There will be a breakthrough in AF ablation coming next week at the ESC meeting

The results of the Study of the Week have yet to be presented. But it may be a biggie because it might sort out the placebo effect of AF ablation.

Atrial fibrillation ablation began around the turn of the century. Millions of people have had this procedure over the past 24 years. Millions.

In population studies, AF associates with worse outcomes. Strokes and heart failure are the main complications of AF. Plus, many patients have symptoms from AF.

Drugs to suppress AF are not the best. Their efficacy is modest; their side effects can be problematic.

And even when drugs suppress AF, trials failed to show that doing so reduces stroke or heart failure. (The one exception is the recent EAST AF trial, though I have noted significant limitations of that early rhythm control trial.)

Ok then. AF drugs may not reduce the complications of AF, but surely, ablation would.

Then came the CABANA trial of ablation vs drugs. In CABANA, ablation reduced AF episodes on monitors, but hard outcomes did not differ significantly.

“No worries,” said the EP community.

AF ablation improves quality of life. Such an idea is easy to believe because patients tell you they feel better after ablation. The problem here is that it’s hard to compare a subjective outcome (like feeling better) when one group of patients get a procedure and the other group gets tablets. Placebo effects can be quite strong.

My EP colleagues have long argued that we don’t need a placebo-controlled trial for AF ablation because there are studies showing that AF ablation reduces AF burden and this correlates with improvement in quality of life.

The problem with that thinking was exposed in the first ORBITA trial of stenting coronary arteries for angina. Patients with severe partial blockages were randomized to a stent or a placebo procedure. In the end, there was no improvement in exercise time or quality of life. It was a shocking result.

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The SHAM-PVI trial

Next weekend at the European Society of Cardiology meeting in London, a UK team of researchers will present results of the SHAM-PVI trial. They have published their rationale and protocol paper.

About 140 patients will be randomized to either standard AF ablation (with cryoballoon ablation) or a sham procedure (with phrenic nerve pacing and cardioversion if persistent AF).

All patients receive an implantable loop recorder, which will provide the primary endpoint of AF burden at 6 months. Secondary endpoints include to time to symptomatic and asymptomatic AF, total atrial tachyarrhythmia episodes and patient reported outcome measures.

I question the choice of endpoint. To me, it would have been better to have quality of life as the primary endpoint.

Why? We know that AF ablation reduces episodes of AF. What we want to know is whether that reduction in AF produces a placebo-resistant effect of improved well being. Stents produce better looking arteries and reduction of ischemia on stress testing, but in the first ORBITA trial, it made no difference in exercise time.

Nonetheless, quality of life in SHAM-PVI is a secondary endpoint. I love that the investigators had the courage to design and conduct such a bold study.

I really do believe that AF ablation has more than a placebo effect. But it would have been good to know that before millions of patients have had the procedure. Placebo effects have fooled us many times over in the history of medicine.

Stay tuned. I will let you know how the study comes out. JMM