99mTc-FAPI SPECT/CT for Evaluation of Myocardial Fibrosis and Cardiac Function in Valvular Heart Disease

Background Active myocardial fibrosis plays a pivotal role in valvular heart disease (VHD) progression. While conventional imaging modalities primarily detect established fibrosis, the detection of active fibroblast activation remains challenging. 99mTc-FAPI SPECT/CT, offering advantages of wider availability and lower cost compared to PET imaging, represents a promising tool for evaluating active myocardial fibrosis.

We conducted a prospective study of 30 VHD patients who underwent 99mTc-FAPI SPECT/CT imaging with comprehensive clinical evaluation. Patients were categorized into FAPI-positive (n=24) and FAPI-negative (n=6) groups based on myocardial tracer uptake patterns. Thirteen FAPI-positive patients completed a three-month follow-up to assess therapeutic response.

FAPI uptake parameters showed robust correlations with established myocardial injury markers (Hs-cTnI vs SUVmax: r=0.831, p<0.001; vs SUVmean: r=0.795, p<0.001) and disease severity indices (VHD staging: r=0.812, p<0.001). FAPI-positive patients demonstrated significantly higher atrial fibrillation prevalence (54.2% vs 0%, P=0.024). Post-treatment follow-up revealed significant improvements in FAPI parameters (SUVmax: 2.8±0.4 to 1.9±0.3, p<0.0001; SUVmean: 2.3±0.3 to 1.6±0.2, p<0.0001), accompanied by enhanced left ventricular ejection fraction (45.3±5.2% to 52.1±4.8%, p=0.0176) and NYHA functional status (p=0.0011), despite unchanged structural parameters.

This study demonstrates that 99mTc-FAPI SPECT/CT enables non-invasive visualization and quantification of active myocardial fibrosis in VHD patients. The strong associations between FAPI parameters and clinical indices, coupled with its ability to monitor therapeutic response, suggest its potential as a valuable tool for risk stratification and treatment optimization in VHD management. Trial registration ChiCTR2400094867. Registered 30 December 2024. Public site: https://www.chictr.org.cn/index.html. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was supported by Natural Science Foundation of Fujian Province (2021J05066); Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant number: 2023Y9299). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board of Fujian Provincial Hospital gave ethical approval for this work (approval number: K2024-12-075) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors