Kanjana S Perera1,2, Danielle de Sa Boasquevisque1,2, Purnima Rao-Melacini1,3, Amanda Taylor2, Anna Cheng2, Graeme J Hankey4,5, Sarah Lee6,7, Joan Marti Fabregas8, Sebastian F Ameriso9, Thalia S Field10, Antonio Arauz11, Shelagh B Coutts12, Marcel Arnold13, Robert Mikulik14,15, Danilo Toni16, Jennifer Mandzia17, Roland C Veltkamp18, Elena Meseguer19, Karl Georg Haeusler20, Robert G Hart2. 1. Department of Medicine, Neurology, McMaster University, Hamilton, Ontario, Canada. 2. Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada. 3. Department of Statistics, Hamilton Health Sciences, Hamilton, Ontario, Canada. 4. Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia. 5. Department of Neurology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. 6. Department of Neurology & Neurological Sciences, Stanford Stroke Center, Stanford, California. 7. Stanford Children's Health, Stanford, California. 8. Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 9. Institute for Neurological Research-FLENI, Buenos Aires, Argentina. 10. Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 11. National Institute of Neurology, La Fama, Tlalpan, México. 12. Department of Clinical Neurosciences, University of Calgary, Foothills Medical Calgary, Calgary, Alberta, Canada. 13. Department of Neurology, University Hospital Bern, Bern, Switzerland. 14. International Clinical Research Center and Neurology Department, St Anne's University Hospital, Brno, Czech Republic. 15. Masaryk University, Brno, Czech Republic. 16. Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy. 17. Department of Neurosciences, Western University, London, Ontario, Canada. 18. Division of Brain Sciences, Imperial College, The Hammersmith Hospital, London, United Kingdom. 19. Neurology Service, Bichat Hospital, Paris, France. 20. Department of Neurolog, Universitätsklinikum Würzburg, Würzburg, Germany.
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 Participants: This 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 Measures: Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). Results: The 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, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). Conclusions and Relevance: In 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.
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 Participants: This 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 Measures: Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). Results: The 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, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). Conclusions and Relevance: In 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.
Authors: Roland Veltkamp; Lesly A Pearce; Eleni Korompoki; Mukul Sharma; Scott E Kasner; Danilo Toni; Sebastian F Ameriso; Hardi Mundl; Turgut Tatlisumak; Graeme J Hankey; Arne Lindgren; Scott D Berkowitz; Antonio Arauz; Serefnur Ozturk; Keith W Muir; Ángel Chamorro; Kanjana Perera; Ashfaq Shuaib; Salvatore Rudilosso; Ashkan Shoamanesh; Stuart J Connolly; Robert G Hart Journal: JAMA Neurol Date: 2020-10-01 Impact factor: 18.302
Authors: Paula M Janssen; Nora A Visser; Sanne M Dorhout Mees; Catharina J M Klijn; Ale Algra; Gabriel J E Rinkel Journal: Cerebrovasc Dis Date: 2009-12-01 Impact factor: 2.762
Authors: Kanjana S Perera; Balakumar Swaminathan; Roland Veltkamp; Antonio Arauz; Sebastian Ameriso; Joan Marti-Fabregas; Marcel Arnold; Graeme J Hankey; Helmi Lutsep; Robert G Hart Journal: Eur Stroke J Date: 2018-01-24
Authors: Rita V Krishnamurthi; Andrew E Moran; Valery L Feigin; Suzanne Barker-Collo; Bo Norrving; George A Mensah; Steve Taylor; Mohsen Naghavi; Mohammed H Forouzanfar; Grant Nguyen; Catherine O Johnson; Theo Vos; Christopher J L Murray; Gregory A Roth Journal: Neuroepidemiology Date: 2015-10-28 Impact factor: 3.282
Authors: M Nassif; M E Annink; H Yang; Tcd Rettig; Ybwem Roos; Rba van den Brink; Jgp Tijssen; Bjm Mulder; R J de Winter; B J Bouma Journal: Int J Stroke Date: 2019-11-03 Impact factor: 5.266