CAN INTRAVENOUS BETA-BLOCKADE PREDICT LONG-TERM HEMODYNAMIC BENEFIT IN CHRONIC CONGESTIVE-HEART-FAILURE SECONDARY TO ISCHEMIC-HEART-DISEASE - A COMPARISON OF INTRAVENOUS WITH ORAL CARVEDILOL

Several studies have demonstrated the long-term beneficial effects of beta-blockers in the treatment of congestive heart failure. Despite interest in this mode of therapy, clinical application of beta-blockers has been limited due to their negative inotropic effect. A subset of the heart failure patients do not show improvements with standard beta-blocker therapy. Carvedilol, a new nonselective beta-blocking agent with concurrent alpha-blocking properties, was evaluated in 17 patients with chronic heart failure secondary to ischemic heart disease. All had resting left ventricular ejection fraction less-than-or-equal-to 45% and were maintained on diuretic therapy. Acute hemodynamic measurements were made after administration of intravenous carvedilol (2.5-7.5 mg) and after chronic therapy for 8 weeks (12.5 to 50 mg b.i.d.). Radionuclide ventriculography, ambulatory intra-arterial blood pressure monitoring, and right heart catheterization were performed before and after 8 weeks of chronic therapy. Twelve patients completed the study (five were withdrawn). Symptomatic and hemodynamic improvements were demonstrated in 11 of the 12 patients after 8 weeks of therapy. Mean +/- SD systolic intra-arterial blood pressure (133 +/- 20 to 114 +/- 17 mm Hg, p < 0.005), heart rate (81 +/- 11 to 61 +/- 5 beats/min, p < 0.0001), pulmonary artery wedge pressure (19 +/- 7 to 12 +/- 5 mm Hg, p < 0.001), and systemic vascular resistance (1,748 +/- 398 to 1,497 +/- 310 dynes/s/cm-5/m2, p < 0.02) decreased and mean +/- SD stroke volume index (31 +/- 6 to 40 +/- 6 ml/m2/beat, p < 0.0005) and left ventricular ejection fraction (25 +/- 9% to 32 +/-10%, p < 0.01) increased after 8 weeks of therapy with carvedilol. This contrasts with the acute hemodynamic effects of carvedilol. which showed reductions in heart rate (81 +/- 11 to 74 +/- 10 beats/min, p < 0.0001), systolic intra-arterial blood pressure (133 +/- 20 to 117 +/- 22 mm Hg, p < 0.0005), and pulmonary artery wedge pressure (19 +/- 7 to 14 +/- 6 mm Hg, p < 0.002) 10 min after injection. Systemic vascular resistance, left ventricular ejection fraction, and stroke volume index failed to show any significant improvement. Thus, intravenous carvedilol produces a reduction in filling pressure that is maintained after chronic treatment. This effect is clearly beneficial for chronic heart failure patients and differs from that of standard beta-blockers. The discrepancy of hemodynamic changes for acute and chronic long-term responses to carvedilol lends further support to the concept of upregulation of beta-adrenoceptors in congestive heart failure.