Cardiac safety of off-label COVID-19 drug therapy: a review and proposed monitoring protocol

Abstract

More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection , yet there is no effective medical therapy. Multiple off-label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre-clinical data and are currently used for treatment of COVID-19. However, some of these medications have potential cardiac adverse effects. This is important because up to one-third of patients with COVID-19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias. Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal. Both drugs have an anti-arrhythmic property and are proarrhythmic. The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity. Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes. Many antibiotics commonly used for the treatment of patients with COVID-19, for instance azithromycin, can also prolong QT interval. This review summarizes evidenced-based data regarding potential cardiac adverse effects due to off-label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID-19. The article focuses on practical points and offers a point-of-care protocol for providers who are taking care of patients with COVID-19 in an inpatient and outpatient setting. The proposed protocol is taking into consideration that resources during the pandemic are limited.

Influence of Prone Positioning on Electrocardiogram in a Patient With COVID-19

“…1 Hydroxychloroquine and chloroquine have also been associated with conduction disorders, widened QRS duration and T-wave inversion on ECG, myocardial toxic effects, and exacerbation of underlying myocardial dysfunction. 2,3 Therefore, hospitals have been implementing ECG-based monitoring protocols whenever these agents are used for treatment of patients with COVID-19. However, severely ill patients placed in prolonged prone positioning to treat refractory hypoxemia secondary to acute respiratory distress syndrome often will have ECG leads placed on their back side instead, directly posterior to lead placement in the traditional supine position ( Figure 2).…”

Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review

“…As of now, favipiravir is not available in the U.S. or European countries, perhaps because the animal experiments showed that the antiviral agent can be associated with teratogenic effects. Favipiravir is contraindicated in women with known or suspected pregnancy [ 75 ]. Favipiravir is also associated with QT prolongation [ 76 ].…”

The Complex Management of Atrial Fibrillation and Cancer in the COVID-19 Era: Drug Interactions, Thromboembolic Risk, and Proarrhythmia

“…In this intricate scenario, there is no consensus on optimal management to mitigate the underlying torsadogenic substrate. Different guidelines and authors have proposed recommendations for QT monitoring [104][105][106][107]: although there is general agreement on the need for baseline QT assessment and general discontinuation rules (e.g., QT interval, corrected for cardiac frequency, > 500 ms, and increases > 60 ms), the timing for electrocardiographic re-assessment and re-check may vary depending on the drug (e.g., after 3-4 days of therapy initiation with hydroxychloroquine/azithromycin), as well as underlying expected susceptibility (e.g., in patients with borderline QT and structural heart disease, telemetry should be considered, also with wearable devices for out-of-hospital monitoring). Notwithstanding practicalities in carrying out home monitoring, timely correction of electrolyte imbalances before prescribing QT-prolonging agents (and monitoring relevant blood levels) is recommended, although it is unclear whether an empirical approach through preventive administration of potassium and magnesium is actually effective in mitigating the risk of TdP occurrence.…”