Literature DB >> 28942951

The algorithmic performance of J-Tpeak for drug safety clinical trial.

Simon C Chien1, Richard E Gregg2.   

Abstract

INTRODUCTION: The interval from J-point to T-wave peak (JTp) in ECG is a new biomarker able to identify drugs that prolong the QT interval but have different ion channel effects. If JTp is not prolonged, the prolonged QT may be associated with multi ion channel block that may have low torsade de pointes risk. From the automatic ECG measurement perspective, accurate and repeatable measurement of JTp involves different challenges than QT. We evaluated algorithm performance and JTp challenges using the Philips DXL diagnostic 12/16/18-lead algorithm. Measurement of JTp represents a different use model. Standard use of corrected QT interval is clinical risk assessment on patients with cardiac disease or suspicion of heart disease. Drug safety trials involve a very different population - young healthy subjects - who commonly have J-waves, notches and slurs. Drug effects include difficult and unusual morphology such as flat T-waves, gentle notches, and multiple T-wave peaks.
METHODS: The JTp initiative study provided ECGs collected from 22 young subjects (11 males and females) in randomized testing of dofetilide, quinidine, ranolazine, verapamil and placebo. We compare the JTp intervals between DXL algorithm and the FDA published measurements. The lead wise, vector-magnitude (VM), root-mean-square (RMS) and principal-component-analysis (PCA) representative beats were used to measure JTp and QT intervals. We also implemented four different methods for T peak detection for comparison.
RESULTS: We found that JTp measurements were closer to the reference for combined leads RMS and PCA than individual leads. Differences in J-point location led to part of the JTp measurement difference because of the high prevalence of J-waves, notches and slurs. Larger differences were noted for drug effect causing multiple distinct T-wave peaks (Tp). The automated algorithm chooses the later peak while the reference was the earlier peak. Choosing among different algorithmic strategies in T peak measurement results in the tradeoff between stability and the accurate detection of calcium or sodium channel block.
CONCLUSION: Measurement of JTp has different challenges than QT measurement. JTp measurement accuracy improved with combined leads RMS and PCA over lead II or V5.
Copyright © 2017 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Drug safety study; ECG; Electrocardiogram; Fiducial point detection; J point; J-Tpeak; JTp; QT; T peak

Mesh:

Substances:

Year:  2017        PMID: 28942951     DOI: 10.1016/j.jelectrocard.2017.08.018

Source DB:  PubMed          Journal:  J Electrocardiol        ISSN: 0022-0736            Impact factor:   1.438


  2 in total

1.  An evaluation of multiple algorithms for the measurement of the heart rate corrected JTpeak interval.

Authors:  Jean-Philippe Couderc; Shiyang Ma; Alex Page; Connor Besaw; Jean Xia; W Brian Chiu; Johan de Bie; Jose Vicente; Martino Vaglio; Fabio Badilini; Saeed Babaeizadeh; Cheng-Hao Simon Chien; Mathias Baumert
Journal:  J Electrocardiol       Date:  2017-09-01       Impact factor: 1.438

Review 2.  Mechanistic Model-Informed Proarrhythmic Risk Assessment of Drugs: Review of the "CiPA" Initiative and Design of a Prospective Clinical Validation Study.

Authors:  Jose Vicente; Robbert Zusterzeel; Lars Johannesen; Jay Mason; Philip Sager; Vikram Patel; Murali K Matta; Zhihua Li; Jiang Liu; Christine Garnett; Norman Stockbridge; Issam Zineh; David G Strauss
Journal:  Clin Pharmacol Ther       Date:  2017-11-16       Impact factor: 6.875

  2 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.