Acute endothelin A receptor antagonism improves pulmonary and systemic haemodynamics in patients with pulmonary arterial hypertension that is primary or autoimmune and related to congenital heart disease

Objective: To evaluate the acute haemodynamic effect of BQ-123, a selective endothelin A receptor antagonist, in severe chronic pulmonary arterial hypertension (PAH) of primary or autoimmune origin or related to congenital heart disease. Design: Prospective open clinical study. Setting: Cardiology tertiary referral centre. Patients: 26 patients with chronic PAH were studied, with mean (SEM) age 29 (3) years (range 4-71 years), mean pulmonary artery pressure 68 (4) mm Hg, and pulmonary vascular resistance index 1694 (170) dyne.s.cm(-5). Patients were divided in three groups according to PAH aetiology: primary or autoimmune PAH (n=12), and PAH associated with congenital heart defects with (n=6) or without (n=8) complete mixing. Intervention: BQ-123 200 nmol/min was infused for 60 minutes in the right atrium with sequential haemodynamic measurements at 30 minute intervals. Results: BQ-123 improved mean pulmonary artery pressure from 68 (4) to 64 (4) mm Hg (p<0.05), pulmonary vascular resistance index from 1694 (170) to 1378 (145) dyne.s.cm(-5) (p<0.001), pulmonary cardiac index from 3.0 (0.2) to 3.4 (0.3) l/min/m(2) (p<0.001), and effective cardiac index from 2.5 (0.2) to 2.7 (0.2) l/min/m(2) (p<0.01). Haemodynamic response was similar in all groups except for systemic cardiac index where a different (p=0.0001, F=5.53) response was observed; systemic cardiac index increased from 2.7 (0.2) to 2.9 (0.2) l/min/m(2) (p<0.001) when patients with complete mixing were excluded, in whom systemic cardiac index tended to decrease from 3.4 (1.0) to 3.0 (0.6) l/min/m(2) (p=0.06). Conclusions: Acute endothelin A receptor antagonism induces substantial haemodynamic improvement in severe chronic PAH of primary or autoimmune origin or related to congenital heart disease.