Impact of iron deficit in exercise capacity in heart failure patients: the role of VE/VCO2 slope and VO2peak

Aims Iron Deficit (ID) is frequently observed in HF patients even in the absence of anemia. In Heart Failure (HF) patients ID is associated to a reduced exercise performance regardless of anemia, related to abnormality in O2 delivery and utilization (evaluated by VO2 peak) and/or to inefficiency in ventilation during exercise (evaluated by VE/VCO2 slope), respectively. Of note, both peak VO2 and VE/VCO2 are independent predictors of HF severity being in ID HF patients reduced and increased, respectively. The aim of this study is evaluating whether it is possible to indicate as the leading cause of exercise limitation in HF patients with ID, but not anemia oxygen delivery abnormalities or reflex induced hyperventilation or whether both are concomitant. Methods and Results We analysed data of 1043 patients hospitalized for HF. 413 patients have ID (transferrin saturation, TSAT <20%) and 630 have TSAT≥20%. Patients with TSAT<20% showed a significantly lower VO2 anerobic threshold (AT) and VO2 peak and a higher VE/VCO2 slope, also when parameters were adjusted for hemoglobin (Hb), left ventricular ejection fraction (LVEF), age, gender and serum creatinine. In particular, in patients with TSAT< 20% VO2AT= 688 ± 290 ml/min, VO2 peak= 967 ± 377 ml/min, VO2 peak/Kg= 15 ± 3 ml/min, and VE/VCO2= 38 ± 9 while in patients with TSAT≥20% VO2AT= 881 ± 357 ml/min; VO2 peak= 1269 ± 529 ml/min, VO2peak/Kg= 16 ± 6 ml/min, and VE/VCO2= 33 ± 8 (Table 1). Finally, adjusting also for VO2 peak difference between TSAT< and ≥ 20% for VE/VCO2 persists as after adjusting for VE/VCO2 VO2 peak differences did (Fig 1a and 1b). Conclusion In HF patients ID is associated with exercise performance impairment independently from anaemia, age, left ventricle ejection fraction and serum creatinine. Both peakVO2 and VE/VCO2 relationship slope are pivotal and independent causes of exercise limitation in these patients.