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Evaluation of the QT interval in patients with drug-induced QT prolongation and torsades de pointes.Journal of Cardiovascular... Oct 2020Data on the optimal location of the electrocardiogram (ECG) leads for the diagnosis of drug-induced long QT syndrome (diLQTS) with torsades de pointes (TdP) are lacking.
BACKGROUND
Data on the optimal location of the electrocardiogram (ECG) leads for the diagnosis of drug-induced long QT syndrome (diLQTS) with torsades de pointes (TdP) are lacking.
METHODS
We systematically reviewed the literature for the ECGs of patients with diLQTS and subsequent TdP. We assessed T wave morphology in each lead and measured the longest QT interval in the limb and chest leads in a standardized fashion.
RESULTS
Of 84 patients, 61.9% were female and the mean age was 58.8 years. QTc was significantly longer in chest versus limb leads (mean (SD) 671 (102) vs. 655 (97) ms, p = .02). Using only limb leads for QT interpretation, 18 (21.4%) ECGs were noninterpretable: 10 (11.9%) due to too flat T waves, 7 (8.3%) due to frequent, early PVCs and 1 (1.2%) due to too low ECG recording quality. In the chest leads, ECGs were noninterpretable in nine (10.7%) patients: six (7.1%) due to frequent, early PVCs, one (1.2%) due to insufficient ECG quality, two (2.4%) due to missing chest leads but none due to too flat T waves. The most common T wave morphologies in the limb leads were flat (51.0%), broad (14.3%), and late peaking (12.6%) T waves. Corresponding chest lead morphologies were inverted (35.5%), flat (19.6%), and biphasic (15.2%) T waves.
CONCLUSIONS
Our results indicate that QT evaluation by limb leads only underestimates the incidence of diLQTS experiencing TdP and favors the screening using both limb and chest lead ECG.
Topics: Electrocardiography; Female; Humans; Long QT Syndrome; Middle Aged; Pharmaceutical Preparations; Torsades de Pointes; Ventricular Premature Complexes
PubMed: 32700358
DOI: 10.1111/jce.14687 -
Annals of Noninvasive Electrocardiology... Jan 2015
Review
Topics: Diagnosis, Differential; Electrocardiography; Humans; Takotsubo Cardiomyopathy
PubMed: 25367822
DOI: 10.1111/anec.12228 -
Journal of Athletic Training Dec 2017Reference/Citation: Harmon KG, Zigman M, Drezner JA. The effectiveness of screening history, physical exam, and ECG to detect potentially lethal cardiac disorders in... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Reference/Citation: Harmon KG, Zigman M, Drezner JA. The effectiveness of screening history, physical exam, and ECG to detect potentially lethal cardiac disorders in athletes: a systematic review/meta-analysis. J Electrocardiol. 2015;48(3):329-338.
CLINICAL QUESTION
Which screening method should be considered best practice to detect potentially lethal cardiac disorders during the preparticipation physical examination (PE) of athletes?
DATA SOURCES
The authors completed a comprehensive literature search of MEDLINE, CINAHL, Cochrane Library, Embase, Physiotherapy Evidence Database (PEDro), and SPORTDiscus from January 1996 to November 2014. The following key words were used individually and in combination: ECG, athlete, screening, pre-participation, history, and physical. A manual review of reference lists and key journals was performed to identify additional studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for this review.
STUDY SELECTION
Studies selected for this analysis involved (1) outcomes of cardiovascular screening in athletes using the history, PE, and electrocardiogram (ECG); (2) history questions and PE based on the American Heart Association recommendations and guidelines; and (3) ECGs interpreted following modern standards. The exclusion criteria were (1) articles not in English, (2) conference abstracts, and (3) clinical commentary articles. Study quality was assessed on a 7-point scale for risk of bias; a score of 7 indicated the highest quality. Articles with potential bias were excluded.
DATA EXTRACTION
Data included number and sex of participants, number of true- and false-positives and negatives, type of ECG criteria used, number of cardiac abnormalities, and specific cardiac conditions. The sensitivity, specificity, false-positive rate, and positive predictive value of each screening tool were calculated and summarized using a bivariate random-effects meta-analysis model.
