scholarly journals Predictors of QT Interval Prolongation in Critically-ill Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine

Author(s):  
Frederico Scuotto ◽  
Rogério Marra ◽  
Lilian Leite de Almeida ◽  
Mariana Santa Rita Soares ◽  
Gabriela Kurita Silva ◽  
...  

AbstractBackgroundHydroxychloroquine (HCQ) has been described as a potential treatment for SARS-CoV-2 infection. However, there are safety concerns regarding its QT interval and pro-arrhythmic effects.ObjectiveThis trial aimed to determine the predictors of QT interval prolongation and pro-arrhythmic effects in patients hospitalized for SARS-CoV-2 infection and receiving HCQ.MethodsWe performed a retrospective observational study of 45 critically-ill patients hospitalized because of SARS-CoV-2 infection and treated with 800 mg of HCQ at day 1 and 400 mg on days 2–5. Clinical aspects and outcomes, basal and final corrected QT (QTc) interval, and the incidence of arrhythmias and arrhythmogenic death were observed. Independent predictors of QTc prolongation were identified using multivariable logistic regression analysis. QT interval prolongation was considered substantial at final QTc ≥ 480 ms.ResultsThe mean age was 60.9 ± 16.67 years and 28 (62.2%) patients were men. Basal QTc was 442 ± 28 ms, and the final QTc interval was 458 ± 34 ms, for a mean QTc interval variation of 15 ± 11 ms. There was no arrhythmogenic death. The need for hemodialysis remained a statistically significant predictor of QT interval enlargement (odds ratio, 10.34; 95% confidence interval, 1.04 – 102.18; p = 0.045).ConclusionsHCQ promotes mild to moderate QT interval prolongation. The risk of QT interval prolongation is higher among patients with acute renal failure requiring hemodialysis.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Juan Jiménez-Jáimez ◽  
Rosa Macías-Ruiz ◽  
Francisco Bermúdez-Jiménez ◽  
Ricardo Rubini-Costa ◽  
Jessica Ramírez-Taboada ◽  
...  

AbstractSARS-CoV-2 is a rapidly evolving pandemic causing great morbimortality. Medical therapy with hydroxicloroquine, azitromycin and protease inhibitors is being empirically used, with reported data of QTc interval prolongation. Our aim is to assess QT interval behaviour in a not critically ill and not monitored cohort of patients. We evaluated admitted and ambulatory patients with COVID-19 patients with 12 lead electrocardiogram at 48 h after treatment initiation. Other clinical and analytical variables were collected. Statistical analysis was performed to assess the magnitude of the QT interval prolongation under treatment and to identify clinical, analytical and electrocardiographic risk markers of QT prolongation independent predictors. We included 219 patients (mean age of 63.6 ± 17.4 years, 48.9% were women and 16.4% were outpatients. The median baseline QTc was 416 ms (IQR 404–433), and after treatment QTc was prolonged to 423 ms (405–438) (P < 0.001), with an average increase of 1.8%. Most of the patients presented a normal QTc under treatment, with only 31 cases (14.1%) showing a QTc interval > 460 ms, and just one case with QTc > 500 ms. Advanced age, longer QTc basal at the basal ECG and lower potassium levels were independent predictors of QTc interval prolongation. Ambulatory and not critically ill patients with COVID-19 treated with hydroxychloroquine, azithromycin and/or antiretrovirals develop a significant, but not relevant, QT interval prolongation.


2021 ◽  
Vol 2021 ◽  
pp. 1-7 ◽  
Author(s):  
Seyed Parsa Eftekhar ◽  
Sohrab Kazemi ◽  
Mohammad Barary ◽  
Mostafa Javanian ◽  
Soheil Ebrahimpour ◽  
...  

Background. Hydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin. Methods. This study was a retrospective cohort study. One hundred seventy-two confirmed COVID-19 patients were included in this study, hospitalized at Babol University of Medical Sciences hospitals between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment. Results. 83.1% of patients received hydroxychloroquine plus azithromycin vs. 16.9% of patients who received only hydroxychloroquine. The mean age of patients was 59.2 ± 15.4 .The mean of posttreatment QTc interval in the monotherapy group was shorter than the mean of posttreatment QTc interval in the combination therapy group, but it had no significant statistical difference ( 462.5 ± 43.1 milliseconds vs. 464.3 ± 59.1 milliseconds; p = 0.488 ). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline QTc ≥ 450 milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, fourteen patients did not continue therapy after four days. Conclusions. Hospitalized patients treated by hydroxychloroquine with or without azithromycin had no significant difference in prolongation of QT interval and outcome. The numbers of patients with prolonged QT intervals in this study emphasize careful cardiac monitoring during therapy, especially in high-risk patients.


