Impressions from the 2012 Boston AF Symposium

Issue: March 2012

This year marked another excellent Boston Atrial Fibrillation Symposium covering the broad swath of atrial fibrillation.

Albert L. Waldo

For me, in many ways, among the most interesting sessions was one on pulmonary vein reconnection. It seems clear that the most widely accepted ablation technique with recognized success that is not largely empiric is pulmonary vein isolation to prevent triggers from initiating AF. It has been clear for some time now, especially to those who perform AF ablation procedures, but especially in the presentations at this session, that isolation of the pulmonary veins remains critical for ablation of virtually all forms of AF. It now seems widely accepted that incomplete pulmonary vein isolation or pulmonary vein reconnection with the left atrium remains a major culprit in the recurrence of AF after ablation procedures, including late recurrences (≥1 year). Considerable time was spent discussing very early recurrence of pulmonary vein connection with the left atrium, ie, with the initial ablation procedure.

Thus, how long should one wait after ostensibly isolating the pulmonary veins before one considers that the apparent isolation is indeed adequate? The data, particularly as presented by Hans Kottkamp, MD, of Clinic Hirslanden, Zurich, Switzerland, suggest that the longer one waits, the more reconnection reveals itself, especially with use of adenosine. Although waiting 30 minutes seems to be the standard, data presented indicate that 1 hour, or even 1.5 hours, can identify more initial failures of complete pulmonary vein isolation. And, as is also well recognized, recurrence of AF or even initial failure of ablation may be due to the presence of non-pulmonary vein triggers. Clearly, identifying these sites and ablating them successfully are very important. However, many feel that additional lesions, although largely empiric, are helpful, as they add to the short- and long-term efficacy of the ablation procedure.

Atrial substrate

But to this listener, the real story is that the vulnerable atrial substrate remains a problem. AF remains virtually the only rhythm that is treated with ablation in which we do not target the mechanism that sustains the arrhythmia, but rather target the triggers that initiate it. Thus, in atrioventricular nodal reentrant tachycardia, we target the slow pathway; in AV reentrant tachycardia, we target the accessory AV connection. Then we know that, despite the continued presence of triggers, there is no reentrant circuit to engage, so there is no tachycardia. We do not have an equivalent for AF. So, for this listener, “It’s the substrate, stupid.”

We need to understand far better what the mechanism is in the atrial substrate that sustains AF. We have a lot of data from animal models that a driver or drivers of one sort or another are the culprit. But such data, as yet, are largely lacking in patients. Later in the session, there was some discussion of that. Sanjiv Narayan, MD, of the University of California, San Diego, presented his patient data in which his unique mapping system seems to have identified reentrant circuits that, when ablated, seem to terminate AF and eliminate its recurrence. Shih-Ann Chen, MD, of Veterans General Hospital, Taipei, Taiwan, presented data that reentrant circuits are infrequent (3% incidence), but when identified and ablated, successfully prevent AF. The recent data from the laboratory of Yoram Rudy, PhD, using ECGI (body surface potential mapping to mathematically determine the sequence of activation on the epicardial surface of the heart) in a series of studies in patients with AF rarely found anything suggestive of reentry, but rather suggested the presence of foci.

New oral anticoagulants

Another session of interest was one on stroke prevention in AF. Clearly, the new oral anticoagulants have already made an impact and will continue to do so. Dabigatran (Pradaxa, Boehringer Ingelheim) was approved in the United States in 2010; rivaroxaban (Xarelto, Janssen) was approved in 2011; and it is anticipated that apixaban (Eliquis, Bristol-Myers Squibb and Pfizer) will be approved sometime in the spring or early summer of 2012.

The advantages of the new oral anticoagulants include fast onset and offset of action; less intracerebral bleeding compared with warfarin; no routine coagulation monitoring; predictable pharmacodynamics and pharmacokinetics; a broad therapeutic window; a short half-life; and minimal influence of comedications and foods. The problems with warfarin have been appreciated for a long time. They include delayed onset and offset of action; a narrow therapeutic range; unpredictable dose responses; metabolism by the cytochrome P450 enzymes, especially the 2C9; common genetic polymorphisms (especially 2C9) affecting dose requirements; numerous drug-drug and drug-food interactions; variable anticoagulant response necessitating coagulation monitoring and dose adjustments; slow reversibility; inconvenience for patients and physicians; and their demonstrated underuse, even in patients without contraindications to oral anticoagulation despite the indications for its use.

The overall impression presented was that the new oral anticoagulants are quite good, but that comparison between these new agents is difficult because the patient populations of the several studies were rather different. However, the question of who is not a candidate for the new oral anticoagulants was discussed. Jeffrey Weitz, MD, of McMaster University, Ontario, Canada, suggested it was patients who were stable on warfarin; whose creatinine clearance was <30 mL/min, and even 30 mL/min to 40 mL/min; who had severe hepatic dysfunction (as the new oral anticoagulants have significant liver metabolism) or mechanical heart valves; and patients who were noncompliant with warfarin. Other issues still being sorted out include switching from warfarin to one of these new drugs or from one of these new drugs back to warfarin, and include monitoring, as it seems that these drugs also have to be monitored in some way, eg, for changes in creatinine clearance, for gastrointestinal bleeding and for periprocedure management. Then, the absence of a reversing agent is an issue.

Finally, worth mentioning is an important clinical implication from AVERROES, a trial of apixaban vs. aspirin in patients with AF at risk for stroke who could not receive vitamin K antagonist therapy because it was demonstrated or was expected to be unsuitable. The trial was stopped early because of clear benefit of apixaban. Compared with aspirin, not only did apixaban significantly reduce the risk for stroke or systemic embolism, but it did so without significantly increasing the risk for bleeding or intracranial hemorrhage. The implication is that aspirin, already recognized as not an especially effective agent in stroke prophylaxis in AF patients, now has even less to recommend it. In short, it is hard to imagine why one would any longer select aspirin for thromboprophylaxis in patients with AF?

In the end, we were left with the clear impression that a new era in stroke prevention in patients with AF is at hand.

Albert L. Waldo, MD, is the Walter H. Prichard professor of cardiology, medicine, and biomedical Engineering at Case Western Reserve University/University Hospitals Case Medical Center in Cleveland. He is also a member of the Cardiology Today Editorial Board.

Disclosure: Dr. Waldo reports consulting for AtriCure, Biosense Webster, Biotronik, Boehringer Ingelheim, Bristol-Myers Squibb, CardioInsight, Daiichi Sankyo, Janssen, Medtronic Ablation Frontiers, Merck, Sanofi and St. Jude Medical. He also reports speaking for Janssen and Sanofi.