OBJECTIVES : Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare and fatal disease caused by the deposition of transthyretin amyloid fibrils in the heart. Two subtypes of ATTR-CM are hereditary ATTR-CM and wild-type ATTR-CM (ATTRwt). ATTRwt is caused by age-related changes in the wild-type transthyretin and is thought to be more common in male patients. This study aimed to estimate the gender distribution in patients diagnosed with ATTRwt and investigate evidence of clinical differences by gender.

METHODS : A systematic review of the literature (EMBASE, Pubmed, and CENTRAL) and a meta-analysis of the male proportion in diagnosed ATTRwt patients were conducted using the PRISMA guidelines and the DerSimonian-Laird random-effects model with Freeman-Tukey double arcsine transformation. For the primary analysis, pooled estimates were based on all unique studies. In secondary analyses, we considered predefined subsets of studies based on study sample size, recruitment years, geography, study design, age at diagnosis, and method of diagnosis. Additional meta-regression analyses were performed to test for potential effect modifiers.

RESULTS : In total, 104 studies were identified from the systematic review. Twenty-nine unique studies (2,811 patients) were included in the meta-analysis. Male proportion in patients with ATTRwt was 87.5% (95%CI:82.4-91.9%). Studies, including older ATTRwt patients (≥80 years at diagnosis), had a 29.3% (P-value: <0.001) lower male proportion compared to studies including younger ATTRwt patients (<80 years at diagnosis). After adjusting for age, studies using autopsy as a method of diagnosis had 21.1% (P-value: <0.001) lower male proportion compared to non-autopsy studies.

CONCLUSIONS : Studies conducted to date show ATTRwt disproportionally affects males. The proportion of males was significantly impacted by the age at diagnosis and method of diagnosis (autopsy vs. non-autopsy) which may suggest important gender-based differences in the clinical manifestation and diagnostic challenges of ATTRwt in females that warrant future research.