Sildenafil is as effective in secondary as in primary pulmonary hypertension: impact on acute and short term haemodynamics

ABSTRACT

Patients with pulmonary hypertension [PH] usually present with limited exercise tolerance, heart failure, and diminished life expectancy. Vasodilators might cause hypotension and deterioration in gas exchange. Sildenafil, a selective phosphodiestrase inhibitor [PDEI-type 5] has been used as an alternative to prostacyclin and nitric oxide in primary PH with reports of early success. Our aim was to assess the acute and short term effects of Sildenafil in patients [pts] with pulmonary hypertension due to different etiologies. Ten pts have been studied [7 females, 3 males, mean age 37 +/- 10 y, range=23-56ys.]. They included 4 pts with primary PH, 2 with Eisenmenger syndrome, 2 with thromboembolic and 2 with Bilharzial PH. Following clinical evaluation and functional class assessment [NYHA], all pts were subjected to Swan-Ganz catheterization whereby mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR] and mixed venous oxygen saturation [mVo2] were invasively measured. Echocardiography where right ventricular diameter [RVD] in short axis view, left ventricular stroke volume [SV] and cardiac output [COP] were evaluated. Readings were recorded before, 3 days and 3 months after start of oral Sildenafil therapy [25 mg 6 hourly] for all pts. Out of the 10 pts, 8 [including 3 with PPH] showed significant clinical, hemodynamic and echocardiographic improvement 3 days after therapy. Two pts failed to show improvement [one primary and one Eisenmenger PH]. The former 8 pts showed improvement of NYHA class [from IV to III], a substantial reduction of mPAP [95 to 76 mmHg, p<0.01] of mean PVR [1797 to 1128 dynes. sec cm-5, p<0.01] with insignificant rise in mVo2 [53 to 57 Torr]. All hemodynamic changes occurred without change of arterial BP or heart rate. Echocardiography showed insignificant mild reduction in mean RVD [6.6 to 6.4 cm] with marginally significant rise in SV [44 to 51 Ml, p<0.05], and COP [3.7 to 3.9 L/min, P < 0.01]. Follow up three months later showed sustained improvement in 7 out of the latter 8 pts [one Bilharzial pt died suddenly after discharge] clinically [NYHA-III to II], further reduction of mPAP [from 77 to 67 mmHg, p<0.05], mean PVR [from 1128 to 958 dynes sec. cm -5, p<0.01] with further rise in mVo2 [from 57 to 61 Torr, P<.01]. Echocardiography showed continued significant reduction of the RVD to 4.1 cm [P<0.01] with further rise in SV to 56 ml [P<0.05], and COP to 4.1 L/min [P < 0.01]. 1] Sildenafil proved to be effective in the acute and short term conditions both subjectively and objectively and in both primary and secondary PH. 2] In Bilharzial PH, sildenafil looks promising, however larger number of Bilharzial PH pts should be studied.3] Sildenafil and other selective PDE5 inhibitors with improved selectivity and longer half-lives merit further therapeutic studies in pulmonary hypertension