Associations of Prolonged QTc in Sickle Cell Disease

Abstract

Sudden death is a leading cause of mortality in sickle cell disease, implicating ventricular tachyarrhythmias. Prolonged QTc on an electrocardiogram (ECG), commonly seen with myocardial ischemia, is a known risk for polymorphic ventricular tachycardia (VT). We hypothesized that prolonged QTc is associated with mortality in sickle cell disease. ECG were analyzed from a cohort of 224 sickle patients (University of Illinois at Chicago, UIC) along with available laboratory, and echocardiographic findings, and from another cohort of 38 patients (University of Chicago, UC) for which cardiac MRI and free heme values were also measured. In the UIC cohort, QTc was potentially related to mortality with a hazard ratio (HR) of 1.22 per 10ms, (P = 0.015), and a HR = 3.19 (P = 0.045) for a QTc>480ms. In multivariate analyses, QTc remained significantly associated with survival after adjusting for inpatient ECG status (HR 1.26 per 10ms interval, P = 0.010) and genotype status [HR 1.21 per 10ms interval, P = 0.037). QTc trended toward association with mortality after adjusting for both LDH and hydroxyurea use (HR 1.21 per 10ms interval, P = 0.062) but was not significant after adjusting for TRV. In univariate analyses, QTc was related to markers of hemolysis including AST (P = 0.031), hemoglobin (P = 0.014), TR velocity (P = 0.036), higher in inpatients (P<0.001) and those with an SS compared to SC genotype (P<0.001) in the UIC cohort as well as to free heme in the UC cohort (P = 0.002). These findings support a relationship of prolonged QTc with hemolysis and potentially mortality in sickle cell disease.

Sickle cell disease‐associated arrhythmias and in‐hospital outcomes: Insights from the National Inpatient Sample

“…The SCD cohort with arrhythmia demonstrated a higher odd of in- Indik and colleagues studied two cohorts of SCD and established that a prolonged QT interval and ventricular tachyarrhythmias were significant predictors of mortality in this population. 17 We observed a nearly threefold higher odds of in-hospital mortality among SCD hospitalized patients with arrhythmias as compared to those without arrhythmias on multivariate analysis. In keeping with this finding was a study that suggested that a prolonged QT was an independent predictor of increased sudden deaths in patients with SCD.…”

“…The reason for the increased frequency of arrhythmias in SCD patients remains largely unclear, but a predilection to cardiac autonomic dysfunction, QT prolongation, and myocardial fibrosis have been posited as possible explanations 15,16 . Indik and colleagues studied two cohorts of SCD and established that a prolonged QT interval and ventricular tachyarrhythmias were significant predictors of mortality in this population 17 . We observed a nearly threefold higher odds of in‐hospital mortality among SCD hospitalized patients with arrhythmias as compared to those without arrhythmias on multivariate analysis.…”

Association of circulating transcriptomic profiles with mortality in sickle cell disease

“…There is significant heterogeneity in the rate of development of acute and chronic pain, cerebrovascular disease, acute chest syndrome, 8,9 pulmonary hypertension (PH), diastolic dysfunction, renal failure, hemolytic anemia, and premature or sudden death. [10][11][12][13] Therefore, the development of biomarkers for risk stratification is vital. The utility of such biomarkers in the management of SCD is underscored by their potential application as tools to provide early diagnosis of complications, to identify a subset of individuals at risk for a severe clinical course, to define disease relevant molecular pathways, or to monitor response to therapy.…”

Impact of relative systemic hypertension on the heart in sickle cell anaemia

“… 17 It has also been shown to be related to increased serum aspartate transaminase, increased haemoglobin, tricuspid regurgitation velocity and if the ECG was done as an in-patient. 18 Now, patients with SCA and RSH have been shown to have significantly prolonged QTc as compared to controls in this study.…”