yet widely used for chronic atrial fibrillation and are still rapidly evolving. Further technical advances are being made that are likely to improve procedural outcomes. Catheter ablation is not first-line therapy for chronic atrial fibrillation. Physicians considering this therapy for their patients should refer them to experienced centers and recognize that the elderly and those with severe structural heart disease may not be good candidates for ablation.
No potential conflict of interest relevant to this article was reported.
Source Information
From Virginia Commonwealth University Medical Center, Richmond.
References
Haisaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659-666.
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;293:2634-2640.
Oral H, Knight BP, Tada H, et al. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation 2002;105:1077-1081.
Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC Revision of the 2001 Guidelines for the Management of Patients with Atrial Fibrillation. Circulation (in press).
Lazar S, Dixit S, Marchlinski FE, Callans DJ, Gerstenfeld EP. Presence of left-to-right atrial frequency gradient in paroxysmal but not persistent atrial fibrillation in humans. Circulation 2004;110:3181-3186.
Oral H, Pappone C, Chugh A, et al. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. N Engl J Med 2006;354:934-941.
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;347:1825-1833.
Corley SD, Epstein AE, DiMarco JP, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study. Circulation 2004;110:1509-1513.
Senatore G, Stabile G, Bertaglia E, et al. Role of transtelephonic electrocardiographic monitoring in detecting short-term arrhythmia recurrences after radiofrequency ablation in patients with atrial fibrillation. J Am Coll Cardiol 2005;45:873-876.
Chen MS, Marrouche NF, Khaykin Y, et al. Pulmonary vein isolation for the treatment of atrial fibrillation in patients with impaired systolic function. J Am Coll Cardiol 2004;43:1004-1009.(Mark A. Wood, M.D., and K)
The importance of the pulmonary veins and surrounding left atrium in the initiation of atrial fibrillation is now widely accepted by electrophysiologists. Electrical isolation of the pulmonary veins by radiofrequency catheter ablation has a success rate approaching 75 to 85 percent in patients without clinically significant structural heart disease.2,3 According to the latest guidelines of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology, catheter ablation is considered standard therapy for patients who have symptomatic paroxysmal atrial fibrillation after having had no response to a single antiarrhythmic drug.4
In contrast to its established use for paroxysmal atrial fibrillation, the role of catheter ablation for chronic atrial fibrillation is less well studied. Evidence to date suggests that the mechanisms of chronic atrial fibrillation are more complex than those causing paroxysmal atrial fibrillation.5 The use of more extensive ablation procedures that modify the electrical substrate as well as the initiators of atrial fibrillation is often necessary to prevent chronic atrial fibrillation. Few studies have systematically examined the results of catheter ablation in patients with chronic atrial fibrillation.
The study by Oral et al. in this issue of the Journal evaluates the potential of catheter ablation as a treatment for chronic atrial fibrillation.6 In this report, 146 patients with medically refractory, chronic atrial fibrillation were randomly assigned to undergo circumferential pulmonary-vein ablation or to receive short-term medical therapy with amiodarone. Clinically significant structural heart disease was present in 8 percent of patients. All patients had received at least two ineffective antiarrhythmic drugs and had undergone at least one cardioversion before participating in the trial. At the 12-month follow-up visit, 74 percent of patients who had undergone ablation were in sinus rhythm without antiarrhythmic-drug therapy, as compared with only 4 percent of control patients who did not cross over to ablation therapy.
This study is noteworthy for several reasons. It convincingly demonstrates that catheter ablation alone can lead to sustained sinus rhythm in specific patients with chronic atrial fibrillation. The nonpharmacologic maintenance of sinus rhythm is an important clinical goal with far-reaching implications. Although recent trials have demonstrated no advantage to pharmacologic rhythm control, as compared with rate control, for most clinical outcomes, there is genuine concern that the benefits of sinus rhythm are negated by the deleterious effects of antiarrhythmic drugs.7 For example, the maintenance of sinus rhythm has been associated with a survival advantage that may be offset by the use of antiarrhythmic drugs.8 The ability to maintain sinus rhythm without drugs may shift the current balance between rate- and rhythm-control strategies and require a complete reassessment of their relative benefits.
