Title:Cardiac Complications Attributed to Hydroxychloroquine: A Systematic Review of the Literature Pre-COVID-19
VOLUME: 16
Author(s):Georgi Fram, Dee Dee Wang*, Kelly Malette, Pedro Villablanca, Guson Kang, Kent So, Mir B. Basir, Arfaat Khan, John E. McKinnon, Marcus Zervos and William W. O’Neill
Affiliation:Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, Section of Cardiac Electrophysiology, Henry Ford Health System, Detroit, Michigan, Divison of Infectious Disease, Henry Ford Health System, Detroit, Michigan, Divison of Infectious Disease, Henry Ford Health System, Detroit, Michigan, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan
Keywords:Clinical cardiology, hydroxychloroquine, infectious disease, covid-19, cardiac complications, SLE.
Abstract: Introduction: Hydroxychloroquine has been used for rheumatological diseases for many decades and is
considered a safe medication. With the COVID-19 outbreak, there has been an increase in reports associating
cardiotoxicity with hydroxychloroquine. It is unclear if cardiotoxic profile of hydroxychloroquine is previously
underreported in the literature, or a new manifestation of COVID-19 and therapeutic interventions. This manuscript
evaluates the incidence of cardiotoxicity associated with hydroxychloroquine prior to onset of COVID-19.
Methods: PubMED, EMBASE, and Cochrane databases were searched for keywords derived from MeSH terms, prior to
4/9/2020. Inclusion eligibility was based on appropriate reporting of cardiac conditions and study design.
Results: Sixty-nine articles were identified (58 case reports, 11 case series). Majority (84%) of patients were female, with
a median age of 49.2(range 16-92) years. Fifteen of 185 patients with cardiotoxic events were in the setting of acute
intentional overdose. In acute overdose, the median ingestion was 17,857 14,873 mg. Two of 15 patients died after
acute intoxication. In patients with long-term hydroxychloroquine use (10.5 ± 8.9 years), new onset systolic heart failure
occurred in 54 of 155 patients (35%) with median cumulative ingestion of 1,493,800 ± 995,517 mg. The majority of
patients improved with withdrawal of hydroxychloroquine and standard therapy.
Conclusions: Millions of hydroxychloroquine doses are prescribed annually. Prior to COVID-19 pandemic, cardiac
complications attributed to hydroxychloroquine were uncommon. Further studies are needed to understand the impact of
COVID-19 on the cardiovascular system to understand presence or absence of potential medication interactions with
hydroxychloroquine in this new pathophysiological state.
