Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings.
Identifieur interne : 000B53 ( Main/Corpus ); précédent : 000B52; suivant : 000B54Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings.
Auteurs : Alessio Gasperetti ; Mauro Biffi ; Firat Duru ; Marco Schiavone ; Matteo Ziacchi ; Gianfranco Mitacchione ; Carlo Lavalle ; Ardan Saguner ; Antonio Lanfranchi ; Giacomo Casalini ; Marco Tocci ; Davide Fabbricatore ; Francesca Salghetti ; Marco Valerio Mariani ; Mattia Busana ; Alfonso Bellia ; Chiara Beatrice Cogliati ; Pierluigi Viale ; Spinello Antinori ; Massimo Galli ; Nazzareno Galiè ; Claudio Tondo ; Giovanni Battista ForleoSource :
- Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology [ 1532-2092 ] ; 2020.
English descriptors
- KwdEn :
- Arrhythmias, Cardiac (chemically induced), Arrhythmias, Cardiac (virology), COVID-19 (drug therapy), COVID-19 (epidemiology), Electrocardiography (MeSH), Female (MeSH), Humans (MeSH), Hydroxychloroquine (administration & dosage), Hydroxychloroquine (adverse effects), Italy (epidemiology), Male (MeSH), Middle Aged (MeSH), SARS-CoV-2 (MeSH).
- MESH :
- chemical , administration & dosage : Hydroxychloroquine.
- chemical , adverse effects : Hydroxychloroquine.
- geographic , epidemiology : Italy.
- chemically induced : Arrhythmias, Cardiac.
- drug therapy : COVID-19.
- epidemiology : COVID-19.
- virology : Arrhythmias, Cardiac.
- Electrocardiography, Female, Humans, Male, Middle Aged, SARS-CoV-2.
Abstract
AIMS
The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings.
METHODS AND RESULTS
COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36-72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9-16) ms]. Baseline QT/QTc length and presence of fever (P = 0.001) at admission represented the most important determinants of QT/QTc prolongation. No arrhythmic-related deaths were reported. The overall major ventricular arrhythmia rate was low (1.1%), with all events found not to be related to QT or HCQ therapy at a centralized event evaluation. No differences in QT/QTc prolongation and QT-related arrhythmias were observed across different clinical settings, with non-QT-related arrhythmias being more common in the intensive care setting.
CONCLUSION
HCQ administration is safe for a short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths.
DOI: 10.1093/europace/euaa216
PubMed: 32971536
PubMed Central: PMC7543547
Links to Exploration step
pubmed:32971536Le document en format XML
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<author><name sortKey="Gasperetti, Alessio" sort="Gasperetti, Alessio" uniqKey="Gasperetti A" first="Alessio" last="Gasperetti">Alessio Gasperetti</name>
<affiliation><nlm:affiliation>Heart Rhythm Center, Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:affiliation>
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<affiliation><nlm:affiliation>University Heart Center, University Hospital Zürich, Zürich, Switzerland.</nlm:affiliation>
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<author><name sortKey="Biffi, Mauro" sort="Biffi, Mauro" uniqKey="Biffi M" first="Mauro" last="Biffi">Mauro Biffi</name>
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<author><name sortKey="Duru, Firat" sort="Duru, Firat" uniqKey="Duru F" first="Firat" last="Duru">Firat Duru</name>
<affiliation><nlm:affiliation>University Heart Center, University Hospital Zürich, Zürich, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Schiavone, Marco" sort="Schiavone, Marco" uniqKey="Schiavone M" first="Marco" last="Schiavone">Marco Schiavone</name>
<affiliation><nlm:affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ziacchi, Matteo" sort="Ziacchi, Matteo" uniqKey="Ziacchi M" first="Matteo" last="Ziacchi">Matteo Ziacchi</name>
<affiliation><nlm:affiliation>Unit of Cardiology, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mitacchione, Gianfranco" sort="Mitacchione, Gianfranco" uniqKey="Mitacchione G" first="Gianfranco" last="Mitacchione">Gianfranco Mitacchione</name>
<affiliation><nlm:affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lavalle, Carlo" sort="Lavalle, Carlo" uniqKey="Lavalle C" first="Carlo" last="Lavalle">Carlo Lavalle</name>
<affiliation><nlm:affiliation>Department of Cardiovascular Disease, Policlinico Umberto I Hospital, Rome, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Saguner, Ardan" sort="Saguner, Ardan" uniqKey="Saguner A" first="Ardan" last="Saguner">Ardan Saguner</name>
<affiliation><nlm:affiliation>University Heart Center, University Hospital Zürich, Zürich, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lanfranchi, Antonio" sort="Lanfranchi, Antonio" uniqKey="Lanfranchi A" first="Antonio" last="Lanfranchi">Antonio Lanfranchi</name>
<affiliation><nlm:affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Casalini, Giacomo" sort="Casalini, Giacomo" uniqKey="Casalini G" first="Giacomo" last="Casalini">Giacomo Casalini</name>
