Effectiveness of PAH-specific treatment is comparable in PAH-CTD and IPAH: data from the Polish National Registry (BNP-PL)

Effectiveness of PAH-specific treatment is comparable in PAH-CTD and IPAH: data from the Polish National Registry (BNP-PL) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Effectiveness of PAH-specific treatment is comparable in PAH-CTD and IPAH: data from the Polish National Registry (BNP-PL) Anna Smukowska-Gorynia, Sylwia Iwańczyk, Michał Ciurzyński, Marcin Waligóra, and 23 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7622601/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Pulmonary arterial hypertension (PAH) is a rare disease with poor prognosis. The same treatment is recommended in patients with PAH associated with connective tissue disease (CTD) and idiopathic PAH (IPAH). However, the effectiveness of PAH-specific treatment in these both groups is inconsistent. Methods The study incorporated data from the prospective, multicentre polish registry (BNP-PL) by comparison of baseline vs. 1-year follow-up clinical, laboratory, echocardiographic and hemodynamic parameters in PAH-CTD vs. IPAH group. The all-cause 1-year mortality was also analyzed. Results 624 patients were included in the study: 176 (28%) PAH-CTD and 448 (72%) IPAH. 48 (8% of the total 624) patients died during 1-year follow up: 32 (7%) with IPAH and 16 (9%) with PAH-CTD (p = 0.4). The effectiveness of treatment was examined in 421 patients: 115 (27%) PAH-CTD and 306 (73%) IPAH. The improvement of treatment was effective in both groups in terms of WHO FC (p < 0.001 in both groups), 4-strata risk model (p < 0.001 in both groups), six minute walking test (6MWT, p < 0.001 in IPAH, p = 0.001 in PAH-CTD), Δ6MWT (p = 0.19 between PAH-CTD and IPAH), tricuspid annular plane systolic excursion (p < 0.001 in both groups), NT- proBNP (p < 0.001 in IPAH and p < 0.01 in PAH-CTD), mean pulmonary arterial pressure (p = 0.043 in IPAH and p = 0.01 in PAH-CTD), pulmonary vascular resistance (p < 0.001 in both groups) and cardiac output (p < 0.001 in IPAH and p = 0.034 in PAH-CTD). Conclusions PAH specific treatment in PAH-CTD patients is as effective as in IPAH patients during 1-year observation. 1-year all-cause mortality was not significantly higher in PAH-CTD patients compared to IPAH patients. Health sciences/Cardiology Health sciences/Diseases Health sciences/Medical research effectiveness of treatment PAH-specific treatment PAH PAH-CTD registry Figures Figure 1 Introduction Idiopathic pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) are the most common sub-groups of pulmonary hypertension [ 1 ]. Among PAH-CTD, systemic scleroderma (SSc) is the most prevalent multisystem connective tissue disease [ 2 , 3 ], followed by systemic lupus erythematosus (SLE) [ 4 – 6 ], mixed CTD [ 4 ], rheumatoid arthritis [ 7 ], dermatomyositis [ 8 ], and Sjögren’s syndrome [ 9 ]. According to the European Society of Cardiology (ESC) and European Respiratory Society (ERS) Guidelines patients with PAH-CTD should be treated as the patients suffering from IPAH [ 10 ] with the PAH specific drugs including molecules affecting prostacyclin pathway (epoprostenol, treprostinil, iloprost, selexipag), endothelin receptor pathway (macitentan, bosentan, ambrisentan) and nitric oxide/natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase five inhibitors (PDE5i: sildenafil, tadalafil). Novel drugs modifying the activin pathway related to bone morphogenetic protein receptor 2 ( BMPR2, e.g. sotatercept) are promising [ 11 – 13 ]. In addition, several sub-analyses of randomized trials investigating mentioned above PAH specific drugs were performed in the sub-groups of patients with PAH-CTD: epoprostenol [ 14 ], treprostinil [ 15 ], bosentan [ 16 ], ambrisentan [ 17 ], selexipag [ 18 ]. However, in literature, the data about effectiveness of PAH specific treatment in PAH-CTD compared to IPAH are inconclusive. In the past, there were studies indicating that results of PAH specific treatment is less effective in patients with CTD comparing to those without CTD [ 19 – 21 ]. In contrast, there are data showing that introducing PAH specific treatment in PAH-CTD in the modern era of treatment, especially at the early stage of the disease as patients in World Health Organization (WHO) functional class (FC) I or II is related with a better prognosis [ 22 – 25 ]. Thus, the aim of the present study was to compare the effectiveness of the PAH-specific treatment in IPAH group (including familial and toxin/drug induced PAH) vs. PAH-CTD group in real life settings. Methods The study incorporated data from the national Database of the Pulmonary Hypertension in the Polish Population (BNP-PL, ClinicalTrials.gov NCT03959748), a prospective, multicentre registry. The details of the registry have been described previously [ 26 ].The registry included patients from 21 PH reference centres in Poland accredited by the National Health Fund to treat PAH. For the aim of the current study we analyzed only prospectively enrolled incident cases who were diagnosed with IPAH or PAH-CTD between March 1, 2018 and August 30, 2023. The effectiveness of the treatment was examined by comparison of baseline vs. 1-year follow-up WHO FC, 6-minute walking test (6MWT), Borg dyspnea scale, right atrium area (RAA), tricuspid annular plane systolic excursion (TAPSE), NT- fragment pro brain natriuretic peptide (NT-proBNP), 4-strata risk assessment model (including all four parameters: WHO-FC, 6MWT and NT-proBNP) and hemodynamic measurements derived from right heart catheterization in both groups. In addition, the all-cause 1-year mortality was analyzed. All procedures in the study were carried out in accordance with Declaration of Helsinki. The protocol of the study was reviewed and accepted by the Bioethical Committee of Physicians and Dentists Chamber in Krakow (OIL/KBL/27/2018). Written informed consent was obtained from all participants and/or their legal guardians. Data availability The datasets generated and analysed during the current study are not publicly available due to privacy policy of the registry (BNP-PL), but are available from the corresponding author upon reasonable request and permission of the board of the registry. Statistical Analyses Statistical analyses were done with the use of PQStat version 1.6.6 (PQStat Software, Poland). The distribution of data was assessed with Shapiro-Wilk test. Data were showed as mean ± standard deviation (SD) or median values (first-third quartile) as appropriate. Group comparison was performed by Chi 2 test or Fisher exact test. The effectiveness of treatment (baseline vs. 1 year follow-up) was checked with Wilcoxon test or Mann-Whitney test. Given that the majority of patients were classified as intermediate mortality risk based on the 3-strata baseline risk assessment outlined in the ESC 2022 guidelines [ 10 ], we adopted a more granular risk stratification approach to improve long-term survival prediction. For this purpose, we utilized the validated COMPERA 2.0 four-strata model [ 27 ], which incorporates assessments of functional class, 6-minute walking distance (6MWD), and NT-proBNP levels, measured both at diagnosis and after 1 year of follow-up. Patients were categorized into four risk groups: low, intermediate-low, intermediate-high, or high mortality risk. To enable a direct comparison of clinical outcomes, risk strata at baseline and follow-up were analyzed separately for patients with IPAH and PAH-CTD. To illustrate transitions between risk groups over time, we employed a Sankey diagram, which visualizes changes in risk strata from baseline to follow-up. This approach effectively captured the dynamic nature of risk evolution, offering valuable insights into disease progression and response to treatment in these patient populations. This analysis was restricted to patients who underwent follow-up assessments (i.e., those with at least 12 months of observation who survived through this period). P-value < 0.05 was the cut-off value of statistical significance. Results In total 624 patients were included in the study: 448 (72%) in IPAH group and 176 (28%) in PAH-CTD group. The most common CTD was SSc (65%). Significantly more women were in PAH-CTD group compared to IPAH group (p<0.001). Patients with CTD more often suffered from interstitial lung disease (ILD, p<0.001), hypothyroidism (p=0.001) and used oxygen at home (p=0.03) compared to IPAH group. In addition, patients with CTD were more common treated with glucocorticoids (GCS, p< 0.001) and other immunosuppressants (p< 0.001), proton pump inhibitors (IPP, p<0.001) compared to IPAH group. Patients in IPAH group had higher baseline 4-strata risk model (p=0.01) and more often suffered from hyperthyroidism (p= 0.04), diabetes mellitus type 2 (DM2, p< 0.001), chronic obstructive pulmonary disease (COPD, p=0.002) and sleep apnea (p= 0.048) and had more often history of cigarettes smoking and were significantly more often treated with torasemide (p=0.001) and mineral corticosteroid receptor antagonist (MRA, p=0.01). Baseline PAH- specific treatment more often contained triple therapy (p=0.03) and epoprostenol (p=0.03) in IPAH group compared to PAH-CTD group, while the patients with PAH-CTD were more often treated with monotherapy (p< 0.001). Patients detailed baseline characteristics is presented in Table 1. Table 1 Baseline characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) IPAH, n= 448 PAH-CTD, n= 176 P value IPAH vs. PAH-CTD Gender Female n (%) Male n (%) 270 (60) 178 (40) 142 (80) 34 (20) <0.001 CTD n (%): SSc MCTD RA SLE Overlapped Sjogren Dermatomyositis 115 (65) 18 (10) 13 (7) 10 (6) 8 (5) 7 (4) 5 (3) Age years 64 (±15) 64 (±12) 0.99 WHO FC 3 (3-3) 3 (3-3) 0.15 4-strata risk model 2 3 (3-4) 3 (2-3) 0.01 Ca-blocker n (%) Sildenafil n (%) Tadalafil n (%) Bosentan n (%) Macitentan n (%) Selexypag n (%) Riociguat n (%) Treprostinil (iv and sc) n (%) Epoprostenol iv n (%) Iloprost inhaled n (%) Monotherapy n (%) Double therapy n (%) Triple therapy n (%) 94 (21) 364 (81) 1 (0.2) 141 (32) 71 (16) 6 (1) 9 (2) 50 (11) 30 (7) 30 (7) 161 (36) 174 (39) 67 (15) 29 (17) 144 (82) 1 (0.6) 48 (27) 19 (11) 1 (0.6) 3 (2) 21 (12) 4 (2) 6 (4) 94 (53) 54 (31) 15 (9) 0.20 0.91 0.49 0.30 0.1 0.41 0.80 0.72 0.03 0.11 <0.001 0.06 0.03 VKA n (%) LMWH n (%) NOAC n (%) 25 (6) 5 (1) 107 (24) 4 (2) 3 (2) 36 (21) 0.08 0.56 0.35 Beta-blocker n (%) ACEI n (%) Sartan n (%) Ivabradine n (%) Amiodarone n (%) Furosemide n (%) Torasemide n (%) Hydrochlorothiazide n (%) MRA n (%) SSRI n (%) ASA n (%) IPP n (%) Statin n (%) GCS n (%) Immunosuppressants n (%) 252 (56) 124 (28) 42 (9) 11 (2) 10 (2) 114 (25) 250 (51) 28 (6) 181 (40) 13 (3) 101 (23) 166 (37) 211 (47) 22 (5) 15 (3) 97 (55) 56 (32) 19 (11) 1 (0.6) 2 (1) 42 (24) 73 (41) 16 (9) 48 (27) 8 (5) 46 (26) 96 (55) 81 (46) 67 (38) 69 (39) 0.81 0.31 0.6 0.12 0.37 0.67 0.001 0.21 0.01 0.31 0.35 <0.001 0.79 <0.001 <0.001 Diabetes Mellitus n (%) 157 (35) 29 (16) < 0.001 Hypertension n (%) 273 (61) 117 (67) 0.20 Coronary artery disease n (%) 107 (24) 33 (19) 0.17 History of cigarettes smoking n (%) 135 (30) 37 (22) 0.02 History of myocardial infarction n (%) 34 (8) 15 (9) 0.70 Depression n (%) 15 (3) 10 (6) 0.18 COPD n (%) 73 (16) 12 (7) 0.002 Asthma n (%) 27(6) 6 (3) 0.19 ILD n (%) 31 (7) 66 (38) <0.001 Sleep apnea n (%) 15 (3) 1 (0.6) 0.048 Hypothyroidism n (%) 75 (17) 46 (26) 0.01 Hyperthyroidism n (%) 25 (6) 3 (2) 0.04 Home oxygen use n (%) 70 (16) 37 (21) 0.03 Chronic kidney disease n (%) 104 (23) 35 (20) 0.37 Hemodialysis n (%) 2 (0.5) 1 (0.6) 0.84 History of pulmonary embolismn (%) 34 (8) 9 (5) 0.27 History of deep veins thrombosis n (%) 22 (5) 12 (7) 0.35 Malignancy n (%) 35 (8) 7 (4) 0.09 Pacemaker n (%) 13 (3) 4 (2) 0.66 Atrial fibrillation n (%) 89 (20) 29 (17) 0.33 Atrial flutter n (%) 8 (2) 3 (2) 0.94 Death n (%) 32 (7) 16 (9) 0.41 1 IPAH group also included familial and toxin induced pulmonary arterial hypertension. 