Refining Prediction of Atrial Fibrillation-Related Stroke Using the P₂-CHA₂DS₂-VASc Score: ARIC and MESA

Background: In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs) - prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothesized that the addition of PWIs to the CHA₂DS₂-VASc score would improve its ability to predict AF-related ischemic stroke. Methods: We included 2229 participants from the ARIC study (Atherosclerosis Risk in Communities) and 700 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with incident AF who were not on anticoagulants within 1 year of AF diagnosis. PWIs were obtained from study visit ECGs before development of AF. AF was ascertained using study visit ECGs and hospital records. Ischemic stroke cases were based on physician adjudication of hospital records. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of PWIs for ischemic stroke. Improvement in 1-year stroke prediction was assessed by C-statistic, categorical net reclassification improvement, and relative integrated discrimination improvement. Results: Abnormal P-wave axis was the only PWI associated with increased ischemic stroke risk (hazard ratio, 1.84; 95% CI, 1.33-2.55) independent of CHA₂DS₂-VASc variables, and that resulted in meaningful improvement in stroke prediction. The β estimate was approximately twice that of the CHA₂DS₂-VASc variables, and thus abnormal P-wave axis was assigned 2 points to create the P₂-CHA₂DS₂-VASc score. This improved the C-statistic (95% CI) from 0.60 (0.51-0.69) to 0.67 (0.60-0.75) in ARIC and 0.68 (0.52-0.84) to 0.75 (0.60-0.91) in MESA (validation cohort). In ARIC and MESA, the categorical net reclassification improvements (95% CI) were 0.25 (0.13-0.39) and 0.51 (0.18-0.86), respectively, and the relative integrated discrimination improvement (95% CI) were 1.19 (0.96-1.44) and 0.82 (0.36-1.39), respectively. Conclusions: Abnormal P-wave axis - an ECG correlate of left atrial abnormality - improves ischemic stroke prediction in AF. Compared with CHA₂DS₂-VASc, the P₂-CHA₂DS₂-VASc is a better prediction tool for AF-related ischemic stroke.