Associations of prolonged QTc in sickle cell disease

Julia H. Indik, Vineet Nair, Ruslan Rafikov, Iwan S. Nyotowidjojo, Jaskanwal Bisla, Mayank Kansal, Devang S. Parikh, Melissa Robinson, Anand Desai, Megha Oberoi, Akash Gupta, Taimur Abbasi, Zain Khalpey, Amit R. Patel, Roberto M. Lang, Samuel C. Dudley, Bum Rak Choi, Joe G.N. Garcia, Roberto F. Machado, Ankit A. Desai

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Article numbere0164526
JournalPloS one
Volume11
Issue number10
DOIs
StatePublished - Oct 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Indik, J. H., Nair, V., Rafikov, R., Nyotowidjojo, I. S., Bisla, J., Kansal, M., Parikh, D. S., Robinson, M., Desai, A., Oberoi, M., Gupta, A., Abbasi, T., Khalpey, Z., Patel, A. R., Lang, R. M., Dudley, S. C., Choi, B. R., Garcia, J. G. N., Machado, R. F., & Desai, A. A. (2016). Associations of prolonged QTc in sickle cell disease. PloS one, 11(10), [e0164526]. https://doi.org/10.1371/journal.pone.0164526