COMMENTARY

CardioStim 2014, Day 3: Treating Atrial Fibrillation: Drugs, Ablation, or Neither?

John Mandrola

Disclosures

June 20, 2014

In the era of catheter ablation of atrial fibrillation, antiarrhythmic drugs will become obsolete. This was the title of a pro/con debate here at CardioStim 2014 .

Dr Douglas Packer (Mayo Clinic, Rochester MN) took the pro side while Dr Paulus Kirchhof (University of Birmingham, UK) opposed. Also noteworthy were the distinguished session chairs, Dr John Camm (St. George's University of London, UK) and Dr David Wilbur (Loyola, Chicago, IL).

There's a lot to say about what was (and was not) covered during this session. So let's get started.

The Pro Side

As a modifier, obsolete means something is no longer used and out of date. Dr Packer began by admitting, as many debaters at medical sessions do, that his opponent had the easier task and that his side was doomed. He then launched into a detailed critical appraisal of the literature. He made many useful points:

— The problem with AF drugs is that we may not be looking at the right type of drugs. The literature and clinical experience with AF drugs thus far has included only those chemicals that alter cardiac ion channels— eg, rhythm drugs. Dr Packer expressed the notion that future (novel) drugs may be more important. He used, as an example the preliminary data on galectin-3, which may be able to reverse fibrosis. "The answer may be further upstream from the rhythm." (More on "upstream" at the end.)

— Current antiarrhythmic drugs are not so good. It's an easy task to cull data showing the limits of rhythm drugs. Dr Packer showed numerous slides on the problems of antiarrhythmics: increased mortality with dronedarone in the PALLAS trial and amiodarone in SCD-HeFT ; nuisance side effects; proarrhythmia; and in trials testing strategies of treatment, rhythm drugs proved no better than rate-control drugs.

— AF ablation is getting better, and compared with drugs, looks far superior. Dr Packer was up-front about the imperfection of ablation but then made three major points on recent progress in catheter ablation:

  • Do not discount the value of the redo procedure, which can increases success rates significantly.

  • The data on rotor ablation indicates the possibility of increased long-term success.

  • Improvements in catheter design, such as contact-force measurements, may allow for improved safety and efficacy.

No talk from Dr Packer would be complete without mention of the CABANA trial, which has now enrolled 1600 patients and aims to gather hard-end-point (stroke mortality) data on the matter of AF ablation vs drugs. He admitted that without randomized controlled clinical trials, it would be impossible to know whether AF drugs are truly obsolete. He reminded us that there are whole-person issues such as stroke, dementia, quality of life, and mortality to think about when we treat people with AF, not just the rhythm.

Always the futurist, his closing point was that nobody said we had to be talking about the present day. "By 2016–2022, of course drugs will be obsolete, because by then we will not be doing ablation with radiofrequency, we will be doing ablation with carbon particles."

The Con Side

Dr Paulus Kirchhof was up next and immediately took issue with Packer's hedge on the future. He reminded the audience of the AF-ablation promises made a decade ago; despite those promises, AF ablation remains only 75% successful today.

Dr Kirchhof started his defense with a picture of what healthy atria should look like. He showed a picture of red cardiac muscle free of fibrosis or fat. He immediately went to the concept of AF as a structural disease—not just a fluke of nature. He showed the famous slide of the molecular and cellular basis of AF. The predominant message of that slide is that the electrical changes (decreased refractoriness and increased conduction velocity) predisposing to AF come about as means of cell survival from intracellular calcium overload. Then, once AF occurs, a cascade of events in the atria rapidly progresses and ultimately results in fibrosis. The key to his point about AF drugs not being obsolete was simple: How could a focal strategy (ablation) that creates more fibrosis ever be the answer to a global fibrosis/electrical problem?

I could almost stop my post right there. But Dr Kirchhof went on to make a few other worthy points:

— The potential complications of AF ablation are significant. He underscored the often-suppressed issue of postprocedure cerebral lesions and the possibility of cognitive dysfunction after ablation.

— The success of AF ablation depends on how hard one looks for AF. It is clear, he pointed out, that aggressive monitoring after ablation reveals many asymptomatic episodes. This is important because the ultimate goal of treating heart disease is to decrease the chance of stroke or death. And if AF is still ongoing, stroke risk remains.

— Early intervention in AF may be important. Dr Kirchhof is a primary investigator of the EAST trial, which is a prospective, randomized, multicenter trial designed to determine whether an early, standardized rhythm-control therapy strategy can prevent cardiovascular outcomes attributable to AF. The idea is that if one stops AF early, the vicious cycles of structural changes in AF could be stopped—and the disease modified. For example, prolongation of the action potential (with antiarrhythmic drugs) may be a desirable way to prevent recurrent AF, especially if started early after cardioversion.

— Dr Krichhof's final point gets to the core of doctoring: treating patients with AF means choosing an individualized approach based on a person's situation. Not all AF is the same. (This is what makes treating AF so hard.) He argued there are many ways to classify AF, and though none are agreed upon, it is clear that some patients have genetic origins, others have clear focal drivers, and many have global structural processes (obesity, hypertension, sleep apnea) that predispose to increased atrial stretch and wall fibrosis. "In the future we will not think about who is 5% better in ablation, but rather, who is the right patient for AF ablation."

Wrap-up

The rebuttal and question-and-answer period after the debate was rich with connecting themes. I perked up when Dr Kirchhoff used an oncology analogy for AF. He likened AF to a low-grade lymphoma, connecting the two diseases in four ways:

  • You know it's going to recur and you accept it.

  • You are happy to achieve disease-free survival for a few years.

  • Some patients are best suited for surgery (catheter ablation) while others for chemotherapy (AF drugs).

  • Oncologists have learned to differentiate the cell type of lymphoma (B or T) just as electrophysiologists should determine the type of atrial disease.

Session chair Dr Camm then asked whether a quite crude approach [ablation], currently at least, can really improve sufficiently to deal with the improvements in the biochemical personalized approach that could be applied with drugs. "AF is a biochemical process, and it ought to be affected with drugs."

Packer responded by saying the most exciting drug therapies are not the antiarrhythmics, but rather the ones in development that address the upstream notion of preventing fibrosis.

The Missing Link

Can you see what is missing? Perhaps it is so close, it is in the blind spot.

I'll give you a hint: "AF is a biochemical problem and it ought to be affected with . . . "

. . . No. No. Not drugs.

Drugs (or ablation for that matter) are rarely the answer to systemic and acquired diseases.

In fact, thinking drugs or ablations are the answer is, in my opinion, a major impediment to improving the health of our patients. Although the lymphoma-AF analogy is useful in some ways, the causes of AF are not quite as mysterious as lymphoma. Just look at maps of obesity and wealth and tell me that AF incidence and prevalence is not a lifestyle problem. Of course the problem is farther upstream than cardiac ion channels.

Dr Prashanthan Sanders (University of Adelaide, Australia) and colleagues have shown (in sheep and man) that AF may not be necessary. Sports cardiologists will tell you that detraining the overtrained might reverse structural changes in the heart. And any clinician can tell you AF often resolves itself with attention to sleep disorder or alcohol cessation.

When we see start seeing those calcium-overloaded cells and structural derangements in the atria as problems to be addressed by the way we live rather than something to be burned or drugged, then, and only then, will we have made major progress in AF care.

JMM

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....

Recommendations