INDIANAPOLIS — A new multicenter study led by Indiana University School of Medicine researchers shows heart attack patients who experience bleeding into the heart muscle — also known as hemorrhagic myocardial infarction (MI) — after a stent is placed, carry the highest risk of death while they are hospitalized. Results of the study were recently published in NEJM Evidence and will be presented at the European Society of Cardiology’s ESC Congress 2025 on Aug. 31 in Madrid.
These results open the door for rapid identification of hemorrhagic MI. Prior to this study, identification of hemorrhagic MI was only possible with cardiac MRI days after percutaneous coronary intervention (PCI), a minimally invasive procedure used to treat narrowing of the coronary arteries that is often used to restore blood flow from a blocked artery but can also cause injury to the heart muscle.
Currently, PCI is the standard of care for treating ST-segment elevation myocardial infarction (STEMI), a more severe type of heart attack that occurs when there is a total blockage to the heart's blood supply in the arteries that needs to be quickly restored. The sooner blood flow is restored, the greater the chance to prevent permanent heart muscle damage and minimize injury.
A bleeding heart muscle poses the highest risk
Bleeding within the heart muscle is a complication associated with PCI in approximately 40% STEMI patients and is known to carry the highest risk for adverse outcomes in the months and years after the heart attack. However, whether hemorrhagic MI patients are at greater risk for in-hospital mortality was not known, mainly because of the lack of a diagnostic test to broadly identify bleeding within the heart muscle in acute care settings, such as hospitals. While cardiac MRI is currently the only method capable of diagnosing hemorrhagic MI, it is challenging to perform in every STEMI patient given the limitations in patient stability and access to MRI, particularly in community hospitals.
The study examined whether a cardiac-specific protein — high-sensitivity cardiac troponin concentration (hs-cTn-I) — found in the blood can be used post-PCI as a diagnostic tool to rapidly identify hemorrhagic MI. The results were validated using cardiac MRI. Researchers then used the post-PCI troponin test to identify hemorrhagic MI patients and investigated whether hemorrhagic MI patients are at greater risk for in-hospital mortality compared to those without hemorrhagic MI using STEMI registries across seven United States hospitals in a large health system.
"Our results indicate post-PCI troponin levels can be used to identify hemorrhagic transformation of the MI zone within the first hour after PCI and that the extent of intramyocardial hemorrhage based on peak post-PCI troponin levels within the first six hours," said senior author Rohan Dharmakumar, PhD, vice chair of research for the Department of Radiology and Imaging Sciences, executive director of the Medical Imaging Research Institute and director of the Cardiovascular Imaging Research Center at the IU School of Medicine. "These findings demonstrate it is feasible to rapidly diagnose hemorrhagic MI among patients in coronary care units following PCI for STEMI and that hemorrhagic MI patients carry a multi-fold higher risk of in-hospital mortality over non-hemorrhagic patients."
Troponin tests across seven Indiana hospitals provide data
Researchers enrolled 207 consecutive STEMI patients who underwent primary PCI between June 2022 and November 2023 in the study. They used high-sensitivity cardiac troponin I levels to derive a threshold to split patients with and without bleeding within the heart muscle.
The STEMI registry comprised of 6,180 patients enrolled between 2015 to 2024 with post PCI cardiac troponin I. In-hospital mortality of STEMI was captured using electronic health record data across seven hospitals within the IU Health system where uniform standards of care, including troponin tests, were provided. Among the registry patients, 1,323 patients were deemed to have hemorrhagic MI, and 4,857 patients were non-hemorrhagic based on post-PCI troponin thresholds. Records indicate that hemorrhagic MI was more common among men in the registry.
"Findings from this study should be used to better inform the cardiac care team on which heart attack patients post PCI are hemorrhagic," said co-author, Ankur Kalra, MD, an interventional cardiologist and the division chief of cardiology at the State University of New York Upstate Medical University Hospital. "While PCI is widely considered a safe procedure to restore blood flood flow, complications can occur, so methods that could stratify risk of patients for hemorrhagic MI prior to PCI could be beneficial, but that would require further investigations."
Results show that more expedient post-PCI troponin diagnostics can help overcome limitations associated with cardiac MRI based diagnosis of hemorrhagic MI.
"Ability to assess microvascular tissue injury in acute myocardial infarction based on a broadly available blood biomarker has significant implications in STEMI critical care and future of acute MI clinical trials," said co-author Richard Kovacs, MD, chief medical officer of the American College of Cardiology and interim division chief of cardiovascular medicine at IU School of Medicine and IU Health.
Advances in cardiac MRI over the last two decades have led to a deeper understanding of reperfused myocardial injury, where compositional, structural and functional changes are recognized within the heart muscle. Therefore, triaging STEMI patients with bleeding within the heart muscle is expected to enhance the utility of cardiac MRI.
Keyur P. Vora, MD, director of clinical imaging research at the Cardiovascular Imaging Research Center within the Medical Imaging Research Institute and Radiology & Imaging Sciences at IU School of Medicine and lead author of the study, said cardiac MRI provides a critical tool in assessing the extent of heart damage among heart attack patients post-PCI.
"Cardiac MRI should be utilized in tandem with cardiac troponin hs-cTn-I diagnostic of hemorrhagic MI, one of the primary factors behind adverse remodeling of the heart, even after successful PCI," said Vora, a noninvasive cardiologist and lead author of the study. "Hemorrhagic MI patients are the ones with the most severe form of tissue injury as per the classifications outlined by the Canadian Cardiovascular Society (CCS-AMI Stages I-IV); hence, the ability to diagnose these high-risk patients on the basis of a circulating blood marker is a major advance in medicine with the capacity to propel development of novel therapies."
About the Indiana University School of Medicine
The IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability. According to the Blue Ridge Institute for Medical Research, the IU School of Medicine ranks No. 13 in 2024 National Institutes of Health funding among all public medical schools in the country.
Writer: Angie Antonopoulos, eantonop@iu.edu
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