Introduction: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) develop pathologic hemodynamic responses during exercise. Biomarkers that reflect specific pathophysiological pathways might help to understand mechanisms in HFpEF. We hypothesized that novel biomarkers reflect hemodynamic abnormalities at rest and during exercise. Methods: Subjects with invasively-diagnosed HFpEF (n = 38) and controls free of HF (n = 20) underwent invasive catheterization at rest and during exercise with blood sample collection for assessment of novel biomarkers: hs troponin T, copeptin, NT-proBNP, mid regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), and mid regional pro-adrenomedullin (MR-proADM). Results: Compared to controls, subjects with HFpEF displayed elevations in biomarkers of myocardial injury/stress (troponin T, copeptin), myocyte stretch (NT-proBNP, MR-proANP), and neurohormonal activation (CT-proET-1, MR-proADM) both at rest and during exercise (Table 1). As compared to controls, HFpEF subjects displayed greater increases in troponin T, copeptin and NT-proBNP during exercise (Fig. A), and the increase in troponin T varied directly with changes in left filling pressures (r = 0.27, P = .04). CT-proET-1 and MR-proADM levels were highly correlated with PA mean pressures (r = 0.73 and r = 0.65, both P < .0001)(Fig. B), which were driven by both increases in left heart filling pressure (r = 0.67 and r = 0.62, both P < .0001) and pulmonary vascular resistance (r = 0.32, P = .02 and r = 0.26, P = .05). Conclusions: Biomarkers might reflect specific pathophysiology of HFpEF, including pulmonary vascular disease and an increase in filling pressure during exercise.Table 1Biomarker levels at rest and exerciseControl (n = 20)HFpEF (n = 38)PBaselinehs troponin T (pg/mL)5.2 (4.2, 8.6)12.4 (7.8, 22.3)<0.0001Copeptin (pmol/L)5.3 (3.4, 12.8)11.0 (6.0, 20.8)0.04NT-proBNP (pg/mL)100 (54, 236)436 (147, 978)0.0002MR-proANP (pmol/L)128 (90, 147)239 (139, 300)0.001CT-proET-1 (pmol/L)69 (56, 74)105 (83, 130)<0.0001MR-proADM (nmol/L)0.6 (0.5, 0.7)1.0 (0.8, 1.4)<0.0001Peak Exercisehs troponin T (pg/mL)6.3 (4.8, 9.7)13.8 (8.9, 26.2)0.0002Copeptin (pmol/L)5.8 (3.4, 9.3)14.5 (8.4, 35.1)0.001NT-proBNP (pg/mL)122 (47, 279)484 (155, 1133)0.0009MR-proANP (pmol/L)174 (128, 226)267 (184, 359)0.007CT-proET-1 (pmol/L)73 (62, 85)118 (87, 138)<0.0001MR-proADM (nmol/L)0.6 (0.5, 0.7)1.0 (0.8, 1.3)<0.0001 Open table in a new tab