Search

Drug-induced prolongation of the QT interval is common in a variety of pharmaceutical treatments and can lead to serious clinical outcomes. Although substantial efforts have been made to prevent drug-induced QT interval prolongation, the lack of a centralized data source remains the main obstacle to further study of the underlying mechanism and the development of effective prediction strategies. To fill this gap, we propose a schema for stratifying the risk of marketed QT prolonging drugs based on US Food and Drug Administration (FDA)-approved drug labeling and developed a Drug-Induced QT Prolongation Atlas (DIQTA). Potential application of DIQTA was shown by precision dosing in off-label use and therapeutic strategy optimization, as well as the facilitation of artificial intelligence (AI)-based modeling in predictive toxicity.

Background: QTc prolongation is common in dangerous clinical conditions, associated with an increased risk of life-threatening arrhythmia torsades de pointes. The goal of this short communication is to evaluate the principal causes of risk of QTc prolongation that are observed in an emergency department and discuss the differences between drug- and non-drug-associated factors. Methods: The retrospective analysis was carried out on 130 patients that presented a QTc prolongation (>480 ms for man and >470 for female, respectively), admitted to the emergency department of a single Italian hospital. Patients with pace-maker (22) were excluded from this study. For each patient, a minimum of 3 ECGs (12 leads) were recorded. Attention was paid on electrolytes disturbances and to the pharmacotherapy, with a particular emphasis to the use of antibiotics. Results: Mean age of the patients was 79.6 years (SD=11.3) and females and males were almost equally present (46.6% F, 53.7% M). The average QTc value was 492.2 ms (493.3 ms F, 492.8 M). The patients were divided in those with electrolytes disturbances (24.0%), antimicrobial therapy (35.2%), both antimicrobial therapy and electrolytes disturbances (24.1%), and other causes of QTc prolongation (16.7%). Conclusion: This analysis shows the relevance of the empirical therapy established at the admission, in particular for infective diseases, as an important risk factor for the prolongation of QTc. Other factors that can increase the risk are electrolytes alterations, advanced age, cardiovascular diseases, and drug-drug interaction.

Prolongation of the QTc interval is associated with an increased risk of malignant ventricular dysrhythmias, such as ventricular tachycardia (VT), and sudden cardiac death. The quantifiable risk rates of adverse dysrhythmic outcome in relation to specific QTc interval length are not known. We conducted a literature review on the topic of QT interval prolongation in adult patients and the associated risk of malignant dysrhythmic event. We specifically formulated our literature search and subsequent literature review to address the following question: Can the clinician identify specific QTc intervals at which a specific quantifiable risk of malignant dysrhythmic event (malignant ventricular dysrhythmia and/or cardiac arrest) occurs in an undifferentiated adult patient population? In the literature search, we identified 701 studies; upon review using specific, pre-determined inclusion criteria, we identified 16 articles for inclusion in the review. From this literature, we were unable to answer the question in a quantifiable manner and only noted that the risk of malignant dysrhythmic event increases with progressively longer QTc interval. The current literature on this topic is inadequate to answer this important question due to heterogenous study methodology, patient populations, endpoints, and periods of observation. Additional prospective research is required on this topic, aimed at addressing the important issue of specific, quantifiable risk and its relation to degree of prolongation of the QTc interval.

Pharmacokinetics-matched digital electrocardiogram data (n = 503 measurements from 180 patients) collected in a first-in-human, multi-part, dose-escalation (from 80 to 800 mg) and dose expansion (at 480 mg) phase 1 study in patients with advanced solid malignancies, were used to assess potential risk of QT prolongation associated with the AKT inhibitor capivasertib. The relationship between plasma drug concentrations and baseline-adjusted Fridericia-corrected QT (ΔQTcF) values was estimated using a prespecified linear mixed-effects model. The model provided an unbiased reproduction of the experimental data set, estimating a small but positive correlation between capivasertib concentration and ΔQTcF. At the expected therapeutic dose (400 mg twice daily) the predicted mean ΔQTcF at the steady state maximum concentration was 3.97 ms with an upper limit of the 90% CI of 5.07 ms; below the 10 ms limit proposed by ICH E14 guidance. This analysis suggests that capivasertib is not expected to present a clinically significant risk for QT prolongation that is associated with pro-arrhythmic effects.

A case report of unusual QT interval prolongation after ventricular premature beat is presented.

Background: Drug-induced prolongation of cardiac repolarization limits the treatment with many psychotropic drugs. Recently, the contribution of polygenic variation to the individual duration of the QT interval was identified. Aims: To explore the interaction between antipsychotic drugs and the individual polygenic influence on the QT interval. Methods: Retrospective analysis of clinical and genotype data of 804 psychiatric inpatients diagnosed with a psychotic disorder. The individual polygenic influence on the QT interval was calculated according to the method of Arking et al. Results: Linear regression modelling showed a significant association of the individual polygenic QT interval score (ßstd = 0.176, p < 0.001) and age (ßstd = 0.139, p < 0.001) with the QTc interval corrected according to Fridericia’s formula. Sex showed a nominal trend towards significance (ßstd = 0.064, p = 0.064). No association was observed for the number of QT prolonging drugs according to AZCERT taken. Subsample analysis ( n = 588) showed a significant association of potassium serum concentrations with the QTc interval (ßstd = −0.104, p = 0.010). Haloperidol serum concentrations were associated with the QTc interval only in single medication analysis ( n = 26, ßstd = 0.101, p = 0.004), but not in multivariate regression analysis. No association was observed for aripiprazole, clozapine, quetiapine and perazine, while olanzapine and the sum of risperidone and its metabolite showed a negative association. Conclusions: Individual genetic factors and age are main determinants of the QT interval. Antipsychotic drug serum concentrations within the therapeutic range contribute to QTc prolongation on an individual level.

