How to predict subsequent chronic thromboembolic hypertension after acute pulmonary embolism already at the acute phase: from D-dimer/NT-proBNP ratio to echocardiographic findings

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, but severe late complication of acute pulmonary embolism (APE). Efforts are made to identify patients at risk during acute stage. In some cases, CTEPH is presumed to develop as a result of an acute-on-chronic thromboembolic event. Hence, assessing the patients for both laboratory and echocardiographic signs of chronicity may identify group at risk of subsequent CTEPH. Purpose Our goal was to establish whether biochemical markers combined with transthoracic echocardiography (TTE) findings will identify a group of APE patients requiring strict follow-up for CTEPH development. Methods We followed consecutive APE patients for whom baseline D-dimer and N-terminal pro-B type natriuretic peptide (NT-proBNP) concentrations were available, and who had TTE performed. All patients were followed up in an outpatient clinic. If residual dyspnoea was present, they were diagnosed for CTEPH. Eventually, this complication was confirmed when elevated mean pulmonary artery systolic pressure above 20 mmHg was found on right heart catheterisation. Results We included 342 patients, of whom 22 (6.4%) developed CTEPH during follow-up. They had higher median baseline NT-proBNP (1860 vs 550 ng/L, p < 0.05) and lower, though not statistically significant, D-dimer (4210 vs 5330 mcg/L, p = 0.1) concentrations. They differed remarkably in D-dimer/NT-proBNP ratio (DD/NT-proBNP; 2.9 vs 12.0 mcg/ng, p < 0.001). This parameter provided high negative predictive value of 98.3% (95% CI 95.7-99.7%) for subsequent CTEPH diagnosis at a threshold of 10 mcg/ng, increasing two-fold CTEPH incidence rate in the remaining group (20/171 cases, OR 11.2, 95%CI 2.6-48.6; p = 0.0013). As shown previously, the CTEPH(+) group had higher mean tricuspid peak regurgitation gradient (TRPG; 46.5 vs 32 mmHg, p < 0.001) as well. Combining TRPG of at least 36 mmHg with abovementioned DD/NT-proBNP cutoff point allowed to design a two-step decision model, which narrowed down initial cohort to a group of 87 patients, with 17 CTEPH cases among them (19.5% positive predictive value). Conclusion Patients with DD/NT-proBNP ratio above 10 mcg/ng constitute a group of low risk of CTEPH development. The remaining APE survivors with baseline TRPG of 36 mmHg or more required a close monitoring, as one out of five may develop CTEPH during follow-up.