QT Interval Length Research Articles

Acute, dose-response effects of guayusa leaf extract on mood, cognitive and motor-cognitive performance, and blood pressure, heart rate, and ventricular repolarization.

We conducted a randomized, double-blind, placebo-controlled crossover trial in young adults to examine the dose-dependent (600 mg versus 1200 mg), acute effects of consumption of an Ilex guayusa tea extract (GLE) on mood, cognitive and motor-cognitive performance, as well as its acute cardiovascular effects. Twenty-five adults (mean ± SD, age = 28 ± 7 y; 9 M/16 F) completed familiarization and then three randomly ordered experimental visits where they consumed either 600 mg (GLE600) or 1200 mg (GLE1200) GLE or placebo (PLA). Following supplement consumption, participants completed a mood state survey, assessments of perceived jitteriness, energy, and focus, and neurocognitive and motor-cognitive testing. Blood pressure (BP), heart rate, and QT interval length were determined before and after supplementation. GLE600 significantly improved total mood disturbance (mean ± SE difference = -6.9 ± 2.6 au, p = 0.034), fatigue-inertia (-2.84 ± 0.89 au, p = 0.008), perceived energy (+13.00 ± 4.49 au; p = 0.02), motor speed (+4.52 ± 1.42 au, p = 0.008), and psychomotor speed (+7.20 ± 2.16 au, p = 0.005) relative to PLA. GLE1200 also improved psychomotor speed (+5.08 ± 2.16 ms, p = 0.045) and uniquely increased motor-cognitive performance as reflected by a decrease in reaction time (-0.106 ± 0.04 ms, p = 0.026) during a neurocognitive hop test. The effect of GLE on jitteriness was both dose- and sex-dependent. Jitteriness increased with increasing GLE dose in women only (p < 0.001). Both GLE600 and GLE1200 similarly increased systolic and diastolic BP by 4-5 mmHg (p ≤ 0.022). Neither GLE600 nor GLE1200 acutely influenced QTc length (p = 0.31). The goal of GLE supplementation should be considered when selecting a dosing strategy. Lower dosages of GLE (e.g. 600 mg) appear to optimize cognitive and mood-related outcomes while limiting side-effects such as jitteriness in women, and higher dosages may be necessary (e.g. 1200 mg) to promote improvements in motor-cognitive performance.

Cold pressor stress effects on cardiac repolarization

The cold pressor test (CPT) elicits strong cardiovascular reactions via activation of the sympathetic nervous system (SNS), yielding subsequent increases in heart rate (HR) and blood pressure (BP). However, little is known on how exposure to the CPT affects cardiac ventricular repolarization. Twenty-eight healthy males underwent both a bilateral feet CPT and a warm water (WW) control condition on two separate days, one week apart. During pre-stress baseline and stress induction cardiovascular signals (ECG lead II, Finometer BP) were monitored continuously. Salivary cortisol and subjective stress ratings were assessed intermittently. Corrected QT (QTc) interval length and T-wave amplitude (TWA) were assessed for each heartbeat and subsequently aggregated individually over baseline and stress phases, respectively. CPT increases QTc interval length and elevates the TWA. Stress-induced changes in cardiac repolarization are only in part and weakly correlated with cardiovascular and cortisol stress-reactivity. Besides its already well-established effects on cardiovascular, endocrine, and subjective responses, CPT also impacts on cardiac repolarization by elongation of QTc interval length and elevation of TWA. CPT effects on cardiac repolarization share little variance with the other indices of stress reactivity, suggesting a potentially incremental value of this parameter for understanding psychobiological adaptation to acute CPT stress.

Effect of Video laryngoscope on Tp-e Interval, Qtc and Tp-e/Qtc Ratio Compared with Direct Laryngoscope in Patients With Double-Lumen Tube Undergoing Thoracic Surgery

