• Intramyocardial Hemorrhage Is Determinant of MI Size in Reperfusion Injury Setting, Small-Scale Study Shows

    Myocardial hemorrhage could play a crucial clinical role in the acute-care management of patients undergoing reperfusion, say researchers on a new study demonstrating a link between hemorrhage and myocardial infarction (MI) size in the reperfusion injury setting.

    The findings were reported Monday online ahead of the Jan. 4 – 11 issue of the Journal of the American College of Cardiology.

    The paradox of lifesaving reperfusion therapy for acute MI is the risk of reperfusion injury, meaning benefits diminish and the possibility of MI increasing in size – a phenomenon known as “infarct surge.” Data suggest that reperfusion injury can contribute to as much as 50% of the final infarct size.

    Yet, despite observations that large MIs are accompanied by intramyocardial hemorrhage (IMH), whether hemorrhage plays a role in reperfusion-mediated MI expansion has remained unknown.

    And although “extensive efforts” have been taken, there are still no therapies to limit infarct surge from reperfusion injury and improve patient prognosis, or any in large Phase III trials, said the researchers, led by Ting Liu, MD, PhD, Cedars-Sinai Medical Center, Los Angeles, and First Affiliated Hospital of China Medical University, Shenyang, China, and Andrew G. Howarth, MD, PhD, also from Cedars-Sinai as well as University of Calgary, Alberta.

    However, it is known that the externalization of red blood cells into the interstitial space (IMH) can be detrimental. IMH can exacerbate microvascular compromise, extending the zone of hypoxia, and “the hemolysis of red blood cells in the extracellular environment can expose cardiomyocytes to heme, an iron-binding component of hemoglobin that is cytotoxic,” they added.

    “Both effects emanating from the introduction of IMH into the myocardium may drive expansion of infarction zone.”

    The researchers, therefore, hypothesized that hemorrhagic transformation of reperfused MI catalyzes a time-dependent expansion of the MI zone, which contributes to a larger final MI size compared with infarctions without hemorrhage, independent of microvascular obstruction.

    The current study was established to observe cardiac troponin kinetics (cTn) of 64 patients with ST-segment elevation MI (STEMI) presenting to a large tertiary-care hospital. The patients were classified by cardiovascular magnetic resonance to be as either hemorrhagic (70%) or nonhemorrhagic following reperfusion via primary percutaneous coronary intervention (PCI).

    Blood samples were taken from the cohort before PCI, and within 6, 12, 24 and 72 hours post-PCI, as well as 5 – 7 days after the procedure, and cardiac magnetic resonance (CMR) imaging were performed post-PCI. All patients received dual antiplatelet therapy at time of PCI.

    Controlled studies in 25 canines were also performed to isolate the effects of hemorrhage from ischemic burden.

    A total 45 of the 64 patients were identified as having an IMH, while 19 did not have IMH. The culprit vessel was identified as the left anterior descending (41 patients), left circumflex (9 patients), and right coronary artery (14 patients), and myocardial hemorrhage was detected in 70% of the patients.

    There was no significant difference in patient age, time from symptom onset to revascularization, history of angina, or cardiovascular risk factors identified between those with or without IMH. However, patients with IMH had lower blood pressure (P < 0.05), were more likely to show reduced left ventricular ejection fraction (P < 0.001) and a higher proportion of demonstrated reduced thrombolysis in myocardial infarction (TIMI) flow before PCI (P < 0.001).

    There was no difference in cTn compared with pre-reperfusion levels; however, an increase in cTn following primary PCI peaked earlier (12 hours vs 24 hours; P < 0.05) and was significantly higher in patients with hemorrhage (P < 0.01), the researchers found.

    In the hemorrhagic animal models, reperfusion led to rapid expansion of myocardial necrosis culminating in epicardial involvement, which was not present in nonhemorrhagic cases (P < 0.001). Although there was no difference in MI size and salvage at 1-hour postreperfusion in animals with and without hemorrhage (P = 0.65), there was a fourfold greater loss in salvageable myocardium in hemorrhagic MIs within 72 hours of reperfusion (P < 0.001).

    “This paralleled observations in patients with larger MIs occurring in hemorrhagic cases,” the researchers said (P < 0.01).

    “Myocardial hemorrhage is a determinant of MI size. It drives MI expansion after reperfusion and compromises myocardial salvage,” they concluded. “This introduces a clinical role of hemorrhage in acute care management, risk assessment, and future therapeutics.”

    In an accompanying editorial, Colin Berry, MBChB, PhD, from the University of Glasgow and West of Scotland Heart and Lung Centre, Clydebank, Scotland, and Borja Ibáñez, MD, PhD, from IIS-Hospital Universitario Fundación Jiménez Díaz, and CIBERCV, Madrid, stressed that IMH represents “the final frontier for preventing heart failure post-MI.”

    “It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”


    Liu T, Howarth AG, Chen Y, et al. Intramyocardial Hemorrhage and the “Wave Front” of Reperfusion Injury Compromising Myocardial Salvage. J Am Coll Cardiol 2022;79:35-48.

    Berry C, Ibáñez B. Intramyocardial Hemorrhage: The Final Frontier for Preventing Heart Failure Post-Myocardial Infarction. J Am Coll Cardiol 2022;79:49-51.

    Image Credit: Africa Studio – stock.adobe.com

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