title: 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.
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Julia H
authors.initials: JH
authors.lastname: Indik
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Vineet
authors.initials: V
authors.lastname: Nair
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Rafikov
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Iwan S
authors.initials: IS
authors.lastname: Nyotowidjojo
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Jaskanwal
authors.initials: J
authors.lastname: Bisla
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL, United States of America.
authors.forename: Mayank
authors.initials: M
authors.lastname: Kansal
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL, United States of America.
authors.forename: Devang S
authors.initials: DS
authors.lastname: Parikh
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Robinson
authors.affiliation: Department of Family Medicine, Creighton University Medical Center, Omaha, NE, United States of America.
authors.forename: Anand
authors.initials: A
authors.lastname: Desai
authors.affiliation: Department of Medicine, Oakhill Hospital, Brooksville, FL, United States of America.
authors.forename: Megha
authors.initials: M
authors.lastname: Oberoi
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Akash
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Department of Medicine, Mercy Hospital and Health Center, Chicago, IL, United States of America.
authors.forename: Taimur
authors.initials: T
authors.lastname: Abbasi
authors.affiliation: Department of Surgery and Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Zain
authors.initials: Z
authors.lastname: Khalpey
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL, United States of America.
authors.forename: Amit R
authors.initials: AR
authors.lastname: Patel
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL, United States of America.
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lang
authors.affiliation: Lifespan Cardiovascular Institute and Brown University, Providence, RI, United States of America.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Dudley
authors.affiliation: Lifespan Cardiovascular Institute and Brown University, Providence, RI, United States of America.
authors.forename: Bum-Rak
authors.initials: BR
authors.lastname: Choi
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL, United States of America.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ, United States of America.
authors.forename: Ankit A
authors.initials: AA
authors.lastname: Desai
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015331:Cohort Studies; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006321:Heart / Q000000981:diagnostic imaging; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008133:Long QT Syndrome / Q000209:etiology* / Q000401:mortality; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D006454:Hemoglobins; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D006918:Hydroxyurea