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

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.

Figure 1

Number of female patients assessed at the National Amyloidosis Centre with a new diagnosis of transthyretin amyloid cardiomyopathy. Patients divided into groups of 2‐year blocks. Patient data from 1 January 2021 to censor date were not included in this graph as this represents only an 8‐month period of time.

Figure 2

Average interventricular septum in diastole (IVSd) indexed to body surface area in males and females at presentation from 2005 to 2020. Patients divided into groups of 2‐year blocks. Patients presenting between 2000 and 2004 were not included due to limited patient numbers. Patients data from 1 January 2021 to censor date were not included as this represents only an 8‐month period of time.

Figure 3

Kaplan–Meier survival curves comparing males and females, divided by genotype. Kaplan–Meier curves displaying the prognostic impact of sex on survival in patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) when separated for each genotype: all patients (top left), wild‐type (wt)ATTR‐CM (top right), T60A‐ATTR‐CM (bottom left), V122I‐ATTR‐CM (bottom right). Analysis time (in months) on horizontal axis and cumulative survival probability on vertical axis. CI, confidence interval; HR, hazard ratio.