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MeSH Disease

Human Phenotype

Transmission

Seroprevalence

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    Mitigating Arrhythmia HP Arrhythmia MESHD Risk in Hydroxychloroquine and Azithromycin Treated COVID-19 Patients using Arrhythmia HP Arrhythmia MESHD 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/rs.3.rs-50501/v1 Date: 2020-07-29 Source: ResearchSquare

    Background: Hydroxychloroquine and Azithromycin use is associated with QT interval prolongation MESHD and arrhythmias HP arrhythmias MESHD. 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 arrhythmia MESHD risk management plan.Methods and results: We retrospectively examined arrhythmia HP arrhythmia MESHD 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 HP pneumonia MESHD. 7 patients (8.6%) had QTc prolongation MESHD 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 HP ventricular tachycardia MESHD. The risk factors significantly associated with QTc≥500 ms were hypokalemia HP hypokalemia MESHD (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 ventricular arrhythmias MESHD.Conclusion: We recorded a low incidence of QTc prolongation MESHD ≥500 ms and no ventricular tachycardia HP ventricular tachycardia MESHD events in COVID-19 patients treated with Hydroxychloroquine and Azithromycin using cardiac arrhythmia MESHD arrhythmia HP risk management plan.

    The Cardiac Toxicity MESHD 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 MESHD 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 HP torsades de pointes MESHD ( TdP MESHD) 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 MESHD arrhythmia or ventricular HP ventricular tachycardia MESHD tachycardia HP ( VT MESHD) or cardiac arrest HP cardiac arrest MESHD, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias MESHD 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 MESHD were reported; the pooled incidence of TdP arrhythmia MESHD arrhythmia HP or VT MESHD or cardiac arrest HP cardiac arrest MESHD 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 MESHD 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 HP hypertension MESHD, diabetes MESHD, 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 MESHD, which is a harbinger for drug-induced TdP MESHD/ VT MESHD or cardiac arrest HP cardiac arrest MESHD. CQ/HCQ use resulted in a relatively higher incidence of TdP MESHD 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 MESHD, with adequate safety monitoring.

    Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring

    Authors: Archana Ramireddy; Harpriya S. Chugh; Kyndaron Reinier; Joseph Ebinger; Eunice Park; Michael Thompson; Eugenio Cingolani; Susan Cheng; Eduardo Marban; Christine Albert; Sumeet S. Chugh

    doi:10.1101/2020.04.22.20075671 Date: 2020-04-25 Source: medRxiv

    Background: Despite a paucity of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19. Both drugs may increase risk of lethal arrhythmias HP arrhythmias MESHD associated with QT interval prolongation MESHD. Methods: We performed a case series of COVID-19 positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett) using 12-lead ECGs. Critical QTc prolongation MESHD was defined as: a) maximum QTc [≥]500 ms (if QRS <120 ms) or QTc [≥]550 (if QRS [≥]120 ms) and b) increased QTc of [≥]60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Results: Of 490 COVID-19 positive/suspected patients, 314 (64%) received either/both drugs, and 98 (73 COVID-19 positive, 25 suspected) met study criteria ( age TRANS 62{+/-}17 yrs, 61% male TRANS). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448{+/-}29 ms and increased to 459{+/-}36ms (p=0.005) with medications. Significant prolongation MESHD was observed only in men (18{+/-}43 ms vs -0.2{+/-}28 ms in women, p=0.02). 12% of patients reached critical QTc prolongation MESHD. In a multivariable logistic regression, age TRANS, sex, Tisdale score, Elixhauser score, and baseline QTc were not associated with critical QTc prolongation MESHD (p>0.14). Changes in QTc were highest with the combination compared to either drug, with many-fold greater prolongation with the combination vs. azithromycin alone (17{+/-}39 vs. 0.5{+/-}40 ms, p=0.07). No patients manifested torsades de pointes HP torsades de pointes MESHD. Conclusions: Overall, 12% of patients manifested critical QTc interval prolongation MESHD, and traditional risk indices failed to flag these patients. With the drug combination, QTc prolongation MESHD was several-fold higher compared to azithromycin alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients with these drugs should be carefully assessed prior to use.

    The QT Interval in Patients with SARS-CoV-2 Infection MESHD Treated with Hydroxychloroquine/Azithromycin

    Authors: Ehud Chorin; Matthew Dai; Eric Shulman; Lailt Wadhwani; Roi Bar Cohen; Chirag Barbhaiya; Anthony Aizer; Douglas Holmes; Scott Bernstein; Michael Soinelli; David S Park; Larry Chinitz; Lior Jankelosn

    doi:10.1101/2020.04.02.20047050 Date: 2020-04-03 Source: medRxiv

    We report the change in the QT interval in 84 adult TRANS patients with SARS-CoV-2 infection MESHD treated with Hydroxychloroquine/Azithromycin combination. QTc prolonged maximally from baseline between days 3 and 4. in 30% of patients QTc increased by greater than 40ms. In 11% of patients QTc increased to >500 ms, representing high risk group for arrhythmia HP arrhythmia MESHD. The development of acute renal failure MESHD but not baseline QTc was a strong predictor of extreme QTc prolongation MESHD.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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