Corpus overview


MeSH Disease

Human Phenotype


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    Mitigating Arrhythmia HP Risk in Hydroxychloroquine and Azithromycin Treated COVID-19 Patients using Arrhythmia HP Risk Management Plan

    Authors: Kazimieras Maneikis M.D.; Ugne Ringeleviciute M.D.; Justinas Bacevicius M.D.; Egle Dieninyte-Misiune M.D.; Emilija Burokaite M.D.; Gintare Kazbaraite M.D.; Marta Monika Janusaite M.D.; Austeja Dapkeviciute M.D.; Andrius Zucenka M.D.; Valdas Peceliunas M.D. Ph.D.; Lina Kryzauskaite M.D.; Vytautas Kasiulevicius M.D. Ph.D.; Donata Ringaitiene M.D. Ph.D.; Birute Zablockiene M.D. Ph.D.; Tadas Zvirblis; Germanas Marinskis M.D. Ph.D.; Ligita Jancoriene M.D. Ph.D.; Laimonas Griskevicius M.D. Ph.D.

    doi:10.21203/ Date: 2020-07-29 Source: ResearchSquare

    Background: Hydroxychloroquine and Azithromycin use is associated with QT interval prolongation and arrhythmias HP. Despite ongoing multiple clinical trials for treatment of COVID19 infection MESHD, no definite cardiac safety protocols were proposed. The aim of our study was to assess cardiac safety in COVID-19 patients treated with the combination of Hydroxychloroquine and Azithromycin using close monitoring and arrhythmia HP risk management plan.Methods and results: We retrospectively examined arrhythmia HP safety of treatment with Hydroxychloroquine and Azithromycin in the setting of pre-defined cardiac arrhythmia MESHD arrhythmia HP risk management plan. 81 patients were included from March 23rd to May 10th 2020. The median age TRANS was 59 years, 58.0% were female TRANS. The majority of the study population (82.7%) had comorbidities, 98.8% had radiological signs of pneumonia MESHD pneumonia HP. 7 patients (8.6%) had QTc prolongation of ≥500 ms. The treatment was discontinued in 4 patients (4.9%). 14 patients (17.3%) experienced QTc≥480 ms and 16 patients (19.8%) had an increase of QTc≥60 ms. None of the patients developed ventricular tachycardia MESHD ventricular tachycardia HP. The risk factors significantly associated with QTc≥500 ms were hypokalemia MESHD hypokalemia HP (p = 0.032) and use of diuretics during the treatment (p = 0.020). Three patients had a lethal outcome; none of them associated with ventricular arrhythmias HP.Conclusion: We recorded a low incidence of QTc prolongation ≥500 ms and no ventricular tachycardia MESHD ventricular tachycardia HP events in COVID-19 patients treated with Hydroxychloroquine and Azithromycin using cardiac arrhythmia MESHD arrhythmia HP risk management plan.

    Beta-Adrenergic Receptor Stimulation Limits the Cellular Proarrhythmic Effects of Chloroquine and Azithromycin

    Authors: Henry Sutanto; Jordi Heijman

    id:10.20944/preprints202007.0418.v1 Date: 2020-07-19 Source:

