Acute or chronic? Failing left ventricle in a 34 year old

Submission content Introduction: An unusual case of a very young patient without previously known cardiac disease presenting with severe left ventricular failure, detected by a point of care echocardiogram. Main Body: A 34 year old previously well man was brought to hospital after seeing his general practitioner with one month of progressive shortness of breath on exertion. This began around the time the patient received his second covid-19 vaccination. He was sleeping in a chair as he was unable to lie flat. Abnormal observations led the GP to call an ambulance. In the emergency department, the patient required oxygen 5L/min to maintain SpO2 >94%, but he was not in respiratory distress at rest. Blood pressure was 92/53mmHg, mean 67mmHg. Point of care testing for COVID-19 was negative. He was alert, with warm peripheries. Lactate was 1.0mmol/L and he was producing more than 0.5ml/kg/hr of urine. There was no ankle swelling. ECG showed sinus tachycardia. He underwent CT pulmonary angiography which demonstrated no pulmonary embolus, but there was bilateral pulmonary edema. Troponin was 17ng/l, BNP was 2700pg/ml. Furosemide 40mg was given intravenously by the general medical team. Critical care outreach asked for an urgent intensivist review given the highly unusual diagnosis of pulmonary edema in a man of this age. An immediate FUSIC Heart scan identified a dilated left ventricle with end diastolic diameter 7cm and severe global systolic impairment. The right ventricle was not severely impaired, with TAPSE 18mm. There was no significant pericardial effusion. Multiple B lines and trace pulmonary effusions were identified at the lung bases. The patient was urgently discussed with the regional cardiac unit in case of further deterioration, basic images were shared via a cloud system. A potential diagnosis of vaccination-associated myocarditis was considered,1 but in view of the low troponin, the presentation was felt most likely to represent decompensated chronic dilated cardiomyopathy. The patient disclosed a family history of early cardiac death in males. Aggressive diuresis was commenced. The patient was admitted to a monitored bed given the potential risk of arrhythmia or further haemodynamic deterioration. Advice was given that in the event of worsening hypotension, fluids should not be administered but the cardiac centre should be contacted immediately. Formal echocardiography confirmed the POCUS findings, with ejection fraction <35%. He was initiated on ACE inhibitors and beta adrenergic blockade. His symptoms improved and he was able to return home and to work, and is currently undergoing further investigations to establish the etiology of his condition. Conclusion(s): Early echocardiography provided early evidence of a cardiac cause for the patient's presentation and highlighted the severity of the underlying pathology. This directed early aggressive diuresis and safety-netting by virtue of discussion with a tertiary cardiac centre whilst it was established whether this was an acute or decompensated chronic pathology. Ultrasound findings: PLAX, PSAX and A4Ch views demonstrating a severely dilated (7cm end diastolic diameter) left ventricle with global severe systolic impairment.

Management of cardiovascular complications of BTKis: Are we complying with the good practice guidelines?

Bruton tyrosine kinase inhibitors (BTKis) were approved for use at the end of 2013 and have since been used for indications including chronic lymphocytic leukaemia (CLL), Waldenstrom's macroglobulinaemia and mantle cell lymphoma. The use of BTKis has increased significantly in the UK since they achieved NICE (National Institute for Health and Care Excellence) approval for frontline treatment of CLL in 2021. However, they are associated with significant adverse cardiovascular events. In September 2021 the British Journal of Haematology published good practice guidelines for the management of cardiovascular complications of BTKis. Our aim was to see whether these guidelines had been adhered to for patients taking BTKis. Method(s): Data was collected for all patients being prescribed BTKis (ibrutinib and acalabrutinib) in the South Tees NHS Trust in July 2022. Patients' medical records were used to assess whether their management adhered to the good practice guidelines. Data was collated for 67 patients in total. Result(s): The data showed that although all patients were consented for the risk of atrial fibrillation only 6% were consented for hypertension and only 1.5% for ventricular arrhythmias and sudden cardiac death. The guidelines recommend a baseline ECG (electrocardiogram) on commencement of treatment;however, only 7% had this completed and 0% had the minimum monitoring recommendation of 6-monthly ECGs. Thirty patients (45%) had an indication for a baseline echocardiogram;however, only one had this completed. For patients reporting symptoms of syncope, dizziness or palpitations only 50% had an ECG completed. Three patients developed worsening heart failure. The recommendations suggest referral to a cardio-oncologist;however, due to lack of availability of this service the referrals were instead made to the usual cardiologist. Conclusion(s): Although there was a lack of compliance with guideline recommendations, it should be considered that most usual checks were affected by COVID-19 outbreaks and a drop in face-to- face clinics, which were replaced by phone clinics and home delivery of medications. However, the premade consent forms for BTKis need to be updated to include consent for ventricular arrhythmias and sudden cardiac death. There also needs to be routine procedures in place to ensure that regular blood pressure testing and ECG monitoring occurs and that there is prompt recognition of cardiovascular complications. Action and implementation: To ensure improved compliance with these guidelines we plan to update our consent forms and create a proforma for clinic use to ensure that clinicians are aware of the various monitoring criteria required.