<affiliation><nlm:affiliation>III Division of Infectious Diseases, ASST-Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences, University of Milan, Italy.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Tocci, Marco" sort="Tocci, Marco" uniqKey="Tocci M" first="Marco" last="Tocci">Marco Tocci</name>
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</affiliation>
</author>
<author><name sortKey="Fabbricatore, Davide" sort="Fabbricatore, Davide" uniqKey="Fabbricatore D" first="Davide" last="Fabbricatore">Davide Fabbricatore</name>
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</affiliation>
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<author><name sortKey="Salghetti, Francesca" sort="Salghetti, Francesca" uniqKey="Salghetti F" first="Francesca" last="Salghetti">Francesca Salghetti</name>
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</affiliation>
</author>
<author><name sortKey="Mariani, Marco Valerio" sort="Mariani, Marco Valerio" uniqKey="Mariani M" first="Marco Valerio" last="Mariani">Marco Valerio Mariani</name>
<affiliation><nlm:affiliation>Department of Cardiovascular Disease, Policlinico Umberto I Hospital, Rome, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Busana, Mattia" sort="Busana, Mattia" uniqKey="Busana M" first="Mattia" last="Busana">Mattia Busana</name>
<affiliation><nlm:affiliation>Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bellia, Alfonso" sort="Bellia, Alfonso" uniqKey="Bellia A" first="Alfonso" last="Bellia">Alfonso Bellia</name>
<affiliation><nlm:affiliation>Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cogliati, Chiara Beatrice" sort="Cogliati, Chiara Beatrice" uniqKey="Cogliati C" first="Chiara Beatrice" last="Cogliati">Chiara Beatrice Cogliati</name>
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</affiliation>
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<author><name sortKey="Viale, Pierluigi" sort="Viale, Pierluigi" uniqKey="Viale P" first="Pierluigi" last="Viale">Pierluigi Viale</name>
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</affiliation>
<affiliation><nlm:affiliation>Unit of Infectious Diseases, Department of Medical and Surgical Sciences, S. Orsola Hospital, University of Bologna, Bologna, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Antinori, Spinello" sort="Antinori, Spinello" uniqKey="Antinori S" first="Spinello" last="Antinori">Spinello Antinori</name>
<affiliation><nlm:affiliation>III Division of Infectious Diseases, ASST-Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences, University of Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Galli, Massimo" sort="Galli, Massimo" uniqKey="Galli M" first="Massimo" last="Galli">Massimo Galli</name>
<affiliation><nlm:affiliation>III Division of Infectious Diseases, ASST-Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences, University of Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Galie, Nazzareno" sort="Galie, Nazzareno" uniqKey="Galie N" first="Nazzareno" last="Galiè">Nazzareno Galiè</name>
<affiliation><nlm:affiliation>Unit of Cardiology, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Tondo, Claudio" sort="Tondo, Claudio" uniqKey="Tondo C" first="Claudio" last="Tondo">Claudio Tondo</name>
<affiliation><nlm:affiliation>Heart Rhythm Center, Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Forleo, Giovanni Battista" sort="Forleo, Giovanni Battista" uniqKey="Forleo G" first="Giovanni Battista" last="Forleo">Giovanni Battista Forleo</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings.</title>
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<affiliation><nlm:affiliation>University Heart Center, University Hospital Zürich, Zürich, Switzerland.</nlm:affiliation>
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<author><name sortKey="Biffi, Mauro" sort="Biffi, Mauro" uniqKey="Biffi M" first="Mauro" last="Biffi">Mauro Biffi</name>
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</affiliation>
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<author><name sortKey="Duru, Firat" sort="Duru, Firat" uniqKey="Duru F" first="Firat" last="Duru">Firat Duru</name>
<affiliation><nlm:affiliation>University Heart Center, University Hospital Zürich, Zürich, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Schiavone, Marco" sort="Schiavone, Marco" uniqKey="Schiavone M" first="Marco" last="Schiavone">Marco Schiavone</name>
<affiliation><nlm:affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ziacchi, Matteo" sort="Ziacchi, Matteo" uniqKey="Ziacchi M" first="Matteo" last="Ziacchi">Matteo Ziacchi</name>
<affiliation><nlm:affiliation>Unit of Cardiology, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mitacchione, Gianfranco" sort="Mitacchione, Gianfranco" uniqKey="Mitacchione G" first="Gianfranco" last="Mitacchione">Gianfranco Mitacchione</name>
