Sinus bradycardia during COVID-19: Cases report

December 2019 marked the history of modern medicine and a new chapter began to be written focusing on the emergence ofa new disease called COVID-19. Globally, there have been more than 140 million people infected with the virus and more than three million deaths due to this disease, declared a pandemic in 2020. COVID-19, characterized by a dominant presence ofrespiratory symptoms, has demonstrated its capacity to affect the cardiovascular system with the appearance of cardiac arrhythmias, myocarditis, heart failure and acute coronary syndrome;which contributed to the poor prognosis of the disease. This article presents two cases with sinus bradycardia during the course of COVID-19, an arrhythmia described in some of the SARS-CoV-2 infected cases.

The arrhythmic events and short-term cardiovascular outcomes in patients hospitalized with COVID-19 infection in Taiwan

Objective: The aim of this study is to investigate the arrhythmic events and short-term cardiovascular (CV) outcomes in patients hospitalized with COVID-19 infection in a single Taiwan tertiary center. Method(s): A retrospective study was carried out on 186 confirmed COVID-19 infection patients admitted to our hospital between May, 2021 and September, 2021. We investigate their CV symptoms, vital signs, laboratory examinations, arrhythmic events, and major adverse cardiovascular events (MACE), including ischemic stroke or systemic embolism, myocardial infarction, CV death, and heart failure (HF) during hospitalization. Result(s): During the hospitalization, 29.6% of patients had an elevation of cardiac enzymes, 67.2% had an elevation of d-dimer level, and 7.5% had abnormal NT-pro BNP level. The most common recorded arrhythmia is sinus tachycardia (22%), followed by atrial arrhythmia (12.4%, including atrial fibrillation 7.0%), sinus bradycardia (3.2%), ventricular arrhythmia (1.6%), and paroxysmal supraventricular tachycardia (1.1%). A total of 68 patients (36.6%) had arrhythmic events during hospitalization. During the mean follow-up of 2.8 months, 17 patients (9.1%) developed MACE, including 6 ischemic strokes, one pulmonary embolism, one peripheral artery occlusive disease, 3 HF, and 7 CV death. The total mortality rate is 19.9%. The hospitalized patients with arrhythmic events were associated with a higher incidence of intubation (32% vs 15%, p = 0.0062), MACE (22% vs 2%, p < 0.001), and mortality (37% vs 10%, p < 0.001) than those without arrhythmic events. Conclusion(s): The patients hospitalized with COVID-19 infection were associated with higher CV manifestations and arrhythmic events in Taiwan. Those patients with arrhythmic events were associated with higher morbidity and mortality.

Pseudo-ventricular tachycardia- Diagnostic enigma in the emergency department: A case report

Ventricular tachycardia (VT) is a type of broad complex tachycardia originating from a focus in the ventricle. It is one of the four important rhythms which can lead to cardiac arrest. Accurate and timely diagnosis of true VT is the cornerstone for proper management in the emergency department (ED). We present an interesting case of an electrocardiographic artifact mimicking VT, which led to a diagnostic dilemma in the ED.Copyright © 2023 Rehman, Albaroudi, Akram, Ahmad, licensee HBKU Press.

Symptomatic Bradycardia in Covid-19 Hospitalized Patients: A Case Series.

SARS COV-2 infection has become a global threat. Cardiovascular manifestations associated with Covid-19 have been noted in several publications, and bradycardia related to Covid-19 is a commonly reported complication. This study reports six serial cases of bradycardia attributable to Covid-19; four of them developed complete atrioventricular block. These patients experienced clinical symptoms related to bradycardia and initially required permanent pacemaker implantation. However, one patient did not require permanent pacing later on due to spontaneous conversion to sinus rhythm. In comparison, the other two patients who developed transient sinus bradycardia experienced a self-limiting condition during their hospitalization period without requiring any cardiac pacing device or medication to increase heart rate. Complete atrioventricular block and transient sinus bradycardia in these patients, despite not having any history of bradycardia, might be due to complex processes in the systemic inflammatory response in Covid-19. Cardiac monitoring, hemodynamic evaluation, and strategy for permanent pacemaker in these patients should be treated on a case-by-case basis.

Our experience of using Dexmedetomidine-Propofol sedation in patients undergoing treatment planning Magnetic resonance imaging scan for Deep brain stimulator insertion surgery during Covid 19 pandemic