Aim: QT interval is generally related to the increased risk of polymorphic ventricular tachycardias and ventricular arrythmias. Intubation and laryngoscopy might change in cardiac repolarization and an increase in QT interval length. Video laryngoscopes provide better laryngeal view, higher intubation success, and better correct positioning on double-lumen tube (DLT) intubation. We aimed to compare McGRATH MAC 5 video laryngoscope to direct Macintosh laryngoscope and their effects on Tp-e interval, QTc and Tp-e/QTc ration in those patients requiring intubation having DLT. Materials and Methods: The randomly controlled prospective work is carried out on 94 patients, scheduled for thoracic surgery, aged between 18-65. After anaesthetic induction and before tracheal intubation, all patients airway were evaluated Cormack and Lehane in using a Macintosh laryngoscope and patients having Cormack and Lehane grade-1 or -2a views included in study. The patients who are intubated with video laryngoscope (McGRATH MAC) are allocated into Group V and intubated with direct Macintosh Laryngoscope was allocated into Group L. The primary aim was compared between the two devices on Tp-e interval, QTc and Tp-e/QTc ratio with ECG recordings. The secondary goal was assessment of hemodynamic status and intubation conditions. Results: In Group V, QTc interval, Tp-e intreval and Tp-e/QTc ratio was lower in a significant way than Group L. There has not been a significant difference in terms of hemodynamic assessment among those two groups at all measurement periods. Cormack-Lehane scores, intubation times, DLT types and sizes were similar between two groups. Conclusion: McGRATH MAC video laryngoscope decreased Tp-e interval, QTc and Tp-e/QTc ratio compared to direct Maintosh laryngoscope. Hemodynamic response and intubation parameters are seen as similar to each other in both of the present groups.

Cardiac safety assessment of a novel recombinant bispecific antibody targeting the ether-à-go-go related gene 1 (hERG1)-β1 integrin macromolecular complex.

Introduction: In the last decades, mounting evidence has pointed out the human ether-á-go-go-related gene (hERG1) potassium channel as a novel biomarker in human cancers. However, hERG1 sustains the cardiac repolarizing current IKr and its blockade can induce a prolonged QT interval at the ECG, which increases the risk of life-threatening arrhythmias. This represents a major hindrance for targeting hERG1 for antineoplastic therapeutic purposes. Based on our discovery that hERG1 resides in a macromolecular complex with the β1 subunit of integrin adhesion receptors only in tumors, and not in the heart, we generated (and patented WO2019/015936) a novel engineered, single chain, bispecific antibody in the format of a diabody (scDb-hERG1-β1). This antibody has been proven to target with high affinity the hERG1/β1 integrin complex and to exert a good antineoplastic activity in preclinical mouse models. Methods: In the present study, we evaluated the cardiac safety of the scDb-hERG1-β1, determining the action potential duration (APD) of human cardiomyocytes, either atrial (from valve-disease patients) or ventricular (from aortic stenosis patients). Cardiac cells were incubated in vitro with i) the scDb-hERG1-β1, ii) the full length anti-hERG1 monoclonal antibody (mAb-hERG1) and iii) its single chain Fragment variable derivative (scFv-hERG1), from which the scDb-hERG1-β1 was assembled. All the tests were performed before and after treatment with the specific hERG1 blocker E4031. In addition, we have performed preliminary experiments, analyzing the effects of the scDb-hERG1/β1 in vivo measuring the QT interval length of the surface ECG after its injection intravenously in farm-pigs. Results: The scDb-hERG1-β1 did not produce any lengthening of APD compared to control (vehicle) conditions, either in atrial or ventricular cardiomyocytes, whereas both the hERG1-mAb and the scFv-hERG1 produced a significant APD prolongation. The addition of E4031 further prolonged APD. The scDb-hERG1-β1 did not produce any alterations of the QT (and QTc) interval values, once injected intravenously in farm pigs. Discussion: Overall, the above evidences plead for the cardiac safety of the scDb-hERG1-β1, suggesting that an application of this antibody for anti-cancer therapy will be untainted by cardiotoxicity.

Evaluation of the Corrected QT Interval with Bazett’s Method in Cavalier King Charles Spaniel Dogs with Myxomatous Mitral Valve Disease

Abstract Myxomatous mitral valve disease (MMVD) is one of the most common heart diseases in dogs. The disease progresses faster in Cavalier King Charles Spaniel (CKCS) dogs and occurs at an earlier age. QT interval length reflects abnormalities in ventricular repolarization which may predispose to the formation of fatal arrhythmias such as torsades de pointes. A fast and accurate assessment is therefore essential. The study aimed to examine the changes in QT duration in MMVD cases of CKCS and to calculate the corrected QT durations with Bazett’s formula in various stages of the disease. The study included 20 CKCS dogs of both genders, various ages and weights, and different stages of MMVD (n=6 in B1 stage, n=6 in B2 stage, and n=8 in C stage), and 5 healthy CKCS which were included in the control group. Clinical, radiological, hematological, biochemical, echocardiographic, and electrocardiographic examinations were performed. The corrected QT interval duration in the MMVD group was longer than the control (p&lt;0.05). However, there was no significant difference between B1, B2, and C. It was concluded that the corrected QT interval can give a significant distinction between healthy and MMVD CKCS dogs.

