IMPROVED EXERCISE HEMODYNAMIC STATUS IN DILATED CARDIOMYOPATHY AFTER BETA-ADRENERGIC-BLOCKADE TREATMENT

Objectives. This study was performed to investigate exercise hemodynamic status in a double-blind, placebo controlled trial and was a substudy in the Metoprolol in Dilated Cardiomyopathy Trial. Background. Previous open studies have shown beneficial effects on exercise hemodynamic status after beta-adrenergic blocking agent therapy in patients with congestive heart failure. Methods. The study included 41 patients with idiopathic dilated cardiomyopathy with ejection fraction < 0.40 (metoprolol, 20 patients; placebo, 21 patients) whose hemodynamic status was investigated at rest and during supine submaximal exercise, at baseline and after 6 and 12 months of treatment. Myocardial metabolism was evaluated in a subset of 19 patients. Results. Metoprolol-treated patients responded favorably, as expressed by improved exercise cardiac index ([mean +/- SD] placebo 4.8 +/- 1.6 to 4.7 +/- 1.8 liters/min per m(2), metoprolol 4.3 +/- 1.1 to 5.4 +/- 1.9 liters/min per m(2), p = 0.0001) and stroke work index (placebo 44 +/- 20 to 41 +/- 27 g.m/m(2), metoprolol 35 +/- 16 to 58 +/- 28 g.m/m(2), p < 0,0001). Exercise systolic arterial pressure increased (placebo 161 +/- 25 to 151 +/- 23 mm Hg, metoprolol 155 +/- 29 to 165 +/- 37 mm Hg, p = 0.0003) as well as exercise oxygen consumption index (placebo 463 +/- 194 to 474 +/- 232 ml/min per m(2), metoprolol 406 +/- 272 to 507 +/- 298 ml/min per m(2), p = 0.045). There was a significant increase in exercise duration in the metoprolol group (63 +/- 38 s) compared with the placebo group (-24 +/- 42 s) (p = 0.01). Net myocardial lactate extraction increased in the metoprolol group, suggesting less myocardial ischemia (placebo 17 +/- 22 to 9.5 +/- 6.4 mmol/min, metoprolol -32 +/- 100 to 42 + 45 mmol/min, p = 0.03). Peripheral levels of norepinephrine tended to decrease at rest and during exercise, whereas myocardial net spillover was unchanged. Conclusions. Metoprolol improved hemodynamic status in patients with dilated cardiomyopathy at rest and had a more pronounced effect during exercise. These positive effects were achieved along with improved or stable myocardial metabolic data.