Can Intravenous β-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 in the past have shown the long-term beneficial effects of β-blockers in congestive heart failure. Despite the interest in this mode of therapy, their clinical application has been limited due to their negative inotropic effect. A subset of the heart failure patients do not show any improvements with standard β-blocker therapy. Carvedilol, a new, non-selective β-blocking agent with concurrent α-blocking properties, was evaluated in 17 patients with chronic heart failure secondary to ischaemic heart disease. All had resting left ventricular ejection fraction ≤45% and were maintained on diuretic therapy. Acute haemodynamic measurements were made after intravenous carvedilol (2.5–7.5 mg) and also after chronic therapy for 8 weeks (carvedilol 12.5–50 mg b.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 Twelve patients completed the study and 5 were withdrawn. Symptomatic and haemodynamic improvement was demonstrated in 11 of the 12 patients after 8 weeks of therapy. Mean±standard error systolic intraarterial blood pressure (133 ± 6 to 114 ± 5 mmHg, P <0.005), heart rate (81 ± 3 to 61 ± 1 beats/min, P <0.0001), pulmonary artery wedge pressure (19 ± 2 to 12 ± 1 mmHg, P <0.001) and systemic vascular resistance (1748 ± 115 to 1497 ± 89 dynes/ s/cm5/m2, P < 0.02) were reduced with an increase in mean ± SE of stroke volume index (31 ± 1.8 to 40 ± 1.6 ml/m2/beat, P < 0.0005) and left ventricular ejection fraction (25 ± 3 % to 32 ± 3 %, P < 0.01) after 8 weeks of therapy with carvedilol. This is in contrast to the acute haemodynamic effects of carvedilol, which only showed a reduction in heart rate (81 ± 3 to 74 ± 3 beats/min, P < 0.0001), systolic intra-arterial blood pressure (133 ± 6 to 117 ±6 mmHg, P < 0.0005) and pulmonary artery wedge pressure (19 ± 2 to 14 ± 2 mmHg, P < 0.002) at 10 min post-injection. The 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, which is maintained after chronic treatment. This property is clearly beneficial for chronic heart failure patients and differs from standard β-blockers. The discrepancy of the haemodynamic changes between the acute and chronic long-term response to carvedilol lends further support to the concept of upregulation of β-adrenoceptors in cognestive heart failure.