2 4-strata risk model assesses NYHA/WHO FC, NT-proBNP and 6MWT dividing patients into low risk, low intermediate risk, high intermediate risk and high risk Abbreviations: ACEI: angiotensin-converting-enzyme inhibitors, ASA: acetylsalicylic acid, Ca-blocker: calcium channel blockers, COPD: chronic obstructive pulmonary disease, GCS: glucocorticoids, ILD: interstitial lung disease, IPP: proton pump inhibitors, LMWH: low molecular weight heparin, MCTD: mixed connective tissue disease, MRA: mineral corticosteroid receptor antagonists, NOAC: non-vitamin K oral antagonists, RA: rheumatoid arthritis, SLE: systemic lupus erythematosus, SSc: scleroderma complex, SSRI: selective serotonin reuptake inhibitor, VKA: vitamin K oral antagonists; An analysis evaluating PAH-specific treatment effectiveness included 421 patients: 306 (73%) in IPAH group and 115 (27%) in PAH-CTD group with completed clinical data of 1-year follow-up (Table 2). Data regarding the number of deaths were available for total 624 patients. 48 (8% of the total 624) patients died during 1-year follow up: 32 (7%) with IPAH and 16 (9%) with PAH-CTD (p=0.4, Table 1); in 98 (16 %) patients observation was shortened than 1-year (patients included to the registry after 30 August 2022) and 57 (9%) patients were lost from the follow-up. At 1-year follow-up significant improvement in WHO FC, 4-strata risk model, 6MWT, TAPSE, NT-proBNP, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output (CO) was achieved in both groups: IPAH and PAH-CTD (Table 2). Median Δ6MWT for PAH-CTD group was 21m (-20; 90) and 37m (-21,126) for IPAH group (p=0.19). Right atrium area (RAA) was the only parameter which improved significantly in IPAH group (p<0.001) and did not reached significance cut-off in PAH-CTD group (p=0.38, Table 2). Either mean right atrium pressure (mRAP) and mixed oxygen saturation (mixSatO 2 ) did not significantly improved in both groups (Table 2). Table 2 Change in different parameters during 1-year follow-up in idiopathic pulmonary arterial hypertension 1 (IPAH) and pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) patients. IPAH n= 306; PAH-CTD n=115 Baseline 1 FU P value 6MWT m IPAH 280 (150-410) 350 (180-475) <0.001 PAH-CTD 295 (198-400) 349 (234-455) 0.001 Borg dyspnea IPAH 5 (2-7) 4 (1-6) <0.001 PAH-CTD 5 (3-7) 4 (3-7) 0.14 mPAP mmHg IPAH 45 (36-57) 44 (35-56) 0.043 PAH-CTD 40 (31-47) 37 (29-45) 0.01 PVR WU IPAH 9.4 (6.4-13.3) 6.9 (4.7-10.0) <0.001 PAH-CTD 8.5 ( 5.5-10.7) 5.8 (4.2-8.7) <0.001 CO l/min IPAH 3.9 (3.2-5.2) 4.8 (4.0-5.8) <0.001 PAH-CTD 4.0 (3.4-4.8) 4.7 (3.6-5.3) 0.034 TAPSE mm IPAH 17 (14-20) 20 (16-24) <0.001 PAH-CTD 17 (14-20) 20 (15-24) <0.001 RAA cm 2 IPAH 25 (21-31) 24 (18-30) <0.001 PAH-CTD 22 (19-27) 20 (18-28) 0.38 NT-proBNP pg/ml IPAH 1629 (664-3463) 625 (194-2397) <0.001 PAH-CTD 1531 (386-3381) 560 (271-2659) <0.01 WHO FC IPAH 3 (3-3) 3 (2-3) <0.001 PAH-CTD 3 (3-3) 3 (2-3) <0.001 4-strata risk model 2 IPAH 3 (3-4) 2 (2-3) <0.001 PAH-CTD 3 (2-3) 2 (2-3) <0.001 mRAP mmHg IPAH 6 (4-10) 7 (4-10) 0.14 PAH-CTD 7 (5-9) 6.8 (3.0-9.0) 0.67 SatO 2 mix % IPAH 66 (61-73) 71 (63-76) 0.06 PAH-CTD 69 (65-72) 69 (64-74) 0.76 1 IPAH group also included familial and toxin induced pulmonary arterial hypertension. 2 4-strata risk model assesses NYHA/WHO FC, NT-proBNP and 6MWT dividing patients into low risk, low intermediate risk, high intermediate risk and high risk Abbreviations: CO: cardiac output; IPAH: idiopathic pulmonary arterial hypertension; mPAP: mean pulmonary artery pressure; mRAP: mean pulmonary right atrium pressure; NT-proBNP: NT- fragment pro brain natriuretic peptide; PAH-CTD: pulmonary arterial hypertension associated with connective tissue disease; PVR: pulmonary vascular resistance; RAA: right atrium area; SatO 2 mix: mixed oxygen saturation ; 6MWT: six minute walking test; TAPSE: tricuspid annular plane systolic excursion; WHO FC: World Health Organization Functional Class. Changes of 4-strata risk model between baseline and 1-year follow-up in IPAH and PAH-CTD groups are showed in Fig.1. Discussion The main finding from our study is that effectiveness of PAH treatment with PAH specific drugs was similar in patients suffered from IPAH and PAH-CTD. Clinical improvement in terms of WHO FC, 4-strata risk model, 6MWT, TAPSE, NT-proBNP, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output (CO) was statistically significant in both groups at 1-year follow-up. In addition, Δ6MWT at 1 year follow-up did not differ significantly between PAH-CTD and IPAH group. The only parameter which achieved significant improvement in IPAH group but not in PAH-CTD group was RAA assessed in echocardiography (p<0.001, p=0.38). Our findings indicate that in real life settings, effectiveness of PAH-specific treatment is comparable in both investigating groups. In contrast, the study of Rhee et al. showed that patients with PAH-CTD had less improvement in 6MWT when ascribed to active treatment compared with patients with IPAH [28]. One of the explanations is that currently most of patients with SSc are annually screened for PAH development according to ESC/ERS Guidelines and PAH specific treatment is introduced earlier [2,10]. Second, the mentioned study included patients from randomized control trials and after adjusting for potential confounders, Δ6MWT did not also differ significantly between CTD-PAH and IPAH. Moreover, as in our study, mortality was not significantly higher in PAH-CTD group compared to IPAH group [28]. In our study 1-year survival was 91% in PAH-CTD group, which is similar to previous studies conducted in SSc-PAH (85%-95%) [1, 20, 29-32]. In one of the recent meta-analysis eight studies with the total of 530 PAH-CTD patients were included. The pooled one year survival was 90% which is comparable to our results [33]. One should note that overall mortality could be affected by COVID-19, especially in the early phase of the pandemic [34-36], or overtreatment with β-blockers [37]. Moreover, it is proven that among patients with CTD, the poorest prognosis characterized patients with co-existing pulmonary hypertension and ILD [38]. In our study, patients with PAH-CTD more often suffered from ILD and used oxygen at home compared to IPAH group, but on the other hand COPD was more prevalent in IPAH group. Next to ILD and oxygen usage, the fact that PAH-CTD patients were more likely to be treated with baseline monotherapy could also influence negatively on prognosis. Monotherapy compared to combined therapy worsened survival in SSc-PAH in the previous study [29] and in the most recent study based on COMPERA registry [1]. In addition, patients in immunosuppression are more susceptible to infection, thus in our registry, patients in PAH-CTD group were more often treated with immunosuppressants and in turn, they were significantly less likely to be treated with epoprostenol iv. However, at baseline patients in IPAH group had more advanced disease according to higher baseline 4-strata risk model and this could be an another explanation of more often introducing baseline triple therapy in IPAH group compared to PAH-CTD group. Moreover, diabetes mellitus type 2 was more often comorbidity in IPAH patients compared to PAH-CTD and DM2 worsened survival in previous study [39]. In our study hypothyroidism was more prevalent in PAH-CTD patients compared to IPAH patients which is in line with the study of Antonelli, et al. demonstrating that among patients with SSc hypothyroidism was much more common than in control group [40]. Moreover, in several studies hypothyroidism was more common in PAH patients compared to general population [41,42]. Previously, hyperthyroidism was associated with high prevalence of estimated pulmonary hypertension assessed by echocardiography in which tricuspid valve regurgitation velocity was evaluated [43-45]. However, detailed characterization of thyrotoxicosis in patients suffering from PAH needs further investigations. In summary, despite heterogeneity and significant clinical differences between PAH-CTD and IPAH group, there were no significant differences in clinical improvement and all-cause mortality between these two groups in 1-year follow-up. Strengths and limitations Our study has several strengths. First of all we present the results of the large multicentre PAH registry recruiting patients in the modern era of pharmacological PAH treatment. Second, by including all polish canters which diagnose and treat PAH patient we are able to estimate the outcome in large group of IPAH and PAH-CTD patients. Finally we assessed IPAH and PAH-CTD patients data in real world clinical practise. The main limitation of our study is that the data 57 (9%) of patients were lost during 1 year follow up. Moreover, the group of PAH-CTD patients seems to be underrepresented in our registry which probably results from the lack of national screening programs in CTD population. Lastly, we collect data on the baseline characteristics of our patients rather than any analysis of their prognosis. The methodological limitations inherent to registry-based studies have been recently acknowledged [46]. Conclusion PAH specific treatment in PAH-CTD patients is as effective as in IPAH patients in terms of WHO FC, 4-strata risk model, 6MWT, Δ6MWT, TAPSE, NT-proBNP, mPAP, PVR and CO improvement at 1 year follow-up. 1-year all-cause mortality was not significantly higher in PAH-CTD patients compared to IPAH patients. Declarations Competing Interests Marcin Kurzyna reports grants and personal fees from Janssen, AOP Orphan, MSD, Ferrer, Roivant, Pfizer and GossamerGrzegorz Kopeć received lecture honoraria from MSD, AOP Orphan, Janssen, Pfizer, travel expenses coverage from MSD, Janssen, AOP Orphan, research grants from Ferrer, consultancy fees from MSD, AOP Orphan, Janssen, Acceleron, Aerovate, LiquidiaTatiana Mularek-Kubzdela reports lecture honoraria and travel expenses from AOP Orphan, MSD, Janssen Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author Contribution All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Anna Smukowska-Gorynia, Sylwia Iwańczyk, Michał Ciurzyński, Marcin Waligóra, Tatiana Mularek-Kubzdela; Marcin Kurzyna, Piotr Pruszczyk, Grzegorz Kopeć, Katarzyna Mizia-Stec, Ilona Skoczylas, Łukasz Chrzanowski, Piotr Błaszczak, Katarzyna Ptaszyńska, Grzegorz Grześk1, Ewa Malinowska, Małgorzata Peregud-Pogorzelska, Michał Tomaszewski, Ewa Mroczek, Miłosz Jaguszewski, Ewa Lewicka, Katarzyna Widejko, Agnieszka Pawlak, Wojciech Jacheć, Zbigniew Gąsior, Katarzyna Betkier-Lipińska, Judyta Winowska-Józwa, Marta Banaszkiewicz: made substantial contributions to the acquisition, analysis, and interpretation of data and revised it critically. The first draft of the manuscript was written by Anna Smukowska-Gorynia and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgements not applicable Data Availability The datasets generated and analysed during the current study are not publicly available due to privacy policy of the registry (BNP-PL), but are available from the corresponding author upon reasonable request and permission of the board of the registry. References Distler, O. et al. Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis. Rheumatology 2 , 1139–1146 (2024). Coghlan, J. G. et al. DETECT study group. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann. Rheum. Dis. 7 , 1340–1349 (2014). Avouac, J. et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and meta-analysis of 5 studies. J. Rheumatol. 37 , 2290–2298 (2010). Jais, X. et al. