Cardiac iron concentration in relation to systemic iron status and disease severity in non‐ischaemic heart failure with reduced ejection fraction

Abstract

Aims Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction (HFrEF), CI has never been measured in non‐advanced HFrEF. We measured CI in left ventricular (LV) endomyocardial biopsies (EMB) from patients with non‐advanced HFrEF and explored CI association with systemic iron status and disease severity. Methods and results We enrolled 80 consecutive patients with non‐ischaemic HFrEF with New York Heart Association class II or III symptoms and a median (interquartile range) LV ejection fraction of 25 (18–33)%. CI was 304 (262–373) μg/g dry tissue. CI was not related to immunohistological findings or the presence of cardiotropic viral genomes in EMBs and was not related to biomarkers of systemic iron status or anaemia. Patients with CI in the lowest quartile (CIQ1) had lower body mass indices and more often presented with heart failure histories longer than 6 months than patients in the upper three quartiles (CIQ2–4). CIQ1 patients had higher serum N‐terminal pro‐B‐type natriuretic peptide levels than CIQ2–4 patients [3566 (1513–6412) vs. 1542 (526–2811) ng/L; P = 0.005]. CIQ1 patients also had greater LV end‐diastolic (P = 0.001) and end‐systolic diameter indices (P = 0.003) and higher LV end‐diastolic pressures (P = 0.046) than CIQ2–4 patients. Conclusion Low CI is associated with greater disease severity in patients with non‐advanced non‐ischaemic HFrEF. CI is unrelated to systemic iron homeostasis. The prognostic and therapeutic implications of CI measurements in EMBs should be further explored.

November 2020 at a glance: focus on comorbidities and medical treatment

“…Iron deficiency impairs cardiac contractility through decreased mitochondrial function 4 . Hirsch et al 5 . assessed iron concentrations in non‐ischaemic HF with reduced ejection fraction (HFrEF), using endomyocardial biopsies.…”

Myocardial iron content in non‐ischaemic cardiomyopathy: how much is known?

“…Among patients with mild symptomatic non-ischaemic cardiomyopathy examined by Hirsch et al, 14 there was no direct relationship between myocardial iron content and circulating biomarkers reflecting systemic iron status [ferritin, transferrin saturation, soluble transferrin receptor (sTfR), hepcidin]. However, it needs to be acknowledged that the reported study did not include the control group.…”

“…transferrin receptor seen in these failing hearts reflects inadequate intracellular iron amount required for metabolic needs. 13 Hirsch et al 14 provide novel evidence regarding myocardial iron status in middle-aged patients with cardiomyopathy. The authors performed left ventricular (LV) endomyocardial biopsy in patients with a short history of symptomatic, non-ischaemic HF (New York Heart Association class II > III, a median duration of the disease -around 2 months, no lesions in coronary arteries).…”

“…15 Particularly low hepcidin is also seen in patients with acute HF, and low hepcidin combined with high sTfR identify patients with unfavourable outcomes. 3 In the study of Hirsch et al 14 there is complementary evidence of the lack of association between iron status and inflammation demonstrated directly within failing myocardium itself. Indeed, there was no relationship between myocardial inflammation reflected by immuno-histological assessments (cellular density of inflammatory cells, such as CD3+, CD45R0+, LFA-1+, or MAC-1+) and myocardial iron content in patients with non-ischaemic cardiomyopathy.…”

“…14 Moreover, subjects in the lowest quartile of cardiac iron had lowest circulating hepcidin with a median of 17.3 ng/mL, indicating a lack of significant systemic inflammatory drive. 14 The study of Hirsch et al provides novel data on myocardial iron status in patients with non-ischaemic cardiomyopathy using an unique access to LV endomyocardial biopsy. Accumulated evidence make us distinctly differentiate between easily to be investigated systemic ID and depleted iron stores within the myocardium, 17 and interpret ID beyond local and systemic inflammatory responses.…”