Relationship Between Cardiac Fibroblast Activation Protein Activity by Positron Emission Tomography and Cardiovascular Disease
Markus Heckmann, Finn Reinhardt, Daniel Finke, Hugo A. Katus, Uwe Haberkorn, Florian Leuschner, Lorenz Lehmann
Abstract
Background: FAP (fibroblast activation protein) plays an important role in cardiac wound healing and remodeling. Although initially developed as a theranostic ligand for metastasized cancer, FAPI (FAP inhibitor) tracers have recently been used to study cardiac remodeling following myocardial infarction in small-animal models. The aim of the study was to evaluate the activity of FAP via FAPI–positron emission tomography–computed tomography scans in human hearts. Methods: FAPI–positron emission tomography–computed tomography scans of 229 patients of 2 consecutive cohorts (modeling cohort: n=185; confirmatory cohort: n=44) suffering from metastasized cancer were analyzed applying the American Heart Association 17-segment model of the left ventricle. Logistic regression models were created using data from the modeling cohort. Multivariate regression models were established using Akaike information criterion in a step-down approach. Results: Fourteen percent of patients had preexisting coronary artery disease (n=31), 33% arterial hypertension (n=75), and 12% diabetes mellitus type II (n=28). Forty-three percent had been treated with platin derivatives (n=100), 14% with anthracyclines (n=32), and 10% had a history of prior radiation to the chest (n=23). High left ventricular FAPI signals correlated with the presence of cardiovascular risk factors (odds ratio [OR], 4.3, P =0.0029), a focal myocardial signal pattern (OR, 3.9, P =0.0068), diabetes mellitus type II (OR, 4.1, P =0.046), and beta-blocker use (OR, 3.8, P =0.049) in univariate regression models. In a multivariate analysis, increased signal intensity was significantly higher in patients with cardiovascular risk factors (overweight [OR, 2.6, P =0.023], diabetes mellitus type II [OR, 2.9, P =0.041], certain chemotherapies [platinum derivatives; OR, 3.0, P =0.034], and a history of radiation to the chest [OR, 3.5, P =0.024]). A focal enrichment pattern was more frequently observed in patients with known cardiovascular risk factors ( P <0.0001). Conclusions: FAPI–positron emission tomography–computed tomography scans represent a new imaging modality to investigate cardiac FAP. High signal intensities correlate with cardiovascular risk factors and metabolic disease.