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum. 58 , 521–531 (2008). Hachulla, E. et al. French Collaborators Recruiting Members(∗). Pulmonary Arterial Hypertension Associated With Systemic Lupus Erythematosus: Results From the French Pulmonary Hypertension Registry. Chest 153 , 143–151 (2018). Qian, J. et al. Long-term prognosis of patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study. Eur. Respir J. 14 , 53 (2019). Kopeć, G. et al. Characterization of Patients with Pulmonary Arterial Hypertension: Data from the Polish Registry of Pulmonary Hypertension (BNP-PL). J. Clin. Med. 8 , 173 (2020). Sanges, S. et al. Pulmonary arterial hypertension in idiopathic inflammatory myopathies: Data from the French pulmonary hypertension registry and review of the literature. Med. (Baltim). 95 , e4911. 10.1097/MD.0000000000004911 (2016). Wang, J. et al. Pulmonary arterial hypertension associated with primary Sjögren's syndrome: a multicentre cohort study from China. Eur. Respir J. 19 (5), 56 (2020). Humbert, M. et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Endorsed by the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on rare respiratory diseases (ERN-LUNG). Eur. Heart J. 43 , 3618–3731 (2022). Smukowska-Gorynia, A. et al. Recent Advances in the Treatment of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases. Pharmaceuticals (Basel) . 5 , 161252 (2023). Humbert, M. et al. Sotatercept for the treatment of pulmonary arterial hypertension. N Engl. J. Med. 384 , 1204–1215 (2021). Hoeper, M. M. et al. for the STELLAR Investigators. Phase 3 trial sotatercept for treatment of pulmonary arterial hypertension. N Engl. J. Med. Published March . 6 10.1056/NEJMoa2213558 (2023). Badesch, D. B. et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann. Intern. Med. 132 , 425–434 (2000). Oudiz, R. J. et al. Treprostinil Study Group. Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease. Chest 126 , 420–427 (2004). Denton, C. P., Humbert, M., Rubin, L. & Black, C. M. Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions. Ann. Rheum. Dis. 65 , 1336–1340 (2006). Fischer, A. et al. Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial. Respir Med. 117 , 254–263 (2016). Gaine, S. et al. Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension. Eur. Respir J. 17 , 1602493. 10.1183/13993003.02493-2016 (2017). Launay, D. et al. Clinical phenotypes and survival of pre-capillary pulmonary hypertension in systemic sclerosis. PLoS One 2018 15 ;13: e0197112. 10.1371/journal.pone.0197112 Launay, D. et al. Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era. Ann. Rheum. Dis. 72 , 1940–1946 (2013). Ramjug, S. et al. Idiopathic and Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: A Comparison of Demographic, Hemodynamic, and MRI Characteristics and Outcomes. Chest 152 , 92–102 (2017). Hachulla, E. et al. French PAH-SSc Network. Pulmonary arterial hypertension associated with systemic sclerosis in patients with functional class II dyspnea: mild symptoms but severe outcome. Rheumatology 49 , 940–944 (2010). Gadre, S. K. et al. Lung or heart-lung transplant in pulmonary arterial hypertension: what is the impact of systemic sclerosis? Exp. Clin. Transpl. 15 , 676–684 (2017). Khanna, D. et al. Long-Term outcomes in patients with connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era: meta-analyses of randomized, controlled trials and observational registries. Arthritis Rheumatol. 73 , 837–847 (2021). Hassan, H. J. et al. Improved Survival for Patients with Systemic Sclerosis-associated Pulmonary Arterial Hypertension: The Johns Hopkins Registry. Am. J. Respir Crit. Care Med. 207 (3), 312–322. 10.1164/rccm.202204-0731OC (2023). Kopeć, G. et al. Database of Pulmonary Hypertension in the Polish Population (BNP-PL): design of the registry. Kardiol Pol. ; 25;77:972–974. Erratum in: Kardiol Pol. 2019;19:77:1230. (2019). 10.33963/KP.15109 Hoeper, M. M. et al. COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension. Eur Respir J. ; 7;60:2102311. (2022). 10.1183/13993003.02311-2021 Rhee, R. L. et al. Comparison of Treatment Response in Idiopathic and Connective Tissue Disease-associated Pulmonary Arterial Hypertension. Am. J. Respir Crit. Care Med. 1 , 1111–1117 (2015). Morrisroe, K. et al. Australian Scleroderma Interest Group (ASIG). Survival and quality of life in incident systemic sclerosis-related pulmonary arterial hypertension. Arthritis Res. Ther. 19 , 122. 10.1186/s13075-017-1341-x (2017). Chung, L. et al. Survival and predictors of mortality in systemic sclerosis-associated pulmonary arterial hypertension: outcomes from the pulmonary hypertension assessment and recognition of outcomes in scleroderma registry. Arthritis Care Res. (Hoboken) . 66 , 489–495 (2014). Kolstad, K. D., Li, S., Steen, V. & Chung, L. PHAROS Investigators. Long-Term Outcomes in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension From the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry (PHAROS). Chest 154 , 862–871. 10.1016/j.chest.2018.05.002 (2018). Gaine, S. et al. Selexipag in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD): Real-world experience from EXPOSURE. Pulm Circ. 28 , 14e12403. 10.1002/pul2.12403 (2024). Barkhane, Z. et al. Independent Predictors of Mortality in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis. Cureus 30;15 , e39730. 10.7759/cureus.39730 (2023). Mamzer, A. et al. Impact of the COVID-19 Pandemic on Pulmonary Hypertension Patients: Insights from the BNP-PL National Database. Int. J. Environ. Res. Public. Health . 10 , 19. 10.3390/ijerph19148423 (2022). Smukowska-Gorynia, A. et al. Patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension during the COVID-19 pandemic (2020–2022): clinical outcomes, prognostic factors, and response to vaccination. Pol. Arch. Intern. Med. 27 , 134. 10.20452/pamw.16706 (2024). Schmidt, K. H. et al. Trends in COVID-19-associated mortality in patients with pulmonary hypertension: a COMPERA analysis. Eur. Respir J. 27 , 612202440. 10.1183/13993003.02440-2022 (2023). Waligóra, M. et al. Effects of β-blockers on the Outcomes in Patients with Pulmonary Arterial Hypertension Stratified by the Presence of Comorbid Conditions: a Multicenter Prospective Cohort Study (BNP-PL). Chest. ; 9:S0012-3692(24)05471-0. (2024). 10.1016/j.chest.2024.10.051 Moinzadeh, P. et al. Impact of Systemic Sclerosis-Associated Interstitial Lung Disease With and Without Pulmonary Hypertension on Survival: A Large Cohort Study of the German Network for Systemic Sclerosis. Chest 165 , 132–145 (2024). Jonas, K. et al. Impact of diabetes mellitus on disease severity and patient survival in idiopathic pulmonary arterial hypertension: data from the Polish multicentre registry (BNP-PL). Cardiovasc. Diabetol. 13 , 22:177 (2023). Antonelli, A. et al. Clinical and subclinical autoimmune thyroid disorders in systemic sclerosis. Eur. J. Endo crinol . 156 , 431–437 (2007). Curnock, A. L., Dweik, R. A., Higgins, B. H., Saadi, H. F. & Arroliga, A. C. High prevalence of hypothyroidism in patients with primary pulmonary hypertension. Am. J. Med. Sci. 318 , 289–292 (1999). Chu, J. W., Kao, P. N., Faul, J. L. & Doyle, R. L. High Prevalence of autoimmune thyroid disease in pulmonary arterial hypertension. Chest 122 , 1668–1673 (2002). Gazzana, M. L., Souza, J. J., Okoshi, M. P. & Okoshi, K. Prospective Echocardiographic Evaluation of the Right Ventricle and Pulmonary Arterial Pressure in Hyperthyroid Patients. Heart Lung Circ. 28 , 1190–1196 (2019). Song, X. et al. Characteristics and Risk Factors of Pulmonary Hypertension in Patients With Hyperthyroidism. Endocr. Pract. 27 , 918–924 (2021). Marvisi, M. et al. Pulmonary hypertension is frequent in hyperthyroidism and normalizes after therapy. Eur. J. Intern. Med. 17 , 267–271 (2006). Weatherald, J., Reis, A., Sitbon, O. & Humbert, M. Pulmonary arterial hypertension registries: Past, present and into the future. Eur. Respir Rev. 28 , 190128 (2019). Additional Declarations Competing interest reported. Marcin Kurzyna reports grants and personal fees from Janssen, AOP Orphan, MSD, Ferrer, Roivant, Pfizer and Gossamer Grzegorz Kopeć received lecture honoraria from MSD, AOP Orphan, Janssen, Pfizer, travel expenses coverage from MSD, Janssen, AOP Orphan, research grants from Ferrer, consultancy fees from MSD, AOP Orphan, Janssen, Acceleron, Aerovate, Liquidia Tatiana Mularek-Kubzdela reports lecture honoraria and travel expenses from AOP Orphan, MSD, Janssen Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7622601","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":528201933,"identity":"5b522079-57ee-4a7f-b037-64598748f81f","order_by":0,"name":"Anna Smukowska-Gorynia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYFACxgYQacAP5hSQokUSQpFgl4HBAWK18M9ubvz4M+ewsfGN3APMBcRokbhzsFmad9thM7MbeQnMM4hy2I3EBmnGbYdtzG7nGDDzEKNF/kZi88+fQC3Gs4nVYnAjsU0C5DADaWK1GAK1WPNuSzeWuP8u4TBRfpG7kf745s9t1ob9PWcPPi6oIEILEuBhOEyaBpAWZlK1jIJRMApGwcgAADnGNe422nurAAAAAElFTkSuQmCC","orcid":"","institution":"Poznan University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Anna","middleName":"","lastName":"Smukowska-Gorynia","suffix":""},{"id":528201934,"identity":"ac0471a6-0dbf-49cb-b3fc-79843d1b5e2d","order_by":1,"name":"Sylwia Iwańczyk","email":"","orcid":"","institution":"Poznan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Sylwia","middleName":"","lastName":"Iwańczyk","suffix":""},{"id":528201935,"identity":"2f8d8366-384c-470f-a32d-11e2d4da4946","order_by":2,"name":"Michał Ciurzyński","email":"","orcid":"","institution":"Medical University of Warsaw","correspondingAuthor":false,"prefix":"","firstName":"Michał","middleName":"","lastName":"Ciurzyński","suffix":""},{"id":528201936,"identity":"4f591f6a-3b02-4afd-bd6f-35561a69d555","order_by":3,"name":"Marcin Waligóra","email":"","orcid":"","institution":"Jagiellonian University Medical College","correspondingAuthor":false,"prefix":"","firstName":"Marcin","middleName":"","lastName":"Waligóra","suffix":""},{"id":528201937,"identity":"036f4be7-3e53-4d5b-8e0d-889f8851df8b","order_by":4,"name":"Marcin Kurzyna","email":"","orcid":"","institution":"Centre of Postgraduate Medical Education,","correspondingAuthor":false,"prefix":"","firstName":"Marcin","middleName":"","lastName":"Kurzyna","suffix":""},{"id":528201938,"identity":"8da70957-e947-420f-8c37-cf8625031efd","order_by":5,"name":"Piotr Pruszczyk","email":"","orcid":"","institution":"Medical University of Warsaw","correspondingAuthor":false,"prefix":"","firstName":"Piotr","middleName":"","lastName":"Pruszczyk","suffix":""},{"id":528201939,"identity":"a82c5a1e-b1d8-4d77-b565-8da5fa919218","order_by":6,"name":"Grzegorz Kopeć","email":"","orcid":"","institution":"Jagiellonian University Medical College","correspondingAuthor":false,"prefix":"","firstName":"Grzegorz","middleName":"","lastName":"Kopeć","suffix":""},{"id":528201940,"identity":"6bae674e-8cd9-4a5b-b5ef-83fa64221a05","order_by":7,"name":"Katarzyna Mizia-Stec","email":"","orcid":"","institution":"Medical University of Silesia","correspondingAuthor":false,"prefix":"","firstName":"Katarzyna","middleName":"","lastName":"Mizia-Stec","suffix":""},{"id":528201941,"identity":"cf58b75c-7a46-4e80-8f2d-c9080307e4ee","order_by":8,"name":"Ilona Skoczylas","email":"","orcid":"","institution":"Medical University of Silesia","correspondingAuthor":false,"prefix":"","firstName":"Ilona","middleName":"","lastName":"Skoczylas","suffix":""},{"id":528201942,"identity":"40f2c9a8-8b05-4f47-a79d-3f6bcea168fc","order_by":9,"name":"Łukasz Chrzanowski","email":"","orcid":"","institution":"Medical University of Lodz","correspondingAuthor":false,"prefix":"","firstName":"Łukasz","middleName":"","lastName":"Chrzanowski","suffix":""},{"id":528201943,"identity":"8fec2980-4b11-4c0c-8a6e-ede6958f84ab","order_by":10,"name":"Piotr Błaszczak","email":"","orcid":"","institution":"Cardinal Wyszynski