Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk.
Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk.
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DOI：
10.1371/journal.pone.0166925
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Strauss DG
中科院分区：
文献类型：
--
作者：
Johannesen L;Vicente J;Hosseini M;Strauss DG
心率校正QT间期的延长是椎体扭转风险的敏感指标；然而，它不是特异性的，因为QTc延长药物阻断内向电流通常与扭转无关。最近的研究表明，对心率校正后的J-Tpeakc （J-Tpeakc）和Tpeak-Tend间隔的单独分析可以识别具有内向电流阻滞的QTc延长药物，并被提议作为新药心脏安全新范式的一部分（“CiPA”倡议）。在这项工作中，我们描述了一种使用矢量幅度领先来评估j - tpeak和Tpeak-Tend间隔的自动测量方法。自动测量方法是根据一个临床试验的数据开发的，并使用来自第二个临床试验的独立数据进行评估。自动化和先前的半自动测量结果的比较表明，自动化算法再现的半自动测量结果的单δ均值差<1 ms，时间内点变异性没有差异（p为所有> 0.39）。此外，63%的时间点基线和安慰剂调整后的变化在1 ms内（86%在2 ms内）。重要的是，自动化结果得出了关于所研究药物的电生理机制的相同结论。我们开发了一种自动评估J-Tpeakc和Tpeak-Tend间隔的算法，可用于临床药物试验。在CiPA倡议下，这项心电图评估将确定与临床前研究相比，人类是否存在意想不到的离子通道效应。该算法将作为开源软件发布。NCT02308748和NCT01873950
Prolongation 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). In 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. Comparison 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. We 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. NCT02308748 and NCT01873950
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影响因子：
3.7
作者：
Lux RL;Sower CT;Allen N;Etheridge SP;Tristani-Firouzi M;Saarel EV
通讯作者：
Saarel EV
影响因子：
37.8
作者：
LEPESCHKIN, E;SURAWICZ, B
通讯作者：
SURAWICZ, B
影响因子：
6.1
作者：
Dubois, Remi;Maison-Blanche, Pierre;Dreyfus, Gerard
通讯作者：
Dreyfus, Gerard
DOI：
10.2307/2987937
发表时间：
1983-01-01
期刊：
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES D-THE STATISTICIAN
影响因子：
--
作者：
ALTMAN, DG;BLAND, JM
通讯作者：
BLAND, JM
影响因子：
6.7
作者：
Johannesen, L.;Vicente, J.;Strauss, D. G.
通讯作者：
Strauss, D. G.