Intramyocardial Hemorrhage and the "Wave Front" of Reperfusion Injury Compromising Myocardial Salvage

Authors

Ting Liu, Cedars-Sinai Medical Center, Los Angeles, California, USA; Department of Radiology, the First Affiliated Hospital of China Medical University, Shenyang, China.
Andrew G. Howarth, Cedars-Sinai Medical Center, Los Angeles, California, USA; University of Calgary, Calgary, Alberta, Canada.
Yinyin Chen, Cedars-Sinai Medical Center, Los Angeles, California, USA; Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai, China.
Anand R. Nair, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Hsin-Jung Yang, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Daoyuan Ren, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai, China.
Richard Tang, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Jane Sykes, Lawson Research Institute, University of Western Ontario, London, Ontario, Canada.
Michael S. Kovacs, Lawson Research Institute, University of Western Ontario, London, Ontario, Canada.
Damini Dey, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Piotr Slomka, Cedars-Sinai Medical Center, Los Angeles, California, USA.
John C. Wood, University of Southern California, Los Angeles, California, USA.
Robert Finney, Cardio-theranostics, Los Angeles, California, USA.
Mengsu Zeng, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai, China.
Frank S. Prato, Lawson Research Institute, University of Western Ontario, London, Ontario, Canada.
Joseph Francis, Louisiana State University, Baton Rouge, Louisiana, USA.
Daniel S. Berman, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Prediman K. Shah, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Andreas Kumar, Northern Ontario School of Medicine, Sudbury, Ontario, Canada.
Rohan Dharmakumar, Cedars-Sinai Medical Center, Los Angeles, California, USA; Krannert Cardiovascular Research Center, Indiana University School of Medicine/IU Health Cardiovascular Institute, Indianapolis, Indiana, USA. Electronic address: rdkumar@iu.edu.

Document Type

Article

Publication Date

1-4-2022

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: Hemorrhage is known to occur in reperfused MIs, but whether hemorrhage 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 nonhemorrhagic following primary percutaneous coronary intervention. To isolate the effects of hemorrhage from ischemic 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 hemorrhage (P < 0.01). In hemorrhagic animals, reperfusion led to rapid expansion of myocardial necrosis culminating in epicardial involvement, which was not present in nonhemorrhagic cases (P < 0.001). MI size and salvage were not different at 1 hour postreperfusion in animals with and without hemorrhage (P = 0.65). However, within 72 hours of reperfusion, a 4-fold greater loss in salvageable myocardium was evident in hemorrhagic MIs (P < 0.001). This paralleled observations in patients with larger MIs occurring in hemorrhagic cases (P < 0.01). CONCLUSIONS: Myocardial hemorrhage is a determinant of MI size. It drives MI expansion after reperfusion and compromises myocardial salvage. This introduces a clinical role of hemorrhage in acute care management, risk assessment, and future therapeutics.

Publication Source (Journal or Book title)

Journal of the American College of Cardiology

First Page

35

Last Page

48

Recommended Citation

Liu, T., Howarth, A. G., Chen, Y., Nair, A. R., Yang, H., Ren, D., Tang, R., Sykes, J., Kovacs, M. S., Dey, D., Slomka, P., Wood, J. C., Finney, R., Zeng, M., Prato, F. S., Francis, J., Berman, D. S., Shah, P. K., Kumar, A., & Dharmakumar, R. (2022). Intramyocardial Hemorrhage and the "Wave Front" of Reperfusion Injury Compromising Myocardial Salvage. Journal of the American College of Cardiology, 79 (1), 35-48. https://doi.org/10.1016/j.jacc.2021.10.034