Drug-Induced Proarrhythmia: QT Interval Prolongation and Torsades de Pointes

Drug-induced torsades de pointes (TdP), a life-threatening polymorphic ventricular tachycardia associated with prolongation of the QT interval, has been the main safety reason for the withdrawal of non-cardiac agents from clinical use over the last decade. This complication is commonly referred to as drug-induced proarrhythmia. The present review highlights on the mechanisms underlying the drug-induced QT interval prolongation and TdP as well as on the identification of easily recognized risk factors that predispose to this potentially life-threatening condition

Electrocardiographic and Electrophysiologic Characteristics of Ventricular Extrasystoles Arising from the Aortomitral Continuity

Left ventricular outflow tract arrhythmias originating from the aortomitral continuity, the left coronary cusp, the superior basal septum, and the epicardial left ventricular summit display common electrocardiographic and electrophysiological features, probably due to the close proximity of those locations. Catheter ablation of these arrhythmias can be challenging. The case of a 68-year-old male with frequent premature ventricular extrasystoles arising from the aortomitral continuity of the basal left ventricle is described. The electrocardiographic and electrophysiologic characteristics of this arrhythmia are discussed

Machine learning techniques for arrhythmic risk stratification: a review of the literature

Ventricular arrhythmias (VAs) and sudden cardiac death (SCD) are significant adverse events that affect the morbidity and mortality of both the general population and patients with predisposing cardiovascular risk factors. Currently, conventional disease-specific scores are used for risk stratification purposes. However, these risk scores have several limitations, including variations among validation cohorts, the inclusion of a limited number of predictors while omitting important variables, as well as hidden relationships between predictors. Machine learning (ML) techniques are based on algorithms that describe intervariable relationships. Recent studies have implemented ML techniques to construct models for the prediction of fatal VAs. However, the application of ML study findings is limited by the absence of established frameworks for its implementation, in addition to clinicians’ unfamiliarity with ML techniques. This review, therefore, aims to provide an accessible and easy-to-understand summary of the existing evidence about the use of ML techniques in the prediction of VAs. Our findings suggest that ML algorithms improve arrhythmic prediction performance in different clinical settings. However, it should be emphasized that prospective studies comparing ML algorithms to conventional risk models are needed while a regulatory framework is required prior to their implementation in clinical practice

Sinus node disease in subjects with type 1 ECG pattern of Brugada syndrome

AbstractBackgroundThe spectrum of phenotypes related to mutations of the SCN5A gene include Brugada syndrome (BS), long QT syndrome, progressive cardiac conduction defect, and sinus node disease (SND). The present study investigated the incidence of SND in subjects with type 1 electrocardiogram (ECG) pattern of BS.Methods and resultsThe study population consisted of 68 individuals (55 males, mean age 44.8±12.8 years) with spontaneous (n=27) or drug-induced (n=41) type 1 ECG pattern of BS. Twenty-eight subjects were symptomatic with a history of syncope (41.2%). SND was observed in 6 symptomatic subjects (8.8%), and was mainly attributed to sino-atrial block with sinus pauses. Two patients were initially diagnosed with SND, and received a pacemaker. Patients with SND displayed an increased P-wave duration in leads II and V2, PR interval in leads II and V2, QRS duration in leads II and V2, and increased QTc interval in lead V2 (p<0.05). AH and HV intervals as well as corrected sinus node recovery time (cSNRT) were significantly prolonged in subjects with SND (p<0.05). During a mean follow-up period of 5.0±3.6 years, five subjects with a history of syncope suffered appropriate implantable cardioverter defibrillator (ICD) discharges due to ventricular arrhythmias (7.4%). None of those diagnosed with SND suffered syncope or ICD therapies.ConclusionSND is not an uncommon finding in subjects with type 1 ECG pattern of BS. The occurrence of SND in relatively young patients may deserve meticulous investigation including sodium channel blocking test

Comparing the performance of published risk scores in Brugada syndrome: a multi-center cohort study.

