The role of impaired iron transport on exercise performance and prognosis in patients with chronic heart failure

Background: Iron deficiency (ID) is frequent in chronic heart failure (HF). Among HF-ID patients those with impaired iron transport (IIT) (Transferrin saturation (TSAT) < 20 %) have the worst prognosis. In HF survival is strictly related to exercise limitation but the link between IIT, exercise limitation and survival is at present undefined. Methods: We evaluated in 999 consecutive patients hospitalized for worsening HF whether IIT affects prognosis through cardiopulmonary exercise test (CPET), i.e. peak oxygen uptake (VO2) and ventilation vs. carbon dioxide (VE/VCO2) slope. In all patients at stabilization iron metabolism and maximal CPET were performed. Survival was assessed as all cause death, urgent LVAD and heart transplant were considered death equivalents. The causal relationship between survival and IIT, peakVO2 and VE/VCO2slope was assessed applying path analysis. Results: PeakVO2 VE/VCO2slope and TSAT were 68 ± 44 %pred, 35 ± 9 and 24.4 ± 12.9, respectively. PeakVO2 and VE/VCO2slope were 61 ± 18 vs. 72 ± 53 %pred and 38 ± 10 vs. 33 ± 8, in IIT vs. non IIT patients (p < 0.0001 in both). At univariable and multivariable analysis a correlation between survival and VO2, VE/VCO2slope and TSAT was observed; at Kaplan-Myer lower peakVO2, higher VE/VCO2slope and lower TSAT showed worst survival; at path analysis IIT showed both an important effect on survival independent from peakVO2 and VE/VCO2slope (48 %) and an effect on survival independently mediated by VE/VCO2slope and peakVO2 (52 %), contributing to the IIT negative effect on survival. Conclusions: The adverse impacts of low TSAT on prognosis are in part direct and in part mediated by mechanisms related to reduced peakVO2 and increased @VE/VCO2slope