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</affiliation>
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<author><name sortKey="Lavalle, Carlo" sort="Lavalle, Carlo" uniqKey="Lavalle C" first="Carlo" last="Lavalle">Carlo Lavalle</name>
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</affiliation>
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<author><name sortKey="Saguner, Ardan" sort="Saguner, Ardan" uniqKey="Saguner A" first="Ardan" last="Saguner">Ardan Saguner</name>
<affiliation><nlm:affiliation>University Heart Center, University Hospital Zürich, Zürich, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lanfranchi, Antonio" sort="Lanfranchi, Antonio" uniqKey="Lanfranchi A" first="Antonio" last="Lanfranchi">Antonio Lanfranchi</name>
<affiliation><nlm:affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Casalini, Giacomo" sort="Casalini, Giacomo" uniqKey="Casalini G" first="Giacomo" last="Casalini">Giacomo Casalini</name>
<affiliation><nlm:affiliation>III Division of Infectious Diseases, ASST-Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences, University of Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tocci, Marco" sort="Tocci, Marco" uniqKey="Tocci M" first="Marco" last="Tocci">Marco Tocci</name>
<affiliation><nlm:affiliation>Department of Cardiovascular Disease, Policlinico Umberto I Hospital, Rome, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Fabbricatore, Davide" sort="Fabbricatore, Davide" uniqKey="Fabbricatore D" first="Davide" last="Fabbricatore">Davide Fabbricatore</name>
<affiliation><nlm:affiliation>Division of Cardiology, Spedali Civili Hospital, Brescia, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Salghetti, Francesca" sort="Salghetti, Francesca" uniqKey="Salghetti F" first="Francesca" last="Salghetti">Francesca Salghetti</name>
<affiliation><nlm:affiliation>Division of Cardiology, Spedali Civili Hospital, Brescia, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mariani, Marco Valerio" sort="Mariani, Marco Valerio" uniqKey="Mariani M" first="Marco Valerio" last="Mariani">Marco Valerio Mariani</name>
<affiliation><nlm:affiliation>Department of Cardiovascular Disease, Policlinico Umberto I Hospital, Rome, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Busana, Mattia" sort="Busana, Mattia" uniqKey="Busana M" first="Mattia" last="Busana">Mattia Busana</name>
<affiliation><nlm:affiliation>Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bellia, Alfonso" sort="Bellia, Alfonso" uniqKey="Bellia A" first="Alfonso" last="Bellia">Alfonso Bellia</name>
<affiliation><nlm:affiliation>Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cogliati, Chiara Beatrice" sort="Cogliati, Chiara Beatrice" uniqKey="Cogliati C" first="Chiara Beatrice" last="Cogliati">Chiara Beatrice Cogliati</name>
<affiliation><nlm:affiliation>Department of Internal Medicine, Luigi Sacco Hospital, University of Milan, Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Viale, Pierluigi" sort="Viale, Pierluigi" uniqKey="Viale P" first="Pierluigi" last="Viale">Pierluigi Viale</name>
<affiliation><nlm:affiliation>Heart Rhythm Center, Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Unit of Infectious Diseases, Department of Medical and Surgical Sciences, S. Orsola Hospital, University of Bologna, Bologna, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Antinori, Spinello" sort="Antinori, Spinello" uniqKey="Antinori S" first="Spinello" last="Antinori">Spinello Antinori</name>
<affiliation><nlm:affiliation>III Division of Infectious Diseases, ASST-Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences, University of Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Galli, Massimo" sort="Galli, Massimo" uniqKey="Galli M" first="Massimo" last="Galli">Massimo Galli</name>
<affiliation><nlm:affiliation>III Division of Infectious Diseases, ASST-Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences, University of Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Galie, Nazzareno" sort="Galie, Nazzareno" uniqKey="Galie N" first="Nazzareno" last="Galiè">Nazzareno Galiè</name>
<affiliation><nlm:affiliation>Unit of Cardiology, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tondo, Claudio" sort="Tondo, Claudio" uniqKey="Tondo C" first="Claudio" last="Tondo">Claudio Tondo</name>
<affiliation><nlm:affiliation>Heart Rhythm Center, Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Forleo, Giovanni Battista" sort="Forleo, Giovanni Battista" uniqKey="Forleo G" first="Giovanni Battista" last="Forleo">Giovanni Battista Forleo</name>
<affiliation><nlm:affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</nlm:affiliation>
</affiliation>
</author>
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<term>Arrhythmias, Cardiac (virology)</term>
<term>COVID-19 (drug therapy)</term>
<term>COVID-19 (epidemiology)</term>
<term>Electrocardiography (MeSH)</term>
