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. 2024 Apr 9;149(15):1157-1168.
doi: 10.1161/CIRCULATIONAHA.123.066524. Epub 2024 Feb 8.

Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy

Aldostefano Porcari  1   2   3 , Marianna Fontana  1   2 , Marco Canepa  4   5 , Elena Biagini  3   6 , Francesco Cappelli  7   8   9 , Christian Gagliardi  3   6 , Simone Longhi  3   6 , Linda Pagura  2   3 , Giacomo Tini  10 , Franca Dore  9 , Rachele Bonfiglioli  11 , Matteo Bauckneht  12   13 , Alberto Miceli  14 , Francesca Girardi  9 , Anna Lisa Martini  15 , Giulia Barbati  16 , Egidio Natalino Costanzo  15 , Angelo Giuseppe Caponetti  17 , Andrea Paccagnella  11 , Maurizio Sguazzotti  3   17 , Giovanni La Malfa  4 , Mattia Zampieri  8 , Roberto Sciagrà  15 , Federico Perfetto  7 , Dorota Rowczenio  1 , Janet Gilbertson  1 , David F Hutt  1 , Philip N Hawkins  1 , Claudio Rapezzi  18   19 , Marco Merlo  3 , Gianfranco Sinagra #  2   3 , Julian D Gillmore #  1
Affiliations

Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy

Aldostefano Porcari et al. Circulation. .

Abstract

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.

Keywords: amyloidosis; prognosis; tomography, emission-computed, single-photon; transthyretin.

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Conflict of interest statement

Disclosures The authors report no conflicts in relation to the submitted work. They report the following conflicts outside the submitted work: Dr Rapezzi served on the Italian scientific advisory board of Pfizer and received unrestricted research grants and personal fees from Pfizer and personal fees from Alnylam Pharmaceuticals. Dr Biagini received advisory board fees from Sanofi, Genzyme, and Takeda. Dr Cappelli received advisory board fees from Pfizer and Akcea and research grants from Pfizer. Dr Sinagra received personal fees for occasional educational activities from Biotronik, Boston Scientific, AstraZeneca, and Novartis. Dr Canepa received speaker and advisor fees from Akcea Therapeutics, Menarini, Novartis, Pfizer, Sanofi e Sanofi Genzyme, and Vifor Pharma, as well as 2 investigator-initiated grants from Pfizer. Dr Fontana is supported by a British Heart Foundation intermediate clinical research fellowship (FS/18/21/33447). Dr Merlo received congress fees from Novartis and Vifor Pharma and research grant and congress fees from Pfizer. Dr Gillmore receives advisory board fees from Pfizer, Alnylam, ATTRalus, Intellia, AstraZeneca, and BridgeBio.

Figures

Figure 1.
Figure 1.
Extent of RV retention leading to biventricular uptake of bone tracers on planar and SPECT scintigraphy in transthyretin amyloid cardiomyopathy. Top, Whole-body scans, anterior view. Bottom, Cross-sectional views of cardiac single-photon emission computed tomography (SPECT) in the same patients. Left, Focal right ventricular (RV) uptake: absent planar RV uptake but focal uptake in the basal RV free wall on SPECT. Right, Diffuse RV uptake: planar left ventricular and RV uptake with diffuse uptake in the RV free wall on SPECT.
Figure 2.
Figure 2.
Kaplan-Meier survival curves stratified by (top) presence of focal vs diffuse RV uptake on SPECT imaging, (bottom left) in Perugini grade 2, and (bottom right) in Perugini grade 3. RV indicates right ventricular; and SPECT, single-photon emission computed tomography.
Figure 3.
Figure 3.
Kaplan-Meier survival curves stratified according to (left) genotype (ATTRwt vs ATTRv-CM) and (right) NAC stage. The table shows the absolute numbers of patients at risk at different follow-up times. ATTRv-CM indicates variant transthyretin amyloid cardiomyopathy; ATTRwt-CM, wild-type transthyretin amyloid cardiomyopathy; NAC, National Amyloidosis Centre; RV, right ventricular; and V122I ATTRv-CM, variant transthyretin amyloid cardiomyopathy associated with the valine-to-isoleucine substitution.
Figure 4.
Figure 4.
Proposal of a flowchart for prognostic stratification of patients with ATTR-CM according to the extent of right ventricular uptake on SPECT imaging. ATTR-CM indicates transthyretin amyloid cardiomyopathy; IT, Italy; LV, left ventricular; NAC, National Amyloidosis Centre; SPECT, single-photon emission computed tomography; 99mTc-DPD, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid; 99mTc-HMDP, 99mTc-hydroxymethylene diphosphonate; 99mTc-PYP, 99mTc-pyrophosphate; V122I, valine-to-isoleucine substitution; and WT, wild-type.
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References

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