Is remdesivir-induced symptomatic bradycardia persistent? A two case report of COVID-19 infection

Rime Mehannek; Krunal Truvedi; Kinjal Patel; Ahsan Khan

doi:10.4103/ACCJ.ACCJ_12_22

CASE REPORT

Year : 2022 | Volume : 4 | Issue : 2 | Page : 89-91

Is remdesivir-induced symptomatic bradycardia persistent? A two case report of COVID-19 infection

Rime Mehannek¹, Krunal Truvedi¹, Kinjal Patel², Ahsan Khan²
¹ Department of Internal Medicine, St. Michael's Medical Center, Affiliated with New York Medical College, Newark, New Jersey, USA
² Department of Cardiology, St. Michael's Medical Center, Affiliated with New York Medical College, Newark, New Jersey, USA

Date of Submission	08-Jun-2022
Date of Decision	01-Aug-2022
Date of Acceptance	26-Aug-2022
Date of Web Publication	07-Dec-2022

Correspondence Address:
Dr. Rime Mehannek
111 Central Avenue, Newark, New Jersey, 07102
USA

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ACCJ.ACCJ_12_22

Abstract

As of May 2022, a total of over 528 million cases of coronavirus 19 disease (COVID-19) worldwide with over 6 million deaths. Remdesivir is a broad-spectrum antiviral medication approved worldwide; it acts by inhibiting the RNA-dependent RNA polymerase, used for moderate-to-severe COVID-19 which requires supplemental oxygen but not intubation. Not shown to improve mortality but shorten the recovery time, especially if given within the first 10 days of symptom initiation. Despite its worldwide use, its cardiovascular safety profile has not been determined as yet. Herein, we report two cases of COVID-19 infection who develop symptomatic bradycardia on a 5-day course of remdesivir.

Keywords: Bradycardia, COVID-19 infection, remdesivir

How to cite this article:
Mehannek R, Truvedi K, Patel K, Khan A. Is remdesivir-induced symptomatic bradycardia persistent? A two case report of COVID-19 infection. Ann Clin Cardiol 2022;4:89-91

How to cite this URL:
Mehannek R, Truvedi K, Patel K, Khan A. Is remdesivir-induced symptomatic bradycardia persistent? A two case report of COVID-19 infection. Ann Clin Cardiol [serial online] 2022 [cited 2023 May 29];4:89-91. Available from: http://www.onlineacc.org/text.asp?2022/4/2/89/362955

Introduction

As of May 2022, a total of over 528 million cases of Covid worldwide with over 6 million deaths.^[1] COVID-19 disease is a global pandemic, over the past 2 years, it developed a total of three different genetic strains worldwide, affecting multiple organs including but not limited to the lungs, kidneys, liver, and thromboembolic,^[2] and remdesivir has become the standard of care in the management of patients affected with COVID-19 pneumonia, a loading dose of 200 mg followed by a 4-day course of 100 mg. We will describe two patients who developed sinus bradycardia following COVID-19 infection after a course of remdesivir. In one of the patients, the bradycardia was persistent.

Case Reports

Case #1

A 31-year-old female with no medical history presents to the emergency department with complaints of generalized body aches, dry cough, loss of taste, headache, nausea, and shortness of breath with ambulation for a 1-day duration. She stated that her daughter recently tested positive for COVID-19.

On admission, the vitals were stable with a respiratory rate of 18 beats/min, a blood pressure of 119/68 mmHg, a heart rate (HR) of 102 beats/min, and oxygen saturation (Spo2) of 89% on room air.

On a physical examination, the patient had a normal breathing effort and the lungs were clear to auscultation with no wheezes, rhonchi, or rales. On cardiac examination, the patient had a regular rate and rhythm, with no murmurs appreciated.

Laboratory data revealed a positive test for both the SARS-CoV nucleic acid amplification test and COVID-19 polymerase chain reaction (PCR). The C-reactive protein (CRP) was 3.2 mg/dl, fibrin degradation products (D-dimer) were 642 ng/ml, lactate dehydrogenase was 232U/L, and thyroid-stimulating hormone (TSH) was 0.598 uIU/mL. The rest of the laboratories were within normal limits.

Chest X-ray was within normal limit and computed tomography angiogram scan showed no pulmonary emboli and a mosaic attenuation of the lungs, which may reflect small airway disease.

Her electrocardiogram (ECG) [Figure 1] on admission showed a sinus rhythm with left atrial enlargement, HR 88, and QTc 438 ms.

Figure 1: Sinus rhythm with left atrial enlargement, HR 88, and QT 438 ms

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A diagnosis of COVID-19 was made, and the patient was treated with dexamethasone 6 mg and remdesivir with an initial dose of 200 mg followed by a 3 days course of 100 mg. ceftriaxone, ondansetron, and tylenol were also prescribed during this course.

On day 3 of remdesivir therapy, our patient complained of persistent nausea and telemetry showed a significant bradycardia with a HR of 35–38 beats/min.

ECG [Figure 2] demonstrated sinus bradycardia (HR 45 beats/min and QTc interval 403 ms). Therefore, remdesivir was discontinued and the patient remained in asymptomatic bradycardia, she was followed as an outpatient.

