D-dimer to NT-proBNP ratio in acute pulmonary embolism patients stratifies risk of CTEPH

There are ongoing efforts to identify patients at risk of chronic thromboembolic pulmonary hypertension (CTEPH) during acute pulmonary embolism (APE). Lower D-dimer levels and right heart overload at APE diagnosis were reported to predict CTEPH. We hypothesized that plasma D-dimer to N-terminal pro-B type natriuretic peptide (NT-proBNP) ratio assessed during APE may be useful for early CTEPH screening. We followed 342 APE survivors (median age 64.5 years, females 56.1%), for median 39 (25-64) months. Despite ≥3 months anticoagulation CTEPH was diagnosed in 22 (6.4%) patients (CTEPH(+)). At APE diagnosis, CTEPH(+) compared to subjects without this sequela (CTEPH(-)) presented with advanced right ventricular overload: increased tricuspid regurgitation peak gradient (TRPG) (46.5 mmHg versus 32.0 mmHg; p<0.001) and NT-proBNP (1860 ng·L −1 versus 515 ng·L −1 ; p=0.02). Despite no differences in plasma D-dimer (4210 mcg·L −1 versus 5330 mcg·L −1 ; p=0.10), the ratio of D-dimer to NT-proBNP (DD/NT-proBNP) was significantly lower in the CTEPH(+) cohort versus the CTEPH(-) cohort (2.89 mcg·ng −1 versus 12.0 mcg·ng −1 ; p<0.001). In patients with DD/NT-proBNP≤10 CTEPH was diagnosed in 20 cases (11.7%), whereas in the group with DD/NTproBNP> 10 CTEPH could only be detected in 2/171 cases (1.2%) with an OR 0.09 (95% CI 0.02–0.38; p=0.0013), a sensitivity of 90.9% (95%CI 70.8-98.9%), a specificity 52.8% (95%CI 47.2-58.4%), a negative predictive value 98.8% (95%CI 95.8-99.9%), a and positive predictive value of 11.7% (95%CI 7.3-17.5%). Combination of DD/NT-proBNP≤10 with TRPG≥36 mmHg detected in 87 patients 17 patients with CTEPH (19.5% CTEPH incidence). In conclusion, DD/NT-proBNP>10 mcg·ng −1 identifies patients with low risk of subsequent CTEPH diagnosis, while DD/NT-proBNP≤10, especially presenting TRPG≥36 mmHg at echocardiography, form high risk group at follow up.