Risk stratification has gained an increasing role in predicting outcomes and guiding the treatment of patients with pulmonary arterial hypertension (PAH). The most predictive prognostic factors are three noninvasive parameters (World Health Organization functional class, 6-min walk distance and natriuretic peptides) that are included in all currently validated risk stratification tools. However, suffering from limitations mainly related to reduced specificity of PAH severity, these variables may not always be adequate in isolation for guiding individualised treatment decisions. Moreover, with effective combination treatment regimens and emerging PAH therapies, markers associated with pulmonary vascular remodelling are expected to become of increasing relevance in guiding the treatment of patients with PAH. While reaching a low mortality risk, assessed with a validated risk tool, remains an important treatment goal, preliminary data suggest that invasive haemodynamics and cardiac imaging may add incremental value in guiding treatment decisions.

Pulmonary arterial hypertension is a severe disease with a complex pathogenesis, for which combination therapy is an attractive option.This study aimed to assess the impact of sequential combination therapy on both short-term responses and long-term outcomes in a real-world setting.Patients with idiopathic/heritable pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease or connective tissue disease and who were not meeting treatment goals on either first-line bosentan or sildenafil monotherapy, were given additional sildenafil or bosentan and assessed after 3–4 months. Double combination therapy significantly improved clinical and haemodynamic parameters, independent of aetiology or the order of drug administration. Significant improvements in functional class were observed in patients with idiopathic/heritable pulmonary arterial hypertension. The 1-, 3- and 5-year overall survival estimates were 91%, 69% and 59%, respectively. Patients with pulmonary arterial hypertension associated with connective tissue disease had significantly poorer survival rates compared to other aetiologies (p<0.003).The favourable short-term haemodynamic results and good survival rates, observed in patients receiving both bosentan and sildenafil, supports the use of sequential combination therapy in patients failing on monotherapy in a real-world setting.

Background: Haemodynamic variables like right atrial pressure (RAP), cardiac index (CI), stroke volume index (SVI) and mixed venous oxygen saturation (SvO₂) predict survival in patients with pulmonary arterial hypertension (PAH). However, there is the need to identify further prognostic haemodynamic parameters as well as to redefine their role in PAH risk stratification compared to current risk tools and non-invasive parameters.Methods: This cohort study includes treatment-naïve patients assessed at baseline and after first-line PAH therapy with clinical, functional, exercise, laboratory and haemodynamic evaluations. Using a stepwise multivariate Cox regression analysis, independent prognostic haemodynamic parameters were identified and stratified according to cut-offs already defined in the European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk table or defined based on the highest Chi-squared of the log-rank test. Their discriminatory power was tested for all-cause death and a combined end-point of death, hospitalisation and need of treatment escalation.Results: 794 patients with PAH were enrolled. At first follow-up, RAP and pulmonary artery elastance were independently associated with death. Because of high correlations between haemodynamic parameters, different multivariable analyses were done identifying six other variables (pulmonary arterial compliance, cardiac efficiency, pulmonary vascular resistance,SvO₂, CI and SVI). Haemodynamic parameters were of no added prognostic value compared to ESC/ERS risk tools for the all-cause death end-point but they showed additional value to non-invasive parameters for the combined end-point and, when taken alone, had a discriminatory capacity comparable to ESC/ERS risk tools.Conclusion: Haemodynamics’ discriminative ability for clinical worsening is comparable to current ESC/ERS risk tools and is of added value to non-invasive parameters.