[Effect of barucainide on left ventricular ejection fraction in patients with ventricular cardiac arrhythmias]. / Einfluss von Barucainid auf die linksventrikuläre Auswurffraktion bei Patienten mit ventrikulären Herzrhythmusstörungen.

We studied the effect of barucainide, an investigational class lb antiarrhythmic drug, on ventricular arrhythmias and left-ventricular ejection fraction in 10 patients with frequent and complex ventricular arrhythmias (Lown grade 4a/4b). The study was conducted as a single-blind and placebo-controlled trial. With placebo, mean frequency of ventricular arrhythmias was 6238 VPB/24 h, 510 couplets/24 h, and 24 salvos/24 h. Mean left-ventricular ejection fraction was 37.6%, ranging from 18% to 58%. Therapy with barucainide (300-400 mg/day) resulted in a significant reduction of ventricular arrhythmias in 7 of 10 patients; in one patient barucainide had a clear proarrhythmic effect. Over all, left-ventricular ejection fraction (37.6% +/- 12% with placebo vs 36.1% +/- 11% with barucainide) was not significantly altered. In one patient, however, it was depressed by more than 5%; one patient complained of shortness of breath during exercise. None of the four patients with an initial ejection fraction below 35% showed a drop of ejection fraction during therapy with barucainide. The only main adverse effect was a small, but significant (p less than 0.005) rise of serum-kreatinine (1.13 +/- 0.26 vs 1.39 +/- 0.38 mg%) in all patients. We conclude that barucainide has a good antiarrhythmic effect and is usually well tolerated in patients with markedly depressed left-ventricular function. The mechanism causing the rise of serum-kreatinin, however, needs to be clarified in further studies.

Short-term effects of oral enoximone on hemodynamics, exercise capacity, anaerobic threshold, and arrhythmias in congestive heart failure.

Enoximone, a phosphodiesterase-inhibitor, is a potent inotropic vasodilator agent that causes a marked improvement in hemodynamics in patients with congestive heart failure. The acute effects of oral enoximone on rest and exercise hemodynamics, ejection fraction, aerobic metabolism, exercise capacity, and arrhythmias were studied in 11 patients with moderate to moderately severe dilative cardiomyopathy after 8 days of enoximone (100 mg tid) in addition to baseline therapy (diuretics and digitalis). The cardiac index increased from 2.44 +/- 0.45 to 2.72 +/- 0.50 l/min/m2 (p less than 0.01) at rest and from 4.00 +/- 0.96 to 4.75 +/- 0.95 l/min/m2 (p less than 0.005) during exercise. Pulmonary wedge pressure decreased from 16.8 +/- 7.3 to 12.5 +/- 6.5 mmHg (p less than 0.005) at rest and from 28.2 +/- 8.0 to 24.5 +/- 10.3 mmHg (p less than 0.05) during exercise. Systemic vascular resistance decreased from 1608 +/- 243 to 1495 +/- 300 dynes*sec*cm-5 (p less than 0.05) at rest and from 1152 +/- 155 to 1027 +/- 236 dynes*sec*cm-5 (ns) during exercise. The anaerobic threshold, which was recorded simultaneously, increased from 13.2 +/- 2.7 to 15.5 +/- 2.5 ml/kg/min VO2 (p less than 0.02). The radionuclide ventriculography ejection fraction improved from 21.7 +/- 5.0 to 28.1 +/- 9.1% (p less than 0.01) during exercise; the changes at rest were not significant (20.8 +/- 6.2 vs 25.8 +/- 8.4%). Exercise tolerance showed an increase of 16% (492 +/- 133 to 573 +/- 135 sec, p less than 0.005). The resting heart rate remained unchanged (81.8 +/- 13.4 vs 81.8 +/- 11.9). Interestingly, 24-h Holter monitoring revealed more or new repetitive arrhythmias in 9/11 patients.

Antiarrhythmic therapy with flecainide in combination and comparison with propranolol.

In a prospective study of 10 patients with chronic ventricular arrhythmias, flecainide 50mg tid and propranolol 20mg tid were administered, alone and in combination, in a crossover design. Before and after each treatment phase, routine ECG and 24-hour ECG were recorded, morning plasma concentrations of the drugs were measured, and side effects recorded. Treatment with flecainide alone resulted in a 38% mean reduction (p less than 0.05) of ventricular premature complexes, a 75% (p less than 0.01) mean reduction of couplets, and elimination of ventricular tachycardia. At the dosage administered, propranolol alone had no antiarrhythmic effect. The combination of flecainide and propranolol showed no additional therapeutic benefit although there was a small, but not significant, increase in ventricular premature complexes and couplets. Use of flecainide resulted in a 12% widening of the QRS complex, with no significant change in PQ time, QTc and heart rate. Combined therapy with propranolol and flecainide resulted in a 12% decrease of average heart rate. The same effect was achieved when propranolol was given alone. The average plasma concentration of flecainide increased by 25% during combined therapy with propranolol. There were few side effects related to flecainide at the dosage administered and no additional side effects were recorded during the combined treatment.

Electrophysiological effects of quinidine alone and of the combination quinidine-verapamil on AV conduction in humans.

The influence of 320 mg quinidine administered intravenously (i.v.), as well as subsequent administration of 5 mg verapamil i.v. on atrioventricular conduction was studied in 8 patients during sinus rhythm and atrial stimulation with the aid of His bundle electrography. Among the electrophysiologic parameters of the atrium the sinus rate increased significantly after quinidine and again increased slightly after subsequent administration of verapamil. During sinus rhythm the PA interval was not influenced by either substance. Conversely, during atrial stimulation the STA interval increased significantly under the effect of quinidine, while verapamil had no further influence. As an indicator of conduction time in the AV node, the AH interval was decreased significantly by quinidine during sinus rhythm and atrial stimulation. This effect was significantly counteracted by the additional administration of verapamil. The HV interval as a measure of the His-Purkinje conduction was not significantly affected. The QRS duration was increased significantly by quinidine and was not further influenced by verapamil. The QTc and QT intervals increased significantly after administration of quinidine and were again slightly, but significantly shortened by verapamil. Our investigations show that the combination of quinidine and verapamil, which has clinically been found to have a higher conversion rate than quinidine alone, is well justified from an electrophysiologic point of view and that undesirable quinidine-related effects, such as rapid AV conduction in cases of atrial fibrillation and flutter, can be avoided by the subsequent administration of verapamil.