Prolong Qt

BACKGROUND: The implementation of modified, all-oral shorter regimens for treatment of rifampicin-resistant tuberculosis has started in Armenia since August 2020 under the conditions of operational research. OBJECTIVE: This study aims to evaluate the safety and effectiveness of shorter regimens. METHODS: We evaluated cumulative incidence rates of serious adverse events, adverse events of grade 3 and greater and events resulting in treatment modifications or suspension for 52 study participants...

BACKGROUND: Delamanid (DLM) is a relatively new drug for drug-resistant tuberculosis (DR-TB) that has been used in Indonesia since 2019 despite its limited safety data. DLM is known to inhibit hERG potassium channel with the potential to cause QT prolongation which eventually leads to Torsades de pointes (TdP). OBJECTIVE: This study aims to analyse the changes of QTc interval in DR-TB patients on DLM regimen compared to shorter treatment regimens (STR). METHODS: A retrospective cohort was implemented on secondary data obtained from two participating hospitals...

Sitravatinib (MGCD516) is an orally available, small molecule, tyrosine kinase inhibitor that has been evaluated in patients with advanced solid tumors. Concentration-corrected QT interval (QTc; C-QTc) modeling was undertaken, using 767 matched concentration-ECG observations from 187 patients across two clinical studies in patients with advanced solid malignancies, across a dose range of 10-200 mg, via a linear mixed-effects (LME) model. The effect on heart rate (HR)-corrected QT interval via Fridericia's correction method (QTcF) at the steady-state maximum concentration (Cmax,ss ) for the sitravatinib proposed therapeutic dosing regimen (100 mg malate once daily [q...

IMPORTANCE: Individuals with dialysis-dependent kidney failure have numerous risk factors for medication-related adverse events, including receipt of care by multiple clinicians and initiation of some QT-prolonging medications with known risk of torsades de pointes (TdP), which is associated with higher risk of sudden cardiac death. Little is known about the prescription and dispensation patterns of QT-prolonging medications among people receiving dialysis, hindering efforts to reduce drug-related harm from these and other medications in this high-risk population...

QT interval prolongation is common in patients hospitalized with Takotsubo syndrome (TTS), however, only a minority experience ventricular tachyarrhythmias. Our aim was to characterize the electromechanical window (EMW) in patients with TTS and to evaluate its association with ventricular tachyarrhythmias. We preformed aretrospective analysis of 84 patients hospitalized with TTS in the Tel-Aviv Medical Center between 2013 and 2022. All patients underwent a comprehensive echocardiographic evaluation and the EMW was calculated by subtracting the QT interval from the QRS onset to the aortic valve closure obtained from a continuous-wave Doppler for the same beat...

BACKGROUND: Drug-induced QT prolongation (diLQT) is a feared side effect that could expose susceptible individuals to fatal arrhythmias. The occurrence of diLQT is primarily attributed to unintended drug interactions with cardiac ion channels, notably the hERG (human ether-a-go-go-related gene) channels that generate the delayed-rectifier potassium current (IKr ) and thereby regulate the late repolarization phase. There is an important interindividual susceptibility to develop diLQT, which is of unknown origin but can be reproduced in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs)...

Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms...

Introduction Cirrhotic cardiomyopathy (CCM) is recognized by impaired cardiac responsiveness to stress, prolonged QT interval, and systolic and diastolic dysfunctions. Connexins are a family of transmembrane proteins that play a key role in cardiac physiology. Connexin 43 (Cx43) inhibition showed cardio-protective effects. Peptide drug Cx43 inhibitor, Gap 26, could inhibit gap junction 43. This study was designed to evaluate the effects of a connexin mimetic peptide, Gap 26, in the CCM model in rats. Methods The cirrhosis was induced through carbon tetrachloride (CCl4)...

INTRODUCTION: Trazodone is a serotonin receptor antagonist and reuptake inhibitor commonly used to treat major depression disorder (MDD), anxiety, and sleep disorders. It is considered safe for the heart due to minimal anticholinergic effects. Prolonged QT intervals can cause polymorphic ventricular tachycardia, known as torsades de pointe (TdP). We present a case of a 67-year-old female with a history of MDD who developed trazodone-induced TdP. Case Presentation . The patient was referred to a tertiary hospital with a ten-hour history of nausea and vomiting...

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes due to COVID-19 include QT prolongation and ST-T changes; however, there have not been studies on the ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases...