Anti-SARS-CoV-2 antibodies important in diagnostics of acute hepatitis in children

The most common causes of acute hepatitis in children are hepatitis A and autoimmune hepatitis. Hepatitis in the course of Wilson's disease is sporadically registered in adolescents. An increase of activity of aminotransferases both in the course of multisystem inflammatory syndrome in children (MIS-C) and in the course of COVID-19 has been observed. Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests. To date, no cases of acute hepatitis in children due to COVID-19 have been reported. We present 2 cases of acute hepatitis in children where the only cause seems to be a previous asymptomatic SARS-CoV-2 infection.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.

Report of the Association Between Multisystem Inflammatory Syndrome and Severe Myocarditis

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusion(s): Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.Copyright © 2023, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

A CNN Transfer Learning -Electrocardiogram (ECG) Signal Approach to Predict COVID-19

Deep learning is increasingly gaining traction in cutting-edge medical sciences such as image classification, and genomics due to the high computational performance and accuracy in evaluating medical data. In this study, we investigate the cardiac properties of ECG Images and predict COVID-19 in a binary classification of patients who tested positive for COVID-19 and Normal Persons who tested negative. We analyzed the electrocardiogram (ECG) images by preprocessing the ECG data and building an ECG- Deep Learning- COVID-19 (ECG-DL-COVID) classifier to predict disease. The deep learning models in our experiments constituted CNN, Multi-Layer Perceptron (MLP), and Transfer Learning. Performance evaluation was done to compare the effectiveness of the proposed methodologies with other COVID-19 deep learning-related works. In the three experiments, we achieved an 87% prediction accuracy for MLP, a 90% prediction for CNN and a 93.8% prediction for Transfer Learning. Experimental results and performance evaluation show that the proposed models outperformed previous deep-learning models in the prediction of COVID-19 by a considerable margin. © 2023 IEEE.

ST-SEGMENT-ELEVATION MYOCARDIAL INFARCTION in COVID-19

Introduction: The Severe Acute Respiratory Syndrome Coronavirus-2 have been associated with cardiovascular adverse events including acute myocardial infarction due to a prothrombotic and hypercoagulable status, and endothelial dysfunction. Case report: We report the case of a 62-year-old women, admitted to the hospital via the emergency room for acute chest pain and dyspnea. A nasopharyngeal swab was positive for COVID19 real-time reverse transcriptase-polymerase chain reaction 11 day ago. On admission, she was hypotensive with systolic blood pressure measering 87 mmHg and tachycardic with 117 beats/min, oxygen saturation (SO2) was 94%. An 18-lead ECG revealed an infero-postero-lateral ST-elevation myocardial infarction with right ventricular involvement and a seconddegree- Mobitz Type 1 atrioventricular block. The coronary angiography from the right femoral artery showed acute thrombotic occlusion of the first diagonal branch with TIMI 0 flow and acute thrombotic occlusion of proximal right coronary artery with TIMI 0 flow. The most likely diagnosis was myocardial infarction secondary to a non-atherosclerotic coronary occlusion. The angioplasy was performed with dilatations with a semi compliant balloon, bailout implant of BMS, manual thrombus aspiration and intracoronary injection of tirofiban in the right coronary artery. The myocardial revascularization was ineffective. The patient developed significant severe hemodynamic instability and cardiac arrest for pulseless electric activity after 24 hours. Conclusion(s): The COVID-19 outbreak implies deep changes in the clinical profile and therapeutic management of STEMI patients who underwent PCI. At present, the natural history of coronary embolism is not well understood;however, the cardiac mortality rate are hight. This suggests these patients require further study to identify the natural history of the condition and to optimize management to improve outcome.

