AF Ablation Works…But: The Positive SHAM-PVI Trial

[CDreamer]

I recently read an article with the above title by John M Mandrola which I am sure that some others have already read. It discusses the efficacy of ablation and the results of a recently published study which compared ablation for AF versus a sham procedure. I quote:-

Why We Needed a Placebo- Controlled Ablation Trial

Many of my colleagues have long denied the need for a placebo-controlled trial. They argue that trials of ablation vs drugs show that ablation is superior in reducing AF episodes. Proponents also argue that, at least in some patients, pulmonary vein isolation (PVI) terminates AF while the fibrillation persists in the muscle bundles within the vein, thereby "proving" that PVI results in immediate cure.

I offer three rebuttals:

What about the patient who was highly symptomatic before the ablation procedure and now feels great — but is in persistent AF ? This patient clearly has had a placebo effect.

Why is there such poor temporal correlation between AF and stroke? Further, how much AF, in terms of duration and frequency, is disease modifying? The ARTESIA and NOAH-AFNET 6 trials couldn't tell us the duration of AF that warrants oral anticoagulation. Perhaps AF burden is just something we can measure, a marker of abnormal atrial substrate, and we are ablating a symptom rather than treating a disease..

Finally, if the main reason to ablate AF is to improve the subjective endpoint of quality of life (QOL), you need a placebo control arm. History is replete with examples of placebo controls overturning medical norms.

I have never believed that AF ablation was a complete placebo. My question was how much of it was resistant to placebo effect.

The study referred to:-

Pulmonary Vein Isolation vs Sham Intervention in Symptomatic Atrial Fibrillation

The SHAM-PVI Randomized Clinical Trial

Rajdip Dulai, MBBS1,2,3; Neil Sulke, MD4; Nick Freemantle, PhD5; et al

This article is asking interesting questions about the placebo affect regarding quality of life which may be relevant to us all.

Thoughts?

[Cliff_G]

I think there's some pre-mapping technology thinking going on here. A good map (Carto) shows exactly what the state of the heart is. My EP showed me what they'd found when they went in on Weds. Incredible pictures, really clear as to what tissue was done in my original ablation in 2002, which was all intact, and where they had tackled my recent flutter. With such a graphic presentation, my feeling is the docs can say with a much greater degree of certainty that effective lesions have/haven't been done.

Of course, a map can also show areas of doubt and those would probably be those most contributing to placebo "improvements". My feeling is still that placebo is not that useful a concept in AF ablation, where in those marginal cases there are so many other variables nutrition, stress, potassium levels, coffee, and would you really call those elements "placebo".

I like John M, but I do feel he sometimes writes just to make copy. He's right that comparing ablation to drugs has its problems, in that drugs are definitely prone to placebo themselves and have low effectiveness figures in AF anyway. But if someone has an ablation and remains in AF but feels better, how is that definitely placebo? The ablation could have terminated currents particularly causing bad autonomic effects, for example, but leaving asymptomatic fib. And for those of us with badly symptomatic AF (when it's there), we know (jealously) plenty of other folk who have AF and aren't bothered by it

[Singwell in reply to Cliff_G]

Good points!

[mjames1]

So the conclusion of this unnecessary (imo) trial does not get lost among the ramblings of Mandrola, I'll restate it.

The (trial) authors concluded that PVI resulted in a reduction in AF burden and improvement in symptoms and QOL compared with a sham procedure....(and) no clinically relevant placebo effect with PVI."

  Cliff_G said it well in his previous post, including: "I like John M, but I do feel he sometimes writes just to make copy."

I also like Mandrola, but in this case, C'mon

Jim

[CDreamer]

Thank you both, good points. I think we need provocators such as Mandrola to question and keep questioning.

Doesn’t mean he is right of course but I like the questions he is posing. Especially Perhaps AF burden is just something we can measure, a marker of abnormal atrial substrate, and we are ablating a symptom rather than treating a disease.

The question of placebo/nocebo is an interesting one and I believe a very difficult subject to research without bias. I was therefore rather shocked to in the statement that CRT showed 80% improvement thought to be from placebo affect. I would have never thought that the benefit of CRT comes mostly from placebo effect - In my own case because I believe that CRT has given me the best and sustained improvement both in reducing AF burden and symptoms to a minimum.

We know both placebo and nocebo exist as many studies and anecdotal evidence demonstrate and we know perception is everything eg: your experience of pain may be very different to mine and vice versa so I don’t think it extra ordinary that a percentage of those undergoing the sham ablation procedure could be attributed to placebo but wouldn’t go so far as saying it was placebo.

What is evident is that Mandrola is somewhat anti ablation and would advise caution.

[mhoam in reply to CDreamer]

CDreamer I quite like reading John Mandrola’s posts, however from a UK perspective it looks like he is always pushing back against the financial incentives, many of them perverse, that seem to operate in the USA medical system.

