H-FABP in Pre Capillary Pulmonary Hypertension: Comparison to Other Surrogate Parameters for Prediction of Severity and Outcome

摘要

Background: Heart-type fatty acid-binding protein (H-FABP) is a promising novel biomarker for risk stratification of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Whether disease severity in a group of patients with pre capillary pulmonary hypertension (PH) can be predicted by determination of plasma H-FABP levels remains unknown. Methods: 41 consecutive patients with a mean (±SD) age of 60.6 ± 2.1 years and severe PH were studied with a mean follow up to 541 days (95% CI: 420;661 days). H-FABP, but also the biomarkers NT-Pro-BNP and big-endothelin (Big-ET1), were correlated to parameters derived from right sided cardiac catheterization and cardio-pulmonary exercise test. Results: At baseline H-FABP levels ranged from 620 to 15200 pg/ml (3648 ± 502 pg/ml) and were weakly but significantly correlated to VO2AT (r = –0.37, p = 0.04) and VO2 peak (r =–0.38, p = 0.03). However, invasively measured hemodynamic parameters of PH and right ventricular dysfunction did not correlate with H-FABP levels. In- terestingly, moderate to high correlations between H-FABP and NT-Pro-BNP (r = 0.51, p = 0.01) and Big-ET1 (r = 0.65, p = 0.01) and between Big-ET1 and NT-Pro-BNP (r = 0.5, p = 0.01) could be observed. In contrast to H-FABP, NT-Pro-BNP, and even more Big-ET1, showed significant correlations to different invasively measured hemodynamic parameters of the disease indicating severity and consequently prognosis of severe pre-capillary pulmonary hypertension. However, in a multivariate Cox regression analysis, PVR, mixed venous oxygen saturation and the VE/VCO2 slope (>60) as well as the heart rate recovery within one minute (HRR) but none of the biomarkers were identified as independent factors of poor prognosis. In con- trast, peak workload and mixed venous saturation were identified as risk markers in the idiopathic pulmonary arterial hypertension subgroup. Conclusions: In contrast to the predictive value of H-FABP in CTEPH H-FABP fails to be a reliable marker in PH or to be a novel predictor of mid and long term outcome. The data suggest that an increased slope of VE/VCO2 and a decreased extent of HRR within one minute represent more promising diagnostic non invasive parameters.