Sex-Related Differences and Disparities in wtATTR-CM

To further examine sex-related differences in clinical characteristics, imaging parameters, biomarkers, and diagnostic approaches in wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM), researchers conducted a retrospective analysis of 199 consecutive patients diagnosed with wtATTR-CM at a university hospital in Japan between December 2002 and June 2021.

Several sex-related differences were identified at diagnosis. In total, 29 (15%) patients with wtATTR-CM were female. Female patients were significantly older (82.9 ± 4.8 years) compared with their male counterparts (77.1 ± 6.5 years; P <.001) and had a more advanced New York Heart Association functional class (2.6 ± 0.8 vs 2.2 ± 0.7, respectively; P = .006). Despite laboratory tests revealing no difference in the median high-sensitivity cardiac troponin T-levels (0.050 ng/mL vs 0.055 ng/mL, respectively; P = .765), B-type natriuretic peptide levels were significantly higher in females (394 pg/mL vs 236 pg/mL, respectively; P = .017). In addition, estimated glomerular filtration rate was significantly lower in females (42.2 ± 14.4 mL/min/1.73 m2) than in males (52.8 ± 15.1 mL/min/1.73 m2; P = .001).

On echocardiography, female patients had significantly smaller left ventricle (LV) chamber (P <.001), thinner interventricular septum diameter (P = .004), and lower left ventricular mass index (P = .023). Left ventricular ejection fraction was significantly preserved in female patients (P = .003) and stroke volume index was higher (P = .045). Female patients had a higher frequency of comorbid moderate-to-severe aortic stenosis compared with males (45% vs 5%; P <.001).

Clinical manifestations triggering wtATTR-CM diagnosis, the initial manifestations of wtATTR-CM, and genetic testing frequency were also evaluated. Although heart failure (HF) was the most common trigger in both females and males (66% vs 63%), LV hypertrophy was the trigger in 10% of males and no females. Aortic stenosis was the trigger in more female patients than male patients (10% vs 4%). HF was the most common initial manifestation in both females (52%) and males (44%), and 38% of females and males initially presented with carpal tunnel syndrome. Genetic testing was performed in 149 (75%) patients, and all were negative for TTR mutations. Female patients, however, had a significantly lower rate of genetic testing compared with male patients (48% vs 79%; P <.001).

The authors acknowledged that the diagnosis of wtATTR-CM in females is challenging and that medical unawareness is likely responsible for the underdiagnosis of female patients, thereby preventing optimal medical treatment. The authors underscored the importance of familiarity with the clinical characteristics of female patients with wtATTR-CM. This study revealed several sex-related differences in patients with wtATTR-CM in Japan, but further large prospective studies are needed to better understand these differences and how they can be applied to improve the diagnosis of wtATTR-CM in female patients and their overall care.


Takashio S, Yamada T, Nishi M, et al. Sex-related differences in the clinical characteristics of wild-type transthyretin amyloidosis cardiomyopathy. J Cardiol. 2022;79(1):50-57.

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