Introduction: Patients undergoing Deep brain stimulator (DBS) insertion require a high-resolution MRI for treatment planning prior to DBS surgery. This group of patients has movement disorders therefore traditionally the planning MRI is done under General anaesthesia to ensure patient immobility and to obtain good quality MRI images. Providing sedation/anaesthesia for MRI procedure during COVID-19 pandemic was challenging. When we restarted elective surgery during Covid-19 pandemic we were worried about aerosol generating procedures, therefore we looked at the feasibility of using Dexmedetomidine-Propofol sedation for treatment planning MRI as an alternative to General anaesthesia to prevent aerosol generating procedure. Method(s): We conducted retrospective review of anaesthetic records of all patients who underwent MRI under sedation for DBS planning from August 2020 to July 2021. We collected the data on patient demographics, Indication & target site for DBS, duration of sedation, complications during the scan, cardiovascular side effects like hypotension and bradycardia during scan, quality of image, duration of PACU stay and post scan complications. The quality of MRI imaging was assessed by the neurosurgeon who did the treatment planning. Sedation protocol: sedation was commenced with Propofol target controlled infusion (TCI) using Schneider model with effector site concentration (Cet) of 2 to 3 and Dexmedetomidine bolus dose of 1 microgram per kilogram was infused over 10 minutes. All the patients were induced to a Ramsay Sedation Scale of at least 5 or 6. Sedation was maintained with Dexmedetomidine infusion at 0.5 mcg/kg/hr and Propofol TCI (Schneider model Cet of 2 mcg/mL). Result(s): During our study period 15 patients underwent MRI under sedation with Propofol-Dexmedetomidine for DBS treatment planning. Of this 7 were males and 8 were females. Age range was from 39 to 75 years. The target site was Subthalamic nucleus in 9 patients, Thalamic nuclei in 4 patients and Globus pallidus internus in 2 patients. Duration of sedation ranged from 40 minutes to 100 minutes with a median of 45 minutes. 2 patients developed movement artefacts during scanning and were converted to GA, 3 patients developed hypotension (20% reduction from pre-induction blood pressure) requiring treatment with ephedrine. Five patients had sinus bradycardia (20% reduction from pre-induction heart rate) but did not require treatment. The qualities of images were classified as good in 11 patients and acceptable in 2 patients by the neurosurgeon involved in treatment planning. None of the patients needed repeat MRI scanning. Patient's stay in PACU ranged from 20-50 minutes with a mean of 26.5 minutes. Discussion(s): Dexmedetomidine-Propofol sedation has been widely used for sedation to perform MRI scans in paediatric patients, its use in adult patients is not well documented in the literature. Propofol enables smooth induction of sedation and rapid recovery however it may cause hypotension, decreased respiratory drive and upper airway obstruction. Dexmedetomidine has been used as a single sedative agent for MRI however its onset of action is slow and when used as a sole sedative agent large dose of dexmedetomidine is required and this may contribute to delayed recovery after sedation. Propofol-Dexmedetomidine combination has synergistic effects and is advantageous. Propofol can induce sedation smoothly, Dexmedetomidine can reduce dose required for sedation and suppression of motor response in healthy subjects (1). Combination of Dexmedetomidine- Propofol infusion reduced total Propofol dose and decreased the incidence of airway complications in a paediatric study (2). During our study period 2 patients sedation were converted to General anaesthesia, both patients had raised BMI and had laboured breathing under sedation causing transmitted head movement, therefore patient selection is important for successful scan under sedation. Propofol-Dexmedetomidine sedation can be used safely for treatment planning MRI in selective movement disorder patients.

Stop and smell the onions: Case report of delayed cardiotoxicity post ingestion of veratrum viride

Background: Vertatrum viride (false hellebore) is a perennial commonly found in eastern North America. The most common cause of exposure is misidentification when foraging for wild onion, or skunk cabbage. One regional poison center saw an increase in foraging-related poisonings during initial COVID-19 restrictions. The case report highlights severe delayed cardiac effects after ingestion of Veratrum viride in an otherwise healthy, young, female athlete. Case report: A 24-year-old female presented to an emergency room alongside family with complaints of nausea and vomiting that started 30 min after a meal consisting of foraged wild onion (Allium triccocum). Five others ate the same meal and noted similar symptoms. Vitals upon arrival (3 h post ingestion) are as described: HR 51, BP 88/52, Temp 36.7, RR 18 and O2 sat 100% on room air. The patient had no previous cardiac history and was athletic. Management included D5LR with K replacement, and dopamine infusion at 10mcg/kg/min. Dopamine was tapered slowly, down to 6 mcg/kg/min at 16.5 h. Vitals continued to be stable at 17.5 h post ingestion and dopamine was discontinued. The patient developed severe bradydysrhythmia 15 min later, consisting of complete heart block leading to prolonged sinus pause. She responded to 10 s of CPR with return of spontaneous circulation with a junctional escape rhythm which reverted back to sinus bradycardia. A repeat EKG was unremarkable. The dopamine infusion was reinstituted at 4 mcg/kg/min and continued until 26.5 h post ingestion. She was monitored an additional 9.5 h, and remained in sinus rhythm with mild complaints of dizziness that resolved before discharge. Discussion(s): Veratrum spp. toxicity is due to alkaloids found throughout the plant which cause sodium channel opening when bound to type 2 sodium channels. By increasing sodium ion influx during the resting potential and delaying inactivation to create a late sodium current, these alkaloids increase automaticity in conductive cells. This mechanism, paired with the Bezold-Jarisch reflex, is likely responsible for increased vagal tone leading to bradycardia, hypotension, sinus arrhythmia, and junctional escape rhythm. It is noteworthy that even 18 h post ingestion in a relatively stable patient with no significant cardiac history, cardiac arrest occurred just after treatment tapering. Clinicians should consider prolonged observation time in the setting of discontinuation of vasopressors. Conclusion(s): Both clinicians and amateur foragers should be aware of the risks associated with ingestion of Veratrum viride, especially during early spring when it more closely resembles wild onion. While uncommon, significant delayed cardiac effects are possible. Mistaking the plant for edible wild onions can be the difference between a delectable dinner, and a night in the ICU.

