Longitudinal effect of disease-modifying therapy on left ventricular diastolic function in children with sickle cell anemia

Cardiac abnormalities seen in sickle cell anemia (SCA) include diastolic dysfunction, which has been shown to be associated with high morbidity and early mortality. The effect of disease-modifying therapies (DMT) on diastolic dysfunction is poorly under-stood. We prospectively evaluated the effects of hydroxyurea and monthly erythro-cyte transfusions on diastolic function parameters over 2 years. A total of 204 subjects with HbSS or HbSb0-thalassemia (mean age 11 +/- 3.7 years), unselected for disease severity, had diastolic function assessed with surveillance echocardio-grams twice, 2 years apart. During this 2-year observation period, 112 participants received DMTs (hydroxyurea, n = 72, monthly erythrocyte transfusions, n = 40), 34 initiated hydroxyurea, and 58 did not receive any DMT. The entire cohort showed an increase in left atrial volume index (LAVi) of 3.40 +/- 10.86 mL/m2, p = .001 over 2 years. This increase in LAVi was independently associated with anemia, high base -line E/e ' or LV dilation. Individuals not exposed to DMT were younger (mean age 8.8 +/- 2.9 years), but at baseline their prevalence of abnormal diastolic parameters was similar to that of the DMT-exposed participants who were older (mean age 12 +/- 3.8 years). Participants on DMTs saw no improvement in diastolic function over the study period. In fact, participants on hydroxyurea saw a possible worsening in diastolic parameters (14% increase in LAVi and similar to 5% decrease in septal e ') but also a similar to 9% decrease in fetal hemoglobin (HbF) levels. Further studies are needed to evalu-ate if exposure to DMT for a longer duration or achieving higher HbF might be bene-ficial in alleviating diastolic dysfunction.

Automated summary

Cardiac abnormalities in sickle cell anemia include diastolic dysfunction, which is associated with high morbidity and early mortality. This study evaluated the effects of disease-modifying therapies on diastolic function and found that hydroxyurea and erythrocyte transfusions did not improve diastolic parameters over a 2-year period.