Diphosphonate single-photon emission computed tomography in cardiac transthyretin amyloidosis

https://doi.org/10.1016/j.ijcard.2020.02.030Get rights and content

Highlights

  • In ATTR cardiomyopathy, SPECT allows to characterize regional amyloid burden.

  • SPECT also allows quantifying the intensity of amyloid burden.

  • Amyloid deposition begins in the septal and inferior walls and the basal region.

Abstract

Background

Planar diphosphonate scintigraphy is an established diagnostic tool for amyloid transthyretin (ATTR) cardiomyopathy. Characterization of the amyloid burden up to the segmental level by single photon emission computed tomography (SPECT) has not been evaluated so far.

Methods

Data from consecutive patients undergoing cardiac 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) SPECT and diagnosed with ATTR cardiomyopathy at a tertiary referral center from June 2016 to April 2019 were collected.

Results

Thirty-eight patients were included (median age 81 years, 79% men, 92% with wild-type ATTR). In patients with Perugini score 1, the most intense diphosphonate regional uptake was found in septal segments, particularly in infero-septal segments. Among patients scoring 2, the amyloid burden in the septum became more significant, and extended to inferior and apical segments. Finally, patients scoring 3 displayed an intense and widespread tracer uptake. All patients with Perugini score 1 had LGE in at least one antero-septal, one infero-septal, and one infero-lateral segment. All patients with score 2 displayed LGE in infero-septal, inferior, and infero-lateral segments. LGE became extensive in patients scoring 3, with all patients having at least one LGE-positive segment in each region.

Conclusions

When assimilating different Perugini grades to evolutive stages of the disease, amyloid deposition seem to progress from the septum to the inferior wall and then to the other regions and from the basis to the apex. The potential of segmental analysis might be particularly relevant in patients with very limited cardiac uptake at planar scintigraphy (Perugini score 1).

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.

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Chrysanthos Grigoratos and Alberto Aimo equally contributed.

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