Background/Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease, in which multiple genetic and environmental factors may contribute. This study aimed to identify potential genetic determinants in patients with CTEPH and to compare their occurrence to a control group, which included patients with pulmonary embolism who had not developed CTEPH. Methods: Tier 1 and 2 genes related to coagulation, fibrinolysis and platelet disorders—as recommended by the International Society on Thrombosis and Haemostasis—and genes associated with vascular conditions were analyzed in n = 15 patients with CTEPH and n = 17 controls using next-generation sequencing. Non-synonymous, rare variants were collected and interpreted. Results: As expected, no single gene or variant was consistently present among CTEPH patients. Instead, individuals carried different mutations and combinations of variants. We identified several variants that were not found in the control group. Candidate variants were detected in F12, F13A1, F13B, F5, KNG1, SERPIND1, THBD, ADAMTS13, VWF, STIM1, ETV6, THPO, MPL, SERPINA1, ENG, RASA1, ACVRL1, GDF2, NFE2, SOX17 and RNF213. We did not detect exclusive variants in FGA, CPB2, and BMPR2 although they were suggested as candidates in previous studies. Elevated factor VIII and von Willebrand factor in CTEPH could not be explained by mutations in VWF and F8. Conclusions: Our study supports the hypothesis of heterogeneous genetic background in CTEPH, involving multiple pathways such as coagulation, altered fibrinolysis and impaired angiogenesis. These results provide a basis for more detailed investigations into specific genes and variants potentially associated with CTEPH in larger cohorts.

Background/Objectives:: Right ventricular (RV) pressure assessment is crucial in both the diagnosis and follow-up of patients with chronic thromboembolic pulmonary hypertension (CTEPH). While right heart catheterization (RHC) and pulmonary angiography (PA) are gold-standard invasive methods, transthoracic echocardiography (TTE) offers a safer and more accessible alternative. This study aimed to evaluate the reliability of echocardiographic RV pressure estimation compared to invasive techniques and to identify clinical predictors of response to balloon pulmonary angioplasty (BPA). Methods: In this prospective study, 17 patients with confirmed CTEPH underwent RV pressure assessment via TTE, RHC (Swan-Ganz catheterization), and PA within the same hospitalization period. BPA responders were defined based on clinical improvement and were compared to poor responders using pre- and post-treatment parameters. Results: A strong correlation was found between Swan-Ganz and PA-derived pressures (r = 0.96), with a slightly lower correlation between TTE and PA (r = 0.84), and the lowest between TTE and Swan-Ganz (r = 0.78). In the well-responding group, the 6 min walk distance (6MWD) increased by 60 ± 18 m, compared to 12 ± 10 m in poor responders (p < 0.01). NT-proBNP levels decreased by 40% in responders versus 10% in non-responders (p < 0.01). TAPSE improved significantly in responders (from 16.0 ± 2.0 mm to 19.5 ± 2.5 mm, p < 0.01), while RV basal diameter decreased by 15% (p < 0.05). No significant echocardiographic improvement was observed in poor responders. Conclusions: TTE provides a reliable estimate of RV pressure in CTEPH when standardized protocols are followed. NT-proBNP levels and RV size may serve as useful predictors of BPA response.