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.