Background Toxicity and side effects of long-term use of opioids are well studied, but little information exists regarding electrophysiological disturbances of opium consumption. While natural opium has been regarded safe to a great extent among traditional communities, concerns are emerging owing to the available evidence of QT prolongation that have been exposed during recent outcome surveillance of patients under opioid use. Potential QT prolonging interactions would raise a higher level of such concern in opium users during COVID pandemic and warrant attention. Materials and methods This study was designed to detect the prevalence of QTc prolongation among opium users and nonusers. Two groups were compared with regard to gender, age, and median QTc interval. Normal and prolonged QTc intervals of user group were compared with respect to age, sex, dose of opium consumption, and duration of opium consumption. Results 123 opium users and 39 controls were investigated. Median QTc interval in opium user and non-user group was 460 vs 386 milliseconds, respectively (p value < 0.001). In all, 59.3%, (95% CI: 50.51–67.62%) of cases and none of non-user had prolonged QTc interval (p value < 0.001). There was no significance between normal and prolonged QTc intervals with respect to dose and duration of opium use. Conclusion This study indicated that opium consumption is associated with QTc prolongation. This prolongation does not relate to dose and duration of opium use. Further study is propounded to assess the clinical significance of these results and to determine risk rating of opium compared to other opioids in this regard. How to cite this article Javadi HR, Mirakbari SM, Allami A, Yazdi Z, Katebi K. Opium-associated QT Interval Prolongation: A Cross-sectional Comparative Study. Indian J Crit Care Med 2021;25(1):43–47.

QT Interval prolongation is common in insulin resistance state obesity. Insulin-induced hyperpolarization might be involved in ventricular repolarization leading to QTc lengthening. Therefore, this study is designated to investigate the relationship between corrected QT interval (QTc) prolongation and insulin resistance in obese adult male subjects. Apparently healthy adult male subjects (n=100) aged between 18-35 years residing in Magway Township were recruited by simple random sampling method. Then all the eligible subjects were categorized into 2 groups: non-obese [body mass index (BMI) 18.5 to 24.9 kg/m2, n= 40] and obese group [BMI ≥ 30.0 kg/m2, n=60] by their anthropometric parameters. Serum fasting glucose was measured by glucose oxidase method. Serum insulin level was determined by Enzyme-Linked Immunosorbent Assay (ELISA). Insulin sensitivity was calculated by Homeostatic Model Assessment (HOMA-IR). The QT interval was measured by routine 12-lead ECG and corrected QT interval (QTc) was calculated according to Bazett’s formula. In the present study, insulin sensitivity (HOMA-IR) was higher in obese subjects (4.64±2.3) than that of non-obese subjects (2.5±0.89) (p< 0.001). There was significant positive correlation between QTc and HOMA-IR (r = 0.41, p< 0.001, n = 100) in this study. HOMA-IR >3.8 was considered as insulin resistance (IR) and QTc > 440ms was regarded as QTc interval prolongation. Insulin resistance was significantly associated with prolonged QTc interval in the study population (X2=7.3, p< 0.05, n=100). Risk of QTc interval prolongation was 3.4 times higher in subjects with IR (Odd ratio = 3.4; 95% confidence interval = 1.37 to 8.45). It was concluded that prolonged QTc interval is associated with insulin resistance state.

QTc interval prolongation is common in patients with liver cirrhosis. Cirrhotic patients suffering from complications could also prolong QT interval. We aimed to explore the role of QTc interval prolongation in cirrhotic patients with upper gastrointestinal bleeding (UGIB). Overall, 167 patients were analyzed. QTc interval prolongation presented in 111 patients (66.5%). One hundred and seven patients (64.1%) suffered from acute UGIB. Results showed that RBC, Hb, ALB and calcium (Ca) were significantly lower, and DBIL, GGT, APTT, Child-Pugh score, MELD score and ALBI score were significantly higher in the prolongation group than those without QTc prolongation. AUROC of QTc was .699 (95%CI: .623-.768). In the acute UGIB subgroup, AUROC of QTc was .478 (95%CI: .347-.611). In the HBV subgroup, AUROC of QTc was .722 (95%CI: .616-.812). QTc interval prolongation was prevalent in cirrhotic patients with UGIB and correlated with liver dysfunction. QTc might not be a valid predictor of in-hospital mortality.

QTc stands for heart-rate corrected QT interval on the electrocardiogram and is a measure of the efficiency of repolarization of the left ventricle. Excessive prolongation, generally considered to be >500 ms, can result in a potentially fatal ventricular arrhythmia known as torsade de pointes. Some psychiatric medications can cause this arrhythmia and, therefore, this issue is important to all prescribers of psychiatric medications. It is also important to keep in mind that there are multiple algorithms used to calculate the QTc. The Bazett's algorithm, one of the most commonly used algorithms on electrocardiogram machines, can produce an artificially prolonged QTc; however, the use of this algorithm is not generally identified on the printout from the electrocardiogram machine, which can cause unnecessary concern and delay treatment of patients. For these reasons, this article explains the basic concepts of the QT interval and QTc interval and discusses why it is important for psychiatrists and other prescribers to know this information. A case report is then used to illustrate the clinical application of this knowledge so that effective treatment is not unnecessarily delayed.

Many drug therapies are associated with prolongation of the QT interval. This may increase the risk of Torsades de Pointes (TdP), a potentially life-threatening cardiac arrhythmia. As the QT interval varies with a change in heart rate, various formulae can adjust for this, producing a ‘corrected QT’ (QTc) value. Normal QTc intervals are typically 65 years, uncorrected electrolyte disturbances); the potential risk and degree of QT prolongation associated with the proposed drug; and co-prescribed medicines that could increase the risk of QT prolongation. To support clinicians, who are likely to prescribe such medicines in their daily practice, we developed a simple algorithm to help guide clinical management in patients who are at risk of QT prolongation/TdP, those exposed to QT-prolonging medication or have QT prolongation.

Objective To summarize the proposed mechanisms behind hypertension and QT interval prolongation associated with use of targeted systemic cancer therapies and provide recommendations for monitoring or managing these toxicities. Summary The cardiotoxic effects of targeted systemic cancer therapies represents a new paradigm of cancer treatment associated cardiovascular adverse events. National guidelines regarding optimal monitoring and management strategies for hypertension and QT interval prolongation associated with use of these therapies are lacking. While the pathophysiological drivers of hypertension due to targeted systemic cancer therapies differ by class of targeted therapy, general management strategies do not. Routine blood pressure monitoring throughout the duration of therapy is recommended for all agents. Patients who experience hypertension often can be treated with the addition or modification of antihypertensive therapies. Uncontrolled hypertension despite optimal medical management may require dose modifications or discontinuation of the targeted systemic cancer therapy. Electrocardiogram monitoring is recommended for patients who receive targeted therapies that may prolong the QT interval. Minimizing or managing drug interactions with other QT prolonging medications is recommended in addition to ensuring adequate electrolyte supplementation. Dose modifications or discontinuation of the targeted systemic therapy may be necessary for patients who experience QT interval prolongation. Conclusions Appropriate cardiovascular monitoring and timely management of treatment-emergent toxicities can optimize therapy for patients receiving targeted systemic cancer therapies associated with a risk of drug-induced hypertension or QT interval prolongation.