QTc interval measurement in patients with right bundle branch block: A practical method.

Prolonging the QT interval in the right bundle branch block (RBBB) can create challenges for electrophysiologists in estimating repolarization time and eliminating the effect of depolarization changes on QT interval. In this study, we aimed to develop a practice formula to eliminate the effect of depolarization changes on QT interval in patients with RBBB. This prospective study evaluated accidentally induced RBBB in patients undergoing electrophysiological study. Two expert electrophysiologists recorded the ECG parameters, including QRS duration, QT interval, and cycle length, in the patients. The formula was developed based on QT interval differences (with and without RBBB) and its proportion to QRS. Additionally, the Bazzet, Rautaharju, and Hodge formulas were used to evaluate QTc. We evaluated 96 patients in this study. The mean QT interval without RBBB was 369.39 ± 37.38, reaching 404.22 ± 39.23 after inducing RBBB. ΔQT was calculated as 34.83 ± 17.61, and the ratio of ΔQT/QRS with RBBB was almost 23%. Our formula is: (QTwith RBBB - 23% × QRS). Subtraction of 25% instead of 23% seems more straightforward and practical. Our formula could also predict the QTc interval in RBBB based on the Bazzet, Rautaharju, and Hodge formulas. Previous formulas for QT correction were hard to apply in the clinical setting or were not specified for RBBB. Our new formula allows a rapid and practical method for QT correction in RBBB in clinical practice.

A large genome-wide association study of QT interval length utilizing electronic health records.

QT interval length is an important risk factor for adverse cardiovascular outcomes; however, the genetic architecture of QT interval remains incompletely understood. We conducted a genome-wide association study of 76,995 ancestrally diverse Kaiser Permanente Northern California members enrolled in the Genetic Epidemiology Research on Adult Health and Aging cohort using 448,517 longitudinal QT interval measurements, uncovering 9 novel variants, most replicating in 40,537 individuals in the UK Biobank and Population Architecture using Genomics and Epidemiology studies. A meta-analysis of all 3 cohorts (n = 117,532) uncovered an additional 19 novel variants. Conditional analysis identified 15 additional variants, 3 of which were novel. Little, if any, difference was seen when adjusting for putative QT interval lengthening medications genome-wide. Using multiple measurements in Genetic Epidemiology Research on Adult Health and Aging increased variance explained by 163%, and we show that the ≈6 measurements in Genetic Epidemiology Research on Adult Health and Aging was equivalent to a 2.4× increase in sample size of a design with a single measurement. The array heritability was estimated at ≈17%, approximately half of our estimate of 36% from family correlations. Heritability enrichment was estimated highest and most significant in cardiovascular tissue (enrichment 7.2, 95% CI = 5.7-8.7, P = 2.1e-10), and many of the novel variants included expression quantitative trait loci in heart and other relevant tissues. Comparing our results to other cardiac function traits, it appears that QT interval has a multifactorial genetic etiology.

Physiological QT Interval Changes in Early Infancy Using Post-Menstrual and Post-Natal Age Calculation for Electrocardiogram Long QT Interval Screening in Taiwan.

