Underlying causes of cryptogenic stroke and TIA in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study – the importance of comprehensive clinical evaluation

Abstract

Background Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management. Methods Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis. Results After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA2DS2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). Conclusion Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal. Trial registration ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.

Diagnostic Utility of N-Terminal Pro-B-Type Natriuretic Peptide in Identifying Atrial Fibrillation Post-Cryptogenic Stroke: A Systematic Review and Meta-Analysis

“…This discrepancy likely stems from differences in AF subtypes between the two groups. Paroxysmal AF, known for its elusive detection compared to persistent or permanent AF [ 34 ], is presumed to be more prevalent in the cryptogenic stroke cohort than in patients with known etiology strokes [ 35 ]. Consequently, it is plausible that a larger proportion of patients in the cryptogenic stroke cohorts harbor undiagnosed paroxysmal AF.…”

StrokeClassifier: Ischemic Stroke Etiology Classification by Ensemble Consensus Modeling Using Electronic Health Records

“…In one study, at 21 months, cryptogenic strokes were associated with higher risk of recurrent stroke in comparison with cardioembolic (HR 1.83, p=0.028) and non-cardioembolic stroke patients with known source (HR 2.4, p=0.046). An analysis of the NOR-FIB study demonstrated an annual risk of stroke recurrence of 7.7% versus 2.8% among individuals with cryptogenic versus non-cryptogenic strokes, respectively 14 . In the Athens Stroke Registry, the stroke recurrence rate in patients with cryptogenic stroke was 29% over a mean of 30.5 months, significantly higher compared with all non-cardioembolic stroke subtypes 15 .…”