Background The corrected QT (QTc) interval is a strong predictor of ischaemic heart disease and cardiovascular mortality. It may trigger lethal arrhythmias and sudden death. Risk factors include electrolyte disorders, medications, prior cardiovascular disease and genetic predisposition. We previously demonstrated that QTc intervals are prolonged in patients hospitalised with pneumonia, regardless which antibiotics were given. It is unclear whether QTc prolongation is associated with pneumonia itself or whether it occurs with other infections. Aims To investigate any association between hospitalisation for infection and QTc prolongation. Methods We enrolled 169 patients, 160 of whom were used for analysis. QTc was measured in seconds by routine electrocardiogram (ECG) on admission. Subsequently, daily ECG were performed for 3 days, or until discharge (whichever occurred sooner). When clinically significant QTc prolongation was detected, possible causes were investigated. Results Clinically significant prolongation was not observed in any patient. The QTc was slightly longer in patients hospitalised for pneumonia or upper respiratory tract infections on admission. It was also prolonged in men, in patients with ischaemic heart disease, hypertension, history of cerebrovascular accident or cancer. A very slight trend for prolongation was observed between the first and second day of monitoring, however it later returned to baseline levels. Nearly 54% of study participants had positive systemic inflammatory response syndrome scores, however no association was detected between their score and baseline QTc, or any subsequent prolongation. Conclusions We found no association between hospitalisation due to infection and prolongation of the QTc interval.

Although the association between antipsychotic use and corrected QT interval (QTc) prolongation has been repeatedly confirmed, the relationship has been rarely studied in a practical setting. Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP) survey, our study aimed to investigate the prevalence and clinical correlates of QTc prolongation in 2553 Asian patients with schizophrenia. After adjusting for the potential effect of confounding factors, the baseline and clinical characteristics of the schizophrenia patients with and without QTc prolongation were compared using analyses of covariance and binary logistic analyses. In addition, a binary logistic analysis model with a forward selection method was used to identify the distinctive clinical correlates of QTc prolongation. QTc prolongation was noted in 1.1% of Asian patients with schizophrenia. Schizophrenia patients were characterized by lower proportions of disorganized speech and negative symptoms; higher use of amisulpride and clozapine; and higher proportions of rigidity, hypercholesterolemia, and sedation than those without QTc prolongation. Finally, a binary logistic mode showed that amisulpride, clozapine, rigidity, and hypercholesterolemia might be the distinctive clinical correlates of QTc prolongation in Asian patients with schizophrenia. These findings indicate the clinical implications that the uses of amisulpride and clozapine and the occurrences of rigidity and hypercholesterolemia may be potential risk factors for QTc prolongation of schizophrenia patients.

The assessment of the QT interval has been an integral part of ECG interpretation since the first descriptions of long QT syndrome by Wolff in 1950 and by Jervell and Lange-Nielsen in 1957. The correct measurement of the QT interval as well as a correct interpretation of the causes and of the clinical consequences of a QT prolongation, however, may be difficult even for trained internists and cardiologists. In this review, we give an overview on physiological determinants of cardiac repolarization, its marker in the surface ECG – the QT interval –, methods to correctly assess QT interval duration, causes for pathologically prolonged QT intervals, and resulting clinical consequences. A correct measurement of the QT interval should be performed by using the „tangent method“, excluding possible U waves. A heart rate correction formula should be employed to determine the heart rate corrected QT interval (QTc).Many factors, which may prolong the QT interval, should be checked whenever a QTc prolongation is observed. These include drugs, electrolyte imbalances, hormonal influence, and comorbidities. The correct management of a patient with (genetically determined) LQTS starts with a risk stratification based on genotype, ECG phenotype, clinical history, age, sex, concomitant diseases, drug therapies, and family history for syncope or sudden cardiac death. The therapeutic approaches for LQTS are multimodal. Prevention is the basis of the therapy and includes avoiding known risk factors / and potentially QT-prolonging drugs, and a pharmacological treatment with non-selective beta blockers. According to the risk profile and to the patient’s lifestyle the implantation of an ICD or a pacemaker should be considered.

The QT interval represents the duration of ventricular depolarization and repolarization. It is measured from the beginning of the QRS complex to the end of the T wave. Prolongation of the QT interval may be congenital or acquired. This increases the risk of polymorphic ventricular tachycardia (i.e torsades de pointes) and cardiac arrest. To increase the awareness of this life-threatening phenomenon I outline an illustrative case in which acquired prolongation of the QT interval due to electrolyte derangement and administration of ciprofloxacin resulted in cardiac arrest due to torsade de pointes. Management of a patient with a long QT syndrome includes Immediate cessation of drugs that prolong the QT interval; cardiac monitoring, serial 12 lead ECGs and transthoracic echocardiography; measurement of serum electrolytes; intravenous potassium replacement; intravenous magnesium replacement; beta-blockade. Causes of acquired prolongation of the QT interval are common in critically ill patients. It is important to recognize this and consider screening with 12 lead ECG to reduce the risk of life-threatening ventricular arrhythmias.