The accurate prediction of adverse drug reactions (ADRs) is essential for comprehensive drug safety evaluation. Pre-trained deep chemical language models have emerged as powerful tools capable of automatically learning molecular structural features from large-scale datasets, showing promising capabilities for the downstream prediction of molecular properties. However, the performance of pre-trained chemical language models in predicting ADRs, especially idiosyncratic ADRs induced by marketed drugs, remains largely unexplored...

Andersen-Tawil syndrome (ATS) is a multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias, prolonged QT interval, and facial dysmorphisms occurring in the first/second decade of life. High phenotypic variability and incomplete penetrance of the genes causing the disease make its diagnosis still a challenge. We describe a three-generation family with six living individuals affected by ATS. The proband is a 37-year-old woman presenting since age 16, with episodes of muscle weakness and cramps in the pre-menstrual period...

Atrial fibrillation (AF) is an arrhythmic disease. Prediction of AF development in healthy individuals is important before serious complications occur. We aimed to develop a risk prediction score for future AF using participants' data, including electrocardiogram (ECG) measurements and information such as age and sex. We included 88,907 Japanese participants, aged 30-69 years, who were randomly assigned to derivation and validation cohorts in a ratio of 1:1. We performed multivariate logistic regression analysis and obtained the standardised beta coefficient of relevant factors and assigned scores to them...

Guidelines are important tools to guide the diagnosis and treatment of patients to improve the decision-making process of health professionals. They are periodically updated according to new evidence. Four new Guidelines in 2021, 2022 and 2023 referred to pediatric pacing and defibrillation. There are some relevant changes in permanent pacing. In patients with atrioventricular block, the heart rate limit in which pacemaker implantation is recommended was decreased to reduce too-early device implantation. However, it was underlined that the heart rate criterion is not absolute, as signs or symptoms of hemodynamically not tolerated bradycardia may even occur at higher rates...

INTRODUCTION: Fluconazole is commonly used to treat and prevent fungal infections caused by Candida and Cryptococcus species. Although there have been reports of fatal arrhythmias induced by fluconazole, such as torsades de pointes, there have been minimal reports of mild, non-fatal arrhythmias associated with it, which may have been overlooked in clinical practice. We encountered a case of frequent premature ventricular contractions induced by fluconazole during the treatment of HIV-related pulmonary cryptococcosis...

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions1 . TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A2-6 ...

BACKGROUND: Semaglutide is a relatively new anti-hyperglycemic agent that was shown to carry cardioprotective potentials. However, the exact effects of semaglutide on diabetic cardiomyopathy (DCM) and their underlining mechanism remain unclear. This study aimed to evaluate the effects of semaglutide on myocardium injury and cardiac function in DCM mice and its potential mechanisms, with emphasis on its effects on Cx43 and electrophysiological remodeling. METHODS: C57BL/6 mice were randomly divided into four groups: control group, semaglutide group, diabetes group, and diabetes + semaglutide treatment group...

Torsades de Pointes (TdP) is a malignant polymorphic ventricular tachycardia with heart rate corrected QT interval (QTc) prolongation, which may be attributed to congenital and acquired factors. Although various acquired factors for TdP have been summarized, levosimendan administration in complex postoperative settings is relatively uncommon. Timely identification of potential causes and appropriate management may improve the outcome. Herein, we describe the postoperative case of a 56-year-old female with initial normal QTc who accepted the administration of levosimendan for heart failure, suffered TdP, cardiac arrest, and possible Takotsubo cardiomyopathy, further genetically confirmed as long QT syndrome type 1 (LQT1)...

BACKGROUND: Dysfunction of the left ventricular (LV) apex (apical variant) is the most common form in Takotsubo syndrome (TS). Several less common non-apical variants have been described - mid-ventricular, basal and focal. We hypothesised that the clinical presentation, and electrocardiographic (ECG) findings may vary between apical and non-apical TS. METHODS: We prospectively identified 194 consecutive patients with TS presenting to Middlemore Hospital, Auckland and obtained clinical, echocardiography, coronary angiography, and long-term follow-up data...

Ivosidenib is a first-in-class mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor and has shown efficacy and tolerability in patients with advanced mIDH1 hematologic malignancies, leading to approval in front-line and relapsed/refractory (R/R) mIDH1 AML populations. We report final data from a phase I single-arm substudy (NCT02074839) of patients with R/R mIDH1 MDS following failure of standard-of-care therapies. Oral ivosidenib was taken once daily on days 1-28 in 28-day cycles. Primary objectives were to determine safety, tolerability, and clinical activity...