EDITORIAL COMMENTARY

Catheter ablation of atrial fibrillation: A treatment frontier

Michael Domanski & Albert L. Waldo

Published online: 15 August 2006# Springer Science + Business Media, LLC 2006

Atrial fibrillation is the most common supraventriculararrhythmia. More than two million Americans have atrialfibrillation [1]. The prevalence of atrial fibrillation increaseswith increasing age, from about 1% in individuals over60 years of age to 8–12% in the ninth decade [1]. The prev-alence is expected to increase over time [1, 2].

It has long been recognized that the presence of atrialfibrillation confers an adverse prognosis. For instance, it isassociated with a fivefold increased incidence of stroke [21].For men and women between 55 and 75 years of age enteredinto the Framingham study, the 10-year mortality was 55% inatrial fibrillation patients and 15% in patients without atrialfibrillation [3]. However, most of the studies demonstratingthat AF confers an adverse prognosis predate both the recog-nition of the need for anticoagulation in patients with strokerisk factors, and the much improved treatment of commoncomorbidities such as left ventricular dysfunction and heartfailure. Nevertheless, the prevalence of AF and associatedcomplications will continue to increase as the population ages;the associated risks for stroke, heart failure, and death are asignificant burden on patients and society; living with AFsignificantly diminishes quality of life; and current phar-macologic treatment options are suboptimal [19].

How, then, might catheter ablation be useful in thetreatment of atrial fibrillation? There are three possible roles:

1. improve survival;2. reduce the risk of stroke in the absence of anticoagulation;3. reduce or eliminate symptoms related to atrial fibrillation.

Although atrial fibrillation is a marker of poor prognosis,whether it is causal in generating the poor prognosis or anepiphenomenon of a sick heart, or both, is unclear. In thisregard, the AFFIRM [4] trial did not demonstrate a survivaladvantage of a rhythm control treatment strategy over a ratecontrol strategy. However, an AFFIRM on-treatment anal-ysis substudy which examined survival on the basis ofselected time-dependent variables and baseline clinicalvariables demonstrated that independent of treatment strat-egy, the presence of sinus rhythm was associated with alower risk of death (hazard ratio 0.53; i.e., a 47% lower riskof death) [5]. On the other hand, use of antiarrhythmic drugtherapy was associated with an increased risk of death(hazard ratio 1.49; i.e., a 49% increased risk of death).These data suggest that sinus rhythm enhances survival if itcan be achieved safely. If catheter ablation could cure atrialfibrillation reliably and with minimal complications, thenthe usefulness of maintaining sinus rhythm could be defin-itively assessed. Also, a reliable and safe catheter-based ap-proach to curing atrial fibrillation might obviate the need foranticoagulation to prevent stroke.

So, why not just do randomized trials of catheter ablationversus standard therapy with endpoints of stroke and death?The difficulty with designing any such trial lies both in theincompleteness of our understanding of the mechanism ofatrial fibrillation and the immaturity of our knowledge ofcatheter ablation efficacy in eliminating atrial fibrillation.

Atrial fibrillation is thought to be initiated most often byabnormal impulses from the pulmonary veins [8]. Howatrial fibrillation is maintained is much less well understood,but current suggested mechanisms include the presence ofone or more drivers (their mechanism is uncertain) of veryshort cycle length which activate the atria at very rapid rates,thereby producing fibrillatory conduction [18].

Whether these impulses are needed for continuation ofatrial fibrillation, or simply initiate the arrhythmia in the

J Interv Card Electrophysiol (2006) 15:141–143DOI 10.1007/s10840-006-9024-6

M. Domanski (*)Clinical Trials Group, National Heart, Lung, and Blood Institute,Bethesda, MD 20892, USAe-mail: domanskm@nih.gov

A. L. WaldoDepartment of Medicine, Case Western Reserve University,Cleveland, OH, USA

presence of a vulnerable substrate is not known. More recentdata suggest that there may be biatrial triggers and biatrialrotors that appear at the onset of AF and at its termination,even in paroxysmal atrial fibrillation [16, 17]. Ablation ofsuch rotors or fragmented electrograms would require map-ping to improve outcomes. A clearer understanding of themechanism of sustained atrial fibrillation would likelygreatly improve the success of catheter ablation by identify-ing a vulnerable substrate or substrates. This may requirefurther evolution of current ablation technique.