MAIN RESULTS
Fifteen articles reporting on 47 137 athletes were fully reviewed. The overall quality of the 15 articles ranged from 5 to 7 on the 7-item assessment scale (ie, participant selection criteria, representative sample, prospective data with at least 1 positive finding, modern ECG criteria used for screening, cardiovascular screening history and PE per American Heart Association guidelines, individual test outcomes reported, and abnormal screening findings evaluated by appropriate diagnostic testing). The athletes (66% males and 34% females) were ethnically and racially diverse, were from several countries, and ranged in age from 5 to 39 years. The sensitivity and specificity of the screening methods were, respectively, ECG, 94% and 93%; history, 20% and 94%; and PE, 9% and 97%. The overall false-positive rate for ECG (6%) was less than that for history (8%) or PE (10%). The positive likelihood ratios of each screening method were 14.8 for ECG, 3.22 for history, and 2.93 for PE. The negative likelihood ratios were 0.055 for ECG, 0.85 for history, and 0.93 for PE. A total of 160 potentially lethal cardiovascular conditions were detected, for a rate of 0.3%, or 1 in 294 patients. The most common conditions were Wolff-Parkinson-White syndrome (n = 67, 42%), long QT syndrome (n = 18, 11%), hypertrophic cardiomyopathy (n = 18, 11%), dilated cardiomyopathy (n = 11, 7%), coronary artery disease or myocardial ischemia (n = 9, 6%), and arrhythmogenic right ventricular cardiomyopathy (n = 4, 3%).
CONCLUSIONS
The most effective strategy to screen athletes for cardiovascular disease was ECG. This test was 5 times more sensitive than history and 10 times more sensitive than PE, and it had a higher positive likelihood ratio, lower negative likelihood ratio, and lower false-positive rate than history or PE. The 12-lead ECG interpreted using modern criteria should be considered the best practice in screening athletes for cardiovascular disease, and the use of history and PE alone as screening tools should be reevaluated.
Topics: Athletes; Electrocardiography; Heart Diseases; Humans; Mass Screening; Physical Examination; Prospective Studies; Reproducibility of Results
PubMed: 29154691
DOI: 10.4085/1062-6050-52.11.24 -
Frontiers in Pharmacology 2022Diurnal oscillations in human cardiac electrophysiology are thought to be under the control of the endogenous circadian clock. The incidence of arrhythmic events in...
Diurnal oscillations in human cardiac electrophysiology are thought to be under the control of the endogenous circadian clock. The incidence of arrhythmic events in patients with Long QT syndrome (LQTS) varies diurnally. The diurnal variation in QT interval has previously been identified as a potential for error in clinical trials which utilise ECG measurement. We performed a systematic review of clinical trials for LQTS to identify practice around specification of timing information for point electrocardiogram (ECG) measurements, analysis of continual ECG recordings ≥24 h, and drug delivery. Despite guidelines having been issued around the analysis of 24-h ECG recordings, we identify a lack of usage of detailed time of day information in trial design for LQTS studies, which has the potential to affect the interpretation of the results of drug trials. We identify that, in contrast, clinical trials for QT prolonging drugs demonstrate increased incorporation of time of day information of both QT analysis and drug dosing. We provide a visual portal to allow trial designers and clinicians to better understand timing of common cardiac-targeting drugs, and to bear this concept in mind in the design of future clinical trials.
PubMed: 35370731
DOI: 10.3389/fphar.2022.867131 -
Archives of Cardiovascular Diseases Feb 2023Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease.
AIMS
To identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations.
METHODS
A systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models.
RESULTS
Of the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33-2.12; I=69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08-1.50; I=38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26-3.39; I=78%); stroke (HR 1.59, 95% CI 1.29-1.96; I=45%); sudden cardiac death (HR 1.60, 95% CI 1.14-2.25; I=68%); and atrial fibrillation (HR 1.55, 95% CI 1.31-1.83; I=0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population.
