Molecular Imaging Reveals Persistent Atrial Fibroblast Activation After AF Ablation

Even after catheter ablation has brought atrial fibrillation (AF) under control, the biological machinery driving the arrhythmia may keep working. A study published in EJNMMI Research used a molecular imaging technique, [68Ga]Ga-FAPI-04 PET/CMR, to examine patients who had undergone ablation and reached a stable post-procedural state, and found that fibroblast activation in the left atrium remained widespread in most of them.

The researchers reported that during this stable phase, 74% of the AF patients studied — 23 of 31 — showed increased [68Ga]Ga-FAPI-04 uptake in the left atrium. The signal was predominantly located in the posterior wall of the atrium and around the pulmonary veins, the very regions targeted by ablation catheters.

[68Ga]Ga-FAPI-04 is a radiotracer that binds to fibroblast activation protein, allowing PET imaging to visualize fibroblast activity, a biological process linked to inflammation and fibrosis. The study’s authors note that conventional cardiac magnetic resonance (CMR) alone cannot capture this biological activity, which may be essential for understanding how the arrhythmic substrate progresses over time.

Compared with controls, the AF patients showed significantly higher left atrial FAPI burden together with global impairment of both atrial and ventricular mechanics. Patients whose AF had been persistent, rather than paroxysmal, demonstrated a greater fibroblast activation burden in the left atrium, enlarged left atrial volume, and more severe reductions in left atrial ejection fraction and strain parameters.

Recurrence of the arrhythmia carried a distinctive signature. The study found that patients with recurrence were characterized by a mechanical atrial failure phenotype with markedly increased left atrial surface volume, suggesting that the combination of molecular and functional measures may help distinguish different post-ablation outcomes.

The correlations reported in the study connect the molecular signal to measurable mechanical decline. Left atrial FAPI burden correlated positively with the percent of late gadolinium enhancement and with atrial and ventricular volumes, and inversely with left atrial ejection fraction and atrial and ventricular strain parameters. According to the authors, this indicates a close association between persistent fibroblast activation and atrioventricular mechanical decompensation.

The imaging also extended to the fat surrounding the heart. Epicardial adipose tissue (EAT) FAPI activity showed concordant associations with left atrial structural and functional remodeling, and left atrial FAPI burden was positively related to stroke risk scores, tying the molecular signal to clinically used risk stratification measures.

The study’s conclusions are framed carefully. The authors state that [68Ga]Ga-FAPI-04 PET/CMR provides unique molecular insights into atrial fibroblast activation in post-ablation AF patients, and that integrating molecular and functional imaging offers complementary insights that may help generate hypotheses for future individualized management. The work is presented as hypothesis-generating rather than as establishing new treatment standards.

Several limitations of scope are worth noting. The patient cohort numbered 31, the imaging was performed at a single stable post-procedural time point, and the reported associations between FAPI uptake, mechanics and risk scores are cross-sectional correlations rather than demonstrated causal effects or predictions of who will relapse. The article was published as an open-access, peer-reviewed accepted manuscript, subject to further edits before the final version of record.

Within those limits, the findings add a molecular dimension to the follow-up of ablated AF patients. By combining a fibroblast-activation PET tracer with the structural and functional detail of CMR, the approach makes visible a biological process — ongoing fibroblast activation in the left atrium — that persists in most patients long after the procedure, and links it to the mechanical deterioration of both atria and ventricles.

Subject of Research: Molecular PET/CMR imaging of atrial fibroblast activation in patients after catheter ablation for atrial fibrillation

Article Title: Ongoing atrial fibroblast activation after catheter ablation for atrial fibrillation: insights from [68Ga]Ga-FAPI-04 PET/CMR

Article References: Yin, F., Yang, B., Zhang, W., Wang, K., Chen, X., Zhou, Z., Yuan, Z., Wang, W., Wang, Z., Cheng, X., Yang, Y., Sun, Y., Zhao, J., Ding, J., & Zhang, X. (2026). Ongoing atrial fibroblast activation after catheter ablation for atrial fibrillation: insights from [68Ga]Ga-FAPI-04 PET/CMR. EJNMMI Research. https://doi.org/10.1186/s13550-026-01506-9

Image Credits: AI Generated

DOI: 10.1186/s13550-026-01506-9

Keywords: atrial fibrillation, catheter ablation, fibroblast activation, FAPI PET, CMR, left atrium, epicardial adipose tissue, molecular imaging, atrial remodeling, stroke risk, cardiac fibrosis, EJNMMI Research