This paper is about preventing heart failure after myocardial infarction. One part of the solution is iron chelation done by Deferiprone, maybe later by ATH434. It is a free paper, here is the abstract.

Nat Commun

. 2022 Oct 27;13(1):6394.

doi: 10.1038/s41467-022-33776-x.

Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium

Ivan Cokic ¹, Shing Fai Chan ^{# 2}, Xingmin Guan ^{# 2}, Anand R Nair ^{# 1}, Hsin-Jung Yang ¹, Ting Liu ¹, Yinyin Chen ¹, Diego Hernando ³, Jane Sykes ⁴, Richard Tang ², John Butler ⁴, Alice Dohnalkova ⁵, Libor Kovarik ⁵, Robert Finney ⁶, Avinash Kali ¹, Behzad Sharif ², Louis S Bouchard ⁷, Rajesh Gupta ⁸, Mayil Singaram Krishnam ⁹, Keyur Vora ², Balaji Tamarappoo ², Andrew G Howarth ¹⁰, Andreas Kumar ¹¹, Joseph Francis ¹², Scott B Reeder ³, John C Wood ¹³, Frank S Prato ⁴, Rohan Dharmakumar ¹⁴

Affiliations expand

• PMID: 36302906

PMCID: PMC9613644 DOI: 10.1038/s41467-022-33776-xFree PMC article

Abstract

Sudden blockage of arteries supplying the heart muscle contributes to millions of heart attacks (myocardial infarction, MI) around the world. Although re-opening these arteries (reperfusion) saves MI patients from immediate death, approximately 50% of these patients go on to develop chronic heart failure (CHF) and die within a 5-year period; however, why some patients accelerate towards CHF while others do not remains unclear. Here we show, using large animal models of reperfused MI, that intramyocardial hemorrhage - the most damaging form of reperfusion injury (evident in nearly 40% of reperfused ST-elevation MI patients) - drives delayed infarct healing and is centrally responsible for continuous fatty degeneration of the infarcted myocardium contributing to adverse remodeling of the heart. Specifically, we show that the fatty degeneration of the hemorrhagic MI zone stems from iron-induced macrophage activation, lipid peroxidation, foam cell formation, ceroid production, foam cell apoptosis and iron recycling. We also demonstrate that timely reduction of iron within the hemorrhagic MI zone reduces fatty infiltration and directs the heart towards favorable remodeling. Collectively, our findings elucidate why some, but not all, MIs are destined to CHF and help define a potential therapeutic strategy to mitigate post-MI CHF independent of MI size.