Iron deficiency in heart transplant recipients

Exercise capacity is reduced in heart transplant (HTx) recipients compared to healthy individuals of the same age and gender. Our main hypothesis was that iron deficiency (ID) might partly explain this impairment. Intravenous iron treatment improves physical capacity in patients with heart failure, when ID is defined by liberal cut offs compared to the definition used in the general population. A suitable definition of ID in the HTx population is, however, unestablished. The purpose of this PhD thesis was to identify the prevalence of ID in a contemporary HTx population and to evaluate the effect of intravenous iron substitution on physical performance in HTx recipients with ID, as defined in heart failure. We also sought to assess if known markers of iron metabolism differed between HTx recipients with ID and healthy nontransplanted individuals. We screened most Norwegian HTx survivors and assessed their iron status using several definitions of ID, as suggested in the literature. Patients with ID defined as in heart failure were asked to attend the IronIC trial, a randomised, controlled and double-blind trial, where the effect of a single dose of intravenous iron substitution was compared with placebo. The primary endpoint was the baseline adjusted peak oxygen consumption (ml/kg/min), measured during a treadmill test at 6 months follow-up. Biobank samples collected at baseline and 6 months follow-up were analysed to assess important components of iron homeostasis. Forty-seven percent of the Norwegian HTx survivors had ID as defined in heart failure, and 5% had ID defined as in the normal population. The primary endpoint of the IronIC trial was neutral, as there was no between-group difference in peak oxygen consumption (ml/kg/min) at 6 month follow-up (0.3(-0.9-1.4) ml/kg/min, p for difference= 0.66). However, in a small group of patients (n=12) with ID as defined in the normal population, peak oxygen consumption was improved after iron treatment (between-group difference, 4.37 ml/kg/min (0.01-8.72), p=0.0495). Biobank analyses revealed that markers of iron metabolism did not significantly differ between the HTx recipients in the IronIC trial and a healthy control group. Our results show that ID is prevalent among HTx recipients when defined as in heart failure. However, intravenous iron therapy did not improve physical capacity and markers of iron metabolism were similar to that of a healthy population. This suggests that in HTx recipients, ID should be defined as in the general population, which is also underscored by the improved physical capacity observed in a small group of patients with ID defined in this way. True ID might reduce exercise capacity. On the other hand, iron supplement provided to patients without ID might result in iron overload with subsequent tissue toxicity, reduced graft function and increased infection- and rejection rate. It is important to establish a suitable definition of ID in the HTx population to appropriately provide iron substitution