Cardiomegaly in Sickle Cell Disease: Prevalence, Associated Factors, and Implications for Cardiopulmonary Screening in a Single-Center Retrospective Study
Fatoumata Barry, Jared Taitt, Max Jordan NguemeniAbstract
Background
Cardiomegaly is a common radiographic finding among patients with sickle cell disease (SCD). In the general population, it is a relatively specific marker of underlying structural heart disease and cardiopulmonary pathology. Cardiopulmonary complications, particularly heart failure and pulmonary hypertension, are major contributors to morbidity and mortality in SCD, yet evidence to guide screening remains limited. Given the frequent healthcare encounters among patients with SCD, incidentally noted cardiomegaly may represent an accessible and underutilized trigger for investigation and earlier detection of cardiopulmonary disease. In this study, we aim to estimate the prevalence of cardiomegaly and identify factors associated with its presence among adults with SCD.
Methods
This is a retrospective cohort study of 200 patients diagnosed with SCD who received care at UCLA Heath between January 2016 to March 2026. Data were collected manually via electronic health record review. The primary outcome was evidence of cardiomegaly documented on chest radiography, using radiologic imaging impressions. Covariates included age, sex, SCD phenotype (SS, SC, S/C-Thalassemia, Others), and the number of disease modifying medications (hydroxurea, voxelotor, L-glutamine, crizanlizumab) the patient has ever been prescribed. For bivariate analyses, we used t-tests for continuous variables and chi-squared tests for categorical variables. We performed a multivariate logistic regression with robust standard errors for the primary analysis. All tests were two-tailed and statistical significance was defined as P < 0.05. All analyses were conducted in Stata 18 (statacorp). The study was approved by the UCLA IRB.
Results
Our study population consisted of 200 patients. The mean age was 33.2 (SD 17.6), 48.5% (n = 95) were female, and 69% (n = 136) had a history of being prescribed hydroxyurea at least once. Cardiomegaly was observed in 40.5% (n = 81) of the cohort. Compared to patients without cardiomegaly (mean age 29.4, SD 17.0), patients with cardiomegaly were older (mean age 38.7, SD 17.2; p < 0.001). There was no significant association between sex and cardiomegaly (p = 0.948). Among patients with the HbSS phenotype, 72.8% (n = 59) were found to have cardiomegaly, compared to 13.6% (n = 11) and 12.3% (n = 10) in patients with HbSC and S/C-thalassemia, respectively (p < 0.001). In our multivariate logistic regression, older age was associated with cardiomegaly (OR 1.05, 95% CI 1.02-1.07), as was the number of disease modifying therapies ever prescribed (OR 1.87, 95% CI 1.05-3.32). Compared to patients with HbSS phenotype, patients with HbSC (OR 0.16, 95% CI 0.06–0.41) and S/C-thalassemia (OR 0.22, 95% CI 0.09–0.58) had significantly lower odds of having cardiomegaly.
Conclusions
In this retrospective, single-center cohort study, older age, history of using multiple disease modifying agents and SS phenotype were associated with developing cardiomegaly. These associations likely reflect the effect of cumulative organ damage and disease severity over the life course. Chest radiography is a common test performed among SCD patients, and evidence of cardiomegaly may serve as an opportunity to detect early stage cardiopulmonary disease. Future studies should explore the association between cardiomegaly on chest radiography and the risk of developing cardiopulmonary conditions such as pulmonary hypertension and congestive heart failure.