<term>Female (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Hydroxychloroquine (administration & dosage)</term>
<term>Hydroxychloroquine (adverse effects)</term>
<term>Italy (epidemiology)</term>
<term>Male (MeSH)</term>
<term>Middle Aged (MeSH)</term>
<term>SARS-CoV-2 (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Hydroxychloroquine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Hydroxychloroquine</term>
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<keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>Italy</term>
</keywords>
<keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Arrhythmias, Cardiac</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term>
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<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Arrhythmias, Cardiac</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Electrocardiography</term>
<term>Female</term>
<term>Humans</term>
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<front><div type="abstract" xml:lang="en"><p><b>AIMS</b>
</p>
<p>The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>METHODS AND RESULTS</b>
</p>
<p>COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36-72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9-16) ms]. Baseline QT/QTc length and presence of fever (P = 0.001) at admission represented the most important determinants of QT/QTc prolongation. No arrhythmic-related deaths were reported. The overall major ventricular arrhythmia rate was low (1.1%), with all events found not to be related to QT or HCQ therapy at a centralized event evaluation. No differences in QT/QTc prolongation and QT-related arrhythmias were observed across different clinical settings, with non-QT-related arrhythmias being more common in the intensive care setting.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>CONCLUSION</b>
</p>
<p>HCQ administration is safe for a short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths.</p>
</div>
</front>
</TEI>
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<DateRevised><Year>2021</Year>
<Month>01</Month>
<Day>10</Day>
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<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1532-2092</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>22</Volume>
<Issue>12</Issue>
<PubDate><Year>2020</Year>
<Month>12</Month>
<Day>23</Day>
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<Title>Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology</Title>
<ISOAbbreviation>Europace</ISOAbbreviation>
</Journal>
<ArticleTitle>Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings.</ArticleTitle>
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</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1093/europace/euaa216</ELocationID>
<Abstract><AbstractText Label="AIMS">The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings.</AbstractText>
<AbstractText Label="METHODS AND RESULTS">COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36-72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9-16) ms]. Baseline QT/QTc length and presence of fever (P = 0.001) at admission represented the most important determinants of QT/QTc prolongation. No arrhythmic-related deaths were reported. The overall major ventricular arrhythmia rate was low (1.1%), with all events found not to be related to QT or HCQ therapy at a centralized event evaluation. No differences in QT/QTc prolongation and QT-related arrhythmias were observed across different clinical settings, with non-QT-related arrhythmias being more common in the intensive care setting.</AbstractText>
<AbstractText Label="CONCLUSION">HCQ administration is safe for a short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths.</AbstractText>
<CopyrightInformation>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gasperetti</LastName>
<ForeName>Alessio</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Heart Rhythm Center, Centro Cardiologico Monzino, IRCCS, Milan, Italy.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>University Heart Center, University Hospital Zürich, Zürich, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Biffi</LastName>
<ForeName>Mauro</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Unit of Cardiology, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Duru</LastName>
<ForeName>Firat</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>University Heart Center, University Hospital Zürich, Zürich, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schiavone</LastName>
<ForeName>Marco</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ziacchi</LastName>
<ForeName>Matteo</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Unit of Cardiology, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mitacchione</LastName>
<ForeName>Gianfranco</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lavalle</LastName>
