Persistent myocardial fibrosis contributes to worsening heart failure, but noninvasive tools to characterize active fibroblast biology remain limited. A prospective case-control study published in JAMA Cardiology evaluated whether gallium-68 fibroblast activation protein inhibitor-46 positron emission tomography/magnetic resonance imaging could detect myocardial fibroblast activation in heart failure with reduced ejection fraction (HFrEF).

The study included 81 participants: 42 with HFrEF, 20 with prior myocardial infarction and preserved systolic function, and 19 healthy volunteers. Among patients with HFrEF, 21 had ischemic cardiomyopathy, and 21 had nonischemic cardiomyopathy. The mean age was 66.2 years, 27% were female, and the mean left ventricular ejection fraction was 41%.

Healthy volunteers showed no measurable myocardial fibroblast activation. Patients with HFrEF had higher myocardial uptake than healthy volunteers (SUVmax 2.7 vs 1.5; P < .001). The highest uptake was seen in ischemic cardiomyopathy and concentrated within prior infarct regions (SUVmax 3.2). Nonischemic cardiomyopathy showed a more diffuse lower-intensity pattern (SUVmax 2.3), with the strongest signal in the basal septum regardless of late gadolinium enhancement.

Patients with ischemic cardiomyopathy had higher uptake than those with prior myocardial infarction without HF despite similar infarct size (3.2 vs 2.5; P = .03). Higher baseline uptake was associated with less improvement in left ventricular ejection fraction after optimal medical therapy (r = −0.52; P = .02).

These findings suggest that FAPI PET may help characterize remodeling patterns in HFrEF and warrant further evaluation for prognostic use.