Prognostic significance of incidental suspected transthyretin amyloidosis on routine bone scintigraphy

Abstract

Background Transthyretin amyloidosis (ATTR) is an occasional incidental finding on bone scintigraphy. We studied its prognostic impact in elderly patients. Methods The study population consisted of 2000 patients aged over 70 years who underwent bone scintigraphies with clinical indications in three nuclear medicine departments (Kymenlaakso, Jorvi and Meilahti hospitals) in Finland. All studies were performed using 99mTechnetium labeled hydroxymethylene diphosphonate (HMDP). ATTR was suspected in patients with ≥grade 2 Perugini grade uptake (grade 0-3). Heart-to-contralateral ratio (H/CL) of ≥ 1.30 was considered positive for ATTR. The overall and cardiovascular mortality were obtained from the Finnish National Statistical Service. Results There were a total of 1014 deaths (51%) and 177 cardiovascular deaths (9%) during median follow-up of 4 ± 2 years. ATTR was suspected in 69 patients (3.6%) of which 54 (2.7%) had grade 2 and 15 (.8%) had grade 3 uptake and in 47 patients (2.4%) by H/CL ratio. In multivariate analyses age, bone metastasis, H/CL ratio and grade 3 uptake were independent predictors of overall and cardiovascular mortality. Grade 2 uptake was a predictor of cardiovascular mortality. Conclusions A suspected ATTR as an incidental finding on bone scintigraphy predicts elevated overall and cardiovascular mortality in elderly patients.

Multimodality Imaging in the Evaluation and Prognostication of Cardiac Amyloidosis

“…Per current guidelines, H/CL ≥ 1.5 is positive, < 1.0 is negative, and in between is equivocal ( 75 ). Some physicians use a cutoff of H/CL ≥ 1.3 to increase sensitivity ( 80 ). Other signal ratios are scattered throughout the literature including heart to whole body (H/WBR) and heart to skull (H/S).…”

“…These characteristics also correlate with degree of amyloid deposition on CMR ( 58 ). The initial use in more advanced disease led to high sensitivity and specificity but more contemporary ordering practices aimed at early diagnosis may have less uptake which may not be detectable below a certain amount of total amyloid deposition ( 74 , 80 – 82 ). However, the lower sensitivity is not entirely explained by early disease as some patients with advanced disease by symptoms and other imaging have grade 0/1 uptake ( 83 , 84 ).…”

Incidental detection of ATTR cardiac amyloidosis

“…effects. 7 Aside from solid organ transplantation, the only effective treatment that is currently FDA-approved, the transthyretin stabilizer tafamadis, works by preventing further accumulation of the misfolded protein in cardiac tissues. While this treatment offers a remarkable survival benefit, this benefit was only seen starting approximately 18 months after initiation of therapy.…”

“…Given its many positive attributes, it has been suggested that cardiac scintigraphy could represent a new non-invasive ''gold standard'' for diagnosis, although both pre-test probability of ATTR-CA in a population as well as reader/ technician experience remain important considerations in the utility of this test. 16 Given the importance of early diagnosis of ATTR-CA and the potential of cardiac scintigraphy to identify subclinical disease, in this issue of the Journal of Nuclear Cardiology Suomalainen et al 7 explored whether there was prognostic significance to incidentally found suspected ATTR-CA on bone scintigraphy studies performed for other reasons. This study evaluated 2000 patients over the age of 70 and compared the risk of overall and cardiovascular mortality between patients with positive 99m Tc-HMDP scans (grade 2 uptake or H/ CL ratio [ 1.30 at 3 hours) and those with negative ones.…”

“…9 Newer drugs within ongoing clinical trials, such as doxycycline and anti-sense oligonucleotides, also rely on stopping progression of the disease rather than disease reversal. 7 This makes a population with incidentally noted disease, only 41% of whom have established heart failure, a potentially exciting population with mostly subclinical disease in which targeted therapies might be more effective when started earlier in their disease course.…”