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.

Figure 1

Haemodynamic effects over time of BQ-123 administration in the total patient cohort. The three groups responded similarly in all haemodynamic variables except for the systemic cardiac index. Numbers in parentheses indicate mean values. mAoP, mean aortic pressure; mPAP, mean pulmonary artery pressure; NS, non-significant; PVRI, pulmonary vascular resistance index; Qeff, effective cardiac index; Qp, pulmonary cardiac index; Qs, systemic cardiac index; RAP, right atrial pressure; SVRI, systemic vascular resistance index. *p < 0.05 v baseline; **p < 0.01 v baseline; ***p < 0.001 v baseline.

Figure 2

Haemodynamic effect over time of BQ-123 administration on the systemic cardiac index, showing differential effects in the three studied groups.*p<0.05 v baseline.

Figure 3

Effect over time of BQ-123 administration on pulmonary to aorta (PA/Ao) endothelin 1 (ET-1) concentration ratio in the total cohort, as well as with the exclusion of patients with complete mixing. *p < 0.05 v baseline.