Calcium channel blockers that prolong the QT interval

Abstract

The development of a group of calcium channel blockers that prolong the QT interval has raised interest in their possible proarrhythmic potential. In animal experiments lidoflazine has no observed arrhythmogenic potential and no antiarrhythmic potential in a model sensitive to the antiarrhythmic properties of both conventional and investigational agents. This lack of antiarrhythmic potential reduces the possible proarrhythmic potential even further, since it has been my observation that many of the more potent antiarrhythmic agents may facilitate arrhythmias in a considerable percentage of the most severely ill patients. Bepridil has both slow channel blocking properties and fast channel blocking effects and thus possesses an antiarrhythmic effect beyond the prolongation of repolarization. Even though early studies with humans showed the drug to be no more effective than the conventional reference agent procainamide, its potential cannot be fully assessed by these preliminary studies. The assessment of arrhythmogenicity is determined by use of the technique of PES. This technique has been shown effective in identifying patients with electrical instability and in identifying the effectiveness of antiarrhythmic agents in preventing VT and sudden death. Thus it seems probable that PES studies may be effective in predicting which drug or agent would facilitate arrhythmias. Alcohol, caffeine, cigarette smoke, and catecholamines facilitate PES induction of VT, lending support to the hypothesis that PES studies can be used to identify proarrhythmic drugs. In fact, patients who experience cardiac arrest on a class I agent can have VT provoked on that agent but not on antiarrhythmic drug therapy. PES thus identifies the proarrhythmic effect of the drug in that particular patient.(ABSTRACT TRUNCATED AT 250 WORDS)