Prolonged QTc Interval Is Common In Patients with Sickle Cell Disease and Has An Inverse Relationship to Hemoglobin and Hematocrit: Results From CSSCD

Sudden unexplained premature cardiac death is common among patients with sickle cell disease (SCD). Prolonged QTc (Corrected QT interval) on electrocardiogram (EKG) is an established marker for higher risk of sudden cardiac death. There are limited data on the prevalence of prolonged QTc in SCD patients.

We studied the prevalence, EKG and echocardiographic characteristics correlated with prolonged QTc in SCD patients and assessed for any predictors of prolonged QTc interval in the study subjects.

Data from the National Institutes of Health sponsored Cooperative Study of Sickle Cell Disease (CSSCD), a multi-center, prospective study of the clinical course of SCD were analyzed. HbSS patients > 5 years of age from four clinical centers participated in the study. Each patient underwent a standard 12 lead EKG and echocardiogram and laboratory testing at a steady state. Bazett's square root formula was used for rate correction to calculate QTc. QTc> 440msec was considered as prolonged. Patients with a known diagnosis of congenital prolonged QTc syndrome or those on any medications with a known association with prolonged QTc were excluded from the analysis.

Multivariate logistic regression was used for statistical analysis. P value of <0.05 was considered statistically significant.

Data from 240 patients (62% females, 100% African American with mean age 22.3 +−10.3 years were analyzed. Of these, 33.1% were women. Prolonged QTc, per the above specified definition was seen in 31.3% of the study patients.

Mean serum hemoglobin (7.9 vs. 8.6; p<0.001) and hematocrit value (23.4 vs. 25.1; p = 0.002) were lower in those with prolonged QTc interval. Subjects with prolonged Qtc had slightly higher ventricular septal wall thickness (end diastole 1.23 vs. 1.12 cm, p = 0.03; end systole 1.54 vs. 1.45 cm, p = 0.09). Pericardial effusion (seen in 8.8%) was associated with higher odds of prolonged QTc (odds ratio (95% CI): 3.24 (1.24, 8.46).

In a multivariable model with age, gender, venticular septal thickness, pericardial effusion and hemoglobin%, only hemoglobin% was associated with prolonged QT interval: odds ratio (SD) per unit increase in Hb% = 0.65 (0.49, 0.87).

Age, gender, echocardiography determined left ventricular hypertrophy, X-ray determined cardiomegaly, PR interval, ventricular or atrial thickness or dimensions were not related to prolonged QTc interval.

These data suggest that prolonged QTc is common among patients with sickle cell disease and that hemoglobin and hematocrit are independent and inverse predictors of prolonged QTc interval.

The mechanism of prolonged QTc interval and its role if any, in sudden cardiac deaths in patients with sickle cell disease is unknown. We speculate that chronic anemia and resulting sub-acute cardiac ischemia may be associated with ventricular repolarization defects leading to prolonged QTc interval. These data provide the rationale for mechanistic studies of prolonged QTc interval and its potential relationship to sudden cardiac death in patients with sickle cell disease.

No relevant conflicts of interest to declare.