Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults

Background: Incidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be one of the underlying mechanisms, but this has only been scarcely explored. Objectives: The purpose of this study was to assess the association between increased LA stiffness and CIS in young adults. Methods: In the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e’ velocity (E/e′)/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness. Results: Increased LA stiffness was found in 36% of patients and in 18% of controls (P < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders (P = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P < 0.05). Conclusions: LA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages.