Left ventricular strain and chamber dimensions in pediatric sickle cell disease: agerelated reduction in myocardial deformation independent of hemolysis and hydroxyurea therapy

Abstract

Sickle cell disease (SCD) is associated with cardiovascular complications. Speckle-tracking echocardiography enables early detection of myocardial dysfunction before abnormalities appear in conventional echocardiographic parameters. This study evaluated left ventricular (LV) global longitudinal strain (GLS) in pediatric SCD patients, and its relationship with traditional LV function indices, disease complications, hemolysis markers, and diseasemodifying therapy. We retrospectively analyzed 278 echocardiograms from 185 participants (118 SCD patients, mean age 12.2 years; 67 age- and sex-matched controls, mean age 11.8 years) obtained between 2015 and 2023. Among the SCD cohort, 66.1% had the HbSS genotype, 9.3% had HbSβ°-thalassemia, and 17.8% had HbSβ⁺-thalassemia; the majority (83.9%) were on hydroxyurea. Compared to controls, SCD patients had significantly lower, but still normal, GLS (–21.5% vs. –22.3%; p < 0.001), along with significantly larger chamber diameters, elevated mitral valve E velocity, E/A ratio, and tricuspid regurgitation maximal velocity. Prior stroke (β = 0.9) and avascular necrosis (β = 1.51) were independently associated with worse GLS. The different genotypes did not exhibit significant difference in GLS. The strain values did not correlate with hemolysis markers, suggesting that other mechanisms may underlie myocardial impairment. A significant age-related decline in GLS was detected, with an inflection point at approximately 9.9 years. Longitudinal analysis of LV strain in the SCD cohort demonstrated a small decline from –21.6% to –21.2% over a 3.7-year follow-up period. Finally, pediatric SCD patients exhibit significant cardiac remodeling and diastolic dysfunction with preserved, yet lower, LV GLS, underscoring the need for further research in this population.