A common treatment given to patients experiencing heart attack may not be as successful in halting muscle damage as once thought, found a study in the Journal of the American College of Cardiology.
In heart attack patients, the amount of heart muscle that is irreversibly damaged is directly linked to how much time elapses between the onset of heart attack symptoms and when the blockage is opened up. More damage means higher risk of complications like heart failure after a heart attack. Therefore, treating heart attacks focuses on opening up the coronary arteries as quickly as possible through a procedure called reperfusion, often with a stent.
The common belief in reperfusion therapy is that once the coronary arteries are opened, the damage to the heart muscle is stopped. However, according to the study team, led by Rohan Dharmakumar, of the Indiana University School of Medicine, that is not always the case.
“In our work, we demonstrate that if reperfusion results in internal bleeding, or, haemorrhage, within the heart muscle, the heart muscle can continue to die even after the culprit coronary artery is opened,” said Dharmakumar, executive director of the Krannert Cardiovascular Research Center at IU School of Medicine.
“"Haemorrhage is known to occur in heart muscle of around half of all heart attack patients who undergo reperfusion. We sought to determine what effect that internal bleeding has on progressive heart muscle damage after reperfusion.”
Dharmakumar and his team studied blood samples of heart attack patients obtained before and after they received reperfusion therapy. Using cardiac magnetic resonance imaging (cardiac MRI), they noninvasively identified which patients experienced haemorrhage within their heart muscle after reperfusion.
A key protein called troponin is known to go up with heart muscle damage; in patients with heart muscle haemorrhage, troponin values rose more rapidly reaching higher values when compared with patients without haemorrhage.
The team also used a large animal model to prove that haemorrhage is directly involved in the extent of infarction after reperfusion. Serial cardiac MRIs noninvasively tracked infarct size in animals with and without haemorrhage; similar findings as those seen in patients means that the team can use the animal model to develop new treatments to reduce haemorrhage that can be brought back to help patients.
In the modern era of revascularisation, Dharmakumar asserts in his study that infarct size is not only determined by restricted blood supply to the heart, but also by the effects of reperfusion therapy. The introduction of haemorrhage within the at-risk area might in some cases nearly negate in total the benefits of reperfusion therapy. He said that for physicians, having an awareness of the role reperfusion can play on continued muscle death can help in providing better treatment to patients in the future.
“This all means that although we might not be able to do much when it comes to lost time before a patient arrives at the hospital, minimising the effects of haemorrhage after reperfusion can give us a new opportunity to reduce the size of infarction, and downstream negative consequences, in nearly half a million heart attack patients in the United States alone,” he said.
Next for the study, he said that his team would expand the findings to a larger patient population, working to develop greater insight into how haemorrhage drives expansion of infarction and testing strategies to halt the effects of those haemorrhages.
According to Dr Subha Raman, chief of the Division of Cardiology and director of the Cardiovascular Institute at IU School of Medicine and IU Health, the future real-world applications of this study showcase the research leadership of Dharmakumar and the Krannert Cardiovascular Research Center.
“The work being done by our researchers at the Krannert Cardiovascular Research Center, under the leadership of Dr Dharmakumar, is truly groundbreaking and will fundamentally improve how we take care of patients suffering heart attacks, improving the health of Hoosiers and beyond,” said Raman. “I am proud of the high-impact cardiovascular science happening in our research labs, and look forward to seeing that work pay real dividends in the future of heart health.”
Study details
Intramyocardial Haemorrhage and the “Wave Front” of Reperfusion Injury Compromising Myocardial Salvage.
Ting Liu, Andrew Howarth, Yinyin Chen, Anand Nair, Hsin-Jung Yang, Daoyuan Ren, Richard Tang, Jane Sykes, Michael Kovacs, Damini Dey, Piotr Slomka, John Wood, Robert Finney, Mengsu Zeng, Frank Prato, Joseph Francis, Daniel Berman, Prediman Shah, Andreas Kumar, Rohan Dharmakumar.
Published in Journal of the American College of Cardiology, Volume 79, 4-11 January 2022
Abstract
Background
Reperfusion therapy for acute myocardial infarction (MI) is lifesaving. However, the benefit of reperfusion therapy can be paradoxically diminished by reperfusion injury, which can increase MI size.
Objectives
Haemorrhage is known to occur in reperfused MIs, but whether haemorrhage plays a role in reperfusion-mediated MI expansion is not known.
Methods
We studied cardiac troponin kinetics (cTn) of ST-segment elevation MI patients (n = 70) classified by cardiovascular magnetic resonance to be hemorrhagic (70%) or nonhaemorrhagic following primary percutaneous coronary intervention. To isolate the effects of haemorrhage from ischaemic burden, we performed controlled canine studies (n = 25), and serially followed both cTn and MI size with time-lapse imaging.
Results
CTn was not different before reperfusion; however, an increase in cTn following primary percutaneous coronary intervention peaked earlier (12 hours vs 24 hours; P < 0.05) and was significantly higher in patients with haemorrhage (P < 0.01). In hemorrhagic animals, reperfusion led to rapid expansion of myocardial necrosis culminating in epicardial involvement, which was not present in nonhaemorrhagic cases (P < 0.001). MI size and salvage were not different at 1 hour postreperfusion in animals with and without haemorrhage (P = 0.65). However, within 72 hours of reperfusion, a 4-fold greater loss in salvageable myocardium was evident in haemorrhagic MIs (P < 0.001). This paralleled observations in patients with larger MIs occurring in haemorrhagic cases (P < 0.01).
Conclusions
Myocardial haemorrhage is a determinant of MI size. It drives MI expansion after reperfusion and compromises myocardial salvage. This introduces a clinical role of haemorrhage in acute care management, risk assessment, and future therapeutics.
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