- A new study used animal models to investigate why 50% of people develop chronic heart failure after experiencing a heart attack.
- Researchers found that iron deposits following heart attack lead to the formation of fatty tissue in the heart, which causes chronic heart failure.
- They also found that drugs that remove iron may mitigate some symptoms of chronic heart failure.
- The findings from the study could pave the way toward treatments that mitigate chronic heart failure following a heart attack.
A heart attack occurs when a blood clot blocks blood flow to the heart. Around 1 million people in the United States experience a heart attack each year.
Medical and surgical reperfusion treatments can reopen blocked arteries and save lives. Nevertheless, around 50% of individuals who have a heart attack subsequently develop chronic heart failure and die within 5 years.
Increasing evidence suggests that heart attack can lead to chronic iron deposition and a buildup of pro-inflammatory immune cells.
Other research shows that fat deposition in the heart attack zone is also common and is linked to impaired cardiac function. It remains unknown how fat deposition around the heart attack scar happens.
Understanding more about how chronic heart failure develops post-heart attack could pave the way for new treatment and prevention strategies.
In a new study, researchers investigated canine models of heart attack and reperfusion.
The researchers found that iron buildup precedes the formation of fatty tissue in the heart, which in turn leads to chronic heart failure. They also found that drugs that remove iron from the body could mitigate signs of chronic heart failure following a heart attack.
“The implications of the study suggest a mechanism leading to heart failure, which could potentially be altered to improve outcomes and survival,” Dr. William Kessler, board certified cardiothoracic surgeon with Cardiothoracic & Vascular Surgeons, not involved in the study, told Medical News Today.
The study was recently published in Nature Communications.
The link between iron buildup and heart failure
For the study, the researchers studied a canine model. All the animals had a heart attack, but some also bled into the heart muscle afterward, one of the most common and damaging injuries to the heart after a heart attack.
They monitored the dogs over the next six months with cardiac MRI, microscope evaluations, and Western blot analysis, a way of separating and identifying proteins.
The researchers gave some of the dogs with bleeding into their heart muscles an iron chelator — a drug that removes excess iron from the body — for 8 weeks after they had a heart attack. The remaining dogs did not receive the drug and were kept as controls.
From cardiac MRI imaging, the researchers found that iron deposition in the heart was higher in dogs with a bleed into the heart muscle after a heart attack. They also found that the elevated iron levels remained approximately constant from 3 days to 6 months after the heart attack.
They also found that fat deposition is characteristic of a heart attack and that levels of fat deposition correlate with iron buildup.
Chelators significantly reduced iron and fat buildup and correlated with positive anatomical and functional recovery.
“A heart attack occurs when a blockage occurs when one of the small arteries supplying the heart muscle itself, called a coronary artery blockage, “ Dr. Ronald Grifka, clinical professor of pediatric cardiology and chief medical officer at the University of Michigan Health-West, not involved in the study, told MNT.
“The blockage usually is caused by a buildup of cholesterol and then a small blood clot. This blockage results in reduced blood flow to an area of the heart, which results in a “bruise“ of the heart muscle in this area, very similar to a bruise we might have in an arm or leg muscle. A bruise is a small collection of red blood cells inside the muscle. When all bruises resolve, those red blood cells are broken down, leaving small iron deposits in the muscle.”
– Dr. Ronald Grifka, cardiologist
The researchers noted, however, that after the chelator treatment ceased, iron and fat content began to increase, although to a lesser extent than in the untreated control group.
The researchers noted that their findings suggest a causal relationship between iron buildup following a heart attack and fat deposition in the heart.
What are the effects of chelating iron?
Dr. Richard Wright, a cardiologist at Providence Saint John’s Health Center in Santa Monica, CA, not involved in the study, told MNT that chelating iron might have a “substantial downside.”
“It is well known that patients with chronic heart failure often have a deficiency of iron within their beating heart cells and that such reductions aggravate the heart failure state,” Dr. Wright explained.
“Indeed in such individuals, replacement of iron leads to improvement in their heart function, and hence chelation of iron in this situation would be expected to be detrimental, not helpful.”
“It is not possible to direct chelation therapy to the injured part of the heart, while simultaneously sparing the functional part of the heart. Hence in someone with a large heart attack, initial hemorrhage into that damaged portion of the heart, and inflammation in that segment (perhaps amplified by iron released from the hemorrhage), iron chelation could be harmful if the patient has already developed heart failure,” he added.
– Dr. Richard Wright, cardiologist
More research needed in humans
When asked about the study’s limitations, Dr. Grifka noted that as this study was performed on dogs, it remains to be seen whether similar findings may be replicated in humans.
In addition, Dr. Wright said that the study does not answer the question of whether iron levels should be limited or increased following a heart attack.
He further noted that as most heart attacks are relatively small, the data from this study may not apply to all individuals who’ve had a heart attack. He concluded:
“Further research could potentially distinguish which patients, if any, might have improved outcomes by manipulating iron — perhaps by routine use of cardiac MRI.”
Implications for chronic heart failure
The researchers concluded that their findings explain why some, but not all, heart attacks develop into chronic heart failure.
“This paper outlines an extremely interesting hypothesis that certain heart attacks will result in fatty deposition, chronic deterioration, and heart failure,” Dr. Kessler said.
“Bleeding into the tissues of some heart attacks lays down iron which becomes the substrate for an inflammatory reaction, ultimately leading to the pathological conversion of tissue to fat. This fat, in turn, leads to the pathological development of dysfunctional heart tissue and congestive heart failure,” he added.
The researchers also noted that their findings also might help define potential therapeutic strategies to mitigate chronic heart failure following a heart attack.
“This fat and scar tissue does not ‘squeeze’ like normal heart muscle, resulting in heart failure,” noted Dr. Grifka.
“Administering a medicine that helps remove the iron deposits from the heart muscle results in less scar tissue formation, better heart function, and preventing heart failure.”
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