CONCLUSION
QTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population.
Topics: Male; Humans; Female; Cardiovascular Diseases; Risk Factors; Heart Rate; Diabetes Mellitus, Type 2; Long QT Syndrome; Atrial Fibrillation; Coronary Disease; Electrocardiography
PubMed: 36690508
DOI: 10.1016/j.acvd.2022.11.007 -
Congenital Heart Disease Nov 2019Left cardiac sympathetic denervation (LCSD) has been proposed as useful therapy for long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Left cardiac sympathetic denervation (LCSD) has been proposed as useful therapy for long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT), in addition to anti-arrhythmic agents and implantable cardioverter defibrillators. This study aimed to assess the current evidence for LCSD and compare the open vs the video-assisted thoracoscopic surgery (VATS) approaches.
METHODS
MEDLINE, Embase and Cochrane library databases were searched up to December 2018 for studies reporting the long-term outcomes of LCSD in LQTS, CPVT patients. The incidence of cardiac events (CEs) before and after surgery, the change in QTc interval, and surgical complications were pooled to estimate the efficacy of LCSD. Meta-regression was used to estimate the effects of surgical approach (open vs VATS) on outcomes following LCSD.
RESULTS
Twenty-seven papers met our inclusion criteria (647 patients). VATS was used in 408 patients (63.1%), open surgery in 239 (36.9%). Mean follow-up was 32.3 ± 32.5 months. Postsurgery, 398/585 patients (68.0%) were free of CEs and QTc decreased from 522 ± 61.6 ms to 494 ± 52.3 ms. Meta-regression showed no differences between the two approaches in the incidence of CEs and surgical complications. VATS was associated with a smaller reduction in QTc (β-coefficient -20.04, 95% CI -36.82 to -3.27, P = .019).
CONCLUSIONS
LCSD was associated with a reduction in the incidence of CEs in LQTS, CPVT patients and in the duration of QTc. Open surgery was associated with a greater reduction in QTc. Due to the limitations that hindered our study, a randomized trial is warranted to fully establish LCSD safety and efficacy.
Topics: Adolescent; Adult; Anti-Arrhythmia Agents; Child; Child, Preschool; Defibrillators, Implantable; Electric Countershock; Female; Heart; Heart Rate; Humans; Long QT Syndrome; Male; Postoperative Complications; Risk Factors; Sympathectomy; Tachycardia, Ventricular; Thoracic Surgery, Video-Assisted; Treatment Outcome; Young Adult
PubMed: 31621201
DOI: 10.1111/chd.12855 -
The Cochrane Database of Systematic... Oct 2015Sudden cardiac death is a significant cause of mortality in both the US and globally. However, 5% to 15% of people with sudden cardiac death have no structural... (Review)
Review
BACKGROUND
Sudden cardiac death is a significant cause of mortality in both the US and globally. However, 5% to 15% of people with sudden cardiac death have no structural abnormalities, and most of these events are attributed to underlying cardiac ion channelopathies. Rates of cardiac ion channelopathy diagnosis are increasing. However, the optimal treatment for such people is poorly understood and current guidelines rely primarily on expert opinion.
OBJECTIVES
To compare the effect of implantable cardioverter defibrillators (ICD) with antiarrhythmic drugs or usual care in reducing the risk of all-cause mortality, fatal and non-fatal cardiovascular events, and adverse events in people with cardiac ion channelopathies.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 6), EMBASE, MEDLINE, Conference Proceedings Citation Index - Science (CPCI-S), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) in July 2015. We applied no language restrictions.
SELECTION CRITERIA
We included all randomized controlled trials of people aged 18 years and older with ion channelopathies, including congenital long QT syndrome, congenital short QT syndrome, Brugada syndrome, or catecholaminergic polymorphic ventricular tachycardia. Participants must have been randomized to ICD implantation and compared to antiarrhythmic drug therapy or usual care.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion and extracted the data. We included all-cause mortality, fatal and non-fatal cardiovascular events, and adverse events for our primary outcome analyses and non-fatal cardiovascular events, rates of inappropriate ICD firing, quality of life, and cost for our secondary outcome analyses. We calculated risk ratios (RR) and associated 95% confidence intervals (CIs) for dichotomous outcomes, both for independent and pooled study analyses.
