title: Differential Myocyte Responses in Patients with Cardiac Transthyretin Amyloidosis and Light-Chain Amyloidosis: A Cardiac MR Imaging Study.
abstract: OBJECTIVE
  To investigate cardiac magnetic resonance (MR) imaging measurements of extracellular volume (ECV) and total cell volume in immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) in order to evaluate the amyloid and myocyte volumes.
  
  
  METHODS
  All ethics were approved, and participants provided written informed consent. Of the 257 subjects who were recruited, 92 had AL (mean age, 62 years ± 10), 44 had mutant ATTR (mean age, 68 years ± 10), and 66 had wild-type ATTR (mean age, 75 years ± 7). In addition, eight healthy subjects with ATTR mutations (mean age, 47 years ± 6) and 47 healthy volunteers (mean age, 45 years ± 15) participated. All participants underwent equilibrium contrast material-enhanced cardiac MR imaging. ECV and total cell volume were measured in the heart. T test, χ(2), and one-way analysis of variance with posthoc Bonferroni correction were used.
  
  
  RESULTS
  Both the left ventricular indexed mass and ECV were elevated in patients with amyloidosis. For left ventricular indexed mass, mean AL was 107 g/m(2) ± 30; mean mutant ATTR was 137 g/m(2) ± 29; and mean wild-type ATTR was 133 g/m(2) ± 27 versus 65 g/m(2) ± 15 in healthy subjects (P < .0001 for all measures). For ECV, mean AL was 0.54 ± 0.07, mean mutant ATTR was 0.60 ± 0.07, and mean wild-type ATTR was 0.57 ± 0.06 versus 0.27 ± 0.03 in healthy subjects (P < .0001 for all measures). Patients with ATTR had a higher total cell volume than did healthy subjects (mean, 53 mL/m(2) ± 12 vs 45 mL/m(2) ± 11; P = .001), but in patients with AL, total cell volume was normal (mean, 47 mL/m(2) ± 17 vs 45 mL/m(2) ± 11; P > .99). The result is that, in patients with AL, all of the increase in left ventricular indexed mass is extracellular volume, whereas in patients with ATTR, the increase is extracellular, with an additional 18% increase in the intracellular space.
  
  
  CONCLUSIONS
  Quantification of ECV measures cardiac amyloid deposition in both types of amyloidosis and shows that amyloid deposition is more extensive in patients with ATTR than in those with AL; however, ATTR is associated with higher cell volume, which suggests concomitant cell hypertrophy.
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Marianna
authors.initials: M
authors.lastname: Fontana
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Banypersad
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Treibel
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Amna
authors.initials: A
authors.lastname: Abdel-Gadir
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Viviana
authors.initials: V
authors.lastname: Maestrini
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Thirusha
authors.initials: T
authors.lastname: Lane
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Janet A
authors.initials: JA
authors.lastname: Gilbertson
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: David F
authors.initials: DF
authors.lastname: Hutt
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lachmann
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Whelan
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Ashutosh D
authors.initials: AD
authors.lastname: Wechalekar
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Anna S
authors.initials: AS
authors.lastname: Herrey
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Julian D
authors.initials: JD
authors.lastname: Gillmore
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.affiliation: From the Imaging Centre, the Heart Hospital, 16-18 Westmoreland St, London W1G 8PH, England (M.F., S.M.B., T.A.T., A.A.B., V.M., A.S.H., J.C.M.); Institute of Cardiovascular Science, University College London, London, England (M.F., S.M.B., T.A.T., A.A.G., J.C.M.); and National Amyloidosis Centre, University College London, Royal Free Hospital, London, England (M.F., S.M.B., T.L., J.A.G., D.F.H., H.J.L., C.J.W., A.D.W., J.D.G., P.N.H.).
authors.forename: James C
authors.initials: JC
authors.lastname: Moon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000473:pathology; D000686:Amyloidosis / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D009202:Cardiomyopathies / Q000473:pathology*; D016022:Case-Control Studies; D003287:Contrast Media; D004452:Echocardiography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008536:Meglumine; D008875:Middle Aged; D032342:Muscle Cells / Q000473:pathology*; D009942:Organometallic Compounds; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D009942:Organometallic Compounds; D008536:Meglumine; C072417:gadoterate meglumine