Prolongation of the QT interval is associated with the risk of sudden infant death syndrome. QT interval differs depending on age at the time of screening. Screening protocols have yet to be established for Taiwanese patients. To construct QT interval reference values during early infancy, to investigate whether QT interval change differs according to age calculation methods, and to identify an optimal QT correction method and associated infant factors. Electrocardiographic readings and QT intervals were recorded cross-sectionally in 595 healthy infants and screened prospectively for long QT interval. Corrected QT intervals with Bazett's (QTc-B) and Fridericia's (QTc-F) formulas were compared by post-natal and post-menstrual screening age, sex, body mass index (BMI), heart rate (HR), birth and family history. QTc-B and QTc-F decreased in the second month (31-60 days), and peaked in the third month (61-90 days). QT interval length was similar between post-menstrual and post-natal ages for QTc-B. Simple linear regression showed that post-menstrual age, post-natal age, HR and BMI were associated with QTc-F, while only sex and HR were associated with QTc-B. Although both QTc-B and QTc-F were significantly associated with HR, QTc-B was less affected by HR than QTc-F (β = -0.1, p < 0.05 for QTc-B vs. β = -0.3, p < 0.001 for QTc-F). Female infants tended to have slightly longer QTc intervals. QT interval in early infancy changed physiologically, peaking in the third month. The rate of QT change was not affected by different age correction methods. QTc-B was less affected by age, BMI and HR, although differences in sex should be noted.

Electrophysiological Response to Acehytisine Was Modulated by Aldosterone in Rats with Aorto-Venocaval Shunts.

Aldosterone induces cardiac electrical and structural remodeling, which leads to the development of heart failure and/or atrial fibrillation (AF). However, it remains unknown whether aldosterone-induced remodeling may modulate the efficacy of anti-AF drugs. In this study, we aimed to jeopardize the structural and functional remodeling by aldosterone in rats with aorto-venocaval shunts (AVS rats) and evaluate the effect of acehytisine in this model. An AVS operation was performed on rats (n = 6, male) and it was accompanied by the intraperitoneal infusion of aldosterone (AVS + Ald) at 2.0 µg/h for 28 d. The cardiopathy was characterized by echocardiography, electrophysiologic and hemodynamic testing, and morphometric examination in comparison with sham-operated rats (n = 3), sham + Ald (n = 6), and AVS (n = 5). Aldosterone accelerated the progression from asymptomatic heart failure to overt heart failure and induced sustained AF resistant to electrical fibrillation in one out of six rats. In addition, it prolonged PR, QT interval and Wenckebach cycle length. Acehytisine failed to suppress AF in the AVS + Ald rats. In conclusion, aldosterone jeopardized electrical remodeling and blunted the electrophysiological response to acehytisine on AF.

QT interval prolongation and the risk of malignant ventricular dysrhythmia and/or cardiac arrest: Systematic search and narrative review of risk related to the magnitude of QT interval length.

Prolongation of the QTc interval is associated with an increased risk of malignant ventricular dysrhythmias, such as ventricular tachycardia (VT), and sudden cardiac death. The quantifiable risk rates of adverse dysrhythmic outcome in relation to specific QTc interval length are not known. We conducted a literature review on the topic of QT interval prolongation in adult patients and the associated risk of malignant dysrhythmic event. We specifically formulated our literature search and subsequent literature review to address the following question: Can the clinician identify specific QTc intervals at which a specific quantifiable risk of malignant dysrhythmic event (malignant ventricular dysrhythmia and/or cardiac arrest) occurs in an undifferentiated adult patient population? In the literature search, we identified 701 studies; upon review using specific, pre-determined inclusion criteria, we identified 16 articles for inclusion in the review. From this literature, we were unable to answer the question in a quantifiable manner and only noted that the risk of malignant dysrhythmic event increases with progressively longer QTc interval. The current literature on this topic is inadequate to answer this important question due to heterogenous study methodology, patient populations, endpoints, and periods of observation. Additional prospective research is required on this topic, aimed at addressing the important issue of specific, quantifiable risk and its relation to degree of prolongation of the QTc interval.

How circadian variability of the heart rate and plasma electrolytes concentration influence the cardiac electrophysiology \u2013 model-based case study

