The quest for biomarker discovery in pulmonary arterial hypertension: the right takes lessons from the left

Pulmonary arterial hypertension (PAH) is a severe form of cardiopulmonary disease that is characterised by plexogenic, hypertrophic and fibrotic remodelling of distal pulmonary arterioles. Although abnormal pulmonary vasoreactivity and increased vasoconstriction occur in the setting of these maladaptive changes to blood vessel phenotype, the 5-year mortality rate for PAH remains elevated even in the contemporary era of pulmonary vasodilator therapy.1 An obvious approach to address this is the development of novel therapeutics that target the pathogenesis of vascular remodelling. However, accumulating clinical trial data also suggest that treatment timing and drug class selection when based on clinical status2 and disease subtype,3 respectively, are important factors for optimising therapeutic efficacy and reducing PAH clinical events. Nonetheless, point-of-care risk stratification methods to guide initiation or escalation of treatment in PAH are limited currently to elaborate scoring systems that require invasive haemodynamic data, or metrics such as changes in 6-min walk distance and functional class that hinge on subjective assessment or are of controversial utility in clinical practice.4 This dilemma illustrates a critical, but incompletely met, need in the field of clinical pulmonary vascular disease: the identification …