    Background: The antimalarial drug chloroquine and antimicrobial drug azithromycin have received significant attention during the current COVID-19 pandemic. Both drugs can alter cardiac electrophysiology and have been associated with drug-induced arrhythmias HP. Meanwhile, sympathetic activation is commonly observed during systemic inflammation MESHD and oxidative stress (e.g., in SARS-CoV-2 infection MESHD), and may influence the electrophysiological effects of chloroquine and azithromycin. Here, we investigated the effect of beta-adrenergic stimulation on proarrhythmic properties of chloroquine and azithromycin using a detailed in silico model of ventricular electrophysiology. Methods: Concentration-dependent chloroquine and azithromycin-induced alterations in ion-channel function were incorporated into the Heijman canine ventricular cardiomyocyte model. Single and combined drug effects on action-potential (AP) properties were analyzed using a population of 592 models accommodating inter-individual variability. Sympathetic stimulation was simulated by an increase in pacing rate and experimentally validated isoproterenol-induced changes in ion-channel function. Results: At 1 Hz pacing, therapeutic doses of chloroquine and azithromycin (5 and 20 µM, respectively) individually prolonged AP duration (APD) by 33% and 13%. Their combination produced synergistic APD prolongation (+161%) with incidence of proarrhythmic early afterdepolarizations in 53.5% of models. Increasing the pacing frequency to 2 Hz shortened APD and together with 1 µM isoproterenol corrected the drug-induced APD prolongation. No afterdepolarizations occurred following increased rate and simulated application of 0.1-1 µM isoproterenol. Conclusion: Sympathetic stimulation limits chloroquine- and azithromycin-induced proarrhythmia by reducing their APD-prolonging effect, suggesting the importance of heart rate and autonomic status monitoring in particular conditions (e.g., COVID-19).

    Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial.

    Authors: Peter Horby; Marion Mafham; Louise Linsell; Jennifer L Bell; Natalie Staplin; Jonathan R Emberson; Martin Wiselka; Andrew Ustianowski; Einas Elmahi; Benjamin Prudon; Anthony Whitehouse; Timothy Felton; John Williams; Jakki Faccenda; Jonathan Underwood; J Kenneth Baillie; Lucy Chappell; Saul N Faust; Thomas Jaki; Katie Jeffery; Wei Shen Lim; Alan Montgomery; Kathryn Rowan; Joel Tarning; James A Watson; Nicholas J White; Edmund Juszczak; Richard Haynes; Martin J Landray

    doi:10.1101/2020.07.15.20151852 Date: 2020-07-15 Source: medRxiv

    Background: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease MESHD 2019 (COVID-19) on the basis of in vitro activity, uncontrolled data, and small randomized studies. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of hydroxychloroquine vs. usual care alone. The primary outcome was 28-day mortality. Results: 1561 patients randomly allocated to receive hydroxychloroquine were compared with 3155 patients concurrently allocated to usual care. Overall, 418 (26.8%) patients allocated hydroxychloroquine and 788 (25.0%) patients allocated usual care died within 28 days (rate ratio 1.09; 95% confidence interval [CI] 0.96 to 1.23; P=0.18). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to hydroxychloroquine were less likely to be discharged from hospital alive within 28 days (60.3% vs. 62.8%; rate ratio 0.92; 95% CI 0.85-0.99) and those not on invasive mechanical ventilation at baseline were more likely to reach the composite endpoint of invasive mechanical ventilation or death MESHD (29.8% vs. 26.5%; risk ratio 1.12; 95% CI 1.01-1.25). There was no excess of new major cardiac arrhythmia MESHD arrhythmia HP. Conclusions: In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death MESHD.

    Impact of Congestive Heart Failure HP Heart Failure MESHD and Role of Cardiac Biomarkers in COVID-19 patients: A Systematic Review and Meta-Analysis

    Authors: Tarun Dalia; Shubham Lahan; Sagar Ranka; Prakash Acharya; Archana Gautam; Ioannis Mastoris; Andrew Sauer; Zubair Shah

