Phosphodiesterase-5 inhibitor in Eisenmenger syndrome - A preliminary observational study

Background - Phosphodiesterase-5 inhibitors produce a significant decrease in pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension. We studied the effects of tadalafil, a phosphodiesterase-5 inhibitor, on short-term hemodynamics, tolerability, and efficacy over a 12-week period in patients of Eisenmenger syndrome having a pulmonary vascular pathology similar to idiopathic pulmonary arterial hypertension. Methods and Results - Sixteen symptomatic Eisenmenger syndrome patients (mean age, 25 +/- 8.9 years) were assessed hemodynamically at baseline and 90 minutes after a single dose of tadalafil (1 mg/kg body weight up to a maximum of 40 mg). The same dose was then continued daily for 12 weeks, and the patients were restudied. There was a significant decrease in mean pulmonary vascular resistance immediately (24.75 +/- 8.49 to 19.22 +/- 8.23 Woods units; P < 0.005) and at 12 weeks (19.22 +/- 8.23 to 17.02 +/- 6.19 Woods units; P = 0.03 versus 90 minutes). Thirteen of 16 patients (81.25%) showed a >= 20% decrease in pulmonary vascular resistance and were defined as responders. The mean systemic oxygen saturation improved significantly both immediately (84.34 +/- 5.47% to 87.39 +/- 4.34%; P < 0.005) and at 12 weeks (87.39 +/- 4.34% to 89.16 +/- 3.8%; P < 0.02 versus 90 minutes) without a significant change in systemic vascular resistance. None of the patients had a fall in systemic arterial pressure, worsening of systemic oxygen saturation, or any adverse reactions to the drug. The mean World Health Organization functional class improved from 2.31 +/- 0.47 to 1.25 +/- 0.44 (P < 0.0001), and the 6- minute walk distance improved from 344.56 +/- 119.06 to 387.56 +/- 117.18 m (P < 0.001). Conclusions - Preliminary evaluation of tadalafil has shown efficacy and safety in selected patients with Eisenmenger syndrome, warranting further investigation in this subgroup of patients.