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

• Published in: European heart journal Vol. 37; no. 23; pp. 1826 - 1834
• Main Authors: Damy, Thibaud, Costes, Bruno, Hagège, Albert A, Donal, Erwan, Eicher, Jean-Christophe, Slama, Michel, Guellich, Aziz, Rappeneau, Stéphane, Gueffet, Jean-Pierre, Logeart, Damien, Planté-Bordeneuve, Violaine, Bouvaist, Hélène, Huttin, Olivier, Mulak, Geneviève, Dubois-Randé, Jean-Luc, Goossens, Michel, Canoui-Poitrine, Florence, Buxbaum, Joel N
• Format: Journal Article
• Language: English
• Published: England Oxford University Press (OUP) 14-06-2016
• Subjects: Aged; Aged, 80 and over; Amyloid - genetics; Amyloid Neuropathies, Familial - epidemiology; Amyloid Neuropathies, Familial - genetics; Amyloid Neuropathies, Familial - pathology; Cardiomyopathy, Hypertrophic - epidemiology; Cardiomyopathy, Hypertrophic - genetics; Cardiomyopathy, Hypertrophic - pathology; Cross-Sectional Studies; Female; France - epidemiology; Heart Failure - epidemiology; Heart Failure - genetics; Heart Failure - pathology; Heart Ventricles - pathology; Humans; Life Sciences; Male; Middle Aged; Mutation - genetics; Prealbumin - genetics; Prevalence; Prospective Studies; Cardiac amyloidosis; Hypertrophic cardiomyopathy; Transthyretin
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehv583

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.