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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 -
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 -
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 -
European Journal of Clinical... Feb 2021The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide resulting in significant morbidity and mortality. Arrhythmias are prevalent...
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide resulting in significant morbidity and mortality. Arrhythmias are prevalent and reportedly, the second most common complication. Several mechanistic pathways are proposed to explain the pro-arrhythmic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A number of treatment approaches have been trialled, each with its inherent unique challenges. This rapid systematic review aimed to examine the current incidence and available treatment of arrhythmias in COVID-19, as well as barriers to implementation.
METHODS
Our search of scientific databases identified relevant published studies from 1 January 2000 until 1 June 2020. We also searched Google Scholar for grey literature. We identified 1729 publications of which 1704 were excluded.
RESULTS
The incidence and nature of arrhythmias in the setting of COVID-19 were poorly documented across studies. The cumulative incidence of arrhythmia across studies of hospitalised patients was 6.9%. Drug-induced long QT syndrome secondary to antimalarial and antimicrobial therapy was a significant contributor to arrhythmia formation, with an incidence of 14.15%. Torsades de pointes (TdP) and sudden cardiac death (SCD) were reported. Treatment strategies aim to minimise this through risk stratification and regular monitoring of corrected QT interval (QTc).
CONCLUSION
Patients with SARS-CoV-2 are at an increased risk of arrhythmias. Drug therapy is pro-arrhythmogenic and may result in TdP and SCD in these patients. Risk assessment and regular QTc monitoring are imperative for safety during the treatment course. Further studies are needed to guide future decision-making.
Topics: Anti-Arrhythmia Agents; Anti-Bacterial Agents; Antimalarials; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Azithromycin; Bradycardia; COVID-19; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Electric Countershock; Hospitalization; Humans; Hydroxychloroquine; Incidence; Long QT Syndrome; SARS-CoV-2; Tachycardia, Ventricular; Torsades de Pointes; Ventricular Fibrillation; COVID-19 Drug Treatment
PubMed: 33043453
DOI: 10.1111/eci.13428 -
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 -
Medicine Aug 2021Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause...
BACKGROUND
Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir.
METHODS
In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies.
RESULTS
We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment.
CONCLUSION
Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.
Topics: Adult; Atazanavir Sulfate; Cytochrome P-450 CYP3A Inhibitors; Drug Therapy, Combination; Electrocardiography; Humans; Long QT Syndrome; Lopinavir; Ritonavir; Saquinavir
PubMed: 34397829
DOI: 10.1097/MD.0000000000026787 -
Drug Safety Oct 2022Electrocardiogram (ECG) monitoring is an important tool to detect and mitigate the risk of potentially fatal drug-induced QT prolongation and remains fundamental in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Electrocardiogram (ECG) monitoring is an important tool to detect and mitigate the risk of potentially fatal drug-induced QT prolongation and remains fundamental in supporting the quality use of high-risk QT interval prolonging medicines.
OBJECTIVE
The aim of this systematic review was to determine the prevalence of baseline and/or follow-up ECG use in adult patients taking high-risk QT interval prolonging medicines in clinical practice.
METHODS
CINAHL, Cochrane Library, Embase, PubMed, EThOS, OpenGrey and Proquest were searched for studies in adults that reported ECG use at baseline and/or at follow-up in relation to the initiation of a high-risk QT interval prolonging medicine in any clinical setting; either hospital or non-hospital. Two reviewers independently assessed the methodological quality of included studies. Proportional meta-analysis was conducted with all studies reporting baseline ECG use, before medicine initiation, and follow-up ECG use, within 30 days of medicine initiation.
RESULTS
There was variability in baseline ECG use according to the practice setting. The prevalence of baseline ECG use for high-risk QT interval prolonging medicines was moderate to high in the hospital setting at 75.1% (95% CI 64.3-84.5); however, the prevalence of baseline ECG use was low in the non-hospital setting at 33.7% (95% CI 25.8-42.2). The prevalence of follow-up ECG use was low to moderate in the hospital setting at 39.2% (95% CI 28.2-50.8) and could not be determined for the non-hospital setting.
CONCLUSIONS
The use of ECG monitoring for high-risk QT interval prolonging medicines is strongly influenced by the clinical practice setting. Baseline ECG use occurs more in the hospital setting in comparison to the non-hospital setting. There is lower use of follow-up ECG in comparison to baseline ECG.
Topics: Adult; Electrocardiography; Humans; Long QT Syndrome; Prevalence; Risk Factors
PubMed: 35947343
DOI: 10.1007/s40264-022-01215-x