Author + information
- Received March 24, 2020
- Revision received May 18, 2020
- Accepted May 20, 2020
- Published online October 5, 2020.
- Paul R. Scully, MBBS, MResa,b,
- Kush P. Patel, MBBS, BSca,b,
- Bunny Saberwal, MBBSa,
- Ernst Klotz, Diply Physc,
- João B. Augusto, MDa,b,
- George D. Thornton, MBBS, BSca,
- Rebecca K. Hughes, MBBSa,b,
- Charlotte Manisty, PhDa,b,
- Guy Lloyd, MDa,b,d,
- James D. Newton, MBChB, MDe,
- Nikant Sabharwal, DMe,
- Andrew Kelion, DMe,
- Simon Kennon, MDa,
- Muhiddin Ozkor, MBBS, MDa,
- Michael Mullen, MBBS, MDa,
- Neil Hartman, PhDf,
- João L. Cavalcante, MDg,
- Leon J. Menezes, BA, BM BCha,h,i,
- Philip N. Hawkins, PhDj,
- Thomas A. Treibel, PhDa,b,
- James C. Moon, MDa,b,∗ and
- Francesca Pugliese, PhDa,d,k,∗∗ ()
- aBarts Heart Centre, St. Bartholomew’s Hospital, London, United Kingdom
- bInstitute of Cardiovascular Sciences, University College London, London, United Kingdom
- cSiemens Healthineers, Forchheim, Germany
- dWilliam Harvey Research Institute, Queen Mary University of London, London, United Kingdom
- eJohn Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom
- fNuclear Medicine, Swansea Bay UHB, Port Talbot, United Kingdom
- gMinneapolis Heart Institute, Minneapolis, Minnesota
- hInstitute of Nuclear Medicine, University College London, London, United Kingdom
- iNIHR University College London Hospitals Biomedical Research Centre, London, United Kingdom
- jNational Amyloidosis Centre, University College London, London, United Kingdom
- kNIHR Barts Biomedical Research Centre, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Francesca Pugliese, Barts Heart Centre, St. Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, United Kingdom.
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.
↵∗ Drs. Moon and Pugliese are joint last authors.
Dr. Scully is supported by a British Heart Foundation Clinical Research Training Fellowship (FS/16/31/32185). Dr. Patel is supported by an unrestricted educational grant from Edwards Lifesciences. Dr. Treibel is supported by a clinical lecturer grant by the National Institute of Health Research (NIHR). Dr. Saberwal is supported by an educational grant from Siemens Healthineers. Mr. Klotz works for Siemens Healthineers. Dr. Mullen has received grants and personal fees from Edwards Lifesciences and personal fees from Abbotts Vascular. Prof. Moon is directly and indirectly supported by the University College London Hospitals NHS Foundation and Barts Health NHS Trusts biomedical research and unit, respectively. Dr. Pugliese has received research support from Siemens Healthineers; and this work forms part of the translational research portfolio of the NIHR Cardiovascular Biomedical Research Centre at Barts Heart Centre, which is supported and funded by the NIHR. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Cardiovascular Imaging author instructions page.
- Received March 24, 2020.
- Revision received May 18, 2020.
- Accepted May 20, 2020.
- 2020 The Authors