Iron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear.
Consecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography (CPETecho) in a tertiary care dyspnea clinic. ID was defined as ferritin <300µg/l and transferrin saturation (TSAT)<20% and its impact on peak oxygen uptake (peakVO), biventricular response to exercise, and peripheral oxygen extraction was assessed.
Of 272 CPETecho patients, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO (14.6±7.6 vs 17.8±8.8ml/kg/min; p=0.009) and maximal workload (89±50 vs 108±56 watt p=0.047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (p<0.05) and depressed RV function by tricuspid s' (p=0.004), tricuspid annular plane systolic excursion (TAPSE; p=0.034) and RV end-systolic pressure-area ratio (RVESPAR; p=0.038), with more RV-pulmonary artery uncoupling measured by TAPSE/systolic pulmonary arterial pressure ratio (p=0.023). RVESPAR change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09±0.72 vs. 2.58±1.14 mmHg/cm; p<0.001). ID was associated with impaired peripheral oxygen extraction (peakVO/peak cardiac output; p=0.036). CPETecho resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e' ratio above 14, with equal distribution in patients with (28.6%) or without ID (25.4%, p=0.611). None of the aforementioned findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea.
In patients with unexplained dyspnea without clear HF at rest, ID is common and associated with reduced exercise capacity, diminished biventricular contractile reserve and reduced peripheral oxygen extraction.

Copyright © 2021. Published by Elsevier Inc.