2022 ◽  
Vol 27 ◽  
pp. 107424842110694
Author(s):  
Wasim S. El Nekidy ◽  
Khalid Almuti ◽  
Hazem ElRefaei ◽  
Bassam Atallah ◽  
Lana M. Mohammad ◽  
...  

Background: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population. Methods: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms). Results: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation ( P = .004 for the likelihood-ratio test). Conclusion: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.


Author(s):  
Juan J Jaimez ◽  
Rosa Macias ◽  
Francisco Bermudez ◽  
Ricardo Rubini ◽  
Miguel Alvarez ◽  
...  

Objectives. SARS-CoV-2 is a rapidly evolving pandemic causing great morbimortality. Medical therapy with hydroxicloroquine, azitromycin and protease inhibitors is being empirically used, with reported data of QTc interval prolongation. Our aim is to assess QT interval behaviour in a not critically ill and not monitored cohort of patients. Design. We evaluated admitted and ambulatory patients with COVID-19 patients with 12 lead electrocardiogram at 48 hours after treatment initiation. Other clinical and analytical variables were collected. Statistical analysis was performed to assess the magnitude of the QT interval prolongation under treatment and to identify clinical, analytical and electrocardiographic risk markers of QT prolongation independent predictors. Results. We included 219 patients (mean age of 63.6 +/- 17.4 years, 48.9% were women and 16.4% were outpatients. The median baseline QTc was 416 ms (IQR 404-433), and after treatment QTc was prolonged to 423 ms (405-438) (P < 0.001), with an average increase of 1.8%. Most of the patients presented a normal QTc under treatment, with only 31 cases (14,1 %) showing a QTc interval > 460 ms, and just one case with QTc > 500 ms. Advanced age, longer QTc basal at the basal ECG and lower potassium levels were independent predictors of QTc interval prolongation. Conclusions. Ambulatory and not critically ill patients with COVID-19 treated with hydroxychloroquine, azithromycin and/or antiretrovirals develop a significant, but not relevant, QT interval prolongation.


