Rate-dependent failure of ventricular capture in patients treated with oral propafenone

The effects of propafenone on ventricular excitability were studied in 18 patients after 9 +/- 6 days on oral propafenone (900 mg/day). Late diastolic double threshold right ventricular stimulation was performed at variable rates. In five patients (28%, group I) an intermittent, rate-dependent failure of ventricular capture was reproducibly observed during stimulation at rates above the sinus rhythm but not exceeding 150 beats min-1. In four patients loss of capture was preceded by gradual prolongation of the interval between the stimulus artifact and the local right ventricular bipolar electrogram. Such findings were not observed in the remaining 13 patients (group II) on propafenone nor in 28 studies in the same patients on different antiarrhythmic agents. Group I vs group II patients were older (72 +/- 4 vs 53 +/- 18 years, P = 0.002), had longer right ventricular effective refractory periods on the baseline (P = 0.004) and on propafenone (P = 0.0003), and had longer QRS duration on propafenone. The increase produced by propafenone in sinus rhythm QRS duration, paced QRS duration and ventricular effective refractory period was greater in group I than in group II: 42 +/- 36 vs 14 +/- 12 ms, P = 0.01, 94 +/- 43 vs 34 +/- 26 ms, P = 0.0002, 88 +/- 64 vs 22 +/- 37 ms, P = 0.025, respectively. Thus propafenone can produce rate-dependent failure of ventricular capture which is associated with marked prolongation of refractoriness and QRS duration suggesting a marked use-dependent drug effect in selected patients.