Post-Covid Myocarditis Simulating Acute Coronary Syndrome

Background: Acute myocarditis corresponds to an acute inflammation of the myocardium whose origin is most often viral. Several viruses can be incriminated to note the parvovirus B19, the virus herpes of the group 6 and to a lesser degree the virus of the hepatitis C (VHC) [18,19]. Since 2019 and with the discovery of SARS COV2 some cases of myocarditis associated with covid have been noted, this last association is rare and is present in only 5% of cases [8]. The diagnosis of myocarditis is sometimes difficult and can lead to confusion with acute coronary syndrome, especially in cases of ST-segment elevation on the EKG, hence the interest of magnetic resonance imaging, which has made it possible in recent years to reduce the rate of unnecessary coronary angiography, especially in the case of young subjects with no cardiovascular risk factors. in this context we report the case of a 33 year old patient with no cardiovascular risk factors and no medical or surgical antecedents who was admitted to the emergency department for the management of acute chest pain related to acute post-covid myocarditis, the patient was initially admitted to the cardiology intensive care unit where he was put in condition and under analgesic treatment and under therapeutic protocal of covid 19 and under anticoagulation based on low molecular weight heparin at preventive dose with a good clinical evolution he was transferred thereafter to the clinical cardiology then declared outgoing under treatment of covid 19 with an appointment of control in 1 month.

Intravenous Thrombolysis for Acute Ischemic Stroke during COVID-19 Pandemic in Srinagarind Hospital

Background: Stroke is the leading cause of death and disability worldwide. In COVID-19 pandemic, stroke remains to be a medical emergency. To treat patients with acute ischemic stroke [AIS], early intravenous thrombolysis is highly time sensitive. This research investigated the impact of regionally imposed social and healthcare restrictions of COVID-19 on the time metrics in the management of AIS patients admitted at the stroke unit center in Srinagarind Hospital. Objective(s): Comparison of door to needle time for intravenous thrombolysis for AIS patients before and after the COVID-19 outbreak. Material(s) and Method(s): The present study is a retrospective analysis of patients with AIS who received intravenous tissue plasminogen activator [tPA] from 1 January 2019 to 31 December 2020 in Srinagarind Hospital, Khon Kaen. The patients admitted before and after the COVID-19 outbreak [January 13, 2020, as officially announced by the World Health Organization] were screened to collect sociodemographic data, medical history information, and symptom onset status from clinical medical records and to compared door-to-needle time (DNT) for intravenous thrombolysis before and after the outbreak. Result(s): A total of 239 patients were included, of which 113 were enrolled before and 126 after the COVID-19 outbreak. According to the findings, DNT is 35.3 minutes before the pandemic and 35.8 minutes after the epidemic. Conclusion(s): COVID-19 has remarkable impacts on the management of AIS. However, DNT for before and after COVID-19 outbreak is nearly identical. It was established that administering intravenous thrombolysis to patients in the emergency room rather than the stroke unit allowed for speedier access. Therefore, a policy which provides quick AIS treatments in COVID-19 situations should be implemented.Copyright © 2023 Journal of the Medical Association of Thailand.

Using Machine Learning Algorithms to Determine the Post-COVID State of a Person by Their Rhythmogram.

