Bosentan in pulmonary hypertension secondary to left heart failure

ABSTRACT

Background: Pulmonary hypertension (PH) secondary to left ventricular failure not only predicts a poor clinical outcome, but also excludes patients from orthotopic heart transplantation (HTX). Recent clinical and laboratory findings indicate comparable pathophysiological mechanisms in PH secondary to left ventricular dysfunction and pulmonary arterial hypertension (PAH), a clinical situation in which endothelin (ET)-1 is an established key pathogenetic mediator. In addition to ET-1-mediated constriction and remodelling of the pulmonary vasculature, ET-1 further contributes to cardiac hypertrophy and aldosterone secretion in left heart failure (HF).

Results: Initial results with the oral, dual ET receptor antagonist bosentan in patients with advanced left HF and secondary PH (presented herein as two case studies of patients with Class III and IV HF and a case series of 19 patients with PH secondary to left HF of different aetiologies) has shown promising results: cardiopulmonary haemodynamics improved significantly with a concomitant clinical stabilization.

Conclusion: As illustrated by these initial results, bosentan may expand the therapeutic arsenal in PH secondary to left ventricular dysfunction and may not only help to bridge the time to HTX, but may also allow the improvement of cardiopulmonary haemodynamics and thus listing of patients that would be otherwise excluded from HTX.

Key words: :

• Bosentan
• Endothelin
• Left ventricular failure
• Pulmonary hypertension