title: Short-term variability of ventricular arrhythmia and rapid assessment of drug efficacy.
abstract: Statistical criteria for suppression and aggravation of ventricular arrhythmia were defined by means of 50 short-term drug tests performed in 24 patients. Each patient's spontaneous variability (SV) was evaluated by linear regression analysis of hour-to-hour changes in ectopy during 24- to 48-hour Holter monitoring. The response to a single oral dose of disopyramide, 300 mg, flecainide, 200 mg, and propafenone, 450 mg, was measured during a trial lasting 4 hours. Lidocaine was administered intravenously in incremental doses of up to 4 mg/min and was evaluated over 3 hours. Threshold values of ventricular arrhythmia corresponding to 95% confidence limits were calculated from baseline recordings and were used to ascertain the likelihood of a true drug effect. The minimum decrease in hourly ectopy indicating arrhythmia suppression averaged 90.9%, while an increase of at least 947% was required for a proarrhythmic effect. When these efficacy criteria were applied, 16 of 50 short-term tests revealed no drug effect. In contrast, when a 70% threshold derived from studies of daily variability was employed, only 7 of 50 trials were negative. Thus individual determination of hourly arrhythmia variability yields more stringent criteria than extrapolation from day-to-day spontaneous variation.
authors.affiliation: Cardiology Division, State University of New York, Stony Brook.
authors.forename: E A
authors.initials: EA
authors.lastname: Raeder
authors.forename: S
authors.initials: S
authors.lastname: Hohnloser
authors.forename: S C
authors.initials: SC
authors.lastname: Vlay
authors.forename: L
authors.initials: L
authors.lastname: Olson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D002908:Chronic Disease; D004341:Drug Evaluation / Q000379:methods; D015716:Electrocardiography, Ambulatory; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents