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Serial testing of antiarrhythmic drugs by programmed electrical stimulation can be costly in time, expense and risk. The purpose of this study was to evaluate the results of serial electropharmacologic tests for similarities that might obviate the need for protracted drug testing, Serial electropharmacologic testing was performed in 283 patients with coronary artery disease and clinical sustained ventricular tachycardia (VT) or fibrillation (VF). Drug tests were defined as concordant if sustained VT or VF could be consistently induced, or failed to be consistently induced during all such trials in a given patient. The following drugs were included for testing; procainamide, quinidine and disopyramide (class IA); phenytoin, mexiletine and tocainide (class IB); and flecainide and encainide (class IC). All patients were serially tested with [greater than or equal to]2 (mean and median, 3) antiarrhythmic agents regardless of results from drug-free testing or initial acute drug testing. Overall, the results of serial drug trials directed by programmed stimulation were concordant in more than two thirds of patients. Concordance was comparably high whether patients were serially tested with drugs within the same antiarrhythmic class, or with drugs from differing classes, and was not related to patients' clinical or electrophysiologic characteristics. Protracted serial electropharmacologlc testing does not appear necessary for predicting successful or unsuccessful antiarrhythmic drug therapy in survivors of clinical VT or VF. Single drug testing can identify most patients whose arrhythmia will or will not respond to medications.

Forty-nine patients with coronary artery disease and documented clinical sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) were studied twice in the drug-free state and twice during treatment with an identical antiarrhythmic medication at therapeutic plasma concentrations using an identical programmed electrical stimulation protocol. Tested drugs included procainamide, quinidine, disopyramide and phenytoin. During their 2 paired tests, 11 patients had nearly identical therapeutic plasma concentrations of antiarrhythmic agents (group I) and 38 patients had therapeutic plasma concentrations, but with more variation in drug levels between otherwise identical paired drug tests (group II). Overall, 71% of patients had inducible sustained VT or VF during drug testing. induced ventricular arrhythmias were not reproducible in 45% of group I patients, despite restudy at nearly identical therapeutic plasma concentrations of an identical antiarrhythmic agent. induced arrhythmias were also not reproducible in 16% of group II patients. This variability could not be attributed to the electrophysiologic characteristics of the patients studied. Drug trials directed by programmed stimulation should be cautiously interpreted because time-associated changes can mimic a change attributed to a beneficial or deleterious drug effect. (Am J Cardiol 1990;66:725-730), Ventricular tachycardia (VT) refers to a very rapid heart rate and ventricular fibrillation (VF) describes a tremulous, ineffective heart beat. They are often considered together as tachyarrhythmias, which are irregular, rapid heart rhythms. Studies have revealed daily variations in ventricular tachyarrhythmias, induced during programmed intracardiac electrophysiologic stimulation (PIES). In fact, clinically significant variations in induced tachyarrhythmias have been reported in up to 27 percent of patients with VT or VF when they undergo repeated electrophysiologic testing. This indicates that studies designed to evaluate the effects of drugs on VT and VF must be interpreted with caution. To determine the day-to-day reproducibility of antiarrhythmic drug testing, 49 patients with coronary artery disease, VT or VF were treated with the same antiarrhythmic drugs, using identical PIES protocols. Of the patients tested, 11 patients had identical blood concentrations of the test drug (group 1), while 38 showed variability in blood levels of the drug during identical, paired drug tests (group 2). VT or VF occurred in 71 percent of the patients during drug testing. In 45 percent of the group 1 patients, and in 16 percent of group 2, the induced arrhythmias were not reproducible. These results indicate that drug trials using programmed stimulation should be interpreted with caution, since day-to-day variations could be misinterpreted as resulting from the drug treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

In order to characterize the day to day reproducibility of arrhythmias provoked during electrophysiologic stimulation, 114 patients with documented sustained clinical ventricular tachyarrhythmias were studied. Two baseline electrophysiologic tests were performed in the drugfree state and within 6 to 24 hours of one another. There was a significant increment (p ≤ 0.02) in the induction of sustained ventricular tachyarrhythmias as the number of programmed extrastimuli increased from one (10% induction) to four (64% induction). Provoked arrhythmias were observed to be more frequently nonreproducible (as reflected in a major change in rate or duration, or both, of an induced ventricular arrhythmia between baseline tests) as the number of extrastimuli increased from one (7%) to four (27%). Nonreproducibility with three and four extrastimuli was not significantly greater than when two extrastimuli were utilized. Electrophysiology-directed drug trials should be interpreted in light of this observed variability in induced arrhythmias.