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

Eur Heart J. 2016 Jun 14;37(23):1826-34. doi: 10.1093/eurheartj/ehv583. Epub 2015 Nov 3.

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.

Keywords: Cardiac amyloidosis; Hypertrophic cardiomyopathy; Transthyretin.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Male
  • Middle Aged
  • Mutation / genetics
  • Prealbumin / genetics
  • Prevalence
  • Prospective Studies

Substances

  • Amyloid
  • Prealbumin
  • transthyretin-related amyloid fibril protein, human

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related