Hospital","correspondingAuthor":false,"prefix":"","firstName":"Piotr","middleName":"","lastName":"Błaszczak","suffix":""},{"id":528201944,"identity":"587a6e9b-afd9-42d6-ac52-6dcf2f72ba9e","order_by":11,"name":"Katarzyna Ptaszyńska","email":"","orcid":"","institution":"Medical University of Bialystok","correspondingAuthor":false,"prefix":"","firstName":"Katarzyna","middleName":"","lastName":"Ptaszyńska","suffix":""},{"id":528201947,"identity":"acd1fbe5-5329-4319-a662-930986183d65","order_by":12,"name":"Grzegorz Grześk","email":"","orcid":"","institution":"Nicolaus Copernicus University","correspondingAuthor":false,"prefix":"","firstName":"Grzegorz","middleName":"","lastName":"Grześk","suffix":""},{"id":528201948,"identity":"8b76edb3-9a1d-4652-971f-7bd96e0198bb","order_by":13,"name":"Ewa Malinowska","email":"","orcid":"","institution":"University of Warmia and Mazury","correspondingAuthor":false,"prefix":"","firstName":"Ewa","middleName":"","lastName":"Malinowska","suffix":""},{"id":528201950,"identity":"f6b7cd29-03fa-456e-a750-3a7c2230e41a","order_by":14,"name":"Małgorzata Peregud-Pogorzelska","email":"","orcid":"","institution":"Pomeranian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Małgorzata","middleName":"","lastName":"Peregud-Pogorzelska","suffix":""},{"id":528201951,"identity":"44b54546-36f4-492c-9381-55e962cd119c","order_by":15,"name":"Michał Tomaszewski","email":"","orcid":"","institution":"Medical University of Lublin","correspondingAuthor":false,"prefix":"","firstName":"Michał","middleName":"","lastName":"Tomaszewski","suffix":""},{"id":528201953,"identity":"bfe8179f-8e70-4552-989d-82b6093cfdc6","order_by":16,"name":"Ewa Mroczek","email":"","orcid":"","institution":"Wroclaw Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ewa","middleName":"","lastName":"Mroczek","suffix":""},{"id":528201954,"identity":"a851389c-fab1-4333-b1a6-e31e7ddef2d0","order_by":17,"name":"Miłosz Jaguszewski","email":"","orcid":"","institution":"Medical University of Gdansk","correspondingAuthor":false,"prefix":"","firstName":"Miłosz","middleName":"","lastName":"Jaguszewski","suffix":""},{"id":528201956,"identity":"f77f2e03-2d26-4a5a-b26b-65268741e1cc","order_by":18,"name":"Ewa Lewicka","email":"","orcid":"","institution":"Medical University of Gdansk","correspondingAuthor":false,"prefix":"","firstName":"Ewa","middleName":"","lastName":"Lewicka","suffix":""},{"id":528201958,"identity":"00187c9d-bc25-44d3-befc-ca3ccf047651","order_by":19,"name":"Katarzyna Widejko","email":"","orcid":"","institution":"Copper Health Center","correspondingAuthor":false,"prefix":"","firstName":"Katarzyna","middleName":"","lastName":"Widejko","suffix":""},{"id":528201960,"identity":"82f8439b-e71c-405e-bcab-e0129b158a0e","order_by":20,"name":"Agnieszka Pawlak","email":"","orcid":"","institution":"Polish Academy of Sciences, Central Clinical Hospital of the Ministry of Interior","correspondingAuthor":false,"prefix":"","firstName":"Agnieszka","middleName":"","lastName":"Pawlak","suffix":""},{"id":528201961,"identity":"ae96c90d-08a7-4810-9ffa-36691b3330cb","order_by":21,"name":"Wojciech Jacheć","email":"","orcid":"","institution":"Medical University of Silesia in Katowice","correspondingAuthor":false,"prefix":"","firstName":"Wojciech","middleName":"","lastName":"Jacheć","suffix":""},{"id":528201963,"identity":"f710f2f5-3dd7-43c1-b901-45de33093536","order_by":22,"name":"Zbigniew Gąsior","email":"","orcid":"","institution":"Medical University of Silesia in Katowice","correspondingAuthor":false,"prefix":"","firstName":"Zbigniew","middleName":"","lastName":"Gąsior","suffix":""},{"id":528201965,"identity":"08030f51-b28a-4805-9646-cf7b3be77dc0","order_by":23,"name":"Katarzyna Betkier-Lipińska","email":"","orcid":"","institution":"Military Institute of Medicine-National Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Katarzyna","middleName":"","lastName":"Betkier-Lipińska","suffix":""},{"id":528201967,"identity":"823c0761-2f64-4128-852e-effe23b32763","order_by":24,"name":"Judyta Winowska-Józwa","email":"","orcid":"","institution":"Samodzielny Publiczny Wojewódzki Szpital Zespolony","correspondingAuthor":false,"prefix":"","firstName":"Judyta","middleName":"","lastName":"Winowska-Józwa","suffix":""},{"id":528201969,"identity":"a3e09ffb-0f9c-4933-a650-427d8b9d0f63","order_by":25,"name":"Marta Banaszkiewicz","email":"","orcid":"","institution":"Centre of Postgraduate Medical Education,","correspondingAuthor":false,"prefix":"","firstName":"Marta","middleName":"","lastName":"Banaszkiewicz","suffix":""},{"id":528201971,"identity":"0b87104a-a8f9-4b26-8634-dc63b4f8974d","order_by":26,"name":"Tatiana Mularek-Kubzdela","email":"","orcid":"","institution":"Poznan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Tatiana","middleName":"","lastName":"Mularek-Kubzdela","suffix":""}],"badges":[],"createdAt":"2025-09-15 16:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7622601/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7622601/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":93637791,"identity":"7526442b-741b-462b-a636-84a3c0db22b2","added_by":"auto","created_at":"2025-10-16 01:55:50","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":354808,"visible":true,"origin":"","legend":"","description":"","filename":"manuscriptIPAHCTD3.docx","url":"https://assets-eu.researchsquare.com/files/rs-7622601/v1/c1d938f9b06af8294f5b616c.docx"},{"id":93637789,"identity":"30b596ee-63b2-4147-8c8e-5560a3176e87","added_by":"auto","created_at":"2025-10-16 01:55:50","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":24495,"visible":true,"origin":"","legend":"","description":"","filename":"cc6617b5fbbb4e469720e5573160ce7c.json","url":"https://assets-eu.researchsquare.com/files/rs-7622601/v1/7adae1460fceabc6be4ba5e6.json"},{"id":93637793,"identity":"9b7980ad-2595-4b68-9bc0-6eb2237b841c","added_by":"auto","created_at":"2025-10-16 01:55:50","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":136846,"visible":true,"origin":"","legend":"","description":"","filename":"cc6617b5fbbb4e469720e5573160ce7c1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7622601/v1/165062f98ab58a3a3a36d343.xml"},{"id":93639036,"identity":"5223a5cc-4023-493b-b39d-6274dbf13d60","added_by":"auto","created_at":"2025-10-16 02:03:50","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":193069,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7622601/v1/77395d3aee103f2c20c16d74.png"},{"id":93637790,"identity":"3ea616be-a369-4fb4-b31f-edcfe938ed19","added_by":"auto","created_at":"2025-10-16 01:55:50","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":133986,"visible":true,"origin":"","legend":"","description":"","filename":"cc6617b5fbbb4e469720e5573160ce7c1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7622601/v1/5ef468e3b198d5e9610a8091.xml"},{"id":93639037,"identity":"027f8358-63f6-4d93-990b-55c99fc04705","added_by":"auto","created_at":"2025-10-16 02:03:50","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":151528,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7622601/v1/470aa129f84fc05c4610cfbe.html"},{"id":93637792,"identity":"8e329cd2-988e-4df0-b580-79948b29f745","added_by":"auto","created_at":"2025-10-16 01:55:50","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":776754,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in clinical status in patients with IPAH (A) and PAH-CTD (B) at baseline and 1 year follow-up. Improvement in PAH-CTD group achieved 51 patients (44%) and in IPAH group 149 patients (49%), p=0.42. Clinical worsening occurred in 15 patients (13%) in PAH-CTD group and in IPAH group 38 patients (12%), p=0.86.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7622601/v1/550bd8921904921e86209105.jpeg"},{"id":99308603,"identity":"3f1e17c7-8c98-4430-bb4e-9d950053829d","added_by":"auto","created_at":"2025-12-31 16:08:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1721548,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7622601/v1/738afdee-b8e6-4b27-80d6-c34989b1dd29.pdf"}],"financialInterests":"Competing interest reported. Marcin Kurzyna reports grants and personal fees from Janssen, AOP Orphan, MSD, Ferrer, Roivant, Pfizer and Gossamer\nGrzegorz Kopeć received lecture honoraria from MSD, AOP Orphan, Janssen, Pfizer, \ntravel expenses coverage from MSD, Janssen, AOP Orphan, research grants from Ferrer, \nconsultancy fees from MSD, AOP Orphan, Janssen, Acceleron, Aerovate, Liquidia\nTatiana Mularek-Kubzdela reports lecture honoraria and travel expenses from AOP Orphan, MSD, Janssen","formattedTitle":"Effectiveness of PAH-specific treatment is comparable in PAH-CTD and IPAH: data from the Polish National Registry (BNP-PL)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIdiopathic pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) are the most common sub-groups of pulmonary hypertension [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Among PAH-CTD, systemic scleroderma (SSc) is the most prevalent multisystem connective tissue disease [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], followed by systemic lupus erythematosus (SLE) [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], mixed CTD [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], rheumatoid arthritis [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], dermatomyositis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and Sj\u0026ouml;gren\u0026rsquo;s syndrome [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. According to the European Society of Cardiology (ESC) and European Respiratory Society (ERS) Guidelines patients with PAH-CTD should be treated as the patients suffering from IPAH [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] with the PAH specific drugs including molecules affecting prostacyclin pathway (epoprostenol, treprostinil, iloprost, selexipag), endothelin receptor pathway (macitentan, bosentan, ambrisentan) and nitric oxide/natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase five inhibitors (PDE5i: sildenafil, tadalafil). Novel drugs modifying the activin pathway related to bone morphogenetic protein receptor 2 ( BMPR2, e.g. sotatercept) are promising [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In addition, several sub-analyses of randomized trials investigating mentioned above PAH specific drugs were performed in the sub-groups of patients with PAH-CTD: epoprostenol [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], treprostinil [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], bosentan [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], ambrisentan [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], selexipag [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, in literature, the data about effectiveness of PAH specific treatment in PAH-CTD compared to IPAH are inconclusive. In the past, there were studies indicating that results of PAH specific treatment is less effective in patients with CTD comparing to those without CTD [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In contrast, there are data showing that introducing PAH specific treatment in PAH-CTD in the modern era of treatment, especially at the early stage of the disease as patients in World Health Organization (WHO) functional class (FC) I or II is related with a better prognosis [\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Thus, the aim of the present study was to compare the effectiveness of the PAH-specific treatment in IPAH group (including familial and toxin/drug induced PAH) vs. PAH-CTD group in real life settings.