Although there is lots of justified disaffection with the NHS in the UK, especially at the moment, we rarely have to question the motives of our medics.

[Cliff_G]

Having seen the Carto map of my atria yesterday, which my EP showed me, showing the original ablation work I had done (2002, so early days and I went to Haissaguerre), I'd certainly agree that this is a treatment, not a cure, or as Mandrola puts it "we are ablating a symptom rather than the disease". But then that's not been in doubt from day one. As my EP put it "all those red areas are scar tissue - dead areas" (they were huge). Nice, and a bit sobering! But for anyone who, like me back in 2002, had badly symptomatic AF, all you want to happen is for the horrible nauseous feelings and breathlessness etc to JUST STOP! And to get released from the tyranny of start-stop AF - Oh no, not another episode. Mandrola's page about how to deal with AF without pills and ablation is all well and good, but many of us have done all those things and the AF just laughs back at you.

[CDreamer in reply to Cliff_G]

Been there and done that also. My AF was very symptomatic despite doing all I could. CRT pacemaker was the only thing that helped as I can’t tolerate any meds.

[mike1961 in reply to Cliff_G]

Hi Cliff,

Interesting that you have the large areas of scarring as my take of the Bordeaux team both past and present (I have had two ablations by Jais 2018 and 2023) is they adhere to the ‘do only what’s required’ philosophy. One of Jais’ stated aims is to try and preserve as much atrial function as possible.

[Cliff_G in reply to mike1961]

Hi Mike,

My ablations (1+a quick redo) were done in the pretty early days, 2002, when only one hospital in London was doing them, hence I went to Bordeaux. I was also on the edge, or more probably in, permanent AF, which H&J were still working on solutions for and is still not a done deal these days. The main areas done on me were the PVs so not affecting atrial function. I know Bordeaux also did a bunch of trials for other lesions, mitral line, back wall etc. so perhaps they concluded more is not necessarily better.

I hope you had a good result.

[mike1961 in reply to Cliff_G]

You definitely did the right thing going over to Bordeaux back in 2002 !

I had a PVI for PAF (first had it in 1999 but which in 2018 had become monthly rather than twice yearly) in Aug 2018, then in Oct 22 I had a bad run-in with covid and went into pers AF (alternating AF and AT) and went back to Jais in Jan 23. He did more extensive work this time. Marshall Vein ethanol converted AF to AT, then AT converted to NSR with further work to left posterior atrium (done with PFA) . Touch up to a PV (PFA). Line done to prevent any future typical Aflutter too (RF).

Outcome not too bad. No AF so far as I'm aware, but plenty of runs of ectopics, some AT (a few seconds to a couple of minutes) now and again (particularly if lifting something heavy whilst bending). Still take 100mg Flec BID + 10mg propanolol BID as I basically don't have the bottle - yet - to try and quit what has been a valuable ally this last 16 years !

It is what it is Cliff. My mum and both her sisters had AF since their mid-30s so it was pretty much nailed on for me. I think it might have done as much good as harm though as I've certainly looked after myself a lot better this last 20 years than I would have done otherwise (very heavy binge drinker and 30BMI until PAF struck) .... it's an ill wind and all that !

All the best,

Mike

[FraserB]

From my understanding, Dr. Mandrola supports the use of ablation when necessary but views AF as a symptom of broader systemic issues that have historically been overlooked in a holistic context until even this year by the European Society of Cardiology which brought it even more forward. It emphasizes the importance of addressing the whole patient's and their underlying factors much earlier in the care process, upstream, to prevent AF from progressing and leading to more severe structural changes in the heart downstream. And of course ablation is absolutely necessary to give QOL at this stage.

[Cliff_G in reply to FraserB]

Yes, I'm sure my AF came about due to vagal hypertonicity.

[Singwell]

Thanks for sharing. I understand what these words mean, but what is he talking about here? Anyone able to explain? "Why is there such poor temporal correlation between AF and stroke?" And I thought the point about AF effectively being blocked by the procedure but actually continuing behind fhe scenes as it were was very interesting. I'm seeing my EP ina couple of weeks and shall ask! I think it explains something he told me back in March- with ageing there's a normal fibrosis of the heart scar tissue, which means AF is more likely to break through.

[CDreamer]

“Why is there such poor temporal correlation between AF and stroke?"

He seems to be questioning why there is no direct correlation between the number of episodes of AF and stroke in the temporal area as most strokes tend to occur in a different region of the brain. The middle cerebral artery (MCA) is the most common artery involved in acute stroke

Where stroke occurs can affect rehabilitation.

[WildIris in reply to CDreamer]

I took him to mean that the time between AF and stroke is not directly correlated, AF just makes ischemic stroke statistically more likely

[Auriculaire in reply to WildIris]

That was my understanding too. I had a TIA before I went on Apixaban 6 months after the previous afib attack.

[Efka]

I like his articles (on substack) a lot and highly value his open minded questions around cardiology and beyond.