Prognostic utility of the Perugini grading of 99mTc-DPD scintigraphy in transthyretin (ATTR) amyloidosis and its relationship with skeletal muscle and soft tissue amyloid.
OBJECTIVE
High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR amyloidosis.


RESULTS
Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P < 0.005). There were no differences in survival between patients with a grade 1, grade 2 or grade 3 99mTc-DPD scan in ATTRwt (n = 369), V122I-associated ATTRm (n = 92) or T60A-associated ATTRm (n = 59) amyloidosis. Cardiac amyloid burden, determined by equilibrium contrast cardiac magnetic resonance imaging, was similar between patients with Perugini grade 2 and Perugini grade 3 99mTc-DPD scans but skeletal muscle/soft tissue to femur ratio was substantially higher in the latter group (P < 0.001).


CONCLUSIONS
99mTc-DPD scintigraphy is exquisitely sensitive for identification of cardiac ATTR amyloid, but stratification by Perugini grade of positivity at diagnosis has no prognostic significance.
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
David F
DF
Hutt
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Marianna
M
Fontana
Department of Nuclear Medicine, Royal Free London NHS Foundation Trust, Pond Street, London, NW3 2QG, UK.
Maria
M
Burniston
Department of Nuclear Medicine, Royal Free London NHS Foundation Trust, Pond Street, London, NW3 2QG, UK.
Ann-Marie
AM
Quigley
Eastman Dental Institute, University College London, 256 Grays Inn Road, London, WC1X 8LD, UK.
Aviva
A
Petrie
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
James C
JC
Ross
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Joanne
J
Page
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Ana
A
Martinez-Naharro
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Ashutosh D
AD
Wechalekar
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Helen J
HJ
Lachmann
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Candida C
CC
Quarta
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Tamer
T
Rezk
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Shameem
S
Mahmood
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Sajitha
S
Sachchithanantham
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Taryn
T
Youngstein
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Carol J
CJ
Whelan
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Thirusha
T
Lane
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Janet A
JA
Gilbertson
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Dorota
D
Rowczenio
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Philip N
PN
Hawkins
National Amyloidosis Centre, Division of Medicine, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Julian D
JD
Gillmore
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000000981:diagnostic imaging* / Q000401:mortality* / Q000503:physiopathology; D000686:Amyloidosis; D015331:Cohort Studies; D004452:Echocardiography / Q000379:methods; D005260:Female; D006331:Heart Diseases / Q000000981:diagnostic imaging* / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000503:physiopathology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D017256:Technetium Tc 99m Sestamibi; D055815:Young Adult
D017256:Technetium Tc 99m Sestamibi
99mTc-DPD; ATTR amyloidosis; Perugini grade; prognosis; skeletal muscle; soft tissue