Editorial for “Detection of Intramyocardial Iron in Patients Following ST‐Elevation Myocardial Infarction Using Diffusion Tensor Imaging”

Despite enormous progress in research and clinical care, myocardial infarction (MI) remains the most frequent cause of premature death worldwide according to the World Health Organization. An in-depth understanding of tissue pathology is key to the development of future therapies. MI is primarily defined by cardiomyocyte necrosis. However, the cardiac microvasculature can also be damaged by ischemic injury: Kloner et al first observed that myocardial blood flow could not be completely restored after severe ischemic myocardial injury. Microvascular obstruction was identified as the culprit leading to “no-reflow” in reperfused MI. Bresnahan et al, followed by others, identified microvascular disruption as the most severe form of microvascular damage, with microvascular necrosis leading to intramyocardial hemorrhage after reperfusion. With the advancement of noninvasive imaging techniques over the last decades, primarily using cardiovascular magnetic resonance, it became possible to study those tissue changes in vivo, both, in experimental models an in patients. Clinical imaging studies identified hemorrhage to occur frequently in reperfused ST-elevation myocardial infarction (STEMI) patients, usually between 40–70% of patients are affected. Multiple clinical studies have associated hemorrhage with adverse outcome, independent of infarct size. Translational studies have also started to shed further insight on hemorrhagic MI. A recent study showed that hemorrhage is a key driver of reperfusion injury in canines with infarcts doubling in size post reperfusion, independent of the area-at-risk. The same study showed that troponin peaked earlier and higher, and infarct size was twice the size in hemorrhagic infarction patients compared to nonhemorrhagic counterparts. The damage that hemorrhage imposes on the heart may not be limited to the acute phase only. A translational study demonstrated that chronic hemorrhagic infarction leads to a unique pathophysiology, culminating in chronic iron deposition, iron crystal formation, and chronic inflammatory activity, which is not observed in nonhemorrhagic infarction. Chronic hemorrhagic infarction may thus be triggering a novel pathway towards post-MI heart failure. In effect, previous studies collectively point toward a unique and critical role of hemorrhage in the acute and chronic phases of MI. Additional studies are needed to further characterize hemorrhagic MI, its pathophysiology and clinical impact, and to explore therapeutic options. In the current issue of the Journal, Das et al investigated the capability of cardiac diffusion weighted imaging (cDWI) for the assessment of myocardial hemorrhage. They studied a population of 50 patients with ST-elevation MI, of whom 24 were positive for hemorrhage, in the acute and chronic phases of MI. Using T2* maps as the reference standard for detecting hemorrhage, they found reduced mean diffusivity (MD) and increased fractional anisotropy (FA) specifically in the hemorrhagic but not in the nonhemorrhagic infarcts. When analyzing the extent of the hemorrhage, there was a very good match between hemorrhage size on cDWI and the T2* reference (cutoff <20 msec), translating into excellent sensitivity and specificity, with a combined AUC of 0.981 for the pooled acute and chronic data. Acquisition time for the DWI sequences was in the range of 13 minutes. The values for MD and FA remained significantly abnormal in the chronic phase, when hemorrhage is known to resolve into iron deposition. The authors need be congratulated on exploring a new approach for imaging myocardial hemorrhage, with this initial study yielding very promising results. So, will cDWI replace T2* imaging of myocardial hemorrhage? At a basic level, cDWI is sensitive to water diffusivity in the myocardium, which yields great potential for the assessment of myocardial microstructure. Paramagnetic effects of hemoglobin degradation products may interfere with cDWI signal, which may explain the findings observed in the paper by Das et al