This study introduces a novel method for detecting the post-COVID state using ECG data. By leveraging a convolutional neural network, we identify "cardiospikes" present in the ECG data of individuals who have experienced a COVID-19 infection. With a test sample, we achieve an 87 percent accuracy in detecting these cardiospikes. Importantly, our research demonstrates that these observed cardiospikes are not artifacts of hardware-software signal distortions, but rather possess an inherent nature, indicating their potential as markers for COVID-specific modes of heart rhythm regulation. Additionally, we conduct blood parameter measurements on recovered COVID-19 patients and construct corresponding profiles. These findings contribute to the field of remote screening using mobile devices and heart rate telemetry for diagnosing and monitoring COVID-19.

COVID Detection Using ECG Image Reports: A Survey

COVID-19 is one of the greatest pandemics that threaten individuals, especially the elders. It was first reported inWuhan, China in 2019. It was discovered recently that COVID-19 disease can be detected using three main protocols. The first protocol is based on Polymerase Chain reaction (PCR), while the second protocol is based on lung chest (ultrasound, X-ray, and CT-Scan), and the final protocol is based on the ECG image reports. This review aims to present a survey on the methodologies and algorithms applied for the detection of COVID disease using electrocardiogram (ECG). In this study, various papers were presented for determining how the COVID can be diagnosed using ECG image reports relying on symptoms and changes in the ECG peaks and intervals. In addition to this, other studies are presented on techniques applied to the ECG reports for the detection of COVID. Also, the main limitations and future works are illustrated. It can be concluded that COVID can be detected with high accuracy using ECG reports and it is even more efficient than other protocols. Finally, based on the performance of the studies it can be shown that the ECG image report is close to an acceptable level in the detection of COVID disease.

Covid-19 in Male Elite Irish-Based Athletes at a National Sports Institute

Background/Aims The impact of COVID-19 has not been previously documented in an elite sporting population. Previous reports have documented cardiorespiratory sequelae in athletes, and expert opinion-based guidance is generally employed in their rehabilitation. However, there still persists a lack of information on how COVID-19 affects elite athletes, and a standardised approach to graduated return to play (GRTP). This case series describes a cohort of six elite Irish-based athletes diagnosed with COVID-19. Methods Six athletes were followed from symptom onset until their GRTP. A retrospective case series was performed using a standardised audit form for COVID-19 among elite athletes. Results Headache and fatigue (6/6) were the commonest presenting symptoms, with mean duration 4.5 days;all athletes experienced mild illness, none required further investigation. 3/6 athletes supplemented vitamin D. Mean rest period was 11.5 days and mean GRTP 19.2 days. All athletes had an unremarkable screening electrocardiogram. Conclusion This case series presents the first clinical summary of COVID-19 illness in elite athletes based in Ireland. Treatment is largely supportive although further consideration should be given to implementing supplementation, such as vitamin D, in the management of COVID- 19. Larger, longer term studies are required to better understand the impact of COVID-19 in athletes and across different sports.

Pediatric Cardiac Screening Data Warehouse: A National Public Health Resource

Background: Cardiac screening of youth for prevention of sudden cardiac death in the young (SCDY) has been debated due to the absence of large population-specific screening data with outcomes. Despite years of screening by US public screening groups (PSG), there is minimal coordination of effort and no standardized methods for real-world data collection. Objective(s): To understand the methods, quality, outcomes, and best practices of youth screening, the Cardiac Safety Research Consortium Pediatric Cardiology Working Group, in collaboration with FDA and PSGs, developed and enabled a scalable system to collect a uniform pediatric cardiac screening dataset including digital ECGs and post-screening electronic follow-up data. Method(s): Front end data collection (figure) was developed to include use of a universal unique ID system to align paper/digital collection of health and ECG data. PSGs use secure data transfer portals for digital ECG data upload for conversion to device-agnostic standardized FDA format to store in the national pediatric cardiac screening data warehouse. Follow-up data are obtained at designated post-screening intervals (one week, one and 3 months for pilot study) using initial text message contact followed by electronic consent (REDCap) and answering online health surveys. Result(s): Fourteen PSGs in ten states participated in the pilot study. PSG warehouse data include 33840 retrospective ECG datasets collected from 2010 to 2021 containing limited screened history/symptoms but demographics similar to US census as follows: Age 13-30y, Male/Female 57/43%, Asian 6%, Black 19%, Native American <1%, Pacific Islander <1%, White 68%, Other 4%;Hispanic/Non-Hispanic 27%/79%. Individual PSG site demographics reflected local populations. Prospective data collection since 2021 include >4000 uniform screening datasets (age, sex, race, ethnicity, ht, wt, screening H&P, COVID history, medications, digital ECG with results, screening outcome, and, if applicable, ECHO results). Follow up participation allowing initial cellular contact was high (avg 73%, range 51-91%/screening). Conclusion(s): Establishment of a national pediatric cardiac data warehouse enables large-scale aggregation of pediatric cardiac screening information to address deficits in the understanding and prevention of SCDY. This large real-world dataset will help establish normative data for pediatric ECGs which can facilitate development of new diagnostic tools such as machine learning and support pediatric drug and device development. [Formula presented]Copyright © 2023

