TY - JOUR
T1 - Characteristics of Patients with Late- vs. Early-Onset Val30Met Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS)
AU - the THAOS investigators
AU - Waddington-Cruz, Márcia
AU - Wixner, Jonas
AU - Amass, Leslie
AU - Kiszko, Jan
AU - Chapman, Doug
AU - Ando, Yukio
AU - Barroso, Fabio Adrian
AU - Rugiero, Marcelo
AU - Van Cleemput, Johan
AU - Tarnev, Ivaylo
AU - Kyriakides, Theodoros
AU - Kristen, Arnt
AU - Schmidt, Hartmut
AU - Darstein, Felix
AU - Gess, Burkhard
AU - Plana, Josep Maria Campistol
AU - Moreno, Juan Gonzalez
AU - Costello, Jose Gonzalez
AU - Pavia, Pablo Garcia
AU - Torrón, Roberto Fernandéz
AU - Beamud, Francisco Munoz
AU - Planté-Bordeneuve, Violaine
AU - Adams, David
AU - Lairez, Olivier
AU - Rapezzi, Claudio
AU - Merlini, Giampaolo
AU - Luigetti, Marco
AU - Sekijima, Yoshiki
AU - Yamashita, Taro
AU - Misawa, Sonoko
AU - Low, Soon Chai
AU - Nienhuis, Hans
AU - Coelho, Teresa
AU - Conceição, Isabel
AU - Press, Rayomand
AU - Parman, Yesim
AU - Maurer, Mathew
AU - Gottlieb, Stephen
AU - Wang, Annabel
AU - Drachman, Brian
AU - Dispenzieri, Angela
AU - Zivkovic, Sasa
AU - Lenihan, Daniel
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Introduction: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a clinically heterogeneous disease caused by mutations in the transthyretin (TTR) gene. The most common mutation, Val30Met, can manifest as an early- or late-onset disease. Methods: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease and asymptomatic patients with TTR mutations. This is a descriptive analysis of symptomatic patients with ATTRv Val30Met amyloidosis with late- (age at least 50 years) vs. early-onset (age less than 50 years) disease in THAOS (data cutoff August 1, 2019). Results: Of 1389 patients with ATTRv Val30Met amyloidosis, 491 (35.3%) had late-onset disease. Compared with early-onset, patients with late-onset were more likely to be male (66.2% vs. 53.6%) and have a longer mean (standard deviation [SD]) time from onset to diagnosis (3.8 [3.4] vs. 2.7 [4.1] years). Late-onset disease was associated with more severe neurological impairment at enrollment (median [10th, 90th percentile] derived Neuropathy Impairment Score in the Lower Limbs, 25.0 [4.0, 69.3] vs. 8.0 [0, 54.8]; Neurologic Composite Score, 42.0 [2.0, 155.0] vs. 21.0 [0, 102.0]). Cardiac findings were more prominent in late-onset disease. An overall interpretation of electrocardiogram as abnormal was reported in 72.1% of late-onset patients (vs. 44.3% early-onset). A left-ventricular septal thickness of at least 12 mm was reported in 69.7% of late-onset patients (vs. 14.6% early-onset). All differences were statistically significant (p < 0.001). Conclusion: In THAOS, late-onset ATTRv Val30Met amyloidosis is common, presenting with more severe neurologic and cardiac findings at enrollment. Heterogeneity of disease may make it more difficult to diagnose. Increased recognition of late-onset ATTRv Val30Met amyloidosis could lead to more timely diagnosis and improve patient outcomes. Trial Registration: ClinicalTrials.gov NCT00628745.
AB - Introduction: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a clinically heterogeneous disease caused by mutations in the transthyretin (TTR) gene. The most common mutation, Val30Met, can manifest as an early- or late-onset disease. Methods: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease and asymptomatic patients with TTR mutations. This is a descriptive analysis of symptomatic patients with ATTRv Val30Met amyloidosis with late- (age at least 50 years) vs. early-onset (age less than 50 years) disease in THAOS (data cutoff August 1, 2019). Results: Of 1389 patients with ATTRv Val30Met amyloidosis, 491 (35.3%) had late-onset disease. Compared with early-onset, patients with late-onset were more likely to be male (66.2% vs. 53.6%) and have a longer mean (standard deviation [SD]) time from onset to diagnosis (3.8 [3.4] vs. 2.7 [4.1] years). Late-onset disease was associated with more severe neurological impairment at enrollment (median [10th, 90th percentile] derived Neuropathy Impairment Score in the Lower Limbs, 25.0 [4.0, 69.3] vs. 8.0 [0, 54.8]; Neurologic Composite Score, 42.0 [2.0, 155.0] vs. 21.0 [0, 102.0]). Cardiac findings were more prominent in late-onset disease. An overall interpretation of electrocardiogram as abnormal was reported in 72.1% of late-onset patients (vs. 44.3% early-onset). A left-ventricular septal thickness of at least 12 mm was reported in 69.7% of late-onset patients (vs. 14.6% early-onset). All differences were statistically significant (p < 0.001). Conclusion: In THAOS, late-onset ATTRv Val30Met amyloidosis is common, presenting with more severe neurologic and cardiac findings at enrollment. Heterogeneity of disease may make it more difficult to diagnose. Increased recognition of late-onset ATTRv Val30Met amyloidosis could lead to more timely diagnosis and improve patient outcomes. Trial Registration: ClinicalTrials.gov NCT00628745.
KW - ATTRv amyloidosis
KW - Cardiac
KW - Disease onset
KW - Neurologic
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U2 - 10.1007/s40120-021-00258-z
DO - 10.1007/s40120-021-00258-z
M3 - Article
AN - SCOPUS:85106565173
SN - 2193-8253
VL - 10
SP - 753
EP - 766
JO - Neurology and Therapy
JF - Neurology and Therapy
IS - 2
ER -