Since current catheter ablation techniques have devel-oped with an incomplete mechanistic understanding of atrialfibrillation, the mechanism of benefit is also not clear. Inaddition to electrical isolation of initiators and drivers, ab-lation of a vulnerable substrate and changes in parasympa-thetic tone may play a role [11]. Although the few availablestudies suggest that success rates of 70% or more can beachieved in carefully selected patients [12, 15], variations inablation technique, short follow-up in most of the studies, andthe absence of continuous monitoring call into question theactual cure rate. This is of particular concern because of theknown high rate of asymptomatic recurrence of atrial fibrilla-tion in the face of antiarrhythmic drug therapy [10, 13, 20].

In this issue of the Journal, Cheema et al. report the longterm success rate of catheter ablation to cure atrial fibril-lation [7]. They followed 200 consecutive patients, abouthalf of whom had paroxysmal atrial fibrillation. At the endof follow-up, only 28% were free of atrial fibrillation offantiarrhythmic drugs. As would be expected, the success ratewas much greater in patients with paroxysmal atrial fibril-lation. The major complication rate in this series was 7.9%.

This study has the important limitation of reporting atechnique that the authors themselves regard as obsolete. Itdoes report long term follow-up of ablation patients, a nota-ble deficiency of most studies in the literature. In so doing,the authors underscore the problem of failure to permanentlysuppress atrial fibrillation, highlighting the need to developa practical approach to detecting asymptomatic, as well assymptomatic, recurrences. They also add to accumulatingdata indicating that atrial fibrillation, even chronic atrialfibrillation, may be amenable to a transcatheter cure, at leastin some individuals.

Beyond a lack of demonstrated efficacy, there is also theissue of safety. Catheter ablation has been associated withserious complications including pulmonary vein stenosis,stroke, atrial–esophageal fistula, tamponade, and atrial flut-ter/tachycardia [6, 14]. Current techniques have reduced therisk of pulmonary vein stenosis (1,2). Nonetheless, despitesubstantial variation in reported results, recent data suggestthat the rate of serious complications may remain in therange of 6% [14]. Further improvements in ablation tech-nique and the identification of ablation target(s) would beexpected to reduce the complication rate.

Further research into catheter ablation should have severalfacets:

1. Improve our understanding of the mechanism of atrialfibrillation as a basis for a rational approach to furtherdeveloping catheter ablation technique.

2. Optimize and standardize catheter ablation to maximizeefficacy in the permanent elimination of atrial fibrillation.This implies the need to develop practical approaches tomore effective monitoring of study patients over longperiods of time in order in order to assess results. Addi-tionally, the safety of the technique needs to be improved.

3. Clinical trials are needed to determine whether catheterablation of atrial fibrillation improves survival and/orreduces stroke in the absence of anticoagulation. Decid-ing upon timing of a trial must take into account thepotential for technical improvements or new insightsinto the mechanism(s) of atrial fibrillation which mightmake a multi-year trial obsolete when it is completed.Nonetheless, waiting to do controlled studies risks cath-eter ablation becoming common practice making ran-domization into a controlled trial infeasible. The best,but more expensive approach, might be to recognize thatmore than a single trial may be needed to fully define thefield as the technique matures.

For the present, catheter ablation of atrial fibrillationshould most often be a backup therapy reserved for patientswith poorly tolerated symptoms who are refractory tomedication. Presently, catheter ablation is most likely to bebeneficial in patients with structurally normal hearts andparoxysmal atrial fibrillation. Recent data showing thatcatheter ablation is also beneficial in patients with heartfailure and with coronary artery disease are also quite en-couraging but these patients are more likely to have a widerspectrum of tachycardias initiating AF [9, 16]. Nevertheless,with the current absence of supportive multicenter clinicaltrial data and the presence of significant procedural risk,catheter ablation of atrial fibrillation should be regarded asan evolving therapy with as yet unproven outcome withrespect to improving survival and reducing stroke risk.

References

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