Cardiovascular manifestation in multisystem inflammatory syndrome in children temporally associated with COVID-19-single center experience

Background and Aim: Cardiovascular manifestations are common (35-100%) in multisystem inflammatory syndrome in children (MIS-C), including ventricular dysfunction, shock, coronary artery dilation, pericardial effusion and conduction abnormalities. Our study aimed to analyse cardiovascular involvement in our patients with MIS-C treated in our hospital. Method(s): The retrospective cohort study included all patients with MIS-C treated from April 2020 to December 2021 in the Mother and Child Health Institute of Serbia. In every case, cardiovascular manifestations were analysed: ventricular dysfunction, coronary artery dilatation, pericardial effusion, shock and ECG changes. Result(s): The study included 77 patients, 45 boys and 32 girls, aver-age years of age 9.3 +/- 4.8. Elevated cardiac troponin I and pro-BNP were observed in 35.9% and 87.8% of patients, respectively. Myocardial dysfunction was observed in half of our patients (50.6%), with an average ejection fraction of 50.5 +/- 8.9%. Children older than 10 years had 4 times higher chances for myo-cardial dysfunction (OR 4.3, 95%CI 1.6-10.8;p = 0.003). Shock syndrome had 21.1% of children on admission, while 5.3% devel-oped shock during the in-hospital stay. Transient coronary artery (CA) dilatation was observed in 6.5% of patients;left CA in 3 pts (Z score +2,95 +/- 0.3), right CA in one patient (Z score +2), and in one LCA and RCA (RCA Z score 2.6). Transient CA dilatations were observed only in patients with KD-like clinical presentation (5/54 pts). Mild pericardial effusion with spontaneous resolution was detected in 28.6% of children, while one female adolescent had severe pericardial effusion with threatening cardiac tamponade. On the standard ECG, 53% of children had negative T wave in inferior or/and precordial leads averagely on day 2 (IQR 1-3 day);transient QTc prolongation was registered in 46% of patients, averagely on day 7 (IQR 5-9). Sinus bradycardia and coronary rhythm were registered in 42.1% of patients, while premature ven-tricular beats were observed in 2.7% of pts. left ventricle thrombus was detected in one patient with normal echocardiography find-ing. In this patient, increased activity of Factor VIII and XII was proven. Conclusion(s): Cardiac manifestations are common and potentially life-threatening in MIS-C and should be assessed for at presenta-tion and during the clinical course as indicated.

TIME TO SLOW DOWN: A DEEPER LOOK INTO REMDESIVIR-ASSOCIATED BRADYCARDIA

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The use of remdesivir in critical care setting has been utilized treatment of covid, but not without risk. Many cases have reported severe cardiac effects with bradycardia being the most common. CASE PRESENTATION: The patient was a 15-year-old female with a history of asthma, hyperinsulinemia who required hospitalization for acute hypoxic respiratory failure secondary to COVID-19 pneumonia. She received ceftriaxone, azithromycin, and a 10-day course of remdesivir (RDV). On her third day of admission, the patient developed significant sinus bradycardic with heart rate nadir of 30-40 bpm but denied any symptoms. She completed her remdesivir course on day five of hospitalization and was discharged on day nine with a heart rate of 47 bpm. She later presented to ED the night of discharge following acute onset of lightheadedness and blurry vision at home secondary to orthostatic hypotension and bradycardia. Her pulse was 48 bpm, temperature 36.1 C, respirations 24/min, blood pressure 119/50 mmHg and SpO2 99% on room air. Her physical exam was unremarkable. EKG showed sinus bradycardia with a PR interval of 124 ms and QTc of 406 ms. Echocardiogram showed normal cardiac anatomy and function. Patient was diagnosed with persistent RDV-associated bradycardia and discharged home with a Holter monitor and cardiology follow-up. Bradycardia resolved by her follow-up visit two weeks later. DISCUSSION: According to the WHO pharmacovigilance database, bradycardia is a relatively new adverse effect and 3.6% of the 2,603 adverse effects reported since the onset of the pandemic, with 2 million RDV doses administered during this time [1]. The mechanism of RDV-associated bradycardia is proposed to be an effect of adenosine triphosphate, an active metabolite, which reduces SA node automaticity via stimulation of vagal nerve, as well as RDV cross-reactivity with mRNA polymerase, leading to cardiotoxicity that usually resolves within 24 hours of medication discontinuation. In our patient's case bradycardia did not resolve until eight days after discontinuation of medication [2]. Review of previously case reports does not identify any association with patient age but could be related to timing of when medication reaches therapeutic window, as many patients had onset of bradycardia on day 3 of treatment [3]. We report a pediatric case of severe acute COVID-19 who developed sinus bradycardia on day 3 of RDV treatment as previously described, but the bradycardia persisted long after the discontinuation of RDV. CONCLUSIONS: With over 50 thousand pediatric COVID-19 hospitalizations to date, this case serves as a timely reminder that medication side effects should be monitored closely, and that more research needs to be done into the effects of RDV on cardiac function in pediatric patients. Reference #1: Jung SY, Kim MS, Li H, Lee KH, Koyanagi A, Solmi M, Kronbichler A, Dragioti E, Tizaoui K, Cargnin S, Terrazzino S, Hong SH, Abou Ghayda R, Kim NK, Chung SK, Jacob L, Salem JE, Yon DK, Lee SW, Kostev K, Kim AY, Jung JW, Choi JY, Shin JS, Park SJ, Choi SW, Ban K, Moon SH, Go YY, Shin JI, Smith L. Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database. Clin Transl Sci. 2022 Feb;15(2):501-513. doi: 10.1111/cts.13168. Epub 2021 Oct 31. PMID: 34719115;PMCID: PMC8841455. Reference #2: Touafchia A, Bagheri H, Carrié D, Durrieu G, Sommet A, Chouchana L, Montastruc F. Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns. Clin Microbiol Infect. 2021 Feb 27;27(5):791.e5–8. doi: 10.1016/j.cmi.2021.02.013. Epub ahead of print. PMID: 33647441;PMCID: PMC7910147. Reference #3: Rau, Cornelius MPhil;Apostolidou, Sofia MD;Singer, Dominique MD, PhD;Avataneo, Valeria PhD;Kobbe, Robin MD Remdesivir, Sinus Bradycardia and Therapeutic Drug Monitoring in Children With Severe CO

