Avni Madhani, Bhavya Ancha, Kevin M Alexander, Joban Vaishnav
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure, resulting from the deposition of misfolded transthyretin protein in the myocardium. While historically considered to be a male-predominant disease, an increasing number of studies have shown that ATTR-CM may be under-recognized in women, likely due to differences in disease presentation compared with men. Notably, left ventricular wall thickness ≥ 12 mm is frequently used as a marker for ATTR-CM workup; however, women with ATTR-CM often have a lower left ventricular wall thickness than men and may not meet this threshold despite significant myocardial involvement. Moreover, hormonal differences between male and female patients may result in distinct cardiac phenotypes. Socioeconomic factors disproportionately impacting women, such as increased caregiving burden, symptom dismissal, and fewer financial resources, are likely additional contributing factors. As a result, diagnostic delays up to several years have been noted in women. Improving the diagnosis of ATTR-CM in women requires a multifactorial approach, including reforming screening guidelines to reflect sex-specific differences in disease presentation and increasing awareness of ATTR-CM in the community. Furthermore, given the historical underrepresentation of women in clinical studies on ATTR-CM, further investigation is necessary to better understand the prevalence, treatment efficacy, and outcomes of ATTR-CM in women.