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History, Early Modern 1451-1600↗
Biomedical subjects
S Rhein
Publications and source records attributed to S Rhein.
[Enoximone and ventricular arrhythmia in chronic heart failure].
Potentially malignant ventricular arrhythmias are common in chronic heart failure. The aggravation of such arrhythmias has many causes in these patients and cannot be predicted. Therefore, proarrhythmia due to PDE-inhibitors which increase cytosolic calcium levels by specific inhibition of the degradation of cyclo-AMP may be difficult to recognize. A retrospective analysis of 24-h Holter ECG was performed in 31 patients (NYHA classes III and IV) under long-term enoximone therapy. At baseline, 68% of the patients had ventricular couplets and nonsustained ventricular tachycardia. After a mean treatment period of 7 months, 10% of the patients showed a significant increase, 16% a significant decrease (greater than 90%) of ventricular couplets and salvos, and an additional 32% of the patients showed a significant decrease (greater than 70%) of single PVCs. The change of the arrhythmia profile was not related to the clinical course in these patients. Furthermore, 24-h Holter recordings were analyzed in a randomized long-term trial with captopril and enoximone that included 20 patients of NYHA class II. Despite comparable baseline findings, a reduction of cardiopulmonary exercise capacity was observed in patients treated with enoximone, but not with captopril. However, the arrhythmia profile was similar in both treatment groups. These findings suggest that, in most patients with advanced chronic heart failure, long-term enoximone therapy is not associated with an important increase of ventricular arrhythmias. According to the 24-h Holter findings of the European Enoximone Data Bank, proarrhythmia can be expected in 12% of all patients. Control of the arrhythmia profile, however, is mandatory, because the incidence of proarrhythmia cannot be predicted in the individual patient.
Angiotensin-Converting Enzyme Inhibitors↗
[Cardiopulmonary stress: control of the function of frequency variable pacemaker systems].
Based on the linear relationship between cardiac output and oxygen uptake direct breath-to-breath gas exchange measurements during exercise allow accurate determinations of cardiopulmonary function. We used cardiopulmonary exercise testing to assess the physiologic benefit of rate response VVIR pacing in 17 patients with chronotropic incompetence. 13 patients had an activity-rate-response pacemaker, two patients had a temperature-controlled pacemaker and two patients a respiratory-dependent system. Exercise testing was performed with the pacemaker, either programmed to fixed rate VVI or to rate variable VVIR pacing. All patients were exercised on a bicycle using a ramp protocol with 10 to 20 watts/min increments. Maximal oxygen uptake and the anaerobic threshold were determined. Compared with findings in the VVI mode, rate response VVIR pacing increased maximal exercise heart rate from 74 +/- 10 to 118 +/- 21 bpm (p less than 0.001). This increase in heart rate was associated with an increase of maximal oxygen uptake from 14.3 +/- 5 to 18.3 +/- 6 ml/kg per min (p less than 0.04) and a delay of the anaerobic threshold to a higher oxygen consumption of 14.6 +/- 5 vs 10.6 +/- 5 ml/kg per min (p less than 0.04). The individual increase in oxygen uptake was a direct function of the change in exercise heart rate independent of the implanted pacing device. The improved aerobic capacity resulted in a 17% increase in exercise tolerance and a 19% increase of exercise time. Cardiopulmonary exercise testing appears to be a useful noninvasive technique to quantify the cardiopulmonary benefit of rate response pacing.
Adult↗
Additive effects of enoximone and nitroprusside in unstable chronic heart failure.
In the present study, the safety and efficacy of the combined administration of intravenous nitroprusside and oral enoximone, an experimental compound with phosphodiesterase inhibitory properties, were evaluated. Ten patients with unstable chronic heart failure maintained on digitalis and diuretics were selected to receive enoximone because of their poor response to intravenous nitroprusside. For a mean peak dose of 115 micrograms min-1 nitroprusside, cardiac index increased from 1.8 +/- 0.4 to 2.0 +/- 0.4 l min-1 m-2, while pulmonary artery diastolic pressure and mean right atrial pressure decreased from 29 +/- 6 to 24 +/- 5 and from 15 +/- 6 to 11 +/- 3 mmHg respectively; mean arterial pressure and heart rate were unchanged. The addition of 1.6 mg kg-1 oral enoximone t.i.d. to nitroprusside resulted in a substantial improvement of cardiac function: cardiac index increased further to 2.8 +/- 0.5 l min-1 m-2 (P less than 0.001), pulmonary artery diastolic pressure and right atrial pressure decreased to 18 +/- 5 and 7 +/- 3 mmHg (P less than 0.01), respectively, while mean arterial pressure rose from 90 +/- 11 mmHg to 95 +/- 0 mmHg (P less than 0.05); heart rate was unchanged. The salutary haemodynamic response to combined nitroprusside-enoximone therapy persisted for more than 32 h, and cardiac performance remained improved on enoximone for a further 8 h despite the discontinuation of nitroprusside. No serious side-effects or changes in the arrhythmia profile were observed. The addition of oral enoximone to nitroprusside has beneficial haemodynamic effects in unstable chronic heart failure.
Aged↗
Long-term enoximone therapy in unstable chronic heart failure.
Long-term safety and efficacy of oral enoximone were evaluated in 32 patients with unstable chronic heart failure despite digitalis, diuretics, and vasodilator therapy. Oral enoximone, 75-150 mg t.i.d. was given for an average of 32 weeks. At baseline, 21 patients were in NYHA functional class IV, 10 patients in class III, and 1 patient in class II. Within 12 weeks, 14 of 20 patients surviving for more than 26 weeks had improved by at least one functional class. Hemodynamic data showed an 18% increase of cardiac index and a 34% decrease of diastolic pulmonary artery pressure. Echocardiographic recordings revealed an increase of fractional shortening from 13.9 +/- 7 to 15.6 +/- 5% after 12 weeks and 20.3 +/- 5% after 26 weeks. The 1-year survival rate was 40%. Sudden death occurred in three patients and pump failure in 11 patients. No serious side effects were reported. Holter monitoring did not show a significant proarrhythmic drug effect. Thus, long-term enoximone therapy is safe and produces sustained clinical and functional improvement in unstable chronic heart failure. However, overall survival appears not to be influenced in this patient group.
Adult↗
[Effect of oral long-term enoximone therapy on the arrhythmia profile in chronic heart failure].
The arrhythmogenic potential of long-term treatment with Enoximone in patients with severe chronic heart failure has not been determined. We analysed retrospectively 24 h Holter recordings in 31 patients with chronic heart failure, predominantly NYHA functional class III and IV, before and during chronic Enoximone therapy between 4 and 52 weeks. At baseline ventricular couplets and salvos were found in 68% of patients. Ventricular arrhythmia response was variable with no significant overall change. During a mean follow-up of 28 weeks, however, 3 (10%) patients showed a significant increase and 4 (16%) patients a more than 90% decrease of repetitive ventricular arrhythmias. In another 10 (32%) patients a more than 70% decrease of singular ventricular arrhythmias was observed. There was no correlation between the change of the patient's arrhythmia profile, the degree of functional impairment of the underlying heart disease, and the clinical response to long-term Enoximone therapy. Two patients died suddenly, one with a significant increase, the other with a significant reduction of ventricular arrhythmias. Two patients died of pump failure with no change of the arrhythmia profile. Enoximone appears to have a low arrhythmogenic profile during long-term treatment. However, careful monitoring of ventricular arrhythmias is mandatory as the occurrence of proarrhythmic drug effects cannot be predicted.
Administration, Oral↗
Long-term treatment with oral enoximone for chronic congestive heart failure: the European experience.
The long-term safety and efficacy of the inotropic/vasodilatory agent enoximone (50 to 100 mg 3 times daily) were evaluated in 30 patients with chronic congestive heart failure (New York Heart Association classes II to IV). Nineteen patients had idiopathic dilated cardiomyopathy and 11 had ischemic heart disease. Patients were receiving maintenance therapy of digitalis and diuretics. Cardiac function was assessed at 12 week intervals (physical examination, exercise testing, chest x ray, echocardiography, radionuclide angiography, 24-hour Holter monitoring and blood chemistry). During a mean follow-up of 40 weeks, 6 patients died, due to noncardiac (n = 1) and sudden death (n = 1) and to cardiac failure (n = 4) within 36 weeks of drug treatment. In the remaining patients New York Heart Association class improved in 18, was stationary in 5 and deteriorated in 1. Exercise capacity increased during the first 26 weeks and was maintained improved thereafter. Clinical improvement appeared not to wane with time. No change in heart rate, blood pressure and cardiothoracic ratio was observed. Echocardiographic left ventricular dimensions did not change significantly; however, the fractional shortening increased from baseline (14%) to 19% after 12 weeks, 17% after 26 weeks and 21% after 52 weeks (p less than 0.05). The preejection period/left ventricular ejection time ratio decreased from 0.74 to 0.35, 0.44 and 0.43 (p less than 0.05), respectively. There was an increase in radionuclide ejection fraction from 23% to 27% (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Long-term therapy of chronic cardiac insufficiency using enoximone].
Effect and tolerance of the oral phosphodiesterase inhibitor Enoximone was tested in 14 patients with advanced cardiac failure (New York Heart Association groups II-IV). During a mean observation period of 40 weeks there were four deaths; one patient became therapy-resistant. The remainder reported sustained clinical improvement. During the observation period there were no changes in heart rate or arterial blood pressure. There were no significant changes in cardiothoracic ratio on the chest X-ray or of the echocardiographically determined left-ventricular diameters. However, there was a rise in shortening fraction from 13.5 +/- 6.4% to 16.8 +/- 6.5% after 26 weeks, and to 21.1 +/- 8.1 after 52 weeks (P less than 0.05). The ratio of the systolic time intervals, PEP/LVET, decreased correspondingly from 0.74 +/- 0.23 to 0.44 +/- 0.09 and 0.43 +/- 0.10 (P less than 0.05). Hemodynamic measurements after one-year treatment revealed an increase in cardiac index from 2.4 +/- 0.7 to 3.6 +/- 0.6 l/min X m2, and a fall in pulmonary artery wedge pressure from 25.5 +/- 9.7 to 12.6 +/- 13.0 mm Hg (P less than 0.001). The drug was well tolerated and there were no significant biochemical changes. Long-term ECG monitoring revealed no significant changes in the arrhythmia profiles. Enoximone thus proved to be a successful therapeutic agent in the management of advanced heart failure.
Adult↗