Objective: In hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer (MBC), endocrine therapy (Tx) combined with an inhibitor of cycline-dependent kinases 4/6 (CDK4/6i) has now widely been accepted as the new standard-of-care in the first- and second-line setting. Among different agents available, the CDK4/6i ribociclib (RIBO) has been documented to be able to prolong cardiac repolarization as measured by the corrected QT interval (QTc). Cardiac monitoring by consecutive echocardiograms (ECGs) is thus recommended in MBC patients (pts) while being on RIBO treatment. However, little is known about the incidence and severity of QTc prolongation during RIBO therapy which should thus be further analyzed in the present investigation. Methods: A total of 29 pts were included, 7 pts were premenopausal and 22 were postmenopausal. All premenopausal pts underwent ovarian suppression with goserelin (ZOL). Endocrine treatment consisted of letrozole (LET) in 23 pts, exemestane (EXE) in 1 pt and fulvestrant (FULV) in 5 pts. In all pts, QTc was measured at start of RIBO and thereafter every 2-4 weeks (wks) for a maximum of 262 days while being on treatment. Mean QTc values were calculated at baseline (BL) and at 6 consecutive time points: #1 (d7-21 from BL), #2 (22-42d from BL), #3 (d43-63 from BL), #4 (d64-84 from BL), #5 (d85-105 from BL), #6 (d105-126 from BL). Changes of mean QTc values were analyzed with repeated measure ANOVA with p≤0.05 indicating statistical significance. Results: QTc showed a slight but not significant increase during RIBO Tx (p=0.306) with a maximum at #3. Whenever observed, QTc prolongation did not exceed 110% from BL in all but 4 pts. In the latter, QTc returned to normal values in all but 1 pt. OTc exceeding 480 ms were not observed at any time of the observation time. At BL, 17 pts had a normal ECG whereas 9 pts had preexisting ECG abnormalities other than long QT syndrome. 3 pts with normal ECG at BL developed ECG abnormalities during Tx with RIBO. No patient experienced a significant deterioration of cardiac ejection fraction while being on Tx. Conclusion: Clinically meaningful QTc prolongations did not occur in this real-world population of MBC pts treated with RIBO and endocrine agents. Moreover, cardiac function did not deteriorate during RIBO Tx neither in patients with normal ECG nor in those with (preexisting or newly diagnosed) ECG abnormalities. QTc prolongations induced by RIBO may thus be of minor importance in the clinical routine and the necessity of intensive ECG monitoring in pts subjected to RIBO is thus a matter of debate. Citation Format: Christian M Kurbacher, Alexander Schott, Ann T Kurbacher, Susanne Herz, Lotta A Fischer, Jutta A Kurbacher, Mathias Warm. QT-interval prolongation during the treatment with ribociclib and endocrine agents in patients with hormone receptor-positive, human epidermal growth factor 2-negative metastatic breast cancer: A real-world experience [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-22.

“Torsades de pointes”, a life-threatening rhythm disorder, is a polymorphic ventricular tachycardia that usually develops in association with a prolonged QT interval. Fluconazole, an anti-fungal drug, may also induce QT prolongation, in some cases subsequent torsades de pointes. Herein, we report a 16-year-old female presenting “torsades de pointes” after administration of fluconazole and rapidly improved upon cessation of the drug.

Background The QT interval prolongation was associated with fatal arrhythmias and cardiac death. However, there were not adequate data to clarify the situation of QT interval prolongation in primary biliary cholangitis (PBC) patients. The aim of this study was to clarify the rate and the associated risk factors of corrected QT (QTc) interval prolongation in PBC patients. Methods From January 2016 to December 2020, PBC patients were retrospectively enrolled. The rate of QTc interval prolongation was surveyed and the associated risk factors were clarified by univariate and multivariate analyses. Results Among the 189 PBC patients, 24.3% (46/189) had the QTc interval prolongation. The univariate analysis showed that age, Child‐Pugh classification, creatinine, international normalized ratio (INR), and platelet (PLT) were associated with QTc interval prolongation in the PBC patients. The multivariate analysis further showed only age (p = .028) and Child‐Pugh classification (p = .035) were the associated risk factors. It had the highest risk of QTc interval prolongation (as high as 64.3%) in the patients who were more than 62.5 years old and with Child‐Pugh C. Conclusion The QTc interval prolongation was frequent in PBC patients, especially in the patients with decompensated cirrhosis. The rate of QTc interval prolongation was as high as 64.3% in the PBC patients who were more than 62.5 years old and classified as Child‐Pugh C.

The correct measurement of the QT interval (using the QT correction formulas, preferably Fridericia and Framingham) as well as a correct interpretation of the causes and of the clinical consequences of a QT prolongation is very important in clinical practice. Drug-induced long QT syndrome (DILQTS) is one of the most common causes of LQTS. In the diagnosis and management of the DILQTS, it can be useful to follow the three-step rule presented in this article: detailed pharmacological anamnesis and correct ECG interpretation; database search and clinical interpretation; confirmatory test.

Background Ondansetron is one of the commonly prescribed anti-emetic in emergency department however, high dose of the drug is associated with prolonged QT interval. This study was designed to evaluate the effect of ondansetron on prolongation of QT interval among patients referred to our emergency department. Methods In this cross-sectional study patients referred to the emergency department of Imam Reza hospital from June 2019 to December 2019 were included. Before the administration of ondansetron 12-lead electrocardiography was performed in all the patients. 4 mg of i.v. ondansetron was administered to these patients and ECG was obtained again. QT interval was calculated automatically from the system from these electrocardiographs. Demographic data of these patients along with QT interval findings was recorded in the questionnaire and analyzed statistically using SPSS software. Results A total of 55 patients were included with the mean age of 58 ± 13 years, where 36 were females (65.5%) and 19 were males (34.5%). The mean QT interval before and after injection of 4 mg intravenous ondansetron was not statistically significant, p-value = 0.073. Similarly, QT interval before and after the administration of the drugs was also not significantly different among females and males, p = 0.479 and p = 0.078, respectively. The age of the patients was also not associated with prolonged QT interval, p = 0.948. Conclusions The findings of our study indicated that 4 mg i.v. administration of ondansetron among non-cardiac patients referred to emergency department is not associated with QT interval prolongation., Highlights • Ondansetron is one of the commonly prescribed anti-emetic in emergency department. • High dose of the drug is associated with prolonged QT interval. • The findings indicated that 4 mg i.v. administration of ondansetron among non-cardiac patients.

Background Oliceridine is a biased ligand at the μ-opioid receptor recently approved for the treatment of acute pain. In a thorough QT study, corrected QT (QTc) prolongation displayed peaks at 2.5 and 60 minutes after a supratherapeutic dose. The mean plasma concentration peaked at 5 minutes, declining rapidly thereafter. Objective The purpose of this study was to examine the basis for the delayed effect of oliceridine to prolong the QTc interval. Methods Repolarization parameters and tissue accumulation of oliceridine were evaluated in rabbit left ventricular wedge preparations over a period of 5 hours. The effects of oliceridine on ion channel currents were evaluated in human embryonic kidney and Chinese hamster ovary cells. Quinidine was used as a control. Results Oliceridine and quinidine produced a progressive prolongation of the QTc interval and action potential duration over a period of 5 hours, paralleling slow progressive tissue uptake of the drugs. Oliceridine caused modest prolongation of these parameters, whereas quinidine produced a prominent prolongation of action potential duration and QTc interval as well as development of early afterdepolarization (after 2 hours), resulting in a high torsades de pointes score. The 50% inhibitory concentration values for the oliceridine inhibition of the rapidly activating delayed rectifier current (human ether a-go-go current) and late sodium channel current were 2.2 and 3.45 μM when assessed after traditional acute exposure but much lower after 3 hours of drug exposure. Conclusion Our findings suggest that a gradual increase of intracellular access of drugs to the hERG channels as a result of their intracellular uptake and accumulation can significantly delay effects on repolarization, thus confounding the assessment of QT interval prolongation and arrhythmic risk when studied acutely. The multi-ion channel effects of oliceridine, late sodium channel current inhibition in particular, point to a low risk of devloping torsades de pointes.

