Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism: A Prospective Cohort Study

Abstract

Background: Pulmonary embolism (PE) is associated with increased risk for ischemic stroke, but the underlying mechanism remains unclear. The authors hypothesized that paradoxical embolism through patent foramen ovale (PFO) should be the main mechanism.

Objective: To determine the frequency of recent ischemic stroke in patients with symptomatic PE according to whether PFO was detected.

Design: Prospective cohort study with masked assessment of stroke outcomes. (ClinicalTrials.gov: NCT01216423).

Setting: 4 French hospital centers.

Participants: 361 consecutive patients with symptomatic acute PE from 13 November 2009 through 21 December 2015.

Intervention: Systematic contrast transthoracic echocardiography (TTE) and cerebral magnetic resonance imaging (MRI) within 7 days after enrollment.

Measurements: Recent symptomatic or silent ischemic stroke was diagnosed on the basis of clinical examination and cerebral MRI showing a hypersignal on the trace diffusion-weighted image with reduction or pseudonormalization of apparent diffusion coefficient.

Results: Contrast TTE was conclusive in 324 of 361 patients and showed PFO in 43 patients (13%). The median age was 66 years (interquartile range, 54 to 77 years). In total, 51% of patients (145/284) had associated deep venous thrombosis, 91% (279/306) had cardiovascular risk factors, and 10% (16/151) presented with arrhythmia (no difference between PFO and non-PFO groups). Cerebral MRI was conclusive in 315 patients. Recent ischemic stroke was more frequent in the PFO group than in the non-PFO group (9 of 42 patients [21.4%] vs. 15 of 273 patients [5.5%]; difference in proportions, 15.9 percentage points [95% CI, 4.7 to 30.7 percentage points]).

Limitation: Because of inconclusive contrast TTE or MRI, 46 patients were excluded from analysis.

Conclusion: Frequency of recent ischemic stroke in patients with symptomatic PE was higher in patients with PFO than in those without PFO. This finding supports the hypothesis that paradoxical embolism is an important mechanism of ischemic stroke in patients with PFO.

Primary funding source: French Ministry of Health.