Myocardial inflammation imaging in fabry disease of the heart using somatostatin receptor PET/MRI

Background Cardiac involvement is a major cause of morbidity and mortality in Fabry disease, progressing from early myocardial injury to fibrosis, arrhythmia, and chronic heart failure. While cardiovascular magnetic resonance imaging (MRI) can reliably detect myocardial oedema and fibrosis in Fabry disease, there is a need for a more sensitive imaging marker for distinguishing early active inflammation driving disease progression. Purpose To evaluate the use of hybrid somatostatin receptor 2 (SST2) positron emission tomography (PET)/MRI using 68Ga-DOTATATE for imaging myocardial inflammation in Fabry disease. Methods Consenting participants with genetically confirmed Fabry disease and established cardiac involvement underwent prospective 68Ga-DOTATATE PET/MRI of the heart. PET imaging was analysed visually by expert readers and quantified using maximum standardized uptake values (SUVmax) in each of the 17 myocardial segments and the right ventricle. Associations with clinical, biochemical, and MRI markers of disease activity and severity were assessed using non-parametric tests and mixed-effects models accounting for within-patient clustering. Results A total of 12 patients (mean age 62 [IQR 57–70] years; 42% female) were enrolled, of whom 6/12 (50%) had classical Fabry disease. All were receiving disease-specific treatment. Myocardial 68Ga-DOTATATE PET imaging showed focal left ventricular uptake in all patients with heterogeneous regional distribution. PET uptake occurred most often in the inferolateral segments, where late gadolinium enhancement (LGE) also frequently occurred (Fig.1A, arrows). PET signal was higher in segments with T2-weighted oedema and/or LGE on MRI (p<0.05 for both, Fig.1B). There was right ventricular PET uptake with corresponding LGE in 2/12 (17%) patients. Global PET signal was also positively correlated with age, NT-pro-BNP, serum C-reactive protein, and the proportion of left ventricular segments with T2 oedema (p<0.05 for all). PET signal often extended beyond areas of established scar, and 5/12 (42%) patients had focal PET signal in segments without structural MRI abnormality. Conclusion In this first study of SST2 PET/MRI in cardiac Fabry disease, 68Ga-DOTATATE detected focal myocardial inflammation associated with clinical, biochemical, and MRI markers of disease severity. PET uptake beyond areas of established scar, including in segments without structural MRI abnormality, suggests potential sensitivity for earlier active disease. Given that cardiac disease progression may continue despite current enzyme-targeted Fabry therapies, imaging myocardial inflammation may improve disease characterization and help identify novel therapeutic targets.