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.

Assessment of Contractility in Human iPS Cell-Derived Cardiomyocytes Using Motion Vector Analysis.

Human-induced pluripotent stem cell (iPSC) technology paves the way for next-generation drug-safety assessment. In particular, human iPSC-derived cardiomyocytes, which exhibit electrical activity, are useful as a human cell model for assessing QT-interval prolongation and the risk of the lethal arrhythmia Torsade de Pointes (TdP). In addition to proarrhythmia assay, contractile behavior has received increased attention in drug development. In this study, we developed a novel high-throughput in vitro assay system using motion vectors to evaluate the contractile activity of iPSC-derived cardiomyocytes as a physiologically relevant human platform. The methods presented here highlight the use of commercially available iPSC-derived cardiomyocytes, iCell cardiomyocytes, for contractility evaluation recorded by the motion vector system.

How to Prescribe Drugs With an Identified Proarrhythmic Liability.

This is an article in the Journal of Clinical Pharmacology's Core Entrustable Professional Activities in Clinical Pharmacology series that discusses drug-induced proarrhythmia and is offered as a teaching aid for medical students and residents. Drugs from diverse pharmacological classes can lead to multiple types of arrhythmias including the polymorphic ventricular tachycardia torsades de pointes (TdP). Although typically occurring in self-limiting bursts with or without associated symptoms, which can range from mild lightheadedness and palpitations to syncope and seizures, TdP can also occasionally progress to ventricular fibrillation and sudden cardiac death. To provide patients with the optimal therapeutic benefits of potentially proarrhythmic drugs, prescribers are responsible for obtaining a good understanding of the compound's benefit-risk properties and perform a judicious assessment of the patient's clinical characteristics and individual risk factors. Dose adjustments and/or additional monitoring of electrocardiograms and electrolyte balances may be appropriate in some cases. This article explains the pharmacological mechanism of action of drug-induced proarrhythmia associated with compounds that prolong the repolarization period, illustrates how this liability is conveyed in a drug's prescribing information (label), details the clinical characteristics of patients most susceptible to this type of proarrhythmia, and describes interventions that can be made if TdP occurs. Three clinical vignettes are provided at the end of the article to highlight the relevance of the preceding discussions.

Quantitative T-wave morphology assessment from surface ECG is linked with cardiac events risk in genotype-positive KCNH2 mutation carriers with normal QTc values.

INTRODUCTION: Long QT syndrome (LQTS) mutation carriers have elevated the risk of cardiac events even in the absence of QTc prolongation; however, mutation penetrance in patients with normal QTc may be reflected in abnormal T-wave shape, particularly in KCNH2 mutation carriers. We aimed to assess whether the magnitude of a three-dimensional T-wave vector (TwVM) will identify KCNH2-mutation carriers with normal QTc at risk for cardiac events. METHODS: Adult LQT2 patients with QTc < 460 ms in men and <470 ms in women (n = 113, age 42 ± 16 years, 43% male) were compared with genotype-negative family members (n = 1007). The TwVM was calculated using T-wave amplitudes in leads V6, II, and V2 as the square root of (TV62 + TII2 + (0.5*TV2)2 ). Cox regression analysis adjusted for gender and time-dependent beta-blocker use was performed to assess cardiac event (CE) risk, defined as syncope, aborted cardiac arrest, implantable cardioverter-defibrillator therapy, or sudden death. RESULTS: Dichotomized by median of 0.30 mV, lower TwVM was associated with elevated CE risk compared to those with high TwVM (HR = 2.95, 95% CI, 1.25-6.98, P = .014) and also remained significant after including sex and time-dependent beta-blocker usage in the Cox regression analysis (HR = 2.64, 95% CI, 1.64-4.24, P < .001). However, these associations were found only in women but not in men who had low event rates. CONCLUSION: T-wave morphology quantified as repolarization vector magnitude using T-wave amplitudes retrieved from standard 12-lead electrocardiogram predicts cardiac events risk in LQT2 women and appears useful for risk stratification of KCNH2-mutation carriers without QTc prolongation.

