Biological Sciences Division
Published October 13, 2016 | Version v1
Journal article Open

Associations of Prolonged QTc in Sickle Cell Disease

Creators

  • 1. University of Arizona
  • 2. University of Illinois Hospitals and Health Sciences System
  • 3. University of Washington
  • 4. Creighton University Medical Center
  • 5. Oakhill University
  • 6. Mercy Hospital and Health Center
  • 7. University of Chicago
  • 8. Lifespace Cardiovascular Institute and Brown University

Description

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.

Data availability

All relevant data are within the paper and its Supporting Information files.

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Additional details

Identifiers

DOI
10.1371/journal.pone.0164526
Other
oai:uchicago.tind.io:6677

Funding

National Institutes of Health
UL1RR029879
American Heart Association
14CRP18910051
American Thoracic Society Foundation/Pulmonary Hypertension Association
National Institutes of Health
R01 HL127342
National Institutes of Health
R01 HL111656

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine