Atrial fibrillation (AF) affects approximately two million people in the US. It is a major cause of stroke, adversely impacts quality of life, and is associated with increased mortality.1-4 Treatment with antiarrhythmic drugs and anticoagulation is still considered first-line therapy in patients with symptomatic AF.
Recent randomized trials4,5 have shown that a strategy of rate control and anticoagulation as indicated is comparable with a strategy of rhythm control using antiarrhythmic drugs in treating many patients with AF. In these trials,4,5 mostly elderly patients had well tolerated AF. Restoring sinus rhythm may be of greater benefit in younger patients because doing so may prevent the progressive atrial remodeling that leads to chronic AF.6
These studies only showed that a strategy of rhythm control using antiarrhythmic drugs was comparable with a strategy of rate control without using antiarrhythmic drugs. A limitation of all these trials is that the rhythm control strategy was not efficacious. For example, in one trial,4 only 39% of patients randomized to the antiarrhythmic drug group were in sinus rhythm at the end of the study. Furthermore, in an analysis of one study7 that evaluated predictors of mortality, sinus rhythm was associated with a 47% reduction in risk of death, whereas use of antiarrhythmic drug therapy was associated with a 49% increase in mortality. This suggests that the neutral results in the rate control compared with rhythm control trials might be explained by the fact that offsetting the detrimental effects of antiarrhythmic drug therapy negated the benefits of antiarrhythmic drugs in restoring sinus rhythm. In theory, a therapy that restores and maintains sinus rhythm while avoiding the deleterious effects of automatic atrial defibrillators (AADs) would improve survival. AF catheter ablation would be one such therapy.
In contrast to antiarrhythmic medications, catheter ablation eliminates the triggers of AF. Haissaguerre et al.8 showed that the triggers of AF originate from the pulmonary veins in most patients with AF. Only a minority of patients have extra-pulmonary vein foci as triggers of AF. The pulmonary veins have been shown to play a critical role in both triggering and maintaining AF. The goal of present-day AF ablation (AFA) is to electrically 'disconnect' the pulmonary veins from the rest of the atrium by ablating around the origin of the veins. Currently, there are at least two techniques of AFA—a purely anatomical approach, guided by non-fluoroscopic navigation systems. In these anatomically guided techniques, radio frequency ablations (RFA) are delivered circumferentially outside the pulmonary vein ostia with a variety of additional ablation lesions.9
However, most techniques target electrical isolation of the entire pulmonary vein musculature from the left atrium as the end-point. This can be guided by either angiography or intracardiac echocardiography. The approach at the Cleveland Clinic Foundation is summarized below.
Cleveland Clinic Approach
Patients are brought to the electrophysiologic laboratory in a fasting, non-sedated state. A multipolar mapping catheter is placed into the coronary sinus via the right internal jugular vein to record right atrial and coronary sinus electrograms. The ablation catheter and circular mapping catheter are placed via the right femoral vein to the left atrium using a double transseptal puncture technique. In addition, pulmonary vein (PV) isolation (PVI) is performed using phased array intracardiac echocardiographic (ICE) monitoring using an ICE catheter introduced to the right atrium via the left femoral vein.
ICE is utilized to ensure circular mapping catheter positioning, appropriate site of energy delivery, and to guide energy titration by monitoring microbubble formation.10 RF energy is delivered using either an 8mm tip or an irrigated 4mm tip ablation catheter. Intravenous (IV) heparin is administered to achieve an activated clotting time of 350 to 400 seconds.11 Heparin is given before the transseptal puncture to prevent clot formation on the transseptal sheath.
RFA is performed wherever PV potentials are recorded around the PV antra. The end-point of ablation is complete electrical disconnection of the PV antrum from the left atrium. This is considered to be achieved when no PV potentials could be recorded along the antrum or inside the vein by the circular mapping catheter, or if there was electrical dissociation of the PV from the left atrium. At the end of the procedure, all four pulmonary venous antra are extensively remapped with the circular mapping catheter to check for any persisting PV potentials and, if necessary, further ablation is performed to eliminate these. All four PVs are isolated. Neurologic checks are performed intermittently during the procedure, at the end of the procedure, and the following day just before discharge.12
Anticoagulation with warfarin is started on the evening of the PVI procedure and continued for at least three to five months with a target international normalized ratio (INR) of two to three.Warfarin is continued if patients experienced recurrence of AF or if ≥70% narrowing of a PV is detected by spiral computerized tomography (CT) scan, three months post-ablation. In both treatment arms, continuation of beta-blocker therapy was left to the treating physician.
