Iron Deficiency: A New Target for Patients With Heart Failure.

Caterina Rizzo,Roberta Ruggieri,Andrea Passantino,Domenico Scrutinio,Rosa Carbonara

doi:10.3389/fcvm.2021.709872

Abstract

Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF). ID is estimated to be present in up to 50% of outpatients and is a strong independent predictor of HF outcomes. ID has been shown to reduce quality of life, exercise capacity and survival, in both the presence and absence of anemia. The most recent 2016 guidelines recommend starting replacement treatment at ferritin cutoff value <100 mcg/l or between 100 and 299 mcg/l when the transferrin saturation is <20%. Beyond its effect on hemoglobin, iron plays an important role in oxygen transport and in the metabolism of cardiac and skeletal muscles. Mitochondria are the most important sites of iron utilization and energy production. These factors clearly have roles in the diminished exercise capacity in HF. Oral iron administration is usually the first route used for iron repletion in patients. However, the data from the IRONOUT HF study do not support the use of oral iron supplementation in patients with HF and a reduced ejection fraction, because this treatment does not affect peak VO2 (the primary endpoint of the study) or increase serum ferritin levels. The FAIR-HF and CONFIRM-HF studies have shown improvements in symptoms, quality of life and functional capacity in patients with stable, symptomatic, iron-deficient HF after the administration of intravenous iron (i.e., FCM). Moreover, they have shown a decreased risk of first hospitalization for worsening of HF, as later confirmed in a subsequent meta-analysis. In addition, the EFFECT-HF study has shown an improvement in peak oxygen consumption at CPET (a parameter generally considered the gold standard of exercise capacity and a predictor of outcome in HF) in patients randomized to receive ferric carboxymaltose. Finally, the AFFIRM AHF trial evaluating the effects of FCM administration on the outcomes of patients hospitalized for acute HF has found significantly fewer hospital readmissions due to HF among patients treated with FCM rather than placebo.

Highlights

Heart failure (HF) is a major cause of morbidity and mortality worldwide, and a growing public health problem: the incidence of HF with reduced ejection fraction is 1–2% in the general population and as high as 10% in the population over 65 years of age.Patients with HF have many comorbidities that affect their quality of life, clinical management and prognosis [1]; treatment of comorbidities does not always improve patients outcomes; Iron Deficiency and Heart Failure for example, anemia treatment with agents stimulating erythropoiesis have not demonstrated any benefit in HF or sleep related breathing disorders
In a study population of 387 patients with HF with reduced ejection fraction, both transferrin saturation (TSAT) ≤ 19.8% and serum iron ≤ 13 μmol/l (ID criteria validated by bone marrow staining) have been found to be predictors of death during a 2 year follow-up, whereas isolated low ferritin was not associated with the risk of death [6]
The AFFIRM-AHF trial is the first placebo-controlled trial the designed to evaluate the effect of ferric carboxymaltose (FCM) in patients hospitalized for acute HF [53]

Summary

INTRODUCTION

Heart failure (HF) is a major cause of morbidity and mortality worldwide, and a growing public health problem: the incidence of HF with reduced ejection fraction is 1–2% in the general population and as high as 10% in the population over 65 years of age. In a study population of 387 patients with HF with reduced ejection fraction, both TSAT ≤ 19.8% and serum iron ≤ 13 μmol/l (ID criteria validated by bone marrow staining) have been found to be predictors of death during a 2 year follow-up, whereas isolated low ferritin was not associated with the risk of death [6]. The Effect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency (EFFECTHF) study [51] showed that FCM improves the VO2 peak, as measured by CPET In this randomized study, in a nonblinded fashion, 172 patients in NYHA class II or III, with ejection fraction

Results

Iron in Acute HF

CONCLUSION