Sex-related differences in the clinical characteristics of wild-type transthyretin amyloidosis cardiomyopathy.

BACKGROUND A significant male predominance has been reported in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Hence, female cases of ATTRwt-CM are overlooked, and sex-related differences in ATTRwt-CM remain unclear. This study aimed to examine sex-related differences in clinical characteristics and diagnostic approaches in ATTRwt-CM. METHODS We retrospectively analyzed 199 consecutive patients who were diagnosed with ATTRwt-CM and evaluated sex-related differences in clinical characteristics, imaging parameters, biomarkers, and diagnostic approaches. RESULTS Twenty-nine patients (15%) were female. These female patients were significantly older at diagnosis (77.1 ± 6.5 years vs. 82.9 ± 4.8 years; p<0.001) and had a more advanced New York Health Association functional class (2.2 ± 0.7 vs. 2.6 ± 0.8; p = 0.006) than their male counterparts. The median B-type natriuretic peptide levels were significantly higher (236 pg/mL vs. 394 pg/mL; p = 0.017) in female patients. Echocardiography revealed that the mean interventricular septum diameter was thinner (15.7 ± 2.6 mm vs. 14.1 ± 2.5 mm; p = 0.004) and left ventricular ejection fraction (LVEF) was preserved (51.2 ± 10.2% vs. 57.2 ± 9.1%; p = 0.003) in female patients. The mean heart-to-contralateral ratio obtained using 99mTc-labeled pyrophosphate (99mTc-PYP) was significantly lower (1.89 ± 0.33 vs. 1.63 ± 0.20; p < 0.001), moderate to severe aortic stenosis was more frequently observed (5% vs. 45%; p < 0.001), and the frequency of histological diagnosis was significantly lower (77% vs. 59%; p = 0.036) in female patients. CONCLUSIONS Female patients with ATTRwt-CM were predominantly octogenarians and less hypertrophic and had preserved LVEF and weaker cardiac uptake of the 99mTc-PYP tracer compared with male patients. These characteristics contribute to the underdiagnosis of ATTRwt-CM in female patients.