Intramyocardial Hemorrhage in Acute Myocardial Infarction: Prognostic Biomarker and Treatment Target?

T imely primary percutaneous coronary intervention to restore myocardial perfusion is pivotal in acute ST elevation myocardial infarction. The major determinants to reduce myocardial injury before intervention are reducing ischemia duration and severity, and the major determinants after intervention are restoring microvascular flow and minimizing reperfusion injury. When necrosis within the myocardium at risk reaches substantial extent, however, restoration of flow may risk to aggravate the injury by causing intramyocardial hemorrhage (IMH). If microvascular perfusion is restored within ≈30 minutes, myocardial injury is usually detected by troponins, whereas late gadolinium enhancement magnetic resonance imaging (MRI) 1 may demonstrate little or no enhancement as a sign of necrosis. Myocardial function is often restored completely. With increasing duration of isch-emia, however, myocardial cells will progressively lose control of intracellular homeostasis. This leads to progressive myocyte necrosis as a function of time within the myocardium at risk from endocardium to epicardium called the " wavefront phenomenon " by Reimer et al 4 and Reimer and Jennings. 5 The rate at which the amount of infarcted myocardium increases as a result of this process is slower in man compared with most animal experiments. 2 Also, with increasing ischemia duration the swelling of ischemic tissue on reperfusion impedes microvascular flow. This no-reflow phenomenon, as described in experimental studies by Kloner and Jennings, 6 is likely the mechanism behind the phenomenon that can be seen clinically after reperfusion as a progressive increase of hypoin-tense regions on late gadolinium enhancement MRI 7 called microvascular obstruction (MVO). Later during this ischemic process, also the microvasculature, which is more resistant to ischemia than myocardial cells, 8 eventually becomes irreversibly injured by disruption of the endothelial wall, and this has been postulated as one of the causes of IMH. By using MRI to depict the inflow of GdDTPA-albumin into reperfused experimental infarction the decrease of microvascular flow has been shown to be a function of duration of reperfusion within the first hour. 9 Downstream displacement of thrombus material, either spontaneously or as a result of mechanical reperfusion, may also lead to impaired microvascular flow. Intramyocardial hemorrhage, however, does not occur without reperfusion. Standard care in acute myocardial infarc-tion includes both reperfusion and antithrombotic therapy to keep macro-and microvasculature open. This means that the therapy in itself may promote IMH. Few therapies except for timely reperfusion are aimed at reducing postreperfusion edema or hemorrhage. Both MVO and IMH have been shown …