Title:Cardiac Complications Attributed to Hydroxychloroquine: A Systematic Review of the Literature Pre-COVID-19
VOLUME: 17 ISSUE: 3
Author(s):Georgi Fram, Dee D. 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, MI 48202, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, MI 48202, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, MI 48202, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, MI 48202, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, MI 48202, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, MI 48202, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, MI 48202, Section of Cardiac Electrophysiology, Henry Ford Health System, Detroit, Michigan, MI 48202, Divison of Infectious Disease, Henry Ford Health System, Detroit, MMichigan, MI 48202, Divison of Infectious Disease, Henry Ford Health System, Detroit, MMichigan, MI 48202, Center for Structural Heart Disease, Henry Ford Health System, Detroit, Michigan, MI 48202
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 the cardiotoxic
profile of hydroxychloroquine is previously underreported in the literature or is it a manifestation
of COVID-19 and therapeutic interventions. This manuscript evaluates the incidence of cardiotoxicity
associated with hydroxychloroquine prior to the onset of COVID-19.
Methods: PubMED, EMBASE, and Cochrane databases were searched for keywords derived from
MeSH terms prior to April 9, 2020. Inclusion eligibility was based on appropriate reporting of cardiac
conditions and study design.
Results: A total of 69 articles were identified (58 case reports, 11 case series). The majority (84%)
of patients were female, with a median age of 49.2 (range 16-92) years. 15 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. 2 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 the withdrawal of hydroxychloroquine and standard therapy.
Conclusion: Millions of hydroxychloroquine doses are prescribed annually. Prior to the
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 the presence or absence of potential medication interactions with hydroxychloroquine
in this new pathophysiological state.
