Chronic Manifestation of Postreperfusion Intramyocardial Hemorrhage as Regional Iron Deposition

Abstract

Background— Intramyocardial hemorrhage frequently accompanies large reperfused myocardial infarctions. However, its influence on the makeup and the ensuing effect on the infarcted tissue during the chronic phase remain unexplored. Methods and Results— Patients (n=15; 3 women), recruited after successful percutaneous coronary intervention for first segment–elevation myocardial infarction, underwent cardiovascular magnetic resonance imaging on day 3 and month 6 after percutaneous coronary intervention. Patients with hemorrhagic (Hemo+) infarctions, as determined by T2* cardiovascular magnetic resonance on day 3 (n=11), showed persistent T2* losses colocalized with scar tissue on the follow-up scans, suggesting chronic iron deposition. T2* values of Hemo+ territories were significantly higher than nonhemorrhagic (Hemo−) and remote territories ( P <0.001); however, T2* values of nonhemorrhagic (Hemo−) and remote territories were not different ( P =0.51). Canines (n=20) subjected to ischemia-reperfusion injury (n=14) underwent cardiovascular magnetic resonance on days 3 and 56 after ischemia-reperfusion injury. Similarly, sham-operated animals (Shams; n=3) were imaged using cardiovascular magnetic resonance at similar time points. Subsequently, hearts were explanted and imaged ex vivo, and samples of Hemo+, Hemo−, remote, and Sham myocardium were isolated and stained. The extent of iron deposition ([Fe]) within each sample was measured using mass spectrometry. Hemo+ infarcts showed significant T2* losses compared with the other (control) groups ( P <0.001), and Perls stain confirmed localized iron deposition. Mean [Fe] of Hemo+ was nearly an order of magnitude greater than that of the control groups ( P <0.001), but no significant differences were observed among the control groups. A strong linear relationship was observed between log(T2*) and −log([Fe]); R 2 =0.7 and P <0.001. The monoclonal antibody Mac387 stains, along with Perls stains, showed preferential localization of newly recruited macrophages at the site of chronic iron deposition. Conclusions— Hemorrhagic myocardial infarction can lead to iron depositions within the infarct zones, which can be a source of prolonged inflammatory burden in the chronic phase of myocardial infarction.

Magnetic resonance hypointensive signal primarily originates from extracellular iron particles in the long-term tracking of mesenchymal stem cells transplanted in the infarcted myocardium

“…20 It is well known that iron overload could cause cardiomyopathy with clinical manifestations, including decreasing the cardiac ejection fraction and arrhythmia. [37][38][39] Acidic environments prompt the transformation of iron from the oxidation state (Fe 3+ ) to the reduced state (Fe 2+ ), resulting in the generation of oxygen free radicals. Therefore, the toxic effect of myocardial iron is dynamic and is increased in the presence of metabolic acidosis.…”

Detection of Acute Reperfusion Myocardial Hemorrhage with Cardiac MR Imaging: T2 versus T2*

“…Discussion Recent studies have shown that intramyocardial hemorrhage may be one of the strongest predictors of adverse outcome (15)(16)(17)(18)(19)(20). This has generated substantial interest in understanding the effects of reperfusion hemorrhage showed extensive myocardial damage accompanied by extensive inflammatory response.…”

“…Intramyocardial hemorrhage has been widely reported to be associated with larger infarctions and MVO after reperfusion both in animal models (8)(9)(10)(11) and in humans (12)(13)(14). It is important to note that intramyocardial hemorrhage has been shown to be a significant predictor of poor left ventricular (LV) remodeling (15)(16)(17)(18), late arrhythmogenic risk (19), and major adverse cardiovascular events (20).…”

“…Cardiac magnetic resonance (MR) imaging based on either T2*-weighted (16,18,(21)(22)(23)(24) or T2-weighted (15,17, Implication for Patient Care n The occurrence of myocardial reperfusion hemorrhage, which has been associated with acute myocardial damage and adverse chronic remodeling, is expected to be more reliably assessed with T2* cardiac MR imaging than with T2-based cardiac MR imaging.…”

Myocardial Iron and Arrhythmia Risk: Magnetic “Shades of Gray”?

“…11,12 Interestingly, in a canine model of MI using T2* imaging CMR, these investigators have established that hemorrhage during the index MI is associated with late iron deposition and subsequent macrophage infiltration in the infarct zone, as well as important changes in surrogate markers of arrhythmic risk, including late potentials and QT dispersion. 13,14 However, validation of the association between infarct zone iron deposition with SCA risk in a population of patients with chronic MI has heretofore been lacking. The data presented by Cokic et al 15 LGE imaging (with a 5-SD cutoff) and peri-infarct zone assessment (with a 2/3-SD cutoff) were performed.…”