REMDESIVIR-ASSOCIATED ASYMPTOMATIC BRADYCARDIA IN AN ICU PATIENT ON DEXAMETHASONE FOR COVID-19

SESSION TITLE: Cardiovascular Complications in Patients with COVID-19 SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Even though COVID-19 is the largest pandemic of the twenty-first century, little is known about the disease or its management. Remdesivir has demonstrated some activity against severe ARDS associated with COVID-19. There is a dearth of data on the adverse effects of Remdesivir. We report a case of a COVID-19 patient who developed bradycardia following the administration of Remdesivir. CASE PRESENTATION: A 64-year-old man, who tested positive for COVID-19, presented with shortness of breath (SOB) for a week. SOB was accompanied by a cough with tan-colored sputum. Past medical history included hypertension and benign prostatic hyperplasia. Physical examination showed regular rate and rhythm of the heart and diffusely decreased breath sounds. His blood pressure was 104/60 mmHg and his heart rate was 80 bpm. Oxygen saturation was 58% at room air. Significant lab results showed elevated CRP: 17.13 mg/dl, D-Dimer: 10.16 ug/mL FEU, Lactic acid: 2.5 mg/dl, Creatinine: 1.8 mg/dl, BUN: 60 mg/dl, and AST: 46 U/L. Chest x-ray showed bilateral patchy interstitial airspace opacities. Calculated Well's score of 3 indicated a moderate risk for pulmonary embolism. CT scan showed moderate bilateral diffuse areas of ground-glass lung consolidation concerning diffuse atypical infection. The patient was admitted to the ICU and started on CPAP with PEEP of 12 and FiO2 of 100%. The management included dexamethasone 6 mg oral for 10 days, Remdesivir for 5 days, and Tocilizumab given elevated CRP level. The patient was found to develop asymptomatic bradycardia with a heart rate as low as 40 bpm. An EKG obtained demonstrated sinus bradycardia without any heart block. Echocardiography showed mildly dilated right ventricle & mild aortic regurgitation. Bradycardia resolved after the last dose of Remdesivir. DISCUSSION: Remdesivir is frequently used in severe COVID-19 infections. The commonly reported adverse events affect the gastrointestinal and renal systems. The reported cardiovascular adverse events include hypotension, atrial fibrillation, and cardiac arrest. However, bradycardia is becoming increasingly encountered. Although corticosteroids are known to cause bradycardia, the patient we managed developed bradycardia following remdesivir therapy. The baseline EKG was normal and the history was non-contributory. Given the asymptomatic nature of the finding, cardiac monitoring alone sufficed. The heart rate picked up following the last dose of remdesivir further suggesting its causative role. CONCLUSIONS: Bradycardia is becoming more common with Remdesivir use. If the patient is not exhibiting any symptoms, cardiac monitoring alone should suffice;bradycardia is expected to resolve when the drug is stopped. Reference #1: Elsawah HK, Elsokary MA, Abdallah MS, ElShafie AH. Efficacy and safety of remdesivir in hospitalized Covid-19 patients: Systematic review and meta-analysis including network meta-analysis. Rev Med Virol. 2021;31(4):e2187. Reference #2: Taqi M, Gillani SFUHS, Tariq M, Raza ZA, Haider MZ. Current updates on clinical management of COVID-19 infectees: a narrative review. Rev Assoc Med Bras (1992). 2021 Aug;67(8):1198-1203. doi: 10.1590/1806-9282.20210582. PMID: 34669870. DISCLOSURES: No relevant relationships by AISHA ADIGUN No relevant relationships by Mobeen Haider No relevant relationships by Yousra Khalid No relevant relationships by Muhammad Hasib Khalil No relevant relationships by Aleena Naeem No relevant relationships by Zarlakhta Zamani

