Incremental Diagnostic and Prognostic Value of 68Ga-DOTA-SA-FAPI PET/CT Imaging in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease characterized by progressive fibro-fatty replacement of the ventricular myocardium, predominantly involving the right ventricle, although left ventricular and biventricular forms are increasingly recognized. The disease is associated with ventricular arrhythmias, progressive ventricular dysfunction, heart failure, and sudden cardiac death. Because phenotypic expression is variable and may evolve over time, early diagnosis remains challenging, particularly in patients with subtle structural abnormalities or incomplete expression of conventional diagnostic criteria.

Current diagnostic evaluation relies on a multiparametric approach integrating electrocardiographic, arrhythmic, structural, functional, histopathological, and genetic findings. The revised 2010 Task Force Criteria improved standardization of diagnosis, and the Padua criteria further expanded the disease concept by incorporating left ventricular involvement. However, despite these advances, important limitations remain, especially in the early stages of disease, when conventional imaging may not adequately detect active myocardial remodeling.

Echocardiography and cardiac magnetic resonance imaging are central imaging modalities in ARVC. Echocardiography allows assessment of chamber dimensions, ventricular systolic function, and regional wall motion abnormalities, whereas cardiac magnetic resonance imaging provides more detailed characterization of ventricular volumes, function, and tissue abnormalities. Nevertheless, both techniques primarily reflect structural and functional consequences of disease and may be less sensitive for detecting early or biologically active fibrotic remodeling. This limitation is particularly relevant in a disease in which myocardial fibrosis is a major pathological substrate for electrical instability and arrhythmogenesis. It may also be especially important in patients who are unable to undergo cardiac magnetic resonance imaging because of contraindications or technical limitations. In such cases, 68Ga-DOTA-SA-FAPI PET/CT may provide complementary diagnostic information by enabling non-invasive assessment of active myocardial fibrotic remodeling.

Molecular imaging with fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPI PET/CT) has emerged as a promising non-invasive technique for visualizing activated fibroblasts in vivo. Fibroblast activation protein is overexpressed in activated fibroblasts involved in tissue remodeling and fibrogenesis. In cardiovascular disease, FAPI-based imaging has attracted growing interest as a potential marker of active fibrosis. In ARVC, where fibro-fatty myocardial replacement is a defining pathological feature, 68Ga-DOTA-SA-FAPI PET/CT may offer additional biological information beyond conventional imaging by identifying active fibroblast-related remodeling.

The present study is a prospective single-group diagnostic imaging study designed to evaluate the incremental value of protocol-specified 68Ga-DOTA-SA-FAPI PET/CT imaging in adult patients with ARVC. The central hypothesis is that FAPI PET/CT may improve the non-invasive assessment of myocardial fibrotic activity and provide complementary information to conventional multimodality evaluation.In particular, the study seeks to explore whether myocardial FAPI uptake is detectable in patients with ARVC and whether uptake patterns correlate with established clinical, electrocardiographic, echocardiographic, and previously obtained cardiac magnetic resonance findings. The study will also explore the potential usefulness of FAPI PET/CT in patients in whom cardiac magnetic resonance imaging is unavailable or cannot be performed.