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Electrocardiographic manifestations of COVID-19.
Long, B, Brady, WJ, Bridwell, RE, Ramzy, M, Montrief, T, Singh, M, Gottlieb, M
The American journal of emergency medicine. 2021;:96-103
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Abstract
INTRODUCTION Coronavirus disease of 2019 (COVID-19) is a lower respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease can impact the cardiovascular system and lead to abnormal electrocardiographic (ECG) findings. Emergency clinicians must be aware of the ECG manifestations of COVID-19. OBJECTIVE This narrative review outlines the pathophysiology and electrocardiographic findings associated with COVID-19. DISCUSSION COVID-19 is a potentially critical illness associated with a variety of ECG abnormalities, with up to 90% of critically ill patients demonstrating at least one abnormality. The ECG abnormalities in COVID-19 may be due to cytokine storm, hypoxic injury, electrolyte abnormalities, plaque rupture, coronary spasm, microthrombi, or direct endothelial or myocardial injury. While sinus tachycardia is the most common abnormality, others include supraventricular tachycardias such as atrial fibrillation or flutter, ventricular arrhythmias such as ventricular tachycardia or fibrillation, various bradycardias, interval and axis changes, and ST segment and T wave changes. Several ECG presentations are associated with poor outcome, including atrial fibrillation, QT interval prolongation, ST segment and T wave changes, and ventricular tachycardia/fibrillation. CONCLUSIONS This review summarizes the relevant ECG findings associated with COVID-19. Knowledge of these findings in COVID-19-related electrocardiographic presentations may assist emergency clinicians in the evaluation and management of potentially infected and infected patients.
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Absence of effect of steady state bempedoic acid on cardiac repolarization: Results of a thorough QT/QTc study in healthy volunteers.
Amore, BM, Cramer, CT, MacDougall, DE, Sasiela, WJ, Emery, MG
Clinical and translational science. 2021;(6):2487-2496
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Abstract
Bempedoic acid is an inhibitor of adenosine triphosphate-citrate lyase approved for use in adults with hypercholesterolemia. Nonclinical studies assessed binding to the human ether-a-go-go-related gene (hERG) potassium channel in vitro and the effect of bempedoic acid on QT/QTc in cynomolgus monkeys. A randomized, double-blind, parallel-design clinical study assessed the effects of steady-state bempedoic acid at a supratherapeutic dose (240 mg/day, 33.3% higher the180 mg/day therapeutic dose), placebo, and moxifloxacin (400 mg) in healthy subjects. In vitro binding potency for bempedoic acid to the hERG potassium channel was weak, with half-maximal inhibition (IC50 ) estimated at greater than 1000 μM (>1670-fold the bempedoic acid 180 mg/day steady-state unbound maximum concentration). In monkeys, individual rate-corrected QT intervals showed no time- or dose-dependent changes up to 100 mg/kg of bempedoic acid. In human subjects, the upper 90% confidence interval (CI) for the difference in QTc interval, corrected using Fridericia's formula (QTcF), between bempedoic acid and placebo was less than 5 msec at all time points. Concentration-QTcF analysis showed that maximum bempedoic acid concentration at steady-state was attained at a median 2.1 h postdose, and the predicted mean change (90% CI) in QTcF at the observed mean bempedoic acid concentration 2 h postdose was -0.5 (-5.0, 4.0) msec. The lower bound of the moxifloxacin 90% CI exceeded 5 msec at prespecified time points, establishing study sensitivity. Steady-state bempedoic acid at a supratherapeutic dose of 240 mg was generally well-tolerated and not associated with QTc prolongation in healthy subjects.
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Prediction of arrhythmia susceptibility through mathematical modeling and machine learning.
Varshneya, M, Mei, X, Sobie, EA
Proceedings of the National Academy of Sciences of the United States of America. 2021;(37)
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Abstract
At present, the QT interval on the electrocardiographic (ECG) waveform is the most common metric for assessing an individual's susceptibility to ventricular arrhythmias, with a long QT, or, at the cellular level, a long action potential duration (APD) considered high risk. However, the limitations of this simple approach have long been recognized. Here, we sought to improve prediction of arrhythmia susceptibility by combining mechanistic mathematical modeling with machine learning (ML). Simulations with a model of the ventricular myocyte were performed to develop a large heterogenous population of cardiomyocytes (n = 10,586), and we tested each variant's ability to withstand three arrhythmogenic triggers: 1) block of the rapid delayed rectifier potassium current (IKr Block), 2) augmentation of the L-type calcium current (ICaL Increase), and 3) injection of inward current (Current Injection). Eight ML algorithms were trained to predict, based on simulated AP features in preperturbed cells, whether each cell would develop arrhythmic dynamics in response to each trigger. We found that APD can accurately predict how cells respond to the simple Current Injection trigger but cannot effectively predict the response to IKr Block or ICaL Increase. ML predictive performance could be improved by incorporating additional AP features and simulations of additional experimental protocols. Importantly, we discovered that the most relevant features and experimental protocols were trigger specific, which shed light on the mechanisms that promoted arrhythmia formation in response to the triggers. Overall, our quantitative approach provides a means to understand and predict differences between individuals in arrhythmia susceptibility.
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In-silico human electro-mechanical ventricular modelling and simulation for drug-induced pro-arrhythmia and inotropic risk assessment.
Margara, F, Wang, ZJ, Levrero-Florencio, F, Santiago, A, Vázquez, M, Bueno-Orovio, A, Rodriguez, B
Progress in biophysics and molecular biology. 2021;:58-74
Abstract
Human-based computational modelling and simulation are powerful tools to accelerate the mechanistic understanding of cardiac patho-physiology, and to develop and evaluate therapeutic interventions. The aim of this study is to calibrate and evaluate human ventricular electro-mechanical models for investigations on the effect of the electro-mechanical coupling and pharmacological action on human ventricular electrophysiology, calcium dynamics, and active contraction. The most recent models of human ventricular electrophysiology, excitation-contraction coupling, and active contraction were integrated, and the coupled models were calibrated using human experimental data. Simulations were then conducted using the coupled models to quantify the effects of electro-mechanical coupling and drug exposure on electrophysiology and force generation in virtual human ventricular cardiomyocytes and tissue. The resulting calibrated human electro-mechanical models yielded active tension, action potential, and calcium transient metrics that are in agreement with experiments for endocardial, epicardial, and mid-myocardial human samples. Simulation results correctly predicted the inotropic response of different multichannel action reference compounds and demonstrated that the electro-mechanical coupling improves the robustness of repolarisation under drug exposure compared to electrophysiology-only models. They also generated additional evidence to explain the partial mismatch between in-silico and in-vitro experiments on drug-induced electrophysiology changes. The human calibrated and evaluated modelling and simulation framework constructed in this study opens new avenues for future investigations into the complex interplay between the electrical and mechanical cardiac substrates, its modulation by pharmacological action, and its translation to tissue and organ models of cardiac patho-physiology.
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Contemporary Application of Cardiovascular Magnetic Resonance Imaging.
Han, Y, Chen, Y, Ferrari, VA
Annual review of medicine. 2020;:221-234
Abstract
Cardiovascular magnetic resonance imaging (CMR) is a comprehensive and versatile diagnostic and prognostic imaging modality that plays an increasingly important role in management of patients with cardiovascular disease. In this review, we discuss CMR applications in nonischemic cardiomyopathy, ischemic heart disease, arrhythmias, right ventricular diseases, and valvular heart disease. We emphasize the quantitative nature of CMR in current practice, from volumes, function, myocardial strain analysis, and late gadolinium enhancement to parametric mapping, including T1, T2, and T2* relaxation times and extracellular volume fraction assessment.
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Cardiomyocyte mitochondrial dysfunction in diabetes and its contribution in cardiac arrhythmogenesis.
El Hadi, H, Vettor, R, Rossato, M
Mitochondrion. 2019;:6-14
Abstract
Cardiovascular disease is the leading cause of diabetes-related morbidity and mortality. It is widely accepted that heart failure risk is increased in diabetic patients even after adjusting for coronary artery disease and hypertension. Mitochondria are the center of fatty acid (FA) and glucose metabolism and thus are likely to be impacted by impaired metabolism associated with diabetes. Although the cause of this increased heart failure risk is multifactorial, increasing evidence points toward a crucial role for cardiomyocyte mitochondria dysfunction. Altered energy metabolism, defects in mitochondrial dynamics, increased oxidative stress, impaired calcium (Ca2+) handling and mitochondria-induced cell death are observed in mitochondria of diabetic myocardium. In addition, mitochondrial dysfunction appears to contribute substantially to the origin of arrhythmias in diabetic hearts. The current review will describe these mitochondrial abnormalities in cardiomyocytes attempting to provide an overview of underlying mechanisms. Finally, we briefly discuss the potential link between mitochondrial malfunction and arrhythmogenesis.
