QT interval prolongation and torsade de pointes in patients with COVID-19 treated with hydroxychloroquine/azithromycin

被引:149
作者
Chorin, Ehud [1 ]
Wadhwani, Lalit [1 ]
Magnani, Silvia [2 ]
Dai, Matthew [1 ]
Shulman, Eric [1 ]
Nadeau-Routhier, Charles [1 ]
Knotts, Robert [1 ]
Bar-Cohen, Roi [1 ]
Kogan, Edward [1 ]
Barbhaiya, Chirag [1 ]
Aizer, Anthony [1 ]
Holmes, Douglas [1 ]
Bernstein, Scott [1 ]
Spinelli, Michael [1 ]
Park, David S. [1 ]
Stefano, Carugo [2 ]
Chinitz, Larry A. [1 ]
Jankelson, Lior [1 ]
机构
[1] NYU, Grossman Sch Med, Leon H Charney Div Cardiol, Cardiac Electrophysiol,NYU Langone Hlth, 560 1st Ave, New York, NY 10016 USA
[2] Univ Milan, Div Cardiol, Dept Hlth Sci, San Paolo Hosp, Milan, Italy
关键词
COVID-19; QT interval; Torsade de pointes; Hydroxy-chloroquine; Azithromycin; ABORTED CARDIAC-ARREST; RISK-FACTORS; AZITHROMYCIN; DEATH;
D O I
10.1016/j.hrthm.2020.05.014
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND There is no known effective therapy for patients with coronavirus disease 2019 (COVID-19). Initial reports suggest-ing the potential benefit of hydroxychloroquine/azithromycin (HY/ AZ) have resulted in massive adoption of this combination world-wide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT in-terval prolongation and induction of torsade de pointes (TdP). OBJECTIVE The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ. METHODS This is a retrospective study of 251 patients from 2 cen-ters who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality. RESULTS The QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc interval prolongation to .500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required prema-ture termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal. CONCLUSION The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.
引用
收藏
页码:1425 / 1433
页数:9
相关论文
共 31 条
[1]  
Borba MGS, 2020, CHLOROQUINE DIPHOSPH, DOI [10.1101/2020.04.07.20056424, DOI 10.1101/2020.04.07.20056424]
[2]   Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia [J].
Chen, CY ;
Wang, FL ;
Lin, CC .
CLINICAL TOXICOLOGY, 2006, 44 (02) :173-175
[3]   Azithromycin plus chloroquine: combination therapy for protection against malaria and sexually transmitted infections in pregnancy [J].
Chico, R. Matthew ;
Chandramohan, Daniel .
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2011, 7 (09) :1153-1167
[4]   The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin [J].
Chorin, Ehud ;
Dai, Matthew ;
Shulman, Eric ;
Wadhwani, Lalit ;
Bar-Cohen, Roi ;
Barbhaiya, Chirag ;
Aizer, Anthony ;
Holmes, Douglas ;
Bernstein, Scott ;
Spinelli, Michael ;
Park, David S. ;
Chinitz, Larry A. ;
Jankelson, Lior .
NATURE MEDICINE, 2020, 26 (06) :808-809
[5]  
Drew BJ, 2010, J AM COLL CARDIOL, V55, P934, DOI [10.1016/j.jacc.2010.01.001, 10.1161/CIRCULATIONAHA.109.192704]
[6]   Chloroquine and hydroxychloroquine in covid-19 [J].
Ferner, Robin E. ;
Aronson, Jeffrey K. .
BMJ-BRITISH MEDICAL JOURNAL, 2020, 369
[7]   Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [J].
Gautret, Philippe ;
Lagier, Jean-Christophe ;
Parola, Philippe ;
Van Thuan Hoang ;
Meddeb, Line ;
Mailhe, Morgane ;
Doudier, Barbara ;
Courjon, Johan ;
Giordanengo, Valerie ;
Vieira, Vera Esteves ;
Dupont, Herve Tissot ;
Honore, Stephane ;
Colson, Philippe ;
Chabriere, Eric ;
La Scola, Bernard ;
Rolain, Jean-Marc ;
Brouqui, Philippe ;
Raoult, Didier .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2020, 56 (01)
[8]   Genetic susceptibility for COVID-19-associated sudden cardiac death in African Americans [J].
Giudicessi, John R. ;
Roden, Dan M. ;
Wilde, Arthur A. M. ;
Ackerman, Michael J. .
HEART RHYTHM, 2020, 17 (09) :1487-1492
[9]   Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19) [J].
Giudicessi, John R. ;
Noseworthy, Peter A. ;
Friedman, Paul A. ;
Ackerman, Michael J. .
MAYO CLINIC PROCEEDINGS, 2020, 95 (06) :1213-1221
[10]   Risk factors for aborted cardiac arrest and sudden cardiac death in children with the congenital long-QT syndrome [J].
Goldenberg, Ilan ;
Moss, Arthur J. ;
Peterson, Derick R. ;
McNitt, Scott ;
Zareba, Wojciech ;
Andrews, Mark L. ;
Robinson, Jennifer L. ;
Locati, Emanuela H. ;
Ackerman, Michael J. ;
Benhorin, Jesaia ;
Kaufman, Elizabeth S. ;
Napolitano, Carlo ;
Priori, Silvia G. ;
Qi, Ming ;
Schwartz, Peter J. ;
Towbin, Jeffrey A. ;
Vincent, Michael ;
Zhang, Li .
CIRCULATION, 2008, 117 (17) :2184-2191