Abstract
BACKGROUND: Activated myocardial fibroblasts are key contributors to cardiac fibrosis and drive progression toward heart failure (HF). This study aimed to investigate the characteristics of myocardial fibroblast activation imaging and its predictive value for improved cardiac function in non-ischemic HF. METHODS: This double-center prospective study enrolled 38 patients who underwent (99m)Tc-labeled-hydrazinonicotinamide-fibroblast activation protein inhibitor-04 ((99m)Tc-HFAPi) and cardiac magnetic resonance (CMR) imaging. For comparison, 18 healthy volunteers were recruited to undergo (99m)Tc-HFAPi imaging as controls, while another 18 controls were selected from the CMR database. Myocardial (99m)Tc-HFAPi activity was quantified by intensity, extent, and amount. CMR-derived T1 values, extracellular volume (ECV), and strain were analyzed. Baseline and follow-up echocardiographic data were used to evaluate improved cardiac function. RESULTS: All patients exhibited intense but inhomogeneous (99m)Tc-HFAPi uptake in the left ventricular (LV) myocardium, and the intensity was higher than that of controls (4.1 ± 1.8 vs. 1.2 ± 0.1, p < 0.001). LV (99m)Tc-HFAPi amount negatively correlated with LVEF (r = -0.43, p = 0.008). At the segmental level, abnormal (99m)Tc-HFAPi uptake was present in 79.8 % of segments, exceeding the prevalence of increased native T1 values (66.1 %) (p < 0.001). At median follow-up of 3 months, patients without improved cardiac function demonstrated significantly higher intensity (5.0 ± 2.0 vs. 3.5 ± 1.6, p = 0.022). CONCLUSION: Patients with non-ischemic HF showed intense but heterogeneous (99m)Tc-HFAPi activity. The (99m)Tc-HFAPi activity was negatively correlated with baseline cardiac systolic function and associated with poor improvement in cardiac function during follow-up.