Intramyocardial Hemorrhage and the "Wave Front" of Reperfusion Injury Compromising Myocardial Salvage.
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
Salvage Therapy
Time-to-Treatment
Troponin
/ blood
hemorrhage
infarct expansion
myocardial infarction
reperfusion injury
Journal
Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365
Informations de publication
Date de publication:
04 01 2022
04 01 2022
Historique:
received:
08
07
2021
revised:
04
10
2021
accepted:
12
10
2021
entrez:
7
1
2022
pubmed:
8
1
2022
medline:
15
2
2022
Statut:
ppublish
Résumé
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. Hemorrhage is known to occur in reperfused MIs, but whether hemorrhage plays a role in reperfusion-mediated MI expansion is not known. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 34991787
pii: S0735-1097(21)08081-5
doi: 10.1016/j.jacc.2021.10.034
pii:
doi:
Substances chimiques
Troponin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
35-48Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL133407
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136578
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147133
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Funding Support and Author Disclosures This work was supported by grants from National Institutes of Health/NHLBI HL133407, HL136578, and HL147133. Drs Finney and Dharmakumar have ownership interest in Cardiotheranostics, LLC. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.