Follow-up
Follow-up is scheduled at three months. A loop event-recorder is used in all patients to monitor events during the first three months. During the monitoring period, patients are asked to record when they experienced symptoms and at regular intervals even if asymptomatic. Additional event recorder monitoring is obtained beyond the three-month period for patients with recurrence of symptoms. Patients were also monitored with a 24-hour Holter recording before discharge and repeated at six, nine and 12 months. All patients are given a spiral-CT scan after three months. This is repeated at six and 12 months if there is evidence of any degree of pulmonary venous narrowing.
Efficacy
Using the previously mentioned approach in a randomized trial comparing medical therapy with AFA as first-line therapy, the authors found that at the end of one-year follow-up, the majority of patients (63%) in the antiarrhythmic drugs treatment group had at least one recurrence of symptomatic AF compared with only 13% in the pulmonary vein isolation group. They also found that at six months follow-up, the PVI group had significant improvement in six of eight parameters measured by the short form (SF)-36 quality of life health survey questionnaire.13 Other groups have also had similar success results in patients refractory to medical therapy.
Current Practice
Ablation therapy for AF is still reserved for symptomatic patients who have failed antiarrhythmic drugs.The primary concern is that complications from the procedure can occur. A recent worldwide survey of more than 8,000 AFA procedures reported an overall major complication rate of 6%.9 However, many of the complications, while serious, typically result only in acute and not long-term morbidity. The most serious complications resulting in permanent disability were uncommonÔÇödeath in 0.05% and stroke in 0.28%. Significant PV stenosis was reported in 1.3%. However, with intracardiac ECG monitoring the incidence of this complication has been less than 1%.
A recently recognized complication of catheter-based AFA is atrio-esophageal fistulae. Among the three published case reports of this complication, two resulted in death.14,15 The authors have not had this complication at their institution, primarily due to use of ICE microbubble formation monitoring for guidance with energy delivery. Restricting energy delivery and output to avoid microbubble formation results in less charring, fewer thromboembolic events, and less tissue disruption;10 therefore, reduced pulmonary vein stenosis and stroke risk, and no left atrio-esophageal fistula formation.
In contrast to pulmonary vein isolation, the risks associated with antiarrhythmic drug therapy are not trivial. In one study, antiarrhythmic medications were associated with a 49% increased risk of death after taking into account the presence of sinus rhythm.7 In addition, because antiarrhythmic medications are ineffective in maintaining sinus rhythm, patients on AADs may remain at risk for long-term complications of AF, such as stroke.
Outcome
Catheter-based ablation for AF is recommended for patients who have failed antiarrhythmic medications at this time. Results of on-going studies will determine whether ablation will become first-line therapy for AF. The best ablation technique has not been established; this will also be addressed in future studies.
Future Perspective
Catheter ablation for AF is not yet an established therapy because the procedure is technically challenging and satisfactory results cannot be replicated in every laboratory. Devices are being developed to address this issue, such as expandable stents, balloon systems using laser, high focus ultrasound, or cryo energy, as well as remote navigational systems where either a variable magnetic field or a robotic sheath help the operator reach sites relevant to the ablation procedure.
The adjunctive benefit of vagal denervation and ablation of sites selected based on electrogram characteristics or spectral analysis of the local recordings is being evaluated. In addition, better understanding of the genetic basis of AF may pave the way to innovative and patient-specific therapies.
Conclusion
Catheter-based ablation for AF is recommended for patients who have failed antiarrhythmic medications. In the future, a better understanding of the basic mechanisms of AF, along with the on-going development of devices and perfecting of techniques, will make ablation more reproducible and enticing to more laboratories, in spite of the fact that the best ablation technique is yet to be determined.