The management of Brugada Syndrome (BrS) patients at intermediate risk of arrhythmic events remains controversial. The present study evaluated the predictive performance of different risk scores in an Asian BrS population and its intermediate risk subgroup. This retrospective cohort study included consecutive patients diagnosed with BrS from January 1 , 1997 to June 20 , 2020 from Hong Kong. The primary outcome is sustained ventricular tachyarrhythmias. Two novel risk risk scores and seven machine learning-based models (random survival forest, Ada boost classifier, Gaussian naïve Bayes, light gradient boosting machine, random forest classifier, gradient boosting classifier and decision tree classifier) were developed. The area under the receiver operator characteristic (ROC) curve (AUC) [95% confidence intervals] was compared between the different models. This study included 548 consecutive BrS patients (7% female, age at diagnosis: 50±16 years, follow-up: 84±55 months). For the whole cohort, the score developed by Sieira et al. showed the best performance (AUC: 0.806 [0.747-0.865]). A novel risk score was developed using the Sieira score and additional variables significant on univariable Cox regression (AUC: 0.855 [0.808-0.901]). A simpler score based on non-invasive results only showed a statistically comparable AUC (0.784 [0.724-0.845]), improved using random survival forests (AUC: 0.942 [0.913-0.964]). For the intermediate risk subgroup (N=274), a gradient boosting classifier model showed the best performance (AUC: 0.814 [0.791-0.832]). A simple risk score based on clinical and electrocardiographic variables showed a good performance for predicting VT/VF, improved using machine learning. Abstract: The management of Brugada Syndrome (BrS) patients at intermediate risk of arrhythmic events remains controversial. This study evaluated the predictive performance of published risk scores in a cohort of BrS patients from Hong Kong (N=548) and its intermediate risk subgroup (N=274). A novel risk score developed by modifying the best performing existing score (by. Sieira et al.) showed an area under the curve of 0.855 and 0.760 for the whole BrS cohort and the intermediate risk subgroup, respectively. The performance of the different scores was significantly improved machine learning-based methods, such as random survival forests and gradient boosting classifier. [Abstract copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Meta-analysis of T peak –T end and T peak –T end /QT ratio for risk stratification in congenital long QT syndrome

Background and objectives: Congenital long QT syndrome (LQTS) predisposes affected individuals to ventricular tachycardia/fibrillation (VF/VF), potentially resulting in sudden cardiac death. The Tpeak–Tend interval and the Tpeak–Tend/QT ratio, electrocardiographic markers of dispersion of ventricular repolarization, were proposed for risk stratification but their predictive values in LQTS have been controversial. A systematic review and meta-analysis was conducted to examine the value of Tpeak–Tend intervals and Tpeak–Tend/QT ratios in predicting arrhythmic and mortality outcomes in congenital LQTS. Method: PubMed and Embase databases were searched until 9th May 2017, identifying 199 studies. Results: Five studies on long QT syndrome were included in the final meta-analysis. Tpeak–Tend intervals were longer (mean difference [MD]: 13 ms, standard error [SE]: 4 ms, P = 0.002; I2 = 34%) in congenital LQTS patients with adverse events [syncope, ventricular arrhythmias or sudden cardiac death] compared to LQTS patients without such events. By contrast, Tpeak–Tend/QT ratios were not significantly different between the two groups (MD: 0.02, SE: 0.02, P = 0.26; I2 = 0%). Conclusion: This meta-analysis showed that Tpeak–Tend interval is significant higher in individuals who are at elevated risk of adverse events in congenital LQTS, offering incremental value for risk stratification

Right ventricular outflow tract endocardial unipolar substrate mapping: implications in risk stratification of Brugada syndrome

Brugada syndrome (BrS) is a complex arrhythmogenic disease displaying electrical and micro-structural abnormalities mainly located at the epicardium of the right ventricular outflow tract (RVOT). It is well-known that fibrosis, fatty infiltration, inflammation and reduced gap junction expression have been demonstrated at the epicardial anterior aspect of the RVOT providing the arrhythmogenic substrate for ventricular arrhythmic events in BrS. A number of models have been proposed for the risk stratification of patients with BrS. Endocardial unipolar electroanatomical mapping is an emerging tool that has been reintroduced to identify and quantify epicardial electrical abnormalities. Interestingly, current findings correlate the presence of large-sized endocardial unipolar electroanatomical abnormalities with either ventricular fibrillation inducibility during programmed ventricular stimulation or symptom status. This review aims to present existing data about the role of endocardial unipolar electroanatomical mapping for the identification of RVOT epicardial abnormalities as well as its potential clinical implications in risk stratification of BrS