The study by Oral et al. also establishes a standard for the design and electrocardiographic follow-up of future ablation trials. Such trials have rarely used a prospective, randomized design. The intensity with which Oral et al. assessed the rhythm status of their patients — assessments were made on 85 percent of all patient-days during one year of follow-up — is unprecedented for ablation trials. The importance of this methodologic achievement should not be underestimated. Asymptomatic atrial fibrillation is common after the initiation of any treatment for atrial fibrillation.9 Failure to recognize these episodes leads to an overestimate of treatment efficacy. Such an intensive and rigorous assessment of procedural efficacy is necessary to advance the science of ablation.
This study also calls attention to the difficulty in selecting meaningful end points for atrial-fibrillation trials. The end point used by Oral and colleagues requires interpretation. According to the study design, the end point would be met if a patient had a single brief episode of atrial fibrillation 12 months after ablation. Although a single brief recurrence of atrial fibrillation represents a technical failure and a study end point, it is hard to argue that the procedure is not a clinical success. Readers of articles on future clinical studies will need to distinguish between scientific and clinical outcomes.
Despite the contributions of this study to determining the role of catheter ablation in patients with chronic atrial fibrillation, these results must be kept in perspective. Catheter ablation is not yet a proven therapeutic option for the general population with chronic atrial fibrillation, and the present study leaves some issues unresolved. Most important, the study group is not representative of the greater population of patients with chronic atrial fibrillation — such patients are generally elderly and have structural heart disease and coexisting conditions. The electrical substrate for atrial fibrillation in such patients may be less responsive to ablation.10 Oral et al. do not put their results into the context of other treatment strategies, including pharmacologic rate control or evolving surgical therapy. The relative merits of each strategy are unknown.
Another potential drawback of this and other studies of ablation is that follow-up was brief. It is unclear whether atrial fibrillation may occur later in the course owing to the progression of structural heart disease. Finally, even though these investigators are highly skilled innovators of circumferential pulmonary-vein ablation, one third of the patients required additional ablation procedures. Although Oral et al. reported no complications, stroke and fatal complications are known risks of left atrial ablation, and major complications have been reported to occur in 1 to 5 percent of patients who undergo this procedure. It is not clear whether less experienced operators will be able to duplicate these safety and efficacy results.
Catheter ablation for chronic atrial fibrillation is at that interim stage of clinical development between demonstrating its promise and defining its role in clinical practice. Although it is possible to use catheter ablation to eliminate chronic atrial fibrillation, it is premature to recommend this procedure for all patients. A large, prospective clinical trial comparing the short- and long-term outcomes among patients undergoing catheter ablation with those receiving antiarrhythmic drug therapy or drug therapy to control the heart rate is needed to define the role of catheter ablation in various populations of patients. Until such trials are performed, younger patients who are refractory to medical treatment and who have limited or no structural heart disease may be most likely to benefit from this procedure. Ablation procedures are not yet widely used for chronic atrial fibrillation and are still rapidly evolving. Further technical advances are being made that are likely to improve procedural outcomes. Catheter ablation is not first-line therapy for chronic atrial fibrillation. Physicians considering this therapy for their patients should refer them to experienced centers and recognize that the elderly and those with severe structural heart disease may not be good candidates for ablation.
No potential conflict of interest relevant to this article was reported.
Source Information
From Virginia Commonwealth University Medical Center, Richmond.
References
Haisaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659-666.
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;293:2634-2640.
Oral H, Knight BP, Tada H, et al. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation 2002;105:1077-1081.
Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC Revision of the 2001 Guidelines for the Management of Patients with Atrial Fibrillation. Circulation (in press).
Lazar S, Dixit S, Marchlinski FE, Callans DJ, Gerstenfeld EP. Presence of left-to-right atrial frequency gradient in paroxysmal but not persistent atrial fibrillation in humans. Circulation 2004;110:3181-3186.
Oral H, Pappone C, Chugh A, et al. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. N Engl J Med 2006;354:934-941.
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;347:1825-1833.
Corley SD, Epstein AE, DiMarco JP, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study. Circulation 2004;110:1509-1513.
Senatore G, Stabile G, Bertaglia E, et al. Role of transtelephonic electrocardiographic monitoring in detecting short-term arrhythmia recurrences after radiofrequency ablation in patients with atrial fibrillation. J Am Coll Cardiol 2005;45:873-876.
Chen MS, Marrouche NF, Khaykin Y, et al. Pulmonary vein isolation for the treatment of atrial fibrillation in patients with impaired systolic function. J Am Coll Cardiol 2004;43:1004-1009.(Mark A. Wood, M.D., and K)