CASE SERIES OF SEVERE BRADYCARDIA IN COVID-19 PATIENTS: AN UNUSUAL CARDIAC MANIFESTATION

SESSION TITLE: Cardiovascular Complications in Patients with COVID-19 SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Cardiac manifestations of coronavirus disease 2019 (COVID-19) including bradyarrhythmias (BA) are well documented. Postulated mechanisms include direct myocardial injury through viral invasion, myocyte hypoxia, angiotensin-II receptor downregulation, hypercytokinemia and medication-related adverse events. Currently, there are no clear guidelines on the management of severe BA in the setting of COVID-19, including the threshold for permanent pacemaker (PPM) placement. We present a retrospective case series involving five COVID-19 patients with no prior history of cardiovascular disease, who developed severe BA of heart rate < 45 beats per minute. CASE PRESENTATION: Three females and two males were included in the series, with a median age of 50 years (IQR 36-61.5). Sinus bradycardia and high degree heart block were seen in two patients each. Most of the patients were noted to have sinus pauses. Inflammatory markers including D-dimer, LDH, and CRP were elevated. The median CRP in our patients was 106 mg/L (IQR 83.2-208.1) and median D-dimer was 5.63 ug/ml (IQR 1.8-13.2). All patients were treated with dexamethasone and remdesivir. However only one patient was on remdesivir on the day of onset of bradycardia. Four patients were critically ill, requiring ICU care with mechanical ventilation. Two patients required temporary transvenous pacing, one was supported on extracorporeal membrane oxygenation, and one was given atropine. No patient required PPM placement. Two deaths were observed but were not due to BA. DISCUSSION: In this single center, retrospective case series, 5 patients with COVID-19 infection developed severe BA prompting intervention. Laboratory findings demonstrated significantly elevated inflammatory markers in all our patients. The median CRP and D-Dimer in our patients was higher than the median inflammatory markers seen in a systematic review of patients with COVID-19 associated bradycardia showing that the patients in our series were suffering from severe inflammatory state. It was also observed that despite having no prior cardiac history, those more critically ill with COVID-19 infection developed severe BA requiring intervention. Conservative management and reversal of the underlying etiology prevented need for PPM implantation despite two patients developing high-grade atrioventricular-block, and one recurrent asystole. CONCLUSIONS: This preliminary data suggests that even severe BA that develops after COVID-19 infection may not require PPM placement. Further studies are required to elucidate implications, assess the reversibility, and clarify potential therapeutic targets including the indications for PPM in COVID-19 associated bradycardia. Reference #1: Nagamine, Todd et al. "Characteristics of bradyarrhythmia in patients with COVID-19: Systematic scoping review.” Pacing and clinical electrophysiology : PACE, 10.1111/pace.14466. 19 Feb. 2022, doi:10.1111/pace.14466 Reference #2: Chinitz, Jason S et al. "Bradyarrhythmias in patients with COVID-19: Marker of poor prognosis?.” Pacing and clinical electrophysiology : PACE vol. 43,10 (2020): 1199-1204. doi:10.1111/pace.14042 DISCLOSURES: No relevant relationships by Dipanjan Banerjee No relevant relationships by Monika Bernas No relevant relationships by Sandeep Randhawa No relevant relationships by Parthav Shah

Bradyarrhythmia After Remdesivir Administration in SARS-CoV-2: A Review of Literature and Meta-Analysis of Observational Studies in Epidemiology.

Background: The coronavirus disease 2019 (COVID-19) pandemic has required timely and informed decisions about treatment recommendations for clinical practice. One such drug used for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is remdesivir (RDV), and several cardiac side effects have been reported including bradyarrhythmia (e.g., transient sinus bradycardia, symptomatic sinus bradycardia, complete atrioventricular (AV) block). The current study aimed to explore the association between RDV treatment for SARS-CoV-2 infection and the risk of bradyarrhythmia by presenting a review and meta-analysis of available published studies. Methods: We presented a review of published literature and meta-analysis of observational studies (MOOSE). A narrative summary of RDV and bradyarrhythmia in COVID-19 infection and pooled analysis of observational studies that meet inclusion criteria was included. Studies included were published between January 2020 and December 2021 (identified through PubMed and ScienceDirect) and examined the association between treatment with RDV in SARS-CoV-2 infection and the risk of bradyarrhythmia. Results: Three studies (two retrospective cohort studies and one prospective cohort study) met inclusion criteria for pooled meta-analysis of bradyarrhythmia and RDV therapy in COVID-19 patients. Treatment with RDV was associated with increased risk of sinus bradycardia when compared to controls (odds ratio 3.27 (95% confidence interval 1.90 - 5.63)). In the pooled analysis, the incidence of bradycardia in those that received RDV was 34.07% vs. 18.13% among controls. Thirteen case reports, three case series, and three disproportionality analyses were identified in review of the literature. Conclusion: Data from real-world observational studies suggest that treating COVID-19 patients with RDV may predispose the development of bradyarrhythmia. The importance of this observation is of uncertain clinical significance as some observational studies have reported more favorable outcomes among patients who experience bradycardia after RDV therapy. The current study is limited by the small number of studies that could be meaningfully pooled and more well-designed cohort studies are needed to explore this association.

Prevalence and impact of dysrhythmias in COVID-19 intensive care patients

Background: The COVID-19 pandemic has had a dramatic impact on clinical practice, amounting to more emergency department and intensive care unit (ICU) admissions. Due to their frequent multiple comorbidities, management in the ICU is challenging. Early studies suggest that cardiac injury is frequent in hospitalized patients with COVID-19, and it is plausible that these patients have a higher risk of cardiac dysrhythmias. Purpose: To determine the prevalence of dysrhythmias in ICU patients with COVID-19 pneumonia, identify major predictors and determine the impact on in-hospital mortality. Methods: A retrospective study of 98 consecutive patients with COVID-19 Pneumonia admitted to the ICU of a tertiary hospital in 2020. The main outcome was dysrhythmias (including significant bradycardia, high/slow ventricular rate or new-onset atrial fibrillation (AF) or atrial flutter, other supraventricular tachycardias, ventricular tachycardia and ventricular fibrillation). Significant bradycardia was defined as heart rate lower than 40 or need of treatment. Sociodemographic variables and clinical data were retrieved for each patient, severity scores at admission (Apache II, SOFA and SAPS II), number of days on mechanical ventilation or high-flow oxygen and placement on Venovenous Extracorporeal Membrane Oxygenation (ECMO) or prone position were recorded. Statistical comparison was made between groups, including logistic regression adjusting for confounding variables. Results: The most frequent arrhythmia was significant sinus bradycardia (28, 28.5%) followed by high ventricular rate AF (14, 14.2%). Patients who had dysrhythmias were older (66.24 ± 10.13 vs 60.85 ± 12.69 years, p 0.024), more severe (SAPS II score 42.55 ± 11.08 vs 35.98 ± 11.26, p 0.006), had more atrial fibrillation (AF) (p 0.022), had higher maximum C-reactive protein (mCRP) (6.56 ± 2.68 vs 6.24 vs 2.86, p 0.009), were mechanically ventilated for a longer time (15.64 ± 13.18 vs 8.92 ± 8.85 days, p 0.004), had longer intubation time (14.52 ± 9.39 vs 8.70 ± 8.21 days, p 0.002) and had higher usage of dexamethasone (p 0.042) and prone position (p 0.016). When adjusted for confounding variables, prone was the most significant predictor (OR 2.800;95% CI 1.203-6.516) followed by use of dexamethasone (OR 2.484;95% CI 1.020-6.050). Days intubated, days on mechanical ventilation, age, mCRP and SAPS II on admission were also predictors of dysrhythmia. Regarding mortality, patients with arrhythmic events had a tendency for greater in-hospital death (OR 2.440;95% CI 0.950-6.310;p 0.065). Conclusions: COVID-19 ICU patients are a subset of patients at risk of cardiac arrhythmias. Use of prone position was the main contributor to these events, but clinical history, severity and treatment may also play an important role. Efforts must be made to optimize ventilatory support and treatment in order to reduce the risk of dysrhythmias. (Figure Presented).

Temporary sinus bradycardia and COVID-19 Report of a case and review of the bibliography

A cytokine storm, probably due to an imbalance in T-cell activation, could contribute to cardiovascular disease in COVID-19. Cohort studies estimated that 7-80% of hospitalized patients presented acute myocardial injury, with a greater expression in patients admitted to the intensive care unit vs. those who did not (22.2% vs. 2.0%), and in those who died vs. survivors (59% vs 1%). The first reports from China suggested an incidence of arrhythmias in hospitalized patients of 17%, rising in critical care to 44%. We present the case of a patient with a positive swab for SARS-CoV-2 infection with an interstitial-alveolar parenchymal infiltrate distributed in a genera-lized way in both lung fields, who required respiratory mechanical assistance. On the fourth day of hospitalization, he developed sinus bradycardia, requiring treatment with atropine and infu-sion of isoproterenol, resolving the clinical picture after 24 hours. The causal mechanism of sinus bradycardia is not exactly known, it is believed that it could be multifactorial, including severe hypoxia, hypotension, intrinsic imbalances of the autonomic nervous system, alteration in the regulation of the angiotensin-converting enzyme 2, drug interactions and immune-inflammatory direct damage on the sinus node.

