The sensitivity of DPD scintigraphy to detect transthyretin cardiac amyloidosis in V30M mutation depends on the phenotypic expression of the disease

Abstract

Background: There is a growing need for a non-invasive test to detect cardiac involvement in patients with transthyretin-related hereditary amyloidosis (ATTR) caused by V30M mutation. ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy is a promising method, but its accuracy in this particular mutation remains unknown.

Methods: A cohort of 179 patients: 92 with early-onset disease (EoD, symptoms <50-years-old), 33 with late-onset disease (LoD) and 54 asymptomatic carriers were prospectively evaluated and underwent DPD scintigraphy, which was compared with the results of echocardiogram, ambulatory blood pressure monitoring, 24 h-Holter, myocardial ¹²³I-metaiodobenzylguanidine imaging and NT-proBNP.

Results: Amyloid cardiomyopathy, defined as septal thickness ≥13 mm, was present in 32 patients (17.9%) and was more frequent in those with LoD (OR: 3.68, p = .003). Cardiac DPD uptake was present in 22 individuals (12.3%) and correlated with parameters indicative of cardiac amyloidosis. DPD imaging was strongly influenced by the age of disease onset: among patients with myocardial thickening, cardiac DPD retention was present in 11/15 (73.3%) with LoD, in contrast to only 4/17 (26.7%) with EoD (p = .005). Two patients with myocardial thickening and normal DPD scintigraphy underwent endomyocardial biopsy that confirmed ATTR amyloidosis.

Conclusion: DPD scintigraphy presents suboptimal sensitivity to detect cardiac involvement in ATTRV30M, particularly in symptomatic patients with EoD.

Keywords:

• Amyloidosis
• DPD scintigraphy
• Scintigraphy
• Transthyretin

Acknowledgements

We thank all the clinical and nursing staff at the Santa Maria University Hospital. We thank Prof. Dulce Brito and Dr. Artur Costa e Silva for cardiac biopsies and histology; Dr. Rui Plácido and Prof. Ana G. Almeida for echocardiographic studies; and Ms. Irina Neves, Mrs Carla Inácio, Mrs. Ana Paixão and Mrs. Fernanda Gaspar for non-invasive cardiac evaluations.

Disclosure statement

Dr. Isabel Conceição received honoraria from serving on the scientific advisory board of FoldRx Pharmaceuticals/Pfizer and currently she serves on the THAOS (natural history disease registry) scientific advisory board (Pfizer Inc). Other authors reported no conflicts of interest.