    doi:10.1101/2020.07.06.20147421 Date: 2020-07-07 Source: medRxiv

    Background: Coronavirus disease MESHD 2019 (COVID-19) has been reported to cause worse outcomes in patients with underlying cardiovascular disease MESHD, especially in patients with acute cardiac injury, which is determined by elevated levels of high- sensitivity SERO troponin. There is a paucity of data on the impact of congestive heart failure HP heart failure MESHD (CHF) on outcomes in COVID-19 patients. Methods: We conducted a literature search of PubMed/Medline, EMBASE, and Google Scholar databases from 11/1/2019 till 06/07/2020, and identified all relevant studies reporting cardiovascular comorbidities, cardiac biomarkers, disease MESHD severity, and survival. Pooled data from the selected studies were used for metanalysis to identify the impact of risk factors and cardiac biomarker elevation on disease MESHD severity and/or mortality. Results: We collected pooled data on 5,967 COVID-19 patients from 20 individual studies. We found that both non-survivors and those with severe disease MESHD had an increased risk of acute cardiac injury and cardiac arrhythmias MESHD arrhythmias HP, our pooled relative risk (RR) was - 8.52 (95% CI 3.63-19.98) (p<0.001); and 3.61 (95% CI 2.03-6.43) (p=0.001), respectively. Mean difference in the levels of Troponin-I, CK-MB, and NT-proBNP was higher in deceased and severely infected patients. The RR of in-hospital mortality was 2.35 (95% CI 1.18-4.70) (p=0.022) and 1.52 (95% CI 1.12-2.05) (p=0.008) among patients who had pre-existing CHF and hypertension MESHD hypertension HP, respectively. Conclusion: Cardiac involvement in COVID-19 infection MESHD appears to significantly adversely impact patient prognosis and survival. Pre-existence of CHF and high cardiac biomarkers like NT-pro BNP and CK-MB levels in COVID-19 patients correlates with worse outcomes. Keywords: Acute cardiac injury; cardiac arrhythmia MESHD arrhythmia HP; mortality risk; cardiac biomarkers, COVID-19.

    Chloroquine and Hydroxychloroquine for the treatment of COVID-19: A Systematic Review and Meta-analysis

    Authors: Arunmozhimaran Elavarasi; Manya Prasad; Tulika Seth; Ranjit Kumar Sahoo; Karan Madan; Neeraj Nischal; Manish Soneja; Atul Sharma; Subir Kumar Maulik; Shalimar; Pramod Garg

    doi:10.1101/2020.07.04.20146381 Date: 2020-07-06 Source: medRxiv

    Background: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. Objective: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. Methods: Two reviewers searched for published and pre-published relevant articles between December 2019 to 8th June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa scale. The quality of evidence was graded as per the GRADE approach. Results: We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46] , time to fever MESHD fever HP resolution [mean difference -0.54 days (-1.19-011)] or clinical deterioration MESHD/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/ arrhythmia HP with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. Conclusions: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.

    Cardiovascular Implications of Coronavirus Disease MESHD 2019 (COVID-19): A Systematic Review

    Authors: Ravi Ranjan Pradhan; Ajay Kumar Yadav; Shobha Mandal

    doi:10.21203/ Date: 2020-07-02 Source: ResearchSquare

    Background: World Health Organization has declared Coronavirus disease MESHD (COVID-19) as a Public Health Emergency MESHD of International Concern. It has killed thousands and millions are infected worldwide. Though COVID-19 is supposed to be primarily a disease MESHD of respiratory system, it also has widespread implications on other systems as well. The aim of this systematic review is to summarize the cardiovascular implications of COVID-19. Methods: PubMed, PubMed Central, EMBASE, and Google Scholar were searched for peer-reviewed articles which aimed to delineate the cardiovascular implications of COVID-19.Results: A total of six articles (five original articles and one case report) were included. We found diverse cardiovascular implications of COVID-19 ranging from acute cardiac injury to death MESHD. New onset abnormalities in electrocardiogram or echocardiogragram, elevated plasma SERO levels of cardiac troponin, NT-proBNP, and D-dimer have role in early identification of acute cardiac injury in such patients. Additionally, cardiac troponin and NT-proBNP can be used to evaluate prognosis and possible need for intensive care in these patients.Conclusion: Acute cardiac injury is common in patients with COVID-19. Aggressive supportive management based on prognostic indicators along with management of heart failure MESHD, arrhythmias HP, acute coronary syndrome MESHD and thrombosis MESHD can improve clinical outcomes in such patients.

