Prognosis and its predictors for pulmonary hypertension associated with connective tissue diseases (data of the first Ukrainian register)

Yu.M. Sirenko, G.D. Radchenko, I.O. Zhyvylo, E.Yu. Titov, S.I. Deyak


Background. This study is the first analysis of patient survival after treatment in the only Ukrainian pulmonary hypertension (PH) referral center that was organized in 2014 and mainly focused on pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The aim of the study was: to evaluate the structure of patients who were treated in referral center; to evaluate Ukrainian reality in surviving of patients with PAH and CTEPH (we did not have any Ukrainian data before); to determine predictors of death. Materials and methods. Tree hundred and fifty-nine patients with PH were included in database: with idiopathic PAH — 72 (20.1 %), PAH associated with connective tissue diseases (CTD) — 20 (5.6 %), PAH associated with HIV — 8 (2.2 %), PAH associated with portal hypertension — 4 (1.1 %), PAH associated with congenital heart diseases (CHD) — 171 (47.6 %), PH due to left heart diseases — 8 (2.2 %), PH associated with lung diseases — 6 (1.7 %), CTEPH — 62 (17.3 %), with multifactorial PH — 8 (2.2 %). Two hundred and eighty-one patients were enrolled (52 (18.5 %) with CTEPH, 229 (81.5 %) with PAH) in survival analysis. Long-term survival (Kaplan-Meier) and its predictors (Stepwise binary logistic regression and Cox’s proportional hazards analyses) were evaluated in adult patients with PH (diagnosed by right heart catheterization) within a prospective registry at a single referral center in Kyiv, Ukraine. Follow-up period was up to 51 (mean 23.6 ± 14.1) months. Only two specific drugs are available in Ukraine for the treatment of PH: inhaled iloprost and sildenafil. Results. The Kaplan-Meier survival rate for the total cohort was 93.3, 86.8, and 81.5 % at 1, 2 and 3 years, respectively. Survival was better in patients with CHD as compared to idiopathic PAH (log-rank P = 0.002), CTD (log-rank P = 0.001) and CTEPH (log-rank P = 0.04). Univariate Cox’s predictors of death were: functional class IV (odds ratio (OR) = 4.94; 95% confidence interval (CI) 2.12–11.48), pre-sence of ascites (OR = 4.52; 95% CI 2.21–9.24), CTD etiology of PAH (OR = 3.07; 95% CI 1.07–8.87), CHD etiology of PAH (OR = 0.28; 95% CI 0.11–0.68), heart rate during treatment > 105 bpm (OR = 7.85; 95% CI 1.83–33.69), office systolic blood pressure < 100 mmHg (OR = 2.78; 95% CI 1.26–6.1), 6-minute walk test during treatment < 340 m (OR = 3.47; 95% CI 1.01–12.35), NT-proBNP > 300 pg/ml (OR = 4.98; 95% CI 1.49–16.6), right atrial area > 22 cm2 (OR = 14.2; 95% CI 1.92–104.89), right ventricular area in diastole (OR = 1.08; 95% CI 1.03–1.14), right ventricular area in systole (OR = 1.08; 95% CI 1.02–1.11), mean pressure in right atrium per each 1-mmHg increase (OR = 1.02; 95% CI 1.02–1.19). In multivariate Cox regression analysis, only presence of ascites, office systolic BP < 100 mmHg, CHD etiology of PAH, NT-proBNP > 300 pg/ml were associated with survival. Conclusions. This is the first Ukrainian single-center PH cohort study results. It was shown that the structure of PAH patients in Ukraine was different from that in other countries. However, our data of survival are almost similar to data of centers from other countries. The worst survival was observed in PAH associated with CTD as compared to all other its forms: survival was only 49.7 % over 3 years. The simple indicators were revealed that can be evaluated in routine practice and are independent predictors of death: the presence of ascites and elevated levels of NT-proBNP.


pulmonary hypertension associated with connective tissue diseases; register of patients with pulmonary hypertension; survival; predictors of poor prognosis


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