EFFECTS OF SHORT-TERM AND LONG-TERM CARVEDILOL ADMINISTRATION ON REST AND EXERCISE HEMODYNAMIC VARIABLES, EXERCISE CAPACITY AND CLINICAL CONDITIONS IN PATIENTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY

Objectives. The study evaluated the effects of short- and long-term administration of carvedilol in patients with idiopathic dilated cardiomyopathy. Background. Carvedilol is a beta-adrenergic blocking agent with vasodilator activity that might be well tolerated in patients with heart failure. Methods. Forty patients with idiopathic dilated cardiomyopathy treated with digoxin, furosemide and angiotensin-converting enzyme inhibitors were randomized in a double-blind manner to receive either placebo or carvedilol. Right heart hemodynamic variables were evaluated up to 8 h after short-term drug administration and, on the next day, during cardiopulmonary exercise testing before and 3 h after drug ingestion. Placebo or carvedilol was added to standard therapy, starting with a dose of 6.25 mg twice a day with weekly increments up to the maximum of 25 mg twice a day. Patients were reevaluated after 4 months by cardiopulmonary exercise testing and measurement of right heart hemodynamic variables 12 h after last drug ingestion and 3 h after drug readministration. Left ventricular ejection fraction and volume, measured by equilibrium radionuclide ventriculography, quality of life and submaximal exercise duration were assessed before and after long-term therapy. Results. Compared with placebo, carvedilol produced a short-term reduction in heart rate and pulmonary artery and pulmonary wedge pressures and, after long term administration, increased both rest and peak exercise cardiac, stroke volume and stroke work indexes, with a further reduction in right atrial, pulmonary artery and pulmonary wedge pressures. Long -term carvedilol administration also improved rest left ventricular ejection fraction (from 20 +/- 7% to 30 +/- 12%, p < 0.001), submaximal exercise capacity, quality of life and New York Heart Association functional class. No baseline variable was predictive of the response to therapy. Conclusions. Short-term carvedilol administration reduces heart rate and mean pulmonary artery and pulmonary wedge pressures, whereas it improves both long term rest and exercise left ventricular systolic function, reduces heart failure symptoms and improves submaximal exercise tolerance in patients with idiopathic cardiomyopathy.