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe study incorporated data from the national Database of the Pulmonary Hypertension in the Polish Population (BNP-PL, ClinicalTrials.gov NCT03959748), a prospective, multicentre registry. The details of the registry have been described previously [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].The registry included patients from 21 PH reference centres in Poland accredited by the National Health Fund to treat PAH. For the aim of the current study we analyzed only prospectively enrolled incident cases who were diagnosed with IPAH or PAH-CTD between March 1, 2018 and August 30, 2023. The effectiveness of the treatment was examined by comparison of baseline vs. 1-year follow-up WHO FC, 6-minute walking test (6MWT), Borg dyspnea scale, right atrium area (RAA), tricuspid annular plane systolic excursion (TAPSE), NT- fragment pro brain natriuretic peptide (NT-proBNP), 4-strata risk assessment model (including all four parameters: WHO-FC, 6MWT and NT-proBNP) and hemodynamic measurements derived from right heart catheterization in both groups. In addition, the all-cause 1-year mortality was analyzed.\u003c/p\u003e\u003cp\u003e All procedures in the study were carried out in accordance with Declaration of Helsinki. The protocol of the study was reviewed and accepted by the Bioethical Committee of Physicians and Dentists Chamber in Krakow (OIL/KBL/27/2018). Written informed consent was obtained from all participants and/or their legal guardians.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and analysed during the current study are not publicly available due to privacy policy of the registry (BNP-PL), but are available from the corresponding author upon reasonable request and permission of the board of the registry.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStatistical Analyses\u003c/h3\u003e\n\u003cp\u003eStatistical analyses were done with the use of PQStat version 1.6.6 (PQStat Software, Poland). The distribution of data was assessed with Shapiro-Wilk test. Data were showed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median values (first-third quartile) as appropriate. Group comparison was performed by Chi \u003csup\u003e2\u003c/sup\u003e test or Fisher exact test. The effectiveness of treatment (baseline vs. 1 year follow-up) was checked with Wilcoxon test or Mann-Whitney test. Given that the majority of patients were classified as intermediate mortality risk based on the 3-strata baseline risk assessment outlined in the ESC 2022 guidelines [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], we adopted a more granular risk stratification approach to improve long-term survival prediction. For this purpose, we utilized the validated COMPERA 2.0 four-strata model [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], which incorporates assessments of functional class, 6-minute walking distance (6MWD), and NT-proBNP levels, measured both at diagnosis and after 1 year of follow-up.\u003c/p\u003e\u003cp\u003ePatients were categorized into four risk groups: low, intermediate-low, intermediate-high, or high mortality risk. To enable a direct comparison of clinical outcomes, risk strata at baseline and follow-up were analyzed separately for patients with IPAH and PAH-CTD.\u003c/p\u003e\u003cp\u003eTo illustrate transitions between risk groups over time, we employed a Sankey diagram, which visualizes changes in risk strata from baseline to follow-up. This approach effectively captured the dynamic nature of risk evolution, offering valuable insights into disease progression and response to treatment in these patient populations. This analysis was restricted to patients who underwent follow-up assessments (i.e., those with at least 12 months of observation who survived through this period).\u003c/p\u003e\u003cp\u003eP-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was the cut-off value of statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn total 624 patients were included in the study: 448 (72%) in IPAH group and 176 (28%) in PAH-CTD group. The most common CTD was SSc (65%). Significantly more women were in PAH-CTD group compared to IPAH group (p\u0026lt;0.001). Patients with CTD more often suffered from interstitial lung disease (ILD, p\u0026lt;0.001), hypothyroidism (p=0.001) and used oxygen at home (p=0.03) compared to IPAH group. In addition, \u0026nbsp;patients with CTD were more common treated with glucocorticoids (GCS, p\u0026lt; 0.001) and other immunosuppressants (p\u0026lt; 0.001), proton pump inhibitors (IPP, p\u0026lt;0.001) compared to IPAH group. Patients in IPAH group had higher baseline 4-strata risk model (p=0.01) and more often suffered from hyperthyroidism (p= 0.04), diabetes mellitus type 2 (DM2, p\u0026lt; 0.001), chronic obstructive pulmonary disease (COPD, p=0.002) and sleep apnea (p= 0.048) and had more often history of cigarettes smoking and were significantly more often treated with torasemide (p=0.001) and mineral corticosteroid receptor antagonist (MRA, p=0.01). Baseline PAH- specific treatment more often contained triple therapy (p=0.03) and epoprostenol (p=0.03) in IPAH group compared to PAH-CTD group, while the patients with PAH-CTD were more often treated with monotherapy (p\u0026lt; 0.001). Patients detailed baseline characteristics is presented in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Baseline characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH, n= 448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD, n= 176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003cp\u003eIPAH vs. PAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Female n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Male n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e270 (60)\u003c/p\u003e\n \u003cp\u003e178 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e142 (80)\u003c/p\u003e\n \u003cp\u003e34 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eCTD n (%):\u003c/p\u003e\n \u003cp\u003eSSc\u003c/p\u003e\n \u003cp\u003eMCTD\u003c/p\u003e\n \u003cp\u003eRA\u003c/p\u003e\n \u003cp\u003eSLE\u003c/p\u003e\n \u003cp\u003eOverlapped\u003c/p\u003e\n \u003cp\u003eSjogren\u003c/p\u003e\n \u003cp\u003eDermatomyositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e115 (65)\u003c/p\u003e\n \u003cp\u003e18 (10)\u003c/p\u003e\n \u003cp\u003e13 (7)\u003c/p\u003e\n \u003cp\u003e10 (6)\u003c/p\u003e\n \u003cp\u003e8 (5)\u003c/p\u003e\n \u003cp\u003e7 (4)\u003c/p\u003e\n \u003cp\u003e5 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e64 (\u0026plusmn;15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e64 (\u0026plusmn;12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWHO FC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (3-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (3-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4-strata risk model\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (3-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Ca-blocker n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Sildenafil n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Tadalafil n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Bosentan n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Macitentan n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Selexypag \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Riociguat \u0026nbsp; n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Treprostinil (iv and sc) n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Epoprostenol iv n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Iloprost inhaled n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Monotherapy n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Double therapy n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Triple therapy n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e94 (21)\u003c/p\u003e\n \u003cp\u003e364 (81)\u003c/p\u003e\n \u003cp\u003e1 (0.2)\u003c/p\u003e\n \u003cp\u003e141 (32)\u003c/p\u003e\n \u003cp\u003e71 (16)\u003c/p\u003e\n \u003cp\u003e6 (1)\u003c/p\u003e\n \u003cp\u003e9 (2)\u003c/p\u003e\n \u003cp\u003e50 (11)\u003c/p\u003e\n \u003cp\u003e30 (7)\u003c/p\u003e\n \u003cp\u003e30 (7)\u003c/p\u003e\n \u003cp\u003e161 (36)\u003c/p\u003e\n \u003cp\u003e174 (39)\u003c/p\u003e\n \u003cp\u003e67 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29 (17)\u003c/p\u003e\n \u003cp\u003e144 (82)\u003c/p\u003e\n \u003cp\u003e1 (0.6)\u003c/p\u003e\n \u003cp\u003e48 (27)\u003c/p\u003e\n \u003cp\u003e19 (11)\u003c/p\u003e\n \u003cp\u003e1 (0.6)\u003c/p\u003e\n \u003cp\u003e3 (2)\u003c/p\u003e\n \u003cp\u003e21 (12)\u003c/p\u003e\n \u003cp\u003e4 (2)\u003c/p\u003e\n \u003cp\u003e6 (4)\u003c/p\u003e\n \u003cp\u003e94 (53)\u003c/p\u003e\n \u003cp\u003e54 (31)\u003c/p\u003e\n \u003cp\u003e15 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; VKA n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;LMWH n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; NOAC n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25 (6)\u003c/p\u003e\n \u003cp\u003e5 (1)\u003c/p\u003e\n \u003cp\u003e107 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (2)\u003c/p\u003e\n \u003cp\u003e3 (2)\u003c/p\u003e\n \u003cp\u003e36 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Beta-blocker \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;ACEI \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Sartan \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Ivabradine \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Amiodarone \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Furosemide \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Torasemide \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Hydrochlorothiazide n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;MRA \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; SSRI \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003eASA \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003eIPP \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003eStatin \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003eGCS \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003eImmunosuppressants \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e252 (56)\u003c/p\u003e\n \u003cp\u003e124 (28)\u003c/p\u003e\n \u003cp\u003e42 (9)\u003c/p\u003e\n \u003cp\u003e11 (2)\u003c/p\u003e\n \u003cp\u003e10 (2)\u003c/p\u003e\n \u003cp\u003e114 (25)\u003c/p\u003e\n \u003cp\u003e250 (51)\u003c/p\u003e\n \u003cp\u003e28 (6)\u003c/p\u003e\n \u003cp\u003e181 (40)\u003c/p\u003e\n \u003cp\u003e13 (3)\u003c/p\u003e\n \u003cp\u003e101 (23)\u003c/p\u003e\n \u003cp\u003e166 (37)\u003c/p\u003e\n \u003cp\u003e211 (47)\u003c/p\u003e\n \u003cp\u003e22 (5)\u003c/p\u003e\n \u003cp\u003e15 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e97 (55)\u003c/p\u003e\n \u003cp\u003e56 (32)\u003c/p\u003e\n \u003cp\u003e19 (11)\u003c/p\u003e\n \u003cp\u003e1 (0.6)\u003c/p\u003e\n \u003cp\u003e2 (1)\u003c/p\u003e\n \u003cp\u003e42 (24)\u003c/p\u003e\n \u003cp\u003e73 (41)\u003c/p\u003e\n \u003cp\u003e16 (9)\u003c/p\u003e\n \u003cp\u003e48 (27)\u003c/p\u003e\n \u003cp\u003e8 (5)\u003c/p\u003e\n \u003cp\u003e46 (26)\u003c/p\u003e\n \u003cp\u003e96 (55)\u003c/p\u003e\n \u003cp\u003e81 (46)\u003c/p\u003e\n \u003cp\u003e67 (38)\u003c/p\u003e\n \u003cp\u003e69 (39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Diabetes Mellitus n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e157 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHypertension \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e273 (61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e117 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCoronary artery disease \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e107 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e33 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHistory of cigarettes smoking \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e135 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHistory of myocardial infarction \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e34 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDepression \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCOPD \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e73 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAsthma \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e27(6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eILD \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e66 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSleep apnea \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.048\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHypothyroidism \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e75 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e46 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHyperthyroidism \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.04\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHome oxygen use \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e70 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChronic kidney disease \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e104 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHemodialysis \u0026nbsp; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHistory of pulmonary embolismn (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e34 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHistory of deep veins thrombosis \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMalignancy \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePacemaker \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAtrial fibrillation \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e89 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAtrial flutter \u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDeath n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eIPAH group also included familial and toxin induced pulmonary arterial hypertension.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003e4-strata risk model assesses NYHA/WHO FC, NT-proBNP and 6MWT dividing patients into low risk, low intermediate risk, high intermediate risk and high risk\u003c/p\u003e\n\u003cp\u003eAbbreviations: ACEI: angiotensin-converting-enzyme inhibitors, ASA: acetylsalicylic acid, Ca-blocker: calcium channel blockers, COPD: chronic obstructive pulmonary disease, GCS: glucocorticoids, ILD: interstitial lung disease, IPP: proton pump inhibitors, LMWH: low molecular weight heparin, MCTD: mixed connective tissue disease, MRA: mineral corticosteroid receptor antagonists, NOAC: non-vitamin K oral antagonists, RA: rheumatoid arthritis, SLE: systemic lupus erythematosus, SSc: scleroderma complex, SSRI: selective serotonin reuptake inhibitor, VKA: vitamin K oral antagonists;\u003c/p\u003e\n\u003cp\u003eAn analysis evaluating PAH-specific treatment effectiveness included 421 patients: 306 (73%) in IPAH group and 115 (27%) in PAH-CTD group with completed clinical data of 1-year follow-up (Table 2). Data regarding the number of deaths were available for total 624 patients. 48 (8% of the total 624) patients died during 1-year follow up: 32 (7%) with IPAH and 16 (9%) with PAH-CTD (p=0.4, Table 1); \u0026nbsp;in \u0026nbsp;98 (16 %) patients observation was shortened than 1-year (patients included to the registry after 30 August 2022) and 57 (9%) \u0026nbsp;patients were lost from the follow-up.\u003c/p\u003e\n\u003cp\u003eAt 1-year follow-up significant improvement in WHO FC, 4-strata risk model, 6MWT, TAPSE, NT-proBNP, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) \u0026nbsp;and cardiac output (CO) was achieved in both groups: IPAH and PAH-CTD (Table 2). Median \u0026Delta;6MWT for PAH-CTD group was 21m (-20; 90) and 37m (-21,126) for IPAH group (p=0.19). Right atrium area (RAA) was the only parameter which improved significantly in IPAH group (p\u0026lt;0.001) and did not reached significance cut-off in PAH-CTD group (p=0.38, Table 2). Either mean right atrium pressure (mRAP) and mixed oxygen saturation (mixSatO\u003csub\u003e2\u003c/sub\u003e) did not significantly improved in both groups (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003eChange in different parameters during 1-year follow-up in idiopathic pulmonary arterial hypertension\u003csup\u003e1\u003c/sup\u003e (IPAH) and pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) patients.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH n= 306; PAH-CTD n=115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 FU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e6MWT m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e280 (150-410)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e350 (180-475)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e295 (198-400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e349 (234-455)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eBorg dyspnea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5 (2-7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (1-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5 (3-7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (3-7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003emPAP mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e45 (36-57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e44 (35-56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.043\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e40 (31-47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e37 (29-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePVR WU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9.4 (6.4-13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.9 (4.7-10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.5 ( 5.5-10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.8 (4.2-8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eCO l/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.9 (3.2-5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.8 (4.0-5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.0 (3.4-4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.7 (3.6-5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.034\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eTAPSE mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17 (14-20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 (16-24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17 (14-20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 (15-24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRAA cm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25 (21-31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24 (18-30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22 (19-27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 (18-28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eNT-proBNP pg/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1629 (664-3463)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e625 (194-2397)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1531 (386-3381)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e560 (271-2659)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eWHO FC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (3-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (3-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e4-strata risk model\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (3-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003emRAP mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 (4-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7 (4-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7 (5-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.8 (3.0-9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSatO\u003csub\u003e2\u003c/sub\u003emix %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIPAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e66 (61-73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e71 (63-76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePAH-CTD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e69 (65-72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e69 (64-74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eIPAH group also included familial and toxin induced pulmonary arterial hypertension.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003e4-strata risk model assesses NYHA/WHO FC, NT-proBNP and 6MWT dividing patients into low risk, low intermediate risk, high intermediate risk and high risk\u003c/p\u003e\n\u003cp\u003eAbbreviations: CO: cardiac output; IPAH: idiopathic pulmonary arterial hypertension; mPAP: mean pulmonary artery pressure; mRAP: mean pulmonary right atrium pressure; NT-proBNP: NT- fragment pro brain natriuretic peptide; PAH-CTD: pulmonary arterial hypertension associated with connective tissue disease; PVR: pulmonary vascular resistance; RAA: right atrium area; SatO\u003csub\u003e2\u003c/sub\u003emix: mixed oxygen saturation ; 6MWT: six minute walking test; TAPSE: tricuspid annular plane systolic excursion; WHO FC: World Health Organization Functional Class.\u003c/p\u003e\n\u003cp\u003eChanges of 4-strata risk model between baseline and 1-year follow-up in IPAH and PAH-CTD groups are showed in Fig.1.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main finding from our study is that effectiveness of PAH treatment with PAH specific drugs was similar in patients suffered from IPAH and PAH-CTD. Clinical improvement in terms of WHO FC, 4-strata risk model, 6MWT, TAPSE, NT-proBNP, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) \u0026nbsp;and cardiac output (CO) was statistically significant in both groups at 1-year follow-up. In addition,\u0026nbsp;Δ6MWT at 1 year follow-up did not differ significantly between PAH-CTD and IPAH group.\u0026nbsp;The only parameter which achieved significant improvement in \u0026nbsp;IPAH group but not in PAH-CTD group was RAA assessed in echocardiography (p\u0026lt;0.001, p=0.38). Our findings indicate that in real life settings, effectiveness of PAH-specific treatment is comparable in both investigating groups. In contrast, the study of Rhee et al. \u0026nbsp;showed that\u0026nbsp;patients with PAH-CTD had less improvement in 6MWT when ascribed to active treatment compared with patients with IPAH [28].\u0026nbsp;One of the explanations is that currently most of patients with SSc are annually screened for PAH development according to ESC/ERS Guidelines and PAH specific treatment is introduced earlier [2,10]. Second, the mentioned study included patients from randomized control trials and after adjusting for potential confounders,\u0026nbsp;Δ6MWT did not also differ significantly between CTD-PAH and IPAH. Moreover, as in our study, mortality was not significantly higher in PAH-CTD group compared to IPAH group [28]. In our study 1-year survival was 91% in PAH-CTD group, which is similar to previous studies conducted in SSc-PAH (85%-95%) [1, 20, 29-32]. In one of the recent meta-analysis eight studies with the total of 530 PAH-CTD patients were included. The pooled one year survival was 90% \u0026nbsp;which is comparable to our results [33]. One should note that overall mortality could be affected by COVID-19, especially in the early phase of the pandemic [34-36], or overtreatment with β-blockers [37]. Moreover, \u0026nbsp;it is proven that among patients with CTD, the poorest prognosis characterized patients with co-existing pulmonary hypertension and ILD [38]. In our study, patients with PAH-CTD more often suffered from ILD and used oxygen at home compared to IPAH group, but on the other hand COPD was more prevalent in IPAH group. Next to ILD and oxygen usage, the fact that PAH-CTD patients were more likely to be treated with baseline monotherapy could also influence negatively on \u0026nbsp;prognosis. Monotherapy compared to combined therapy worsened survival in SSc-PAH in the previous study [29] and in the most recent study based on COMPERA registry [1]. In addition, patients in immunosuppression are more susceptible to infection, thus in our registry, patients in PAH-CTD group were more often treated with immunosuppressants and in turn, they were significantly less likely to be treated with epoprostenol iv. However, at baseline patients in IPAH group had more advanced disease according to higher baseline 4-strata risk model and this could be an another explanation of more often introducing baseline triple therapy in IPAH group compared to PAH-CTD group. Moreover, diabetes mellitus type 2 was more often comorbidity in IPAH patients compared to PAH-CTD and DM2 worsened survival in previous study [39].