Viral Myopericarditis and Viral Encephalitis as Manifestations of Covid-19 Infection: A Case Report

Intro: Coronavirus disease (COVID-19) is currently a global health crisis and is caused by a new strain of coronavirus. However, emerging literature of case reports noted possible extrapulmonary manifestations of the disease. Because COVID 19 is a relatively new disease, at present, little existing literature tackles the diagnosis and therapeutic management of COVID-19-related conditions outside the pulmonary system. Method(s): This is a case of a 24-year-old male presented with the chief complaint of sudden stiffening of all extremities. Non-contrast computed tomography (CT) scan was unremarkable. Chest X-ray revealed interstitial pneumonia and SARS-CoV-2 RT-PCR (OPS/NPS) was positive. Electrocardiogram (ECG) findings showed supraventricular tachycardia and had elevated Troponin I levels. Pertinent physical findings noted were slurring of speech, dysmetria, and vertical nystagmus. Finding(s): The patient was initially treated as a case of Bacterial Abscess versus Viral encephalitis. Pericardial ultrasound revealed small pericardial effusion and was started on Colchicine. Repeat cranial CT scan noted unremarkable results but due to persistence of symptoms, the patient was started with Dexamethasone. On Day 16 of illness, the patient was noted to have full resolution of symptoms. Rapid antibody testing was done which revealed positive for both IgG and IgM hence the patient was discharged with the final diagnosis of Viral Myopericarditis resolved, Viral encephalitis resolved, COVID-19 pneumonia recovered. Conclusion(s): Extrapulmonary manifestations have been reported increasingly as an atypical presentation of COVID 19 infection. Early recognition of viral myopericarditis and viral encephalitis as a manifestation of COVID 19 can lead to the initiation of proper treatment and management. More reports on these cases can aid future studies on diagnostics and therapeutic approaches during the COVID-19 pandemic.Copyright © 2023

On-Site Whole-Genome Sequencing of Sars-Cov-2 Reveals C3037t Mutation in Patient with Atrioventricular Nodal Reentry Tachycardia (Avnrt)

Intro: The spike protein of the SARS-CoV-2 virus targets the human cell receptor of angiotensin-converting enzyme (ACE2), including the myocardium and heart's conduction system. Patients diagnosed with COVID-19 have also been found to exhibit cardiac arrhythmia. Here, a whole-genome sequencing analysis using long-read sequencing was proposed to evaluate the virus genome in a patient who presented with AVNRT as a main presentation of COVID-19. Method(s): The sample was recovered from nasopharyngeal and oropharyngeal swab specimens of a 46-year-old female with no comorbidities who presented with palpitation, and ECG showed typical AVNRT features. The RT-qPCR of SARS- CoV-2 was confirmed positive with a CT-value of 15.82. The total RNAs were extracted and proceeded for RT-qPCR and proceeded with Oxford Nanopore Flongle sequencing. The genomics data of the virus was deposited in GISAID (EPI_ISL_3241561) and further analysed using online bioinformatics tools such as Nextclade CLI 2.3.0. Ethical approval (IREC 2021-080) for the study was obtained from IIUM Research Ethics Committee. Finding(s): Here, we reported a total of 29,775 bp near-complete whole-genome belonging to clade 21J (Delta) of AY.79 lineage (also known as B.1.617.2.79), which formed a dominant variant in Malaysia during the time of sampling. Discussion(s): While a previous study showed an association between Delta variant infection with fulminant myocarditis, the present study reported the benign AVNRT as the main presentation of SARS-CoV-2 infection. Furthermore, we observed the presence of the C3037T mutation previously described in the endomyocardial biopsy of a patient with persistent arrhythmia. Conclusion(s): Even though SARS-CoV-2 targets the respiratory tract, the present study supports the evidence that the ACE2 receptors are present in the heart. In addition, COVID19 is causing more and more damage to heart tissue, and viral transcription has been confirmed on cardiomyocytes. Further functional studies are needed to explore the associated mutations and their relation to cardiac manifestation.Copyright © 2023

