Influence of age in the assessment of therapeutic response in patients with pulmonary arterial hypertension

Background In patients with pulmonary arterial hypertension (PAH), current European guidelines recommend achieving a low-risk profile, primarily based on World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD) and natriuretic peptides. However, these noninvasive parameters are influenced by age. We investigated the impact of age on treatment response and evaluated the prognostic role of haemodynamic-based risk assessments. Methods Treatment-naïve PAH patients from a single-centre registry were included, stratified by age. Clinical and functional measures and haemodynamics were assessed at baseline and after initial PAH-targeted therapy. Prognostic discrimination was performed using noninvasive (European Society of Cardiology/European Respiratory Society 4-strata, REVEAL Lite 2) and haemodynamic-based risk models (including a purely haemodynamic-RHC-risk tool) with Cox regression and C-statistics. Results 794 PAH patients were enrolled. Elderly individuals exhibited worse WHO-FC, higher levels of natriuretic peptides and shorter 6MWD, despite lower right ventricular (RV) afterload, likely due to comorbidities and worse RV function. Improvement of WHO-FC, levels of natriuretic peptides and 6MWD is lower in the elderly, despite comparable haemodynamic changes across the age groups. In older patients, noninvasive risk tools overestimated RHC risk tool severity and demonstrated a reduced prognostic accuracy. In patients aged >65 years reaching a low-risk haemodynamic profile, noninvasive risk tools were of no added prognostic value. Conversely, haemodynamics provided independent prognostic information in younger patients. Conclusions Haemodynamics is less influenced by age than noninvasive risk assessment and is of added prognostic value to noninvasive assessment in younger patients. Achieving a low-risk haemodynamic profile can be a valid therapeutic target when noninvasive criteria are not met in patients aged >65 years.