Sources of variability in quantification of CMR infarct size and their impact on sample size calculations - reproducibility among three core laboratories

Background Infarct size is increasingly used as an efficacy endpoint in randomized trials comparing acute myocardial infarct (AMI) therapies. Infarct size, depicted by delayedenhancement-CMR, is quantified using manual planimetry (MANUAL), visual scoring (VISUAL), or automated techniques using signal-intensity thresholding to define infarct borders (AUTO). Although AUTO is considered the most reproducible, prior studies did not account for the subjective determination of endocardial/epicardial borders, which all methods require. For MANUAL and VISUAL, prior studies have not explicitly defined how to treat intermediate signal-intensities due to partial volume. We wanted to assess sources of variability among 6 methods in quantification of AMI size, and illustrate the significance of these findings on sample size calculations for clinical trials.