Diagnostic and prognostic contribution of DPD scintigraphy in transthyretin V30M cardiac amyloidosis

Abstract

Background

Early diagnosis and prognostic stratification of cardiac transthyretin amyloidosis are crucial. Although ^99mTc 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) scintigraphy is the preferred method for the non-invasive diagnosis, its accuracy appears to be limited in transthyretin amyloidosis protein (ATTR) V30M mutation. Furthermore, its prognostic value in this mutation is unknown. This study investigated the diagnostic value of DPD scintigraphy to detect ATTR cardiomyopathy in V30M mutation and explored its prognostic value regarding mortality.

Methods

A total of 288 ATTR V30M mutation carriers (median age: 46 years; 49% males) without myocardial thickening (defined as septal thickness ≥13mm) attributable to other causes and who underwent DPD scintigraphy were enrolled. ATTR cardiomyopathy was defined by septal thickness ≥13mm and at least one of the criteria: late heart-to-mediastinum (H/M) ¹²³I-metaiodobenzylguanidine (MIBG) uptake ratio <1.60; electrical heart disease or biopsy-documented amyloidosis.

Results

ATTR cardiomyopathy was identified in 41 (14.2%) patients and cardiac DPD uptake in 34 (11.8%). During a mean follow-up of 33.6 ± 1.2 months, 16 patients died (5.6%). Mortality was 14 times higher in patients with ATTR cardiomyopathy, 13 times higher in those with DPD uptake and 10 times higher in those with late H/M MIBG <1.60. The combined assessment of septal thickness and cardiac DPD uptake improved risk stratification: patients without septal thickening and without DPD retention had an excellent prognosis while those who presented either or both of them had a significantly worse prognosis, with 5-year mortality rates ranging from 39.9 to 53.3%.

Conclusions

DPD scintigraphy is useful for prognostic stratification of ATTR V30M mutation carriers. Patients without septal thickening and no DPD uptake present the best prognosis compared to those with any signs of cardiac involvement.

Keywords:

• Amyloidosis
• DPD-scintigraphy
• prognosis
• scintigraphy
• transthyretin

Disclosure statement

Dr. Isabel Conceição received honoraria from serving on the scientific advisory board of FoldRx Pharmaceuticals/Pfizer Inc. and currently she serves on the THAOS (natural history disease registry) scientific advisory board (Pfizer Inc).

All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Author contributions

Maria C. Azevedo Coutinho, MD PhD FESC FACC Conception, design of the study Interpretation of data, Manuscript preparation Nuno Cortez-Dias, MD Conception, design of the study Interpretation of data, Manuscript preparation Guilhermina Cantinho, MD Interpretation of data Final approval of the manuscript Susana Gonçalves, MSc Interpretation of data Nelson Cunha, MD Interpretation of data Tiago Rodrigues, MD Interpretation of data Laura Santos, MSc Interpretation of data Isabel Conceição, MD Interpretation of data Final approval of the manuscript João Agostinho, MD Interpretation of data Fausto J. Pinto, MD PhD FESC FACC Interpretation of data Final approval of the manuscript

Additional information

Funding

This study was supported by Santa Maria University Hospital and all exams were done according to the local protocol for evaluation of hereditary transthyretin amyloidosis patients.