18F-Florbetaben-PET/CT extracardiac uptake in patients with suspected cardiac amyloidosis: prevalence, distribution, and prognostic significance
P M Paolo Morfino, G D Giovanni Dugo, D G Dario Genovesi, V C Vincenzo Castiglione, A A Alberto Aimo, G B Gabriele Buda, M L G Maria Livia Del Giudice, M E Michele Emdin, A G Assuero Giorgetti, G V Giuseppe VergaroAbstract
Background
18F-Florbetaben-PET/CT is an emergent tool for the diagnosis and prognostic stratification of patients with suspected light-chain cardiac amyloidosis (AL-CA). Extracardiac uptake has been reported but its prevalence, distribution, and clinical significance has not been systematically assessed.
Purpose
To describe patterns and prognostic impact of 18F-Florbetaben-PET/CT extracardiac uptake in patients with suspected CA.
Methods
Patients referred to a tertiary centre with suspected CA and undergoing 18F-Florbetaben-PET/CT late scans (50–60 min) were retrospectively enrolled. Diagnosis of CA or other mimicking conditions was established using current invasive or non-invasive criteria. Follow-up started at time of PET/CT scan; patients were followed-up for the endpoint of all-cause death. Likelihood ratio chi-square test and Fisher tests with Holm-Bonferroni correction were used for pairwise comparison of frequencies. Kaplan-Meier with log-rank test and Cox regression (adjusted for age, sex, amyloid type and NYHA class) were performed for survival analysis. P-value <0.05 was considered significant.
Results
Between January 2020 and January 2025, 162 patients (mean age: 73 years, males: 75%) were enrolled. Patients were diagnosed with AL-CA (n=44; 27.2%), transthyretin (ATTR)-CA (n=33; 20.4%), dual-CA (AL+ATTR; n=4; 2.5%), hypertensive heart disease, aortic stenosis, hypertrophic cardiomyopathy (n=12; 7.4%), plasma cell dyscrasia without cardiac involvement (n=69; 42.6%). Patients were followed-up for a median of 20 months (IQR: 7-38 months); death occurred in 75 (46.3%) patients.
As reported in Figure 1, prevalence of extracardiac uptake was similar in patients with and without CA (62.2% vs 75.3%, p=0.12), tended to be higher in AL-CA (73%) compared to ATTR-CA patients (49%, p=0.14) and similar between AL-CA and patients with plasma cell dyscrasia alone (81%, p=0.70). AL-CA patients showed a high prevalence of thyroid (34%) and lung (30%) uptake, which were absent in ATTR-CA (p<0.001). Bone marrow uptake was common in patients with plasma cell dyscrasia either without cardiac involvement (66.7%, p<0.05 vs all other groups) or in those with concomitant ATTR-CA (5 out of 6; 83%). Only AL-CA patients showed >2 sites of extracardiac uptake.
Among CA patients, presence of any extracardiac uptake was associated with lower survival (54 vs 25 months, log-rank p=0.015, Figure 2). Increasing number of uptake sites (n=0, 1, ≥2) was associated with lower 1-year survival rate (83% vs 69% vs 50%, log-rank p=0.022) in CA. Extracardiac uptake in CA was an independent predictor of death at multivariate Cox regression analysis (HR 2.42, 95% CI 1.1-5.3, p=0.028). Survival analysis in the overall cohort confirmed these findings (HR 2.26, 95% CI 1.26-4.04, p=0.006).
Conclusions
18F-Florbetaben-PET/CT extracardiac uptake is common and shows different patterns across CA subtypes. Extracardiac uptake is associated with increased risk of death.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.