PET/MRI Detects Fibroblast Activity in Cardiomyopathy, Signals Prognosis

Myocardial fibrosis and adverse remodeling are central drivers of disease progression in heart failure with reduced ejection fraction (HFrEF).¹ However, tools to directly assess fibroblast activation—believed to play a pivotal role in fibrotic progression—remain limited.

A new case-control study published in JAMA Cardiology demonstrates that molecular imaging using gallium-68–labeled fibroblast activation protein inhibitor 46 ([68Ga]FAPI-46) combined PET/MR) can noninvasively identify fibroblast activation in patients with HF and provide insight into prognosis.

“Fibroblast activation persisted over 6 months, was associated with changes in systolic function, and showed distinct etiology-specific patterns,” wrote the researchers of the study.

Prior research highlights why this imaging approach is significant: conventional cardiac MRI can detect established fibrosis but cannot distinguish active, ongoing fibrotic processes, whereas fibroblast activation protein–targeted PET imaging enables visualization of early, active fibrosis and may improve risk stratification and monitoring of treatment response.²

The researchers conducted a prospective analysis of 81 individuals across 3 groups: patients with HFrEF, patients with prior myocardial infarction (MI) but preserved systolic function, and healthy volunteers.¹ The HFrEF group included both ischemic and nonischemic etiologies. All participants underwent PET/MRI to measure myocardial fibroblast activation, quantified as maximum standardized uptake values (SUVmax). A subset of patients with HF also completed repeat imaging after at least 6 months of optimized medical therapy to assess longitudinal changes.

None of the healthy volunteers exhibited evidence of myocardial fibroblast activation. By contrast, all patients with HF demonstrated significantly increased FAPI-46 uptake compared with healthy controls (mean [SD] SUVmax, 2.7 [1.5] vs 1.5 [0.3]; P < .001).

Patterns of fibroblast activation differed based on underlying disease. Patients with ischemic cardiomyopathy showed the highest uptake (mean SUVmax, 3.2 [1.1]), with tracer localization corresponding to areas of prior infarction. Meanwhile, patients with nonischemic cardiomyopathy exhibited more diffuse, lower-intensity uptake (mean SUVmax, 2.3 [0.5]), with the strongest signal observed in the basal septum. These distinct imaging signatures suggest different fibrotic remodeling pathways depending on etiology.

The study also compared patients with ischemic cardiomyopathy to those with prior MI but no HF. Despite similar infarct size, patients with HF had significantly greater fibroblast activation (SUVmax, 3.2 [1.1] vs 2.5 [0.3]; P = .03), reinforcing the role of ongoing fibrotic processes in disease progression beyond initial ischemic injury.

Among patients who underwent follow-up imaging, higher baseline [68Ga]FAPI-46 uptake was associated with less improvement in left ventricular ejection fraction after optimal medical therapy (r = −0.52; P = .02). This finding suggests that increased fibroblast activation may identify individuals at higher risk for persistent dysfunction and could serve as a marker of therapeutic response.

However, the researchers noted some limitations. The study included a relatively small sample size and a limited number of patients undergoing follow-up imaging, which may affect the generalizability of the results. Additionally, the observational design limits causal inference, and variability in underlying HF etiology and treatment regimens could influence imaging findings. Larger, longitudinal studies are needed to confirm the prognostic value of fibroblast-targeted imaging and to determine whether incorporating this approach into clinical decision-making improves patient outcomes.

Despite the limitations, these results underscore the potential for PET/MRI assessment of fibroblast activation to advance personalized care in HF. By enabling earlier identification of patients at risk for adverse remodeling, this approach could support more targeted interventions, including antifibrotic therapies currently under investigation.

“These findings support an important pathophysiological role for activated fibroblasts in heart failure and identify them as a potential therapeutic target,” wrote the researchers.

References

1. Joshi SS, Barton AK, Loganath K, et al. Myocardial fibroblast activation in ischemic and nonischemic cardiomyopathy. JAMA Cardiol. Published online April 15, 2026. doi:10.1001/jamacardio.2026.0661

2. ⁶⁸Ga-FAPI PET/​CT for cardiac fibrosis in heart failure (MY-FAPI). ClinicalTrials.gov. Updated December 29, 2025. Accessed April 13, 2026. https://clinicaltrials.gov/study/NCT07296081