Covid-19 Vaccine-Induced Myositis

Background/Aims Through the COVID pandemic there have emerged reports of autoimmunity or new rheumatic diseases presenting in patients after they had COVID-19. This is thought to be caused by cross-reactivity of the COVID-19 spike protein to human antigens. Given the use of mRNA COVID-19 vaccinations which express the spike protein we might expect to see presentation of new rheumatic diseases following their use. We discuss a case where this appears to have occurred. Methods Our patient is a 24-year-old male with mixed phenotype acute leukaemia who had been treated with allogenic stem cell transplant and was currently in remission. He presented with fevers, palpitations, myalgia and bilateral arm and leg swelling. Symptoms began the day after receiving the first dose of an mRNA COVID-19 vaccination (Pfizer/BioNTech.) There were no other symptoms or recent change in medications. Physical examination revealed tender oedema in his forearms, biceps and thighs bilaterally with sparring of the hands. He had reduced power with shoulder (MRC 3/5), elbow (4), wrist (4+) and hip (4) movements. Observations revealed tachycardia and fevers up to 40C. Results Laboratory studies showed markedly elevated C-reactive protein (202), creatinine kinase (6697) and troponin (593) whilst investigations for infection were negative. An autoimmune panel was positive for anti- PM-SCL-75-Ab. An electrocardiogram showed sinus tachycardia. Echocardiogram was normal. Bilateral upper limb dopplers revealed no deep vein thrombus. An MRI of his thighs showed diffuse symmetrical oedema within the muscles, in keeping with an inflammatory myositis. A quadricep muscle biopsy showed evidence of MHC class 1 up-regulation, suggesting an inflammatory process. In addition, there were numerous macrophages evident in the endomysium. While this can be seen in graft-versus-host disease (GVHD), they would usually be found in the perimysium. After discussion between haematology, rheumatology and neurology, this was felt to be a case of vaccine induced myositis and myocarditis. Autoimmune myositis was thought to be less likely due to the relative sparing of the hands and the absence of Raynaud's phenomenon. 1 gram of intravenous methylprednisolone was then given for 3 days. The patient had a marked response with defervescence, improving laboratory markers, improved myalgia and decreased limb swelling. The patient was stepped down to a reducing regime of prednisolone and discharged. Due to relapse whilst weaning he has started on mycophenalate mofetil and rituximab and now continues to improve. Conclusion There are case reports of myositis following COVID-19 vaccination but our patient's case is complicated by the differential diagnosis of GVHD and concurrent myocarditis. Ongoing work is needed to clarify the exact link between vaccination and the presentation of a new inflammatory myositis, but it is important to recognise and start treatment early in order to preserve muscle bulk and ensure recovery.

