Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) predominantly affects men. It is unknown if women are underdiagnosed or if female sex is protective. We investigated sex differences in clinical presentation and disease outcomes in ATTR-CM. Methods: Patients seen with ATTR-CM at our institution were included for analysis. Chi-squared or Fisher’s exact tests, and Wilcoxon tests were used to assess associations between clinical variables and sex in the overall cohort as well as by genotype (wtATTR and V122I). Hazard ratios with 95% confidence intervals were used to assess outcomes. Results: Of 293 subjects, 235 (80%) were men and 58 (20%) were women. Women vs men were more likely Black in the entire cohort (65% v 39%) and in the wtATTR group (70% v 8.7%, p<0.05). Women were significantly older in wtATTR (84 [6.6] v 79 [7.2] yrs) and V122I (75 [6] v 71 [8.3] yrs), had higher HR (83 v 75 bpm), lower eGFR (54 v 62 mL/min/1.73 m2), and thinner intraventricular septum diameter (1.54 [0.3] v 1.71 [0.3] cm) than men at time of diagnosis (p<0.05). Women with wtATTR had significantly higher mean RAP (14.8 [6.9] v 8.69 [4.8] v mmHg, p<0.05) and a trend toward higher PASP (55.5 [17.0] v 42.9 [12.8] and PCWP (22.5 [6.7] v 17.3 [6.4] mmHg, p=0.06) vs men. There was no difference in HF hospitalization or death at 5 years (HR 0.93 [0.59-1.45], p=0.70) and no significant increase in proportion of women diagnosed over disease eras (pre-2013, 2013-2018, and 2019-2023). Conclusions: In a well characterized cohort with ATTR-CM, women were diagnosed less frequently and at an older age with markers of more advanced disease including higher HR, worse renal function, and higher filling pressures compared to men. Disease recognition in women did not increase over time. While this may be due to the nature of the disease, the characteristics we identified at diagnosis support that women with ATTR-CM are under detected. Future sex-based screening studies are needed to increase detection of ATTR-CM in women.
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