AF Ablation vs Drugs: Lessons From the Rich Peverley Case

It's not often that heart-rhythm news makes the sports page. When it does, there is usually a learning opportunity.

So it was when professional hockey player Rich Peverley collapsed during a game. Within seconds, he underwent "normal" treatment, which included the "delivery of electricity." We soon learned he was being treated for atrial fibrillation.

Peverley's case highlights a challenging problem in current-day electrophysiology practice:

Choosing the best initial rhythm-control strategy for patients with symptomatic AF.

This a tough call because the options are so lousy. AF patients who remain symptomatic after making basic lifestyle improvements (see more below) face three imperfect choices: suffer with the disease; take a precarious medicine; or undergo an invasive and expensive procedure.

The irony of treating AF is that treatment can be more dangerous than the disease. Exhibit A is the case of Peverley. In a press conference given three days after his event, we learned that he had been cardioverted in the preseason, was considering ablation, and was taking "meds," which had been "upped" in the days prior to his collapse. Although there is some debate about the shocked rhythm, (eg, was it 1:1 flutter, VT/VF, or VT/VF due to degeneration of flutter?), there is no debate that he passed out stone cold because of a tachyarrhythmia and then received high-voltage shocks. The likelihood that proarrhythmia caused his near-death experience is strengthened by reports that he had no structural heart disease.

Hindsight is sharp, but the question in the Peverley case centers on the initial rhythm-control strategy for AF. Could his event have been avoided if he and his doctors chose an AF ablation over medical therapy? European and American experts differ in their guidance. The European Society of Cardiology AF treatment guidelines allows for an ablation to be done as first-line therapy^[1], while the American guidelines recommend ablation for those patients in whom medical therapy has failed to control symptoms^[2].

Here, we have a worthy topic. Let's start with the obvious:

We are writing about the AF patient who has multiple (not just one or occasional) symptomatic episodes that have not responded to simple lifestyle measures. The "lifestyle" issue is an important caveat, as no one would suggest embarking on dangerous AF treatment before doing the simple stuff. You know, things like weight loss, attention to blood pressure, treatment of sleep apnea, and avoidance of alcohol. Or, in the case of the endurance athlete, a period of . . . dare we say . . . rest. Any experienced AF doctor will testify that these measures, if undertaken seriously, can reduce if not eliminate AF burden^[3].

Nonetheless, there will be AF patients who remain with episodes. In these cases, clinicians and patients usually look to clinical trials for guidance.

In the last couple of years, two randomized clinical trials have addressed the issue of first-line therapy (excluding the Radiofrequency Ablation vs Antiarrhythmic Drugs as First-Line Treatment of Paroxysmal Atrial Fibrillation [RAAFT-1] trial, which had only 67 patients, lacked long-term follow-up, and was published in 2005^[4]). The most recently published—but hardly contemporary (2006–2010)—trial looking at this matter is the RAAFT-2 trial^[5].

Michael O'Riordan at heartwire does a nice job reporting RAAFT-2, but here is a brief synopsis:

RAAFT-2 compared 61 patients who received antiarrhythmic drugs (AADs) and 66 patients who received AF ablation as initial therapy. Patients were young, low-risk, and mostly free of heart disease. The primary end point was a documented atrial tachyarrhythmia lasting more than 30 seconds over the 24-month follow-up period. More than a third of patients (26/61) in the AAD group crossed over to ablation, while only six of 66 patients in the ablation group received AAD.

AADs failed in 72% of cases and AF ablation in 55%. The p value reached statistical significance, but the word imperfect applies to both treatment arms. Perhaps most important was the major complication rate, which occurred in 9% of patients in the ablation group and 6% in the drug group.

In an editorial that accompanied the study^[6], Dr Hugh Calkins (Johns Hopkins University, Baltimore, MD) cited this sobering review of in-hospital complications from 93 801 AF ablation procedures performed in the real world between 2000 and 2010^[7]. This retrospective analysis revealed a striking increase in complication rates, from 5.33% in 2000 to 7.48% in 2010. This same analysis also found an in-hospital mortality of 0.42%. Calkins was clear with his words when discussing these disturbing findings:

"S  ome operators have limited experience with AF ablation and high complication rates, whereas others have considerable experience and very low complication rates."

The RAAFT-2 trial has not been the only comparison of AADs vs ablation as first-line therapy. In 2012, the MANTRA-PAF investigators reported no significant differences in AF burden between patients treated initially with AF ablation vs AADs^[8]. This 294-patient trial was widely interpreted as negative, but anyone reading the "Methods" section would recognize that the ablation strategy was flawed—pulmonary-vein isolation was not confirmed, and linear ablation was allowed. Plus, more than a third of patients in the medical group crossed over to ablation. Even with an outdated ablation strategy, patients in the ablation arm experienced less AF burden at 24-month follow-up.

That's it for evidence. These two trials, plus the 67 patients in RAAFT-1, constitute the entire evidence base for the initial rhythm-control approach to patients with symptomatic AF.

