Thibaud Damy1, Bruno Costes2, Albert A Hagège3, Erwan Donal4, Jean-Christophe Eicher5, Michel Slama6, Aziz Guellich7, Stéphane Rappeneau7, Jean-Pierre Gueffet8, Damien Logeart9, Violaine Planté-Bordeneuve10, Hélène Bouvaist11, Olivier Huttin12, Geneviève Mulak13, Jean-Luc Dubois-Randé7, Michel Goossens2, Florence Canoui-Poitrine14, Joel N Buxbaum15. 1. 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. 2. Department of Genetics and Biochemistry, UPEC, AP-HP Henri-Mondor Teaching Hospital, Inserm U955, IMRB, Créteil F-94000, France. 3. Department of Cardiology, Paris Descartes University, PRES Paris Sorbonne, AP-HP, Hôpital Européen Georges Pompidou, Inserm UMR970, Paris Cardiovascular Research Center, Paris, France. 4. Department of Cardiology, Université Rennes 1, Rennes Teaching Hospital, LTSI, INSERM 1099, Inserm Clinical Investigation Center-IT U 804, Rennes, France. 5. Department of Cardiology, Dijon Universiy, Hôpital Bocage Central, Dijon Teaching Hospital, Dijon, France. 6. Department of Cardiology, Paris-Sud University, AP-HP A. Béclère Teaching Hospital, Béclère, 92140 Clamart, France. 7. 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. 8. Hopital G et R Laennec, Institut du Thorax, 44093 Nantes Cedex1, France. 9. Department of Cardiology, Denis Diderot University, AP-HP, Lariboisière Hospital, 75010 Paris, France. 10. 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. 11. Department of Cardiology, Grenoble Teaching Hospital, Grenoble, France. 12. Department of Cardiologie, Institut Lorrain du Cœur et des Vaisseaux, 54511 Vandœuvre-lès-Nancy, France. 13. Société Française de Cardiologie, Paris, France. 14. 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. 15. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Abstract
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: 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. METHODS AND RESULTS: 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-FACpatients 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. CONCLUSION: 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. Published on behalf of the European Society of Cardiology. All rights reserved.
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