Effect of Iron Deficiency on skeletal muscle metabolism in HFpEF

Diabetes, obesity and hypertension, all highly present comorbidities in HFpEF, seem to drive this disease by inducing low-grade systemic inflammation which in turn induces microvascular dysfunction and activates a cascade of events. Several studies have demonstrated that HFpEF is a systemic disease that affects not only cardiac, but also peripheral muscle energy metabolism. Iron deficiency (ID) could be an important contributor in this pathophysiological process.

Iron deficiency is present in 50% of chronic HF patients. Although HFpEF was not excluded from these cohort studies, it mainly included HF with reduced ejection fraction (HFrEF).

We hypothesize that ID is an important factor in the limitation of exercise capacity in HFpEF. Systemic low-grade inflammation does not only lead to microvascular dysfunction but also to iron deficiency. Iron deficiency has a direct effect on the muscle. Not only on the cardiac muscle but also the skeletal muscle is affected, impairing muscle contraction strength but also energy metabolism. The primary focus of this study will be delivering proof that the alterations in the muscle are more severe in HFpEF patients with ID compared to without ID.

We hypothesize that ID is an important factor in the limitation of exercise capacity in HFpEF. Systemic low-grade inflammation does not only lead to microvascular dysfunction but also to iron deficiency. Iron deficiency has a direct effect on the muscle. Not only on the cardiac muscle but also the skeletal muscle is affected, impairing muscle contraction strength but also energy metabolism. The primary focus of this study will be delivering proof that the alterations in the muscle are more severe in HFpEF patients with ID compared to without ID.

Not aplicable

o Measurement of PCR recovery time using MR spectroscopy

- Microvascular function

o Glycocalyx thickness (um)

o Heat induced hyperaemic response (% skin hyperaemic response)

- Exercise tolerance

o 6 minute walk test distance (m)

o maximum exercise capacity (METs on exercise test)