title: Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness.
abstract: Increased left ventricular wall thickness (LVWT) is a common finding in cardiology. It is not known how often hereditary transthyretin-related familial amyloid cardiomyopathy (mTTR-FAC) is responsible for LVWT. Several therapeutic modalities for mTTR-FAC are currently in clinical trials; thus, it is important to establish the prevalence of TTR mutations (mTTR) and the clinical characteristics of the patients with mTTR-FAC.
  
  
  
  In a prospective multicentre, cross-sectional study, the TTR gene was sequenced in 298 consecutive patients diagnosed with increased LVWT in primary cardiology clinics in France. Among the included patients, median (25-75th percentiles) age was 62 [50;74]; 74% were men; 23% were of African origin; and 36% were in NYHA Class III-IV. Median LVWT was 18 (16-21) mm. Seventeen (5.7%; 95% confidence interval [CI]: [3.4;9.0]) patients had mTTR of whom 15 (5.0%; 95% CI [2.9;8.2]) had mTTR-FAC. The most frequent mutations were V142I (n = 8), V50M (n = 2), and I127V (n = 2). All mTTR-FAC patients were older than 63 years with a median age of 74 [69;79]. Of the 15 patients with mTTR-FAC, 8 were of African descent while 7 were of European descent. In the African descendants, mTTR-FAC median age was 74 [72;79] vs. 55 [46;65] years in non-mTTR-FAC (P < 0.001). In an adjusted multivariate model, African origin, neuropathy, carpal tunnel syndrome, electrocardiogram (ECG) low voltage, and late gadolinium enhancement (LGE) at cardiac-magnetic resonance imaging were all independently associated with mTTR-FAC.
  
  
  
  Five per cent of patients diagnosed with hypertrophic cardiomyopathy have mTTR-FAC. Mutated transthyretin genetic screening is warranted in elderly subjects with increased LVWT, particularly, those of African descent with neuropathy, carpal tunnel syndrome, ECG low voltage, or LGE.
authors.affiliation: Department of Cardiology, UPEC, AP-HP Henri-Mondor Teaching Hospital, Inserm U955, IMRB GRC Mondor Amyloidosis Network, DHU ATVB and Inserm Clinical Investigation Center 1430, 51 Avenue Maréchal de Lattre de Tassigny, Créteil F-94000, France thibaud.damy@hmn.aphp.fr.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Damy
authors.affiliation: Department of Genetics and Biochemistry, UPEC, AP-HP Henri-Mondor Teaching Hospital, Inserm U955, IMRB, Créteil F-94000, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Costes
authors.affiliation: Department of Cardiology, Paris Descartes University, PRES Paris Sorbonne, AP-HP, Hôpital Européen Georges Pompidou, Inserm UMR970, Paris Cardiovascular Research Center, Paris, France.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Hagège
authors.affiliation: Department of Cardiology, Université Rennes 1, Rennes Teaching Hospital, LTSI, INSERM 1099, Inserm Clinical Investigation Center-IT U 804, Rennes, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Donal
authors.affiliation: Department of Cardiology, Dijon Universiy, Hôpital Bocage Central, Dijon Teaching Hospital, Dijon, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Eicher
authors.affiliation: Department of Cardiology, Paris-Sud University, AP-HP A. Béclère Teaching Hospital, Béclère, 92140 Clamart, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Slama
authors.affiliation: Department of Cardiology, UPEC, AP-HP Henri-Mondor Teaching Hospital, Inserm U955, IMRB GRC Mondor Amyloidosis Network, DHU ATVB and Inserm Clinical Investigation Center 1430, 51 Avenue Maréchal de Lattre de Tassigny, Créteil F-94000, France.
authors.forename: Aziz
authors.initials: A
authors.lastname: Guellich
authors.affiliation: Department of Cardiology, UPEC, AP-HP Henri-Mondor Teaching Hospital, Inserm U955, IMRB GRC Mondor Amyloidosis Network, DHU ATVB and Inserm Clinical Investigation Center 1430, 51 Avenue Maréchal de Lattre de Tassigny, Créteil F-94000, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rappeneau
authors.affiliation: Hopital G et R Laennec, Institut du Thorax, 44093 Nantes Cedex1, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gueffet
authors.affiliation: Department of Cardiology, Denis Diderot University, AP-HP, Lariboisière Hospital, 75010 Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Logeart
authors.affiliation: Department of Neurology, UPEC, AP-HP Henri-Mondor Teaching Hospital, Inserm U955, IMRB GRC Mondor Amyloidosis Network, Inserm Clinical Investigation Center 1430, Créteil F-94000, France.
authors.forename: Violaine
authors.initials: V
authors.lastname: Planté-Bordeneuve
authors.affiliation: Department of Cardiology, Grenoble Teaching Hospital, Grenoble, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bouvaist
authors.affiliation: Department of Cardiologie, Institut Lorrain du Cœur et des Vaisseaux, 54511 Vandœuvre-lès-Nancy, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Huttin
authors.affiliation: Société Française de Cardiologie, Paris, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Mulak
authors.affiliation: Department of Cardiology, UPEC, AP-HP Henri-Mondor Teaching Hospital, Inserm U955, IMRB GRC Mondor Amyloidosis Network, DHU ATVB and Inserm Clinical Investigation Center 1430, 51 Avenue Maréchal de Lattre de Tassigny, Créteil F-94000, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Randé
authors.affiliation: Department of Genetics and Biochemistry, UPEC, AP-HP Henri-Mondor Teaching Hospital, Inserm U955, IMRB, Créteil F-94000, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.affiliation: Department of Public Health, UPEC, EA 4393 CEpiA (Clinical Epidemiology And Ageing), DHU ATVB, AP-HP, Henri-Mondor Teaching Hospital, DHU ATVB, Créteil F-94000, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Canoui-Poitrine
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Joel N
authors.initials: JN
authors.lastname: Buxbaum
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000235:genetics; D028227:Amyloid Neuropathies, Familial / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D002312:Cardiomyopathy, Hypertrophic / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D005602:France / Q000453:epidemiology; D006333:Heart Failure / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011228:Prealbumin / Q000235:genetics; D015995:Prevalence; D011446:Prospective Studies
chemical_list: D000682:Amyloid; D011228:Prealbumin; C076571:transthyretin-related amyloid fibril protein, human
keywords: Cardiac amyloidosis; Hypertrophic cardiomyopathy; Transthyretin