Spontaneous variability of simple and complex ventricular premature contractions during long time intervals in patients with severe organic heart disease

Calculations of the spontaneous variability of ventricular arrhythmias are usually based upon the results of Holter electrocardiograms recorded either successively or separated by a short time interval. Only recently was it shown that the variability of ventricular premature contractions increases with longer intervals. This study was undertaken to investigate the variability of simple and complex ventricular arrhythmias over long periods to derive efficacy criteria for long-term antiarrhythmic therapy. In a prospective study, the influence of the length of the time interval on spontaneous variability was investigated in 100 patients with coronary artery disease or idiopathic dilated cardiomyopathy and untreated ventricular arrhythmia Lown grade IV. Patient follow-up was carried out for 260 ± 387 days. In each of the 498 ambulatory Holter tapes, the mean hourly arrhythmia count (AC) of ventricular premature contractions, couplets, and salvos was verified. The variability of arrhythmia counts between two Holter electrocardiograms was defined as the logarithm of the ratio of (AC(day 2) + 0.01) to (AC(day 1) + 0.01). The 95% intervals for these ratios were calculated as ± 2 SD, considering the fact that all mean values did not differ significantly from zero. The lower limit of these intervals refers to the reduction that is required for assuming drug efficacy, whereas the upper limit refers to an aggravation. The 95% intervals were calculated for each of four ranges of control intervals (0-6, 7-89, 90-364, and ≥ 365 days). They increased significantly with longer control intervals. For ventricular premature contractions, reduction increased from 63% (0-6 days), 79% (7-89 days), and 92% (90-364 days) to 98% (≥ 365 days). The corresponding values of aggravation were 370%, 570%, 1,286%, and 5,495%, respectively. For couplets, reduction extended from 90%, 94%, and 98% to 99%; aggravation increased from 1,114%, 1,895%, and 6,153% to 14,032%. For salvos, reduction remained almost unchanged at a high level at 95%, 98%, 98%, and 99%. The figures for aggravation were 2,189%, 4,650%, 5,698%, and 9,650%, respectively. In individual patients, spontaneous variability at short control intervals was not found to predict long-term variability. We conclude that evaluation of antiarrhythmic drug efficacy by Holter monitoring is most easily distinguishable with short control intervals and is almost impossible after an antiarrhythmic therapy longer than 3 months. In many cases, long-term efficacy of an antiarrhythmic agent can only be proven after discontinuation of the drug and reassessment of spontaneous arrhythmia frequency.