USE OF REMDESEVIR CAUSING SINUS BRADYCARDIA AND EVENTUALLY ASYMPTOMATIC MOBITZ TYPE 1 ATRIOVENTRICULAR BLOCK

Background: Remdesivir has emerged as a novel treatment in hospitalized COVID19 patients not requiring mechanical ventilation. Though there have been several case reports of remdesivir-associated sinus bradycardia, this association is still unclear. Furthermore, remdesivir's interaction with beta blockers has not been studied. Case: A 70-year-old woman with apical hypertrophic cardiomyopathy (HCM), heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation (AF) status post ablation presented with shortness of breath. She was tachycardic to 115 beats per minute (BPM) and hypoxemic to the 80’s, requiring supplemental oxygen via a non-rebreather mask. She was found to have COVID19 pneumonia, for which dexamethasone and remdesivir were started. She developed marked bradycardia and eventually asymptomatic Mobitz type 1 atrioventricular block (AVB). Decision-making: Once COVID19 pneumonia was diagnosed, dexamethasone and remdesivir were started. She immediately became bradycardic and remdesivir and beta blockade were held. Of note, she was taking metoprolol succinate at home for HFrEF. Bradycardia and AVB resolved with cessation of remdesivir and she was discharged home safely on metoprolol succinate. Conclusion: Patients on remdesivir, especially those with underlying cardiomyopathy, are at higher risk for bradyarrhythmia. Remdesivir may potentiate the effects of beta blockers and their concomitant use requires judicious monitoring. [Formula presented]

Sinus bradycardia as a potential side effect of favipiravir treatment / Sinusbradycardia mint lehetséges favipiravir-mellékhatás.

Összefoglaló. A koronavírus-19-pandémia hatalmas kihívás az egészségügyi ellátórendszerek számára. A hatékony kezelés iránti igény felerosítette a terápiás megoldásokra való törekvéseket. Ennek egyik eleme a favipiravir hatóanyag széles köru ambuláns és intézeti alkalmazása. A gyógyszer biztonsági információi korlátozottan említik a lehetséges cardialis mellékhatásokat: mindösszesen az igen ritka mellékhatások között lelheto fel a "szívritmuszavar" megjegyzés. A közlemény a favipiravirkezeléshez kötheto átmeneti sinusbradycardia esetét ismerteti. Orv Hetil. 2022; 163(7): 267-270. Summary. The coronavirus pandemic is an enormously high challenge for medical health services worldwide. The demand for effective treatment amplified the pursuits for therapeutic solutions. One element of the possible treatment is the use of favipiravir in outpatient departments and hospitals. Safety information of favipiravir is limited with the risk of potential cardiac side effects: only the two words of "rhytm disturbances" can be found among the very rare side effects. This article describes the case of favipiravir-induced transient sinus bradycardia. Orv Hetil. 2022; 163(7): 267-270.

Arrhythmia in COVID-19.

The current outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) also known as coronavirus disease 2019 (COVID-19) has quickly progressed to a global pandemic. There are well-documented cardiac complications of COVID-19 in patients with and without prior cardiovascular disease. The cardiac complications include myocarditis, heart failure, and acute coronary syndrome resulting from coronary artery thrombosis or SARS-CoV-2-related plaque ruptures. There is growing evidence showing that arrhythmias are also one of the major complications. Myocardial inflammation caused by viral infection leads to electrophysiological and structural remodeling as a possible mechanism for arrhythmia. This could also be the mechanism through which SARS-CoV-2 leads to different arrhythmias. In this review article, we discuss arrhythmia manifestations in COVID-19.

Transient Sinus Bradycardia in Children with Multisystem Inflammatory Syndrome Associated with COVID-19

Objective: Multisystem inflammatory syndrome in children (MIS-C) may cause cardiovascular involvement and dysrhythmia. Although a variety of arrhythmias may be seen, sinus bradycardia was rarely reported. The aim of this study is to determine the frequency and clinical course of bradycardia in children with MIS-C. Material and Methods: Medical records of patients who were diag-nosed with MIS-C between August 2020 and March 2021 were retro-spectively evaluated. MIS-C diagnosis was made according to US Cen-ters for Disease Control and Prevention (CDC) criteria. All patients who had sinus bradycardia were included in the study. Results: Transient sinus bradycardia was observed in 7 of 40 (17.5%) patients (2 girls, 5 boys) with MIS-C. The median age was 10.8 years (range, 5.4-13.8 years). All patients were initially treated with intravenous immu-noglobulin (IVIG) and six out of the seven patients also received intravenous methylprednisolone (MPZ). Sinus bradycardia developed a median of four days (range, 2-6 days) after MIS-C diagnosis and continued for a median of four days (range, 2-6 days). In six of the seven patients, bra-dycardia was detected a median of 42 hours (range, 11-74 hours) after MPZ treatment and resolved a median of 36 hours (range, 20-50 hours) after tapering MPZ dosage. Electrocardiogram (ECG) of patients showed sinus bradycardia. All patients were asymptomatic and awake when bra-dycardia was observed. No patients had any underlying structural heart defect or electrolyte abnormalities. Bradycardia episodes resolved without any specific intervention. Conclusion: Sinus bradycardia may occur due to the cardiac involvement of MIS-C itself or as a possible side effect of MPZ therapy, which can resolve without any specific treatment.

