Neue Biomarker und Multimarkerstrategien für eine optimierte Risikostratifizierung von Patienten mit Lungenembolie

Abstract

The present study investigated the prognostic value of the novel cardiac biomarkers heart-type fatty acid-binding protein (H-FABP) and growth-differentiation factor-15 (GDF-15) in risk stratification of patients with acute pulmonary embolism. In a population of 107 patients, H-FABP was found to be a reliable prognostic parameter for the occurrence of pulmonary embolism-associated complications. Overall, 29 patients (27%) had elevated (≥6 ng/mL) H-FABP plasma concentrations at presentation. Of these, 12 patients (41%) had a complicated course, whereas all patients with normal baseline H-FABP levels had a favourable in-hospital outcome. At multivariable analysis, H-FABP, but not the established biomarkers troponin T and N-terminal pro-brain natriuretic peptide (NT-proBNP), predicted an adverse outcome. In a combination model with echocardiographic evidence of right ventricular (RV) dysfunction, patients with a negative H-FABP test had an excellent prognosis regardless of their echocardiographic findings, and determination of H-FABP alone appeared to be sufficient for ruling out a complicated course. Conversely, the complication rate of patients with evidence of RV dysfunction in combination with elevation of H-FABP was 57%. Based on these findings, the present study showed that H-FABP is a promising biomarker for the risk stratification of patients with chronic thromboembolic pulmonary hypertension (CTEPH) as well. In 93 patients with CTEPH, H-FABP plasma concentrations at the time of initial diagnostic evaluation were correlated with baseline clinical and haemodynamic parameters and, accordingly, with disease severity. H-FABP could be identified as independent predictor of adverse long-term outcome (median follow-up period, 1,260 days) and the probability of event-free survival decreased with increasing tertiles of H-FABP concentrations. This observation was also confirmed in those (n=52) patients who underwent pulmonary endarterectomy (PEA) during follow-up. In 123 consecutive patients with acute pulmonary embolism that were followed over a median period of 287 days, GDF-15 could be identified as an independent predictor of both a complicated in-hospital outcome and long-term mortality. Patients with GDF-15 levels above the calculated cutoff value of 4,600 ng/mL developed complications in 52% of the cases, as opposed to only 5% of patients with normal GDF-15 concentrations at presentation. Combination with GDF-15 improved the prognostic significance of echocardiography and the established biomarkers troponin T and NT-proBNP. No patient with a normal echocardiogram and low GDF-15 levels developed complications, whereas the presence of RV dysfunction in combination with GDF-15 elevation was associated with a 16-fold increase in the risk to develop complications. Troponin T or NT-proBNP elevation alone was associated with a significant but only moderate increased risk of complications during the in-hospital stay. Combination of either biomarker with GDF-15 improved the prognostic value in both cases, whereas the combination of troponin T and NT-proBNP with each other did not appear to provide additive prognostic information in this patient population. Furthermore, Kaplan Meier analysis demonstrated that patients with GDF-15 levels above 4600 ng/L had a significantly lower probability of long-term survival. In contrast to GDF-15, troponin T and NT-proBNP had no independent prognostic value for the prediction of long-term outcome. In conclusion, the present study shows that H-FABP and GDF-15 are promising novel biomarkers for the risk stratification of patients with acute PE, which are superior to the established biomarkers troponin T and NT-proBNP in terms of prognostic value and provide additive prognostic information when combined with echocardiography or included in multimarker models.