Effects of hydroxychloroquine treatment on QT interval

Matthew Hooks; Bradley Bart; Orly Vardeny; Anders Westanmo; Selçuk Adabag

doi:10.1016/j.hrthm.2020.06.029

Effects of hydroxychloroquine treatment on QT interval

Matthew Hooks, Bradley Bart, Orly Vardeny, Anders Westanmo, Selçuk Adabag

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Abstract

Background: Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns. Objective: The purpose of this study was to determine the effects of HCQ treatment on QT interval. Methods: We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy. Results: Mean patient age was 64.0 ± 10.9 years, and 734 patients (90%) were men. Median dosage of HCQ was 400 mg daily, and median (25th–75th percentile) duration of HCQ therapy was 1006 (471–2075) days. Mean on-treatment QTc was 430.9 ± 31.8 ms. In total, 55 patients (7%) had QTc 470–500 ms, and 12 (1.5%) had QTc >500 ms. Chronic kidney disease (CKD), history of atrial fibrillation (AF), and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pretreatment electrocardiogram, mean QTc increased from 424.4 ± 29.7 ms to 432.0 ± 32.3 ms (P <.0001) during HCQ treatment. Of these patients, 23 (3.9%) had either prolongation of QTc >15% or on-treatment QTc >500 ms. Over median 5.97 (3.33–10.11) years of follow-up, 269 patients (33%) died. QTc >470 ms during HCQ treatment was associated with a greater mortality risk (hazard ratio 1.78; 95% confidence interval 1.16–2.71; P = .008) in univariable but not in multivariable analysis. Conclusion: HCQ is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF, and heart failure, who may benefit from greater scrutiny.

Original language	English (US)
Pages (from-to)	1930-1935
Number of pages	6
Journal	Heart Rhythm
Volume	17
Issue number	11
DOIs	https://doi.org/10.1016/j.hrthm.2020.06.029
State	Published - Nov 2020

Bibliographical note

Funding Information:
Dr Adabag has obtained research grants from the American Heart Association , Medtronic Inc. , and Boston Scientific Inc., unrelated to this project. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This research did not receive specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This manuscript is the result of work supported with resources and use of facilities of the Minneapolis VA Health Care System. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Publisher Copyright:
© 2020

Keywords

Drug-induced arrhythmia
Drugs
Electrocardiogram
Long QT syndrome
Mortality

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.hrthm.2020.06.029

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title = "Effects of hydroxychloroquine treatment on QT interval",

abstract = "Background: Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns. Objective: The purpose of this study was to determine the effects of HCQ treatment on QT interval. Methods: We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy. Results: Mean patient age was 64.0 ± 10.9 years, and 734 patients (90%) were men. Median dosage of HCQ was 400 mg daily, and median (25th–75th percentile) duration of HCQ therapy was 1006 (471–2075) days. Mean on-treatment QTc was 430.9 ± 31.8 ms. In total, 55 patients (7%) had QTc 470–500 ms, and 12 (1.5%) had QTc >500 ms. Chronic kidney disease (CKD), history of atrial fibrillation (AF), and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pretreatment electrocardiogram, mean QTc increased from 424.4 ± 29.7 ms to 432.0 ± 32.3 ms (P <.0001) during HCQ treatment. Of these patients, 23 (3.9%) had either prolongation of QTc >15% or on-treatment QTc >500 ms. Over median 5.97 (3.33–10.11) years of follow-up, 269 patients (33%) died. QTc >470 ms during HCQ treatment was associated with a greater mortality risk (hazard ratio 1.78; 95% confidence interval 1.16–2.71; P = .008) in univariable but not in multivariable analysis. Conclusion: HCQ is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF, and heart failure, who may benefit from greater scrutiny.",

keywords = "Drug-induced arrhythmia, Drugs, Electrocardiogram, Long QT syndrome, Mortality",

