Alan Sugrue

QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update

BACKGROUND Some psychotropic medications have been associated with prolongation of the QT interval and QT prolongation, especially in those with medical illness, and are linked to lethal ventricular arrhythmias, such as Torsades de Pointes (TdP). In 2013, we published a review of QT prolongation, TdP, and psychotropic medications. OBJECTIVE We provide an update over the past 5 years on the specific concerns most relevant to clinicians who see medically ill patients. METHODS In this nonsystematic review, we aimed to carefully and intensively identify new articles by utilizing a structured PubMed search from 2012-present. RESULTS QT prolongation remains an imperfect, though well-established marker of risk for TdP. Among antidepressant medications, citalopram does appear to prolong the QT interval more than other selective serotonin reuptake inhibitors, though the clinical significance of this prolongation remains unclear. Escitalopram appears to prolong the QT interval to a lesser extent. Haloperidol carries a risk for QT prolongation, but the assertion that intravenous haloperidol is inherently riskier may be confounded by its primary use in medically ill populations. Among atypical antipsychotic agents, ziprasidone-and possibly iloperidone-is associated with the greatest QT prolongation, whereas aripiprazole appears safest from this standpoint. CONCLUSIONS The evidence for clinically meaningful QT prolongation with most classes of psychiatric agents remains minimal. The most important risk-reducing intervention clinicians can make is undertaking a careful analysis of other QT risk factors when prescribing psychiatric medications.

Identification of Concealed and Manifest Long QT Syndrome Using a Novel T Wave Analysis Program

Background—Congenital long QT syndrome (LQTS) is characterized by QT prolongation. However, the QT interval itself is insufficient for diagnosis, unless the corrected QT interval is repeatedly ≥500 ms without an acquired explanation. Further, the majority of LQTS patients have a corrected QT interval below this threshold, and a significant minority has normal resting corrected QT interval values. Here, we aimed to develop and validate a novel, quantitative T wave morphological analysis program to differentiate LQTS patients from healthy controls. Methods and Results—We analyzed a genotyped cohort of 420 patients (22±16 years, 43% male) with either LQT1 (61%) or LQT2 (39%). ECG analysis was conducted using a novel, proprietary T wave analysis program that quantitates subtle changes in T wave morphology. The top 3 discriminating features in each ECG lead were determined and the lead with the best discrimination selected. Classification was performed using a linear discriminant classifier and validated on an untouched cohort. The top 3 features were Tpeak–Tend interval, T wave left slope, and T wave center of gravity x axis (last 25% of the T wave). Lead V6 had the best discrimination. It could distinguish 86.8% of LQTS patients from healthy controls. Moreover, it distinguished 83.33% of patients with concealed LQTS from controls, despite having essentially identical resting corrected QT interval values. Conclusions—T wave quantitative analysis on the 12-lead surface ECG provides an effective, novel tool to distinguish patients with either LQT1/LQT2 from healthy matched controls. It can provide guidance while mutation-specific genetic testing is in motion for family members.

Utility of T-wave amplitude as a non-invasive risk marker of sudden cardiac death in hypertrophic cardiomyopathy

Objective Sudden cardiac arrest (SCA) is the most devastating outcome in hypertrophic cardiomyopathy (HCM). We evaluated repolarisation features on the surface electrocardiogram (ECG) to identify the potential risk factors for SCA. Methods Data was collected from 52 patients with HCM who underwent implantable cardioverter defibrillator (ICD) implantation. Leads V2 and V5 from the ECG closest to the time of ICD implant were utilised for measuring the Tpeak-Tend interval (Tpe), QTc, Tpe/QTc, T-wave duration and T-wave amplitude. The presence of the five traditional SCA-associated risk factors was assessed, as well as the HCM risk-SCD score. Results 16 (30%) patients experienced aborted cardiac arrest over 8.5±4.1 years, with 9 receiving an ICD shock and 7 receiving ATP. On univariate analysis, T-wave amplitude was associated with appropriate ICD therapy (HR per 0.1 mV 0.79, 95% CI 0.56 to 0.96, p=0.02). Aborted SCA was not associated with a greater mean QTc duration, Tpeak-Tend interval, T-wave duration, or Tpe/QT ratio. Multivariate analysis (adjusting for cardinal HCM SCA-risk factors) showed T-wave amplitude in Lead V2 was an independent predictor of risk (adjusted HR per 0.1 mV 0.74, 95% CI 0.57 to 0.97, p=0.03). Addition of T-wave amplitude in Lead V2 to the traditional risk factors resulted in significant improvement in risk stratification (C-statistic from 0.65 to 0.75) but did not improve the performance of the HCM SCD-risk score. Conclusions T-wave amplitude is a novel marker of SCA in this high risk HCM population and may provide incremental predictive value to established risk factors. Further work is needed to define the role of repolarisation abnormalities in predicting SCA in HCM.