<ForeName>Carlo</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Cardiovascular Disease, Policlinico Umberto I Hospital, Rome, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Saguner</LastName>
<ForeName>Ardan</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>University Heart Center, University Hospital Zürich, Zürich, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lanfranchi</LastName>
<ForeName>Antonio</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Casalini</LastName>
<ForeName>Giacomo</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>III Division of Infectious Diseases, ASST-Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences, University of Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tocci</LastName>
<ForeName>Marco</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Cardiovascular Disease, Policlinico Umberto I Hospital, Rome, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fabbricatore</LastName>
<ForeName>Davide</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Division of Cardiology, Spedali Civili Hospital, Brescia, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Salghetti</LastName>
<ForeName>Francesca</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Division of Cardiology, Spedali Civili Hospital, Brescia, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mariani</LastName>
<ForeName>Marco Valerio</ForeName>
<Initials>MV</Initials>
<AffiliationInfo><Affiliation>Department of Cardiovascular Disease, Policlinico Umberto I Hospital, Rome, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Busana</LastName>
<ForeName>Mattia</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bellia</LastName>
<ForeName>Alfonso</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cogliati</LastName>
<ForeName>Chiara Beatrice</ForeName>
<Initials>CB</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine, Luigi Sacco Hospital, University of Milan, Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Viale</LastName>
<ForeName>Pierluigi</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Heart Rhythm Center, Centro Cardiologico Monzino, IRCCS, Milan, Italy.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Unit of Infectious Diseases, Department of Medical and Surgical Sciences, S. Orsola Hospital, University of Bologna, Bologna, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Antinori</LastName>
<ForeName>Spinello</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>III Division of Infectious Diseases, ASST-Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences, University of Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Galli</LastName>
<ForeName>Massimo</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>III Division of Infectious Diseases, ASST-Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences, University of Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Galiè</LastName>
<ForeName>Nazzareno</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Unit of Cardiology, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tondo</LastName>
<ForeName>Claudio</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Heart Rhythm Center, Centro Cardiologico Monzino, IRCCS, Milan, Italy.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Forleo</LastName>
<ForeName>Giovanni Battista</ForeName>
<Initials>GB</Initials>
<AffiliationInfo><Affiliation>Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D016448">Multicenter Study</PublicationType>
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</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Europace</MedlineTA>
<NlmUniqueID>100883649</NlmUniqueID>
<ISSNLinking>1099-5129</ISSNLinking>
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<ChemicalList><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber>
<NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D001145" MajorTopicYN="N">Arrhythmias, Cardiac</DescriptorName>
<QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName>
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<MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004562" MajorTopicYN="Y">Electrocardiography</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName>
<QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007558" MajorTopicYN="N" Type="Geographic">Italy</DescriptorName>
<QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName>
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<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Arrhythmias</Keyword>
<Keyword MajorTopicYN="Y">COVID-19</Keyword>
<Keyword MajorTopicYN="Y">Hydroxychloroquine</Keyword>
<Keyword MajorTopicYN="Y">QT interval</Keyword>
<Keyword MajorTopicYN="Y">SARS-CoV-2</Keyword>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year>
<Month>05</Month>
<Day>06</Day>
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<Day>03</Day>
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