MAIN RESULTS
From the 468 references identified after removing duplicates, we found two trials comprising 86 participants that met our inclusion criteria. Both trials included participants with Brugada syndrome who were randomized to ICD versus β-blocker therapy for secondary prevention for sudden cardiac death. Both studies were small, were performed by the same investigators, and exhibited a high risk of bias across multiple domains. In the group randomized to ICD therapy, there was a nine-fold lower risk of mortality compared with people randomized to medical therapy (0% with ICD versus 18% with medical therapy; RR 0.11, 95% CI 0.01 to 0.83; 2 trials, 86 participants). There was low quality evidence of a difference in the rates of combined fatal and non-fatal cardiovascular events, and the results were imprecise (26% with ICD versus 18% with medical therapy; RR 1.49, 95% CI 0.66 to 3.34; 2 trials, 86 participants). The rates of adverse events were higher in the ICD group, but these results were imprecise (28% with ICD versus 10% with medical therapy; RR 2.44, 95% CI 0.92 to 6.44; 2 trials, 86 participants). For secondary outcomes, the risk of non-fatal cardiovascular events was higher in the ICD group, but these results were imprecise and were driven entirely by appropriate ICD-termination of cardiac arrhythmias (26% with ICD versus 0% with medical therapy; RR 11.4, 95% CI 1.57 to 83.3; 2 trials, 86 participants). Approximately 25% of the ICD group experienced inappropriate ICD firing, all of which was corrected by device reprogramming. No data were available for quality of life or cost. We considered the quality of evidence low using the GRADE methodology, due to study limitations and imprecision of effects.
AUTHORS' CONCLUSIONS
Among people with Brugada syndrome who have survived a prior episode of sudden cardiac death, ICD therapy appeared to reduce mortality when compared to β-blocker therapy, but the true magnitude may be substantially different from the estimate of the effect because of study limitations and imprecision. Due to the large magnitude of effect, it is unlikely that there will be additional studies evaluating the role of ICDs for secondary prevention in this population. Further studies are necessary to determine the optimal treatment, if any, to prevent an initial episode of sudden cardiac death in people with cardiac ion channelopathies.
Topics: Adrenergic beta-Antagonists; Brugada Syndrome; Channelopathies; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Diseases; Humans; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 26445202
DOI: 10.1002/14651858.CD011168.pub2 -
European Journal of Preventive... Sep 2022Current exercise recommendations make it difficult for long QT syndrome (LQTS) patients to adopt a physically active and/or athletic lifestyle. The purpose of this...
Current exercise recommendations make it difficult for long QT syndrome (LQTS) patients to adopt a physically active and/or athletic lifestyle. The purpose of this review is to summarize the current evidence, identify knowledge gaps, and discuss research perspectives in the field of exercise and LQTS. The first aim is to document the influence of exercise training, exercise stress, and postural change interventions on ventricular repolarization in LQTS patients, while the second aim is to describe electrophysiological measurements used to study the above. Studies examining the effects of exercise on congenital or acquired LQTS in human subjects of all ages were included. Systematic searches were performed on 1 October 2021, through PubMed (NLM), Ovid Medline, Ovid All EBM Reviews, Ovid Embase, and ISI Web of Science, and limited to articles written in English or French. A total of 1986 LQTS patients and 2560 controls were included in the 49 studies. Studies were mainly case-control studies (n = 41) and examined exercise stress and/or postural change interventions (n = 48). One study used a 3-month exercise training program. Results suggest that LQTS patients have subtype-specific repolarization responses to sympathetic stress. Measurement methods and quality were found to be very heterogeneous, which makes inter-study comparisons difficult. In the absence of randomized controlled trials, the current recommendations may have long-term risks for LQTS patients who are discouraged from performing physical activity, rendering its associated health benefits out of range. Future research should focus on discovering the most appropriate levels of exercise training that promote ventricular repolarization normalization in LQTS.