Diphenhydramine is a widely available, over-the-counter medication used for allergies and as a sleeping aid. When used in prescription doses, it is generally safe. Overdose of the medication has been associated with dangerous and life-threatening outcomes. Our case describes diphenhydramine toxicity manifesting with two rare but potentially life-threatening complications, rhabdomyolysis, and QT prolongation. Laboratory testing for diphenhydramine levels are not widely available. We recommend a high degree of suspicion for these complications when evaluating patients with diphenhydramine overdose, to adequately manage and prevent untoward outcomes.

Introduction Antiretrovirals have immensely increased the average life expectancy of HIV-positive patients. However, the incidence of QT interval prolongation and other arrhythmias has also increased. Methods Pubmed and Google Scholar were searched for relevant literature published between 1990 and 2019. Results and discussion HIV-positive patients with high viral load, low CD4 count, chronic inflammation, and autonomic neuropathy can develop QT interval prolongation. Another factor prolonging QT interval includes exposure to the HIV transactivator protein, which inhibits hERG K (+) channels controlling IKr K (+) currents in cardiomyocytes. Protease inhibitors inhibiting the CYP3A4 enzyme can also lead to QT interval prolongation. QT interval prolongation can potentially be exacerbated by opioids, antipsychotics, antibiotics, and antifungals, the adjunct medications often used in HIV-positive patients. Hepatic insufficiency in seropositive patients on antiretrovirals may also increase the risk of QT interval prolongation. Conclusion Baseline and follow-up EKG in the susceptible population is suggested.

The International Council for Harmonisation (ICH) guidelines have been revised allowing for modeling of concentration-QT (C-QT) data from Phase I dose-escalation studies to be used as primary analysis for QT prolongation risk assessment of new drugs. This work compares three commonly used Phase I dose-escalation study designs regarding their efficiency to accurately identify drug effects on QT interval through C-QT modeling. Parallel group design and 4-period crossover designs with sequential or interleaving cohorts were evaluated. Clinical trial simulations were performed for each design and across different scenarios (e.g. different magnitudes of drug effect, QT variability), assuming a pre-specified linear mixed effect (LME) model for the relationship between drug concentration and change from baseline QT (ΔQT). Analyses suggest no systematic bias in either the predictions of placebo-adjusted ΔQT (ΔΔQT) or the LME model parameter estimates across all evaluated designs. Additionally, false negative rates remained similar and adequately controlled across all evaluated designs. However, compared to the crossover designs, the parallel design had significantly less power to correctly exclude a clinically significant QT effect, especially in the presence of substantial intercept inter-individual variability. In such cases, parallel design is associated with increased uncertainty around ΔΔQT prediction, mainly attributed to the uncertainty around the estimation of the treatment-specific intercept in the model. Throughout all the evaluated scenarios, the crossover design with interleaving cohorts had consistently the best performance characteristics. The results from this investigation will further facilitate informed decision-making during Phase I study design and the interpretation of the associated C-QT modeling output.

Introduction: The frequency of QT interval prolongation as published in the international and local literature has been variable. Aims & Objectives: To determine the frequency of QT interval prolongation in patients with chronic liver disease and resolve the variability in the literature. Place and duration of study: The present study was conducted in Gastroenterology and Hepatology Unit Shaikh Zayed Hospital Lahore from 1st March 2017 to 31st August 2017. Material & Methods: About 240 patients with diagnosed chronic liver disease were selected. Electrocardiography (12 lead) was performed in all patients to look for QT interval prolongation and their mean was calculated for purpose of analysis. Results: Mean age of our patients was 53.7±11.9 and male gender was dominant (55.8%). It was noted that QT interval was prolonged in 62 patients (25.8%) while rest of the 178 patients had normal QT interval. Conclusion: QT interval prolongation is frequently observed (25.8%) in chronic liver disease patients. Therefore, every patient with chronic liver disease should be investigated for QT interval prolongation. Key words: Chronic liver disease, QT interval, Electrocardiography

Background Determination of the prolonged QT interval in left bundle branch block (LBBB), which should be of special concern to identify individuals at high risk of potentially fatal cardiac arrhythmia risk, has been problematic. Methods Electrocardiograms (ECGs) (n = 17) in intermittent LBBB were used to develop a new formula for the calculation of QTc in LBBB. This formula and 5 others were compared in a population with LBBB (n = 2610). The QT was corrected for heart rate (HR) using the Bazett formula (QTcBZT) and the spline QT formula (QTcRBK), which is relatively independent of HR. The JT interval was significantly related to HR. Results The new approach (QTcLBBBNEW = 0.945*QTcRBKLBBB − 26) in LBBB showed the highest correlation with intrinsic QTc (without LBBB) and had minimal HR dependency. Previous formulae to determine the QT interval in LBBB showed significant HR dependency except for one proposed by Rautaharju et al. Inclusion of an HR correction factor in existing formulae blunted HR dependency but not if the QT interval was adjusted by the QTcBZT. In men and women, use of the QTcBZT markedly increases the proportion of individuals with prolonged QTc, which was more evident with increasing HR. The 99th and 97.5th percentiles for QTcLBBBNEW for men and women identified abnormal QT prolongation in LBBB. Conclusions A new formula that modifies the QT and JT intervals in LBBB predicts the QT interval in the absence of LBBB. Abnormal QT intervals in the 99th and 97.5th percentiles can identify patients with LBBB who have QT interval prolongation.

Prolonged QT intervals are a major risk factor for ventricular arrhythmias and a leading cause of sudden cardiac death. Various drugs are known to trigger QT interval prolongation and increase the proarrhythmic potential. Yet, how precisely the action of drugs on the cellular level translates into QT interval prolongation on the whole organ level remains insufficiently understood. Here we use machine learning techniques to systematically characterize the effect of 30 common drugs on the QT interval. We combine information from high fidelity three-dimensional human heart simulations with low fidelity one-dimensional cable simulations to build a surrogate model for the QT interval using multi-fidelity Gaussian process regression. Once trained and cross-validated, we apply our surrogate model to perform sensitivity analysis and uncertainty quantification. Our sensitivity analysis suggests that compounds that block the rapid delayed rectifier potassium current I Kr have the greatest prolonging effect of the QT interval, and that blocking the L-type calcium current I CaL and late sodium current I NaL shortens the QT interval. Our uncertainty quantification allows us to propagate the experimental variability from individual block-concentration measurements into the QT interval and reveals that QT interval uncertainty is mainly driven by the variability in I Kr block. In a final validation study, we demonstrate an excellent agreement between our predicted QT interval changes and the changes observed in a randomized clinical trial for the drugs dofetilide, quinidine, ranolazine, and verapamil. We anticipate that both the machine learning methods and the results of this study will have great potential in the efficient development of safer drugs.

