Correspondence
Sildenafil in Primary Pulmonary Hypertension
N Engl J Med 2000; 343:1342November 2, 2000
- Article
To the Editor:
A 21-year-old man presented with a three-year history of worsening dyspnea and a four-month history of being unable to walk more than 100 yards (90 m) without resting. Physical examination revealed signs of pulmonary hypertension. A chest radiograph showed the typical changes associated with primary pulmonary hypertension. An echocardiogram obtained at the time of admission showed marked right ventricular dilatation; the estimated pulmonary-artery systolic pressure was 120 mm Hg (resulting from tricuspid regurgitation identified on Doppler ultrasonography). Left ventricular systolic function was preserved.
Pulmonary-function tests showed only mild airflow limitation. A computed tomographic scan of the thorax showed massive dilatation of proximal and segmental pulmonary arteries. Cardiac catheterization showed a pulmonary-artery pressure of 128/81 mm Hg (mean, 97) and an aortic pressure of 126/90 mm Hg (mean, 103); there was no increase in oxygen saturation. The myocardial oxygen consumption was 15.2 ml per kilogram per minute (predicted value, 42.9) after seven minutes of exercise. No causes of secondary pulmonary hypertension were identified.
The patient declined treatment with a continuous infusion of epoprostenol and lung transplantation. Subsequently, treatment with sildenafil was begun at a dose of 50 mg once a day and was well tolerated. The dose was then adjusted until a maintenance dose of 100 mg five times per day was reached, and no side effects have been reported. The patient's only other medication was the anticoagulant warfarin.
On follow-up at three months, the patient's condition had improved dramatically, and he was able to perform one hour of regular aerobic exercise. The echocardiogram showed an estimated pulmonary-artery systolic pressure of 90 mm Hg. The myocardial oxygen consumption was 20.3 ml per kilogram per minute after 12 minutes of exercise. An assay of cyclic guanosine monophosphate (cGMP) showed a level of 183 nmol per millimole of creatinine (normal level, less than 51)1 before treatment and a level of 33.5 nmol per millimole of creatinine at follow-up during treatment.
We propose that oral sildenafil may be beneficial as a selective pulmonary vasodilator in patients with primary pulmonary hypertension. A recent study in children suggested a potential role for sildenafil in the management of pulmonary hypertension.2,3 Sildenafil may preferentially inhibit cGMP-specific phosphodiesterase, which is abundant in lung tissue4; this possibility needs to be evaluated prospectively.
4 ReferencesSanjay Prasad, M.R.C.P.
James Wilkinson, M.R.C.P.
Michael A. Gatzoulis, M.D., Ph.D.
Royal Brompton Hospital, London SW3 6NP, United Kingdom1
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Atz AM ,Wessel DL . Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology 1999;91:307-310
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Abrams D ,Schulze-Neick I ,Magee AG . Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Heart 2000;84:e4-e4
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Sanchez LS ,de la Monte SM ,Filippov G ,Jones RC ,Zapol WM ,Bloch KD . Cyclic-GMP-binding, cyclic-GMP-specific phosphodiesterase (PDE5) gene expression is regulated during rat pulmonary development. Pediatr Res 1998;43:163-168
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