Longitudinal analysis of cardiac abnormalities in pediatric patients with sickle cell anemia and effect of hydroxyurea therapy

Abstract

Cardiac abnormalities such as left ventricular hypertrophy, dilation and pulmonary hypertension in sickle cell anemia, have been previously described. Hydroxyurea, a disease modifying therapy for sickle cell anemia, has been used for several decades. Longitudinal assessment of echocardiographic abnormalities in children and young adults with sickle cell anemia on hydroxyurea therapy is lacking. In this retrospective study, we aim to determine the prevalence of echocardiographic abnormalities in children and young adults with sickle cell anemia and to examine the effects of hydroxyurea on reverse cardiac remodeling. We reviewed the records of patients with sickle cell anemia who underwent routine cardiac screening at Cohen Children's Medical Center between 2010 and 2017, followed by retrospective longitudinal analysis of echocardiograms performed on patients receiving treatment with hydroxyurea. Data on a total of 100 patients with sickle cell anemia were analyzed; 60 (60%) were on hydroxyurea. Twenty-five (41.6%) of the patients on hydroxyurea had been treated for less than 1 year; these patients had a significantly greater prevalence of left ventricular dilation compared to those who had been on treatment for more than 1 year. Serial echocardiograms were then analyzed on patients receiving hydroxyurea. Left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment. Additionally, the left ventricular volume and mass correlated negatively with duration of treatment with hydroxyurea. Our study provides evidence that prolonged hydroxyurea therapy may lead to reverse cardiac remodeling. Future studies should attempt to follow this patient cohort for a longer duration.

Factors associated with left ventricular hypertrophy in children with sickle cell disease: results from the DISPLACE study

“…More recently the results of a retrospective longitudinal analysis of echocardiograms in patients with SCD, the authors found a high prevalence of LVH among patients on hydroxyurea, with higher prevalence among those treated for less than a year than those who had been treated longer. 31 Further in the same study, analysis of serial echocardiogram reports showed that left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment, with a negative correlation between the treatment duration and left ventricular volume and mass. 31 …”

“… 31 Further in the same study, analysis of serial echocardiogram reports showed that left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment, with a negative correlation between the treatment duration and left ventricular volume and mass. 31 …”

Pulmonary hypertension screening in children with sickle cell disease

“…Published pediatrics TRV data mostly precede the BABY‐HUG trial, whereby evidence has since suggested prolonged hydroxyurea therapy could lead to cardiac remodeling reversal. An elevated baseline TRV at 37% dropped to 11% after hydroxyurea 23 . Similarly, in a large retrospective study of 630 children, mean TRV declined significantly and only half had an elevated TRV on repeat assessment, with no discernible explanation, although it is possible that there could have been improved adherence to therapies 32 .…”

“…22 ECHO findings included left ventricle dilation, left ventricle hypertrophy, coronary artery dilation, PFO, and physiological valvular insufficiency, consistent with an earlier report. 23 Coronary artery dilation is common in SCD and associated with left ventricular hypertrophy. 24 A higher incidence of left coronary artery dilation is described.…”

“…An elevated baseline TRV at 37% dropped to 11% after hydroxyurea. 23 Similarly, in a large retrospective study of 630 children, mean TRV declined significantly and only half had an elevated TRV on repeat assessment, with no discernible explanation, although it is possible that there could have been improved adherence to therapies. 32 A small prospective study in children reported similar findings of improved ECHO measures after initiating hydroxyurea.…”