author = "Matthew Hooks and Bradley Bart and Orly Vardeny and Anders Westanmo and Sel{\c c}uk Adabag",

note = "Funding Information: Dr Adabag has obtained research grants from the American Heart Association , Medtronic Inc. , and Boston Scientific Inc., unrelated to this project. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This research did not receive specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This manuscript is the result of work supported with resources and use of facilities of the Minneapolis VA Health Care System. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = nov,

doi = "10.1016/j.hrthm.2020.06.029",

language = "English (US)",

volume = "17",

pages = "1930--1935",

journal = "Heart Rhythm",

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T1 - Effects of hydroxychloroquine treatment on QT interval

AU - Hooks, Matthew

AU - Bart, Bradley

AU - Vardeny, Orly

AU - Westanmo, Anders

AU - Adabag, Selçuk

N1 - Funding Information: Dr Adabag has obtained research grants from the American Heart Association , Medtronic Inc. , and Boston Scientific Inc., unrelated to this project. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This research did not receive specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This manuscript is the result of work supported with resources and use of facilities of the Minneapolis VA Health Care System. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Publisher Copyright: © 2020

PY - 2020/11

Y1 - 2020/11

N2 - Background: Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns. Objective: The purpose of this study was to determine the effects of HCQ treatment on QT interval. Methods: We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy. Results: Mean patient age was 64.0 ± 10.9 years, and 734 patients (90%) were men. Median dosage of HCQ was 400 mg daily, and median (25th–75th percentile) duration of HCQ therapy was 1006 (471–2075) days. Mean on-treatment QTc was 430.9 ± 31.8 ms. In total, 55 patients (7%) had QTc 470–500 ms, and 12 (1.5%) had QTc >500 ms. Chronic kidney disease (CKD), history of atrial fibrillation (AF), and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pretreatment electrocardiogram, mean QTc increased from 424.4 ± 29.7 ms to 432.0 ± 32.3 ms (P <.0001) during HCQ treatment. Of these patients, 23 (3.9%) had either prolongation of QTc >15% or on-treatment QTc >500 ms. Over median 5.97 (3.33–10.11) years of follow-up, 269 patients (33%) died. QTc >470 ms during HCQ treatment was associated with a greater mortality risk (hazard ratio 1.78; 95% confidence interval 1.16–2.71; P = .008) in univariable but not in multivariable analysis. Conclusion: HCQ is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF, and heart failure, who may benefit from greater scrutiny.

AB - Background: Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns. Objective: The purpose of this study was to determine the effects of HCQ treatment on QT interval. Methods: We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy. Results: Mean patient age was 64.0 ± 10.9 years, and 734 patients (90%) were men. Median dosage of HCQ was 400 mg daily, and median (25th–75th percentile) duration of HCQ therapy was 1006 (471–2075) days. Mean on-treatment QTc was 430.9 ± 31.8 ms. In total, 55 patients (7%) had QTc 470–500 ms, and 12 (1.5%) had QTc >500 ms. Chronic kidney disease (CKD), history of atrial fibrillation (AF), and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pretreatment electrocardiogram, mean QTc increased from 424.4 ± 29.7 ms to 432.0 ± 32.3 ms (P <.0001) during HCQ treatment. Of these patients, 23 (3.9%) had either prolongation of QTc >15% or on-treatment QTc >500 ms. Over median 5.97 (3.33–10.11) years of follow-up, 269 patients (33%) died. QTc >470 ms during HCQ treatment was associated with a greater mortality risk (hazard ratio 1.78; 95% confidence interval 1.16–2.71; P = .008) in univariable but not in multivariable analysis. Conclusion: HCQ is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF, and heart failure, who may benefit from greater scrutiny.

KW - Drug-induced arrhythmia

KW - Drugs

KW - Electrocardiogram

KW - Long QT syndrome

KW - Mortality

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Effects of hydroxychloroquine treatment on QT interval

Abstract

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Keywords

UN SDGs

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