Illuminating Cardiac Remodeling: Insights From [18F]-Fluorodeoxyglucose Positron Emission Tomography Imaging in Plakoglobin-Associated Arrhythmogenic Cardiomyopathy.

BACKGROUND

Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease, which presents with arrhythmias and sudden cardiac death, along with progressive cardiac remodeling and myocardial inflammation. This study aims to elucidate the patterns of [18F]-fluorodeoxyglucose ([18F]-FDG) uptake in a mouse model of plakoglobin-associated cardiac disease to better understand its diagnostic potential.

METHODS AND

RESULTS

Plakoglobin (Jup) knockout mice developed a cardiomyopathy that presented an ACM-like phenotype at 6 weeks of age. Flow cytometry experiments showed a significant increase of immune cells, for example, an expansion of proinflammatory and tissue-injury macrophages. In vivo positron emission tomography and ex vivo autoradiography showed increased [18F]-FDG uptake in genotype positive hearts. A correlative analysis between [18F]-FDG positivity and macrophage infiltration using CD68 and CD206 staining did not show colocalization. CD68 and CD206 positivity was primarily observed within the fibrotic scar, whereas [18F]-FDG uptake was predominantly identified in CD68 and CD206-negative tissue areas. Instead, [18F]-FDG signal seemed to originate from cardiomyocytes adjacent to areas of fibrotic remodeling. Morphometric analysis revealed hypertrophy of these cardiomyocytes, which may reflect metabolic remodeling as a compensatory response.

CONCLUSIONS

In our murine model of Jup-related ACM, strong cardiac [18F]-FDG uptake was detected, which colocalized with regional hypertrophic cardiomyocytes rather than inflammatory cells. These findings indicate that [18F]-FDG positron emission tomography is a valuable tool for identifying and localizing hypermetabolic areas associated with cardiac remodeling in ACM, providing insights into disease mechanisms and potential diagnostic strategies.