Abstract 15232: Iron Deficiency and Elevated Hepcidin Predict Abnormal Pulmonary Vascular Responses to Exercise in Patients With Preserved Ejection Fraction Undergoing Evaluation of Dyspnea

IntroductionHepcidin is a master regulator of iron homeostasis that reduces iron absorption when circulating levels are elevated. In preclinical models, iron deficiency and inappropriately elevated hepcidin levels have been implicated in pulmonary arterial hypertension. However, the role of hepcidin dysregulation on pulmonary vascular function in patients with dyspnea on exertion (DOE) and preserved ejection fraction remains unclear.HypothesisWe hypothesized that a low ratio of transferrin saturation to hepcidin is associated with abnormal pulmonary vascular responses during exercise.MethodsCardiopulmonary exercise testing (CPET) using cycle ergometry with invasive hemodynamic monitoring was performed in 127 patients with preserved ejection fraction (LVEF ≥ 50%) undergoing evaluation for dyspnea. Serum hepcidin and transferrin saturation (Tsat) were measured at the time of CPET and the ratio (Tsat/Hepcidin) was used as a measure of iron homeostasis and hepcidin dysregulation, with low values reflecting inappropriate elevation in hepcidin level relative to iron bioavailability.ResultsPatients had the following characteristics (mean ± SEM)age 58 ± 1; 28% male; BMI 29.6 ± 0.6 kg/m; Hb 12.0 ± 0.1 g/dL, Tsat 24.8 ± 1.0%; hepcidin 17.9 ± 1.4 ng/ml; Tsat/Hepcidin 2.7 ± 0.2 ml/ng. The Tsat/Hepcidin ratio inversely correlated with pulmonary vascular resistance (PVR) at rest (r = -0.25, p=0.005) and peak exercise (r = -0.27, p=0.002, A-B). Lower Tsat/Hepcidin ratio was also associated with lower peak VO2, lower cardiac index, higher PA pressures, and higher PAP / CO slope (C), but did not associate with exercise pulmonary arterial wedge pressure (PAWP; r = -0.13, p = 0.13).ConclusionHepcidin dysregulation, reflected by low Tsat/Hepcidin ratio, is more closely related to pulmonary vascular dysfunction than left ventricular dysfunction during exercise in patients being evaluated for dyspnea on exertion.