Background Recent studies have provided evidence for an important contribution of the immune system in the pathophysiology of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we investigated whether the inflammatory profile of pulmonary hypertension patients changes over time and correlates with patient WHO subgroups or survival. Methods 50 PAH patients (16 idiopathic (I)PAH, 24 Connective Tissue Disease (CTD)-PAH and 10 Congenital Heart Disease (CHD)-PAH), 37 CTEPH patients and 18 healthy controls (HCs) were included in the study. Plasma inflammatory markers at baseline and after 1-year follow-up were measured using ELISAs. Subsequently, correlations with hemodynamic parameters and survival were explored and data sets were subjected to unbiased multivariate analyses. Results At diagnosis, we found that plasma levels of interleukin-6 (IL-6) and the chemokines (C-X3-C) motif legend CXCL9 and CXCL13 in CTD-PAH patients were significantly increased, compared with HCs. In idiopathic PAH patients the levels of tumor growth factor-β (TGFβ), IL-10 and CXCL9 were elevated, compared with HCs. The increased CXCL9 and IL-8 concentrations in CETPH patients correlated significantly with decreased survival, suggesting that CXCL9 and IL-8 may be prognostic markers. After one year of treatment, IL-10, CXCL13 and TGFβ levels changed significantly in the PAH subgroups and CTEPH patients. Unbiased multivariate analysis revealed clustering of PH patients based on inflammatory mediators and clinical parameters, but did not separate the WHO subgroups. Importantly, these multivariate analyses separated patients with < 3 years and > 3 years survival, in particular when inflammatory mediators were combined with clinical parameters. Discussion Our study revealed elevated plasma levels of inflammatory mediators in different PAH subgroups and CTEPH at baseline and at 1-year follow-up, whereby CXCL9 and IL-8 may prove to be prognostic markers for CTEPH patients. While this study is exploratory and hypothesis generating, our data indicate an important role for IL-8 and CXCL9 in CHD and CTEPH patients considering the increased plasma levels and the observed correlation with survival. Conclusion In conclusion, our studies identified an inflammatory signature that clustered PH patients into WHO classification-independent subgroups that correlated with patient survival.
BackgroundAdults with a systemic right ventricle (sRV) have a high risk of cardiac complications. This study aimed to identify prognostic markers in adults with sRV based on clinical evaluation, echocardiography, and blood biomarkers.Methods and ResultsIn this prospective cohort study, consecutive clinically stable adults with sRV caused by Mustard‐ or congenitally corrected transposition of the great arteries were included (2011–2013). Eighty‐six patients were included (age 37±9 years, 65% male, 83% New York Heart Association functional class I, 76% Mustard transposition of the great arteries, 24% congenitally corrected transposition of the great arteries). Venous blood sampling was performed including N‐terminal pro B‐type natriuretic peptide, high‐sensitive‐troponin‐T, high‐sensitivity C‐reactive protein, growth differentiation factor‐15, galectin‐3, red cell distribution width, estimated glomerular filtration rate, and hemoglobin. Besides conventional echocardiographic measurements, longitudinal, circumferential, and radial strain were assessed using strain analysis. During a median follow‐up of 5.9 (interquartile range 5.3–6.3) years, 19 (22%) patients died or had heart failure (primary end point) and 29 (34%) patients died or had arrhythmia (secondary end point). Univariable Cox regression analysis was performed using dichotomous or standardized continuous variables. New York Heart Association functional class >I, systolic blood pressure, and most blood biomarkers were associated with the primary and secondary end point (galectin‐3 not for primary, N‐terminal pro B‐type natriuretic peptide and high‐sensitivity C‐reactive protein not for secondary end point). Growth differentiation factor‐15 showed the strongest association with both end points (hazard ratios; 2.44 [95% CI 1.67–3.57, P<0.001], 2.00 [95% CI 1.46–2.73, P<0.001], respectively). End‐diastolic basal dimension of the subpulmonary ventricle was associated with both end points (hazard ratio: 1.95 [95% CI 1.34–2.85], P<0.001, 1.70 [95% CI 1.21–2.38, P=0.002], respectively). Concerning strain analysis, only sRV septal strain was associated with the secondary end point (hazard ratio 0.58 [95% CI 0.39–0.86], P=0.006).ConclusionsClinical, conventional echocardiographic, and blood measurements are important markers for risk stratification in adults with a sRV. The value of novel echocardiographic strain analysis seems limited.
Soluble ST2 (sST2) is upregulated in response to myocardial stress and may serve as biomarker in adults with pulmonary hypertension (PH). This prospective cohort study investigated sST2 levels and its association with echocardiographic and hemodynamic measures, and adverse clinical outcomes in adults with PH of different etiologies. sST2 was measured during the diagnostic right heart catheterization for PH, in adult patients enrolled between May 2012 and October 2016. PH due to left heart failure was excluded. The association between sST2 and a primary endpoint composed of death or lung transplantation and a secondary composite endpoint including death, lung transplantation or heart failure, was investigated using Cox regression with adjustment for NT-proBNP. In total 104 patients were included (median age was 59 years, 66% woman, 51% pulmonary arterial hypertension). Median sST2 was 28 [IQR 20–46] ng/mL. Higher sST2 was associated with worse right ventricular dysfunction and higher mean pulmonary and right atrial pressures. Median follow-up was 3.3 [IQR 2.3–4.6] years. The primary and secondary endpoint occurred in 33 (31.7%) and 43 (41.3%) patients, respectively. sST2 was significantly associated with both endpoints (HR per 2-fold higher value 1.53, 95%CI 1.12–2.07, p = 0.007 and 1.45, 95%CI 1.10–1.90, p = 0.008, respectively). However, after adjustment for NT-proBNP, both associations did not reach statistical significance. In conclusions, higher sST2 levels are associated with more severe PH and right ventricular dysfunction and yields prognostic value in adults with PH, although not independently of NT-proBNP.
