Na+ channel blockers vs class III antiarrhythmic drugs in treating sustained ventricular tachycardia: reversing and preventing as different electrophysiological mechanisms.

METHODS

169 selected patients with previous AMI and inducible sustained ventricular tachycardia (sVT) at electrophysiological study (EPS) were followed-up prospectively for recurrent sVT during a five year period. At EPS, ventricular effective refractory period (VERP)/action potential duration (APd) ratio, ventricular conduction velocity, excitable gap, cycle length and QRS duration were measured. The patients with inducible sVT at basic programmed stimulation or after isoproterenol infusion (200 micrograms i.v.) underwent drug suppression tests (amiodarone, procamide, propanolol + procamide, amiodarone + propaphenone). On this basis, they were later assigned to 3 different groups: the amiodarone-treated group (n = 112), the procamide-treated group (n = 22) and the nonresponder group (control group, n = 35).

RESULTS

After procamide infusion (100 mg/min for 10 min), at fast pacing drive the VERP/APd ratio was significantly increased from baseline levels (p < 0.001), the conduction velocity (Vmax) was significantly depressed (by 25%, p < 0.005), the excitable gap was significantly reduced (p < 0.005, 23% of cycle length) and 71 patients were no longer inducible; during sinus rhythm, Vmax was significantly reduced from baseline values (by 14%, p < 0.05), VERP was only moderately increased and the excitable gap was slightly but significantly prolonged (p < 0.01, 53% of cycle length): 147 patients were still inducible, without significant difference from baseline values. After amiodarone infusion (300 mg/100 ml i.v. over 10 min), Vmax was significantly reduced from baseline levels at fast pacing drive (by 21%, p < 0.001), while the excitable gap did not reduce significantly (34%) from baseline levels and 91 patients were still inducible; during sinus rhythm, conduction velocity was moderately depressed (by 7%, p < 0.05), while VERP was significantly increased from baseline levels (p < 0.002) and the excitable gap was significantly reduced (p < 0.001, 29% of cycle length); only 35 patients were still inducible. In the remaining 134 patients the reset curve showed excitable gaps = 24 +/- 3% of the cycle length. The absolute and relative values of the excitable gap measured in the 35 patients who were still inducible were significantly higher than those measured in patients no longer inducible (p < 0.05). At follow-up, the sVT recurrence rate was: 28% in the amiodarone-treated group, 43% in the procamide-treated group and 36% in the control group: control data were significantly different from the former (p < 0.05) but not from the latter group. Significant correlation was reported between the plasmatic concentration of procamide and amiodarone and the percentage of reduction of Vmax at fast pacing drive (r = 0.79, p < 0.05; r = 0.83, p < 0.01). Resulting variability checked by the analysis of variance showed no significant difference between the two series (p < 0.12638). The development of conduction velocity depression was clearly dose-dependent. Drug suppression test with procamide + propanolol resulted in noninducibility of sVT in 115 patients, with strong significant difference from when the drug was used alone (p < 0.0015). Better results at EPS were obtained by the combination amiodarone + propaphenone, although no additional benefit was reported when compared with amiodarone alone.

CONCLUSIONS

In conclusion, antiarrhythmic drugs with class I action may be highly effective in terminating sVI (lidocaine, procamide) but may be ineffective in preventing it or even arrhythmogenic. According to our data, drugs with class III antiarrhythmic action showed significantly different behavior: they were more effective in prolonging refractoriness and reducing the excitable gap at longer cycle lengths and, thus, capable of preventing, rather than terminating. Although statistical difference was reported between the amiodarone-treated group and the control group, the incidence of recurrent sVT remained too high to consider drug therapy as