COVID-19 and Cardiac Arrhythmias

Coronavirus disease-2019 (COVID-19) has impacted the global population, leading to a pandemic, the scale of which the world has never experienced before. This novel coronavirus not only involves the respiratory system, but also affects the heart, leading to significant morbidity and mortality. Arrhythmias in COVID-19 are increasingly being documented and seem to have a prognostic significance, especially in critically ill patients. In patients with COVID-19, a variety of arrhythmias have been reported, ranging from the benign to potentially life-threatening. Multiple mechanisms, such as myocarditis, hypoxia, electrolyte disturbances and QT interval-prolonging drugs (e.g. hydroxychloroquine), are responsible for arrhythmias in patients with COVID-19. The prevalence of cardiac arrhythmias in patients with COVID-19 ranges from 3.6% to 60%, with sinus tachycardia being the most common rhythm abnormality. Other rhythm abnormalities, such as sinus bradycardia, atrial arrhythmias and complete heart block, have also been reported. Malignant ventricular arrhythmias, especially in patients with COVID-19 with multiple comorbidities, portend a bad prognosis. Additionally, the use of QT interval-prolonging drugs, such as hydroxychloroquine or azithromycin, increases the risk of torsades de pointes. Hence, there is a need for continuous rhythm monitoring, with prompt recognition of arrhythmias in critically ill patients and those on QT-prolonging medications. Management of these arrhythmias is similar to those in patients without COVID-19, with a focus on correcting reversible causes and maintaining haemodynamic stability.

Sinus bradycardia in patients with severe CoViD-19

Aim of the study: Aim of this study was to analyse the relations between SB and severe CoViD-19 pneumonia (Pneumonia Severity Index >90). Materials and Methods: An observational retrospective study was performed by analyzing clinical, laboratory and instrumental features from 155 hospitalized patients for CoViD-19 pneumonia in our General Medicine and Semi-intensive Care Units. Results: Bradycardia (heart rate <60 bpm) was found in the 32.2% of the study population, as described in literature. Neither clinical and laboratory characteristics of myocardial damage, thyroid impairment or electrolytes abnormalities were diagnosed among these patients. This cohort of population had only a higher amount of smokers (p=0.001) and blood neutrophils count (p=0.032) without anymore differences compared to the cohort with normal heart rate. The incidence of bradycardia was same in patients treated by remdesivir or not (p=0.495). When viral nucleic acid tests turned negative, the SB disappears. Conclusions: Therefore we speculated that the inhibitory effect of SARS-CoV-2 on sinus node activity was the main cause of sinus bradycardia in these patients.

Cardiac arrhythmias 3 months after hospitalization for COVID-19

Background: The long-term frequencies of cardiac arrhythmias in hospitalized coronavirus disease 2019 (COVID-19) patients have not been thoroughly investigated. Purpose: To describe the prevalence of cardiac arrhythmias, 3-4 months after hospitalization for COVID-19. Methods and results: Participants with COVID-19 discharged from five large Norwegian hospitals were invited to participate in a prospective cohort study. We examined 201 participants (44% females, mean age 58.5 years) with 24-hour electrocardiogram 3-4 months after discharge. Body mass index (BMI) was 28.3±4.5 kg/m2 (mean ± SD), and obesity (BMI >30) was found in 70 participants (34%). Clinically significant arrhythmias were defined as;ventricular tachycardia (non-sustained or sustained), premature ventricular contractions (PVC) exceeding 200/24 h, or coupled PVC, atrial fibrillation/flutter, second-degree atrioventricular block (AV-block) type 2, complete AV-block, sinoatrial (SA) block exceeding 3 s, premature AVnodal beats in bigeminy, supraventricular tachycardia (SVT) exceeding 30 s, and sinus bradycardia with less than 30 beats/min. High-sensitive cardiac troponin T (hs-cTnT) was measured at the 3-month follow-up. Results: Cardiac arrhythmias were found in 27% (n=54) of the participants. Ventricular premature contractions and non-sustained ventricular tachycardia were the most common arrhythmias, found in 22% (n=44) of the participants. Premature ventricular contractions were the most frequent cardiac arrhythmia. More than 200 PVCs per day were observed in 37 participants (18%) with a mean of 1300 PVC/day, and in 35 (95%) of these participants, the PVCs were polymorphic. Among 10 patients experiencing NSVT, 5 participants had previous CVD, including coronary heart disease (n=1), 1 atrial fibrillation, 2 venous thromboembolism, 4 heart failure. Atrial fibrillation was found in seven patients (3%), none of them of new-onset. SA block >3 seconds was only observed in one patient, and no incidence of high degree AV block was discovered. Pre-existing cardiovascular disease or hypertension (CVDH) were reported in 40% (n=81) of the participants. The CVDH group had an increased amount of arrhythmia compared to the group free of CVDH (p=0.04). High PVCs showed a fair correlation with hs-cTnT levels at 3 months (ρ=0.21 p=0.048). Conclusions: Three months following hospital discharge with COVID-19, cardiac arrhythmia was found in every fourth participant and was associated with a higher concentration of hs-cTnT at 3 months. The clinical implications of persistent ventricular arrhythmia following COVID-19 is not clear, but ventricular ectopy has been linked to increased risk of cardiac disease, including cardiomyopathy and sudden cardiac death. (Figure Presented).