Does Minimizing Ventricular Pacing Reduce the Incidence of Atrial Fibrillation? A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Right ventricular pacing disrupts atrioventricular synchrony and increases the risk of atrial fibrillation (AF). However, whether algorithms for minimizing ventricular pacing reduce the incidence of AF remains controversial. Therefore, we conducted a systematic review and meta-analysis to compare the incidence of AF between minimizing ventricular pacing and conventional pacing protocols in patients with pacemakers implanted. Methods: The PubMed, Embase, and Cochrane Library databases were searched up to August 1, 2017, for randomized controlled trials that reported the incidence of AF in patients with and without the use of algorithms for minimizing ventricular pacing. Results: Eleven studies comprising 5705 participants (61% males, mean age 71 years [standard deviation 11 years]) were finally included in the analysis. The mean follow-up duration was 24 months. Use of algorithms for minimizing ventricular pacing significantly reduced the incidence of AF, with an odds ratio of 0.74 (95% confidence interval 0.55–1.00; P<0.05). There was moderate heterogeneity among studies ( I 2 =63%). Conclusions: The incidence of AF was reduced by 26% with use of algorithms for minimizing ventricular pacing. The incorporation of such algorithms in routine clinical practice should in theory lead to a decrease in AF-related morbidity and mortality

Predictive Value of Tpeak – Tend Indices for Adverse Outcomes in Acquired QT Prolongation: A Meta-Analysis

Background: Acquired QT interval prolongation has been linked with malignant ventricular arrhythmias, such as torsade de pointes, in turn predisposing to sudden cardiac death. Increased dispersion of repolarization has been identified as a pro-arrhythmic factor and can be observed as longer Tpeak – Tend interval and higher Tpeak – Tend/QT ratio on the electrocardiogram. However, the values of these repolarization indices for predicting adverse outcomes in this context have not been systematically evaluated.Method: PubMed, Embase and Cochrane Library databases were searched until 14th February 2018, identifying 232 studies.Results: Five studies on acquired QT prolongation met the inclusion criteria and 308 subjects with drug-induced LQTS patients (mean age: 66 ± 18 years old; 46% male) were included in this meta-analysis. Tpeak – Tend intervals were longer [mean difference [MD]: 76 ms, standard error [SE]: 26 ms, P = 0.003; I2 = 98%] and Tpeak – Tend/QT ratios were higher (MD: 0.14, SE: 0.03, P = 0.000; I2 = 29%) in patients with torsade de pointes compared to those without these events.Conclusion: Tpeak – Tend interval and Tpeak – Tend/QT ratio were higher in patients with acquired QT prolongation suffering from torsade de pointes compared to those who did not. These repolarization indices may provide additional predictive value for identifying high-risk individuals

Secular trends of health care resource utilization and costs between Brugada syndrome and congenital long QT syndrome: A territory‐wide study

Background Health care resource utilization (HCRU) and costs are important metrics of health care burden, but they have rarely been explored in the setting of cardiac ion channelopathies. Hypothesis This study tested the hypothesis that attendance-related HCRUs and costs differed between patients with Brugada syndrome (BrS) and congenital long QT syndrome (LQTS). Methods This was a retrospective cohort study of consecutive BrS and LQTS patients at public hospitals or clinics in Hong Kong, China. HCRUs and costs (in USD) for Accident and Emergency (A&E), inpatient, general outpatient and specialist outpatient attendances were analyzed between 2001 and 2019 at the cohort level. Comparisons were made using incidence rate ratios (IRRs [95% confidence intervals]). Results Over the 19-year period, 516 BrS (median age of initial presentation: 51 [interquartile range: 38−61] years, 92% male) and 134 LQTS (median age of initial presentation: 21 [9−44] years, 32% male) patients were included. Compared to LQTS patients, BrS patients had lower total costs (2 008 126 [2 007 622−2 008 629] vs. 2 343 864 [2 342 828−2 344 900]; IRR: 0.857 [0.855−0.858]), higher costs for A&E attendances (83 113 [83 048−83 177] vs. 70 604 [70 487−70 721]; IRR: 1.177 [1.165−1.189]) and general outpatient services (2,176 [2,166−2,187] vs. 921 [908−935]; IRR: 2.363 [2.187−2.552]), but lower costs for inpatient stay (1 391 624 [1 391 359−1 391 889] vs. 1 713 742 [1 713 166−1 714 319]; IRR: 0.812 [0.810−0.814]) and lower costs for specialist outpatient services (531 213 [531 049−531 376] vs. 558 597 [558268−558926]; IRR: 0.951 [0.947−0.9550]). Conclusions Overall, BrS patients consume 14% less health care resources compared to LQTS patients in terms of attendance costs. BrS patients require more A&E and general outpatient services, but less inpatient and specialist outpatient services than LQTS patients