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Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19.
Int J Antimicrob Agents. 2020 Oct; 56(4):106142.IJ

Abstract

This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring.

Authors+Show Affiliations

Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; Universidad Miguel Hernández de Elche, Alicante, Spain. Electronic address: sergiopadurr@gmail.com.Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain.Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain.Statistics, Operational Research Center, Universidad Miguel Hernández, Elche, Alicante, Spain.Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain.Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain.Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain.Section of Respiratory Medicine, Hospital General Universitario de Elche, Alicante, Spain.Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; Universidad Miguel Hernández de Elche, Alicante, Spain. Electronic address: gutierrezfel@gmail.com.Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; Universidad Miguel Hernández de Elche, Alicante, Spain.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32853675

Citation

Padilla, Sergio, et al. "Predictive Factors for Cardiac Conduction Abnormalities With Hydroxychloroquine-containing Combinations for COVID-19." International Journal of Antimicrobial Agents, vol. 56, no. 4, 2020, p. 106142.
Padilla S, Telenti G, Guillén L, et al. Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19. Int J Antimicrob Agents. 2020;56(4):106142.
Padilla, S., Telenti, G., Guillén, L., García, J. A., García-Abellán, J., Ding, C., Mora, A., García-Pachón, E., Gutiérrez, F., & Masiá, M. (2020). Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19. International Journal of Antimicrobial Agents, 56(4), 106142. https://doi.org/10.1016/j.ijantimicag.2020.106142
Padilla S, et al. Predictive Factors for Cardiac Conduction Abnormalities With Hydroxychloroquine-containing Combinations for COVID-19. Int J Antimicrob Agents. 2020;56(4):106142. PubMed PMID: 32853675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19. AU - Padilla,Sergio, AU - Telenti,Guillermo, AU - Guillén,Lucía, AU - García,José A, AU - García-Abellán,Javier, AU - Ding,Carolina, AU - Mora,Antonia, AU - García-Pachón,Eduardo, AU - Gutiérrez,Félix, AU - Masiá,Mar, AU - ,, Y1 - 2020/08/24/ PY - 2020/05/15/received PY - 2020/07/13/revised PY - 2020/08/19/accepted PY - 2020/8/28/pubmed PY - 2020/10/2/medline PY - 2020/8/28/entrez KW - Azithromycin KW - COVID-19 KW - Hydroxychloroquine KW - Lopinavir/ritonavir KW - QT interval KW - Troponin SP - 106142 EP - 106142 JF - International journal of antimicrobial agents JO - Int J Antimicrob Agents VL - 56 IS - 4 N2 - This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/32853675/Predictive_factors_for_cardiac_conduction_abnormalities_with_hydroxychloroquine_containing_combinations_for_COVID_19_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(20)30340-X DB - PRIME DP - Unbound Medicine ER -