Treatment of Pulmonary Hypertension in the Current Era

Case

ND is a 19-year-old woman with Down syndrome, a nonrestrictive ventricular septal defect, and Eisenmenger syndrome.  She has begun to “slow down” and appear more short of breath with exertion.  Her arterial oxygen saturation is 75% and hemoglobin and hematocrit 22.1 and 65% respectively.  How should we treat this patient?

Background

Patients with a VSD and secondary Eisenmenger syndrome have systemic level right ventricular and pulmonary hypertension as well as right-to-left shunt and erythrocytosis.  In fact, the VSD of patients with Eisenmenger syndrome are always nonrestrictive.  That is, there is no pressure difference in the right and left ventricles.  The pressure in both chambers is equal throughout life as is the systolic pressure in the aorta and pulmonary artery.  Severe pulmonary hypertension is present from life.  Because of this hemodynamic anomaly, right ventricular function is typically preserved in patients with Eisenmenger syndrome despite systemic level pulmonary artery pressure.  The preservation of right ventricular function in the setting of pulmonary hypertension is unique to patients with Eisenmenger syndrome.  Our patient is primarily short of breath because of hypoxia secondary to right-to-left shunting.  She is not short of breath because of heart failure.  How can we treat her?

Treatment

There are now some new options for the treatment of severe pulmonary hypertension.  Intravenous epoprostenol (Flolan) is an option to reduce her pulmonary vascular resistance and right-to-left shunt.  However, it requires a central catheter and continuous intravenous infusion 24 hours per day.  The central catheter carries a risk of thrombus and paradoxic embolization in patients with VSD Eisenmenger syndrome.  We elected to treat her with oral bosentan (Tracleer), a nonpeptide inhibitor of the endothelin A and B receptors, and subcutaneous treprostinil,(UT-15, Remodulin), a more stable analog of prostacyclin than epoprostenol.  Remodulin requires 24 hour per day subcutaneous administartion but only has to be mixed every third day.  The risk of an indwelling catheter is eliminated.

Outcome 

After 5-6 months of therapy she feels better.  As proof of improved oxygenation her arterial oxygen saturation has increased to 83-84%, and her hemoglobin and hematocrit have decreased to 18.1 and 56% respectively.