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.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Infarction; Myocardial Injury; Myocardial Inflammation
• Intervention / Treatment: Diagnostic test: Multimodality Imaging

• Study Type: Interventional
• Enrollment (Estimated): 57
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Theresa Reiter, MD; Phone Number: +4993120139944; Email: reiter_t@ukw.de
• Study Contact Backup: Name: Rudolf Werner, MD; Phone Number: +4993120135906; Email: werner_r1@ukw.de

Study Locations

• Germany
  • Wuerzburg, Germany, 97080
    • Recruiting
    • University Hospital Wuerzburg
    • Contact: Theresa Reiter; Phone Number: +4993120139944; Email: reiter_t@ukw.de
    • Contact: Rudolf Werner; Phone Number: +4993120135906; Email: werner_r1@ukw.de
  • Würzburg, Germany, 97070
    • Recruiting
    • Klinikum Würzburg Mitte, Medizinische Klinik
    • Contact: Willibald Hochholzer, Professor
    • Contact: Phone Number: +49 931 7910

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Multimodal imaging; Multimodal imaging approach. This includes a CXCR4 targeted PET/CT ([68Ga]Pentixafor) during the acute hospital stay, and serial CMR and Echo imaging.	Diagnostic test: Multimodality Imaging; Patients receive CXCR4-targeted PET/CT, CMR and Echo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CXCR4 PET-derived uptake after myocardial infarction	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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of quantitative parameters (SUV) with peripheral lymphocytes	SUV of organs of interest are correlated to the phenotype of peripheral lymphocytes in the peripheral blood after myocardial infarction.	12 months
Time course of SUV 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.	12 months
Correlation of myocardial damage to SUV	CMR will determine the extend of myocardial damage as necrotic volume, volume of MVO and myocardial edema. These findings will be correlated to SUV.	12 months
Correlation of SUV with the clincial course	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.	12 months

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Investigators: Principal Investigator: Theresa Reiter, MD, Wuerzburg University Hospital; Principal Investigator: Rudolf Werner, MD, Wuerzburg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: August 24, 2022
• First Posted (Actual): August 29, 2022

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Myocardial Infarction; CMR; CXCR4; Lymphatic organs
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cardiomyopathies; Myocardial Infarction; Infarction; Inflammation; Myocarditis
• Other Study ID Numbers: 192/21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No