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;In our study hypothyroidism was more prevalent in PAH-CTD patients compared to IPAH patients which is in line with the study of Antonelli, et al. \u0026nbsp;demonstrating that among patients with SSc hypothyroidism was much more common than in control group [40]. Moreover, in several \u0026nbsp;studies hypothyroidism was more common in PAH patients compared to general population [41,42]. Previously, hyperthyroidism was associated with high prevalence of estimated pulmonary hypertension assessed by echocardiography in which tricuspid valve regurgitation velocity was evaluated [43-45]. However, detailed characterization of thyrotoxicosis \u0026nbsp;in \u0026nbsp; patients suffering from PAH needs further investigations.\u003c/p\u003e\n\u003cp\u003eIn summary, despite heterogeneity and significant clinical differences between PAH-CTD and IPAH group, there were no significant differences in clinical improvement and all-cause mortality between these two groups in 1-year follow-up.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study has several strengths. \u0026nbsp;First of all we present the results of the large multicentre PAH registry recruiting patients in the modern era of pharmacological PAH treatment. Second, by including all polish canters which diagnose and treat PAH patient we are able to estimate the outcome in large group of IPAH and PAH-CTD patients. Finally we assessed IPAH and PAH-CTD patients data in real world clinical practise.\u003c/p\u003e\n\u003cp\u003eThe main limitation of our study is that the data 57 (9%) of patients were lost during 1 year follow up. Moreover, the group of PAH-CTD patients seems to be underrepresented in our registry which probably results from the lack of national screening programs in CTD population. Lastly, we collect data on the baseline characteristics of our patients rather than any analysis of their prognosis. \u0026nbsp; The methodological limitations inherent to registry-based\u003c/p\u003e\n\u003cp\u003estudies have been recently acknowledged [46].\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePAH specific treatment in PAH-CTD patients is as effective as in IPAH patients in terms of WHO FC, 4-strata risk model, 6MWT, \u0026Delta;6MWT, TAPSE, NT-proBNP, mPAP, PVR and CO improvement at 1 year follow-up. 1-year all-cause mortality was not significantly higher in PAH-CTD patients compared to IPAH patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eCompeting Interests\u003c/h2\u003e\u003cp\u003eMarcin Kurzyna reports grants and personal fees from Janssen, AOP Orphan, MSD, Ferrer, Roivant, Pfizer and GossamerGrzegorz Kopeć received lecture honoraria from MSD, AOP Orphan, Janssen, Pfizer, travel expenses coverage from MSD, Janssen, AOP Orphan, research grants from Ferrer, consultancy fees from MSD, AOP Orphan, Janssen, Acceleron, Aerovate, LiquidiaTatiana Mularek-Kubzdela reports lecture honoraria and travel expenses from AOP Orphan, MSD, Janssen\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Anna Smukowska-Gorynia, Sylwia Iwańczyk, Michał Ciurzyński, Marcin Walig\u0026oacute;ra, Tatiana Mularek-Kubzdela; Marcin Kurzyna, Piotr Pruszczyk, Grzegorz Kopeć, Katarzyna Mizia-Stec, Ilona Skoczylas, Łukasz Chrzanowski, Piotr Błaszczak, Katarzyna Ptaszyńska, Grzegorz Grześk1, Ewa Malinowska, Małgorzata Peregud-Pogorzelska, Michał Tomaszewski, Ewa Mroczek, Miłosz Jaguszewski, Ewa Lewicka, Katarzyna Widejko, Agnieszka Pawlak, Wojciech Jacheć, Zbigniew Gąsior, Katarzyna Betkier-Lipińska, Judyta Winowska-J\u0026oacute;zwa, Marta Banaszkiewicz: made substantial contributions to the acquisition, analysis, and interpretation of data and revised it critically. The first draft of the manuscript was written by Anna Smukowska-Gorynia and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e\u003cp\u003enot applicable\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and analysed during the current study are not publicly available due to privacy policy of the registry (BNP-PL), but are available from the corresponding author upon reasonable request and permission of the board of the registry.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDistler, O. et al. Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis. \u003cem\u003eRheumatology\u003c/em\u003e \u003cb\u003e2\u003c/b\u003e, 1139\u0026ndash;1146 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCoghlan, J. G. et al. DETECT study group. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. \u003cem\u003eAnn. Rheum. Dis.\u003c/em\u003e \u003cb\u003e7\u003c/b\u003e, 1340\u0026ndash;1349 (2014).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAvouac, J. et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and meta-analysis of 5 studies. \u003cem\u003eJ. Rheumatol.\u003c/em\u003e \u003cb\u003e37\u003c/b\u003e, 2290\u0026ndash;2298 (2010).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJais, X. et al. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. \u003cem\u003eArthritis Rheum.\u003c/em\u003e \u003cb\u003e58\u003c/b\u003e, 521\u0026ndash;531 (2008).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHachulla, E. et al. French Collaborators Recruiting Members(\u0026lowast;). Pulmonary Arterial Hypertension Associated With Systemic Lupus Erythematosus: Results From the French Pulmonary Hypertension Registry. \u003cem\u003eChest\u003c/em\u003e \u003cb\u003e153\u003c/b\u003e, 143\u0026ndash;151 (2018).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQian, J. et al. Long-term prognosis of patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study. \u003cem\u003eEur. Respir J.\u003c/em\u003e \u003cb\u003e14\u003c/b\u003e, 53 (2019).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKopeć, G. et al. Characterization of Patients with Pulmonary Arterial Hypertension: Data from the Polish Registry of Pulmonary Hypertension (BNP-PL). \u003cem\u003eJ. Clin. Med.\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e, 173 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSanges, S. et al. Pulmonary arterial hypertension in idiopathic inflammatory myopathies: Data from the French pulmonary hypertension registry and review of the literature. \u003cem\u003eMed. (Baltim).\u003c/em\u003e \u003cb\u003e95\u003c/b\u003e, e4911. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000004911\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000004911\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2016).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang, J. et al. Pulmonary arterial hypertension associated with primary Sj\u0026ouml;gren's syndrome: a multicentre cohort study from China. \u003cem\u003eEur. Respir J.\u003c/em\u003e \u003cb\u003e19\u003c/b\u003e (5), 56 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHumbert, M. et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Endorsed by the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on rare respiratory diseases (ERN-LUNG). \u003cem\u003eEur. Heart J.\u003c/em\u003e \u003cb\u003e43\u003c/b\u003e, 3618\u0026ndash;3731 (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSmukowska-Gorynia, A. et al. Recent Advances in the Treatment of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases. \u003cem\u003ePharmaceuticals (Basel)\u003c/em\u003e. \u003cb\u003e5\u003c/b\u003e, 161252 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHumbert, M. et al. Sotatercept for the treatment of pulmonary arterial hypertension. \u003cem\u003eN Engl. J. Med.\u003c/em\u003e \u003cb\u003e384\u003c/b\u003e, 1204\u0026ndash;1215 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHoeper, M. M. et al. for the STELLAR Investigators. Phase 3 trial sotatercept for treatment of pulmonary arterial hypertension. \u003cem\u003eN Engl. J. Med. Published March\u003c/em\u003e. \u003cb\u003e6\u003c/b\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa2213558\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa2213558\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBadesch, D. B. et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. \u003cem\u003eAnn. Intern. Med.\u003c/em\u003e \u003cb\u003e132\u003c/b\u003e, 425\u0026ndash;434 (2000).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOudiz, R. J. et al. Treprostinil Study Group. Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease. \u003cem\u003eChest\u003c/em\u003e \u003cb\u003e126\u003c/b\u003e, 420\u0026ndash;427 (2004).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDenton, C. P., Humbert, M., Rubin, L. \u0026amp; Black, C. M. Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions. \u003cem\u003eAnn. Rheum. Dis.\u003c/em\u003e \u003cb\u003e65\u003c/b\u003e, 1336\u0026ndash;1340 (2006).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFischer, A. et al. Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial. \u003cem\u003eRespir Med.\u003c/em\u003e \u003cb\u003e117\u003c/b\u003e, 254\u0026ndash;263 (2016).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGaine, S. et al. Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension. \u003cem\u003eEur. Respir J.\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e, 1602493. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1183/13993003.02493-2016\u003c/span\u003e\u003cspan address=\"10.1183/13993003.02493-2016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLaunay, D. et al. Clinical phenotypes and survival of pre-capillary pulmonary hypertension in systemic sclerosis. \u003cem\u003ePLoS One 2018\u003c/em\u003e \u003cb\u003e15\u003c/b\u003e;13: e0197112. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0197112\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0197112\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLaunay, D. et al. Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era. \u003cem\u003eAnn. Rheum. Dis.\u003c/em\u003e \u003cb\u003e72\u003c/b\u003e, 1940\u0026ndash;1946 (2013).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRamjug, S. et al. Idiopathic and Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: A Comparison of Demographic, Hemodynamic, and MRI Characteristics and Outcomes. \u003cem\u003eChest\u003c/em\u003e \u003cb\u003e152\u003c/b\u003e, 92\u0026ndash;102 (2017).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHachulla, E. et al. French PAH-SSc Network. Pulmonary arterial hypertension associated with systemic sclerosis in patients with functional class II dyspnea: mild symptoms but severe outcome. \u003cem\u003eRheumatology\u003c/em\u003e \u003cb\u003e49\u003c/b\u003e, 940\u0026ndash;944 (2010).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGadre, S. K. et al. Lung or heart-lung transplant in pulmonary arterial hypertension: what is the impact of systemic sclerosis? \u003cem\u003eExp. Clin. Transpl.\u003c/em\u003e \u003cb\u003e15\u003c/b\u003e, 676\u0026ndash;684 (2017).