Author(s):  
Amy D Morris ◽  
Jennifer Chen ◽  
Elaine Lau ◽  
Jennifer Poh

<p><strong>ABSTRACT</strong></p><p><strong>Background: </strong>Domperidone is a prokinetic agent used to treat pediatric gastroesophageal reflux disease. Health Canada has issued warnings about an increased risk of domperidone-associated ventricular arrhythmias and sudden cardiac death. However, the supporting data referred only to adult patients; therefore, extrapolating the safety risks to pediatric patients is difficult.</p><p><strong>Objective: </strong>To summarize and evaluate the evidence for domperidone associated QT interval prolongation, ventricular arrhythmias, and sudden cardiac death to determine the safety of this drug for pediatric patients.</p><p><strong>Data Sources: </strong>Two databases (MEDLINE [1946 to August 2015] and Embase [1980 to August 2015]) were searched with the following Medical Subject Headings and keywords: “domperidone”, “arrhythmias, cardiac”, “death, sudden, cardiac”, “electrocardiography”, “heart diseases”, “long QT syndrome”, “tachycardia, ventricular”, “torsades de pointes”, and “ventricular fibrillation”. The search was limited to studies conducted in humans under 18 years of age and published in English.</p><p><strong>Study Selection and Data Extraction:</strong> Original research included in this review reported on the cardiac-related safety of domperidone in nononcologic patients under 18 years of age.</p><p><strong>Data Synthesis: </strong>Of the 5 studies meeting the inclusion criteria (<em>n </em>= 137 patients), one reported a statistically significant change in the corrected QT (QTc) interval, but the clinical significance was unclear. Most of the studies reported rare occurrences of pathological QTc intervals in a limited number of patients. However, confounding factors (e.g., abnormal electrolyte level or concurrent medications) were not consistently considered. Potential bias might have been alleviated by blinding of electrocardiogram (ECG) assessors; however, this was not consistently implemented. The designs of the included studies did not allow assessment of causality. The results should be interpreted with caution.</p><p><strong>Conclusions: </strong>Although the available evidence is limited, pathological QTc intervals were noted among a small number of infants, which supports the possibility of domperidone-associated risk of prolonged QTc interval. Because of the potential severity of QT interval prolongation, individual assessment and routine ECG monitoring should be implemented for patients receiving domperidone.</p><p><strong>RÉSUMÉ</strong></p><p><strong>Contexte : </strong>La dompéridone est un agent gastroprocinétique utilisé pour traiter le reflux gastro-oesophagien chez l’enfant. Santé Canada a publié des mises en garde à propos d’un risque accru d’arythmies ventriculaires et de mort subite cardiaque associées à la dompéridone. Or, comme les données probantes ne concernent que l’adulte, il est difficile de généraliser les risques pour la santé à l’enfant.</p><p><strong>Objectif : </strong>Résumer et analyser les données probantes portant sur l’allongement de l’intervalle QT, les arythmies ventriculaires et la mort subite cardiaque associés à la dompéridone afin de déterminer le degré d’innocuité du médicament chez l’enfant.</p><p><strong>Sources des données : </strong>Deux bases de données (MEDLINE [1946 à août 2015] et EMBASE [1980 à août 2015]) ont été interrogées en utilisant les mots clés et les Medical Subject Headings (MeSH) suivants : « domperidone »  dompéridone), « arrhythmias, cardiac » (arythmies cardiaques), « death, sudden, cardiac » (mort, subite, cardiaque),« electrocardiography » (électrocardiographie), « heart diseases » (cardiopathies), « long QT syndrome » (syndrome du QT long), « tachycardia, ventricular » (tachycardie, ventriculaire), « torsades de pointes » (torsades de pointes) et « ventricular fibrillation » (fibrillation ventriculaire). La recherche se limitait aux études publiées en anglais et effectuées chez l’humain de moins de 18 ans.</p><p><strong>Sélection des études et extraction des données : </strong>Les études retenues dans la présente revue abordaient l’innocuité cardiaque de la dompéridone chez les patients de moins de 18 ans qui ne sont pas atteints d’un cancer.</p><p><strong>Synthèse des données : </strong>Parmi les cinq études qui répondaient aux critères d’inclusion (<em>n </em>= 137 patients), une indiquait un changement statistiquement significatif dans l’intervalle QT corrigé (QTc), mais la signification clinique demeurait floue. La plupart des études signalaient de rares cas d’intervalles QTc pathologiques chez un nombre limité de patients. Cependant, des facteurs de confusion (déséquilibre électrolytique ou emploi concomitant de médicaments, par exemple) n’étaient pas systématiquement pris en compte. Il aurait été possible d’éviter de potentiels biais en tenant les lecteurs d’électrocardiogramme (ECG) dans l’ignorance du traitement, mais cette mesure n’était pas toujours mise en oeuvre. Les plans des études retenues ne permettaient pas d’évaluer la causalité. Il faut donc interpréter les résultats avec prudence.</p><p><strong>Conclusions : </strong>Bien qu’il n’y ait que peu de données probantes, des cas d’intervalles QTc pathologiques ont été relevés chez un petit nombre de nourrissons, ce qui vient appuyer le risque possible d’allongement de l’intervalle QTc associé à la dompéridone. À cause de la potentielle gravité de l’allongement de l’intervalle QT, une évaluation individuelle et une surveillance ECG systématique doit être mise en place pour les patients qui reçoivent de la dompéridone.</p>


2008 ◽  
Vol 109 (2) ◽  
pp. 206-212 ◽  
Author(s):  
Beny Charbit ◽  
Jean Claude Alvarez ◽  
Eric Dasque ◽  
Emuri Abe ◽  
Jean Louis Démolis ◽  
...  

Background Droperidol and ondansetron have previously been found to prolong the QT interval in the treatment of postoperative nausea and vomiting. However, this adverse effect has never been confirmed and compared with both drugs under controlled conditions. The objective was to study the effects of droperidol and ondansetron alone or in combination on QT interval duration in healthy subjects. Methods Sixteen healthy volunteers, eight males and eight females, were enrolled in this prospective, double-blind, randomized, placebo-controlled study. Subjects received 1 mg droperidol, 4 mg ondansetron, 1 mg droperidol plus 4 mg ondansetron, or a placebo, intravenously in a crossover design. Fridericia-corrected QT interval (QTcF) and plasma concentrations were measured repeatedly during 10 h at each study period. The primary endpoint was the maximal placebo time-matched and baseline-subtracted QTcF prolongation (DeltaDeltaQTcF). Results Compared with placebo, both droperidol and ondansetron significantly prolonged the QTcF interval. DeltaDeltaQTcF prolongation was 25 +/- 8 ms after droperidol, significantly greater than the 17 +/- 10-ms prolongation with ondansetron (P = 0.014). The combination of droperidol and ondansetron significantly increased the mean maximal DeltaDeltaQTcF by 28 +/- 10 ms. The combination induced greater QTcF prolongation compared with ondansetron alone (P = 0.001), but not with droperidol alone (P = 0.33). There was no significant pharmacokinetic interaction between droperidol and ondansetron. Conclusions Under controlled conditions, both droperidol and ondansetron either alone or in combination induced significant marked QTc interval prolongation. However, the combination of both drugs did not significantly increase QTc prolongation compared with that induced by droperidol alone.


