Iron deficiency in heart failure

Abstract

Iron deficiency is a major heart failure co-morbidity present in about 50% of patients with stable heart failure irrespective of the left ventricular function. Along with compromise of daily activities, it also increases patient morbidity and mortality, which is independent of anaemia. Several trials have established parenteral iron supplementation as an important complimentary therapy to improve patient well-being and physical performance. Intravenous iron preparations, in the first-line ferric carboxymaltose, demonstrated in previous clinical trials superior clinical effect in comparison with oral iron preparations, improving New York Heart Association functional class, 6 min walk test distance, peak oxygen consumption, and quality of life in patients with chronic heart failure. Beneficial effect of iron deficiency treatment on morbidity and mortality of heart failure patients is waiting for conformation in ongoing trials. Although the current guidelines for treatment of chronic and acute heart failure acknowledge importance of iron deficiency correction and recommend intravenous iron supplementation for its treatment, iron deficiency remains frequently undertreated and insufficiently diagnosed in setting of the chronic heart failure. This paper highlights the current state of the art in the pathophysiology of iron deficiency, associations with heart failure trajectory and outcome, and an overview of current guideline-suggested treatment options.

The Impact of Clinical, Biochemical, and Echocardiographic Parameters on the Quality of Life in Patients with Heart Failure with Reduced Ejection Fraction

“…Interestingly, the serum ferritin levels, one of the most commonly used laboratory parameter in assessing iron status worldwide, tend to increase in inflammatory and chronic diseases and HF is a perfect example of such illnesses [ 68 ]. Nonetheless, the commonly accepted criteria for detecting ID in this population are: serum ferritin < 100 μg/L (identifying absolute ID) or serum ferritin 100–299 μg/L in combination with transferrin saturation (T sat ) < 20% (identifying functional ID) [ 69 , 70 ].…”

Iron Deficiency and Reduced Muscle Strength in Patients with Acute and Chronic Ischemic Stroke

“…Normal iron status was defined by a serum ferritin > 100 µg/mL and transferrin saturation (TSAT) ≥ 20% [21]. Iron deficiency type I (ID I) was considered when plasma ferritin levels were ≤100 µg/mL, and iron deficiency type II (ID II) was considered for plasma ferritin levels of 100-300 µg/L and TSAT < 20% [22]. Anemia was defined by hemoglobin plasma levels of fewer than 12 g/L in females and 13 g/L in males [13].…”

Exercise intolerance in heart failure: beyond mitochondrial dysfunction. Letter regarding the article ‘Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?’

“…3 Iron deficiency is highly prevalent in patients with stable HF and it is associated with progression and worsening of the syndrome, poor quality of life and exercise capacity, which is independent of haemoglobin levels. 2 The impairments in exercise performance are closely related to decreased oxygen availability, transport and utilization in the exercising cardiac and skeletal muscle, all of which can consequently induce irreversible structural changes within muscle tissue. 2 While experimental molecular research of iron deficiency in humans with HF is limited, a recent study has demonstrated an increase in ferritin levels (+84%) and hypoxia-induced factor 1 alfa, and decrease in adenosine triphosphate levels (−74%), which clearly indicated switch from aerobic to anaerobic metabolism.…”

“…2 The impairments in exercise performance are closely related to decreased oxygen availability, transport and utilization in the exercising cardiac and skeletal muscle, all of which can consequently induce irreversible structural changes within muscle tissue. 2 While experimental molecular research of iron deficiency in humans with HF is limited, a recent study has demonstrated an increase in ferritin levels (+84%) and hypoxia-induced factor 1 alfa, and decrease in adenosine triphosphate levels (−74%), which clearly indicated switch from aerobic to anaerobic metabolism. 4 Importantly, such impairments in mitochondrial function and morphology were reversed by a supplementation of transferrin-bound iron within 3 days, 4 that likely is a central mechanism of large randomized controlled trial findings investigating iron supplementation in HF.…”

“…4 Importantly, such impairments in mitochondrial function and morphology were reversed by a supplementation of transferrin-bound iron within 3 days, 4 that likely is a central mechanism of large randomized controlled trial findings investigating iron supplementation in HF. 2 Haemodynamic response to exercise depends on the regulation of sympathetic and parasympathetic nerve activity in heart and vasculature that is modulated by the central nervous system, the arterial baroreceptors, and the exercise pressor reflex. 3 During physical activity, the exercise pressor reflex is activated by the group III (e.g.…”