The circadian rhythm of cardiac electrophysiology is dependent on many physiological and biochemical factors. Provided, that models describing the circadian patterns of cardiac activity and/or electrophysiology which have been verified to the acceptable level, modeling and simulation can give answers to many of heart chronotherapy questions. The aim of the study was to assess the performance of the circadian models implemented in Cardiac Safety Simulator v 2.2 (Certara, Sheffield, UK) (CSS), as well as investigate the influence ofcircadian rhythms on the simulation results in terms of cardiac safety. The simulations which were run in CSS accounted for inter-individual and intra-individual variability. Firstly, the diurnal variations in QT interval length in a healthy population were simulated accounting for heart rate (HR) circadian changes alone, or with concomitant diurnal variations of plasma ion concentrations. Next, tolterodine was chosen as an exemplary drug for PKPD modelling exercise to assess the role of circadian rhythmicity in the prediction of drug effects on QT interval. The results of the simulations were in line with clinical observations, what can serve as a verification of the circadian models implemented in CSS. Moreover, the results have suggested that the circadian variability of the electrolytes balance is the main factor influencing QT circadian pattern. The fluctuation of ion concentration increases the intra-subject variability of predicted drug-triggered QT corrected for HR (QTc) prolongation effect and, in case of modest drug effect on QTc interval length, allows to capture this effect.

Associations between PM2.5 metal components and QT interval length in the Normative Aging Study

BackgroundSeveral studies have found associations between increases in QT interval length, a marker of cardiac electrical instability, and short-term fine particulate matter (PM2.5) exposures. To our knowledge, this is the first study to examine the association between specific PM2.5 metal components and QT interval length. MethodsWe measured heart-rate corrected QT interval (QTc) duration among 630 participants in the Normative Aging Study (NAS) based in Eastern Massachusetts between 2000 and 2011. We utilized time-varying linear mixed-effects regressions with a random intercept for each participant to analyze associations between QTc interval and moving averages (0–7 day moving averages) of 24-h mean concentrations of PM2.5 metal components (vanadium, nickel, copper, zinc and lead) measured at the Harvard Supersite monitoring station. Models were adjusted for daily PM2.5 mass estimated at a 1 km × 1 km grid cell from a previously validated prediction model and other covariates. Bayesian kernel machine regression (BKMR) was utilized to assess the overall joint effect of the PM2.5 metal components. ResultsWe found consistent results with higher lead (Pb) associated with significant higher QTc intervals for both the multi-pollutant and the two pollutant (PM2.5 mass and a PM2.5 component) models across the moving averages. The greatest effect of lead on QTc interval was detected for the 4-day moving average lead exposure. In the multi-pollutant model, each 2.72 ng/m3 increase in daily lead levels for a 4-day moving average was associated with a 7.91 ms (95% CI: 3.63, 12.18) increase in QTc interval. In the two-pollutant models with PM2.5 mass and lead, each 2.72 ng/m3 increase in daily lead levels for a 4-day moving average was associated with an 8.50 ms (95% CI: 4.59, 12.41) increase in QTc interval. We found that 4-day moving average of copper has a negative association with QTc interval when compared to the other PM2.5 metal components. In the multi-pollutant model, each 1.81 ng/m3 increase in daily copper levels for a 4-day moving average was associated with an −3.89 ms (95% CI: -6.98, −0.79) increase in QTc interval. Copper's essential function inside the human body could mediate its cardiotoxicity on cardiac conductivity and explain why we found that copper in comparison to the other metals was less harmful for QTc interval. ConclusionsExposure to metals contained in PM2.5 are associated with acute changes in ventricular repolarization as indicated by QT interval characteristics.

Associations between acute and long-term exposure to PM2.5 components and temperature with QT interval length in the VA Normative Aging Study.

Our study adds to the sparse literature on the effect of multiple fine particulate matter (PM2.5) components on QT interval length, an outcome with high clinical relevance in vulnerable populations. To our knowledge, this is the first study to examine the association between spatiotemporally resolved exposures to PM2.5 components and QT interval length. Among 578 men living in Eastern Massachusetts between 2000 and 2011, we utilized time-varying linear mixed-effects regressions with a random intercept to examine associations between acute (0-3 days), intermediate (4-28 days), and long-term (1 year) exposure to PM2.5 components, temperature, and heart-rate corrected QT interval (QTc). Each of the PM2.5 components and temperature was geocoded to the participant's residential address using validated ensemble and hybrid exposure models and gridMET predictions. We also evaluated whether diabetic status modified the association between PM2.5 components and QTc interval. We found consistent results that higher sulfate levels and colder temperatures were associated with significant longer QTc across all moving averages except the day of exposure. The greatest effect of sulfate and temperature was detected for the 28-day moving average. In the multi-pollutant model, each 1.5 µg/m3 IQR increase in daily sulfate was associated with a 15.1 ms [95% confidence interval (CI): 10.2-20.0] increase in QTc interval and in the single-pollutant models a 15.3 ms (95% CI: 11.6-19.1) increase in QTc interval. Other secondary particles, such as nitrate and organic carbon, also prolonged QT interval, while elemental carbon decreased QT interval. We found that diabetic status did not modify the association between PM2.5 components and QTc interval. Acute and long-term exposure to PM2.5 components and temperature are associated with changes in ventricular repolarization as measured by QT interval.

