PFO and Cryptogenic Stroke: Finding Closure
There’s no denying the impact of stroke. Not only is it the third leading cause of death, but it is in many ways more feared than heart disease or cancer. As interventionists, our sights have turned to three controversial procedures: (1) carotid stenting, (2) left atrial appendage isolation, and (3) PFO closure. While the first two concern older patients, the third affects those younger and often in the prime of life, throwing patient and physician fears and preferences into the debate. The argument for PFO closure goes something like this: (1) patients with cryptogenic stroke, especially those under age 55 but also those older, have a higher prevalence of PFO; (2) PFO has been proven to cause stroke, most likely from paradoxical emboli; (3) observational studies have shown very low procedural complications and recurrent TIA/stroke after closure; (4) PFO closure may avoid long-term coumadin therapy in those with high-risk anatomy, and therefore; (5) PFO should be closed in patients with cryptogenic stroke, especially when there are high-risk features. The argument against closure, in contrast, goes something like this: (1) PFO closure carries procedural and long-term risk, and is also costly; (2) PFO closure has not been proven better than medical therapy after cryptogenic stroke in randomized clinical trials; (3) PFO is incredibly common, and therefore may be merely an innocent bystander; (4) prospective observational studies have failed to associate PFO with even a first stroke, and thus; (5) initial therapy should be medical (anti-platelet or anti-coagulant) with closure reserved only for failures. We as clinicians have three options:
(1) encourage trial participation after a first cryptogenic stroke,
(2) allow off-label closure based on observational studies, or
(3) suggest patients continue medical therapy (anti-coagulant perhaps over anti-platelet therapy) until a second event.
Now, we all know that it has been exceedingly difficult to enroll patients into randomized trials of closure versus medical therapy. For the majority of young patients, the unpredictable long-term safety and efficacy of medical therapy, as well as physician uncertainty over which medical therapy is best, are disconcerting. As a result, it has become hard to take a firm stance against PFO closure in young patients with cryptogenic stroke and high-risk anatomy, especially when meta-analyses of observational studies now show a recurrent TIA/stroke rate <1% at 2 years.
The debate will of course come to a head as randomized trials begin to present their data. I wonder what will happen if “no difference” is noted? Would it be a “win” for PFO closure in those who wish to avoid coumadin or a “loss” due to its cost and potential complications? Regardless, I suspect we may be in store for a long and heated debate. Indeed, finding closure on this topic may not be so easy.
Dr. Srihari S. Naidu is Director of the Cardiac Catheterization Laboratory, Interventional Cardiology Fellowship Program and Hypertrophic Cardiomyopathy Center at Winthrop University Hospital on Long Island, and Assistant Professor of Medicine at SUNY – Stony Brook School of Medicine
Hi Dr. Naidu,
I really liked this article. I'm a young, active patient in my 30s who last year had a TIA and was diagnosed with PFO/ASA. I've talked to a number of physicians and I can personally relate to the stress this debate creates. For those of us who are already afraid of recurrent stroke, the lack of clear treatment options (and in some cases, the lack of insurance coverage) creates even more stress.
A lot hinges on the critical trials, as you point out. Unfortunately I believe they may be flawed from the get-go. Here are a two obvious questions I would ask when reviewing the trial results:
1. The most needy patients - the ones you mention above - are treated in an off-label basis. But doesn't the fact that they're not included in in the trial skew the results in first place? If you add all of the off-label closure patients to the trial results, what is the outcome? (And we should look at the numbers - ratio of of patients treated off-label vs. included in trial)
2. Trial patients dont' have the benefit of the "right device, right patient" approach, since specific occulders are tied to the clinical trial. Would closure have been more successful had the cardiologist had his/her pick of device based the size and shape of the PFO?
One last question I have on this topic, perhaps you can answer it. It's already established that ASDs also allow for neurological events caused by interatrial communication.
Treating ASDs with devices is already approved by the FDA. Why should treatment of PFO be any different? It's just a hole of a different composition.
Again, great article.
Ellie
Reply to this comment »Dear Ellie,
These are fantastic questions, and you raise points that many of us are concerned about. Please feel free to read my earlier blog on Comparative Effectiveness research. In that, I allude to the fact that clinical trials sometimes don't enroll the "proper" patient population, and therefore the information gleaned from them may not be generalizable. I do agree that in many instances those at "highest risk" for recurrent stroke are often treated off-label, and therefore I fear the trial may find no benefit to closure when indeed there is one in the appropriate patient population.
Your point regarding ASDs similarly causing paradoxical emboli and stroke is a good one, and hard to argue against. I agree there is indeed a double-standard.
Srihari S. Naidu, MD
Reply to this comment »Excited to see what the future holds
ES
Reply to this comment »las vegas, NV
Dear Dr. Naidu,
Your article was very informative and brings up several important points when discussing PFO closures. I think it is a disgrace that a patient has to have a stroke first before they can even be considered for PFO closure. We know that PFO's cause strokes this is often how they are first recognized in pts. I think we should be lobbying for closing PFO's before a pt has a stroke. It doesn't make any sense to me for a pt to have a stroke, then risk a second stroke before PFO closure can be an option for them.
Thank you.
Reply to this comment »