BackgroundPatients with sickle cell disease (SCD) have a unique form of cardiomyopathy. However, left ventricular ejection fraction (LVEF) is often preserved. Monoplanar long‐axis strain (LAS) can be assessed from MRI four‐chamber views and may be better at detecting mild systolic dysfunction in these patients.PurposeTo compare LAS (monoplanar and biplanar) with LVEF as a marker of systolic dysfunction in SCD patients.Study TypeRetrospective.SubjectsA total of 20 patients with genetically proven SCD (35 MRI examinations), 39 healthy controls, and 124 patients with systemic iron overload (for validation purposes).Field Strength/Sequence1.5 T/3 T. Cine balanced steady‐state free‐precession.AssessmentRapidly assessed biplanar LAS from four‐ and two‐chamber views was correlated with age and compared to LVEF by two operators. For validation, biplanar LAS was compared to global longitudinal strain (GLS) using MRI feature‐tracking in 124 patients with systemic iron overload.Statistical TestsBland–Altman analysis. Wilcoxon‐Mann–Whitney test and Spearman‐rank correlation (correlation coefficient, rS). Receiver‐operating‐characteristic (ROC) curve analysis (area under the curve, AUC). Bivariate discriminant analysis. Significance level: P < 0.01.ResultsThere was strong correlation between biplanar LAS and GLS using feature tracking (rS = 0.73). Interoperator agreement showed nonsignificant bias for biplanar LAS (−0.02%; ±95%‐agreement interval −2.2%/2.2%, P = 0.9). Biplanar LAS increased significantly with age in controls (rS = 0.70). In SCD patients, biplanar LAS was better correlated with age than monoplanar LAS (r2 = 0.53, standard error of estimate, SEE = 1.4% vs. r2 = 0.37;SEE = 2.0%). ROC analysis of LVEF, biplanar LAS, and age‐adjusted Z‐scores Z (LAS(age)) showed AUCs of 0.69, 0.75, and 0.86 for differentiation between SCD patients and controls. Bivariate discriminant analysis of biplanar Z (LAS(age)) and LVEF revealed a sensitivity of 63% and a specificity of 95%.Data ConclusionRapidly assessed biplanar LAS demonstrated high diagnostic accuracy and was an indicator of mild systolic dysfunction in patients with SCD. Biplanar LAS provided more precise measurements than monoplanar, and normalization to age increased diagnostic accuracy.Evidence Level3.Technical EfficacyStage 2.