Melanie R. F. Greenway, MD

Strambo D, Sirimarco G, Nannoni S, Perlepe K, Ntaios G, Vemmos K, Michel P. Embolic Stroke of Undetermined Source and Patent Foramen Ovale: Risk of Paradoxical Embolism Score Validation and Atrial Fibrillation Prediction. Stroke. 2021;52:1643–1652.

In patients with embolic stroke of undetermined source (ESUS), patent foramen ovale (PFO) is often suspected as a potential mechanism. Recent clinical trials have shown the benefit of PFO closure when patients are properly selected.1-3 Present in 25% of the normal population, when found in the etiology workup for stroke, the most important question to ask is whether this is a pathogenic or incidental finding. The Risk of Paradoxical Embolism (RoPE) score is a commonly used clinical decision tool to estimate the likelihood of PFO as the cause of stroke. The higher the score, the more likely the PFO is the cause of stroke. Using this score, it is also possible to predict whether a patient actually has a PFO. 

In this study, the authors used three independent, international, multicenter stroke registries (ASTRAL, Athens, and Larissa Stroke Outcome Registry) to validate the RoPE score in patients with ESUS to predict both the presence of PFO and the ability to determine if the PFO is the cause of the stroke or not. It is the largest validation cohort of patients with ESUS for the RoPE score to date. They also followed the patients for a period of time to evaluate for incident atrial fibrillation and recurrent stroke. 

Within the three registries, ESUS was diagnosed in 14% (573/4102), 11% (275/2495), and 12% (36/311) of the patients. Out of the 884 patients with ESUS, 455 patients had a known PFO status determined by either transthoracic echocardiogram or transesophogeal echocardiogram. PFO presence was found in 40%. Those with PFO present were more likely to be younger, less likely to have diabetes, atherosclerotic disease, or smoking history. Cortical and infratentorial lesions were associated with presence of PFO. Absence of left ventricular hypertrophy was also associated with presence of PFO. 

In the RoPE score validation, the score was able to stratify PFO prevalence with AUROC of 0.75. Patients who had a RoPE score ≥ 7 had a prevalence of PFO of almost 60%. 

Four hundred forty-four patients were followed for a median 1.7 years.  During that time, 150 (33.8%) had continuous cardiac monitoring for at least 24 hours.  At 10-year follow-up, 34 (7.6%) experienced new onset atrial fibrillation. The probability of atrial fibrillation was lowest in patients with likely pathogenic PFO and highest in those without PFO. During the same follow up period, 8.1% of patients had at least one stroke recurrence. Stroke recurrence was lower in the pathogenic PFO group than the incidental PFO group, even independent of PFO closure.

Their study further confirms the validity of the RoPE score, particularly in patients with ESUS, to predict the prevalence of PFO and to determine whether a found PFO is pathogenic or incidental. These findings should encourage clinicians to calculate the RoPE score in patients with ESUS to help guide advanced diagnostic tests for stroke mechanism. The authors suggest the RoPE score may even be used to triage which patients should undergo investigation for PFO. If the RoPE score is low, based on their findings, the pre-test probability is low, and the identification of PFO in this setting would be unlikely to lead to a change in management. 

The authors provide a graphic abstract (below) outlining their findings. Note, the increase in prevalence of PFO as the RoPE score increases. In particular, a RoPE score of ≥5 increases the prevalence of PFO above the normal population, and a RoPE score ≥7 was more likely to be pathogenic than incidental. When evaluated for atrial fibrillation at 10 year follow up, those with incidental PFO were more likely to have atrial fibrillation than those with pathogenic stroke.

Graphic abstract


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