{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:09:30Z","timestamp":1792447770108,"version":"4.5.0"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,6,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and evaluate the applicability of monitoring it non\u2010invasively in human explanted hearts.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Biventricular tissue iron levels were measured in both failing (n=138) and non\u2010failing control (NFC, n=46) explanted human hearts. Clinical phenotyping was complemented with comprehensive assessment of myocardial remodeling and mitochondrial functional profiles, including metabolic and oxidative stress. Myocardial iron status was further investigated by cardiac magnetic resonance imaging. Myocardial iron content in the left ventricle was lower in HF versus NFC (121.4 [88.1\u2013150.3] versus 137.4 [109.2\u2013165.9] \u03bcg\/g dry weight), which was absent in the right ventricle. With a priori cutoff of 86.1\u00a0\u03bcg\/g d.w. in left ventricle, we identified 23% of HF patients with MID (HF\u2010MID) associated with higher NYHA class and worsened left ventricle function. Respiratory chain and Krebs cycle enzymatic activities were suppressed and strongly correlated with depleted iron stores in HF\u2010MID hearts. Defenses against oxidative stress were severely impaired in association with worsened adverse remodeling in iron\u2010deficient hearts. Mechanistically, iron uptake pathways were impeded in HF\u2010MID including decreased translocation to the sarcolemma, while transmembrane fraction of ferroportin positively correlated with MID. Cardiac magnetic resonance with T2* effectively captured myocardial iron levels in failing hearts.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">MID is highly prevalent in advanced human HF and exacerbates pathological remodeling in HF driven primarily by dysfunctional mitochondria and increased oxidative stress in the left ventricle. Cardiac magnetic resonance demonstrates clinical potential to non\u2010invasively monitor MID.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.022853","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T10:36:38Z","timestamp":1654252598000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":69,"title":["Myocardial Iron Deficiency and Mitochondrial Dysfunction in Advanced Heart Failure in Humans"],"prefix":"10.1161","volume":"11","author":[{"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Medicine Faculty of Medicine and DentistryEdmonton Alberta Canada"},{"name":"Mazankowski Alberta Heart Institute Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3957-8988","authenticated-orcid":false,"given":"K. 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