title: Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis: Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve Replacement.
abstract: Calcific aortic stenosis (cAS) affects 3% of individuals aged >75 years, leading to heart failure and death unless the valve is replaced. Wild-type transthyretin cardiac amyloid is also a disorder of ageing individuals. Prevalence and clinical significance of dual pathology are unknown. This study explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance.
  
  
  
  A total of 146 patients with severe AS requiring surgical valve replacement underwent cardiovascular magnetic resonance and intraoperative biopsies; 112 had cAS (75±6 years; 57% men). Amyloid was sought histologically using Congo red staining and then typed using immunohistochemistry and mass spectrometry; patients with amyloid underwent clinical evaluation including genotyping and (99m)TC-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy. Amyloid was identified in 6 of 146 patients, all with cAS and >65 years (prevalence 5.6% in cAS >65). All 6 patients had wild-type transthyretin amyloid (mean age 75 years; range, 69-85; 4 men), not suspected on echocardiography. Cardiovascular magnetic resonance findings were of definite cardiac amyloidosis in 2, but could be explained solely by AS in the other 4. Postoperative DPD scans demonstrated cardiac localization in all 4 patients who had this investigation (2 died prior). At follow-up (median, 2.3 years), 50% with amyloid had died (versus 7.5% in cAS; 6.9% in age >65 years). In univariable analyses, the presence of transthyretin amyloidosis amyloid had the highest hazard ratio for death (9.5 [95% confidence interval, 2.5-35.8]; P=0.001).
  
  
  
  Occult wild-type transthyretin cardiac amyloid had a prevalence of 6% among patients with AS aged >65 years undergoing surgical aortic valve replacement and was associated with a poor outcome.
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.). Thomas.Treibel.12@ucl.ac.uk.
authors: Thomas A
authors: TA
authors: Treibel
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Marianna
authors: M
authors: Fontana
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Janet A
authors: JA
authors: Gilbertson
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Silvia
authors: S
authors: Castelletti
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Steven K
authors: SK
authors: White
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Paul R
authors: PR
authors: Scully
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Neil
authors: N
authors: Roberts
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: David F
authors: DF
authors: Hutt
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Dorota M
authors: DM
authors: Rowczenio
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Carol J
authors: CJ
authors: Whelan
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Michael A
authors: MA
authors: Ashworth
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Julian D
authors: JD
authors: Gillmore
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: Philip N
authors: PN
authors: Hawkins
authors: From the Cardiovascular Magnetic Resonance Imaging Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (T.A.T., M.F., S.C., S.K.W., P.R.S., N.R., J.C.M.); Institute of Cardiovascular Science (T.A.T., M.F., S.K.W., J.C.M.) and National Amyloidosis Centre, Royal Free Campus (M.F., J.A.G., D.F.H., D.M.R., C.W., J.D.G., P.N.H.), University College London, United Kingdom; and Histopathology Department, Great Ormond Street Hospital for Children, London, United Kingdom (M.A.A.).
authors: James C
authors: JC
authors: Moon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000032:analysis; D028227:Amyloid Neuropathies, Familial / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000601:surgery*; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000401:mortality / Q000601:surgery*; D001706:Biopsy; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D004452:Echocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008131:London; D008279:Magnetic Resonance Imaging; D008297:Male; D013058:Mass Spectrometry; D009154:Mutation; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D012720:Severity of Illness Index; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
chemical_list: D000682:Amyloid; D011228:Prealbumin
keywords: Congo red; aortic stenosis, calcific; aortic valve stenosis; biopsy; mass spectrometry