    Hydroxychloroquine with or without macrolide and standard of care versus standard of care alone for COVID-19 cases: a systematic review and meta-analysis

    Authors: Dhan Bahadur Shrestha; Pravash Budhathoki; Sitaram Khadka; Era Rawal

    doi:10.21203/ Date: 2020-06-29 Source: ResearchSquare

    Background: Coronavirus disease MESHD (COVID-19) pandemic has been a global health threat. The specific treatment of this disease MESHD has not yet been approved. In this review, we aimed at assessing the role of hydroxychloroquine with/without macrolide in terms of efficacy and adverse effects against the standard of care. Methods: Pubmed, Medline, Google Scholar, Cochrane Library, and were searched for the quantitative and qualitative synthesis of 13 studies using PRISMA guidelines for a proper review. Assessment of heterogeneity was done using the I-squared (I2) test and fixed/random effect analysis was done to determine the odds/risk ratio among the selected studies.Results: Meta-analysis of our study demonstrated no significant differences in improvement for the virological cure (RR 0.95, 0.67-1.34), whereas a significant relationship was there in radiological progression ( pneumonia MESHD pneumonia HP resolution) (RR 1.40, 1.03-1.91) between the two arms. There are 1.52 times the odds of intubation during treatment (CI 0.61-3.77), 1.08 times the risk of mortality (CI 0.65-1.79), and about 2.21 times increased risk of development of adverse effect (OR 2.21, 0.95-5.17). Though overall it is of no statistical significance, clinical relevance to thinking while using the treatment for COVID-19 is advised. Among randomized controlled trials, the treatment group has 3.5 times (OR 3.48, 1.64-7.42) higher risk of developing adverse effects. There is 2.5 times the likelihood of severe arrhythmias HP and QT prolongation (OR 2.49, 1.67-3.70) on the treatment arm compared to control.Conclusion: Hydroxychloroquine with/without macrolide has shown no beneficial effect in viral clearance, survival rates while shows significant relation with the radiological improvement compared to standard of care but may increase the risk of intubation, overall side effects, and cardiac complications like arrhythmias HP and QT prolongation. Thus utilizing this treatment needs to be judged in clinical relevance and proper monitoring.

    Cardiac Arrhythmias MESHD Arrhythmias HP and COVID-19 – a Meta-analysis of Recent Reports

    Authors: Husam M. I. Salah; Jawahar L. Mehta

    doi:10.21203/ Date: 2020-06-23 Source: ResearchSquare

    Introduction: The 2019 novel coronavirus disease MESHD (COVID-19) is a current pandemic. Cardiovascular manifestations of COVID-19 have been described in many studies; however, no studies have examined the prevalence SERO and characterizations of cardiac arrhythmias MESHD arrhythmias HP among patients with COVID-19 infection MESHD. The aim of this meta-analysis was to examine the prevalence SERO of cardiac arrhythmias MESHD arrhythmias HP among patients with COVID-19 infection MESHD.Method: PubMed, Google Scholar, and ResearchGate databases were searched for relevant articles from inception until June 14, 2020. Inclusion criteria were: 1) Cohort studies or case series studies; 2) Study population included individuals with confirmed COVID-19 infection MESHD; 3) Arrhythmic events were reported in the study. All other studies were excluded. MedCalc software was used to analyze the pooled data. The random-effect model was utilized to obtain the prevalence SERO of arrhythmia HP among the included patients and its 95% confidence interval. Cohran's Q and I2 index were used for heterogeneity measurements. The main planned outcome was the prevalence SERO of arrhythmia HP among patients with COVID-19 infection MESHD.Results: Thirteen studies with a total of 2861 patients met our inclusion criteria. The prevalence SERO of arrhythmia HP among patients with COVID-19 infection MESHD was 8.1% (95% CI [6.10, 10.37]). 82.8% of the patients who had arrhythmia HP has severe illness (95% CI [70.916, 92.124]).Conclusion: The prevalence SERO of arrhythmias HP among patients with COVID-19 infection MESHD is 8.1%, which is much higher than in the general population (2.35%). 

