Case Presentation: A 71-year-old male with a past medical history of schizophrenia presented with subjective fever, shortness of breath, and altered mental status. Initial vitals were significant for tachypnea at 30 breaths/minutes and hypoxia (spO2 82% on room air) requiring 6L/min of O2. Physical exam was remarkable for drowsiness and confused mental state. Initial labs were significant for positive COVID-19 PCR, thrombocytopenia at 119x10E3/uL, and lymphopenia at 0.9x10E3/uL. Chest x-ray showed a few ill-defined multifocal opacities. CT scan of the head was negative for acute intracranial abnormalities. EEG was negative for seizures. TSH was normal at 1.1 UIU/L. Electrolytes were normal with negative urinalysis and urine drug screening, and no evidence of acute infection other than COVID-19 pneumonia a. Initial EKG showed normal sinus rhythm. He was started on dexamethasone 6mg oral daily for a total of 10 days and a 200mg IV loading dose of remdesivir followed by 4 days of 100mg IV daily dose. About 10 hours after a loading dose of remdesivir, his heart rate began to drop to below 50s followed by 5.19 seconds long sinus pause. The patient remained asymptomatic and hemodynamically stable. EKG after the event showed normal sinus rhythm with normal QTc at 394 ms. The patient was not taking a nodal blocking agent with no history of chronic bradycardia or cardiovascular disease. Cardiology was consulted and deemed remdesivir to be the cause of sinus pause given negative work-up as above. Thus, it was stopped. Other than one more episode of asymptomatic sinus pause lasting for less than 2 seconds, he didn’t have any more events. His heart rate remained above 60 beats/minute with normal repeat EKGs during the rest of hospitalization while he was treated for COVID-19 pneumonia.
Discussion: Remdesivir, an intravenous prodrug of an adenosine analogue, works by inhibiting viral ribonucleic acid (RNA) polymerase. It is active against a broad range of viruses, including the Ebola virus, the Middle East respiratory syndrome coronavirus, SARS, and SARS-CoV-2 [1]. During the COVID-19 pandemic, it was approved by the US Federal Drug Administration through emergency use authorization for use in adult and pediatric patients with severe COVID-19 infection. Although there are few cases reports available in the literature about its association with sinus bradycardia, almost no cases are published about its association with a sinus pause or sinus arrest. There are several proposed mechanisms for remdesivir induced bradycardia or sinus pause. It may cross-react with human mitochondrial RNA polymerase causing deterioration of mitochondrial function and cardiotoxicity [2]. Remdesivir’s active metabolite, which is similar to adenosine triphosphate that has been shown to decrease sinus node automaticity through vagal stimulation, may slow heart rate that way [3]. Additionally, as an adenosine analogue, it could also affect atrioventricular nodal conduction [4].We recommend getting a baseline EKG prior to starting remdesivir. It is important to do continuous cardiac monitoring while the patient is receiving remdesivir, especially in presence of nodal agents and/or other medications implicated in bradycardia.
Conclusions: It is imperative to recognize the association of remdesivir with sinus bradycardia or sinus pause or arrest and stop its use when other reversible causes are ruled out.
