Beta blocking agents in the treatment of dilated cardiomyopathy: review of the literature and clinical experience with 67 patients]

BACKGROUND. Several reports suggest that chronic beta blockade, most often with the beta 1 selective agent metoprolol, may improve hemodynamic and clinical function in patients with idiopathic dilated cardiomyopathy. However, controlled trials are limited and some studies have not shown beneficial effects in short term trials. Mechanisms of effectiveness are still debated and probably concern the capacity to avoid toxic myocardial damage by catecholamines, to induce receptor up-regulation, to contribute to the control of arrhythmias, to improve diastolic relaxation and other mechanisms. METHODS. After a revision of the literature, a preliminary clinical experience with metoprolol in dilated cardiomyopathy diagnosed according to the WHO definition is reported. Sixty-seven patients symptomatic for congestive heart failure or with complex ventricular arrhythmias associated with severe left ventricular dysfunction were submitted to test dose with metoprolol 5 mg bid for 2-7 days. All patients were completely studied, including coronary angiography and endomyocardial biopsy to exclude ischemic heart disease and active myocarditis. Four pts (6%) did not tolerate the first test dosage of metoprolol and twenty-two patients were excluded from analysis because of inadequate follow-up or because they were enrolled in an international trial. Forty-one patients underwent long-term treatment with metoprolol at a final mean dosage of 150 mg a day (range 50-200 mg) and are presently analyzed. The dosage was gradually increased during the first seven weeks. RESULTS. After 6 +/- 2 months and 12 +/- 2 months, 34 patients were stable or ameliorated (Group 1) and experienced an overall significant improvement of functional class (all pts in class I-II NYHA), of left and right ventricular ejection fraction (from 28 +/- 8.8% to 35.8 +/- 13.7% to 33.2 +/- 12.3% and from 38.6 +/- 11.8% to 42.4 +/- 5.8% to 45.2 +/- 12.2% respectively), of clinical signs of congestive heart failure, of cardiothoracic index, of left ventricular diameters and of arrhythmic pattern. Furthermore, the rate of ventricular couplets > 20/24h and of non-sustained ventricular tachycardia changed respectively from 46% and 54% to 4% and 21% at 12 +/- 2 months. None in Group 1 died nor is any waiting for heart transplantation. Eleven patients (Group 2) did not tolerate the drug acutely (4 pts) or deteriorated during the first 6 +/- 2 months (7 pts) of the treatment. In this group a worsening or an insignificant variation of all clinical and instrumental parameters was observed. During follow-up four patients of this group underwent heart transplantation (one died shortly after the operation because of infective complications), one died while waiting, two are currently waiting for heart transplantation, and three are still in heart failure (class III NYHA). No cases of sudden death occurred in any group of patients (15 pts with follow-up > 12 mo). CONCLUSIONS. Our uncontrolled study seems to confirm the beneficial effect of betablockers in a subgroup of patients with idiopathic dilated cardiomyopathy. The characterization of responders to this therapy is still undefined and will constitute the aim of future analyses.