ObjectiveDespite its predictive value for mortality in various diseases, the relevance of growth differentiation factor-15 (GDF-15) as prognostic biomarker in pulmonary hypertension (PH) remains unclear. This study investigated the association between GDF-15 and outcomes in adults with PH.MethodsThis is a single-centre prospective observational cohort study. All adults with PH were included at the day of their diagnostic right heart catheterisation between 2012 and 2016. PH due to left heart disease was excluded. Venous blood sampling was performed and included GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements. Kaplan-Meier curves and Cox regression analysis were used to investigate the association between GDF-15 and a composite endpoint of death or lung transplantation. We adjusted for age and NT-proBNP in multivariable analysis. Reference values were established by GDF-15 measurements in healthy controls.ResultsGDF-15 was measured in 103 patients (median age 59.2 years, 65% women, 51% pulmonary arterial hypertension). GDF-15 was elevated in 76 patients (74%). After a median follow-up of 3.4 (IQR 2.3–4.6) years, 32 patients (31.1%) reached the primary endpoint. Event-free survival 2 years after diagnosis was 100% in patients with normal GDF-15 versus 72.4% in patients with elevated GDF-15 (p=0.007). A significant association was found between GDF-15 and the primary endpoint (HR per twofold higher value 1.77, 95% CI 1.39 to 2.27, p<0.001), also after adjustment for age and NT-proBNP (HR 1.41, 95% CI 1.02 to 1.94, p=0.038).ConclusionsHigh GDF-15 levels are associated with an increased risk of death or transplant in adults with PH, independent of age and NT-proBNP. As non-specific biomarker, GDF-15 could particularly be useful to detect low-risk patients.
ObjectiveSoluble suppression of tumourigenicity-2 (sST2) is upregulated as response to myocardial stress and may be a potential biomarker for risk stratification in patients with adult congenital heart disease (ACHD). This study aimed to investigate the release of sST2 and its association with cardiovascular events in ACHD.MethodsIn this prospective cohort study, 602 consecutive patients with ACHD visiting the outpatient clinic were included (2011–2013). The association between sST2 and a primary composite endpoint of all-cause mortality, heart failure, hospitalisation, arrhythmia, thromboembolic events or cardiac interventions was investigated using multivariable Cox regression.ResultssST2 was measured in 590 (98%) patients (median age 33 [25–41] years, 42% women). After a median follow-up of 5.8 [IQR 5.1–6.2) years, 225 (38.5%) reached the primary endpoint. sST2 was significantly associated with the primary endpoint when adjusted for age, sex, creatinine and N terminal pro-B type brain natriuretic peptide (NT-proBNP) (HR per twofold higher sST2: 1.28, 95% CI 1.03 to 1.58, p=0.025). This association negated when adjusted for clinical variables and NT-proBNP (HR per twofold higher sST2: 1.19, 95% CI 0.96 to 1.48, p=0.106). Stratified analysis in complex ACHD did show a significant association between sST2 and the primary endpoint when adjusted for clinical variables and NT-proBNP (HR per twofold higher sST2: 1.31, 95% CI 1.01 to 1.69, p=0.043). Sex-specific analysis showed an association between sST2 and the primary endpoint in women (HR per twofold higher sST2 1.80, 95% CI 1.30 to 2.49, p<0.001) but not in men (HR per twofold higher sST2 1.19, 95% CI 0.90 to 1.56, p=0.223).ConclusionssST2 is a promising novel biomarker in patients with ACHD, specifically in complex ACHD and women. Future research is warranted to elucidate sex-specific and diagnosis-specific differences.
Background: Single high-sensitivity troponin T (hs-TnT) measurement is predictive of cardiac events in adults with congenital heart disease (ACHD). We aimed to study the prognostic value of serial hs-TnT measurements in stable patients with ACHD. Methods: In total, 602 consecutive patients with ACHD were enrolled in this prospective study (2011)(2012)(2013). Blood sampling was performed at enrollment and thereafter yearly during scheduled visits, up to 4 years. Hs-TnT, N-terminal pro B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured. The composite primary endpoint was defined as all-cause mortality, heart failure, arrhythmia, hospitalization, cardiac (re)interventions, or thromboembolic events. The relationship between changes in serial hs-TnT and the primary endpoint was studied by joint models with adjustment for repeated NT-proBNP and eGFR. Results: In 601 patients (median age, 33 [interquartile range, 25-41] years, 42% women, 90% NYHA I), at least 1 hs-TnT measurement was
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.