Abstract
Background Patients with sickle cell disease (SCD) are at risk for cardiovascular sequelae, most notably pulmonary hypertension and diastolic dysfunction. SCD patients are also at great risk for cardiomyopathy, dysrhythmias, and sudden cardiac death. These complications are a result of the chronic anemia and high cardiac output state seen in SCD, which significantly increase morbidity and mortality in this patient population. With the rise in the number of disease-modifying drug therapies available for sickle cell disease, there may be clinical relevance in identifying if any single drug therapy is associated with a change in cardiac function in SCD patients.
Methods This is a retrospective single-center study of 36 patients with SCD, all ≥18 years old who were following at the UT Physicians Comprehensive Adult Sickle Cell Center in Houston, Texas during the study period (February-April 2025). 100 patients were screened, and only those with HbSS or HS/β⁰ genotype who had undergone ≥2 routine transthoracic echocardiograms at two discrete time points between the years 2021-2025 were selected. Patients were separated into two groups: those on disease-modifying drugs and those not on disease-modifying drugs. Those on disease-modifying drugs were further categorized by treatment type. Demographics, clinical features, laboratory values, and echocardiogram findings were analyzed for each patient. Laboratory parameters including most recent mean hemoglobin, fetal hemoglobin, indirect bilirubin, reticulocyte count, LDH, and creatinine were collected. Echocardiogram findings over time were recorded for each patient, including TR velocity, left ventricular ejection fraction (LVEF),pulmonary artery systolic pressure (PASP), and presence of moderate to severe atrial and/or ventricular chamber dilation. Data was analyzed using simple descriptive statistics.
Results Of the group on disease-modifying drugs (23 patients), patient sex was 44% male and 56% female, and median age was 34 years. 20 patients had the HbSS genotype. Hydroxyurea was the most common disease-modifying drug taken by 18 patients (78%), followed by Crizanlizumab in 3 patients (14%), then Voxelotor in 2 patients (8%). There was no significant difference in laboratory values between the different drug therapy groups.
In those on Hydroxyurea, an absolute increase in TR velocity of 0.05 m/s was observed between their initial and most recent echocardiograms. An absolute increase in LVEF of 4% was noted, and there was an absolute increase of 0.5 mmHg in PASP. In those on Crizanlizumab, a 0.03 m/s absolute decrease in TR velocity, an absolute decrease of 0.03% in LVEF, and an absolute decrease of 1.5 mmHg in PASP were seen. Of those who had received Voxelotor, there was a 0.27 m/s absolute decrease in TR velocity, 0.1% absolute decrease in LVEF, and an absolute decrease of 4.6 mmHg in PASP.
Of the group not on disease-modifying drugs (13 patients), patient sex was 46% male and 54% female, and median age was 43 years. 12 patients had HbSS genotype. An absolute increase in TR velocity of 0.01 m/s was observed between initial and most recent echocardiograms, along with an absolute increase in LVEF of 1% and an absolute increase of 1.3 mmHg in PASP.
A 20% absolute increase in the rate of moderate to severe heart chamber dilation was noted in the group not on disease-modifying drugs when compared to those who are. In patients not on disease-modifying drugs, 46% had chamber dilation at baseline, which increased to 69% on their most recent echocardiograms. Those on disease-modifying drugs had a baseline chamber dilation rate of 30%, which increased to 40% on their most recent echocardiograms. There was no significant difference in laboratory values between those on disease-modifying drugs and those who were not.
ConclusionThis is a simple descriptive analysis of echocardiogram parameters over time in SCD patients. Changes in findings from patients' initial echocardiograms to their most recent were seen and did vary between those taking disease-modifying drugs and those that were not (most notably the chamber dilation rate), however the sample size was too small to establish any statistically significant trend. We intend to expand this study with a larger cohort and screen 1000 SCD patients at our center, with an ultimate objective of identifying whether a specific disease-modifying drug is associated with any significant changes in echocardiogram findings over time.
