In spite of the ratio between plasmatic concentration and antiarrhythmic effects of a drug many factors can be influenced by many factors, the plasma level monitoring plays an important clinical role. The efficacy of the antiarrhythmic therapy should be evaluated not only by means of ECG-Holter monitoring and/or electrophysiological study but also by the means of determination of plasmatic and tissular concentration of a drug and metabolites. This latter is indispensable in the evaluation of new antiarrhythmic drugs and of a dose/effect relationship during acute and chronic therapy.
Interpreting the results of this study, propafenone (Rytmonorm), administered orally in a dose of 900 mg daily, was more effective than disopyramide in a dose of 600 mg daily, in the treatment of patients with complex premature ventricular contractions (PVCs). The study was performed in 12 patients, with several Holter ECG monitorings to obtain quantitative data of the effectiveness in the same patient of the new drug propafenone in comparison with disopyramide in a documented effective oral regimen. A quantitative analysis of PVCs was obtained with a computer assisted detection. Clinical effectiveness, considered as 70--80% reduction of total number of PVCs, was obtained in 8/12 patients for propafenone and 6/12 for disopyramide, or as 50% reduction with suppression of all complex PVCs (couplets, repetitive, multiform and bigeminy) was obtained in 11/12 for propafenone and 9/12 for disopyramide.
Even if the prognostic significance of ventricular arrhythmias (VA) has been documented in post-AMI CAD, which post-AMI patient showing VA should be treated is still controversial, because no beneficial effects of antiarrhythmic treatment has ever been proved in clinical trials using phenytoin, aprindine, tocainide, mexiletine, and the drugs recently utilized in the CAPS for EVBs. Probably, the rationale for antiarrhythmic therapy is more conclusive in patients with ventricular arrhythmias other than EVBs, and the need for antiarrhythmic drugs should be evaluated in each case, considering other clinical variables of prognostic importance (EF%, extent of coronary lesions, etc.). The type of antiarrhythmic drugs to be used is discussed, considering that, while many traditional antiarrhythmic agents are undoubtedly effective in the treatment of an acute arrhythymia, in the chronic setting, most of the time, a significant reduction in ventricular arrhythmias on Holter monitoring can be proved, without a significant reduction in total mortality. Conversely, we comment on the positive results of some empirical studies showing beneficial effects of antiarrhythmic therapy in high-risk patients reported by Lown's group. Furthermore, it can be stated that patients showing efficacy of antiarrhythmic therapy by both non-invasive and invasive evaluation of antiarrhytmic therapy efficacy had better long-term outcomes. To confirm these data, we report the results of a clinical study of the treatment of complex and frequent EVBs in cardiac patients. A different mortality on follow-up was observed in responders and nonresponders vs. patients not receiving drugs (2.2, 28, and 24%, respectively). In 98 post-AMI patients with sustained recurrent VT or life-treathening arrhythmias, we report the data of a clinical protocol, including first empirical use of amiodarone and propafenone as first choice and, in the case of recurrences, therapy guided by EPS. In this group, global mortality was 21% at 5 years mean follow-up and 26% at 6 years mean follow-up. Propafenone showed a recurrence rate of VT of 19% while amiodarone showed a recurrence rate of 20% in the same follow-up period.
Even if the prognostic significance of ventricular arrhythmias (VA) has been documented in post-AMI CAD, which post-AMI patient showing VA should be treated is still controversial, because no beneficial effects of antiarrhythmic treatment has ever been proved in clinical trials using phenytoin, aprindine, tocainide, mexiletine, and the drugs recently utilized in the CAPS for EVBs. Probably, the rationale for antiarrhythmic therapy is more conclusive in patients with ventricular arrhythmias other than EVBs, and the need for antiarrhythmic drugs should be evaluated in each case, considering other clinical variables of prognostic importance (EF%, extent of coronary lesions, etc.). The type of antiarrhythmic drugs to be used is discussed, considering that, while many traditional antiarrhythmic agents are undoubtedly effective in the treatment of an acute arrhythmia, in the chronic setting, most of the time, a significant reduction in ventricular arrhythmias on Holter monitoring can be proved, without a significant reduction in total mortality. Conversely, we comment on the positive results of some empirical studies showing beneficial effects of antiarrhythmic therapy in high-risk patients reported by Lown's group. Furthermore, it can be stated that patients showing efficacy of antiarrhythmic therapy by both noninvasive and invasive evaluation of antiarrhythmic therapy efficacy had better long-term outcomes. To confirm these data, we report the results of a clinical study of the treatment of complex and frequent EVBs in cardiac patients. A different mortality on follow-up was observed in responders and nonresponders vs. patients not receiving drugs (2.2, 28, and 24%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Summary: The acute hemodynamic effects of combining administration of digoxin (DIG)(0.01 mg/kg intravenously) with molsidomine (MLS)(4 mg sublingually) were compared with those of DIG and MLS considered alone in 12 patients with congestive heart failure following acute myocardial infarction. The patients were classified into two subgroups, A (cardiac index [Cl] ≤ 2.2 L/min/m2) and B (CI > 2.2 L/min/m2), to verify differences between the responses to the three drug regimens. MLS significantly reduced systolic blood pressure from 121.2 ± 12.3 (mean ± SD) to 111.7 ± 10.9 mm Hg (p < 0.01) after 60 min, mean right atrial pressure (RAP) from 6.2 ± 3.6 to 2.4 ± 2.1 mm Hg (p < 0.0001), mean pulmonary arterial pressure (PAP), left ventricular filling pressure (LVFP) from 20.6 ± 2.1 to 12.2 ± 2.8 mm Hg (p < 0.0001), and pulmonary vascular resistance (PVR). Left ventricular stroke work index (LVSWI) significantly increased after 60 min. DIG induced a significant reduction in heart rate, RAP, PAP, and LVFP from 20.1 ± 2 to 14.3 ± 2.7 mm Hg (p < 0.0001) after 90 min. Stroke volume index (SVI) increased from 24.7 ± 4.2 to 27.7 ± 3.1 ml/beat/m2 (p < 0.001) and LVSWI from 25.9 ± 7.2 to 31.9 ± 5.4 g - m/m2 (p < 0.0001). The combination of DIG and MLS produced a reduction in RAP, PAP, and LVFP greater than that achieved with either agent alone, with a further shift of the ventricular function curve to the left, thereby leading to an improvement in cardiac performance. The subgroup A patients showed a significant increase in Cl, SVI, and LVSWI, and a significant decrease in SVR and PVR, 90 min after the administration of DIG, while the subgroup B showed a significant change only in LVSWI. No difference in the response of LVFP, Cl, and SVI, to MLS or the combination DIG-MLS was found between the two subgroups.
The purpose of our study was to assess the efficacy of Propafenon in comparison with Disopyramide in the long-term treatment of repetitive ventricular tachycardia. We studied 34 patients suffering from episodes of repetitive ventricular tachycardia of different etiology. Propafenon and Disopyramide was administered in doses of 300 mg and 200 mg three times a day respectively. The number of ventricular tachycardias has been evaluated during a period of 4 months of basal observation and during two periods of 4 months each of treatment respectively with Disopyramide and Propafenon. Moreover a dynamic electrocardiogram was recorded to assess the efficacy of Propafenon in suppressing ventricular ectopic beats in 17 patients. We conclude that Propafenon shows greater efficacy than Disopyramide in the treatment of repetitive ventricular tachycardias and a comparable efficacy in the control of ventricular ectopic beats. Moreover Propafenon shows also a minor incidence of side effects.
