Characteristics and clinical relevance of fibroblast activation detected by 68Ga-FAPI PET/MRI in arrhythmogenic right ventricular cardiomyopathy: a pilot study

Background Myocardial fibrofatty replacement is a hallmark pathological feature of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, non-invasive and accurate detection of right ventricular (RV) myocardial fibrosis remains a significant challenge. 68Ga-FAPI is a highly sensitive marker of fibroblast activation, providing effective detection of myocardial fibrosis. The integrated 68Ga-FAPI PET/MRI technique enables simultaneous assessment of cardiac function and fibrosis, providing a comprehensive disease evaluation. Objectives To assess the characteristics and clinical relevance of fibroblast activation in ARVC and explore the diagnostic performance of integrated 68Ga-FAPI PET/MRI in identifying myocardial fibrosis and its potential clinical application in the management of ARVC. Methods ARVC patients based on the 2010 Task Force Criteria and healthy volunteers who underwent 68Ga-FAPI-4 PET/MRI between August 2025 and February 2026 were enrolled. FAPI uptake and CMR characteristics were analyzed. Correlations between FAPI uptake and CMR parameters, and diagnostic performance were evaluated. Results A total of 41 participants were enrolled, including 20 definite ARVC, 5 borderline ARVC, and 16 healthy controls. RV FAPI uptake was observed in 24/25 (96%) ARVC patients, primarily in the inferior wall and outflow tract. LV uptake was seen in 20/25 (80%) ARVC patients, mostly in the basal to mid-segments of the septum and inferior wall. Definite ARVC patients had significantly higher RV SUVmax, SUVmean, and TBR compared to borderline patients and healthy controls (SUVmax: 1.08±0.25 vs 0.82±0.12 vs 0.65±0.09; SUVmean: 0.79±0.18 vs 0.62±0.11 vs 0.46±0.05; TBR: 1.40±0.28 vs 1.11±0.13 vs 0.85±0.09; all P<0.05). LV SUVmean and LV TBR were also significantly higher in definite ARVC patients compared to healthy controls (P=0.013 and P=0.005, respectively), with no significant differences between definite and borderline patients. All LGE-positive segments showed concordant FAPI uptake. Among definite ARVC patients with LGE-negative segments, FAPI uptake was present in 87.5%(7/8) of the RV and 66.7%(10/15) of the LV. TBR-LV negatively correlated with LVEF (r=-0.69, P<0.001) and positively with LVEDVi (r=0.53, P=0.008); TBR-RV negatively correlated with RVEF (r=-0.45, P=0.026) and positively with RVEDVi (r=0.46, P=0.025). RV TBR had an AUC of 0.984 (95% CI: 0.957–1.000) for diagnosing definite ARVC and 0.810 (95% CI: 0.638–0.982) for distinguishing definite from borderline ARVC. Conclusion Integrated 68Ga-FAPI PET/MRI effectively detects myocardial fibroblast activation in ARVC patients, identifying more extensive myocardial involvement than LGE. It demonstrates strong diagnostic performance and can be used for disease severity stratification, potentially serving as a non-invasive imaging biomarker for active myocardial fibrogenesis in ARVC.68Ga-FAPI-4 PET/MRI protocol workflow of ARVCPatterns of 68Ga-FAPI-4 PET uptake