Muscle function is highly dependent on oxidative phosphorylation as a source of energy. Interestingly, iron deficiency has been shown to have severe effects on muscle function due to its effect on hematopoiesis, as well as muscle bioenergetics. It is this link that prompted Melenovsky et al. to explore the role of iron deficiency in heart failure (HF). With reports showing that approximately half of HF patients suffer from iron deficiency (ID), iron supplementation could be an important point of intervention beyond the correction of hemoglobin levels.
Melenovsky et al. conducted their study on a group of 44 chronic HF and 25 healthy control patients. They used magnetic resonance spectroscopy (31P MRS) method to measure parameters related to muscle function (maximal isometric strength), energy production (concentration of phosphocreatine, ATP and inorganic phosphate), and acidosis. Presented results support the hypothesis that ID correlates with the severity of the HF symptoms, as measured by the skeletal muscle myopathy and greater phosphocreatine change during exercise (PCr drop/work: 5.6 W-1 in controls compared to 9.1W-1 in HF group, p = 0.03). This change was even more pronounced in the HF-ID group (9.4 W-1, p = 0.27 compared to HF group without ID). Furthermore, in HF-ID patients exercise induced change in PCr correlated with muscle acidosis (r = 0.74, p < 0.0001) which was not the case in HF patients without ID nor in control healthy subjects (r = 0.03, p = 0.94). This correlation is likely a result of a shift from oxidative phosphorylation towards anaerobic glycolysis, and it underlies symptoms like fatigue and impaired muscle performance.

In the final experiment, authors tested if iron supplementation by intravenous ferric carboxymaltose administration was sufficient to restore normal muscle function within one month. While such treatment restored the hemoglobin levels, it did not result in a significant improvement of muscle performance. Together, this suggests that iron interventions may require longer durations to become fully effective. Overall, due to the small patient group and short observation time limiting the final conclusion of the study authors postulate that iron should remain in the scope of future, systemic, and prolonged studies.
CLINICAL IMPACT
Heart failure patients commonly show iron deficiency and are more symptomatic (lower peak muscle strength and greater acidification of muscle during exercise).
This is supportive of metabolic shift towards anaerobic glycolysis.
Targeting iron deficiency in HF patients may improve exercise capacity, beyond the correction of hemoglobin levels.
Original article: Circ Heart Fail. 2018 Sep;11(9):e004800.
Author: Gabriela Plucinska