Abstract 2297: Prognostic Value of Growth-Differentiation Factor-15 in Patients with Acute Pulmonary Embolism
Risk stratification of pulmonary embolism (PE) relies on the detection of right ventricular (RV) dysfunction and/or injury. Existing biomarkers, such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), are characterized by high sensitivity but low specificity. Growth-differentiation factor-15 (GDF-15), a stress-responsive member of the TGF-β cytokine superfamily, is induced in the heart following injury and predicts an adverse outcome in acute coronary syndromes and chronic heart failure (CHF). In the present study, we investigated the prognostic value of GDF-15 in acute PE. Circulating levels of GDF-15 (immunoradiometric assay), and of cTnT and NT-proBNP (quantitative electrochemiluminescence) were measured on admission in 123 consecutive patients (52 men, 71 women; age,65±16 years) with confirmed acute PE. GDF-15 levels ranged between 533 and 47274 ng/L (median, 2196; interquartile range, 1333–3457). During the first 30 days, 17 patients (14%) died or suffered hemodynamic collapse. In these patients, median GDF-15 levels were higher than in those without complications, i.e. 6039 (IQR, 2778 –19722) vs. 2036 (IQR, 1279 –3176) ng/L (P<0.001). ROC analysis identified 4600 ng/L as the most appropriate cutoff level (AUC, 0.84) with a prognostic sensitivity of 0.71, a specificity of 0.90, a negative predictive value of 0.95, and a positive predictive value of 0.52. GDF-15 levels ≥4600 ng/L were associated with an elevated risk of a complicated clinical course over the first 30 days (OR, 20.7; 95% CI, 6.2– 69.9; P<0.001). CHF, diabetes, cardiogenic shock on admission, creatinine ≥1.3 mg/dL, RV dysfunction on echocardiography, cTnT ≥0.04 ng/mL, and NT-proBNP ≥1000 ng/L also were associated with an adverse outcome. However, only GDF-15 (OR, 23.4; 95% CI, 1.6–354.1; P=0.023) and cardiogenic shock on admission (P=0.002) emerged as independent predictors of poor prognosis by multivariable analysis. Further analysis using Cox regression demonstrated that GDF-15 ≥4600 ng/L independently predicted 6-month mortality (HR, 5.6; 95% CI, 1.4–22.1; P=0.015). Thus, GDF-15 is a promising new biomarker for the prediction of an unfavorable in-hospital course and long-term outcome in patients with acute PE.