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Cardiac Alternans: Mechanisms and Clinical Utility in Arrhythmia Prevention.
Kulkarni, K, Merchant, FM, Kassab, MB, Sana, F, Moazzami, K, Sayadi, O, Singh, JP, Heist, EK, Armoundas, AA
Journal of the American Heart Association. 2019;(21):e013750
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[Jervell and Lange-Nielsen syndrome].
Zhang, WJ, Sun, Y, Kong, WJ
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery. 2019;(9):825-829
Abstract
Summary Jervell and Lange-Nielsen syndrome(JLNS) is an autosomal recessive hereditary disease characterized by congenital severe sensorineural hearing loss in both ears and severe arrhythmias with QT interval prolongation. Children with JLNS often exhibit sensorineural hearing loss and are easily misdiagnosed as non-syndromic hearing loss before attack of cardiac event. When a cochlear implant is performed, a fatal arrhythmia is likely to occur during the perioperative period, which seriously threatens the life of the child. It is currently found that the pathogenic genes of JLNS are mainly KCNQ1 and KCNE1. This article reviews the clinical manifestations, pathogenic genes, diagnosis and differential diagnosis, intervention measures of JLNS to further draw the attention to the disease, reduce misdiagnosis, improve the survival rate and quality of life of children with JLNS.
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Anorexia nervosa and heart disease: a systematic review.
Giovinazzo, S, Sukkar, SG, Rosa, GM, Zappi, A, Bezante, GP, Balbi, M, Brunelli, C
Eating and weight disorders : EWD. 2019;(2):199-207
Abstract
Anorexia nervosa (AN) is an eating disorder that most frequently afflicts females in adolescence. In these subjects, cardiovascular complications are the main cause of morbidity and mortality. Aim of this review is to analyze the hemodynamic, pro-arrhythmic and structural changes occurring during all phases of this illness, including re-feeding. A systematic literature search was performed on studies in the MEDLINE database, from its inception until September 2017, with PUBMED interface focusing on AN and cardiovascular disease. This review demonstrated that the most common cardiac abnormalities in AN are bradycardia and QT interval prolongation, which may occasionally degenerate into ventricular arrhythmias such as Torsades des Pointes or ventricular fibrillation. As these arrhythmias may be the substrate of sudden cardiac death (SCD), they require cardiac monitoring in hospital. In addition, reduced cardiac mass, with smaller volumes and decreased cardiac output, may be found. Furthermore, mitral prolapse and a mild pericardial effusion may occur, the latter due to protein deficiency and low levels of thyroid hormone. In anorectic patients, some cases of hypercholesterolemia may be present; however, conclusive evidence that AN is an atherogenic condition is still lacking, although a few cases of myocardial infarction have been reported. Finally, refeeding syndrome (RFS), which occurs during the first days of refeeding, may engender a critically increased risk of acute, life-threatening cardiac complications.
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Proton pump inhibitor-induced hypomagnesemia complicated with serious cardiac arrhythmias.
Chrysant, SG
Expert review of cardiovascular therapy. 2019;(5):345-351
Abstract
Introduction: Magnesium is the third most common intracellular ion after potassium and calcium and is an important element in the functions of the body, since it participates in more than 300 enzyme systems. It also, plays a significant role in the transport of calcium and potassium across the cell membranes and protects against cardiac arrhythmias and is useful for their treatment due to hypomagnesemia induced from the proton pump inhibitors (PPIs). Areas covered: PPIs are used for the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD), but have been associated with hypomagnesemia with serious cardiac arrhythmias including torsades de pointes (TdP). To better understand the magnitude of this problem, a Medline search of the English language literature was conducted from 2010 to 2018 and 35 papers with pertinent information were selected. Expert commentary: The review of these papers suggests that PPIs cause hypomagnesemia, which could be associated with serious cardiac arrhythmias including TdP. However, its incidence is not very common considering the millions of people taking PPIs, but the FDA has advised the physicians to be watchful about this serious adverse effect of PPIs and check the magnesium levels before initiation of PPI treatment.