Associations between PM2.5 metal components and QT interval length

Background/Aim: Several studies have found associations between increases in QT interval length, a marker of cardiac electrical instability, and short-term fine particulate matter (PM2.5). To our knowledge, this is the first study to examine the association between specific PM metal components and QT interval length. Methods: We measured heart-rate corrected QT interval (QTc) duration among 630 participants in the Normative Aging Cohort (NAS) based in Eastern Massachusetts between 2000 to 2012. We utilized time-varying linear mixed-effects regressions with a random intercept to analyze associations between QTc interval and moving averages (0 to 7-day moving averages) of 24-hour mean concentrations of PM metal components (vanadium, nickel, copper, zinc and lead) measured at the Harvard Supersite monitoring station. Models were adjusted for daily PM2.5 mass estimated at a 1 km x 1 km grid cell from a previously validated prediction model and other covariates. Bayesian kernel machine regression (BKMR) was utilized to assess the overall effect of the PM components and the exposure-dose response curves. Results: We found consistent results with higher lead (Pb) associated with significant higher QTc intervals for both the multi-pollutant and the two pollutant (PM2.5 and a PM component) models across the moving averages. The greatest effect of lead on QTc interval was detected for the 4-day moving average lead exposure. In the multi-pollutant model, each 2.72 ng/m3 increase in daily lead levels for a 4-day moving average was associated with an 8.77 ms (95% CI: 4.25,13.29) increase in QTc interval. In the two-pollutant models with PM2.5 mass and lead, each 2.72 ng/m3 increase in daily lead levels for a 4-day moving average was associated with a 9.19 ms (95% CI: 5.09,13.30) increase in QTc interval. Conclusions: Our findings suggest that metals contained in PM2.5 are associated with acute changes (0 to 7-day moving averages) in ventricular repolarization.

Silencing of CCR4-NOT complex subunits affects heart structure and function.

ABSTRACTThe identification of genetic variants that predispose individuals to cardiovascular disease and a better understanding of their targets would be highly advantageous. Genome-wide association studies have identified variants that associate with QT-interval length (a measure of myocardial repolarization). Three of the strongest associating variants (single-nucleotide polymorphisms) are located in the putative promotor region of CNOT1, a gene encoding the central CNOT1 subunit of CCR4-NOT: a multifunctional, conserved complex regulating gene expression and mRNA stability and turnover. We isolated the minimum fragment of the CNOT1 promoter containing all three variants from individuals homozygous for the QT risk alleles and demonstrated that the haplotype associating with longer QT interval caused reduced reporter expression in a cardiac cell line, suggesting that reduced CNOT1 expression might contribute to abnormal QT intervals. Systematic siRNA-mediated knockdown of CCR4-NOT components in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) revealed that silencing CNOT1 and other CCR4-NOT genes reduced their proliferative capacity. Silencing CNOT7 also shortened action potential duration. Furthermore, the cardiac-specific knockdown of Drosophila orthologs of CCR4-NOT genes in vivo (CNOT1/Not1 and CNOT7/8/Pop2) was either lethal or resulted in dilated cardiomyopathy, reduced contractility or a propensity for arrhythmia. Silencing CNOT2/Not2, CNOT4/Not4 and CNOT6/6L/twin also affected cardiac chamber size and contractility. Developmental studies suggested that CNOT1/Not1 and CNOT7/8/Pop2 are required during cardiac remodeling from larval to adult stages. To summarize, we have demonstrated how disease-associated genes identified by GWAS can be investigated by combining human cardiomyocyte cell-based and whole-organism in vivo heart models. Our results also suggest a potential link of CNOT1 and CNOT7/8 to QT alterations and further establish a crucial role of the CCR4-NOT complex in heart development and function.This article has an associated First Person interview with the first author of the paper.