Topics: Case-Control Studies; Electrocardiography; Exercise; Exercise Test; Humans; Long QT Syndrome
PubMed: 35537006
DOI: 10.1093/eurjpc/zwac081 -
Psychopharmacology Feb 2021Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management...
RATIONALE
Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The concurrent use of treatments for COVID-19 and antipsychotics should consider eventual drug-drug interactions OBJECTIVE: To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics.
EVIDENCE REVIEW
Three databases were consulted: Lexicomp® Drug Interactions, Micromedex® Solutions Drugs Interactions, and Liverpool© Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and Torsade de Pointes (TdP), the CredibleMeds® QTDrugs List was searched. The authors made a recommendation agreed to by consensus. Additionally, a systematic review of drug-drug interactions between antipsychotics and COVID-19 treatment was conducted.
RESULTS
The main interactions between COVID-19 drugs and antipsychotics are the risk of QT-prolongation and TdP, and cytochromes P450 interactions. Remdesivir, baricinitib, and anakinra can be used concomitantly with antipsychotics without risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Favipiravir only needs caution with chlorpromazine and quetiapine. Tocilizumab is rather safe to use in combination with antipsychotics. The most demanding COVID-19 treatments for coadministration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir because of the risk of QT prolongation and TdP and cytochromes interactions. The systematic review provides highly probable drug interaction between lopinavir/ritonavir plus quetiapine and ritonavir/indinavir plus risperidone.
CONCLUSIONS
Clinicians prescribing antipsychotics should be aware of the likely risk of drug-drug interaction with COVID-19 medication and may benefit from taking into account present recommendations of use to preserve patient safety.
Topics: Antipsychotic Agents; Antiviral Agents; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Long QT Syndrome; SARS-CoV-2; Torsades de Pointes; COVID-19 Drug Treatment
PubMed: 33410987
DOI: 10.1007/s00213-020-05716-4 -
Journal of Arrhythmia Dec 2023Inherited Primary Arrhythmias Syndromes (IPAS), especially Brugada syndrome (BrS), have been associated with arrhythmogenic substrates that can be targeted through...
BACKGROUND
Inherited Primary Arrhythmias Syndromes (IPAS), especially Brugada syndrome (BrS), have been associated with arrhythmogenic substrates that can be targeted through ablation. This meta-analysis evaluated the outcomes of catheter ablation (CA) in different types of IPAS based on procedural guidance and location.
METHODS
A systematic search was conducted across multiple databases to identify studies reporting on ventricular arrhythmia (VA) events before and after CA in IPAS, including BrS, Long-QT syndrome (LQTS), Early repolarization syndrome (ERS), and Idiopathic ventricular fibrillation (IVF). The primary outcomes were VA recurrence and VA burden, evaluated through conditional subgroup analysis. Procedural data were collected as secondary outcomes.
RESULTS
A total of 21 studies involving 584 IPAS patients who underwent CA were included. Following a mean follow-up duration of 33.5 months, substrate-based ablation demonstrated efficacy in reducing VA recurrence across all types of IPAS [RR 0.23; 95% CI (0.13-0.39); < .001; = 74%]. However, activation guidance ablation was found to be effective only in IVF cases. Although recurrences still occurred, CA was successful in reducing VA burden [MD -4.70; 95% CI (-6.11-(-3.29); < .001; = 74%]. The mean size of arrhythmogenic substrate was 15.70 cm [95% CI (12.34-19.99 cm)], predominantly distributed in the epicardial right ventricular outflow tract (RVOT) in BrS cases and LQTS [Proportion 0.99; 95% CI (0.96-1.00) and Proportion 0.82; 95% CI ( 0.59-1.00), respectively].
CONCLUSION
Substrate-based CA has demonstrated effective prevention of VA and reduction in VA burden in IPAS cases.
PubMed: 38045449
DOI: 10.1002/joa3.12947