Risk of Cardiac Involvement in Hereditary Transthyretin Amyloidosis May Be Gender-Biased

Caponetti and colleagues investigated associations between sex and genotype, phenotype, and degree of myocardial involvement in variant transthyretin amyloidosis (ATTRv), based on the recognition that patients with ATTRv cardiomyopathy are more likely to be male.

Caused by the buildup of wild-type (ATTRwt) or variant ATTRv fibrils in the myocardium, transthyretin amyloid cardiomyopathy is considered to be a progressive, fatal disease.

An ongoing global longitudinal observational survey of patients with ATTR and asymptomatic carriers with TTR mutations was carried out and is known as the Transthyretin Amyloidosis Outcomes Survey (THAOS). It is the largest global disease registry for asymptomatic carriers of a pathogenic disease-causing TTR genetic variant involving patients diagnosed with ATTRv and ATTRwt. Data from THAOS were examined to ascertain any sex-based variations in phenotype, genotype, and presence of cardiac and neurologic symptoms in patients with ATTRv and in patients with ATTRv and cardiomyopathy. The data cutoff for the study was January 6, 2020.

To date, 2790 patients with ATTRv were enrolled in THAOS. Results of the survey showed that male patients were more likely to have the cardiac phenotype and symptoms of cardiac involvement.

In patients with more severe cardiac manifestations of disease, male prevalence was greater. The manifestations of disease were assessed with left-ventricular (LV) ejection fraction, LV mass index divided by height, mean LV wall thickness divided by height, and N-terminal pro-B-type natriuretic peptide. Age at disease onset, genotype category, and sex were identified by multivariate analyses as risk factors for the development of cardiomyopathy, which was defined as increased LV septum thickness divided by height.

Myocardial involvement was more common and distinct in male patients with ATTRv, based on this analysis, suggesting that there may be biological characteristics that reduce myocardial amyloid infiltration in females or enable it in males. Investigations of potential prognostic factors and examination of the potential protective mechanisms conferred by female sex may be warranted in future studies.

Source: Caponetti AG, Rapezzi C, Gagliardi C, et al. Sex-related risk of cardiac involvement in hereditary transthyretin amyloidosis: insights from THAOS. JACC Heart Fail. 2021;9:736-746.

Related Items

Subscribe to Amyloidosis News

Stay up to date with Amyloidosis News & updates by subscribing to receive the free AMN e‑Newsletter.

I'd like to receive: