title: A method for constructing and estimating the RR-memory of the QT-interval and its inclusion in a multivariate biomarker for torsades de pointes risk.
abstract: The problem of drug-induced QT-interval prolongation has become a major economic and health issue in the pharmaceutical industry. Little has been done to link analytically the QT-interval prolongation and the risk of torsades de pointes. This paper introduces a method for analyzing the dynamic characteristics of a 24-hour electrocardiograph and offers an algorithm to measure the long-term memory of the RR-interval history in a single statistic. The memory statistic seems to improve the discrimination between healthy normal subjects and arrhythmia cases using only beat-to-beat information from the QT and RR intervals producing an impulse response function, which is completely independent of heart rate.
authors.affiliation: Translational and Molecular Medicine, Pfizer Global Research and Development, Groton, Connecticut, USA. craig.trost@AnalyticDynamics.com
authors.forename: Donald C
authors.initials: DC
authors.lastname: Trost
mesh_terms: D015415:Biomarkers; D017321:Clinical Trials, Phase I as Topic / Q000379:methods / Q000706:statistics & numerical data; D018592:Cross-Over Studies; D004562:Electrocardiography / Q000379:methods* / Q000706:statistics & numerical data; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D016171:Torsades de Pointes / Q000175:diagnosis / Q000503:physiopathology*
chemical_list: D015415:Biomarkers