Acute Hemodynamic Effects of Intravenous Sildenafil Citrate in Congestive Heart Failure: Comparison of Phosphodiesterase Type-3 and -5 Inhibition

Background

The reversibility of elevated pulmonary vascular resistance in heart failure bears an important relation to outcome after cardiac transplantation. The phosphodiesterase 3 (PDE3) and PDE5 inhibitors both increase levels of cyclic nucleotides in the vascular smooth muscle, causing vasodilatation. PDE3 inhibitors also have direct inotropic effects. We contrasted the acute hemodynamic responses to intravenous PDE3 and PDE5 inhibitors in patients with congestive cardiac failure to assess their relative suitability for reversibility testing in this setting.

Methods

Thirty patients undergoing assessment for cardiac transplantation underwent right heart catheterization. Patients were randomized to receive an intravenous bolus of milrinone (0.05 mg/kg) or sildenafil citrate at a high (0.43 mg/kg) or low dose (0.05 mg/kg).

Results

Differences between low- and high-dose sildenafil were not significant. Both agents caused similar reductions in systemic and pulmonary vascular resistance. Milrinone caused significantly greater reductions in pulmonary artery wedge and mean pulmonary artery pressure, and increases in heart rate. In all study groups, greater increases in cardiac index (>25%) were seen in patients with a higher pulmonary artery wedge pressure at baseline (29 ± 1 vs 20 ± 2 mm Hg; p < 0.001).

Conclusions

In end-stage congestive cardiac failure, intravenous milrinone and sildenafil both cause similar reductions in systemic and pulmonary vascular resistance; however, milrinone has more cardiac selective effects on left ventricular filling and heart rate. Both agents appear to have a suitable hemodynamic profile for testing of reversibility of secondary pulmonary hypertension in congestive cardiac failure. Larger studies are needed to confirm these results.