Characterizing the Inflammatory Tissue Response to Acute Myocardial Infarction by Clinical Multimodality Noninvasive Imaging

Background-Myocardial infarction (MI) triggers a systemic inflammatory response which determines subsequent healing. Experimentally, cardiac positron emission tomography and magnetic resonance imaging have been used successfully to obtain mechanistic insights. We explored the translational potential in patients early after MI. Methods and Results-Positron emission tomography/computed tomography and cardiac magnetic resonance were performed in 15 patients <7 days after first MI. Cardiac magnetic resonance showed regional transmural late gadolinium enhancement and edema exceeding the area of late gadolinium enhancement. Using F-18 deoxyglucose with heparin pretreatment, metabolic rate of glucose (MRGlc) was significantly increased in infarct versus remote myocardium (median, 2.0 versus 0.4 mg/min per 100 mL; P=0.0001). MRGlc in infarct correlated with remote myocardium (rho=0.64; P=0.01), spleen (rho=0.82; P=0.0002), and bone marrow(rho=0.57; P=0.03), but not with muscle or liver. Regionally, F-18 deoxyglucose score was highest in segments with late gadolinium enhancement versus edema only and remote (median, 2.0 versus 1.8 versus 0.4; P<0.0001). Patients requiring repeat intervention during preliminary follow-up of 11 +/- 5 months tended to have higher early post-MI MRGlc. Five patients with chronic, stable MI served as controls. Opposite to acute MI, MRGlc was lower in infarct (median infarct/remote ratio, 0.6 versus 3.2 for acute MI; P=0.001), and there was no correlation with bone marrow or spleen MRGlc. Conclusions-Increased glucose utilization after heparin-induced suppression of myocyte uptake appears to mostly reflect inflammatory activity in damaged myocardium early after MI. Consistent with prior preclinical observations, and in contrast to chronic MI, this is associated with activity in spleen and bone marrow as sources of inflammatory cells. Positron emission tomography and cardiac magnetic resonance multimodality characterization of the acutely infarcted, inflamed myocardium may provide multiparametric end points for clinical studies aiming at support of infarct healing.