title: Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis.
abstract: BACKGROUND
  Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed.
  
  
  OBJECTIVE
  To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT.
  
  
  METHODS
  Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area).
  
  
  RESULTS
  ECVCT and ECVCMR results were well correlated (r(2) = 0.85 vs r(2) = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001).
  
  
  CONCLUSIONS
  Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis.
authors.affiliation: The Heart Hospital, 16-18 Westmoreland Street, London, W1G 8PH, UK; Institute of Cardiovascular Science, University College London, London, WC1E 6BT, UK.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Treibel
authors.affiliation: Centre for Medical Imaging, University College London, 250 Euston Road, London, NW1 2PG, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Bandula
authors.affiliation: The Heart Hospital, 16-18 Westmoreland Street, London, W1G 8PH, UK; Institute of Cardiovascular Science, University College London, London, WC1E 6BT, UK; Centre for Amyloidosis and Acute Phase Proteins and National Amyloidosis Centre, Royal Free Campus, University College London, Rowland Hill Street, London, NW3 2PF, UK.
authors.forename: Marianna
authors.initials: M
authors.lastname: Fontana
authors.affiliation: The Heart Hospital, 16-18 Westmoreland Street, London, W1G 8PH, UK; Institute of Cardiovascular Science, University College London, London, WC1E 6BT, UK.
authors.forename: Steven K
authors.initials: SK
authors.lastname: White
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins and National Amyloidosis Centre, Royal Free Campus, University College London, Rowland Hill Street, London, NW3 2PF, UK.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Gilbertson
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins and National Amyloidosis Centre, Royal Free Campus, University College London, Rowland Hill Street, London, NW3 2PF, UK.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Herrey
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins and National Amyloidosis Centre, Royal Free Campus, University College London, Rowland Hill Street, London, NW3 2PF, UK.
authors.forename: Julian D
authors.initials: JD
authors.lastname: Gillmore
authors.affiliation: Centre for Medical Imaging, University College London, 250 Euston Road, London, NW1 2PG, UK.
authors.forename: Shonit
authors.initials: S
authors.lastname: Punwani
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins and National Amyloidosis Centre, Royal Free Campus, University College London, Rowland Hill Street, London, NW3 2PF, UK.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.affiliation: Centre for Amyloidosis and Acute Phase Proteins and National Amyloidosis Centre, Royal Free Campus, University College London, Rowland Hill Street, London, NW3 2PF, UK.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Taylor
authors.affiliation: The Heart Hospital, 16-18 Westmoreland Street, London, W1G 8PH, UK; Institute of Cardiovascular Science, University College London, London, WC1E 6BT, UK. Electronic address: j.moon@ucl.ac.uk.
authors.forename: James C
authors.initials: JC
authors.lastname: Moon
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000097:blood / Q000000981:diagnostic imaging*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001842:Bone and Bones / Q000000981:diagnostic imaging; D055424:Cardiac-Gated Imaging Techniques; D009202:Cardiomyopathies / Q000097:blood / Q000000981:diagnostic imaging*; D016022:Case-Control Studies; D003287:Contrast Media / Q000008:administration & dosage; D004562:Electrocardiography; D005110:Extracellular Space / Q000000981:diagnostic imaging*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011877:Radionuclide Imaging; D012720:Severity of Illness Index; D014283:Triiodobenzoic Acids / Q000008:administration & dosage; D014336:Troponin / Q000097:blood; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D010446:Peptide Fragments; D014283:Triiodobenzoic Acids; D014336:Troponin; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C044834:iodixanol
keywords: Amyloidosis; CCT; CMR; Cardiac imaging techniques; Extracellular space