High-Sensitivity Cardiac Troponin T for Risk Stratification in Patients With Embolic Stroke of Undetermined Source

Abstract

Background and Purpose: Optimal secondary prevention for patients with embolic stroke of undetermined source (ESUS) remains unknown. We aimed to assess whether high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with major vascular events and whether hs-cTnT may identify patients who benefit from anticoagulation following ESUS. Methods: Data were obtained from the biomarker substudy of the NAVIGATE ESUS trial, a randomized controlled trial testing the efficacy of rivaroxaban versus aspirin for secondary stroke prevention in ESUS. Patients were dichotomized at the hs-cTnT upper reference limit (14 ng/L, Gen V, Roche Diagnostics). Cox proportional hazard models were computed to explore the association between hs-cTnT, the combined cardiovascular end point (recurrent stroke, myocardial infarction, systemic embolism, cardiovascular death), and recurrent ischemic stroke. Results: Among 1337 patients enrolled at 111 participating centers in 18 countries (mean age 67±9 years, 61% male), hs-cTnT was detectable in 95% and at/above the upper reference limit in 21%. During a median follow-up of 11 months, the combined cardiovascular end point occurred in 68 patients (5.0%/y, rivaroxaban 28 events, aspirin 40 events; hazard ratio, 0.67 [95% CI, 0.41–1.1]), and recurrent ischemic stroke occurred in 50 patients (4.0%/y, rivaroxaban 16 events, aspirin 34 events, hazard ratio 0.45 [95% CI, 0.25–0.81]). Annualized combined cardiovascular end point rates were 8.2% (9.5% rivaroxaban, 7.0% aspirin) for those above hs-cTnT upper reference limit and 4.8% (3.1% rivaroxaban, 6.6% aspirin) below with a significant treatment modification ( P =0.04). Annualized ischemic stroke rates were 4.7% above hs-cTnT upper reference limit and 3.9% below, with no suggestion of an interaction between hs-cTnT and treatment ( P =0.3). Conclusions: In patients with ESUS, hs-cTnT was associated with increased cardiovascular event rates. While fewer recurrent strokes occurred in patients receiving rivaroxaban, outcomes were not stratified by hs-cTn results. Our findings support using hs-cTnT for cardiovascular risk stratification but not for decision-making regarding anticoagulation therapy in patients with ESUS. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02313909.

Troponin Levels and Outcomes in Patients with Embolic Stroke of Undetermined Source

“…This is the first real-world cohort study on troponin levels in ESUS and validates the finding of a recent clinical trial substudy that the troponin level is a predictor of the risk of vascular events in patients with ESUS [ 5 ]. There is an urgent need to identify prognostic biomarkers related to potential cardiac dysfunction after ESUS [ 1 ].…”

“…Recent studies have suggested that elevated cTn levels are more common in patients with ESUS than in those with noncardioembolic stroke [ 3 ]. Elevated cTn levels may be associated with worse clinical outcomes and a higher risk of vascular events after stroke [ 4 , 5 ]. Therefore, we investigated the effectiveness of conventional cTn I (cTnI) and high-sensitivity cTn T (hs-cTnT) levels in predicting clinical outcomes in patients with ESUS.…”

Promising Biomarker Candidates for Cardioembolic Stroke Etiology. A Brief Narrative Review and Current Opinion

“…However, a most recent substudy of the NAVIGATE-ESUS trial showed that high-sensitivity cardiac troponin T (hs-cTnT) was associated with increased rates of cardiovascular event but did not find any evidence supporting anticoagulation in these patients. This indicates that hs-cTnT is not useful to guide management of anticoagulation (76). Only limited evidence exists for the association of CK-MB with cardioembolism hindering any firm conclusions yet (41,77).…”

Myocardial injury in acute ischemic stroke

“…29 Further, in patients with embolic stroke of undetermined source, elevated cTn was associated with an increased risk for cardiovascular events. 30 Moreover, elevated hs-cTn was linked with more severe matter lesions of the brain, suggesting silent brain infarction as one possible link. 31 This silent brain damage of the white matter may well go along with dementia.…”