Poor Agreement but Good Predictive Value Between Automated and Manual QTc Intervals in Pediatric Emergency Department Electrocardiograms.

QTc interval is significant because prolongation may lead to ventricular dysrhythmia. Computerized electrocardiogram machines typically measure QT interval length and, using an algorithm assessment of multiple leads, calculate a QTc value. Manual measurement of the QT interval used to calculate the QTc value is more time-consuming but potentially more accurate. In this study, we compare the automated QTc calculation with the QTc value calculated using manual QT measurements. We prospectively obtained 350 resting 12-lead electrocardiograms (ECGs) in children aged 2 to 14 years in an academic pediatric emergency department. Manual measurement of the QT interval was performed and the QTc was calculated using the 2 most commonly used correction methods, Bazzet and Fridericia formulas. The paired values were used to perform a Bland-Altman analysis and create a receiver operating characteristic curve. Bland-Altman analysis determined that QT-automated and QTc-Bazett had an average difference of 3.8 milliseconds, with a standard deviation of 86 milliseconds (95% confidence interval = -161 to 176). An automated QTc value of 455 milliseconds was sensitive to detect manual QTc values of greater than 480 milliseconds. In children with resting ECGs, there is a poor agreement between the automated QTc produced by a computerized electrocardiogram and the QTc value obtained using manual QT measurement. Statistically and clinically relevant discrepancy between the automated QTc and QTc values calculated after manual QT measurement was present. Automated QTc values may be used as a screening tool to detect prolonged QTc, but for accurate determination of QTc, manual measurement is necessary.

Association of severity of depression, paroxetine use and markers of liver damage with QT interval duration in patients with alcohol dependence

Background/Aim. Patients suffered from chronic alcoholic disease very often have depression and cardiomyopathy. Treatment with several antidepressants is associated with prolonged QT interval, ventricular arrhythmias and sudden death. The aim of this study was to investigate the relation between the severity of depression, serum levels of gamma-glutamyl transferase (GGT), as a marker of liver damage, and the possible influence of paroxetine use on duration of QT interval in patient who started treatment of chronic alcoholic dependence. Methods. The study included 147 male patients (older than 18 years of age) suffering from alcohol addiction, who were also diagnosed with depressive disorder on the basis of DSM-IV criterion and positive Hamilton Rating Scale for Depression (HRSD) at the beginning of hospitalization. Out of total number of patients, 49 were randomly selected to be treated with antidepressant paroxetine at a dose of 20 mg once daily during 20 days. The global QTc interval was automatically determined. Results. By applying the generalised linear model, the statistically significant positive correlation between the length of QTc interval and serum values of GGT, that is, intensity of alcoholism (p = 0.002) and values of the HRSD score, that is, intensity of depression (p = 0.021) was established in the sample of 147 depressed alcoholic patients before the application of paroxetine. In spite of the vulnerability of patients due to the heart damage and the liver dysfunction arising from alcohol consumption, as well as altered patients' drugs metabolism, no elongation of QTc interval resulting from the application of paroxetine was established. The length of QTc interval 20 days after paroxetine administration was 401.43 ms and before paroxetine administration it was 403.31 ms. The difference in QTc interval length (after and before paroxetine administration) was ?QTc = - 1.88 ms (p = 0.524). Conclusion. The results indicated that the severity of depression and GGT serum levels positively correlated with the length of QT interval. On the other hand, paroxetine after 20 days of usage did not prolong QT interval.

A human in vitro platform for the evaluation of pharmacology strategies in cardiac ischemia.