Background: The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning.Methods: We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. A priori standards were developed for acceptance or rejection of individual criteria.Results: Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented.Conclusions: We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.

dl-Sotalol which can block both K+ channel and s-adrenoceptor has been shown to prolong the J–Tpeakc of electrocardiogram in beagle dogs but tended to shorten it in microminipigs, although the drug prolonged the QT interval in both animals under physiologically maintained experimental condition. In order to estimate how the changes in the J–Tpeakc in the normal hearts would be reflected in the pathologic hearts, we compared proarrhythmic effects of dl-sotalol by using proarrhythmia models of beagle dogs and microminipigs, of which atrioventricular node had been ablated > 2 months and 8–9 weeks before, respectively (n = 4 for each species). dl-Sotalol in an oral dose of 10 mg/kg induced torsade de pointes in three out of four beagle dogs, which degenerated into ventricular fibrillation. In microminipigs, the same dose did not trigger torsade de pointes at all, whereas intermittent ventricular pauses were observed in each animal after the drug treatment. These results indicate that assessment of the J–Tpeakc along with the QT-interval prolongation in healthy subjects may provide reliable information of risk prediction for patients susceptible to the drug-induced torsade de pointes.

Background Some of the drugs used for the treatment of coronavirus disease (COVID‐19) can increase the risk of corrected QT (QTc) interval prolongation, which may trigger arrhythmia or even death. Due to the low sensitivity of the reverse transcriptase‐polymerase chain reaction (RT‐PCR) test, chest computed tomography (CT) imaging is being used for COVID‐19 diagnostic correlation and to evaluate whether there is pneumonic involvement in the lung. Objective In this study, we aimed to investigate the correlation between lung changes on CT and QTc interval changes on ECG in non‐ICU patients with COVID‐19 who have a positive PCR test when using drugs that can prolong the QTc interval. Methods This was a single‐centre retrospective cohort study of hospitalized non‐ICU patients. The study included 344 patients (56.1% men) with a mean age of 46.34 ± 17.68 years. The patients were divided into four groups according to their chest CT results: those having typical, atypical, indeterminate, or no pneumonic involvement. The mean QTc intervals and heart rates calculated from electrocardiograms (ECG) during admission to the hospital and after the treatment were compared. Results No significant differences were found between the groups’ age, gender, and body mass index (BMI). In addition, no significant differences were found between the groups’ mean QTc interval values at admission (P:.127) or after the treatment (P:.205). The groups’ heart rate values were also similar, with no significant differences in the mean heart rate on admission (P:.648) and post‐treatment (P:.229) ECGs. Conclusion This study has demonstrated findings of COVID‐19 infection based on chest CT does not correlate with QT interval prolongation in non‐ICU COVID‐19 patients. There is a need for additional larger studies investigating the effect of chest CT findings on QT interval prolongation and bradycardia in COVID‐19 patients.

Lower dialysate calcium (dCa) concentration and dialysate citric-acidification may positively affect calcification propensity in serum of haemodialysis (HD) patients. However, the accompanying lower ionized blood calcium concentration may lead to a prolonged cardiac action potential, which is possibly pro-arrhythmic. The aim of this study is to investigate the influence of citric-acid dialysate on the QT-interval corrected for heart rate (QTc) compared to conventional dialysate with different dCa concentrations. We conducted a four-week multicentre, randomized cross-over trial. In week one and three patients received acetic-acid dialysate with a dCa of 1.50 mmol/l (A1.5), in week two and four acetic-acid dialysate with a dCa of 1.25 mmol/l (A1.25) or citric-acid dialysate (1.0 mmol/l) with a dCa of 1.50 mmol/l (C1.5) depending on randomization. Patients had continuous ECG monitoring during one session in week one, two and four. The data of 13 patients were available for analysis. Results showed a significant though limited increase of QTc with C1.5 (from 427 to 444 ms (start to end); p = 0.007) and with A1.25 (from 431 to 449 ms; p

Torsade de points (TdP), a life-threatening arrhythmia that can increase the risk of sudden cardiac death, is associated with drug-induced QT-interval prolongation on the electrocardiogram (ECG). While many modern ECG machines provide automated measurements of the QT-interval, these automated QT values are usually correct only for a noise-free normal sinus rhythm, in which the T-wave morphology is well defined. As QT-prolonging drugs often affect the morphology of the T-wave, automated QT measurements taken under these circumstances are easily invalidated. An additional challenge is that the QT-value at risk of TdP varies with heart rate, with the slower the heart rate, the greater the risk of TdP. This paper presents an explainable algorithm that uses an understanding of human visual perception and expert ECG interpretation to automate the detection of QT-prolongation at risk of TdP regardless of heart rate and T-wave morphology. It was tested on a large number of ECGs (n = 5050) with variable QT-intervals at varying heart rates, acquired from a clinical trial that assessed the effect of four known QT-prolonging drugs versus placebo on healthy subjects. The algorithm yielded a balanced accuracy of 0.97, sensitivity of 0.94, specificity of 0.99, F1-score of 0.88, ROC (AUC) of 0.98, precision-recall (AUC) of 0.88, and Matthews correlation coefficient (MCC) of 0.88. The results indicate that a prolonged ventricular repolarisation area can be a significant risk predictor of TdP, and detection of this is potentially easier and more reliable to automate than measuring the QT-interval distance directly. The proposed algorithm can be visualised using pseudo-colour on the ECG trace, thus intuitively ‘explaining’ how its decision was made, which results of a focus group show may help people to self-monitor QT-prolongation, as well as ensuring clinicians can validate its results.