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhanna, D. et al. Long-Term outcomes in patients with connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era: meta-analyses of randomized, controlled trials and observational registries. \u003cem\u003eArthritis Rheumatol.\u003c/em\u003e \u003cb\u003e73\u003c/b\u003e, 837\u0026ndash;847 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHassan, H. J. et al. Improved Survival for Patients with Systemic Sclerosis-associated Pulmonary Arterial Hypertension: The Johns Hopkins Registry. \u003cem\u003eAm. J. Respir Crit. Care Med.\u003c/em\u003e \u003cb\u003e207\u003c/b\u003e (3), 312\u0026ndash;322. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1164/rccm.202204-0731OC\u003c/span\u003e\u003cspan address=\"10.1164/rccm.202204-0731OC\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKopeć, G. et al. Database of Pulmonary Hypertension in the Polish Population (BNP-PL): design of the registry. Kardiol Pol. ; 25;77:972\u0026ndash;974. Erratum in: Kardiol Pol. 2019;19:77:1230. (2019). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.33963/KP.15109\u003c/span\u003e\u003cspan address=\"10.33963/KP.15109\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHoeper, M. M. et al. COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension. Eur Respir J. ; 7;60:2102311. (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1183/13993003.02311-2021\u003c/span\u003e\u003cspan address=\"10.1183/13993003.02311-2021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRhee, R. L. et al. Comparison of Treatment Response in Idiopathic and Connective Tissue Disease-associated Pulmonary Arterial Hypertension. \u003cem\u003eAm. J. Respir Crit. Care Med.\u003c/em\u003e \u003cb\u003e1\u003c/b\u003e, 1111\u0026ndash;1117 (2015).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMorrisroe, K. et al. Australian Scleroderma Interest Group (ASIG). Survival and quality of life in incident systemic sclerosis-related pulmonary arterial hypertension. \u003cem\u003eArthritis Res. Ther.\u003c/em\u003e \u003cb\u003e19\u003c/b\u003e, 122. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13075-017-1341-x\u003c/span\u003e\u003cspan address=\"10.1186/s13075-017-1341-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2017).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChung, L. et al. Survival and predictors of mortality in systemic sclerosis-associated pulmonary arterial hypertension: outcomes from the pulmonary hypertension assessment and recognition of outcomes in scleroderma registry. \u003cem\u003eArthritis Care Res. (Hoboken)\u003c/em\u003e. \u003cb\u003e66\u003c/b\u003e, 489\u0026ndash;495 (2014).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKolstad, K. D., Li, S., Steen, V. \u0026amp; Chung, L. PHAROS Investigators. Long-Term Outcomes in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension From the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry (PHAROS). \u003cem\u003eChest\u003c/em\u003e \u003cb\u003e154\u003c/b\u003e, 862\u0026ndash;871. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.chest.2018.05.002\u003c/span\u003e\u003cspan address=\"10.1016/j.chest.2018.05.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGaine, S. et al. Selexipag in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD): Real-world experience from EXPOSURE. \u003cem\u003ePulm Circ.\u003c/em\u003e \u003cb\u003e28\u003c/b\u003e, 14e12403. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/pul2.12403\u003c/span\u003e\u003cspan address=\"10.1002/pul2.12403\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarkhane, Z. et al. Independent Predictors of Mortality in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis. \u003cem\u003eCureus\u003c/em\u003e \u003cb\u003e30;15\u003c/b\u003e, e39730. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.39730\u003c/span\u003e\u003cspan address=\"10.7759/cureus.39730\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMamzer, A. et al. Impact of the COVID-19 Pandemic on Pulmonary Hypertension Patients: Insights from the BNP-PL National Database. \u003cem\u003eInt. J. Environ. Res. Public. Health\u003c/em\u003e. \u003cb\u003e10\u003c/b\u003e, 19. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijerph19148423\u003c/span\u003e\u003cspan address=\"10.3390/ijerph19148423\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSmukowska-Gorynia, A. et al. Patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension during the COVID-19 pandemic (2020\u0026ndash;2022): clinical outcomes, prognostic factors, and response to vaccination. \u003cem\u003ePol. Arch. Intern. Med.\u003c/em\u003e \u003cb\u003e27\u003c/b\u003e, 134. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.20452/pamw.16706\u003c/span\u003e\u003cspan address=\"10.20452/pamw.16706\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchmidt, K. H. et al. Trends in COVID-19-associated mortality in patients with pulmonary hypertension: a COMPERA analysis. \u003cem\u003eEur. Respir J.\u003c/em\u003e \u003cb\u003e27\u003c/b\u003e, 612202440. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1183/13993003.02440-2022\u003c/span\u003e\u003cspan address=\"10.1183/13993003.02440-2022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWalig\u0026oacute;ra, M. et al. Effects of β-blockers on the Outcomes in Patients with Pulmonary Arterial Hypertension Stratified by the Presence of Comorbid Conditions: a Multicenter Prospective Cohort Study (BNP-PL). Chest. ; 9:S0012-3692(24)05471-0. (2024). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.chest.2024.10.051\u003c/span\u003e\u003cspan address=\"10.1016/j.chest.2024.10.051\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMoinzadeh, P. et al. Impact of Systemic Sclerosis-Associated Interstitial Lung Disease With and Without Pulmonary Hypertension on Survival: A Large Cohort Study of the German Network for Systemic Sclerosis. \u003cem\u003eChest\u003c/em\u003e \u003cb\u003e165\u003c/b\u003e, 132\u0026ndash;145 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJonas, K. et al. Impact of diabetes mellitus on disease severity and patient survival in idiopathic pulmonary arterial hypertension: data from the Polish multicentre registry (BNP-PL). \u003cem\u003eCardiovasc. Diabetol.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e, 22:177 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAntonelli, A. et al. Clinical and subclinical autoimmune thyroid disorders in systemic sclerosis. \u003cem\u003eEur. J. Endo crinol\u003c/em\u003e. \u003cb\u003e156\u003c/b\u003e, 431\u0026ndash;437 (2007).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCurnock, A. L., Dweik, R. A., Higgins, B. H., Saadi, H. F. \u0026amp; Arroliga, A. C. High prevalence of hypothyroidism in patients with primary pulmonary hypertension. \u003cem\u003eAm. J. Med. Sci.\u003c/em\u003e \u003cb\u003e318\u003c/b\u003e, 289\u0026ndash;292 (1999).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChu, J. W., Kao, P. N., Faul, J. L. \u0026amp; Doyle, R. L. High Prevalence of autoimmune thyroid disease in pulmonary arterial hypertension. \u003cem\u003eChest\u003c/em\u003e \u003cb\u003e122\u003c/b\u003e, 1668\u0026ndash;1673 (2002).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGazzana, M. L., Souza, J. J., Okoshi, M. P. \u0026amp; Okoshi, K. Prospective Echocardiographic Evaluation of the Right Ventricle and Pulmonary Arterial Pressure in Hyperthyroid Patients. \u003cem\u003eHeart Lung Circ.\u003c/em\u003e \u003cb\u003e28\u003c/b\u003e, 1190\u0026ndash;1196 (2019).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSong, X. et al. Characteristics and Risk Factors of Pulmonary Hypertension in Patients With Hyperthyroidism. \u003cem\u003eEndocr. Pract.\u003c/em\u003e \u003cb\u003e27\u003c/b\u003e, 918\u0026ndash;924 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarvisi, M. et al. Pulmonary hypertension is frequent in hyperthyroidism and normalizes after therapy. \u003cem\u003eEur. J. Intern. Med.\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e, 267\u0026ndash;271 (2006).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWeatherald, J., Reis, A., Sitbon, O. \u0026amp; Humbert, M. Pulmonary arterial hypertension registries: Past, present and into the future. \u003cem\u003eEur. Respir Rev.\u003c/em\u003e \u003cb\u003e28\u003c/b\u003e, 190128 (2019).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"effectiveness of treatment, PAH-specific treatment, PAH, PAH-CTD, registry","lastPublishedDoi":"10.21203/rs.3.rs-7622601/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7622601/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003ePulmonary arterial hypertension (PAH) is a rare disease with poor prognosis. The same treatment is recommended in patients with PAH associated with connective tissue disease (CTD) and idiopathic PAH (IPAH). However, the effectiveness of PAH-specific treatment in these both groups is inconsistent.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe study incorporated data from the prospective, multicentre polish registry (BNP-PL) by comparison of baseline vs. 1-year follow-up clinical, laboratory, echocardiographic and hemodynamic parameters in PAH-CTD vs. IPAH group. The all-cause 1-year mortality was also analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003e624 patients were included in the study: 176 (28%) PAH-CTD and 448 (72%) IPAH. 48 (8% of the total 624) patients died during 1-year follow up: 32 (7%) with IPAH and 16 (9%) with PAH-CTD (p\u0026thinsp;=\u0026thinsp;0.4). The effectiveness of treatment was examined in 421 patients: 115 (27%) PAH-CTD and 306 (73%) IPAH. The improvement of treatment was effective in both groups in terms of WHO FC (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 in both groups), 4-strata risk model (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 in both groups), six minute walking test (6MWT, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 in IPAH, p\u0026thinsp;=\u0026thinsp;0.001 in PAH-CTD), Δ6MWT (p\u0026thinsp;=\u0026thinsp;0.19 between PAH-CTD and IPAH), tricuspid annular plane systolic excursion (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 in both groups), NT- proBNP (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 in IPAH and p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 in PAH-CTD), mean pulmonary arterial pressure (p\u0026thinsp;=\u0026thinsp;0.043 in IPAH and p\u0026thinsp;=\u0026thinsp;0.01 in PAH-CTD), pulmonary vascular resistance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 in both groups) and cardiac output (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 in IPAH and p\u0026thinsp;=\u0026thinsp;0.034 in PAH-CTD).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003ePAH specific treatment in PAH-CTD patients is as effective as in IPAH patients during 1-year observation. 1-year all-cause mortality was not significantly higher in PAH-CTD patients compared to IPAH patients.\u003c/p\u003e","manuscriptTitle":"Effectiveness of PAH-specific treatment is comparable in PAH-CTD and IPAH: data from the Polish National Registry (BNP-PL)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-16 01:55:45","doi":"10.21203/rs.3.rs-7622601/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"961b09bb-5342-4608-bae6-bff402003fb8","owner":[],"postedDate":"October 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56144643,"name":"Health sciences/Cardiology"},{"id":56144644,"name":"Health sciences/Diseases"},{"id":56144645,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-12-23T06:55:32+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-16 01:55:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7622601","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7622601","identity":"rs-7622601","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}