The ACTIOBIO study aims to evaluate the prognostic value of Activin-A and FSTL3 in a large cohort of patients with precapillary pulmonary hypertension, including pulmonary arterial hypertension (Group 1), pulmonary hypertension associated with lung diseases (Group 3), and chronic thromboembolic pulmonary hypertension (Group 4).

In recent years, major advances have been achieved in understanding the cellular and molecular mechanisms underlying pulmonary arterial hypertension (PAH), a major subtype of precapillary PH. These discoveries have led to the development of novel therapeutic strategies, including agents targeting dysregulated pathways of the transforming growth factor beta (TGF-β) superfamily.

Parallel to therapeutic advances, risk stratification at diagnosis and during follow-up has become a cornerstone of PH management. Validated multidimensional tools now integrate clinical, exercise, biomarker, imaging, and hemodynamic parameters to estimate prognosis, guide initial treatment, and define therapeutic goals for follow-up. However, as new therapeutic targets emerge and influence disease trajectory, there is a growing need for novel biomarkers to refine these tools, making them less invasive and more accurate.

Beyond prognostic markers, identifying biomarkers that predict treatment response is essential to move toward precision medicine in PH. Such biomarkers would help tailor therapy to individual patient profiles and optimize long-term outcomes.

The main objective of this study is to analyze the prognostic value of Activin-A and Follistatin-like 3 (FSTL3) in a large cohort of patients with precapillary pulmonary hypertension, including pulmonary arterial hypertension (PAH, group 1), PH associated with lung disease (group 3), and chronic thromboembolic PH (group 4).

1. Male or female ≥ 18 years of age

2. Precapillary PH documented by right heart catheterization:

   • mean pulmonary arterial pressure (mPAP) > 20 mmHg,
   • pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg;
   • pulmonary vascular resistance (PVR) > 2 WU

3. Pulmonary arterial hypertension (group 1) or PH associated with lung disease (group 3) or chronic thromboembolic PH (group 4)

4. Patient registered in the French PH registry

5. Patient capable of understanding the study procedures

6. Affiliation to a social security regime (or exemption)