RESUMEN
Sotalol was given for extended therapy to 22 of 29 patients with frequent (greater than or equal to 30/hour) complex premature ventricular complexes (PVCs) who had participated in a short-term study of sotalol vs placebo. Open-label sotalol was given in individually titrated divided doses of 160 to 800 mg/day (median 323, mean 386 mg/day). Response was assessed at approximately 1, 6, and 12 months or until patient discontinuation. The period of sotalol therapy averaged 9 months (range, 0.2 to 22.7). At about 1 month, 13 (59%) of 22 patients showed effective control of arrhythmia. The median percentage change in total PVCs for individual patients at 1 month was -70% and for repetitive PVCs it was -95%. At about 6 months, 10 (45%) of the 22 patients continued to be successfully treated; at about 12 months, seven patients continued on sotalol, six (27%) successfully treated according to Holter criteria. Reasons for discontinuation included lack of efficacy in nine, adverse effects in four (fatigue in three, bradycardia with sinus pauses in one), and miscellaneous reasons in two. ECG PR and especially QTc intervals increased significantly during therapy (p less than 0.02, p less than 0.01, respectively). In summary, sotalol is a moderately effective antiarrhythmic agent in patients with complex PVCs, but during long-term therapy a rather high dropout rate was observed because of arrhythmia recurrence or adverse effects.
Asunto(s)
Arritmias Cardíacas/tratamiento farmacológico , Sotalol/uso terapéutico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/fisiopatología , Esquema de Medicación , Evaluación de Medicamentos , Electrocardiografía , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Sotalol/administración & dosificaciónRESUMEN
Sotalol is a unique beta-adrenergic blocking agent with additional actions characteristic of Vaughn-Williams class III antiarrhythmic agents in experimental models. To test the efficacy of sotalol to suppress ventricular arrhythmias, a 6 week parallel, placebo-controlled out-patient study of two doses (320 and 640 mg/day, in two divided doses) was performed in four hospitals in 56 patients with chronic premature ventricular complexes at a frequency of 30/h or more (mean +/- SE, 528 +/- 60/h) on 48 hour ambulatory electrocardiographic recording. During a placebo week, no change occurred in arrhythmia frequency (532 +/- 76/h). Subsequent sotalol therapy significantly reduced median arrhythmia frequency in patients receiving both low (n = 19) and high (n = 18) doses compared with that in patients receiving placebo (by 77 and 83%, respectively, versus 6%; p less than 0.001). Twenty-two (59%) of 37 sotalol-treated patients, 11 in each group, reached the prospectively defined criterion of efficacy (greater than or equal to 75% arrhythmia reduction) versus 2 (11%) of 19 placebo control patients (p less than 0.001). Sotalol reduced the median frequency of couplets by 94% (p less than 0.0001) and that of runs by 89% (p less than 0.0007). The electrocardiographic effects of sotalol included reductions in heart rate (by 17 to 27%) and increases in the QTc (by 6 to 9%) and PR (by 6%) intervals. Ejection fraction was unchanged. The most common adverse side effect was fatigue, but drug discontinuation was required in only three patients taking 640 mg/day. No proarrhythmic events or biochemical abnormalities were observed. In summary, sotalol displays significant antiarrhythmic activity of moderately high degree with good tolerance in doses of both 320 and 640 mg/day. Its antiarrhythmic actions are distinguished from those reported for other beta-blockers by its effects on the QTc interval and its moderately high degree of antiarrhythmic activity.
Asunto(s)
Complejos Cardíacos Prematuros/tratamiento farmacológico , Sotalol/uso terapéutico , Anciano , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Método Doble Ciego , Electrocardiografía , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Distribución Aleatoria , Sotalol/administración & dosificación , Volumen Sistólico/efectos de los fármacosRESUMEN
Milrinone is a promising new inotrope, but its arrhythmogenic potential has not been defined. We monitored ventricular arrhythmias during a 24-hour baseline and 48-hour milrinone infusion period in 12 patients with chronic heart failure. Patients were characterized by a mean age of 58 years and a left ventricular ejection fraction of 21%. Nine (75%) were male, nine had primary idiopathic dilated cardiomyopathy, and three had coronary artery disease. None had a history of cardiac arrest or sustained ventricular tachyarrhythmia. Milrinone was given as a loading dose (mean 53 micrograms/kg/10 min; range 37.5 to 75) followed by a 48-hour maintenance infusion (mean 0.53 micrograms/kg/min; range 0.25 to 0.75). Acutely, cardiac index increased by 27% and pulmonary wedge pressure decreased by 30% during milrinone; changes were maintained during continued therapy. Ventricular arrhythmia response was variable, with no significant overall difference. However, a trend toward increased ectopic activity was noted. No sustained tachyarrhythmias occurred. Mean frequency of premature ventricular complexes (PVCs) was 87 +/- 48 PVCs/hr (x +/- SEM) during baseline monitoring and 141 +/- 69/hr following infusion of the drug (p = 0.08). Mean frequency of couplets was 6.0 +/- 4.9/hr before drug