    Modeling the effect of COVID-19 disease MESHD on the cardiac function: a computational study

    Authors: Francesco Regazzoni; Christian Vergara; Paolo Zunino; Marco Guglielmo; Roberto Scrofani; Laura Fusini; Chiara Cogliati; Gianluca Pontone; Alfio Quarteroni

    doi:10.1101/2020.06.23.166421 Date: 2020-06-23 Source: bioRxiv

    BackgroundThe effect of COVID-19 on the cardiac function and on the vascular system increases the morbidity and mortality of infected subjects with cardiovascular diseases MESHD. ObjectivesTo provide preliminary results on cardiac global outcomes (such as cardiac output, ventricular pressures) obtained by means of computational models in plausible scenarios characterized by COVID-19. MethodsWe considered a lumped parameters computational model of the cardiovascular system, which models, from the mechanical point of view, the systemic and pulmonary circulations, the four cardiac valves and the four heart chambers, through mathematical equations of the underlying physical processes. To study the effect of COVID-19, we varied the heart rate, the contractility and the pulmonary resistances in suitable ranges. ResultsOur computations on individuals with both otherwise normal and impaired cardiac functions revealed that COVID-19 worsen cardiac function, as shown by a decrease of some cardiac biomarkers values such as cardiac output and ejection fraction. In the case of existing impaired cardiac function, the presence of COVID-19 lead to values outside the normal ranges. ConclusionsComputational models revealed to be an effective tool to study the effect of COVID-19 on the cardiovascular system. Such effect could be significant for patients with impaired cardiac function. This is especially useful to perform a sensitivity SERO analysis of the hemodynamics for different conditions. CONDENSED ABSTRACTEmerging studies address how COVID-19 infection MESHD might impact the cardiovascular system. This relates particularly to the development of myocardial injury, acute coronary syndrome MESHD, myocarditis MESHD myocarditis HP, arrhythmia HP, and heart failure MESHD. Prospective treatment approach is advised for these patients. By the assessment of conventional important biomarkers obtained with new sources as a 0-dimentional computational model, we propose a new study protocol as an effective method to evaluate short-term prognosis. The clinical protocol proposed will help to rapidly identify which patients require intensive monitoring, diagnostic strategy and most adequate therapy.

    The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis

    Authors: Imad Tleyjeh; Zakariya Kashour; Oweida AlDosary; Muhammad Riaz; Haytham Tlayjeh; Musa A Garbati; Rana Tleyjeh; Mouaz H Al-Mallah; Rizwan M Sohail; Dana Gerberi; Aref A Bin Abdulhak; John R Giudicessi; Michael John Ackerman; Tarek Kashour

    doi:10.1101/2020.06.16.20132878 Date: 2020-06-18 Source: medRxiv

    Abstract Importance The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects. Objective To systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19. Data Sources A systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists. Study Selection Studies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias MESHD arrhythmias HP. Data Extraction and Synthesis Study characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes MESHD torsades de pointes HP (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori. Main Outcomes and Measures Pooled Incidence of: (1) change in QTc value from baseline [≥] 60 ms, (2) QTc [≥] 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular HP ventricular tachycardia MESHD tachycardia HP (VT) or cardiac arrest HP, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias HP. Results A total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia HP or VT or cardiac arrest HP was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias HP was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of [≥] 60 ms was 7%, 95% CI (3-14), I2=94% (12 studies of 2008 patients). The pooled incidence of QTc [≥] 500 ms was 6%, 95% CI (2-12), I2=95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of [≥] 60 ms or QTc [≥] 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age TRANS, coronary artery disease MESHD, hypertension MESHD hypertension HP, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions and Relevance Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest HP. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.

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MeSH Disease
Human Phenotype

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