Identifying Cardiac Amyloid in Aortic Stenosis: ECV Quantification by CT in TAVR Patients

Abstract

Objectives: The purpose of this study was to validate computed tomography measured ECV (ECVCT) as part of routine evaluation for the detection of cardiac amyloid in patients with aortic stenosis (AS)-amyloid.

Background: AS-amyloid affects 1 in 7 elderly patients referred for transcatheter aortic valve replacement (TAVR). Bone scintigraphy with exclusion of a plasma cell dyscrasia can diagnose transthyretin-related cardiac amyloid noninvasively, for which novel treatments are emerging. Amyloid interstitial expansion increases the myocardial extracellular volume (ECV).

Methods: Patients with severe AS underwent bone scintigraphy (Perugini grade 0, negative; Perugini grades 1 to 3, increasingly positive) and routine TAVR evaluation CT imaging with ECVCT using 3- and 5-min post-contrast acquisitions. Twenty non-AS control patients also had ECVCT performed using the 5-min post-contrast acquisition.

Results: A total of 109 patients (43% male; mean age 86 ± 5 years) with severe AS and 20 control subjects were recruited. Sixteen (15%) had AS-amyloid on bone scintigraphy (grade 1, n = 5; grade 2, n = 11). ECVCT was 32 ± 3%, 34 ± 4%, and 43 ± 6% in Perugini grades 0, 1, and 2, respectively (p < 0.001 for trend) with control subjects lower than lone AS (28 ± 2%; p < 0.001). ECVCT accuracy for AS-amyloid detection versus lone AS was 0.87 (0.95 for 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid Perugini grade 2 only), outperforming conventional electrocardiogram and echocardiography parameters. One composite parameter, the voltage/mass ratio, had utility (similar AUC of 0.87 for any cardiac amyloid detection), although in one-third of patients, this could not be calculated due to bundle branch block or ventricular paced rhythm.

Conclusions: ECVCT during routine CT TAVR evaluation can reliably detect AS-amyloid, and the measured ECVCT tracks the degree of infiltration. Another measure of interstitial expansion, the voltage/mass ratio, also performed well.

Keywords: aortic stenosis; cardiac amyloidosis; computed tomography; extracellular volume.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract

Figure 1

ECVCT Protocol and Offline Analysis Integrated Into TAVR Planning Cardiac CT Text in red represents additional image acquisition/reconstruction in scanning protocol for the extracellular volume quantification by computed tomography (ECVCT). Text in blue represents steps in off-line analysis. ASM = axial shuttle mode; CT = computed tomography; CTCA = computed tomography coronary angiography; ECV = extracellular volume; ROI = region of interest.

Figure 2

Automated ECVCT Heart Model Output With Corresponding 3-h Planar DPD Image ECVCT map superimposed on the CTCA images (A to D) and corresponding 3-h planar DPD image (E). The endocardial and epicardial contours can be edited in the short-axis (A), 4-chamber (B), and 2-chamber (D) views to produce an ECVCT American Heart Association 17-segment polar map (C). This is a patient with aortic stenosis (AS) amyloid (Perugini grade 2 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid [DPD] scintigraphy) with total myocardial ECVCT is globally elevated at 47%. Abbreviations as in Figure 1.

Figure 3

Box and Whisker Plot Showing the Variation in ECVCT Between DPD Perugini Grades p 

Central Illustration

ECVCT for the Detection of Cardiac Amyloidosis in Aortic Stenosis Extracellular volume (ECV) quantification by computed tomography (ECVCT) polar maps (top), 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) planar (middle), and axial single-photon emission computed tomography images (bottom) from control (far left) through lone aortic stenosis (AS), DPD Perugini grade 1, and DPD Perugini grade 2 (far right).

Figure 4

Receiver-Operating Characteristic Curve for the Detection of Any Cardiac Amyloid (DPD Perugini Grade 1 or 2) Using ECVCT With a 3-Min Post-Contrast Acquisition, PWd, and MCF The voltage/mass ratio was not included because this approach would have excluded nearly one-third of patients (32 in total) due to bundle branch block or ventricular paced rhythm. AUC = area under the curve; CI = confidence interval; MCF = myocardial contraction fraction; PWd = posterior wall diameter; other abbreviations as in Figure 1.

Figure 5

Proposed ECVCT Screening Algorithm for Incorporation Into Routine Clinical Workflow The algorithm can be adjusted to an ECVCT threshold of ≥29% for the detection of all grade 1 DPD patients. TAVR = transcatheter aortic valve replacement; other abbreviations as in Figures 1 and 2.