Multi-Panel Biomarkers for Diagnosis of Heart Failure Across the Ejection Fraction Spectrum: A Population-Based Study

We conducted a cohort study to evaluate the diagnostic value of heart failure (HF) biomarkers across the ejection fraction spectrum. Using electronic health record data from Tayside and Fife regions of Scotland (1993-2021), we linked echocardiograms with plasma samples for biomarker analysis. The study included 156 patients with HF with reduced ejection fraction (HFrEF), 236 patients with preserved ejection fraction (HFpEF), and 186 controls without HF. All biomarkers were significantly elevated in patients with HF compared to controls. Patients with HFrEF had higher hs-TnT, NT-proBNP, and ANG-2 concentrations than those with HFpEF. All nine biomarkers demonstrated strong diagnostic accuracy for distinguishing HF from controls (AUC ≥0.90). However, no two-biomarker pair significantly improved discrimination over its best constituent marker in a majority of splits. This population-based study demonstrated significant diagnostic value of biomarkers for patients with HFrEF and HFpEF. All biomarkers discriminated HF from controls, with held-out AUCs from 0.90 to 0.97. Although each of these biomarkers reflects distinct pathophysiological aspects of HF that could potentially provide complementary diagnostic information, combination of biomarkers in our analysis did not improve discrimination over the best single biomarker. Further work is needed in integrating multi-biomarker panels to enhance patient selection efficiency in clinical trials, improve HF surveillance, and facilitate early diagnosis across healthcare systems, particularly for HFpEF