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

J Am Coll Cardiol. 2022 Jan 4;79(1):35-48. doi: 10.1016/j.jacc.2021.10.034.


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.

Keywords: hemorrhage; infarct expansion; myocardial infarction; reperfusion injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dogs
  • Hemorrhage / diagnostic imaging*
  • Humans
  • Magnetic Resonance Imaging, Cine
  • Myocardial Reperfusion Injury / diagnostic imaging*
  • Myocardium / pathology
  • Necrosis
  • Percutaneous Coronary Intervention
  • Positron-Emission Tomography
  • Prospective Studies
  • ST Elevation Myocardial Infarction / diagnostic imaging*
  • ST Elevation Myocardial Infarction / therapy
  • Salvage Therapy
  • Time-to-Treatment
  • Troponin / blood


  • Troponin