[68Ga]FAPI PET imaging revealed visually increased myocardial uptake in 47% of HFpEF patients, with uptake intensity being highest in HFpEF compared to HFrEF patients and healthy volunteers.
Cohort (n=45)
Does [68Ga]FAPI PET/MRI identify and quantify myocardial fibroblast activity in patients with HFpEF compared to HFrEF and healthy volunteers?
[68Ga]FAPI PET imaging can non-invasively visualize and quantify increased myocardial fibroblast activity in patients with HFpEF compared to HFrEF and healthy controls.
Abstract Introduction Heart failure with preserved ejection fraction accounts for 50% of all heart failure presentations and is a leading cause of morbidity and mortality worldwide. Although heart failure with preserved ejection fraction presents with different phenotypes, common pathological features include diastolic dysfunction and interstitial myocardial fibrosis. Gallium-68 Fibroblast Activation Protein Inhibitor (68GaFAPI) binds to activated fibroblasts, the cells which drive myocardial fibrosis. We used 68GaFAPI to investigate the role of activated fibroblasts in patients with heart failure with preserved ejection fraction. Methods In this prospective observational cohort study, patients with an established diagnosis of heart failure with preserved ejection fraction underwent hybrid 68GaFAPI positron emission tomography and magnetic resonance imaging. We qualitatively assessed the presence and distribution of cardiac 68GaFAPI uptake in the myocardium. 68GaFAPI uptake was also quantified in a standardised fashion, with the maximal standardised uptake value recorded within a defined region of interest, and divided by the right atrial blood pool uptake to calculate a target-to-background ratio (TBRmax). Findings were compared to myocardial 68GaFAPI uptake in both healthy volunteers and patients with heart failure with reduced ejection secondary to non-ischaemic cardiomyopathy. Results Fifteen patients with heart failure with preserved ejection fraction (mean age 75±11 years; 47% male), 15 patients with heart failure with reduced ejection fraction (mean age 69±10 years; 73% male) and 15 healthy volunteers (mean age 60±5 years; 50% male) were recruited. Seven patients (47%) had visually increased myocardial 68GaFAPI uptake, of whom 6 (86%) also had late gadolinium enhancement (LGE) corresponding to the region of 68GaFAPI uptake. In addition to the left ventricular myocardium, 68GaFAPI uptake was also observed in the left atrium (n=4; 27%) and the right ventricle (n=2;13%) of patients with heart failure with preserved ejection fraction (figure 1). Intensity of 68GaFAPI uptake was highest in patients with heart failure with preserved ejection fraction versus those with reduced ejection fraction and healthy volunteers (Figure 2). Conclusion We demonstrate for the first time a novel non-invasive approach to visualise and to measure myocardial fibroblast activity in patients with heart failure with preserved ejection fraction using 68GaFAPI positron emission tomography. Patients with heart failure with preserved ejection fraction had highest intensity of fibroblast activity when compared to patients with heart failure with reduced ejection fraction and control volunteers. Further work is needed to establish whether 68GaFAPI molecular PET imaging can enhance disease phenotyping, enabling more personalised treatment particularly in the context of emerging anti-fibrotic therapies.
Ramtoola et al. (Thu,) conducted a cohort in Heart failure with preserved ejection fraction (n=45). [68Ga]FAPI positron emission tomography vs. Patients with HFrEF and healthy volunteers was evaluated on Presence, distribution, and intensity of cardiac [68Ga]FAPI uptake. [68Ga]FAPI PET imaging revealed visually increased myocardial uptake in 47% of HFpEF patients, with uptake intensity being highest in HFpEF compared to HFrEF patients and healthy volunteers.