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Background Exercise right heart catheterization (RHC) unmasks different phenotypes based on hemodynamic response to exertion in patients with heart failure. The prognostic relevance of this approach in patients with heart failure and reduced ejection fraction (HFrEF) is uncertain. Methods We analyzed 167 patients with HFrEF from the Kerckhoff-Klinik Heart Failure Registry who underwent supine exercise RHC with constant external workload between September 2009 and August 2014. The primary outcome was heart transplant/assist device–free survival. Hemodynamic parameters that significantly predicted outcome were identified by multivariate Cox regression analysis and assessed further by Kaplan-Meier analysis after dichotomization using cutoffs derived from receiver operating characteristic analysis. Hemodynamic phenotypes were defined based on a dichotomized flow response (exercise-induced change in cardiac output [∆CO]) combined with a dichotomized pressure response (exercise-induced change in systolic [∆sPAP] or mean pulmonary arterial pressures). Results ∆CO independently predicted transplant/assist device–free survival (multivariate hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.09–2.58; p = 0.02). Patients with ∆CO ≥1.15 liter/min had significantly better 5-year transplant/assist device–free survival than patients with lower ∆CO (72.9% vs 22.5%; log-rank p < 0.001 [Kaplan-Meier analysis]). The hemodynamic phenotype of ∆CO <1.15 liter/min combined with ∆sPAP <17.5 mm Hg was associated with worse transplant/assist device–free survival than ∆CO ≥1.15 liter/min combined with ∆sPAP ≥17.5 mm Hg (multivariate HR 7.39; 95% CI, 2.27–24.05; p = 0.001). Conclusions Exercise RHC parameters are important prognostic indices in HFrEF. Hemodynamic phenotyping using ∆CO and ∆sPAP allows enhanced risk stratification. [ABSTRACT FROM AUTHOR]

Background: Circulating angiopoietin-1 (Ang-1) has been linked to pulmonary hypertension (PH) in experimental studies. However, the clinical relevance of Ang-1 as a biomarker in PH remains unknown. We aimed to investigate the prognostic and clinical significance of Ang-1 in PH using data from the prospectively recruiting Giessen PH Registry. Methods: Patients with suspected PH (without previous specific pulmonary arterial hypertension [PAH] therapy) who underwent initial right heart catheterization (RHC) in our national referral center between July 2003 and May 2012 and who agreed to optional biomarker analysis were included if they were diagnosed with idiopathic PAH, connective tissue disease-associated PAH (CTD-PAH), PH due to left heart disease (PH-LHD), or chronic thromboembolic PH (CTEPH), or if PH was excluded by RHC (non-PH controls). The association of Ang-1 levels with disease severity (6-minute walk distance and pulmonary hemodynamics) was assessed using linear regression, and the impact of Ang-1 levels on transplant-free survival (primary endpoint) and clinical worsening was assessed using Kaplan—Meier curves, receiver operating characteristic (ROC) analyses, and Cox regression. Results: 151 patients (39, 39, 32, and 41 with idiopathic PAH, CTD-PAH, PH-LHD, and CTEPH, respectively) and 41 non-PH controls were included. Ang-1 levels showed no significant difference between groups (p = 0.8), and no significant associations with disease severity in PH subgroups (p ≥ 0.07). In Kaplan—Meier analyses, Ang-1 levels (stratified by quartile) had no significant impact on transplant-free survival (p ≥ 0.27) or clinical worsening (p ≥ 0.51) in PH subgroups. Regression models found no significant association between Ang-1 levels and outcomes (p ≥ 0.31). ROC analyses found no significant cut-off that would maximize sensitivity and specificity. Conclusions: Despite a strong pathophysiological association in experimental studies, this first comprehensive analysis of Ang-1 in PH subgroups suggests that Ang-1 is not a predictive and clinically relevant biomarker in PH. [ABSTRACT FROM AUTHOR]

Background: Patients with pulmonary arterial hypertension (PAH) present with an altered inspiratory capacity (IC) reflecting dynamic hyperinflation (DH) that leads to mechanical constraints and excessive ventilatory demand, particularly during exercise, resulting in exertional dyspnea. Objectives: Assessment of the long-term consequences of altered IC and DH in PAH. Methods: 50 patients with newly diagnosed PAH were prospectively recruited. All patients were assessed by means of right heart catheterization, 6-min walking distance (6MWD) test, lung function and cardiopulmonary exercise testing, including the assessment of IC. Results: 37 patients with idiopathic PAH and 13 patients with conditions associated with PAH (29 female; mean age 51.6 ± 15.1 years; World Health Organization, WHO class, 2.7 ± 0.6) presented with a mean pulmonary arterial pressure of 42.8 ± 15.9 mm Hg and pulmonary vascular resistance (PVR) of 737.2 ± 592.8 dyn*s/cm5. The mean IC at rest was 87.2 ± 17.3% pred. Kaplan-Meier analysis revealed that patients with an IC at rest >89% pred. had a significantly better 5-year survival than those with lower values (94.1 vs. 75.1%; log-rank p = 0.036). Univariate analysis identified IC at rest (% pred.) as a predictor of survival with a hazard ratio (HR) of 5.05 (95% confidence interval, CI, 0.97-26.24, p = 0.054). In multivariate analysis including PVR, WHO class, 6MWD and peak oxygen uptake as covariates, IC at rest remained an independent predictor of survival (HR: 8.06, 95% CI 0.92-70.34; p = 0.059). DH expressed as ΔIC or static hyperinflation expressed as IC/total lung capacity at rest revealed no prognostic significance. Conclusion: In patients with PAH, IC at rest is of prognostic significance at the time of diagnosis. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]