Does Ventricular Substrate Play a Role in Incident Stroke? The Atherosclerosis Risk in Communities (ARIC) Study

Background —The goal of the study was to determine an association of ventricular substrate with thrombotic, cardioembolic, and hemorrhagic stroke. Methods —Participants from the Atherosclerosis Risk in Communities study with analyzable ECGs and no history of stroke were included (n=14,479; age 54±6 y; 55% female; 24% black). Ventricular substrate was characterized by cardiac memory [spatial QRS-T angle (QRS-Ta), sum absolute QRST integral (SAIQRST), spatial ventricular gradient magnitude (SVGmag)], premature ventricular contractions (PVC) and tachycardia-dependent intermittent bundle branch block (TD-IBBB) on 12-lead ECG recorded at visits 1-5. Incident strokes were adjudicated by physician reviewers. Cox proportional hazard risk models were constructed. Results —Over a median 24.5 y follow-up, there were 899 thrombotic, 400 cardioembolic, and 187 hemorrhagic strokes. After adjustment for cardiovascular disease (CVD) and its risk factors, atrial fibrillation / atrial substrate, and ECG-left ventricular hypertrophy, PVC (HR 1.72; 95%CI 1.02-2.92), QRS-Ta (HR 1.15; 95%CI 1.03-1.28), SAIQRST (HR 1.20; 95%CI 1.07-1.34) and time-updated SVGmag (HR 1.19; 95%CI 1.08-1.32) associated with cardioembolic stroke. After adjustment for CVD and its risk factors, PVC (HR 1.53; 95%CI 1.03-2.26), QRS-Ta (HR 1.08; 95%CI 1.01-1.16), SAIQRST (HR 1.07; 95%CI 1.01-1.14), and time-updated SVGmag (HR 1.11; 95%CI 1.04-1.19) associated with thrombotic stroke. In fully adjusted time-updated Cox model QRS-Ta (HR 1.20; 95%CI 1.04-1.38), SAI QRST (HR 1.23; 95%CI 1.06-1.43), SVGmag (HR 1.23; 95%CI 1.06-1.43) associated with hemorrhagic stroke, whereas TD-IBBB trended (HR 1.84; 95%CI 0.25-13.33). Conclusions —PVC burden reflected by cardiac memory is associated with ischemic stroke. Transient cardiac memory (likely through TD-IBBB) precedes hemorrhagic stroke.