Iron Deficiency and Deranged Myocardial Energetics in Heart Failure

Abstract

Among different pathomechanisms involved in the development of heart failure, adverse metabolic myocardial remodeling closely related to ineffective energy production, constitutes the fundamental feature of the disease and translates into further progression of both cardiac dysfunction and maladaptations occurring within other organs. Being the component of key enzymatic machineries, iron plays a vital role in energy generation and utilization, hence the interest in whether, by correcting systemic and/or cellular deficiency of this micronutrient, we can influence the energetic efficiency of tissues, including the heart. In this review we summarize current knowledge on disturbed energy metabolism in failing hearts as well as we analyze experimental evidence linking iron deficiency with deranged myocardial energetics.

Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population: a two-sample bidirectional Mendelian randomization study

“…[14,53] To date, many studies have investigated whether intravenous iron therapy effectively reverses myocardial remodeling and prevents myocardial remodeling owing to ischemic or non-ischemic injury, which is of great interest. [54,55] However, studies on the relationship between circulating iron parameters and myocardial iron are limited, and findings vary between studies; thus, the significance of circulating iron parameters as representatives of myocardial iron content remains unclear. [54,56] Although the relationship between the two is unclear, different studies have shown that ID, defined using circulating iron parameters, aids in diagnosing patients with HF and ID.…”

SIRT6 mediated histone H3K9ac deacetylation involves myocardial remodelling through regulating myocardial energy metabolism in TAC mice

“…More than 95% of ATP in the heart is produced by mitochondrial oxidative phosphorylation, and less than 5% of ATP is produced by glycolysis. 41 Any minor changes in ATP production and metabolism in myocardial tissues will affect the normal function of the heart. Mitochondria are the centre of myocardial energy metabolism, and their structural integrity and normal function are the basis for normal cardiac electrophysiological activity.…”

“…Myocardial energy metabolism disorder is caused by an imbalance of ATP generation or decomposition in the heart. More than 95% of ATP in the heart is produced by mitochondrial oxidative phosphorylation, and less than 5% of ATP is produced by glycolysis 41 . Any minor changes in ATP production and metabolism in myocardial tissues will affect the normal function of the heart.…”

Pathophysiology and Treatment Opportunities of Iron Deficiency in Heart Failure: Is There a Need for Further Trials?

“…Improving the functioning of the bone marrow and the erythroid line cannot be a key element, as iron works across a wide spectrum of Hb and red cell indices, and even in patients without anemia [ 25 , 37 ]. Effects on myocardial energetics are difficult to prove, although we have some limited mechanistic data on improving skeletal muscle energetics [ 38 ••], as well as a few proof-of-concept experiments in rodents and cell lines reviewed in detail elsewhere, demonstrating that abnormal cardiomyocyte energetics due to induced less or more severe ID (and also consequent anemia) can be reversed through the rapid replenishment of the missing iron [ 39 , 40 ]. It remains also unknown why, for example, in non-ischemic HF FCM does not impact “hard” clinical outcomes as it does in patients with primary ischemic etiology of the disease, as demonstrated in one of the sub-analyses of the AFFIRM-AHF trial [ 41 ].…”