Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction

Background: Little information is available about the prevalence and impact on exercise capacity and outcome of iron deficiency in heart failure with mid-range (HFmrEF) and preserved (HFpEF) ejection fraction in comparison to heart failure with reduced ejection-fraction (HFrEF). Furthermore, no data is available about the progression of ID in patients without baseline anaemia.
Methods: We evaluated baseline iron and haemoglobin-status in a single-centre, prospective heart failure database. Baseline functional status, VO2max, echocardiography and clinical-outcome (all-cause mortality and heart failure admissions) were evaluated. ID, anaemia, HFrEF, HFmrEF and HFpEF were defined according to established criteria.
Results: A total of 1197 patients (71% male) were evaluated (HFrEF, n = 897; HFmrEF, n = 229; HFpEF, n = 72). The overall prevalence of ID was 53% (50% in HFrEF; 61% in HFmrEF; 64% in HFpEF) and 36% for anaemia. ID was associated with a lower VO2max in patients with HFrEF, HFmrEF and HFpEF (p < .001 in all). Iron status more closely related to a poor VO2max than anaemia status (p < .001). Furthermore, poor clinical-outcome was more strongly associated with iron status than anaemia status. Exposing eight patients without anaemia to iron deficiency for 39 months resulted in one patient developing new-onset anaemia (defined as progression of ID). Patients with progression of ID exhibited a significant higher risk of heart failure hospitalisation and all-cause mortality (HR = 1.4; CI = 1.01–1.94; p = .046) than patients without progression.
Conclusions: Iron deficiency is common in patients with HFrEF, HFmrEF and HFpEF, and negatively affects VO2max and clinical-outcome. Progression of iron deficiency parallels an increased risk for worsening of heart failure.