Applying rigorous eligibility criteria to studies evaluating prognostic utility of serum biomarkers in pulmonary embolism: A systematic review and meta-analysis.

PURPOSE To evaluate the value of biomarkers to prognosticate outcomes in patients with pulmonary embolism among studies of sound methodical quality. METHODS Ovid MEDLINE, Embase, CENTRAL, and non-indexed citations were searched from inception to March 2019. Biomarkers of interest included troponin I (TnI), troponin T (TnT), high-sensitive TnT (HS-TnT), brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), heart fatty acid binding protein (H-FABP), and D-dimer (DD). Included studies utilized key features of the Reporting Recommendations for Tumour Marker Prognostic Studies (REMARK) checklist and satisfied requirements of the Quality in Prognosis Studies (QUIPS) tool. The primary outcome was 30-day all-cause mortality (ACM). Secondary outcomes included PE-related mortality, or complicated clinical course (CCC). Pooled relative risk ratios (RR) were calculated using inverse-variance-weighted random-effects method. RESULTS Seventeen studies were analyzed. TnT ≥ 0.1 ng/mL and HS-TnT ≥ 14 pg/mL were associated with an increased 30-day ACM with RRs of 6.24 (95% CI, 1.86-20.96, I2 = 35%) and 6.81 (95% CI, 2.46-18.88, I2 = 0%), respectively. In the short-term (≤30 days): (1) TnI can prognosticate PE-related mortality; (2) both TnT and HS-TnT can prognosticate a CCC; (3) H-FABP can prognosticate a CCC; and (4) NT-proBNP can prognosticate a CCC. In the long-term (>30 days): (1) HS-TnT can prognosticate ACM; and (2) NT-proBNP can prognosticate ACM and PE-related mortality. CONCLUSIONS Several methodically sound studies allow for data pooling, and suggest that TnT, HS-TnT, TnI, NT-proBNP and H-FABP have prognostic value in patients with PE but confidence intervals are wide and relatively few patients constitute the analyses. The value of such markers on influencing clinical management remains to be determined. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019129889