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A patent foramen ovale (PFO) was associated with a higher stroke risk in pulmonary embolism (PE), according to the EPIC FOP study from France.

Ischemic strokes, confirmed on cerebral MRI, were more frequent among patients with a PFO than without (21.4% vs 5.5%, RR 3.90, 95% CI 1.62-8.67), according to Emmanuelle Le Moigne, MD, of Hôpital de la Cavale Blanche in Brest, France, and colleagues.

PFOs were also specifically associated with greater risks of symptomatic stroke (9.5% vs 1.5%, RR 6.50, 95% CI 1.08-45.50) and cryptogenic stroke (16.7% vs 1.8%, RR 9.10, 95% CI 2.89-39.00), they reported in the .

"Consistent with other trials, our findings strongly support the mechanism of paradoxical embolism in patients with PE, PFO, and recent ischemic stroke. Such a mechanism is also supported by the results of recent trials in patients with stroke and PFO," according to Le Moigne's group.

Results from their prospective, a 361-person cohort study, were presented in part at the 2017 International Society on Thrombosis and Haemostasis meeting.

The clinical implication of the study is that it may justify systematic screening for PFO to identify patients who may benefit from indefinite anticoagulation to prevent both recurrent PE and stroke, they said. "Such an approach seems reasonable, particularly in patients with a first unprovoked PE: give a moderate recommendation (grade 2B) for indefinite anticoagulation in these patients at high risk for recurrence, and the detection of PFO reinforces such indefinite therapy."

Le Moigne and colleagues conducted EPIC FOP at four hospitals in France.

Study participants were consecutive PE patients who underwent contrast transthoracic echocardiography (TTE) and cerebral MRI within 7 days of enrollment. Median age was 66 and 51% of the cohort were men.

Overall, 51% had deep venous thrombosis, 91% had cardiovascular risk factors, and 10% presented with arrhythmia.

A PFO was identified in 13% of the 324 patients who had conclusive results on TTE. In this group, ischemic stroke was even more common if the patient had an atrial septal aneurysm (50.0% vs 14.7%).

The two arms with and without PFOs shared similar baseline characteristics and risk factors. "Thus, the hypothesis that a higher risk for stroke in patients with PFO might have been caused by hypoxia or arrhythmia is unlikely to be true in our cohort," Le Moigne's group said.

"To our knowledge, our study is the largest prospective trial to assess the frequency of recent ischemic stroke in unselected patients with an acute episode of symptomatic PE. Our exclusion criteria were minimal and were not based on PE severity, which led to enrollment of a population close to that in real life," they commented.

Nevertheless, they acknowledged that they had a small sample that shrank further upon excluding 46 patients due to inconclusive TTE or MRI results.

"Le Moigne and colleagues have provided strong evidence in support of PFO as an independent risk factor for stroke after PE. The logical next step would be interventional studies aiming to modify risk for stroke through prevention of paradoxical embolization," maintained Michael Schmidt, MD, PhD, and Lars Søndergaard, MD, MSc, both of Rigshospitalet in Copenhagen.

In an , the duo noted that the significant variation in the observed prevalence of PFO across studies indicates that standard contrast echocardiography with injection of agitated saline during the Valsalva maneuver is difficult and produces highly variable results with suboptimal sensitivity.

"Transesophageal echocardiography may be justified as an adjunctive examination to increase sensitivity," they suggested.

Schmidt and Søndergaard pointed to timing as a big question in stroke and PE.

"First, when does the embolic stoke occur? If it happens immediately after the PE, clinical benefit could potentially be achieved by reducing the so-called patient delay (time from symptom onset to health care contact) and by promoting early MRI and possibly thrombolytic treatment when indicated by the imaging results," they said.

"Second, is the risk for stroke permanently increased after PE in patients with PFO, even if there is no evidence of silent or clinical stroke during the index admission? If so, this could justify lifelong anticoagulant treatment, as suggested by the authors. Because risk for recurrent PE is much higher than that for first-time PE, this assumption is not ungrounded."

Finally, the editorialists said, if cerebral injury occurs after PE through repetitive embolization in the weeks and months of increased pulmonary arterial pressure, there may be benefit from pulmonary antihypertensive treatment or even subacute PFO closure on admission.