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Cardiovascular Toxicology May 2024The challenge posed by opioid overdose has become a significant concern for health systems due to the complexities associated with drug prohibition, widespread clinical... (Review)
Review
The challenge posed by opioid overdose has become a significant concern for health systems due to the complexities associated with drug prohibition, widespread clinical use, and potential abuse. In response, healthcare professionals have primarily concentrated on mitigating the hallucinogenic and respiratory depressant consequences of opioid overdose to minimize associated risks. However, it is crucial to acknowledge that most opioids possess the capacity to prolong the QT interval, particularly in cases of overdose, thereby potentially resulting in severe ventricular arrhythmias and even sudden death if timely intervention is not implemented. Consequently, alongside addressing the typical adverse effects of opioids, it is imperative to consider their cardiotoxicity. To enhance comprehension of the correlation between opioids and arrhythmias, identify potential targets for prompt intervention, and mitigate the hazards associated with clinical utilization, an exploration of the interaction between drugs and ion channels, as well as their underlying mechanisms, becomes indispensable. This review primarily concentrates on elucidating the impact of opioid drugs on diverse ion channels, investigating recent advancements in this domain, and attaining a deeper understanding of the mechanisms underlying the prolongation of the QT interval by opioid drugs, along with potential interventions.
Topics: Humans; Long QT Syndrome; Analgesics, Opioid; Animals; Cardiotoxicity; Risk Assessment; Risk Factors; Heart Rate; Action Potentials; Heart Conduction System; Ion Channels; Opiate Overdose
PubMed: 38630336
DOI: 10.1007/s12012-024-09853-6 -
Annals of Noninvasive Electrocardiology... May 2024Acquired QT prolongation is frequent and leads to a higher mortality rate in critically ill patients. KardiaMobile 1L® (KM1L) is a portable, user-friendly single lead,...
PURPOSE
Acquired QT prolongation is frequent and leads to a higher mortality rate in critically ill patients. KardiaMobile 1L® (KM1L) is a portable, user-friendly single lead, mobile alternative to conventional 12-lead electrocardiogram (12-L ECG) that could be more readily available, potentially facilitating more frequent QTc assessments in intensive care units (ICU); however, there is currently no evidence to validate this potential use.
METHODS
We conducted a prospective diagnostic test study comparing QT interval measurement using KM1L with conventional 12-L ECG ordered for any reason in patients admitted to an ICU. We compared the mean difference using a paired t-test, agreement using Bland-Altman analysis, and Lin's concordance coefficient, numerical precision (proportion of QT measurements with <10 ms difference between KM1L and conventional 12-L ECG), and clinical precision (concordance for adequate discrimination of prolonged QTc).
RESULTS
We included 114 patients (61.4% men, 60% cardiovascular etiology of hospitalization) with 131 12-L ECG traces. We found no statistical difference between corrected QT measurements (427 ms vs. 428 ms, p = .308). Lin's concordance coefficient was 0.848 (95% CI 0.801-0.894, p = .001). Clinical precision was excellent in males and substantial in females (Kappa 0.837 and 0.781, respectively). Numerical precision was lower in patients with vasoactive drugs (-13.99 ms), QT-prolonging drugs (13.84 ms), antiarrhythmic drugs (-12.87 ms), and a heart rate (HR) difference of ≥5 beats per minute (bpm) between devices (-11.26 ms).
CONCLUSION
Our study validates the clinical viability of KM1L, a single-lead mobile ECG device, for identifying prolonged QT intervals in ICU patients. Caution is warranted in patients with certain medical conditions that may affect numerical precision.
Topics: Male; Female; Humans; Electrocardiography; Critical Illness; Prospective Studies; Long QT Syndrome; Heart Rate
PubMed: 38627955
DOI: 10.1111/anec.13116 -
Critical Care (London, England) Apr 2024Sepsis-induced myocardial injury is a serious complication of sepsis. QT prolongation is a proarrhythmic state which reflects myocardial injury in a group of...
