A Multicenter Retrospective Analysis on the Etiology of Bradycardia in COVID-19 Patients

Umeh, Chukwuemeka A.; Giberson, Curren; Kumar, Sabina; Aseri, Mahendra; Barve, Pranav

doi:10.7759/cureus.21294

Cited by 12 publications

(19 citation statements)

References 28 publications

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“…At difference with another study [ 13 ], where no correlation was found between RDV administration and bradycardia, in our analysis the occurrence of bradycardia was statistically greater in RDV-treated patients compared to the CTR group. This observation suggests a possible causal association between RDV administration and the occurrence of bradycardia, which could not be totally explained by SARS-CoV-2 infection or hospital stay.…”

Section: Discussioncontrasting

confidence: 99%

“…This observation suggests a possible causal association between RDV administration and the occurrence of bradycardia, which could not be totally explained by SARS-CoV-2 infection or hospital stay. The discrepancy with our finding could be due to the different patient selection criteria since the study by Umeh et al [13] was not specifically focused on RDV treatment, but on all the causes of bradycardia in COVID-19 patients, therefore patients treated with RDV and control patients were not matched. Our results are instead in agreement with two previous case-control studies [11,12], which reported an increased incidence of bradycardia in the group of patients treated with RDV although with different percentages probably due to the different HR monitoring methods: Attena et al [11] considered the HR at the day of the hospitalization and at day fifth of RDV therapy, while Pallotto et al [12] considered the days of RDV treatment, as we did, however, without considering the following five day.…”

Section: Discussioncontrasting

confidence: 92%

“…In a subsequent study by Pallotto et al, this observation was confirmed, however the overall incidence of bradycardia was higher than in the Attena study (46.8% vs 27.8%) [ 12 ]. Another retrospective study on the etiology of bradycardia in COVID-19 patients reported that the use of RDV was not associated with cardiac events [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Remdesivir-induced bradycardia in patients hospitalized with SARS-CoV2 infection: a possible vagally-mediated mechanism

et al. 2022

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Recently, case series studies on patients with SARS-CoV-2 infection reported an association between remdesivir (RDV) administration and incidental bradycardia. However, the phenomenon has not yet been described in detail. We conducted a retrospective case–control study to evaluate the occurrence of RDV‐related bradycardia in patients hospitalized for SARS-CoV2 pneumoniae. We retrospectively evaluated 71 patients, hospitalized in six internal medicine wards of the Milan area, affected by mild-to-moderate COVID-19 who received RDV (RDV group) and 54 controls, matched for sex, age and disease severity on admission (CTR group). The mean heart rate value recorded during the first two days of hospitalization was considered as baseline heart rate (HRb). Heart rate values relative to the 5-days treatment and the 5-days post-treatment were extracted for RDV group, while heart rate values relative to 10 days of hospitalization were considered for the CTR group. ΔHR values were calculated as maximum HR drop versus HRb. Possible associations between ΔHR and clinical-demographic factors were assessed through regression analysis. The RDV group experienced a significantly higher incidence of bradycardia compared to the CTR group (56% vs 33%, OR 2.6, 95% CI 1.2–5.4, p value = 0.011). Moreover, the RDV group showed higher ΔHR values than the CTR group. The HR progressively decreased with daily administration of RDV, reaching the maximun drop on day six (–8.6±1.9 bpm). In RDV group, patients who experienced bradycardia had higher drop in HR, higher alanine aminotransferase (ALT) values at the baseline (bALT) and during the RDV administration period. ΔHR was positively associated with HRb ( β = 0.772, p < 0.001) and bALT ( β = 0.245, p = 0.005). In conclusion, our results confirmed a significant association between RDV administration and development of bradycardia. This effect was proportional to baseline HR and was associated with higher levels of baseline ALT, suggesting a possible interaction between RDV liver metabolism and a vagally-mediated effect on HR due to increased availability of RDV metabolites.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 92%

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Remdesivir-induced bradycardia in patients hospitalized with SARS-CoV2 infection: a possible vagally-mediated mechanism

et al. 2022

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“…showed that the incidence of bradycardia was associated with length of hospital stay (OR: 1.071, 95% CI: 1.049-1.094), mortality (OR: 1.600, 95% CI: 1.070-2.394), ventilator use (OR: 0.470, 95% CI: 0.298-0.742), and steroid use (OR: 0.559, 95% CI: 0.402-0.776), whereas remdesivir treatment did not reveal any signi cant difference [23]. Consistent with our results, the multivariate analysis of Umeh et al's study revealed that remdesivir treatment was not associated with bradycardia, suggesting that the hypothesis on the association between remdesivir treatment and bradycardia may have been affected by other confounding factors.…”

