Electrocardiographic abnormalities and QTc prolongation in sickle cell disease: Insights from the CSSCD cardiac ancillary Study

Abstract Objective: Sickle cell disease (SCD) is associated with multiple cardiovascular complications, including QTc interval prolongation—a potentially life-threatening abnormality that may predispose patients to sudden cardiac death. This study aimed to evaluate the prevalence of electrocardiographic (ECG) abnormalities and identify risk factors associated with QTc prolongation in patients with SCD. Methods: Data were analyzed from the Cooperative Study of Sickle Cell Disease (CSSCD) Cardiac Ancillary Study, which included African American patients with steady-state SCD enrolled across four clinical centers. QT intervals were corrected using Bazett's formula, with prolongation defined by sex-specific thresholds (>440 ms for males, >460 ms for females). Results: The study cohort included 238 participants (92 males [38.7%], 146 females [61.3%]) with a median age of 19 years (IQR = 14.0). ECG abnormalities were observed in 58.8% of participants—more frequently in males (72.8%) than females (50%). Left ventricular hypertrophy was noted in 41.1%, and left atrial hypertrophy in 4.2%. QTc prolongation was present in 20.6% (n=49). Significant predictors of QTc prolongation included male sex (OR 3.68, 95% CI: 1.67–8.11, P=.001), history of heart disease (OR 3.53, 95% CI: 1.38–9.01, P=.008), pericardial effusion (OR 3.45, 95% CI: 1.10–10.86, P=.034), and lower hemoglobin levels (OR 0.63, 95% CI: 0.43–0.93, P=.018). Conclusions: QTc prolongation and ECG abnormalities are common in SCD, particularly among males and those with a history of cardiac complications or anemia. Routine ECG screening and regular monitoring of hemoglobin levels are recommended, as these may help identify high-risk individuals and reduce arrhythmic complications.