EFFECTS OF SHORT-TERM AND LONG-TERM CARVEDILOL ADMINISTRATION ON RESTAND 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 ad ministration of carvedilol in patients with idiopathic dilated cardiom yopathy. Background. Carvedilol is a beta-adrenergic blocking agent wi th vasodilator activity that might be well tolerated in patients with heart failure. Methods. Forty patients with idiopathic dilated cardiom yopathy treated with digoxin, furosemide and angiotensin-converting en zyme inhibitors were randomized in a double-blind manner to receive ei ther placebo or carvedilol. Right heart hemodynamic variables were eva luated up to 8 h after short-term drug administration and, on the next day, during cardiopulmonary exercise testing before and 3 h after dru g ingestion. Placebo or carvedilol was added to standard therapy, star ting with a dose of 6.25 mg twice a day with weekly increments up to t he maximum of 25 mg twice a day. Patients were reevaluated after 4 mon ths by cardiopulmonary exercise testing and measurement of right heart hemodynamic variables 12 h after last drug ingestion and 3 h after dr ug readministration. Left ventricular ejection fraction and volume, me asured by equilibrium radionuclide ventriculography, quality of life a nd submaximal exercise duration were assessed before and after long-te rm therapy. Results. Compared with placebo, carvedilol produced a shor t-term reduction in heart rate and pulmonary artery and pulmonary wedg e pressures and, after long term administration, increased both rest a nd peak exercise cardiac, stroke volume and stroke work indexes, with a further reduction in right atrial, pulmonary artery and pulmonary we dge 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 He art Association functional class. No baseline variable was predictive of the response to therapy. Conclusions. Short-term carvedilol adminis tration reduces heart rate and mean pulmonary artery and pulmonary wed ge pressures, whereas it improves both long term rest and exercise lef t ventricular systolic function, reduces heart failure symptoms and im proves submaximal exercise tolerance in patients with idiopathic cardi omyopathy.