This is striking, isn't it? Hundreds and thousands of AF ablations have been done in recent years, and only a few hundred patients have been formally compared in clinical trials looking at first-line therapy. And, of these comparisons, the ablation strategy used was less than contemporary. This dearth of evidence leaves great leeway for clinical judgment.

Here are seven thoughts to consider in the decision-making surrounding advice and counsel of the de novo AF patient with symptoms:

1. Emphasis must be placed on the role of lifestyle. Compelling evidence exists that strict control of lifestyle factors reduces AF burden. AF should no longer be treated as if it occurred mysteriously and is unmodifiable. This logic applies to athletes and overachievers as well, a cohort that might be able to avoid potential AF-treatment complications if they were to pause for a period of balance and rest. (This phenotype might read Thoreau during their respite.)

2. AF ablation is skill dependent. Experience, training, and hand-eye coordination matter. And not just in success rates, but also in safety. These facts make it imperative that AF centers maintain a database for results and complications.

I offer a (very) biased theory: Some experienced private-practice AF centers may actually perform better than academic centers—which have teaching as a mission. Consider, for instance, the risk of pericardial tamponade. How many of these perforations relate to trainees learning exactly how hard to push, as in: a cyclist learning how fast he can corner a bike without crashing.

3. There may be value in waiting, or considering new ablation technology. Two recently published studies suggest second-generation cryoballoon ablation achieves 80% single-procedure success rates^[9,10]. The caveat, of course, is that these data come from highly experienced cryocentric labs. The new balloon gets colder, which is good for making durable lesions, but bad for the risk of collateral damage, such as phrenic-nerve injury. Cryoballoon ablation was designed to make AF ablation easier, but it is now clear that balloon isolation of pulmonary veins is no less daunting than point-to-point RF ablation.

4. FIRM ablation is promising. The long-term results of the CONFIRM trial have held up^[11]. In my opinion, the compelling FIRM ablation results have not been emphasized enough. Consider that in the original CONFIRM trial, investigators randomized a challenging patient population: 72% of the 92 patients had persistent AF. Postablation monitoring was thorough; the majority of patients (88%) had implantable loop recorders^[12]. Then, FIRM ablation has been shown to be equally effective in multiple labs. Most important: there is no magic. The success rates of FIRM ablation are believable because the investigators offer a mechanistic reason why it works. FIRM ablation works because in most cases the lesions ablate the problem rather than the premature atrial complexes (PACs) that initiate the problem. (Think AV nodal reentrant tachycardia: FIRM targets the slow pathway while pulmonary-vein isolation tries to ablate the PACs.)

5. Knowledge of basic pharmacology matters. The case of Rich Peverley highlights the seriousness of antiarrhythmic drugs. Some authors, ones that know electrophysiology well, say things like a "trial of antiarrhythmic drugs should be tried before the more invasive AF ablation." That statement makes AADs seem less risky than ablation. This may be the case when experts prescribe AADs. They understand the issues of use and reverse-use dependence, cycle-length slowing, QT prolongation, drug clearance, and drug interactions. In the real world, where the majority of atrial fibrillation is treated by nonelectrophysiologists, the therapeutic window of AADs is very narrow.

6. AF treatment requires an engaged and informed patient. I have said many times that AF treatment is a team sport. Patients must understand their drugs and procedures. This takes time and energy from both patient and doctor. Warfarin is the classic example. Effective anticoagulation turns on patient education. Likewise, rhythm-control therapy is much about managing expectations of patients. I tell AF patients that we will need to become friends for a while.

7. Athletes are special. Most agree that long-term participation in sports increases the risk of developing AF. Athletes with AF present with special circumstances: they have low resting heart rates, even minor reductions in cardiac output from AADs are not acceptable, and the intensity of exercise increases the risk of proarrhythmia. Small single-center studies have reported good success rates of AF ablation in athletes^[13]. But athletes also need to know ablation lesions cannot be undone.

Summary

Choosing the best approach to initial AF treatment centers on decision quality. In a recent Circulation CV Quality and Outcomes editorial, Dr Rodney Hayward (University of Michigan, Ann Arbor) noted three important truths of medical decisions: medical decisions represent gambles; the chances of benefit and harm exist along a continuum; and these odds are rarely precisely known^[14]. He was writing about the decision to take a statin drug, but the truths apply well to the initial approach to AF.

What an important role electrophysiologists have. We must be able to look inward at our own abilities and biases. Then we must be able to translate these to the patient who seeks, first, our advice and counsel, and then our hard-won skills. That's serious doctoring!

I look forward to the future when this initial AF treatment decision is more like the one for supraventricular tachycardia ablation. We are not there yet, but it's coming.

Editor's note: Since this post was drafted, it has been reported that Peverley underwent heart-rhythm surgery.

Cite this: AF Ablation vs Drugs: Lessons From the Rich Peverley Case - Medscape - Mar 25, 2014.