Gender differences in clinical characteristics in wild-type transthyretin amyloidosis cardiomyopathy

Abstract Aims A significant male predominance has been reported in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). In other words, the female ATTRwt-CM may be overlooked and gender differences in ATTRwt-CM remain unclear. This study aims to examine gender differences in clinical characteristics and diagnostic approaches in ATTRwt-CM. Methods and results We retrospectively evaluated 171 consecutive ATTRwt-CM patients diagnosed at our university hospital between December 2002 and December 2020. Twenty-two patients (12%) were women. Women were significantly older at diagnosis (77.3 years vs. 83.3 years; P<0.001) and had a higher advanced New York Health Association functional class (2.23±0.70 vs. 2.57±0.81; P=0.04) than men. In echocardiography, mean interventricular septum diameter was less thick (15.8 mm vs. 14.5 mm; P=0.03) and ejection fraction was preserved (51.7% vs. 57.7%; P=0.08) in women. The mean heart-to-contralateral ratio obtained using 99mTc-labeled pyrophosphate (99mTc-PYP) was significantly lower in women than in men (1.89 vs. 1.64; P=0.001). There was no significant gender difference in high-sensitivity median cardiac troponin T levels at diagnosis (0.055 ng/mL vs. 0.069 ng/mL; P=0.30) or history of carpal tunnel syndrome (57% vs. 55%; P=0.93) and electrocardiograms findings. However, the median B-type natriuretic peptide level was significantly higher (254 pg/mL vs. 434 pg/mL; P=0.02) in women. Moderate to severe aortic stenosis was more frequently observed in women (5% vs. 50%; P<0.001). Histological (78% vs. 59%; P=0.07) and genetic confirmation (78% vs. 59%; P=0.003) of ATTRwt-CM were not performed in women. Conclusion Women with ATTRwt-CM were predominantly octogenarians, less hypertrophic, and had weaker cardiac uptake of the 99mTc-PYP tracer than men with ATTRwt-CM. These characteristics contribute to the underdiagnosis of ATTRwt-CM in women. The diagnosis of ATTRwt-CM in women is challenging. Therefore, we must be familiar with the clinical characteristics of women with ATTRwt-CM. Funding Acknowledgement Type of funding sources: None.