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Longitudinal effect of disease-modifying therapy on left ventricular diastolic function in children with sickle cell
Parul Rai1, Victoria I Okhomina2, Guolian Kang2
1Departments of Hematology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Insights
Disease-modifying therapies like hydroxyurea did not improve cardiac diastolic function in sickle cell anemia patients over two years. Some patients on hydroxyurea showed worsening diastolic parameters, suggesting further research is needed.
Area of Science:
- Cardiology
- Hematology
- Pediatric Medicine
Background:
- Sickle cell anemia (SCA) is associated with cardiac abnormalities, including diastolic dysfunction, a known risk factor for morbidity and mortality.
- The impact of disease-modifying therapies (DMTs) on cardiac diastolic function in SCA remains poorly understood.
- Diastolic dysfunction contributes significantly to the high morbidity and early mortality observed in SCA patients.
Purpose of the Study:
- To prospectively evaluate the effects of hydroxyurea and monthly erythrocyte transfusions on diastolic function parameters in pediatric patients with SCA over two years.
- To determine if DMTs can mitigate or improve cardiac diastolic dysfunction in individuals with HbSS or HbSβ0-thalassemia.
- To identify factors associated with changes in diastolic function over time in this cohort.
Main Methods:
- Prospective evaluation of 204 pediatric patients (HbSS or HbSβ0-thalassemia) with serial echocardiograms over two years.
- Assessment of diastolic function parameters, including left atrial volume index (LAVi) and septal e'.
- Categorization of participants based on DMT exposure: hydroxyurea, monthly erythrocyte transfusions, or no DMT.
Main Results:
- The entire cohort showed a significant increase in LAVi over two years (p=0.001), indicating worsening diastolic function.
- Increased LAVi was independently associated with anemia, high baseline E/e', and left ventricular dilation.
- Participants receiving DMTs, including hydroxyurea, did not demonstrate improvement in diastolic function; hydroxyurea users showed a trend towards worsening diastolic parameters and decreased fetal hemoglobin (HbF).
Conclusions:
- Current DMTs, including hydroxyurea and erythrocyte transfusions, did not improve cardiac diastolic function in pediatric SCA patients over a two-year period.
- Worsening diastolic parameters were observed in some patients on hydroxyurea, necessitating further investigation.
- Longer-term DMT exposure or achieving higher HbF levels may be required to positively impact diastolic dysfunction in SCA.
Abstract:
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 understood. We prospectively evaluated the effects of hydroxyurea and monthly erythrocyte transfusions on diastolic function parameters over 2 years. A total of 204 subjects with HbSS or HbSβ0-thalassemia (mean age 11 ± 3.7 years), unselected for disease severity, had diastolic function assessed with surveillance echocardiograms 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 baseline 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 ~5% decrease in septal e') but also a ~9% decrease in fetal hemoglobin (HbF) levels. Further studies are needed to evaluate if exposure to DMT for a longer duration or achieving higher HbF might be beneficial in alleviating diastolic dysfunction.
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