Comparison of Two Highly Automated ECG Algorithms for Detection of Drug-Induced Cardiac Ion Channel Block.

Marina Brockway, Anthony A Fossa, Jay W Mason

Journal: Clinical pharmacology and therapeutics 2019;104(2):356-363

PMID: 29127703

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Abstract

US Food and Drug Administration (FDA) investigators recently demonstrated in a crossover study that early (J-T c) and late (T -T ) repolarization duration can differentiate selective potassium block with a high arrhythmia risk from multichannel block with lower risk in subjects receiving dofetilide, verapamil, quinidine, or ranolazine. The purpose of this study was to determine if the findings by the FDA using their published software algorithm could be corroborated using an alternative software algorithm for the same metrics and to determine if methodological differences resulted in clinically meaningful differences in interpretation. Exposure-response relationships computed with linear mixed effects models and mean maximal effects on ECG intervals measured by the two algorithms were similar, corroborating the FDA findings, but with some differences in the modeled slopes and magnitude of changes. The alternative software resulted in an average 25% reduction in the 95% confidence intervals of the mixed effects models with generally lower Akaike Information Criterion values.

Address: VivaQuant LLC, St Paul, Minnesota, USA.; Fossa Consulting LLC, Mystic, Connecticut, USA.; Spaulding Clinical Research, West Bend, Wisconsin, USA.; Division of Cardiology, University of Utah, Salt Lake City, Utah, USA.

DOI: 10.1002/cpt.934

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MeSH Terms: Action Potentials, Algorithms, Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Automation, Calcium Channel Blockers, Data Warehousing, Dose-Response Relationship, Drug, Electrocardiography, Ambulatory, Female, Heart Conduction System, Heart Rate, Humans, Ion Channels, Linear Models, Male, Observer Variation, Potassium Channel Blockers, Predictive Value of Tests, Randomized Controlled Trials as Topic, Retrospective Studies, Signal Processing, Computer-Assisted, Voltage-Gated Sodium Channel Blockers