infusion and 14.3 +/- 11.0/hr during infusion (p = 0.21). Mean frequency of runs was 0.9 +/- 0.8/hr before and 2.7 +/- 2.4/hr during drug infusion (p = 0.29). Two patients met criteria for proarrhythmia (increased PVCs of greater than 4x and/or repetitive forms of greater than 10x. However, neither proarrhythmia patient required reduction in the dosage of milrinone or additional antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Arritmias Cardíacas/inducido químicamente , Cardiotónicos/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Piridonas/efectos adversos , Adulto , Anciano , Arritmias Cardíacas/fisiopatología , Esquema de Medicación , Femenino , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Hemodinámica/efectos de los fármacos , Humanos , Infusiones Parenterales , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Milrinona , Factores de TiempoRESUMEN
The safety of coronary bypass operations after coronary reperfusion with streptokinase for acute myocardial infarction is not well documented. Therefore we studied 23 consecutive patients (mean age, 59.5 years; 22 men) undergoing bypass operations a median of 5 days (range, 1 to 23 days) after thrombolysis (streptokinase). The control group consisted of 169 concurrent patients of similar mean age (58.8 years) having bypass operations for standard indications. The preoperative angiographic ejection fraction was 68 +/- 14% in the control patients and 61 +/- 14% in the streptokinase group (p less than 0.05). The number of diseased vessels (70% stenosis or greater) averaged 2.6 in control and 2.3 in streptokinase patients. A previous myocardial infarction had occurred in 42% of the controls and all of the streptokinase patients. Aortic cross-clamp times did not differ between the two groups (80 +/- 35 minutes for the controls and 68 +/- 25 minutes for the streptokinase group). Cardiopulmonary bypass times were similar: 108 +/- 45 minutes in the controls versus 109 +/- 28 minutes in the streptokinase group. Grafts per patient averaged 3.7 +/- 1.5 for the controls versus 2.8 +/- 1.1 for the streptokinase patients (p less than 0.01). Difficult operative hemostasis was noted in 4% of both groups. Inotropic support was given postoperatively to 11% of the control and 13% of the streptokinase patients (p = not significant). Measured blood loss during the first 48 hours postoperatively was similar, averaging 809 ml in controls and 776 ml in the streptokinase group. Blood product replacement was also comparable: mean, 713 ml in the control group versus 759 ml in the streptokinase group.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Puente de Arteria Coronaria , Infarto del Miocardio/cirugía , Estreptoquinasa/uso terapéutico , Puente Cardiopulmonar , Angiografía Coronaria , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The clinical effects of intravenous streptokinase in patients with acute myocardial infarction were compared with those of intracoronary streptokinase in a randomized, prospective study. Comparisons were also made with a historical control group. Fifty patients were entered into the study at 2.4 +/- 1.2 hr after onset of pain, and 27 were assigned to intravenous and 23 to intracoronary therapy. The doses of streptokinase averaged 212,000 U ic and 845,000 U iv (0.75 X 10(6) U/5 hr, n = 14 or 10(6) U/1 hr, n = 13). Results of studies of the two intravenous dosage schedules were similar and so were combined. Streptokinase was administered at 2.8 +/- 1.0 hr after onset of pain in the intravenous and at 4.3 +/- 1.4 hr in the intracoronary drug group (p less than .001). Convalescent (day 10) radionuclide ejection fractions were 54 +/- 14% for the intravenous and 50 +/- 16% for the intracoronary drug group. Change in ejection fraction from day 1 to 10 tended to be greater after intravenous drug: 5.1% (p less than .08) vs 1.2% (NS). Semiquantitative regional wall motion indexes in the infarct zone showed significant and similar modest improvement from admission to day 10 in both groups (p less than .02). Accelerated enzyme-release kinetics were noted after both therapies. Times of peak enzyme levels for patients on intravenous and intracoronary drug were, respectively, 12.5 +/- 5.0 and 11.5 +/- 4.3 hr for creatine kinase MB isoenzyme and 31.7 +/- 11.8 and 28.1 +/- 12.7 hr for lactic dehydrogenase (LDH). Peak LDH-1 level was lower in patients receiving intravenous drug than in the historical control group (p less than .05). Electrocardiographically summed ST segments diminished rapidly after therapy in both groups; Q wave development was similar and overall R wave loss was equivalent and less extensive compared with in historical control subjects. Infarct pain requiring morphine was diminished similarly in both treatment groups. Incidence of early arrhythmias and heart failure also did not differ. Posttherapy ischemic events and early surgery tended to be more common in the intracoronary group and bleeding was more common in the intravenous group. Intravenous drug did not decrease early hospital mortality (intravenous drug = 5, historical control = 4, intracoronary drug = 1); the differences in this parameter among groups were not significant. At convalescent angiographic evaluation, anterograde perfusion was present in 73% of those receiving intravenous and 76% of those receiving intracoronary drug.(ABSTRACT TRUNCATED AT 400 WORDS)