2018 ◽  
Vol 46 (5) ◽  
pp. 1990-2000 ◽  
Author(s):  
Chengluan Xuan ◽  
Nan Wu ◽  
Yanhui Li ◽  
Xiaoting Sun ◽  
Qunshu Zhang ◽  
...  

Objective This study was performed to observe the occurrence of corrected QT (QTc) interval prolongation during anesthetic induction for laryngeal mask airway insertion and the effects of cisatracurium administration on the QTc interval. Methods Eighty-eight patients were assigned to two groups: the cisatracurium administration group (n = 45) and non-cisatracurium administration group (n = 43). The QTc interval was continuously recorded by a 12-lead Holter electrocardiogram beginning in the hospital ward and continuing until after anesthetic induction. Results In the cisatracurium administration group, the QTc interval significantly increased from 417.9 ± 27.9 to 451.6 ± 32.5 ms after arrival in the operating room and significantly decreased to 432.4 ± 32.5 ms after a 15-minute rest; it significantly increased to 459.7 ± 23.8 ms again after propofol and fentanyl injection. However, the QTc interval decreased after cisatracurium injection. In the non-cisatracurium administration group, the QTc interval initially showed changes similar to those in the cisatracurium group until fentanyl and propofol were injected. Conclusions The QTc interval was significantly prolonged on arrival in the operating room and after propofol and fentanyl injection. The QTc interval did not significantly change by laryngeal mask airway insertion regardless of the administration of cisatracurium.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Abellas Sequeiros ◽  
C Lozano Granero ◽  
C Garcia Sebastian ◽  
E Franco Diez ◽  
A Hernandez Madrid ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Off-label use of drugs with potential for QT interval prolongation was common in COVID-19 patients. We tested a portable EKG recording device to measure and monitor corrected QT (QTc) intervals in a cohort of COVID-19 patients treated with azithromycin, hydroxychloroquine, lopinavir/ritonavir, or combinations of these drugs. Methods and results Sixty-nine patients hospitalized with pneumonia and confirmed SARS-CoV 2 infection were included in an observational single-centre study. Six-lead EKG recordings were obtained using a KardiaMobile6L® at physicians’ discretion. In a subgroup of 16 patients with early discharge, a device was provided for at-home daily monitoring. Significant QTc interval prolongation was observed in patients taking a combination of 2 or 3 drugs (426 ± 33 vs 408 ± 33 ms, p = 0,002; and 435 ± 30 vs 394 ± 31 ms, p = 0,001, respectively). The use of the device prompted a change in the treatment of 9 patients (13%) because of prolongation of QTc interval and anticoagulation was started in one patient because of atrial fibrillation diagnosis. In the subgroup of patients with daily recording, QTc interval prolongation peaked at day 2 ± 1,8, with a shorter final QT interval than that recorded before drug initiation (350,0 ± 31,4 vs 381,0 ± 21,2; p = 0,019), pointing to a possible role of the disease itself in QT interval modification. To assess the consistency of measurements of QTc interval, a random sample of 120 EKG recordings were analyzed by two different physicians. Inter-operator intraclass correlation coefficient was 0,702, 95% CI (0,578-0,789). Conclusions Portable EKG-recording device was useful for QTc interval monitoring in COVID-19 patients receiving drugs with QTc prolonging potential, allowing physicians to adapt management. Significant QT prolongation was observed in these patients. Characteristics of the three groups.Group 1(one drug)N= 9 (13,0%)Group 2(two drugs)N= 37 (53,6%)Group 3(three drugs)N= 23 (33,3%)p-valueClinical characteristicsAge (years)55,0 ± 18,366,0 ± 16,258,0 ± 15,8p = 0,248Male sex (%)6 (66,7%)25 (67,6%)18 (78,3%)p = 0,643Dislipidaemia (%)5 (55,6%)9 (24,3%)7 (30,4%)p = 0,749Diabetes (%)7 (77,8%)4 (10,8%)5 (21,7%)p = 0,525Hypertension (%)3 (33,3%)16 (43,2%)8 (34,8%)p = 0,387Previous cardiopathy (%)6 (66,7%)11 (29,7%)3 (13,0%)p = 0,305COPD (%)7 (77,8%)6 (16,2%)1 (8,7%)p = 0,679COPDchronic obstructive pulmonary disease.Abstract Figure. Baseline and maximum QTc intervals


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