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This is a multicenter, randomized, double-blind, placebo-controlled, cross-over and double-dummy study aimed at testing the efficacy and tolerability of two slow-release propafenone (Pr SR) preparations and compare them with the effect of instant release propafenone (Pr IR). The study was performed in 83 patients with frequent (> 30 premature ventricular contractions/hour) and stable (< 35% variability in two 24-hour ECG monitoring periods) symptomatic premature ventricular contractions. Patients were preliminarily studied in wash-out from antiarrhythmic drugs. After a period of placebo administration, all patients underwent three consecutive periods during which they received Pr IR at the dosage of 150 mg x 3, Pr SR at the dosage of 225 mg x 2, Pr SR at the dosage of 325 mg x 2. The periods lasted 10-14 days each and the sequence was randomly assigned. Twenty-four-hour ECG monitoring periods were obtained at the end of the placebo as well as at the last day of each treatment period. Treatment efficacy was evaluated by intention to treat analysis in 80 patients and by protocol in 61. Treatment was considered efficacious when premature ventricular contraction reduction > or = 75%, couplet reduction > or = 90% and non sustained ventricular tachycardias were completely suppressed. Pr IR 150 mg x 3 was efficacious in 42% of patients, Pr SR 325 mg x 2 in 45.9% and Pr SR 225 mg x 2 in 32%. Tolerability was considered good in the majority of patients. These results show that among the different types studied, Pr SR 325 mg x 2 should be considered the treatment of choice for premature ventricular contractions.

It has been reported that the frequency of premature ventricular contractions in some patients tend to decrease during the hours of sleep when modifications in autonomic tone and bradycardia occur. The aim of this study was to evaluate whether the phenomenon of sleep suppression may be a sensitive and specific parameter for predicting the antiarrhythmic effect of beta-blockers on premature ventricular contractions. The presence of sleep suppression was evaluated in 45 patients (mean age 50 +/- 17 years) with frequent premature ventricular contractions at two baseline Holter recordings. Sleep suppression was defined as > 50% reduction in the number of nighttime as opposed to day-time premature ventricular contractions. Three groups of patients were identified: those with sleep suppression at both Holter recordings (group 1); those with sleep suppression at only one Holter recording (group 2); and those without sleep suppression at either Holter recording (group 3). A third Holter was performed 5 days after nadolol administration. In group 1, nadolol led to a mean reduction in the number of premature ventricular contractions of 90% (> 70% in 21/23 patients). In group 2, the mean reduction was 76% (> 70% in three out of six patients). In group 3, there was a mean increase in the number of premature ventricular contractions of 33%. The positive predictive accuracy of sleep suppression in relation to the antiarrhythmic efficacy of nadolol is very high (88%) when sleep suppression is present during two baseline Holter recordings. Sleep suppression is a sensitive parameter for identifying the premature ventricular contractions likely to benefit from beta-blocker administration.

To evaluate whether the identification of the different types of relations between premature ventricular contractions (PVCs) and the preceding sinus cycle length is capable of predicting the effect of beta-blockers on the PVCs themselves, 55 patients (43 men, 12 women, mean age 52.6 +/- 15.6 years) with different cardiac diseases, and >30 PVCs/hr characterized by stability and the same relation at two Holter monitoring periods were studied. The relation was tachycardia enhanced (the shorter the preceding cycle length, the higher the incidence of PVCs) in 23 patients (group 1); indifferent (no correlation between the preceding cycle length and PVC incidence) in 21 (group 2); and bradycardia enhanced (the longer the preceding cycle length, the higher the incidence of PVCs) in 11 (group 3). A third Holter monitoring was performed 6 days after nadolol administration (80 mg/day) to evaluate its effect on the three types of PVCs. Incidence in all patients (-88;p<0.001). In group 2, it caused a reduction in the majority of patients (-60%;p<0.05) but an increase in five. In group 3, it caused a reduction in only half of the patients (-45%) and a 91% increase in the remainder. The difference in the effect of nadolol in the three groups was highly significant (X2=27.5;p<0.0001). The relation between the incidence of PVCs and the preceding cycle length is a useful means of identifying subsets of patients with PVCs who will benefit from beta-blockers.

The aim of our study was to correlate betablocker effects on premature ventricular beats (PVBs) with different patterns between PVB frequency and cardiac cycle. The computer program we used correlates each PVB to the preceding cycle length in a 24-hour electrocardiogram recording. The arrhythmic patterns obtained were defined as tachycardia-dependent, indifferent and bradycardia-dependent. We selected 51 patients (39 males, 12 females, mean age 52 years) with different cardiac diseases, all in sinus rhythm, with > 25 PVBs/h, characterized by PVB stability and reproducible pattern in 2 Holter monitoring recorded at a 3-5 day interval. A tachycardia-dependent pattern (TDP) was demonstrated in 20 patients; 22 patients showed an indifferent pattern (IP) and 9 a bradycardia-dependent pattern (BDP). A third Holter monitoring was performed 4-5 days after nadolol administration (80 mg/day). Nadolol caused a 87.7% PVB suppression in TDP patients (p < 0.001), a 34.8% PVB reduction in IP patients (p < 0.01) and a 36.3% increase in BDP patients (NS). The different effect of nadolol on these groups was highly significant (chi 2 30.9; p < 0.0001). These results indicate that pattern definitions is useful in identifying PVB subsets which are likely to be improved, or not, by betablockers.

Pentisomide, a new class I anti-arrhythmic drug, was compared to placebo in 50 hospitalized patients with frequent (greater than 30 h-1) and stable ventricular premature beats (VPB) (variation less than 50% between two preliminary and one placebo 24-h Holter recordings). All patients underwent a single-dose acute oral testing followed by a short-term testing with 300 mg t.i.d. for 4 days and then by a 4-day placebo period. For the studied population, a 56.4% reduction of simple VPB and a 98.8% decrease of couplets and runs were the minimum required to define the drug efficacy and to exclude spontaneous variability, using the linear regression analysis. Pentisomide was found effective in 27 (54%) of the 50 patients after the acute test and in 23 (46%) after the short-term test. The drug induced a mild increase of PR and QRS intervals, while QTc, heart rate, blood pressure and ejection fraction showed no significant variations. Subjective tolerability was excellent.