Ischemic Stroke or Systemic Embolism After Transseptal Ablation of Arrhythmias in Patients With Cardiac Implantable Electronic Devices.

Background Incidental mobile thrombi are commonly found on endovascular leads of cardiac implantable electronic devices (CIEDs). Transseptal puncture for catheter ablation of arrhythmia poses a risk for paradoxical embolism. We examined risk of ischemic stroke, transient ischemic attack (TIA), or systemic embolism after transseptal ablation in patients with and without CIEDs. Methods and Results Using a national administrative claims database, 31 720 patients who underwent a transseptal catheter ablation between January 2004 and September 2014 were identified. Two propensity‐matched cohorts were created by matching demographic variables, administrative variables, Charlson Comorbidity Index, CHA 2 DS 2‐Vasc score, and year and indication for ablation (5533 and 11 300 patients with and without CIEDs). Incidence rates and Cox proportional hazards models were used to estimate risk of ischemic stroke, TIA, or systemic embolism for patients with and without CIEDs. Impact of oral anticoagulation (OAC) use on the endpoint was examined. Over a mean follow‐up of 2.1 years, the incidence of the combined endpoint was 1.9 per 100 person‐years in patients with CIEDs and 1.5 per 100 person‐years in patients without CIEDs (P=0.03). Among patients not on OAC, presence of a cardiac device was associated with an increased risk (hazard ratio [HR], 1.71 [1.24–2.35]; P<0.01), whereas there was no association noted among patients treated with OAC (HR, 0.98 [0.75–1.28]). Conclusion CIEDs are associated with an increased risk of stroke, TIA, or systemic embolism after transseptal ablation, but this risk is attenuated with postablation OAC use. Role of anticoagulation post‐transseptal ablation in patients with CIED warrants further investigation.

New electrocardiographic criteria to differentiate the type-2 Brugada pattern from electrocardiogram of healthy athletes with r'-wave in leads V1/V2.

Serra et al .1 present a well-written manuscript on new electrocardiographic criteria to differentiate the type-2 Brugada pattern from electrocardiogram of healthy athletes with r ′-wave in leads V1/V2. They report three new electrocardiographic (ECG) criteria based on the characteristics of the r ′-wave, with varied sensitivity and specificity as well as positive predictive values (PPV) and negative predictive values (NPV). I caution the readers to …

Irreversible electroporation for the treatment of cardiac arrhythmias

ABSTRACT Introduction: Cardiac ablation is an established treatment modality for the management of patients with cardiac arrhythmias. Current approaches to cardiac ablation employ thermal based energy to achieve lesions (damage) within the heart. There are many shortcomings and limitations of thermal based approaches. Electroporation (DC energy) is a non-thermal alternative approach to ablation that has shown significant promise in animal studies. Areas covered: An extensive review of the literature on the application of electroporation for ablation (both cardiac and collateral cardiac tissue) was undertaken. This review explores irreversible electroporation as a cardiac ablation modality. Specifically, it focuses and explains the biophysics of electroporation, the limitations of current thermal based approaches and examines the current data published on electroporation cardiac ablation. Expert commentary: Electroporation is a fast-growing novel ablation modality that has many advantages over current thermal based approaches. Current research in animal models shows its can be safely and efficaciously applied to the heart. Although further research is required, electroporation represents an appealing option for the ablation cardiac arrhythmias.

