Clinical Epidemiology and Ageing

Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness.

Damy T, Costes B, Hagège AA, Donal E, Eicher J-C, Slama M, Guellich A, Rappeneau S, Gueffet J-P, Logeart D, Planté-Bordeneuve V, Bouvaist H, Huttin O, Mulak G, Dubois-Randé J-L, Goossens M, Canoui-Poitrine F, Buxbaum JN Eur Heart J. 2016;37(23):1826-34.

<p><b>AIMS: </b>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.</p><p><b>METHODS AND RESULTS: </b>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.</p><p><b>CONCLUSION: </b>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.</p>

MeSH terms: Aged; Aged, 80 and over; Amyloid; Amyloid Neuropathies, Familial; Cardiomyopathy, Hypertrophic; Cross-Sectional Studies; Female; France; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Mutation; Prealbumin; Prevalence; Prospective Studies
DOI: 10.1093/eurheartj/ehv583