Figure 2: Sinus bradycardia HR 45 beats/min

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Case #2

A 52-year-old female with a past medical history of hypertension. She is a tobacco user and presents to the emergency department with chief complaints of fever, chills, nausea, vomiting, loss of appetite and taste, headache, generalized body aches, nonproductive cough, exertional shortness of breath, and diarrhea for the past week. She tested positive for COVID-19 nuclear amplification test 1 week before admission to our facility.

On admission, she was tachypnic, saturating at 89% on room air, and 96% on 2 L nasal on nasal cannula. On the physical examination, she spoke in full sentences, she was in no acute distress, she had bilateral inspiratory crackles with good air entry and no wheezes were appreciated. During the cardiac examination, she had a regular rate and rhythm, normal S1 and S2 sounds, no S3 sound, no murmurs heard, and no pericardial rub.

Laboratory data were significant for: an arterial blood gas PH 7.4, PCO2 34.6, and PaO2 75; elevated aspartate aminotransferase 361 units/L; alanine aminotransferase 505 units/L; INR 1.0; TSH 1.110uIU/mL; D-dimer 2,139 mg/L; ferritin 4519 ng/mL; CRP 7.1 mg/dL; and lactate dehydrogenase 510 units/L.

On admission, the patient responded to a bolus of normal saline and her BP improved, she was started on standard COVID-19 treatment protocol including antiviral therapy with remdesivir (200 mg on day 1 followed by 4 days of 100 mg IV daily) and a 5-day course of ceftriaxone and doxycycline. A 10-day course of dexamethasone, duoneb, and nebulizer was also administered.

Her ECG [Figure 3] on admission showed a normal sinus rhythm HR 72 beats/min, with no ST or T-wave changes, and QTc 436 ms.

Figure 3: shows a normal sinus rhythm HR 72 beats/min, with no ST or T-wave changes, and QTc 436 ms

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On day 3 of remdesivir, the patient became bradycardic. Telemetry strips were reviewed. The patient developed sinus bradycardia with HR reaching as low as 35 beats/min, no pauses were noted. She was asymptomatic; she denied dizziness or syncope.

A repeat ECG [Figure 4] demonstrated a sinus bradycardia HR 47 beats/min QTc 500 ms.

Figure 4: A sinus bradycardia HR 47 beats/min QTc 500 ms

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She had an echocardiogram done, her left ventricular ejection fraction was 60%–65%, and the left ventricle had a normal wall motion, wall thickness, and diastolic function.

The patient visited the emergency room after her discharge for urinary tract infection, her HR at that time was 70 beats/min but on follow-up visits, she reports that her HR remained low; she also stated that she had a history of low HR for years before it resolved.

Discussion

In the Adaptive COVID-19 Treatment Trial-1 (ACTT-1) experimental group, 0.6% of patients had supraventricular tachycardia, compared to 0.4% in the control group.^[3] Remdesivir was associated with cardiac arrests in 1.9% of patients receiving it, compared to 1.4% of patients receiving placebo. In addition, there was an increase in serious atrial fibrillation in 4% of patients.^[3] The most commonly reported adverse reactions, in terms of safety, were diarrhea, rash, and liver dysfunction.^[4],[5]

Both ACTT-1 and solidarity did not identify bradycardia as an adverse effect, but clinical trials are generally underpowered to detect uncommon adverse events.^[3]

Remdesivir may cause adverse cardiac effects through a variety of mechanisms. The first is an active metabolite of remdesivir that is similar to adenosine triphosphate.^[6] It has been shown that this metabolite causes bradycardia by reducing sinus node automaticity through vagal stimulation.^[6] In addition, remdesivir has an adenosine analog, which may affect nodal conduction in atrioventricular nodes, which explains why some patients may experience QRS prolongation. Remdesivir's inherent safety and effectiveness are dependent on its affinity for viral RNA polymerase as opposed to human mitochondrial RNA polymerase (h-mtRNAP).^[7],[8] Remdesivir has a relatively high affinity for viral polymerases, but it may also cross-react with human mitochondrial RNA polymerase, which has been demonstrated to be a mechanism for drug-induced cardiotoxicity.^[3],[9] In vitro experiments showed that remdesivir can cause cardiomyocyte cytotoxicity when administered to cardiomyocytes derived from human stem cells.

The patients in our study had no prior history of heart disease, and their telemetry monitor and ECG were normal before remdesivir administration. In addition, no other medications were administered to the patients that could have caused bradycardia. The time course of this case story raises the possibility that remdesivir was the causative agent, even though case reports cannot prove causality.

Conclusion

We recommend obtaining a baseline ECG in all patients before receiving remdesivir, especially in patients with underlying cardiac conditions, due to its effect on the cardiac conduction system.

Remdesivir at the present time is used globally in the treatment of COVID-19. Additional investigations are required to further assess its safety and adverse effects.^[10]

Furthermore, between January and June 2020. The Food and Drug Administration documented nine cases of bradycardia that were not associated with an infusion reaction when remdesivir was used for COVID-19.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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