Impact of sedation vs. general anaesthesia on percutaneous epicardial access safety and procedural outcomes

Aims Patient movement while under moderate/deep sedation may complicate percutaneous epicardial access (EpiAcc), mapping and ablation. We sought to compare procedural outcomes in patients undergoing EpiAcc under sedation vs. general anaesthesia (GA) for ablation. Methods and results Patients undergoing EpiAcc between January 2004 and July 2014 were included. Safety, procedural, and clinical outcomes were compared between patients undergoing EpiAcc under sedation or GA for ventricular tachycardia or premature ventricular complex ablation. Between January 2004 and July 2014, 170 patients underwent EpiAcc (mean age, 53.2 ± 15.8 years; average ejection fraction, 44.3 ± 15.3%). The majority (122 [72%] patients) were male. GA was used in 69 (40.6%). There was no difference in route of access (more often anterior, 53.0%) or the rate of successful access (96% overall) between groups. Similarly, the site of ablation (endocardial vs. epicardial vs. combined endocardial/epicardial) was similar between groups. Complications were equally seen between groups-the most frequent event/complication was pericardial effusion, occurring in 10.6% of patients. Finally, procedural and clinical success rates between GA and sedation groups were comparable (93 vs. 91% and 44 vs. 51%, respectively, P > 0.05). Conclusions Choice of anaesthesia for EpiAcc does not appear to significantly affect safety and procedural or clinical outcomes. For patients in whom anaesthesia may pose increased risk, it is reasonable to obtain epicardial access under sedation.

Periprocedural Anticoagulation Management for Atrial Fibrillation Ablation: Current Knowledge and Future Directions

Catheter ablation (CA) for atrial fibrillation (AF) is an established first-line approach to the management of drug-refractory AF. Although, advancements in procedural techniques and technology have improved the efficacy and safety of CA, thromboembolism (TE) remains one of the most feared periprocedural complications. Minimizing the risk of TE during and after CA requires a multifaceted approach, in which periprocedural anticoagulation plays a central role. The goal of anticoagulation before, during, and after CA is to minimize TE risk without excessively increasing the risk of adverse bleeding. Generally, there are two broad approaches to periprocedural anticoagulation management, “interrupted” or “uninterrupted.” Interrupted refers to those patients in whom their oral anticoagulant is stopped before the CA, with or without “bridging” with another anticoagulant, while uninterrupted refers to continuation of oral anticoagulation throughout the periprocedural period. The strongest evidence supports an uninterrupted oral anticoagulation strategy with warfarin, which is currently the standard of care. The introduction of the novel anticoagulants has added some complexity to the decision making. Current data generally supports that these are safe to use and are not associated with any additional procedural risk or adverse events (thromboembolism or bleeding) compared to warfarin. At present, based upon current evidence from randomized trials, dabigatran and rivaroxaban are reasonable alternatives to warfarin for an uninterrupted approach, while further data is needed (and trials are ongoing) for apixaban and edoxaban. In this article, we discuss the different approaches to the management of periprocedural anticoagulation and the data supporting their use.

Automated T-wave analysis can differentiate acquired QT prolongation from congenital long QT syndrome

Prolongation of the QT on the surface electrocardiogram can be due to either genetic or acquired causes. Distinguishing congenital long QT syndrome (LQTS) from acquired QT prolongation has important prognostic and management implications. We aimed to investigate if quantitative T‐wave analysis could provide a tool for the physician to differentiate between congenital and acquired QT prolongation.

Noninvasive assessment of dofetilide plasma concentration using a deep learning (neural network) analysis of the surface electrocardiogram: A proof of concept study

Background Dofetilide is an effective antiarrhythmic medication for rhythm control in atrial fibrillation, but carries a significant risk of pro-arrhythmia and requires meticulous dosing and monitoring. The cornerstone of this monitoring, measurement of the QT/QTc interval, is an imperfect surrogate for plasma concentration, efficacy, and risk of pro-arrhythmic potential. Objective The aim of our study was to test the application of a deep learning approach (using a convolutional neural network) to assess morphological changes on the surface ECG (beyond the QT interval) in relation to dofetilide plasma concentrations. Methods We obtained publically available serial ECGs and plasma drug concentrations from 42 healthy subjects who received dofetilide or placebo in a placebo‐controlled cross‐over randomized controlled clinical trial. Three replicate 10-s ECGs were extracted at predefined time-points with simultaneous measurement of dofetilide plasma concentration We developed a deep learning algorithm to predict dofetilide plasma concentration in 30 subjects and then tested the model in the remaining 12 subjects. We compared the deep leaning approach to a linear model based only on QTc. Results Fourty two healthy subjects (21 females, 21 males) were studied with a mean age of 26.9 ± 5.5 years. A linear model of the QTc correlated reasonably well with dofetilide drug levels (r = 0.64). The best correlation to dofetilide level was achieved with the deep learning model (r = 0.85). Conclusion This proof of concept study suggests that artificial intelligence (deep learning/neural network) applied to the surface ECG is superior to analysis of the QT interval alone in predicting plasma dofetilide concentration.