[Diagnosis, sudden death risk stratification, and treatment of main long QT syndrome molecular-genetic variants].

Inherited long QT syndrome (LQTS) refers to the primary electrical diseases of the heart. It is characterized by QT prolongation on resting ECG and syncope due to life-threatening ventricular arrhythmias. This review focuses on diagnosis, differential diagnosis, risk stratification of sudden cardiac death, and treatment strategy of patients with most prevalent genetic fOrms of LQTS - LQT1, LQT2 and LQT3, which accounted for about 90% of all genetically confirmed cases. Recent advances in understanding of relationship between clinical, electrocardiographic features (on ECG, body surface mapping, stress test) and genetic variants of LQT presented. Characteristics of syncopal events and ECG features of LQTl, LQT2 and LQT3 in the majority of cases are helpful to make an appropriate choice for therapy, even before positive result of molecular genetic testing. Management has focused on the use of beta blockers as first-line treatment and exclusion of triggers of life-threatening arrhythmia which are specific for each molecular-genetic variant. Implantation of cardioverter defibrillator for secondary prevention of sudden death in the high-risk patients or patients with insufficient effect of antiarrhythmic therapy is required.

Cost-effectiveness analysis of genetic testing for familial long QT syndrome in symptomatic index cases.

BACKGROUND: Genetic testing for long QT syndrome (LQTS) has been available in a research setting for the past decade, and a commercial test has recently become available. However, the costs and effectiveness of genetic testing have not been estimated. OBJECTIVES: The purpose of this study was to conduct a cost-effectiveness analysis of genetic testing in the management of patients who have or are suspected to have familial LQTS. METHODS: We examined the incremental cost-effectiveness of genetic testing compared with no genetic testing for symptomatic index cases and how this varied according to changes in assumptions and data inputs. Data were obtained from the published literature and a clinical cohort. RESULTS: We found that genetic testing is more cost-effective than not testing for symptomatic index cases at an estimated cost of 2,500 US dollar per year of life saved. These results were generally robust, although they were sensitive to some data inputs such as the cost of testing and the mortality rate among untreated individuals with LQTS. CONCLUSION: A genetic test for familial LQTS is cost-effective relative to no testing, given our assumptions about the population to be tested and the relevant probabilities and costs. The primary benefit of testing is to more accurately diagnose and treat individuals based on a combination of clinical scores and test results. Future economic analyses of testing for familial LQTS should consider the potential benefits of genetic testing of broader populations, including family members.

Assessment of QT dispersion in symptomatic patients with congenital long QT syndromes.

It has been suggested that QT dispersion recorded on the surface electrocardiogram may be a predictor of arrhythmic events in patients with congenital QT prolongation. To evaluate this, 9 patients (6 female, mean age 17.6 years) with congenital long QT syndromes, all of whom had syncope and documented torsades de pointes, were studied. Patients were studied off treatment and during therapy with beta-blocking agents. Three patients were also studied after left stellate ganglionectomy. An age-matched control group was also studied. Good quality 12-lead electrocardiograms were recorded from all patients. For each lead, QT and RR intervals were measured, and QTc value was calculated. QT and QTc dispersions were calculated for each patient. Patients had a significantly longer mean QT interval compared with that of the control group (450 +/- 100 vs 359 +/- 63 ms; p = 0.015) at similar mean RR intervals (736 +/- 231 vs 783 +/- 289 ms), with a longer mean QTc value (0.53 +/- 0.08 vs 0.41 +/- 0.02 s1/2; p = 0.004). Patients also had longer QT and QTc dispersions compared with those of the control group (110 +/- 45 vs 43 +/- 12 ms [p = 0.004], and 0.108 +/- 0.03 vs 0.05 +/- 0.02 s1/2 [p = 0.002], respectively). QT and QTc dispersions on and off beta-blocking agents were not significantly different. Comparing patients with frequent and those with infrequent symptoms, there was no difference in QT or QTc dispersion either off treatment or during therapy with beta-blocking agents.(ABSTRACT TRUNCATED AT 250 WORDS)