Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19
•Hydroxychloroquine (HCQ) has been widely used to treat COVID-19 worldwide even without good evidence of efficacy.•We analyzed the changes occurring in the QTc interval and their predictors in patients treated with HCQ-containing regimens for COVID-19.•Evidence of myocardial injury with elevated tro...
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| Published in | International journal of antimicrobial agents Vol. 56; no. 4; p. 106142 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Ltd
01.10.2020
Elsevier Ltd and International Society of Antimicrobial Chemotherapy |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0924-8579 1872-7913 1872-7913 |
| DOI | 10.1016/j.ijantimicag.2020.106142 |
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| Abstract | •Hydroxychloroquine (HCQ) has been widely used to treat COVID-19 worldwide even without good evidence of efficacy.•We analyzed the changes occurring in the QTc interval and their predictors in patients treated with HCQ-containing regimens for COVID-19.•Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher neutrophil-to-lymphocyte ratio, were major contributors to moderate-to-severe QTc prolongation requiring careful QTc interval monitoring.•In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed.
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. |
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| AbstractList | 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. 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.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. 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. Highlights•Hydroxychloroquine (HCQ) has been widely used to treat COVID-19 worldwide even without good evidence of efficacy. •We analyzed the changes occurring in the QTc interval and their predictors in patients treated with HCQ-containing regimens for COVID-19. •Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher neutrophil-to-lymphocyte ratio, were major contributors to moderate-to-severe QTc prolongation requiring careful QTc interval monitoring. •In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed. •Hydroxychloroquine (HCQ) has been widely used to treat COVID-19 worldwide even without good evidence of efficacy.•We analyzed the changes occurring in the QTc interval and their predictors in patients treated with HCQ-containing regimens for COVID-19.•Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher neutrophil-to-lymphocyte ratio, were major contributors to moderate-to-severe QTc prolongation requiring careful QTc interval monitoring.•In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed. 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. • Hydroxychloroquine (HCQ) has been widely used to treat COVID-19 worldwide even without good evidence of efficacy. • We analyzed the changes occurring in the QTc interval and their predictors in patients treated with HCQ-containing regimens for COVID-19. • Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher neutrophil-to-lymphocyte ratio, were major contributors to moderate-to-severe QTc prolongation requiring careful QTc interval monitoring. • In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed. 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. |
| ArticleNumber | 106142 |
| Author | García-Pachón, Eduardo Padilla, Sergio García, José A. Masiá, Mar Guillén, Lucía Ding, Carolina Mora, Antonia García-Abellán, Javier Gutiérrez, Félix Telenti, Guillermo |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32853675$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_3389_fphar_2020_593099 crossref_primary_10_1002_pds_5234 crossref_primary_10_1007_s40801_022_00307_5 crossref_primary_10_2217_fvl_2021_0119 crossref_primary_10_1007_s00296_021_04868_6 crossref_primary_10_1016_j_biopha_2021_111642 |
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| Keywords | COVID-19 QT interval Troponin Hydroxychloroquine Lopinavir/ritonavir Azithromycin |
| Language | English |
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| Snippet | •Hydroxychloroquine (HCQ) has been widely used to treat COVID-19 worldwide even without good evidence of efficacy.•We analyzed the changes occurring in the QTc... Highlights•Hydroxychloroquine (HCQ) has been widely used to treat COVID-19 worldwide even without good evidence of efficacy. •We analyzed the changes occurring... This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations... • Hydroxychloroquine (HCQ) has been widely used to treat COVID-19 worldwide even without good evidence of efficacy. • We analyzed the changes occurring in the... |
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| SubjectTerms | adults age Aged Anti-Infective Agents - administration & dosage Anti-Infective Agents - adverse effects arrhythmia Azithromycin Azithromycin - administration & dosage Azithromycin - adverse effects Betacoronavirus - drug effects Betacoronavirus - immunology Betacoronavirus - pathogenicity Biomarkers - blood blood serum cohort studies Coronavirus infections Coronavirus Infections - diagnosis Coronavirus Infections - drug therapy Coronavirus Infections - physiopathology Coronavirus Infections - virology COVID-19 death Disease Progression Drug Combinations Female Humans Hydroxychloroquine Hydroxychloroquine - administration & dosage Hydroxychloroquine - adverse effects Infectious Disease inflammation Intensive Care Units Long QT Syndrome - chemically induced Long QT Syndrome - diagnosis Long QT Syndrome - physiopathology Lopinavir - administration & dosage Lopinavir - adverse effects Lopinavir/ritonavir Lymphocytes - pathology Lymphocytes - virology Male males men Middle Aged monitoring Neutrophils - pathology Neutrophils - virology Pandemics patients Pneumonia, Viral - diagnosis Pneumonia, Viral - drug therapy Pneumonia, Viral - physiopathology Pneumonia, Viral - virology prediction Prognosis Proportional Hazards Models QT interval regression analysis Retrospective Studies risk Ritonavir - administration & dosage Ritonavir - adverse effects SARS-CoV-2 therapeutics Treatment Outcome Troponin troponin I Troponin I - blood women |
| Title | Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19 |
| URI | https://www.clinicalkey.com/#!/content/1-s2.0-S092485792030340X https://www.clinicalkey.es/playcontent/1-s2.0-S092485792030340X https://dx.doi.org/10.1016/j.ijantimicag.2020.106142 https://www.ncbi.nlm.nih.gov/pubmed/32853675 https://www.proquest.com/docview/2438675234 https://www.proquest.com/docview/2498257273 https://pubmed.ncbi.nlm.nih.gov/PMC7444635 |
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