Atrial Torsades De Pointes Post Covid Myocarditis

Background: Among patients with COVID-19 infection, the risk of adverse cardiovascular outcome, particularly myocarditis and dysrhythmias remain elevated at least up to one year after infection. We present a case of atrial tachycardia and atrial Torsades de Pointes from COVID myocarditis, persisted 6 months after infection, which was successfully managed by ablation. Objective(s): A 25-year-old female presented with mild COVID-19 infection, Omicron variant, in May 2022. One month after, her Covid infection resolved;she presented with symptomatic atrial tachycardia, paroxysmal atrial fibrillation and flutter. ECG showed multiple blocked premature atrial contractions (PAC) (Figure 1A). Holter monitor showed PAC triggered atrial tachycardia degenerating to paroxysmal atrial fibrillation, atrial Torsades de Pointes. She has mild persistent troponin elevation. Echocardiography was normal. Cardiac MRI showed evidence of mild myocarditis with subepicardial late Gadolinium enhancement (LEG) along the lateral mid-apical left ventricular wall and edema. (Figure 1B). She was treated with Colchicine for 2 months. Repeat cardiac MRI 4 months after COVID infection showed resolution of edema and LGE. However, her symptomatic PAC and atrial tachycardia did not respond to betablocker and amiodarone. She underwent electrophysiology study. Activation mapping of PAC using CARTO revealed earliest activation at the right anterior atrial wall, with close proximity to tricuspid valve;unipolar signal showed QS pattern, bipolar signal showed 16 msec pre-PAC (Figure 1C and 1D). Mechanical pressure from ThermoCool SmartTouch ablation catheter (Biosense Webster Inc.) at this site suppressed the PAC. Radiofrequency ablation resulted with an initial acceleration and then disappearance of the PAC. We did not isolate pulmonary veins or ablate cavotricuspid isthmus. Post ablation, PAC and atrial fibrillation were not inducible on Isoproterenol. Method(s): N/A Results: Covid myocarditis can result in dysrhythmia that lingers long after Covid myocarditis has resolved. Covid myocarditis can be caused by direct viral invasion of myocytes or more commonly is inflammatory related to cytokine release and edema. Our case demonstrates that dysrhythmias can persist despite resolution of myocarditis. Catheter ablation can successfully to treat these arrhythmias. Conclusion(s): This case highlights the importance of recognizing cardiac dysrhythmia as possible the long-term cardiac complications of COVID-19, requiring specific treatment such as catheter ablation. [Formula presented]Copyright © 2023

Prevalence of arrhythmia in COVID-19 patients with mild/moderate and severe illness: a prospective cohort study.

OBJECTIVES: The type of arrhythmias, and their prevalence in mild/moderate and severe COVID-19 patients admitted to the hospital are unknown from a prospective cohort study. METHODS: We did continuous electrocardiograms along with multiple ECGs in 305 consecutive hospitalized COVID-19 patients. RESULTS: The incidence of arrhythmias was 6.8% (21/305) in the target population. The incidence of arrhythmias was 9.2% (17/185) in patients with severe COVID-19 illness and 3.3% (4/120) in patients with mild/moderate COVID-19 illness with no significant difference (p = 0.063). All the arrhythmias were new-onset arrhythmias in this study. 95% (20/21) of these arrhythmias were atrial arrhythmia with 71.42% (15/21) being atrial fibrillation and one episode of sustained polymorphic ventricular tachycardia. No episode of high-grade atrioventricular block, sustained monomorphic ventricular arrhythmia, or torsades de pointes arrhythmias were observed in this study. The patients with arrhythmias were admitted to the intensive care unit (80.9% vs. 50.7%; p: 0.007), were on a ventilator (47.6% vs. 21.4%; p: 0.006), and had high in-hospital mortality (57.1% vs. 21.1%; p: 0.0001) than patients without arrhythmias. CONCLUSION: Atrial arrhythmias were the most frequent arrhythmias in hospital-admitted COVID-19 patients with atrial fibrillation being the most common arrhythmia. TRIAL REGISTRATION: Clinical Trial Registry India (CTRI) (CTRI/2021/01/030788). (https://www.ctri.nic.in/).

Extracorporeal Membrane Oxygenation (ECMO) Cannula Stimulation of the Carotid Sinus Causing Bradycardic Pauses in a Patient With COVID-19.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) cannulation is a potential cause of episodic bradycardia during an intensive care course because of the proximal cannula insertion site being in the vicinity of the carotid sinus. Herein, we report the case of episodic bradycardia throughout a multi-week intensive care stay of a VV-ECMO recipient due to a severe coronavirus disease 2019 (COVID-19) infection that did not emerge for the rest of the patient's hospitalization after decannulation.

