Unravelling the role of sex in the pathophysiology, phenotypic expression and diagnosis of cardiac amyloidosis

This article refers to ‘Sex differences among patients with transthyretin amyloid cardiomyopathy – from diagnosis to prognosis’ by R.K. Patel et al. , published in this issue on pages 2355–2363. Sex-related differences have been reported in some, but not all, forms of amyloidosis: for example, atrial amyloidosis sec-ondary to permanent atrial fibrillation preferentially occurs in women, 1 ,2 while the men-to-women ratio among patients with amyloid light-chain amyloidosis is quite balanced. The evidence on amyloid transthyretin (ATTR) amyloidosis in men and women is quite fragmentary. The most established finding is that men account for over three-quarters of patients with wild-type ATTR cardiac amyloidosis (ATTRwt-CA). 3–5 A reliable assessment of sex-related differences in variant ATTR (ATTRv) is complicated by the high number of pathogenic mutations in the TTR gene (about 1 30). 6 The study by Patel et al. 7 on the cohort from the National Amyloidosis Centre (NAC) of London represents a meaningful addition to existing literature and to the somehow controversial results from previous studies. 4,5,8– 1 0 The relationship between sex and CA can be usefully investigated on at least four levels: ( 1 ) the probability of acquiring the disease, (2) the phenotypic characteristics of cardiac involvement, (3) disease progression once CA is diagnosed, and (4) non-cardiological phenotypes.