QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection

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.

Drug-Induced QT Interval Prolongation

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.

Prevalence And Risk Factors of Electrocardiogram Abnormalities In Patients With Rheumatoid Arthritis: A Machine Learning Study With Follow-Up Data

OBJECTIVES: Electrocardiogram (ECG) abnormalities could predict some subsequent cardiovascular events. Cardiac involvement is a major extra-articular manifestation in rheumatoid arthritis (RA). We aimed to determine the prevalence of three major ECG abnormalities in RA patients, discover the associated ECG abnormalities associated with machine learning (ML) approaches, and then examine these preselected factors in the follow-up patients with traditional Cox regression. METHODS: Consecutive RA patients’ records were retrieved from the hospital database; about one-third of patients had follow-up data. Abnormal ECGs with clinical significance were grouped into non-specific ST-segment/T-wave changes, QT interval prolongation, and QRS-T angle increase. Machine learning approaches assessed the associated factors of these abnormalities. The top-important factors selected by the most optimal ML would be used to construct Cox regression models. RESULTS: Two hundred twenty-six patients were enrolled for the first step cross-sectional study. Non-specific ST-T changes (27%) were the most prevalent abnormalities among patients with abnormal ECGs. Random forest models had the best performance in the discovery of associated factors for three outcomes. Cox regression validated that rheumatoid factor and low-density lipoprotein were common risk factors within those three abnormalities. Hypertension, ESR, and serum immunoglobulin G were influential factors for non-specific ST-T changes, prolonged QT interval, and increased QRS-T angle specifically. CONCLUSION: Non-specific ST-T changes were the most common abnormalities seen in ECGs of RA patients. Our finding suggests that rheumatoid factor, LDL, hypertension, and inflammatory indicators are important risk factors for these ECG abnormalities.

What’s New in Cirrhotic Cardiomyopathy?—Review Article

Cirrhotic cardiomyopathy (CCM) is a relatively new medical term. The constant development of novel diagnostic and clinical tools continuously delivers new data and findings about this broad disorder. The purpose of this review is to summarize current facts about CCM, identify gaps of knowledge, and indicate the direction in which to prepare an updated definition of CCM. We performed a review of the literature using scientific data sources with an emphasis on the latest findings. CCM is a clinical manifestation of disorders in the circulatory system in the course of portal hypertension. It is characterized by impaired left ventricular systolic and diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. However, signs and symptoms reported by patients are non-specific and include reduced exercise tolerance, fatigue, peripheral oedema, and ascites. The disease usually remains asymptomatic with almost normal heart function, unless patients are exposed to stress or exertion. Unfortunately, due to the subclinical course, CCM is rarely recognized. Orthotopic liver transplantation (OLTx) seems to improve circulatory function although there is no consensus about its positive effect, with reported cases of heart failure onset after transplantation. Researchers indicate a careful pre-, peri-, and post-transplant cardiac assessment as a crucial point in detecting CCM and improving patients’ prognosis. There is also an urgent need to update the CCM definition and establish a diagnostic algorithm for early diagnosis of CCM as well as a specific treatment of this condition.

Antipsychotic Polypharmacy and Adverse Drug Reactions Among Adults in a London Mental Health Service, 2008-2018

Background: Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions. Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2+ antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of adverse drug reactions: QT interval prolongation, hyperprolactinaemia, and increased body weight (body mass index [BMI] > 25). Methods: We extracted anonymised EHR data. Patients aged 16+ receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively. Results: We identified 35,409 observations of antipsychotic prescribing among 13,391 patients. APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% C.I. 1.87-3.24) and of having a BMI > 25 (adjusted odds ratio 1.75; 95% C.I. 1.33-2.31) in the period following the APP prescribing. Conclusions: Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.

Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies

With the development of anti-tumor drugs, tyrosine kinase inhibitors (TKIs) are an indispensable part of targeted therapy. They can be superior to traditional chemotherapeutic drugs in selectivity, safety, and efficacy. However, they have been found to be associated with serious adverse effects in use, such as myocardial infarction, fluid retention, hypertension, and rash. Although TKIs induced arrhythmia with a lower incidence than other cardiovascular diseases, much clinical evidence indicated that adequate attention and management should be provided to patients. This review focuses on QT interval prolongation and atrial fibrillation (AF) which are conveniently monitored in clinical practice. We collected data about TKIs, and analyzed the molecule mechanism, discussed the actual clinical evidence and drug-drug interaction, and provided countermeasures to QT interval prolongation and AF. We also pooled data to show that both QT prolongation and AF are related to their multi-target effects. Furthermore, more than 30 TKIs were approved by the FDA, but most of the novel drugs had a small sample size in the preclinical trial and risk/benefit assessments were not perfect, which led to a suspension after listing, like nilotinib. Similarly, vandetanib exhibits the most significant QT prolongation and ibrutinib exhibits the highest incidence in AF, but does not receive enough attention during treatment.

COVID-19 and Cardiovascular Complications: An Updated Review

COVID-19 has become a global pandemic. Patients with pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease (CVD) are associated with greater severity and higher mortality. COVID-19 can cause cardiovascular complications, including myocardial injury, myocarditis, heart failure, acute coronary syndrome, and coagulation abnormalities. Possible pathophysiology and molecular pathways driving these disease processes are cytokine release syndrome, RAAS system dysregulation, plaque destabilization and coagulation disorders Myocarditis is one concern among persons who received mRNA-Based COVID-19 vaccines. There are several cardiovascular complications that are possibly caused by COVID-19 treatments, such as QT interval prolongation, arrhythmia, and hypotension. Due to increasingly recognized CVD damage in COVID-19, we need to understand about COVID-19 related to cardiovascular complications and treatment strategies.

Detect Drug Interactions with Metronidazole

Introduction: Metronidazole has been prescribed to treat infections for over a century and continues to be helpful in the therapy of amoebiasis, trichomoniasis, and giardiasis. Metronidazole is a cost-effective medication because of its low price, few adverse effects, and favorable pharmacokinetic and pharmacodynamic properties; nevertheless, it interacts with a wide variety of other medications. Some interactions with other medicines diminish its effectiveness, while others increase it. Aims: The study aims to detect and evaluate metronidazole interactions with other medicines at King Abdulaziz Specialist Hospital. Methodology: This retrospective study encompasses the review of 360 computerized prescriptions inside the outpatient clinic at King Abdulaziz Specialist Hospital in Saudi Arabia between March and September 2020 to detect and evaluate interactions among metronidazole and different medications. Results: Metronidazole interactions are mostly major or moderate. Metronidazole had the most common interactions with domperidone (15.83 %), famotidine (13.89 %), and ciprofloxacin (11.67 %). Metronidazole contains a nitroimidazole ring, which suppresses the metabolism in the liver of numerous medications, including those that may be metabolized by the CYP3A4 and/or CYP450 2C9 isoenzymes. The combination of metronidazole with phenytoin or phenobarbital can cause metronidazole elimination to be accelerated and phenytoin clearance to be reduced. Metronidazole may improve warfarin's anticoagulant effects, leading to a longer prothrombin time and a higher risk of bleeding. Concurrent use of metronidazole with alfuzosin, escitalopram, and ondansetron may raise the risks of QT-interval prolongation and arrhythmias. Conclusion: Most metronidazole drug interactions can be avoided by following excellent clinical care and clinical pharmacology concepts, such as avoiding complex treatment regimens, educating patients. and identifying patient risk factors. Furthermore, before prescribing and dispensing medicines, physicians and pharmacists should utilize drug-drug interactions checkers such as Micromedex and Lexicomp or a book such as Stockley's Drug Interactions.