Diphosphonate single-photon emission computed tomography in cardiac transthyretin amyloidosis
Introduction
Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold and deposit in the heart and in other organs as amyloid fibrils [1]. Cardiac involvement in amyloid TTR (ATTR) amyloidosis typically manifests as left ventricular (LV) pseudohypertrophy and/or heart failure (HF) with preserved ejection fraction. ATTR is increasingly recognized as an underdiagnosed condition [2], as well as a crucial determinant of morbidity and mortality.
Cardiac ATTR can be diagnosed through the demonstration of TTR amyloid deposits on endomyocardial biopsy or following a non-invasive algorithm that includes cardiac magnetic resonance (CMR) and diphosphonate scintigraphy [3]. Planar scintigraphy with the use of 99mTc-labelled diphosphonate tracers has proven a valuable tool to detect the presence of myocardial TTR amyloid deposits [4], and to perform a qualitative assessment of the amyloid burden through the Perugini scoring system [5]. Compared to planar imaging, single-photon emission computed tomography (SPECT) examination allows a 3-dimensional assessment of myocardial tracer uptake. Techniques for SPECT imaging are now commonly available, given their role in the diagnostic work-up of coronary artery disease [6], and has been further refined thanks to the introduction of the Cadmium Zinc Telluride (CZT) technique, which allows better spatial resolution and sensitivity [7].
In the present study we evaluated the potential of CZT SPECT imaging for detecting myocardial infiltration in ATTR-related cardiac disease, also in comparison with CMR.
Section snippets
Patient population
Data from consecutive patients evaluated at a tertiary referral center in Italy from June 2016 to April 2019, undergoing both cardiac diphosphonate scintigraphy with SPECT acquisitions and CMR as part of their diagnostic workup, and ultimately diagnosed with ATTR cardiomyopathy were retrospectively collected. Cardiac ATTR amyloidosis was diagnosed according to the algorithm by Gillmore et al., whereby histological confirmation and typing of amyloid is not required when patients score 2–3 on the
Study population, echocardiographic and cardiac magnetic resonance findings
The main characteristics of study population (n = 38) are reported in Table 1. Mean age was 81 years, and 30 patients (79%) were men. The vast majority (n = 35, 92%) was diagnosed with wild-type ATTR, and 3 (8%) with variant ATTR. Interventricular septum and posterior wall thickness, relative wall thickness (RWT), and E/e′ ratio values were all increased. Among patients undergoing CMR scan (n = 35, 92%), median LV ejection fraction was 55% (47–65), and LV mass index was increased (125 g/m2
Discussion
The present study represents the first dedicated assessment of diphosphonate SPECT as a tool for characterizing the segmental amyloid burden in ATTR cardiomyopathy. 99mTc-HMDP SPECT allows estimating the regional amyloid burden and making some assumptions about disease evolution across Perugini stages.
Myocardial scintigraphy with diphosphonate tracers is a pillar of non-invasive diagnosis of ATTR cardiomyopathy [7], given the high specificity of myocardial diphosphonate uptake [10]. This
CRediT authorship contribution statement
Chrysanthos Grigoratos: Data curation, Writing - original draft. Alberto Aimo: Data curation, Writing - original draft. Claudio Rapezzi: Supervision, Writing - review & editing. Dario Genovesi: Visualization, Investigation, Writing - review & editing. Andrea Barison: Visualization, Investigation, Writing - review & editing. Giovanni Donato Aquaro: Visualization, Investigation, Writing - review & editing. Giuseppe Vergaro: Writing - review & editing. Angela Pucci: Visualization, Investigation,
Declaration of competing interest
There is no conflict of interest to disclose.
References (18)
- et al.
Diagnosis, prognosis, and therapy of transthyretin amyloidosis
J. Am. Coll. Cardiol.
(2015) - et al.
Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy
J. Am. Coll. Cardiol.
(2005) - et al.
Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy
J. Am. Coll. Cardiol.
(2005) - et al.
Regional variation in technetium pyrophosphate uptake in transthyretin cardiac amyloidosis and impact on mortality
JACC Cardiovasc. Imaging
(2018) - et al.
THAOS: The Transthyretin amyloidosis outcomes survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis
Curr. Med. Res. Opin.
(2013) - et al.
Nonbiopsy diagnosis of cardiac transthyretin amyloidosis
Circulation.
(2016) - et al.
Bone scintigraphy with (99m)technetium-hydroxymethylene diphosphonate allows early diagnosis of cardiac involvement in patients with transthyretin-derived systemic amyloidosis
Amyloid.
(2014) - Task Force Members, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset...
- et al.
Cardiovascular Committee of the European Association of nuclear medicine (EANM). Performance of cardiac cadmium-zinc-telluride gamma camera imaging in coronary artery disease: a review from the cardiovascular committee of the European Association of Nuclear Medicine (EANM)
Eur. J. Nucl. Med. Mol. Imaging
(2016)
Cited by (9)
Transthyretin amyloid cardiomyopathy: An uncharted territory awaiting discovery
2020, European Journal of Internal MedicineCitation Excerpt :Understanding the real prevalence of ATTR amyloidosis, particularly with the cardiac phenotype, in the various clinical scenarios and differentiating indolent cardiac accumulation of the ‘senile’ form from the authentic infiltrative disease; The use of diphosphonate single photon emission computed tomography to better characterize patients with Perugini score 1 (by detecting localized but intense amyloid deposition, thus allowing an early diagnosis [42]) and possibly to quantify the amyloid burden; Investigating the potential role of PET imaging with amyloid tracers (alone or in combination with bone tracer scintigraphy) for the differential diagnosis between AL and ATTR amyloidosis [43];
Emerging Role of Scintigraphy Using Bone-Seeking Tracers for Diagnosis of Cardiac Amyloidosis: AJR Expert Panel Narrative Review
2024, American Journal of Roentgenology
- 1
Chrysanthos Grigoratos and Alberto Aimo equally contributed.