Application of a Frequency Definition of Ventricular Proarrhythmia

To differentiate spontaneous variability from proarrhythmia in patients with benign or potentially lethal ventricular arrhythmias, 495 patients with 2 or more Holter tracings during placebo therapy were evaluated. The Holter session with the highest frequency of ventricular premature complexes (VPCs) and ventricular tachycardia was compared with the first placebo recording. Patients were segregated by their baseline frequency of VPCs. The percent of patients taking placebo in this trial who had the same increase in VPC frequency as has been ascribed to those with proarrhythmia varied from 0 of 470 patients with a baseline frequency of ventricular arrhythmia of 10 to 50 VPCs/hour, 3 of 44 (7%) with 51 to 100 VPCs/hour, 1 of 139 (0.7%) with 101 to 300 VPCs/hour and 1 of 265 (0.04%) with more than 300 VPCs/hour. Overall, 5 of 496 (1%) patients would have been classified as having proarrhythmia using the algorithm although only placebo was given. A 10-fold or greater increase in ventricular tachycardia beats in patients taking placebo occurred in 9 of 274 patients (3%). Thus, a simple algorithm to define proarrhythmia in patients with mixed cardiac disease and chronic ventricular arrhythmias can be defined and differentiated from spontaneous variability. This arbitrary algorithm defines proarrhythmia as an increase of more than 3 times when baseline VPC frequency is more than 100 VPCs/hour and more than 10 times when that frequency is less than 100 VPCs/hour with a false-positive rate of only 1%.