Diagnostics and prognostic potential of current biomarkers in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Aims Circulating biomarkers are commonly used in diagnosis and prognosis of heart failure with preserved ejection fraction (HFpEF) in clinical practice. However, the diagnostic and prognostic potential of current biomarkers in HFpEF remain unclear. Methods and results We conducted a search of the PubMed, Web of Science, MEDLINE and SCOPUS (1900 to January 2020) databases of all diagnostic (n=1,104) and prognostic (n=53,497) biomarkers investigated in people with HFpEF. B-type natriuretic peptide (BNP) displayed satisfactory sensitivity (0.81, 95% CI: 0.76 to 0.85; I 2 =0) and specificity (0.86, 95% CI: 0.82 to 0.89; I 2 =16.9%) for the diagnosis of HFpEF. Natriuretic peptides (NPs), including N-terminal pro BNP (NT-proBNP) and BNP, were associated with over two-fold increased risk of mortality (NT-proBNP: HR=2.27, 95% CI: 1.69 to 3.06, I 2 =87.6%; BNP: HR=3.01, 95% CI: 1.27 to 7.21, I 2 =97.2%), hospitalisation (NT-proBNP: HR=3.54, 95% CI: 2.83 to 4.43, I 2 =83.4%), and a composite event of both (NT-proBNP: HR=2.55, 95% CI: 2.13 to 3.05, I 2 =78.1%; BNP: HR=2.28, 95% CI: 1.42 to 3.69, I 2 =75.8%) in people with HFpEF. Interestingly, Galectin-3 (Gal-3) (sensitivity: 0.70, 95% CI: 0.63 to 0.75, I 2 =86.7%; specificity: 0.78, 95% CI: 0.69 to 0.85, I 2 =68.6%) and soluble suppression of tumorigenicity 2 (sST2) (sensitivity: 0.58, 95% CI: 0.52 to 0.64, I 2 =88.1%; specificity: 0.59, 95% CI: 0.49 to 0.68, I 2 =69.5%) showed limited diagnostic potential of HFpEF. Conclusion Amongst currently available biomarkers, BNP remains the most reliable diagnostic marker of HFpEF. Although there was high heterogeneity between the studies included, BNP or NT-proBNP could also have promising prognostic potential in HFpEF.