Sex differences among patients with transthyretin amyloid cardiomyopathy - from diagnosis to prognosis

Eur J Heart Fail. 2022 Dec;24(12):2355-2363. doi: 10.1002/ejhf.2646. Epub 2022 Aug 16.

Abstract

Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly diagnosed in men. The few available studies suggest affected women have a more favourable cardiac phenotype. We aimed to characterize sex differences among consecutive patients with non-hereditary and two prevalent forms of hereditary (h)ATTR-CM diagnosed over a 20-year period.

Methods and results: Analysis of deep phenotyping at presentation, changes on serial echocardiography and overall prognosis were evaluated. In total, 1732 consecutive patients were studied, comprising: 1095 with wild-type (wt)ATTR-CM; 206 with T60A-hATTR-CM; and 431 with V122I-hATTR-CM. Female prevalence was greater in T60A-hATTR-CM (29.6%) and V122I-hATTR-CM (27.8%) compared to wtATTR-CM (6%). At presentation, females were 3.3 years older than males (wtATTR-CM: 81.9 vs. 77.8 years; T60A-hATTR-CM: 68.7 vs. 65.1 years; V122I-hATTR-CM: 77.1 vs. 74.9 years). Body size significantly influenced measures of disease severity; when indexed, overall structural and functional phenotype was similar between sexes, the few significant differences suggested a mildly worse phenotype in females. No significant differences were observed in both disease progression on serial echocardiography and mortality across the overall population (p = 0.459) and when divided by genotype (wtATTR-CM: p = 0.730; T60A-hATTR-CM: p = 0.161; V122I-hATTR-CM: p = 0.056).

Conclusion: This study of a well-characterized large cohort of ATTR-CM patients did not demonstrate overall differences between sexes in either clinical phenotype, when indexed, or with respect to disease progression and prognosis. Non-indexed wall thickness measurements may have contributed to both under-representation and delays in diagnosis for affected females and highlights the potential role of utilizing indexed echocardiographic parameters for a more accurate assessment of patients at diagnosis and for disease prognostication.

Keywords: Amyloidosis; Diagnosis; Echocardiography; Prognosis; Sex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Neuropathies, Familial* / diagnosis
  • Amyloid Neuropathies, Familial* / epidemiology
  • Amyloid Neuropathies, Familial* / genetics
  • Cardiomyopathies* / diagnosis
  • Cardiomyopathies* / genetics
  • Disease Progression
  • Female
  • Heart Failure* / genetics
  • Humans
  • Male
  • Prealbumin / genetics
  • Prognosis
  • Sex Characteristics

Substances

  • Prealbumin