Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction

BACKGROUND: Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure-volume loop analysis in HFPEF.

METHODS: 26 HFPEF patients who showed an increase in LV stiffness by pressure-volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin <100 μg/l or ferritin of 100-299 μg/l in combination with transferrin saturation <20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies.

RESULTS: Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p<0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r=-0.636, p<0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency.

CONCLUSION: In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID.