Lymphatic Organs and Myocardium After Myocardial Infarction (LOMI)

Multimodal Characterization of Lymphatic Organs and Myocardium in Patients After Acute Myocardial Infarction

The adaptive immune response plays an important role in myocardial healing and remodeling after acute myocardial infarction in patients. Therefore, the involved lymphocytes represent a novel target for therapeutic interventions. However, there are no established blood-derived biomarkers to predict the quantity and quality of the adaptive immune response to cardiac injury. Multimodal imaging of the heart and immunologic organs might provide such information. Recent retrospective analysis of patients after MI revealed enlarged mediastinal lymph nodes associated with increased CXCR4 radiotracer accumulation, thereby indicating that CXCR4 PET-based lymph node imaging provides a non-invasive quantitative readout of the local adaptive immune response. These considerations are further fuelled by the fact that, within lymph nodes, CXCR4 is expressed almost exclusively on lymphocytes, whereas various other cell types express CXCR4 within the myocardium. This leads to the hypothesis that the size of mediastinal lymph nodes and their respective CXCR4 PET signals correlate with the adaptive immune response to cardiac injury and might provide predictive information for functional cardiac decline during follow-up. This prospective clinical study will use multimodal imaging to monitor chemokine receptor 4 (CXCR4) expression in the lymph nodes, myocardium, spleen, and bone marrow after acute MI. The combination of cardiac magnetic resonance (CMR), echocardiography, and positron emission tomography (PET) along with blood collection for immunophenotyping will allow to determine i) if the size of mediastinal lymph nodes and their respective PET-derived CXCR4 signals at baseline correlate with the adaptive immune response to acute cardiac injury; and ii) if they predict cardiac adverse remodelling during longitudinal follow-up.

Multimodal imaging approach. This includes a CXCR4 targeted PET/CT ([68Ga]Pentixafor) during the acute hospital stay, and serial CMR and Echo imaging.

Semi-quantitative assessment of CXCR4-derived radiotracer accumulation in the myocardium, mediastinal lymph nodes, bone marrow and spleen in patients after myocardial infarction. For quantitative analysis, standardized uptake values (SUV) will be calculated in organs of interest.

SUV of organs of interest are correlated to the phenotype of peripheral lymphocytes in the peripheral blood after myocardial infarction.

PET/CT scans for each patient will be allocated to either day 3-4 or day 5-8 after myocardial infarction. SUV of organs of interest will be correlated to time point of imaging.

CMR will determine the extend of myocardial damage as necrotic volume, volume of MVO and myocardial edema. These findings will be correlated to SUV.

Myocardial function (LVEF) and scar volumes as determined by CMR will be correlated to the intital SUV in order to correlate the clinical outcome to the tracer activity.

Inclusion Criteria: patients with acute myocardial infarction (STEMI) who were treated with immediate catheterization stable clinical course male/female, above 18 years old Exclusion Criteria: hemodynamic instablity > 48 h after immediate catherization known CAD known structural heart disease multi vessel disease NSTEMI sarcoidosis immunosuppressive therapy acute inflammatory disease no consent obtainable contraindiations for CMR impaired renal function active cardiac implants, ferromagnetic implants pregnancy, breast-feeding