Impact of 18 FDG-Avidity and Immunosuppression on Idiopathic and Genetic Cardiomyopathies

BACKGROUND: Myocardial 18 fluorodeoxyglucose ( 18 FDG)-avidity is frequently seen in patients with genetic cardiomyopathy, as well as a growing “idiopathic 18 FDG-avidity” group of genotype-negative patients who do not clearly have cardiac sarcoidosis. The prognostic implications of 18 FDG-avidity in patients with and without genetic cardiomyopathy, and the effects of immunosuppression in the latter, remain uncertain. METHODS: This multicenter, retrospective study included all patients who were referred for both 18 FDG-PET and cardiomyopathy 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, or death) and arrhythmia composite (sustained ventricular arrhythmias [ventricular tachycardia/VF], atrioventricular block, or death) outcomes using survival analysis, including Cox proportional hazards modeling and inverse probability of treatment weighting. RESULTS: Among 372 patients, 142 (38%) were 18 FDG-avid. The prevalence of genetic cardiomyopathy among 18 FDG-avid patients (12%) was similar to that of 18 FDG-negative patients (18%; P =0.11). Unadjusted, 18 FDG-avidity was associated with an increased risk of HF composite (hazard ratio, 1.69 [95% CI, 1.04–2.75]; P =0.034) and arrhythmia composite (hazard ratio, 1.63 [95% CI, 1.1–2.4]; P =0.014) outcomes compared with 18 FDG-negative patients. However, these associations were not statistically significant after multivariable adjustment, nor were there significant differences in 18 FDG-associated risks in patients with genetic cardiomyopathy versus genotype-negative patients. After inverse probability of treatment weighting, immunosuppression of 18 FDG-avid patients (n=49) was not associated with a reduction in HF or arrhythmia composite outcomes compared with those who were not immunosuppressed (n=93). CONCLUSIONS: Myocardial-only 18 FDG-avidity is not significantly associated with HF or arrhythmia risk in patients who do not clearly have cardiac sarcoidosis (including those with genetic cardiomyopathy). Immunosuppression therapy does not seem to modify the disease course, suggesting that not all myocardial 18 FDG uptake reflects clinically significant inflammation.