BACKGROUND
Sepsis-induced myocardial injury is a serious complication of sepsis. QT prolongation is a proarrhythmic state which reflects myocardial injury in a group of heterogeneous disorders. However, the study on the clinical value of QT prolongation in sepsis is limited.
METHODS
We aimed to investigate the clinical characteristics and predictors of new-onset QT prolongation in sepsis and its impact on the outcome in a multicenter retrospective cohort study. Electrocardiographic and clinical data were collected from patients with sepsis from the wards and intensive care units of four centers after exclusion of QT-influencing medications and electrolyte abnormalities. Clinical outcomes were compared between patients with and without QT prolongation (QTc > 450 ms). Multivariate analysis was performed to ascertain whether QT prolongation was an independent predictor for 30-day mortality. The factors predicting QT prolongation in sepsis were also analyzed.
RESULTS
New-onset QT prolongation occurred in 235/1024 (22.9%) patients. The majority demonstrated similar pattern as type 1 long QT syndrome. Patients with QT prolongation had a higher 30-day in-hospital mortality (P < 0.001), which was also associated with increased tachyarrhythmias including paroxysmal atrial fibrillation or tachycardia (P < 0.001) and ventricular arrhythmia (P < 0.001) during hospitalization. QT prolongation independently predicted 30-day mortality (P = 0.044) after multivariate analysis. History of coronary artery disease (P = 0.001), septic shock (P = 0.008), acute respiratory (P < 0.001), heart (P = 0.021) and renal dysfunction (P = 0.013) were independent predictors of QT prolongation in sepsis.
CONCLUSIONS
New-onset QT prolongation in sepsis was associated with increased mortality as well as atrial and ventricular arrhythmias, which was predicted by disease severity and organ dysfunction.
Topics: Humans; Retrospective Studies; Risk Factors; Hospitalization; Electrocardiography; Long QT Syndrome; Sepsis
PubMed: 38594724
DOI: 10.1186/s13054-024-04879-2 -
European Heart Journal. Case Reports Apr 2024Thousands of people suffer from anxiety, depression, and insomnia every day, with benzodiazepines being one of the strategies used to treat these conditions. Withdrawal...
BACKGROUND
Thousands of people suffer from anxiety, depression, and insomnia every day, with benzodiazepines being one of the strategies used to treat these conditions. Withdrawal from its long-term use can lead to potentially life-threatening complications, including Takotsubo syndrome. The authors highlight an atypical case of Takotsubo syndrome secondary to benzodiazepine withdrawal, a rare life-threatening complication of acute substance withdrawal.
CASE SUMMARY
A 58-year-old female presented to the emergency department with altered mental status and acute pulmonary oedema after discontinuing her prescribed benzodiazepines 3 days prior to presentation. Electrocardiogram (ECG) demonstrated anterior ST-segment elevation, with Q-wave and T-wave inversion with prolonged QT interval. Troponin I concentration and B-type natriuretic peptide were elevated to 5407 ng/L (normal ≤ 16 ng/L) and to 1627.0 pg/L (normal ≤ 100 pg/mL), respectively. Echocardiogram showed ballooning of the left ventricle (LV) apex with dyskinesia of the mid and apical segments, with LV function of 15%. Coronary angiography was normal, but left ventriculography showed severe LV systolic dysfunction with akinesis of the mid and apical LV segments and hyperdynamic basal segments. A presumptive diagnosis of benzodiazepine withdrawal-induced Takotsubo syndrome was made, and patients' symptoms, ECG findings, and LV dysfunction resolved after benzodiazepine administration. Six months post discharge, the patient remained asymptomatic with a normal biventricular function, and a beta-blocker was successfully introduced as part of a lifelong plan.
DISCUSSION
A diagnosis of benzodiazepine withdrawal-induced Takotsubo syndrome is an underrecognized and challenging diagnosis, due to its atypical clinical presentation. High degree of clinical suspicion for this syndrome is crucial, since favourable prognosis depends on prompt diagnosis and treatment.
