Myocardial Activity at ¹⁸F-FAPI PET/CT and Risk for Sudden Cardiac Death in Hypertrophic Cardiomyopathy

Background: Myocardial fibrosis contributes to adverse cardiovascular events in hypertrophic cardiomyopathy (HCM). Purpose: To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/CT imaging and its relation-ship with the risk of sudden cardiac death (SCD) in HCM.Materials and Methods: In this prospective study from July 2021 to January 2022, participants with HCM and healthy control par-ticipants underwent cardiac fluorine 18 (18F)-labeled FAPI PET/CT imaging. Myocardial FAPI activity was quantified as intensity (target-to-background uptake ratio), extent (the percent of FAPI-avid myocardium of the left ventricle [LV]), and amount (the percent of FAPI-avid myocardium of LV x target-to-background ratio). Regional wall thickness was analyzed at cardiac MRI. The 5-year SCD risk score was calculated from the 2014 European Society of Cardiology guidelines. Univariable and multivariable lin-ear regression analyses were used to identify factors related to the FAPI amount. The correlation between FAPI amount and 5-year SCD risk was explored. Results: Fifty study participants with HCM (mean age, 43 years +/- 13 [SD]; 32 men) and 22 healthy control participants (mean age, 45 years +/- 17; 14 men) were included. All participants with HCM had intense and inhomogeneous cardiac FAPI activity in the LV myocardium that was higher than that in healthy control participants (median target-to-background ratio, 8.8 vs 2.1, respec-tively; P < .001). In HCM, more segments with FAPI activity were detected than the number of hypertrophic segments (median, 14 vs five, respectively; P < .001); 84% of nonhypertrophic segments showed FAPI activity. Log-transformed FAPI amount had a positive relationship with log-transformed N-terminal probrain natriuretic peptide, high-sensitive troponin I, and left atrial diam-eter and a negative relationship with LV ejection fraction z-score. Degree of FAPI activity positively correlated with the 5-year SCD risk score (r = 0.32; P = .03). Conclusion: Fibroblast activation protein inhibitor (FAPI) PET/CT imaging indicated intense and heterogeneous activity in hyper-trophic cardiomyopathy, and FAPI uptake was associated with 5-year risk of sudden cardiac death.