Treatment of right heart failure on pulmonary arterial hypertension: is going left a step in the right direction?

Abstract

Until in the early 1990s, pulmonary arterial hypertension (PAH) was consistently fatal, with a median life expectancy of ∼2.5 yrs. Uncontrolled studies showed that a small proportion of patients responded to high-dose calcium channel blockers and retrospective studies supported the use of anticoagulants, with heart-lung or lung transplantation remaining the only option. Since then, there has been remarkable progress with the introduction of targeted therapies based on the administration of prostacyclins, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. However, the disease has remained incurable and median survival is still limited to ∼5–6 yrs, with insufficient functional improvement in many of the survivors [1]. Thus, there is room for innovative thinking. This is precisely what Handoko et al. [2] have done in the current issue of the European Respiratory Review . Taking a refreshing physiological point of view, the authors acknowledge that advanced stage P(A)H symptomatology and prognosis is essentially determined by the state of the right ventricle, and that, contrary to prevailing belief, currently prescribed targeted therapies do not act on the right ventricle. As a result, Handoko et al. [2] have come forward with proposals derived from the treatment of left heart failure, including cautious but decisive use of β-blocker therapies and, in selected cases, resynchronisation therapy. 50 years ago, Wood [3] proposed the “vasoconstrictive factor” as the primum movens of severe pulmonary hypertension. The idea was inspired by observations of transient decrease in pulmonary vascular resistance following injection of acetylcholine [3] or tolazaline [4] directly into the pulmonary artery, and reversal of the disease after surgical correction of left-to-right cardiac shunts when lung biopsies showed only pulmonary arteriolar medial hypertrophy [5]. Heath et al. [5] and Wagenvoort [6] …