Iron causes chronic heart failure in half of heart attack survivors, according to a new study

Iron causes chronic heart failure in half of heart attack survivors, according to a new study

Željezo uzrokuje kronično zatajenje srca kod polovice osoba koje su preživjele srčani udar, pokazalo je značajno istraživanje

A comprehensive model of how hemorrhagic infarction promotes chronic heart failure via fat deposition. a) After MI, compensatory remodeling promotes partial recovery of LV function in the first weeks after the index event. In hemorrhagic infarction, extravasated red blood cells stimulate active inflammation and participate in the formation of fat deposits within the infarct zone. This makes hemorrhagic MI very active in relation to functional losses, which define chronic heart failure (CHF). In contrast, nonhemorrhagic MIs are not iron-rich and do not result in prolonged inflammation or promote fat deposition, which stabilizes the infarct zone leading to stable functional remodeling in the chronic phase of infarction. b) Iron mediates a repetitive cycle of events that contribute to fat deposition in the chronic phase of hemorrhagic MI. Iron from hemorrhage promotes the recruitment of nonpolarized macrophages and oxidizes lipids in its vicinity; oxidized lipid and iron are taken up by macrophages, which stimulate their polarization into a pro-inflammatory state and turn into foam cells. Foam cells produce ceroids and destabilize lysosomes and trigger foam cell apoptosis, the remnants of which participate in fat deposition, whereby the released iron is recycled to enter a pathway that continues to continuously support inflammation and the growth of fat depots. Credit: Nature Communications (2022). DOI: 10.1038/s41467-022-33776-x

A multi-institutional study led by Rohan Dharmakumar, Ph.D., of the Indiana University School of Medicine, found that iron promotes the formation of fatty tissue in the heart and leads to chronic heart failure in about 50% of heart attack survivors. The discovery, recently published in Nature Communicationsis paving the way for treatments that have the potential to prevent heart failure in nearly half a million people a year in the United States and many millions more worldwide.

“We identified the main cause for the first time chronic heart failure following a heart attack”, said Dharmakumar.

Dharmakumar is executive director of the IU Krannert Cardiovascular Research Center and associate director of research at the Cardiovascular Institute, a joint venture between the IU School of Medicine and IU Health.

“While advances among populations have made it possible to survive a heart attack for the majority, too many survivors suffer from long-term complications such as cardiac arrest,” said Subha Raman, MD, who is the physician director of the Institute for Cardiovascular Diseases. “Dr. Dharmakumar’s groundbreaking science sheds light on who is at risk and why, and points to an effective way to prevent these complications.”

The study, which involved collaborators from institutions in the United States and Canada, followed large animal models for six months. It found that in heart attacks that result in bleeding inside the heart muscle – which is about half of them – the scar tissue is slowly replaced by fat. Adipose tissue can’t effectively push blood out of the heart, and that’s what leads to heart failure and ultimately death in many hemorrhagic heart attack survivors, Dharmakumar said.

“Using non-invasive imaging techniques, histology and molecular biology, and various other technologies, we have shown that iron from red blood cells is what drives this process,” he explained. “When we removed the iron, we reduced the amount of fat in the heart muscle. This discovery paves the way for clinical research to correct or mitigate iron-related effects in patients with hemorrhagic myocardial infarction.”

Dharmakumar’s team is currently testing iron chelation therapy to do just that in a clinical trial just started.

“Thanks to an ongoing clinical trial led by his team at Indiana University, I’m excited to see how this treatment improves the lives of millions of heart attack survivors around the world,” said Raman.

More information:
Ivan Čokić et al., Intramyocardial hemorrhage causes fatty degeneration of the infarcted myocardium, Nature Communications (2022). DOI: 10.1038/s41467-022-33776-x

Quote: Iron causes chronic heart failure in half of heart attack survivors, new study finds (2022, Nov. 1) Retrieved Nov. 2, 2022, from -failure- survived.html

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