Section: Discussionmentioning

confidence: 89%

The Risk Factor for Bradycardia in COVID-19 Patients: A Potential Harm of Steroid Treatment

Ogiwara

Ihara

Haba

et al. 2022

Preprint

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The coronavirus disease 2019 (COVID-19) is a condition caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) which first emerged in December 2019. Although several papers have reported the presence bradycardia in patients with COVID-19, the pathophysiology behind this remains unclear. Therefore, we investigated the presence of bradycardia in patients with COVID-19. A total of 153 patients with COVID-19 and 90 patients with influenza who were hospitalized in our hospital from January 1, 2020 to December 31, 2021 and from January 1, 2014 to December 31, 2021, respectively, were enrolled. After adjustment, the incidence of bradycardia and steroid use in patients with COVID-19 were significantly higher than those in patients with influenza (P-value = 0.0067 and P-value = 0.0003, respectively). We then compared the detailed characteristics of patients with COVID-19 to evaluate risk factors for bradycardia. Multivariate logistic regression analysis revealed that steroid use was significantly related to bradycardia (P-value = 0.031; odds ratio [OR]: 3.67; 95% confidence interval [CI]: 1.12–11.96). Overall, results showed a higher incidence of bradycardia in patients with COVID-19 who received steroid treatment. To the best of our knowledge, this is the first report to discuss the potential risk of excessive steroid use patients with COVID-19.

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“…Compared to placebo, a number of randomized controlled trials have observed a reduction in LOS and increased hospital discharge rates in patients receiving remdesivir [ 14 , 50 , 51 ]. However, this potential benefit has been challenged in follow-up studies [ 52 – 55 ] under the pretense that completing the full therapeutic course may be taking precedence over earlier discharges in otherwise recovering patients [ 56 – 59 ]. In relation to bradycardia, one study observed extended hospital stays in COVID-19 patients with bradycardia [ 58 ], while another found similar LOS between RAB and non-RAB patients [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Implications of Bradycardia in COVID-19 Patients Treated with Remdesivir: A Single-Center Retrospective Cohort Study

Schreiber

Bauzon

Batra³

et al. 2022

Clin Drug Investig

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Background and Objectives Remdesivir is an antiviral drug used to treat coronavirus disease 2019 (COVID-19) with a relatively obscure cardiac effect profile. Previous studies have reported bradycardia associated with remdesivir, but few have examined its clinical characteristics. The objective of this study was to investigate remdesivir associated bradycardia and its associated clinical characteristics and outcomes. Methods This is a single-institution retrospective study that investigated bradycardia in 600 patients who received remdesivir for treatment of COVID-19. A total of 375 patients were included in the study after screening for other known causes of bradycardia (atrioventricular [AV] nodal blockers). All patients were analyzed for episodes of bradycardia from when remdesivir was initiated up to 5 days after completion, a time frame based on the drug’s putative elimination half-life. Univariate and multivariate statistical tests were conducted to analyze the data. Results The mean age of the sample was 56.63 ± 13.23 years. Of patients who met inclusion criteria, 49% were found to have bradycardia within 5 days of remdesivir administration. Compared to the cohort without a documented bradycardic episode, patients with bradycardia were significantly more likely to experience inpatient mortality (22% vs 12%, p = 0.01). The patients with bradycardia were found to have marginally higher serum D-dimer levels (5.2 vs 3.4 µg/mL, p = 0.05) and were more likely to undergo endotracheal intubation (28% vs 14%, p = 0.008). Male sex, hyperlipidemia, and bradycardia within 5 days of completing remdesivir were significant predictors of inpatient mortality. No significant differences in length of stay were found. Conclusions Bradycardia that occurs during or shortly after remdesivir treatment in COVID-19 patients may be associated with an increased rate of in-hospital mortality. However, COVID-19 and its cardiac complications cannot be excluded as potential contributors of bradycardia in the present study. Future studies are needed to further delineate the cardiac characteristics of COVID-19 and remdesivir. Supplementary Information The online version contains supplementary material available at 10.1007/s40261-022-01187-x.

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A Multicenter Retrospective Analysis on the Etiology of Bradycardia in COVID-19 Patients

Cited by 12 publications

References 28 publications

Remdesivir-induced bradycardia in patients hospitalized with SARS-CoV2 infection: a possible vagally-mediated mechanism

Remdesivir-induced bradycardia in patients hospitalized with SARS-CoV2 infection: a possible vagally-mediated mechanism

The Risk Factor for Bradycardia in COVID-19 Patients: A Potential Harm of Steroid Treatment

Clinical Characteristics and Implications of Bradycardia in COVID-19 Patients Treated with Remdesivir: A Single-Center Retrospective Cohort Study

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