Atrial fibrillation is a mysterious disease. We know a lot but surely not enough. We look at AF but are we really seeing it?
I believe there are hard truths to this disease. Hard in a way that neither patients nor doctors like. More on that later. First to some news on a major AF ablation trial.
AF ablation news:
One of the fundamental questions in electrophysiology today centers on the outcomes of AF ablation. Though most experts agree that AF ablation, when compared with medical therapy, reduces AF symptoms and improves quality of life (important metrics for sure), we don’t know whether ablation reduces the chance of stroke or death. We think it does–preliminary studies look good–but the only way to know for sure is to do a head-to-head comparison.
The long-term outcomes after specific AF treatments are relevant because population data (Framingham Study) show that having AF increases the risk for stroke or early death. So it’s better not to have AF. But populations are not individuals. Some AF patients have little risk while others are quite ill. The vast majority of AF patients are spread across a continuum of risk.
One of the most important AF studies of our time was (or is) the Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial. CABANA is an ongoing multicenter, international study that compares anti-arrhythmic drugs to catheter ablation. Researchers randomize AF patients to either strategy, follow them over years and then count easy things like stroke and death. CABANA aims to tells us whether ablation is just an expensive and invasive way to control AF symptoms or a true disease modifier.
Dr. Wes Fisher broke the story that the leadership of the CABANA trial decided to change its primary outcome from stroke and death to a composite of total mortality, disabling stroke, serious bleeding, or cardiac arrest. I know what you’re thinking…How is this news? As always, Dr Fisher explains it well:
While some may not see this as a significant development, we should understand that clinicians will be left without a definitive answer to which therapy, catheter ablation or anti-arrhythmic drug therapy, will prolong life the best in symptomatic patients with atrial fibrillation. Instead, doctors will have to read tea leaves based on a composite score of several endpoints to make their own personal judgment.
My colleague worries that statistical realities will muddy the issue: that being, of course, the dilemma of how best to approach a not-immediately life-threatening disease with potentially life-threatening treatments (ablation or medications).
I think about this a lot.
Let’s first talk about CABANA and then move on to those hard truths I was mentioning.
The CABANA trial is doomed to fail. Not because it’s a bad trial or bad idea or done by bad investigators. It’s none of that. The problems with CABANA are the following realities:
- Symptomatic AF patients do not want to be randomized to drugs. AF patients go to AF centers for ablation. Recruitment of study volunteers has been slow and will remain slow.
- Eligible AF patients have very low event rates–a good thing. This is important statistically because to show a difference in stroke rate or deaths (infrequent events in AF) between the two treatments, you need a lot of patients and a lot time. This is why investigators changed the endpoint and shortened follow-up. They wanted an answer in their career–not their children’s.
- The techniques of AF ablation will improve. I believe we are on the cusp of big stuff–a new understanding of AF mechanisms, which will lead to better success rates. Consider that the results of CABANA won’t be available for years and by then better techniques will have rendered the results irrelevant.
The Hard Truths of AF:
The second issue is that I’m not sure asking whether AF ablation is better than drugs is the most important question.
My big-picture feelings about AF treatment are evolving rapidly. Let me start this way: Too often AF is treated as if it’s fixable rather than manageable. You have heart disease; heart disease is bad; therefore you need treatment. This logic might be okay if we weren’t prescribing dodgy QT- or QRS-prolonging drugs that fail two-thirds of the time, or if we weren’t delivering burns/freezes in the atrium that fail half the time. Or this: that in most cases, patients with AF could help themselves if we told them the truth—that losing weight and managing major risk factors can reduce atrial fibrillation symptom burden and severity. AF is not appendicitis; there is rarely an easy fix.
More and more, I counsel patients that AF is both a disease and a consequence of actions–your body talking to you. Like it does in the days after lifting weights for the first time in a while. Why else do you think those atrial cells begin to misfire?
Yes, as clinicians in 2014, we aim to prevent complications from AF. We prescribe anticoagulants to lower the risk of stroke and beta-blockers to prevent tachycardia-medicated heart muscle weakness.
But merely prescribing said treatments ignores the inflamed elephant in the room. There is no medical or surgical fix for inflammation overload. And I don’t mean just inflammation from obesity, high blood pressure, sleep apnea, sleep deprivation, alcohol, diabetes, smoking and exercise overload. I mean inflammation from never taking your foot off the gas, physically, mentally or emotionally.
I was recently bragging to a patient about the successful ablation I performed on him. He replied that it may not have been the ablation. “What do you mean”? I asked. “Well…about that time doc, I retired from working nights; I fixed my relationship woes; and now I come home to peace and quiet and a kid who I love. You think that stuff helped?”
If I had a dollar for every time I have heard a version of that story.
You see what I mean? There’s a common thread here. It’s the inflammation.
For athletes with AF, the issue is years of over-inflammation from exercise and inadequate rest. For the obese and hypertensive, it’s the inflammation of atrial stretch and fibrosis. For the executive or engineer, it’s the inflammation of never having enough, or never being exactly correct enough, or maybe the three–not one–glasses of wine.
You think I’m full of beans. Consider also the common scenario of AF occurring after an infection, surgery or trauma, all of which are indeed big wallops of inflammation.
Doctors look at this picture-in-a-picture everyday. But are we putting it together?
Does AF ablation reduce the risk of stroke or death? Okay, okay, yes, of course, it’s an important question.
That we have to ask it, that we look at the problem of AF without really seeing it, speaks to a collective unwillingness to face the hard truths about this disease. Again, we see a disease rather than a human being.
Is it possible that anti-arrhythmic drugs and ablation may just be imperfect ways to buy time for the patient with AF to modify the inflammation overload that stirs the ion channels of highly connected atrial muscle cells?
With humans, it’s all connected.