No Dose Adjustments for Cyp3a4 Substrates When Coadministered with Bemnifosbuvir

Background: Bemnifosbuvir (BEM, AT-527) is a guanosine nucleotide prodrug in development for the treatment of COVID-19 and chronic HCV. BEM was identified in vitro as an inhibitor [competitive and time-dependent inhibition (TDI)] and inducer of CYP3A4, prompting evaluation of the clinical relevance of these results in a Ph 1 drug-drug interaction (DDI) study in healthy participants using midazolam (MDZ), a sensitive CYP3A4 substrate as an index drug. Method(s): Two groups of 12 healthy participants were enrolled and received a single dose of 2mg MDZ alone on Day 1. Between Days 3 and 7 inclusive, all participants received oral BEM 550mg twice daily (BID). On day 3 and day 7, Group A received a single dose of 2mg MDZ simultaneously with BEM;Group B on these two days received 2mg MDZ 2h after BEM. Serial plasma samples were obtained and measured for MDZ and 1-OH-MDZ levels. Result(s): A single dose (simultaneous or staggered) of BEM slightly increased the plasma exposure of MDZ (14%-26%). Staggered BEM had less impact (8%-17%) on 1-OH-MDZ than simultaneous dosing (22%-31%). Inhibitory effect of BEM was more pronounced with repeat dosing, consistent with in vitro data showing TDI on CYP3A4. After repeat dosing, simultaneously administered BEM increased plasma MDZ exposure by 83%-98%, without affecting the exposure of 1-OH-MDZ. With repeat dosing, staggered BEM showed less effect on both MDZ and 1-OH-MDZ. There was no effect on vital signs, ECG, and no SAEs or drug discontinuations. Conclusion(s): BEM is a weak inhibitor (ratio between 1.25 and 2) of CYP3A4. No dose adjustment is needed for drugs that are substrates of CYP3A4 when co-administered with BEM.

BEMNIFOSBUVIR HAS LOW POTENTIAL TO INHIBIT P-gp, BCRP, AND OATP1B1 MEDIATED TRANSPORT

Background: Bemnifosbuvir (BEM, AT-527) is a guanosine nucleotide prodrug candidate for the treatment of COVID-19 and chronic HCV. BEM was identified in vitro as an inhibitor of drug transporters P-glycoprotein, breast cancer resistant protein (BCRP) and organic anion transporting polypeptide 1B1 (OATP1B1). Ph 1 studies in healthy participants were conducted to assess the clinical implications of these results using digoxin (DIG) and rosuvastatin (ROSU) as P-gp and BCRP/ OATP1B1 index drugs, respectively. Method(s): Both studies employed a similar design with 2 groups of 14 healthy participants: Day 1/period 1, all participants received a single dose of DIG 0.25mg or ROSU 10mg alone. In period 2, participants received DIG 0.25mg or ROSU 10mg with BEM 1100mg, simultaneously (n=14) or staggered by 2h (n=14). Serial plasma samples were collected and quantitated for DIG or ROSU concentrations. Result(s): A single dose of BEM 1100mg simultaneously administered slightly increased the Cmax of DIG (78%), yet had no effect on its AUC, consistent with the transient nature of BEM plasma PK. When dosed staggered, BEM did not affect the PK of DIG. A single dose (simultaneous or staggered) of BEM 1100mg slightly increased the plasma exposure of ROSU (20%-40%). There was no effect on vital signs, ECG, and no SAEs or drug discontinuations. Conclusion(s): A single high dose of BEM 1100mg only slightly increased the plasma exposure of the P-gp and BCRP/OATP1B1 index drugs DIG and ROSU. BEM has low potential to exhibit clinical meaningful inhibition of these transporters. No dose adjustment will be needed for drugs that are sensitive substrates of P-gp or BCRP/OAT1B1 when co-administered with BEM, staggered dosing may lessen any DDI risk.