The parallel squint.

Field: Medicine (Health Sciences)

Background

Myocardial fibrosis is a poor prognostic factor and a relevant cause of SSc-related mortality. Current non-invasive screening methods for myocardial fibrosis (MF) include echocardiography, electrocardiography and serum Nt-pro-BNP, which are not specific for MF and not sensitive for early changes. Cardiac MRI predominately visualizes extracellular space changes as consequence of long-standing fibroblast activation. Direct visualization of the remodeling fibrotic remodeling process has not been feasible so far.

Objectives

Here, we use a tracer labeled probe directed against Fibroblast-Activation-Protein (FAP) to visualize activated fibroblasts in the myocardium of SSc patients and healthy individuals to test the hypothesis that FAPI-based PET imaging might enable the assessment of disease activity in SSc-related MF.

Methods

In this exploratory trial, 7 patients with SSc-related myocardial fibrosis (MF) confirmed by cardic MRI and 8 SSc patients without myocardial involvement were enrolled. All participants underwent 68Ga-FAPI-04 PET/CT imaging and cardiac MRI as well as echocardiography, electrocardiogram, and serum NT-pro-BNP. Patients were followed for at least 6 months including a follow-up cardiac MRI. Regional mapping of 68Ga-FAPI-04-uptake, late gadolinium enhancement (LGE) and T1-relaxation times were performed according to the American Heart Association 17 regions model. Myocardial tissue was analysed by immunofluorescence- (aSMA and FAP) and Sirius-Red staining.

Results

Myocardial FAPI-04-accumulation was significantly increased in SSc patients with myocardial fibrosis as defined by LGE in MRI compared to SSc patients without LGE. Consistent with the previously reported widespread remodeling in SSc-associated myocardial disease, the distribution of FAPI uptake was observed across multiple areas and did not correspond to the supply areas of the coronary arteries. Histological analyses of myocardial tissue biopsied from a LGE and 68Ga-FAPI-04-positive region revealed the accumulation of FAP+; SMA+ myofibroblasts in regions of pronounced collagen deposition. Slightly increased 68Ga-FAPI-04 -uptake values were observed in SSc patients without LGE, but with cardiovascular risk factors. Comparing 68Ga-FAPI-04-uptake with cardiac MRI based mapping techniques, we observed a partial overlap for certain regions and differences in others. These observations suggest, that 68Ga-FAPI-PET/CT and cMRI could visualize different aspects of the disease process. To confirm that 68Ga-FAPI-04-uptake assesses current molecular fibroblast activity rather than accumulating disease damage, we analyzed associations of 68Ga-FAPI-04-uptake with changes of clinical parameters of SSc-MF on follow-up: Here we observed different dynamics of change of 68Ga-FAPI-04-uptake and cardiac MRI-based, e.g. in response to start of immunosuppressive therapy.

Conclusion

Our study presents first in human evidence on a limited number of patients that FAPI-04-uptake correlates with fibrotic activity in SSc-associated myocardial fibrosis and that 68Ga-FAPI-04-PET/CT may thus improve risk stratification in this population.

Disclosure of Interests

None declared