Impact of 18 FDG-avidity and immunosuppression on idiopathic and genetic cardiomyopathies

Abstract Background Myocardial 18 fluorodeoxyglucose ( 18 FDG)-avidity is frequently seen in patients with genetic cardiomyopathy (CMP), as well as a growing “idiopathic 18 FDG-avidity” group of genotype-negative patients who do not clearly have cardiac sarcoidosis (CS). Objectives To determine the prognostic implications of 18 FDG-avidity in patients with and without genetic CMP, and the effects of immunosuppression in the latter. Methods This multicenter, retrospective study included all patients who were referred for both 18 FDG-PET and CMP genetic testing. Patients with acute myocarditis, biopsy-proven sarcoidosis or extracardiac 18 FDG-avidity were excluded. We investigated heart failure (HF) composite (left ventricular assist device, heart transplant, HF hospitalization, death) and arrhythmia composite (sustained ventricular arrhythmias (VT/VF), atrio-ventricular block, death) outcomes using survival analysis including Cox proportional hazards modeling and inverse probability of treatment weighting (IPWT). Results Among 372 patients, 142 (38%) were 18 FDG-avid. Prevalence of genetic CMP among 18 FDG-avid patients (12%) was similar to that of 18 FDG-negative patients (19%, p=0.07). 18 FDG-avidity was associated with increased risk of HF composite (HR 1.69 (1.04-2.75), p=0.034) and arrhythmia composite (HR 1.63 (1.1-2.4), p=0.014) outcomes compared to 18 FDG-negative patients. However, these associations were present only in genotype-negative patients, and not in genetic CMP. After IPWT, immunosuppression of 18 FDG-avid patients (n=49) was not associated with a reduction in HF (HR 3.31 (1.25, 8.77), p=0.016) or arrhythmia composite outcomes (HR 1.61 (0.79, 3.25), p=0.19) compared with those who were not immunosuppressed (n=93). Conclusions Myocardial-only 18 FDG-avidity is only associated with adverse HF and arrhythmia outcomes in genotype-negative patients who do not clearly have CS. IST does not seem to modify the disease course, suggesting that not all myocardial 18 FDG uptake reflects clinically significant inflammation.