PubMed: 38586535
DOI: 10.1093/ehjcr/ytae136 -
Journal of Electrocardiology 2024A 69-year-old woman was admitted after a cardiac arrest. She developed status epilepticus and was later found to have variable morphologies of a "spiked helmet sign"...
A 69-year-old woman was admitted after a cardiac arrest. She developed status epilepticus and was later found to have variable morphologies of a "spiked helmet sign" (SHS) on ECGs in the setting of prolonged QT interval, raising the question of whether this sign is a manifestation of QT prolongation.
Topics: Humans; Female; Aged; Electrocardiography; Long QT Syndrome; Diagnosis, Differential; Status Epilepticus; Heart Arrest
PubMed: 38579636
DOI: 10.1016/j.jelectrocard.2024.03.014 -
Biomedicine & Pharmacotherapy =... May 2024Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III... (Review)
Review
Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III antiarrhythmic drugs is the cardiac human ether-a-go-go-related gene (hERG) encoded channel, KCNH2, commonly known as HERG, that conducts the rapidly activating delayed rectifier potassium current (I). Like other class III antiarrhythmic drugs, amiodarone exerts its physiologic effects mainly through I blockade, delaying the repolarization phase of the action potential and extending the effective refractory period. However, while many class III antiarrhythmics, including sotalol and dofetilide, can cause long QT syndrome (LQTS) that can progress to torsade de pointes, amiodarone displays less risk of inducing this fatal arrhythmia. This review article discusses the arrhythmogenesis in LQTS from the aspects of the development of early afterdepolarizations (EADs) associated with Ca current, transmural dispersion of repolarization (TDR), as well as reverse use dependence associated with class III antiarrhythmic drugs to highlight electropharmacological effects of amiodarone on the myocardium.
Topics: Amiodarone; Humans; Anti-Arrhythmia Agents; Animals; Action Potentials; Ion Channels; Myocardium; Electrophysiological Phenomena; Long QT Syndrome
PubMed: 38565056
DOI: 10.1016/j.biopha.2024.116513 -
International Heart Journal 2024Although long-QT syndrome (LQTS) with a normal range QT interval at rest leads to fatal ventricular arrhythmias, it is difficult to diagnose. In this article, we present...
Although long-QT syndrome (LQTS) with a normal range QT interval at rest leads to fatal ventricular arrhythmias, it is difficult to diagnose. In this article, we present a rare case of a patient who suffered a cardiac arrest and was recently diagnosed with LQTS and coronary vasospasm. A 62-year-old man with no syncopal episodes had a cardiopulmonary arrest while running. During coronary angiography, vasospasm was induced and we prescribed coronary vasodilators, including calcium channel blockers. An exercise stress test was performed to evaluate the effect of medications and accidentally unveiled exercise-induced QT prolongation. He was diagnosed with LQTS based on diagnostic criteria. Pharmacotherapy and an implantable cardioverter defibrillator were used for his medical management. It is extremely rare for LQTS and coronary vasospasm to coexist. In cases of exercise-induced arrhythmic events, the exercise stress test might be helpful to diagnose underlying disease.
