Acute and short-term haemodynamic effect of Sildenafil in pulmonary hypertension: Egyptian pilot study of seven patients

Pulmonary hypertension (PH) patients usually present with heart failure, limited exercise tolerance and limited life expectancy. Vasodilators might cause a deterioration in gas exchange. There have been isolated case reports where oral Sildenafil, a selective phosphodiestrase inhibitor (PDEI), has been used as an alternative to prostacyclin in primary PH with early success. Our aim was to assess acute and short-term effect of Sildenafil in patients with PH with different etiologies.

Seven patients have been studied (four female, three male; mean age 49 ± 12 years). They included two patients with primary PH, two patients with Eisinmenger syndrome, two patients with thromboembolic PH and one patient with Bilharzial PH. Following clinical evaluation, all patients were subjected to Swan–Ganz catheterization and the mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and mixed venous oxygen saturation (mVO₂) were invasively measured. Patients were also subjected to echocardiographic evaluation of the right ventricular diameter (RVD) in the short axis, of the left ventricular stroke volume (SV) and of the cardiac output (COP). Readings were recorded before, 3 days and 3 months after the start of Sildenafil. We used oral Sildenafil (25 mg) every 6 hours for all patients.

Results

Out of the seven patients, five showed significant clinical (New York Heart Association [NYHA] class IV to NYHA class III), hemodynamic and echocardiographic improvement 3 days after therapy. The five patients included two patients with primary PH, one patient with Eisenmenger syndrome, one with Bilharzial PH and one thromboembolic patirnt. The latter patients showed significant reduction of mPAP (107 to 73 mmHg, -32%, P < 0.01), mPVR (1988 to 1177 dynes/s/cm⁵, -41%; P < 0.01) with insignificant rise in mVO₂ (48 to 53 Torr). All hemodynamic changes occurred without significant reduction of arterial blood pressure and SVR. Echocardiography showed insignificant mild reduction in RVD (6.6 to 6.4 cm) with a significant rise in SV (35 to 42 ml), and COP (3.7 to 4.2 l/min). Follow-up 3 months later showed improvement in four out of the latter five patients. The fifth patient is the Bilharzial PH one who died suddenly 5 days after discharge. The other four patients showed further subjective improvement (NYHA class III to II), reduction of mPAP (73 to 57 mmHg, -22%; P < 0.05), mean PVR (1177 to 759 dynes/s/cm⁵, -36%; P < 0.05) with a further rise in mVO₂ (53 to 60 Torr). Echocardiography also showed a significant reduction of the RVD (6.4 to 5.6 cm) with a further rise in SV (42 to 48 ml) and COP (4.2 to 4.7 l/min, P < 0.01).

Conclusions

(1) Sildenafil proved to be effective in the acute and short-term condition, subjectively and objectively, especially in patients with primary PH. Yet, the long-term effect and 5-year mortality are to be evaluated. (2) The effect of Sildenafil on Bilharzial PH is guarded. A larger group of Bilharzial PH patients should be studied, especially the milder forms. (3) Sildenafil and other selective PDE5 inhibitors with improved selectivity and longer half-life merit further evaluation.