Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source

Abstract

IMPORTANCE Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. OBJECTIVE To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. DESIGN, SETTING, AND PARTICIPANTSThis multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. MAIN OUTCOMES AND MEASURESRecurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). RESULTSThe mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI,, presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI,. CONCLUSIONS AND RELEVANCEIn this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

Sex differences in etiology and short-term outcome in young ischemic stroke patients receiving mechanical thrombectomy

“…The rate of detected AF was low and did not differ between female and male AIS patients in our cohort. This is consistent with data from the Young ESUS longitudinal Cohort Study including 535 young adult patients with embolic stroke of undetermined source which also reported low rates of newly detected AF (2.8%) [ 6 ]. Arterial dissection was detected in 17.8% of our patient cohort, and did not significantly differ between young female and male AIS patients.…”

Atrial Fibrillation Risk Assessment after Embolic Stroke of Undetermined Source

“…Particularly in patients poststroke of undetermined source based on the TOAST criteria, the CRYSTAL AF study identified 12.4% AF at 12 months in patients randomized to receive an ICM 5 . In contrast, patients aged younger than 50 years with ESUS had a significantly lower incidence of AF, even when equipped with ICM 24 . More recently, the FIND‐AF‐randomized trial used three times 10‐day Holter recordings in patients after an ischemic stroke and detected AF in 13.5% after 6 months 25 .…”

“…5 In contrast, patients aged younger than 50 years with ESUS had a significantly lower incidence of AF, even when equipped with ICM. 24 More recently, the FIND-AF-randomized trial used three times 10-day Holter recordings in patients after an ischemic stroke and detected AF in 13.5% after 6 months. 25 In our current investigation, the overall cumulative incidence of AF was 9.1% after 6 months and 12.5% after 12 months follow-up, and it was 10.6% (6 months) and 14.5% (12 months) when restricted to those patients equipped with an ICM.…”

Stroke in the young

“…Smoking, too, is an important contributor to outcome, as smoking was recently associated with a higher 3 month NIHSS in a study in China [19]. Cryptogenic stroke has been associated with higher rates of recurrence in young adults than those with other causes [20,21 ]. Patent foramen ovale closure, previously considered controversial, has been recently shown to have clear benefit in stroke prevention in young adults without an alternative explanation for stroke [22].…”