Cardiac ischemic events increase the risk for arrhythmia, heart attack, heart failure, and death and are the leading mortality condition globally. Reperfusion therapy is the first line of treatment for this condition, and although it significantly reduces mortality, cardiac ischemia remains a significant threat. New therapeutic strategies are under investigation to improve the ischemia survival rate; however, the current preclinical models to validate these fail to predict the human outcome. We report the development of a functional human cardiac in vitro system for the study of conduction velocity under ischemic conditions. The system is a bioMEMs platform formed by human iPSC derived cardiomyocytes patterned on microelectrode arrays and maintained in serum-free conditions. Electrical activity changes of conduction velocity, beat frequency, and QT interval (the QT-interval measures the period from onset of depolarization to the completion of repolarization) or action potential length can be evaluated over time and under the stress of ischemia. The optimized protocol induces >80% reduction in conduction velocity, after a 4 h depletion period, and a partial recovery after 72 h of oxygen and nutrient reintroduction. The sensitivity of the platform for pharmacological interventions was challenged with a gap junction modulator (ZP1609), known to prevent or delay the depression of conduction velocity induced by ischemic metabolic stress. ZP1609 significantly improved the drastic drop in conduction velocity and enabled a greater recovery. This model represents a new preclinical platform for studying cardiac ischemia with human cells, which does not rely on biomarker analysis and has the potential for screening novel cardioprotective drugs with readouts that are closer to the measured clinical parameters.

Can laypeople identify a drug-induced QT interval prolongation? A psychophysical and eye-tracking experiment examiningthe ability of nonexperts to interpret an ECG.

ObjectiveThe study sought to quantify a layperson’s ability to detect drug-induced QT interval prolongation on an electrocardiogram (ECG) and determine whether the presentation of the trace affects such detection.Materials and MethodsThirty layperson participants took part in a psychophysical and eye-tracking experiment. Following training, participants completed 21 experimental trials, in which each trial consisted of 2 ECGs (a baseline and a comparison stimulus, both with a heart rate of 60 beats/min). The experiment used a 1 alternative forced-choice paradigm, in which participants indicated whether or not they perceived a difference in the QT interval length between the 2 ECGs. The ECG trace was presented in 3 ways: a single complex with the signals aligned by the R wave, a single complex without alignment, and a 10-second rhythm strip. Performance was analyzed using the psychometric function to estimate the just noticeable difference threshold, along with eye-tracking metrics.ResultsThe just noticeable difference 50% and 75% thresholds were 30 and 88 ms, respectively, showing that the majority of laypeople were able to detect a clinically significant QT-prolongation at a low normal heart rate. Eye movement data indicated that people were more likely to appraise the rhythm strip stimulus systematically and accurately.ConclusionsPeople can quickly be trained to self-monitor, which may help with more rapid identification of drug-induced long QT syndrome and prevent the development of life-threatening complications. The rhythm strip is a better form of presentation than a single complex, as it is less likely to be misinterpreted due to artifacts in the signal.

Analysis of effect of antidepressant drug venlafaxine on length of QT interval in patients with depressive disorder and alcohol dependence

&amp;lt;p&amp;gt;Introduction. Depressive disorder is common in patients with the diagnosis of alcoholism. Comorbidity of depression and alcoholism significantly worsens the clinical status of patients and represents a major therapeutic challenge. The aim of the study was to investigate the effect of the antidepressant drug venlafaxine on the length of QT interval in patients with depressive disorder and alcohol dependence. Methods. The research included 49 male patients (&amp;amp;gt;18 years of age) with alcohol dependence, who were also diagnosed with depressive disorder by using DSM-IV criterion and positive Hamilton Rating Scale for Depression (HRSD) at the very beginning of hospitalization. The patients had been given 37.5 mg of the antidepressant drug venlafaxine twice a day for twenty days. The global QTc interval (12 leads) was determined automatically using ECG device Schiller Cardiovit AT-1, which used &amp;quot;SCHILLER ECG Measurement and Interpretation Software for Children and Adult ECGs&amp;quot;. Statistical data processing was performed using SPSS 16.0 programme package for Windows. Results. There was a statistically significant positive association between HRSD score (depression intensity) and the serum levels of creatine kinase isoenzyme MB, i.e. the degree of myocardial damage (p = 0.048). A statistically significant positive correlation between serum gamma-glutamyltransferase levels and the length of QTc interval (p &amp;amp;lt; 0.001) was also found. There was no statistically significant difference in the length of QTc interval before and after venlafaxine administration (p = 0.827), and the average prolongation of the QTc interval was 0.776 ms (95% CI = -6.323 ms-7.874 ms). Conclusion. In our study, we did not prove the negative effect of antidepressant drug venlafaxine on QT interval in patients with depressive disorder and alcohol dependence. In patients with alcohol dependence, the therapy for depression must have a priority due to the proven negative association between depression and the degree of myocardial damage.&amp;lt;/p&amp;gt;