Sex Differences in Wild-Type Transthyretin Amyloidosis: An Analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS)
Courtney Campbell, Samantha LoRusso, Angela Dispenzieri, Arnt V. Kristen, Mathew S. Maurer, Claudio Rapezzi, Olivier Lairez, Brian Drachman, Pablo García‐Pavía, Martha Grogan, Doug Chapman, Leslie Amass, The THAOS investigators, Michele Emdin, Mazen Hanna, Olga Azevedo, Calogero Lino Cirami, Daniel Jacoby, José González‐Costello, David Slosky, H. Moelgaard, Scott L. Hummel, José Nativi-Nicolau, Srinivas Murali, Nowell M. Fine, Eun‐Seok Jeon, Sanjiv J. Shah, Ronald Witteles, Daniel J. Lenihan, Márcia Waddington‐Cruz, Yoshiki Sekijima, José Tallaj, Christopher R. Mueller, Johan Van Cleemput, Violaine Planté‐Bordeneuve, Hans Nienhuis, Dianna Quan, D. Eric Steidley, Hartmut Schmidt, Jonas Wixner, Michael Polydefkis, Jeffrey Ralph, Hector Ventura, Saša Živković, Burkhard Gess, Roberto Fernández‐Torrón, Stephen S. Gottlieb, William Cotts, James M. Tauras, Nitasha Sarswat, Juan González Moreno, Yeşim Parman, Jin Luo
Abstract
INTRODUCTION: Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) is a progressive disease resulting from the accumulation of wild-type transthyretin (TTR) amyloid fibrils, and is diagnosed primarily in males. This analysis examined sex differences in patients with ATTRwt amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS). METHODS: THAOS is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of TTR mutations. THAOS data were analyzed to identify potential differences in demographic and clinical characteristics between males and females with ATTRwt amyloidosis (data cutoff: August 1, 2021). RESULTS: Of 1386 patients with ATTRwt amyloidosis, 84 (6%) were female and 1302 (94%) were male. Females had a higher median age at enrollment (80 vs. 78 years; p = 0.002) and symptom onset (75 vs. 73 years; p = 0.045) than males. Mean left ventricular (LV) ejection fraction was higher (53% vs. 48%; p = 0.001) and mean LV diastolic diameter lower (42 vs. 46 mm; p < 0.001) in females versus males, but sex was not identified as a predictor of LV mean wall thickness adjusted for height (beta coefficient - 0.22; p = 0.460) or a predominantly cardiac phenotype (odds ratio 1.60; p = 0.191). Modified polyneuropathy disability scores differed between groups (p < 0.001), with a larger proportion of scores ≥ IIIa among females (23% vs. 7%). CONCLUSIONS: Females with ATTRwt amyloidosis in THAOS tended to present at a later age and showed signs of less severe cardiac impairment and more severe walking impairment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00628745.