New Classification Urged for PFO-Associated Stroke

April 21, 2020

A call has been made for a new classification of ischemic stroke for patients who have a patent foramen ovale (PFO) that is thought to have been the likely cause of the stroke.

The new classification ― PFO-associated stroke ― has been proposed by a large group of experts in the field in an article published online in JAMA Neurology on April 13.

"The idea for this paper started 2 years ago after randomized trials came out showing PFO closure was preferable to medical therapy in terms of reducing recurrent stroke for patients with a cryptogenic stroke and a PFO," senior author Jonathan M. Tobis, MD, David Geffen School of Medicine, University of California, Los Angeles, told Medscape Medical News.

These trials have also provided some evidence that, among medical therapy options, anticoagulants may be more effective than antiplatelet agents for these patient, the authors note.

"We believe the guidelines now need to be changed to be in line with that new information, and that a new classification of stroke likely to have been caused by a PFO will help raise awareness and improve detection and treatment of these patients," Tobis said.

"In the US, PFO closure is now approved after stroke if the PFO is thought to be related to the stroke, so it is important to try to define these patients," he said.

At present, an ischemic stroke in a patient who has a PFO is classified as a cryptogenic stroke, implying no known mechanism. The current article is proposing that if a patient has a PFO and no other etiology is likely to have caused a stroke, then that stroke should be referred to as a PFO-associated stroke.

"This implies that the stroke is connected to the presence of a PFO, but it doesn't infer definite causation, as that is very difficult to prove," Tobis said.

He explained that there are different degrees of certainty as to whether the PFO caused the stroke. "For example, we can say it is definite only if we can see a blood clot straddling the PFO, which is very unlikely to happen," he said.

But he outlined several scenarios in which the PFO is likely to have been the culprit. These include cases involving younger patients who have no other comorbidities that may cause stroke; the presence of a pulmonary embolism (which shows that there is a venous clot, so it is likely that a clot could have passed from the venous to the arterial circulation); or the presence of an atrial septal aneurysm or a large shunt PFO.

Then there are patients in whom the PFO is unlikely to have been the cause of the stroke ― for example, those who have a small PFO, and older patients with cardiovascular disease.

"Ultimately, the neurologist treating the patient has to take all these factors into consideration and decide whether the PFO was the likely cause of the stroke," Tobis notes.

He estimates that around 20% of the population have a PFO, but only around 1 in 1000 people have a stroke. "So if all PFOs were closed routinely, 999 of these procedures would be unnecessary," he said.

But if a patient has had a stroke and is also found to have a PFO that is thought to have been the likely cause, there is a 1% risk per year of that patient's having another stroke. Many of these patients are young, so they may have a 50% chance of having another stroke over the course of their life, he said, "so it is definitely worth closing the PFO in this situation.

"We think a new classification of PFO-associated stroke would result in the neurology community becoming more aware of this and the diagnosis becoming better recognized in line with other causes of stroke. It would also encourage clinicians to look more thoroughly for a PFO after stroke. In the past, routine scanning for PFO has not always happened," Tobis said.

The authors estimate that 5% of all strokes are related to a PFO; in patients younger than 60 years, the rate rises to 10%. "These figures are probably underestimates because the best technologies have not been used to detect PFO," Tobis suggested.

He pointed out that transthoracic echocardiography has a high false negative rate, missing up to 50% of PFOs. Transesophageal echocardiography is much better, with a false negative rate of about 10%, but the gold stand is transcranial Doppler ultrasound, which only misses around 1%.

Over the years, the number of patients classified as having a cryptogenic stroke has decreased significantly, owing to improvements in technology and in the ability to ascertain the underlying cause. It is estimated that at present, around 20% of ischemic strokes are defined as cryptogenic, and about half of these could be related to a PFO, Tobis said.

"We propose the term PFO-associated stroke as a distinct entity of ischemic stroke for all patients presenting with superficial, large deep, or retinal infarcts in the presence of a medium-risk to high-risk PFO and no other identified likely cause," the authors conclude.

"The diagnosis of PFO-associated stroke has intrinsic explanatory value for epidemiologic research, clinical trial design, and patients, families, and physicians regardless of any therapy outcome that might result. In addition, it can inform therapeutic decision-making: patients with PFO-associated stroke who meet the regulatory device label criteria may benefit from PFO closure, additional patients may benefit from consideration for anticoagulation, and many patients may benefit from hydration and activity interventions to avert venous thromboembolism. Neurology and cardiology society guidelines should be updated to adopt nomenclature consistent with the evidence base to improve patient care and outcome," they add.

JAMA Neurol. Published online April 13, 2020. Abstract

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