The Application of Root Mean Square Electrocardiography (RMS ECG) for the Detection of Acquired and Congenital Long QT Syndrome

Lux, Robert L.; Sower, Christopher T.; Allen, Nancy A.; Etheridge, Susan P.; Tristani‐Firouzi, Martin; Saarel, Elizabeth V.

doi:10.1371/journal.pone.0085689

Cited by 16 publications

(10 citation statements)

References 17 publications

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“…We analysed the P-wave in individual torso leads by means of the root mean square (RMS) value, to simplify the analysis of the spatial and morphological variations of the P-wave and BSPM [ 72 , 73 ]. This method therefore allowed us to extract information on total P-wave morphology and amplitude by observing the RMS distribution map ( Fig 8 ).…”

Section: Discussionmentioning

confidence: 99%

Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation

et al. 2015

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Atrial arrhythmias, and specifically atrial fibrillation (AF), induce rapid and irregular activation patterns that appear on the torso surface as abnormal P-waves in electrocardiograms and body surface potential maps (BSPM). In recent years both P-waves and the BSPM have been used to identify the mechanisms underlying AF, such as localizing ectopic foci or high-frequency rotors. However, the relationship between the activation of the different areas of the atria and the characteristics of the BSPM and P-wave signals are still far from being completely understood. In this work we developed a multi-scale framework, which combines a highly-detailed 3D atrial model and a torso model to study the relationship between atrial activation and surface signals in sinus rhythm. Using this multi scale model, it was revealed that the best places for recording P-waves are the frontal upper right and the frontal and rear left quadrants of the torso. Our results also suggest that only nine regions (of the twenty-one structures in which the atrial surface was divided) make a significant contribution to the BSPM and determine the main P-wave characteristics.

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Section: Discussionmentioning

confidence: 99%

Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation

et al. 2015

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“…Effects on cardiac repolarization were measured from a digitized signal recorded continuously with a Mortara H12+ ™ Holter monitor (Milwaukee, WI, USA). The QT interval was calculated as described and corrected for heart rate using Bazett's formula .…”

Section: Methodsmentioning

confidence: 99%

“…Legal guardian consent was obtained for all patients, and children's assent was obtained. Arterial blood samples for methadone assay were obtained at 0, 5, 10, 15, 20, and 40 min as well as 1,2,4,5,6,8,10,12,24, and 48 h. Gas chromatography-mass spectrometry was used for assay. The limit of quantitation was determined to be 10 mcgÁl À1 , and the upper end of the linear range is 3000 mcgÁl À1 .…”

Section: Study 1 (University Of Virginia; Nct 01205256)mentioning

confidence: 99%

The pharmacokinetics of methadone and its metabolites in neonates, infants, and children

Ward

Drover

Hammer

et al. 2014

Pediatric Anesthesia

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Background The lack of methadone pharmacokinetic data in children and neonates restrains dosing to achieve the target concentration in these populations. A minimum effective analgesic concentration of methadone in opioid naïve adults is 0.058 mg.L−1, while no withdrawal symptoms were observed in neonates suffering opioid withdrawal if plasma concentrations of methadone were above 0.06 mg.L−1. The racemate of methadone which is commonly used in pediatric and anaesthetic care is metabolized to EDDP (2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine) and EMDP (2-ethyl-5-methyl-3,3-diphenylpyrroline). Methods Data from 4 studies (age 33 weeks PMA-15 years) were pooled (n=56) for compartment analysis using nonlinear mixed effects modeling. Parameter estimates were standardized to a 70 kg person using an allometric model approach. Investigation was made of the racemate and metabolite (EDDP and EMDP) dispositions. In addition, neonatal data (n=7) allowed further study of R and S enantiomer pharmacokinetics. Results A three-compartment linear disposition model best described the observed time-concentration profiles with additional compartments for metabolites. Population parameter estimates (between subject variability) were central volume (V1) 21.5 (29%) L.70kg−1, peripheral volumes of distribution V2 75.1 (23%) L.70kg−1, V3 484 (8%) L.70kg−1, clearance (CL) 9.45 (11%) L.h−1.70kg−1 and inter-compartment clearances Q2 325 (21%) L.h−1.70kg−1, Q3 136 (14%) L.h−1.70kg−1. EDDP formation clearance was 9.1 (11%) L.h−1.70kg−1, formation clearance of EMDP from EDDP 7.4 (63%) L.h−1.70kg−1, elimination clearance of EDDP was 40.9 (26%) L.h−1.70kg−1, and the rate constant for intermediate compartments 2.17 (43%) /h. Conclusions Current pharmacokinetic parameter estimates in children and neonates are similar to those reported in adults. There was no clearance maturation with age. Neonatal enantiomer clearances were similar to those described in adults. A regimen of 0.2 mg.kg−1 per 8 h in neonates achieves a target concentration of 0.06 mg.L−1 within 36 h. Infusion, rather than intermittent dosing should be considered if this target is to be achieved in older children after cardiac surgery.

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“…Prior studies evaluating changes in T peak -T end have focused on the left precordial leads, primarily V5, because they were thought to provide an index of transmural dispersion of the left ventricular wall [13, 15]. Another study has used the RMS lead [36]. Rather than making measurements on a single lead, we used the vector magnitude lead to provide a global index of repolarization and reduce influence of changes in the cardiac axis [37].…”

Section: Discussionmentioning

confidence: 99%

Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk

et al. 2016

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BackgroundProlongation of the heart rate corrected QT (QTc) interval is a sensitive marker of torsade de pointes risk; however it is not specific as QTc prolonging drugs that block inward currents are often not associated with torsade. Recent work demonstrated that separate analysis of the heart rate corrected J-Tpeakc (J-Tpeakc) and Tpeak-Tend intervals can identify QTc prolonging drugs with inward current block and is being proposed as a part of a new cardiac safety paradigm for new drugs (the “CiPA” initiative).MethodsIn this work, we describe an automated measurement methodology for assessment of the J-Tpeakc and Tpeak-Tend intervals using the vector magnitude lead. The automated measurement methodology was developed using data from one clinical trial and was evaluated using independent data from a second clinical trial.ResultsComparison between the automated and the prior semi-automated measurements shows that the automated algorithm reproduces the semi-automated measurements with a mean difference of single-deltas <1 ms and no difference in intra-time point variability (p for all > 0.39). In addition, the time-profile of the baseline and placebo-adjusted changes are within 1 ms for 63% of the time-points (86% within 2 ms). Importantly, the automated results lead to the same conclusions about the electrophysiological mechanisms of the studied drugs.ConclusionsWe have developed an automated algorithm for assessment of J-Tpeakc and Tpeak-Tend intervals that can be applied in clinical drug trials. Under the CiPA initiative this ECG assessment would determine if there are unexpected ion channel effects in humans compared to preclinical studies. The algorithm is being released as open-source software.Trial RegistrationNCT02308748 and NCT01873950

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The Application of Root Mean Square Electrocardiography (RMS ECG) for the Detection of Acquired and Congenital Long QT Syndrome

Cited by 16 publications

References 17 publications

Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation

Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation

The pharmacokinetics of methadone and its metabolites in neonates, infants, and children

Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk

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