Topics: Male; Humans; Middle Aged; Ventricular Fibrillation; Coronary Vasospasm; Electrocardiography; Long QT Syndrome; Arrhythmias, Cardiac; Heart Arrest
PubMed: 38556343
DOI: 10.1536/ihj.23-397 -
Clinical Lung Cancer Jun 2024A systematic literature review was conducted to determine the incidence and mortality of QT-interval prolongation (QTp), torsades de pointes (TdP), and heart failure... (Review)
Review
A systematic literature review was conducted to determine the incidence and mortality of QT-interval prolongation (QTp), torsades de pointes (TdP), and heart failure (HF) in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR) TKIs. Of 296 identified publications, 95 met eligibility criteria and were abstracted for QTp/TdP and HF outcomes (QTp/TdP: 83 publications, including 5 case study publications; HF: 79 publications, including 6 case study publications [involving 8 patients]). QTp incidence ranged from 0% to 27.8% in observational studies and from 0% to 11% in clinical trials, with no deaths due to QTp. There were no TdP events or deaths due to TdP. The incidence of HF ranged from 0% to 8%, and HF mortality rates ranged from 0% to 4%. Patients receiving treatment with EGFR TKIs should be monitored for signs of QTp, TdP, and HF per prescribing information. Standardized definitions and methods to improve monitoring of QTp, TdP, and HF-related events are needed in patients with NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Heart Failure; Lung Neoplasms; ErbB Receptors; Torsades de Pointes; Protein Kinase Inhibitors; Long QT Syndrome; Incidence; Tyrosine Kinase Inhibitors
PubMed: 38553324
DOI: 10.1016/j.cllc.2024.02.005 -
Stem Cell Research Jun 2024KCNH2 (Potassium Voltage-Gated Channel Subfamily H Member) encodes a voltage-activated potassium channel role as rapidly activating-delayed rectifier potassium channel...
KCNH2 (Potassium Voltage-Gated Channel Subfamily H Member) encodes a voltage-activated potassium channel role as rapidly activating-delayed rectifier potassium channel that plays an essential role in the final repolarization of the ventricular action potential. Mutations in this gene can cause long QT syndrome and short QT syndrome. Transcript variants encoding distinct isoforms were also identified. In this study, we generated induced pluripotent stem cells (iPSC) from a healthy individual by electroporation of peripheral blood mononuclear cells and generated a KCNH2 heterozygous knockout human iPSC line via CRISPR/Cas9 gene editing. The resulting iPSCs had a normal karyotype, were free of genomically integrated epitomal plasmids, expressed pluripotency markers, and maintained trilineage differentiation potential.
Topics: Induced Pluripotent Stem Cells; Humans; ERG1 Potassium Channel; Long QT Syndrome; Heterozygote; Cell Line; CRISPR-Cas Systems; Gene Knockout Techniques; Cell Differentiation; Gene Editing; Arrhythmias, Cardiac
PubMed: 38547667
DOI: 10.1016/j.scr.2024.103400 -
Parkinsonism & Related Disorders May 2024Autonomic dysfunction (AuD) is a significant clinical challenge in patients with Dementia with Lewy Bodies (DLB). Manifestations of AuD such as orthostatic hypotension... (Comparative Study)
Comparative Study
INTRODUCTION
Autonomic dysfunction (AuD) is a significant clinical challenge in patients with Dementia with Lewy Bodies (DLB). Manifestations of AuD such as orthostatic hypotension (OH) is associated with falls and decreased quality of life. Cardiac autonomic denervation is an early phenomenon in DLB and a potential contributor to OH. This retrospective study was undertaken to explore whether routine ECG tracings could be used to identify signs of autonomic dysfunction in DLB.
METHODS
18 patients with DLB and 18 age-matched patients with Alzheimer's disease (AD) were included. ECGs and clinical data were analyzed retrospectively for heart rate variability (HRV) and QTc interval prolongation.
RESULTS
During an average of 10 years observation time (first to last ECG recording), the QTc interval increased in the DLB group, but not in the AD group. HRV was significantly lower at end of follow-up in the DLB group than in the AD group. DLB patients with OH had greater QTc prolongation.
CONCLUSION
Longitudinal ECG analysis indicates that signs of AuD in DLB are reflected on routine ECG tracings. If confirmed in larger cohorts, this could influence risk stratification and help direct preventive measures.
Topics: Humans; Male; Female; Aged; Alzheimer Disease; Lewy Body Disease; Heart Rate; Electrocardiography; Retrospective Studies; Aged, 80 and over; Long QT Syndrome; Disease Progression; Hypotension, Orthostatic; Middle Aged
PubMed: 38547558
DOI: 10.1016/j.parkreldis.2024.106947