Reopening the case for closing PFOs in stroke
Last August, we put out a show on closure of PFO in cryptogenic stroke patients. The results were underwhelming to say the least. However, after 6 years of follow up from some of the earlier trials and with the implementation of a new closure device, the GORE CARDIOFORM septal occluder, our management of these patients is expected to change dramatically. This week on BrainWaves, we’re replaying that older episode on PFO closure. And then, Dr. Chris Favilla will wrap up the show with an update on some of these newer clinical data.
Let me first remind you that PFO is common. For every 4 readers of this blog, 1 will have a PFO. And you probably don’t even know it. [This doesn’t mean you should see a cardiologist and get the PFO closed!] But it is clinically significant for some people, in that it can provide a conduit through which a venous thromboembolism can pass into the systemic (arterial) circulation, and travel to the brain. Ultimately causing stroke. And we see PFOs in a lot of patients with stroke, simply because we see a lot of PFOs. But does this mean PFO causes every stroke? Likely not.
One of the earliest risk stratification schemes to determine if PFO was causal in the development of stroke was the ROPE score (above). In its essence, points are assigned based on risk of not having other risk factors for stroke. [Meaning typical stroke risk factors make it less likely for PFO to be the cause, because those are the patient’s stroke risk factors.] Things like older age, which increases your risk of stroke for innumerable reasons. You’ve also got your vascular risk factors, like hypertension and diabetes, which increase risk of small and large vessel disease. And if there is a cortical infarction, this is highly suggestive of an embolic stroke, rather than a lacunar (or “small vessel”) infarct. The more points you get, the less likely the mechanism of stroke can be attributed to typical vascular risk factors. And the more likely PFO is to blame.
In one of the earliest papers by Di Tullio and colleagues, patients with a cryptogenic stroke were seven times more likely to have a PFO than not to. This effect was observed regardless of age and other comorbidities. Later, studies like the aptly named, PELVIS study, found that patients with cryptogenic stroke and PFO were five times more likely to have DVTs than patients without PFO. While a causal mechanism could not be definitively proven from these data, the findings were quite suggestive.
In the autumn of 2016, with the American Academy of Neurology having just published a Practice Parameter advising against routine PFO closure, the Amplatzer PFO occluder was approved by the Food and Drug Administration to be used in patients 18-60 years of age with cryptogenic stroke. This came from the wake of the long-term follow up data from the RESPECT trial, which were presented at the Transcatheter Cardiovascular Therapeutics meeting. Full details of their preliminary results can be found here and are expected to be published imminently. To briefly summarize, over a mean follow-up of 5.9 years, there was 45% reduction in recurrent ischemic strokes in favor of PFO closure (HR 0.55, 95% CI 0.31-1.0, p = 0.046). No device embolizations or erosions were reported. 6 months later, the REDUCE trial results would be presented at the European Stroke Organization Conference, confirming superiority of PFO closure over medical therapy in these patients.
Special circumstances. PFO is associated with atrial septal aneurysm in 1/3 of cases, and when both are identified, the risk of recurrent cryptogenic stroke is even greater than in patients with PFO alone. To specifically target this population, one recent study based out of France included only PFO patients at high risk–meaning they had to have a PFO with an atrial septal aneurysm or a large shunt. Their results were incredibly positive, favoring closure of the PFO in this circumstance.
Needless to say, we eagerly await as the American Academy of Neurology plans to update their 2016 Practice Parameter on the management of PFO in patients with cryptogenic stroke. As the newer devices are improved and patients more carefully selected for correction, we will one day close the case on this topic in stroke.
BrainWaves’ podcasts and online content are intended for medical education purposes only. Jim is not a cardiac surgeon. Just a guy who’s trying to bring you all the latest updates for what smarter doctors are doing.
- Kent DM, Ruthazer R, Weimar C, Mas JL, Serena J, Homma S, Di Angelantonio E, Di Tullio MR, Lutz JS, Elkind MS, Griffith J, Jaigobin C, Mattle HP, Michel P, Mono ML, Nedeltchev K, Papetti F and Thaler DE. An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke. Neurology. 2013;81:619-25.
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- Kent DM, Dahabreh IJ, Ruthazer R, Furlan AJ, Reisman M, Carroll JD, Saver JL, Smalling RW, Juni P, Mattle HP, Meier B and Thaler DE. Device Closure of Patent Foramen Ovale After Stroke: Pooled Analysis of Completed Randomized Trials. Journal of the American College of Cardiology. 2016;67:907-17.