Background: Shorter Treatment Regimen (STR) is a combination of treatments with a shortened periodfrom 20-24 months to 9-11 months. Shortened treatment requires a higher dose of drug to kill resistantbacteria. Corrected QT (QTc) interval prolongation is one of the severe side effects of treatment.Objective: This study aimed to find the factors of QTc prolongation in Drug Resistant-Tuberculosis (DRTB) patients treated with STR during an intensive phase.Method: An analytical retrospective study was conducted at Dr. Soetomo General Academic Hospital,Surabaya, Indonesia. DR-TB patients on the STR regimen were collected based on medical records betweenSeptember 2017 to August 2018. QTc interval was calculated by Fredericia formula. The relationshipbetween QTc interval at baseline and occurrence of QTc prolongation was analyzed using Chi-Square offisher’s exact test.Results: Among 108 patients on the STR regimen, there were 20 (28%) patients experienced moderateQTc prolongation (471-500 ms), and 31 (28%) patients had severe QTc prolongation (>500 ms) during fourmonths observation period in STR treatment. The prolonged QTc interval was significantly related to QTcinterval at baseline (p = 0.001). The QTc interval at baseline correlated significantly with the start time ofQTc prolongation (p < 0.001). Risk factors of age, gender, comorbid, hypertension, and potassium level atbaseline had a significant negative correlation to QTc prolongation.Conclusion: The prolonged QTc interval was significantly related to QTc interval at baseline. The QTcinterval at baseline correlates significantly with the start time of QTc prolongation.

Savolitinib is an oral, potent, and highly selective MET-tyrosine kinase inhibitor under investigation in various tumor types. A thorough QT study evaluated effects on QT interval after a 600-mg single savolitinib dose in healthy subjects. We report exposure-response (E-R) modeling from this study to characterize the effects of savolitinib and its metabolites, M2 and M3, on QTc changes. In a novel application, in vitro potencies against hERG current provided mechanistic support to model the metabolites' effects. The hERG IC50 estimates (95% CI) were 25.8 (22.2-29.9) and 22.6 (14.7-34.6) μM for parent and M2, respectively. The E-R was described by both linear and Emax models, with exposure captured by an active moiety that consisted of savolitinib and M2 concentrations, weighted by the hERG IC50 ratio (1.14). The maximal increase in ΔΔQTcF and EC50 estimates (95% CI) was 18.5 (9.2-27.7) ms and 5709 (2889-8529) nM, respectively. Ignoring M2 contribution resulted in under prediction of QTcF prolongation in the hypothetical case of inhibited M2 clearance; at 300 mg Cmax, the mean (90% CI) of ∆∆QTcF was 9.0 (5.7-12.6) and 5.9 (2.9-8.9) ms using the hERG-informed and parent-only linear models, respectively. Simulations in normal setting confirmed modest QTcF prolongation with 600 mg, but not 300 mg. Using the linear model, the mean (90% CI) maximum ΔΔQTcF were 12.3 (8.6-16.2) and 5.5 (2.6-8.5) ms for 600 and 300 mg, respectively. Further clinical studies will monitor cardiac safety to assess the clinical significance of QT-interval prolongation with savolitinib.

We herein report the case of a 20-year-old man with a history of epilepsy who presented with frequent transient loss of consciousness (T-LOC) and polymorphic ventricular tachycardia (VT) with QT interval prolongation. Blood investigations revealed panhypopituitarism. Following a biopsy, he was diagnosed with brain germinoma. During the biopsy, he had an episode of polymorphous VT with QT prolongation. There was no recurrence of T-LOC following chemotherapy and hormone replacement therapy. This case indicates the importance of checking the QT interval in patients with T-LOC, including those with seizures and brain tumors, to ensure appropriate treatment.

Multimodal anesthesia and analgesia play a key role in the Early Recovery After Surgery (ERAS) protocols and locoregional...

Multidrug resistant tuberculosis (MDR-TB) and non-tuberculous mycobacterium (NTM) infections present challenges due to complex treatment regimens Extended use of multiple antibiotics exposes patients to higher risks of side effects from anti-mycobacterial medications A high drug toxicity profile necessitates closer monitoring One of the more challenging issues is QTc prolongation with non-injectable regimens This study investigates the portable AliveCor device and Kardia app to record and measure the QT interval on a 6-lead ECG This handheld device can record an ECG trace in a minimum of 30 seconds by establishing three points of contact with electrodes to skin: two thumbs and left ankle or knee A 6-Lead ECG by AliveCor was recorded for each patient at risk of QT prolongation (n=16) and compared to the existing 12-Lead ECG The automated QTc readout from the 12-Lead ECG for each patient and mean QTc value calculated from each patients' respective AliveCor tracing were shown alongside each other (figure 1) The general trend suggests the AliveCor underestimates the QTc as 12/13 cases (92%) calculated the AliveCor QTc as lower than their corresponding 12-Lead QTc readout The mean%difference between the automated 12-Lead and manually calculated AliveCor readings was 3% The largest%difference between the two readings was 12% The larger discrepancies could be reflected by the varying quality of the AliveCor tracings Three patients were excluded due to poor tracings or lack of corresponding 12-Lead ECG This study aimed to provide pilot data and evaluate the feasibility of a portable device to monitor QTc intervals for patients on potential cardiotoxic medications It has allowed us to place in context the role for mobile monitoring in (Figure presented) modern-day clinical practice Moreover, the recent COVID-19 pandemic has seen increasing relevance for remote monitoring Remote monitoring can aid progression of treatment whilst protecting vulnerable patients from risk of exposure to illness The use of AliveCor could potentially be translated into current clinical practice using calculated QTcs from the device with caution of percentage variation either side This could facilitate the use of AliveCor as a promising and convenient screening tool before further evaluation by a 12-Lead ECG is required

Introduction Polymorphic ventricular tachycardia (VT) is defined as a rapid rhythm with continuously changing ventricular activation. In the absence of QT interval prolongation, its evaluation is a challenging activity with a series of differential diagnoses. The present study reports on a case of a young man who had an out-of-hospital cardiac arrest and and who later presented an episode of exercise-induced polymorphic VT. A rational investigation is discussed based on the patient’s clinical findings and baseline ECG. […] Cardiac Arrest [...]

Background Insulin-induced hypoglycemia has been demonstrated to prolong the corrected QT (QTc) interval. Prolongation of the QTc interval, especially in diabetic patients using insulin, can cause fatal ventricular arrhythmias. The aim of this study was to evaluate the effects of metoprolol, diltiazem, and pilocarpine on hypoglycemia-induced QTc prolongation. Methods Thirty male rats were randomly distributed into the following five groups: Group 1 (1 mL/kg saline, n=6), Group 2 (40 U/kg crystalline insulin + saline, n=6), Group 3 (40 U/kg crystalline insulin + 1 mg/kg metoprolol, n=6), Group 4 (40 U/kg crystalline insulin + 0.8 mg/kg pilocarpine, n=6), and Group 5 (40 U/kg crystalline insulin + 2 mg/kg diltiazem, n=6). Three hours after insulin injection, the blood glucose level was measured in all groups. Blood glucose

[EN] The prolongation of the QT interval represents the main feature of the long QT syndrome (LQTS), a life-threatening genetic disease. The heterozygous SCN5A V411M mutation of the human sodium channel leads to a LQTS type 3 with severe proarrhythmic effects due to an increase in the late component of the sodium current (INaL). The two sodium blockers flecainide and ranolazine are equally recommended by the current 2015 ESC guidelines to treat patients with LQTS type 3 and persistently prolonged QT intervals. However, awareness of pro-arrhythmic effects of flecainide in LQTS type 3 patients arose upon the study of the SCN5A E1784K mutation. Regarding SCN5A V411M individuals, flecainide showed good results albeit in a reduced number of patients and no evidence supporting the use of ranolazine has ever been released. Therefore, we ought to compare the effect of ranolazine and flecainide in a SCN5A V411M model using an in-silico modeling and simulation approach. We collected clinical data of four patients. Then, we fitted four Markovian models of the human sodium current (INa) to experimental and clinical data. Two of them correspond to the wild type and the heterozygous SCN5A V411M scenarios, and the other two mimic the effects of flecainide and ranolazine on INa. Next, we inserted them into three isolated cell action potential (AP) models for endocardial, midmyocardial and epicardial cells and in a one-dimensional tissue model. The SCN5A V411M mutation produced a 15.9% APD90 prolongation in the isolated endocardial cell model, which corresponded to a 14.3% of the QT interval prolongation in a one-dimensional strand model, in keeping with clinical observations. Although with different underlying mechanisms, flecainide and ranolazine partially countered this prolongation at the isolated endocardial model by reducing the APD90 by 8.7 and 4.3%, and the QT interval by 7.2 and 3.2%, respectively. While flecainide specifically targeted the mutation-induced increase in peak INaL, ranolazine reduced it during the entire AP. Our simulations also suggest that ranolazine could prevent early afterdepolarizations triggered by the SCN5A V411M mutation during bradycardia, as flecainide. We conclude that ranolazine could be used to treat SCN5A V411M patients, specifically when flecainide is contraindicated., This work was partially supported by Fondo Europeo de Desarrollo Regional (FEDER, "Union Europea, Una forma de hacer Europa") with the Ministerio de Economia y Competitividad (DPI2015-69125-R), Direccion General de Politica Cientifica de la Generalitat Valenciana (PROMETEO/2020/043) and Instituto de Salud Carlos III (La Fe Biobank PT17/0015/0043), as well as by Vicerrectorado de Investigacion, Innovacion y Transferencia de la Universitat Politecnica de Valencia with Ayuda a Primeros Proyectos de Investigacion (PAID-06-18), and by Memorial Nacho Barbera.

Background and aims High rates of sudden cardiac death are mostly attributed to ventricular arrhythmias including QTc prolongation in hemodialysis patients. We aimed to investigate the correlation of electrolyte and volume changes with QTc interval prolongation in hemodialysis patients. Study design The present study is designed as a cross-sectional study. Methods The study was conducted at the hemodialysis unit of a training and research hospital and its' satellite dialysis unit. Patients were divided into three groups. Group-1: with normal QTc interval both at the beginning and during dialysis session; group-2: with prolonged QTc interval at the beginning and remained prolonged during dialysis session; group-3: with normal QTc interval at the beginning but prolonged during the dialysis session. In addition, patients were evaluated in terms of QTc change between the beginning and 2nd hour (delta-QTc-1) and between 2nd hour and 4th hour (delta-QTc-2), respectively, and defined as 'patients with increased QTc interval' and 'patients without increased QTc interval'. Results A total of 45 prevalent hemodialysis patients were enrolled in the study. 14 patients (31.1%) had normal QTc interval (group-1), 13 patients (28.9%) had prolonged QTc interval at the beginning and remained prolonged during dialysis session (group-2) and 18 patients (40%) had normal QTc interval at the beginning but prolonged during dialysis session (group-3). There was no statistically significant difference between groups in terms of baseline electrolyte levels. Calcium change in the first 2 h was lower in patients with QTc prolongation from the start or during the dialysis session (group-2 and group-3). In addition, systolic blood pressure (SBP) levels at the beginning of the session (118 ± 15 mmHg vs 124 ± 28 mmHg vs138 ± 24 mmHg; p = 0.04) and intradialytic ultrafiltration (UF) rate were higher (1.96 ± 0.6 L/4 h vs 2.6 ± 1.0 L/4 h vs 2.8 ± 0.9 L/4 h; p = 0.03) in group-2 and group-3 compared to patients in group-1. Increase in QTc interval was found higher in patients with less calcium increase (Rho: - 0.36; p = 0.01) and with greater magnesium decrease in the first 2 h (Rho: 0.31; p = 0.04). Conclusion QTc interval prolongation is common among hemodialysis patients. High intradialytic UF rates, change in serum magnesium and calcium levels in the first 2 h were found associated with QTc prolongation. However, QTc prolongation was found independently associated only with UF volume and calcium change in the first 2 h.

BackgroundMany of the drugs commonly used for the treatment of COVID-19 cause QT interval prolongation and increase the risk of life-threatening cardiac arrhythmias. It has been shown that maintaining serum potassium and magnesium levels above 4 and 3 mg/dL, respectively, would prevent the QTc prolongation.ObjectiveTo determine if keeping only the serum magnesium level above 3 mg/dL could be considered an effective measure to prevent QTc prolongation in patients with COVID-19 receiving these drugs.MethodsIn a retrograde observational study, QTc interval was measured in 14 patients diagnosed with COVID-19 before and 3 days after initiation of treatment with either hydroxychloroquine or lopinavir-ritonavir, while their serum magnesium levels were kept ≥3 mg/dL.ResultsThe baseline QTc interval of 412 (SD 36) ms significantly increased by an average of 34 (95% CI 13 to 55) ms after 3 days of treatment. 5 patients, mostly those with lower serum potassium levels, had QTc prolongation ≥60 ms.ConclusionAlthough it seems that the risk of fatal cardiac arrhythmias in this setting is not high, it is prudent to monitor the serum electrolytes, particularly potassium, in patients with COVID-19 who are treated with either hydroxychloroquine or lopinavir-ritonavir.