digoxin and Dilatation--Pathologic

Topics: Activities of Daily Living; Azathioprine; Blood Pressure; Digoxin; Dilatation, Pathologic; Drug Therapy, Combination; Female; Furosemide; Humans; Hypertension, Pulmonary; Mixed Connective Tissue Disease; Pulmonary Artery; Radiography; Treatment Outcome

Recent clinical trials have suggested that therapy with angiotensin-converting enzyme inhibitors in asymptomatic patients with reduced left ventricular (LV) function can significantly reduce the incidence of congestive heart failure compared with patients receiving placebo. In the present study, we examined the effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF).. LV dysfunction was produced in 28 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after the last embolization, dogs were randomized to 3 months of oral therapy with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n = 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n = 7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/- 1%, P < .001) and LV end-systolic volume (ESV) and end-diastolic volume (EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/- 6 mL, P < .001, and 61 +/- 6 versus 78 +/- 8 mL, P < .002, respectively). In dogs treated with enalapril or metoprolol, LVEF remained unchanged or increased after therapy compared with before therapy (35 +/- 1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P < .05), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased significantly.. In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfunction and LV chamber dilation. Therapy with digoxin maintains LV systolic function but does not prevent progressive LV enlargement.

Topics: Animals; Digoxin; Dilatation, Pathologic; Dogs; Enalapril; Metoprolol; Myocardium; Stroke Volume; Time Factors; Ventricular Function, Left

Prognosis in congestive cardiomyopathy (COCM) with marked dilatation and heart failure is poor. A low rate of spontaneous recovery was observed. A high level of circulating catecholamines is often found, which may explain the common finding of resting tachycardia. An early series of COCM patients with tachycardia responded surprisingly well when chronic beta-blockade was added to the conventional treatment of failure. Later, even patients without tachycardia were included with a period of placebo preceding beta-blocker treatment in order to exclude patients with spontaneous recovery. Acute beta-blockade was surprisingly well tolerated, possibly because the reduction in contractility was compensated for by an increase in myocardial compliance. After long-term beta-blockade, improvement was observed after 6 months and further improvement was seen after 24 months. In patients improving functionally, there was reduction in heart size and left ventricular end diastolic diameter and increase in working performance. For the whole group, there was a decrease in rapid filling wave in apex cardiogram, reduction in third heart sound and increase in ejection fraction. Changes in the reverse way were seen in these three variables after beta-blocker withdrawal and relapse into heart failure occurred in 6/15 patients. Changes in diastolic function may be an early important effect of beta-blockade in COCM. Increase in survival was seen when beta-blocker-treated patients with COCM were compared to well matched COCM controls. It is suggested that increased sensitivity to sympathetic stimulation contributes to the pathogenesis in some patients with COCM and that improvement in myocardial function explains prolonged survival.

Topics: Administration, Oral; Adult; Aged; Digoxin; Dilatation, Pathologic; Drug Therapy, Combination; Female; Follow-Up Studies; Furosemide; Heart Failure; Hemodynamics; Humans; Lactates; Male; Metoprolol; Middle Aged; Myocardium; Oxygen Consumption; Propanolamines; Spironolactone; Time Factors