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.

ABSTRACT

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 x s x 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 x s x cm(-5) (p < 0.001), pulmonary cardiac index from 3.0 (0.2) to 3.4 (0.3) l/min/m2 (p < 0.001), and effective cardiac index from 2.5 (0.2) to 2.7 (0.2) l/min/m2 (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/m2 (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/m2 (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.