In the Setting of PFO, Time to Retire ‘Cryptogenic’ Stroke

Experts agree the better term to use is PFO-associated stroke in order to foster better diagnosis and, ultimately, treatment.

In the Setting of PFO, Time to Retire ‘Cryptogenic’ Stroke

Strokes that occur in patients with diagnosed patent foramen ovale (PFO) should no longer be deemed “cryptogenic” but rather “PFO-associated,” according to a new statement compiled by a team of both cardiologists and neurologists.

The once-controversial strategy PFO closure for the prevention of recurrent stroke in patients who have had a stroke without an obvious cause—long-termed cryptogenic strokes—was put to rest in 2017 with the publication of data supporting the procedure. British, European, and American guidelines have been since updated to recommend the use of PFO closure in these patients.

But calling these strokes cryptogenic is doing a disservice to patients, Jonathan Tobis, MD (University of California, Los Angeles), the statement’s senior author, told TCTMD. “I just want to see this whole field move forward so that instead of talking about cryptogenic stroke when you have a PFO and no other cause, let's call it ‘something to do with the PFO is causing the stroke.’” The only strokes that should be called cryptogenic should now be those occurring in patients without PFOs and without a known cause, he added.

In their paper published online this week ahead of print in JAMA Neurology, Akram Elgendy, MD (University of Florida, Gainesville), Tobis, and colleagues lay out new nomenclature and a classification scheme for determining the potential causative mechanism of stroke, especially in patients with PFO.

“Patients with no other causes of ischemic stroke and with a medium risk to high risk of PFO should no longer be designated as having so-called cryptogenic stroke, implying a stroke of unknown causative mechanism,” they write. “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 cause.”

This change in nomenclature will have implications for “epidemiologic research, clinical trial design, and patients, families, and physicians regardless of any outcome that might result,” the authors argue. “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.”

Both neurology and cardiology guidelines should be updated to reflect this change, Tobis said. “This will help the neurologists in their evaluation and workup to first of all think of PFO more commonly in that setting of ‘Why did this person have a stroke?’ if it's not obvious. [It] therefore will help the workup and evaluation of in particular getting multiple studies looking for right-to-left shunts.”

Transcranial doppler is the most sensitive modality compared with transthoracic and transesophageal echocardiography so should be used more often, he argued. “A lot of the numbers that are in the literature, even in this paper, I think underestimate the PFO-associated stroke incidence because the sensitivity of tests in past studies was not as high. Transthoracic echo misses maybe 50% of PFOs. Transesophageal echo misses 10% of PFOs.”

While the ultimate goal of this publication is not to specifically promote the use of PFO closure, Tobis said, if a diagnosis of PFO-associated stroke is made, randomized clinical trial data “demonstrate that the best thing to do is to close the PFO in terms of preventing recurrent stroke. So yes, also we want people to be treated appropriately and the appropriate treatment nowadays is to close the PFO.”

  • Gore, as a co-investigator of the RESPECT trial, reports serving on the steering committee of the PREMIUM trial, and as a proctor for Cardiac Dimensions.
  • Elgendy reports no relevant conflicts of interest.