Efficacy and Safety of Riociguat in Incipient Pulmonary Vascular Disease as an Indicator for Early PAH

Inclusion Criteria: 1. ≥18 years of age at time of inclusion. 2. Male and female patients with early pulmonary vascular disease, defined as either a) mean pulmonary arterial pressure (mPAP) ≥25 mmHg with pulmonary vascular resistance (PVR) ≥2 to \<3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg or b) mPAP 21-\<25 mmHg with PVR ≥2 WU, and PAWP ≤15 mmHg associated with connective tissue disease (CTD) or as idiopathic/heritable form (see Group I / Nice Clinical Classification of Pulmonary Hypertension) (acc. to Simonneau et al. 2019). Patients with rheumatoid arthritis or connective tissue disease of any kind, except systemic lupus erythematosus, may also be included. Patients in group b will be mainly enrolled as long as patients in group a are not defined as having pulmonary arterial hypertension according to European pulmonary hypertension guidelines. 3. Treatment naïve patients (with respect to PAH specific medication) 4. Unspecific treatments which may also be used for the treatment of pulmonary hypertension such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. Permitted are also treatments of the rheumatologic disease. However, these drugs must have been started at least 1 month before right heart catheterization. 5. Right-heart catheterization results must not be older than 1 month at Visit 1 (will be considered as baseline values, the time frame can be prolonged up to 6 months, if the patient has had no signs of clinical changes defined as \>10% change of 6MWD, WHO FC, \> 30% change in NT-proBNP) and must have been measured in the participating center under standardized conditions (refer to the study specific Swan Ganz catheterization manual). If the respective measurements have not been performed in context with the patient's regular diagnostic work up, they have to be performed as a part of the study during the pre-study phase (after the patient signed the informed consent). 6. Women without childbearing potential defined as postmenopausal women aged 55 years or older, women with bilateral tubal ligation, women with bilateral ovariectomy, and women with hysterectomy can be included in the study. 7. Women of childbearing potential can only be included in the study if all of the following applies (listed below): 1. Negative serum pregnancy test at screening and at study start (visit 1). 2. Agreement to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation. These tests should be performed by the patient at home. 3. Agreement to use a highly effective contraception method as specified from screening until at least 30 days after last dose of study medication. 8. Patients who are able to understand and follow instructions and who are able to participate in the study for the entire period. 9. Patients must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures. Exclusion Criteria: 1. Patients with systemic lupus erythematosus. 2. Concomitant PAH-targeted treatment is not allowed during the study. 3. Concomitant treatment with phosphodiesterase 5 inhibitors, endothelin receptor antagonists and prostacyclin analogues due to digital ulcers is contraindicated and must not be taken during the study period. Such drugs must have a washout-phase of 3 days at the time of right heart catheterization at screening. Intravenous treatment with prostacyclin analogues should not be performed within 1 week of right heart catheterization. Any decision to discontinue above-mentioned drugs will be made by the clinicians and the patient at screening, which takes part during the patients' regular routine visit. The discontinuation of above-mentioned drugs will be evaluated by considering the presence or absence of digital ulcers and their frequency of appearance in the patient's medical history. 4. Pulmonary hypertension explained by other cause including group 2, 3, 4 and 5 PH according to the current guidelines. 5. Cardiac comorbidity, defined with three or more of the following conditions: uncontrolled arterial hypertension, diabetes mellitus, body mass index \>35, left atrial enlargement \>20 cm², atrial fibrillation, left ventricular ejection fraction \<50%. 6. Pulmonary comorbidity, defined as forced vital capacity (FVC) ≤70; forced expiratory volume in 1 second (FEV1) ≤50%; diffusion capacity of the lung (DLCO) ≤40%. FVC may be \<70/ if high resolution computed tomography shows \<20% lung fibrosis. 7. Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator. 8. Patients with underlying medical disorders with an anticipated life expectancy below 2 years (e.g. active cancer disease with localized and/or metastasized tumor mass). 9. Patients with a history of severe or multiple drug allergies (defined as allergic reactions to three or more structurally unrelated drugs). 10. Patients with hypersensitivity to the investigational drug or any of the excipients. 11. Contraindications according to summary of product characteristics of riociguat (e.g. arterial hypotension with systolic blood pressure \<95 mmHg; nitrates) 12. Participation in any clinical drug trial within 4 weeks prior to screening of this study and/or patient, who is scheduled to receive an investigational medicinal product (IMP) during the course of this study 13. Background therapy with highly anti-fibrotic drugs (pirfenidone) or nintedanib, prednisolone \>10 mg/day