BACKGROUND: The extent of myocardial bone tracer uptake with technetium pyrophosphate, hydroxymethylene diphosphonate, and 3,3-diphosphono-1,2-propanodicarboxylate in transthyretin amyloid cardiomyopathy (ATTR-CM) might reflect cardiac amyloid burden and be associated with outcome. METHODS: Consecutive patients with ATTR-CM who underwent diagnostic bone tracer scintigraphy with acquisition of whole-body planar and cardiac single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre and 4 Italian centers were included. Cardiac uptake was defined according to the Perugini classification: 0=absent cardiac uptake; 1=mild uptake less than bone; 2=moderate uptake equal to bone; and 3=high uptake greater than bone. Extent of right ventricular (RV) uptake was defined as focal (basal segment of the RV free wall only) or diffuse (extending beyond basal segment) on the basis of SPECT imaging. The primary outcome was all-cause mortality. RESULTS: Among 1422 patients with ATTR-CM, RV uptake accompanying left ventricular uptake was identified by SPECT imaging in 100% of cases at diagnosis. Median follow-up in the whole cohort was 34 months (interquartile range, 21 to 50 months), and 494 patients died. By Kaplan-Meier analysis, diffuse RV uptake on SPECT imaging (n=936) was associated with higher all-cause mortality compared with focal (n=486) RV uptake (77.9% versus 22.1%; P <0.001), whereas Perugini grade was not associated with survival ( P =0.27 in grade 2 versus grade 3). On multivariable analysis, after adjustment for age at diagnosis (hazard ratio [HR], 1.03 [95% CI, 1.02–1.04]; P <0.001), presence of the p.(V142I) TTR variant (HR, 1.42 [95% CI, 1.20–1.81]; P =0.004), National Amyloidosis Centre stage (each category, P <0.001), stroke volume index (HR, 0.99 [95% CI, 0.97–0.99]; P =0.043), E/e’ (HR, 1.02 [95% CI, 1.007–1.03]; P =0.004), right atrial area index (HR, 1.05 [95% CI, 1.02–1.08]; P =0.001), and left ventricular global longitudinal strain (HR, 1.06 [95% CI, 1.03–1.09]; P <0.001), diffuse RV uptake on SPECT imaging (HR, 1.60 [95% CI, 1.26–2.04]; P <0.001) remained an independent predictor of all-cause mortality. The prognostic value of diffuse RV uptake was maintained across each National Amyloidosis Centre stage and in both wild-type and hereditary ATTR-CM ( P <0.001 and P =0.02, respectively). CONCLUSIONS: Diffuse RV uptake of bone tracer on SPECT imaging is associated with poor outcomes in patients with ATTR-CM and is an independent prognostic marker at diagnosis.

L’amiloidosi sistemica è una patologia, ereditaria o acquisita, causata dalla deposizione di fibrille insolubili di amiloide con conseguente alterazione della struttura tissutale e della funzione di diversi organi, compreso il muscolo cardiaco. La classificazione della malattia si basa sulla proteina precursore che forma i depositi di amiloide: l’amiloidosi da catene leggere delle immunoglobuline, quella da transtiretina e quella da apolipoproteina A1 sono le forme che più frequentemente presentano un coinvolgimento cardiaco, la cui espressione fenotipica è rappresentata tipicamente da un aumento simmetrico degli spessori parietali biventricolari con funzione sistolica relativamente conservata e marcata disfunzione diastolica. La prevalenza e l’incidenza dell’amiloidosi cardiaca da transtiretina nei pazienti affetti da cardiomiopatia a fenotipo ipertrofico è aumentata negli ultimi anni grazie al miglioramento degli algoritmi diagnostici e allo sviluppo di tecniche di imaging sempre più sofisticate. La diagnosi precoce rappresenta una delle sfide più importanti per il cardiologo poiché oggi sono disponibili terapie “disease-modifying” la cui efficacia è tanto maggiore quanto prima venga intrapreso il trattamento.Questa rassegna ha l’obiettivo di rispondere ai principali quesiti in tema di amiloidosi cardiaca da transtiretina: quando sospettarla, come diagnosticarla e come trattarla.

(1) Background: The visual and semiquantitative analysis of Technetium-99metastable-3,3-diphospono-1,2-propanodicarboxylic acid (^99mTc-DPD) bone scintigraphy is promising for diagnosing cardiac amyloidosis but time-consuming. We validated a faster method, the geometric mean (GM) method with a semi-automated workflow, for heart–whole body (WB) ratio (H/WBr), heart retention (Hr), and WB retention (WBr) calculations compared to the classic method (CM) established in the literature. The capability of semiquantitative scintigraphy indexes to differentiate the etiology in transthyretin-related cardiac amyloidosis (cATTR) patients was investigated. (2) Methods: H/WBr, Hr, and WBr were calculated by extracting counts for WB, kidneys, bladder, and heart on early and late planar image scans and applying background, scan-time, and decay corrections, using CM and GM both on a referring workstation and on a semi-automated workflow in external software. The comparison between CM and GM was assessed with Pearson’s correlation, Lin’s Concordance Correlation Coefficient (CCC), and Bland–Altman analysis. H/WBr, Hr, and WBr and several clinical variables were used to implement LASSO, Random Forest (RF), and Neural Network (NN) models to predict mutated and wild-type ATTR etiologies. ROC curves and AUC were calculated. (3) Results: Hr, WBr, and H/WBr using CM and GM were highly correlated. Bland–Altman analysis between CM and GM showed biases of 0.12% [CI:0.04%;0.19%] for H/WBr, 0.07% [CI: 0.01%; 0.13%] for Hr, and -0.50% [CI: −1.22%; 0.22%] for WBr. LASSO and NN models had good performance in predicting etiologies with AUC values of 87.3% and 73.6%, respectively. The RF model showed a poorer AUC of 55.8%. (4) Conclusions: The GM in the assisted workflow was validated against the CM. LASSO and NN approaches allowed a good prediction performance to be obtained for patient etiology.