Background:
Systemic iron deficiency is present in up to 50% of patients with chronic heart failure (HF) and it is associated with impaired exercise tolerance and poor prognosis. Myocardial iron deficiency (MID) in HF patients has recently been described; however, its causes and consequences remain unknown.
Purpose:
We examined impact of HF and dietary iron content on systemic iron status, myocardial iron content, cardiac structure, function, expression of iron regulator hepcidin and other iron-related genes and survival in well-defined rat HF model induced by volume overload due to aorto-caval fistula (ACF).
Methods:
8-week old male Sprague Dawley rats fed defined synthetic diets with low, normal or high iron content underwent needle ACF/sham operation (n = 28/30). After 21 weeks, we performed echocardiography and laboratory analyses. Separate animal cohort served for survival analysis.
Results:
MID developed in HF animals. In pooled data, there was positive relation of left ventricular function and inverse relation of pulmonary congestion to myocardial iron content. Iron suplementation did not normalize myocardial iron content; however, it improved survival. Cardiac hepcidin was markedly upregulated in HF animals. It was not related to systemic or cardiac iron levels, but strongly correlated with markers and parameters of heart injury. Identical iron-independent pattern was observed for several iron-related gene expression.
Conclusions:
In rat HF model, MID is not caused by defective iron absorption or decreased systemic iron levels, but rather by intrinsic myocardial iron deregulation. Altered cardiac hepcidin and other iron-related gene expression is driven by iron-independent stimuli. Although the mechanisms of MID development remain incompletely understood, myocardial iron content enhancement may improve cardiac function and survival.
