BACKGROUND: The distinction of hypertrophic cardiomyopathy (HCM) or cardiac amyloidosis (CA) from hypertensive heart disease may be difficult. The aim of this study was to determine the impact of parametric (polar) maps of regional longitudinal strain on identification of the etiology of mild to moderate left ventricular hypertrophy (LVH). METHODS: Twenty-four consecutive echocardiographic studies with mild to moderate LVH (eight with CA, eight with HCM, and eight with hypertensive heart disease) were selected on the basis of the availability of adequate images to assess longitudinal strain and absence of electrocardiographic criteria for low voltage or LVH or a pseudoinfarct pattern. Twenty level 3-trained readers provided the most likely of three diagnoses (CA, HCM, or hypertensive heart disease) and scored their confidence in making the diagnosis from two-dimensional images and diastolic parameters. A teaching exercise was provided on the interpretation of longitudinal strain in these cohorts, and interpretation was repeated with the addition of the strain polar map. RESULTS: Baseline concordance among the readers was poor (κ = 0.28) and improved with the addition of strain data (κ = 0.57). Accuracy was improved with the addition of polar maps for the entire study cohort (P < .001), with 22% of cases reclassified correctly. The largest improvements in sensitivity (from 40% to 86%, P < .001), specificity (from 84% to 95%, P < .001), and accuracy (from 70% to 92%, P < .001) were seen for CA. The strain polar map significantly improved reader confidence in making the correct diagnosis overall (P < .001). CONCLUSIONS: Regional variations in strain are easily recognizable, accurate, and reproducible means of differentiating causes of LVH. The detection of LVH etiology may be a useful clinical application for strain.