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BACKGROUND: Autonomic dysfunction is common in transthyretin amyloidosis (ATTR amyloidosis), but its frequency, characteristics, and quality-of-life (QoL) impact are not well understood. METHODS: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal survey of patients with ATTR amyloidosis, including patients with inherited (ATTRv) and wild-type (ATTRwt) disease and asymptomatic patients with TTR mutations (ClinicalTrials.gov: NCT00628745). In a descriptive analysis, characteristics and Norfolk QoL-DN total (TQoL) scores at enrolment were compared in patients with vs without autonomic dysfunction (analysis cut-off: 1 August 2020). RESULTS: Autonomic dysfunction occurred in 1181/2922 (40.4%) symptomatic patients, and more commonly in ATTRv (1107/1181 [93.7%]) than ATTRwt (74/1181 [6.3%]) amyloidosis. Time (mean [SD]) from ATTR amyloidosis symptom onset to first autonomic dysfunction symptom was shorter in ATTRv (3.4 [5.7] years) than ATTRwt disease (9.7 [10.4]). In ATTRv disease, patients with vs without autonomic dysfunction had worse QoL (TQoL, 47.3 [33.2] vs 16.1 [18.1]); in ATTRwt disease, those with vs without autonomic dysfunction had similar QoL (23.0 [18.2] vs 19.9 [20.5]). CONCLUSIONS: Autonomic dysfunction was more common and presented earlier in symptomatic ATTRv than ATTRwt amyloidosis and adversely affected QoL in ATTRv disease. These THAOS findings may aid clinicians in diagnosing and treating patients with ATTR amyloidosis. Trial registration: ClinicalTrials.gov: NCT00628745.
Assuntos
Neuropatias Amiloides Familiares , Disautonomias Primárias , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/genética , Humanos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
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.
RESUMO
Patients with transthyretin amyloid polyneuropathy (ATTR-PN) show decreased motor and sensory nerve amplitudes and conduction. Electrophysiological changes over time may be sensitive indicators of progression. This analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS) assessed longitudinal changes in nerve conduction as signals of neurologic disease progression in patients with hereditary ATTR (ATTRv) amyloidosis. Patients with ATTRv in THAOS with recorded nerve conduction values were included (data cut-off: January 6, 2020); changes in nerve amplitude and velocity over time were assessed. Patients (n = 1389) were 45.0% male; 80.4% were the Val30Met (p.Val50Met) genotype. Mean (SD) age at enrollment was 43.6 (14.5) years; duration of symptoms was 9.3 (6.4) years. Median (10th, 90th percentile) sural nerve amplitude and velocity was 18.0 (4.9, 35.0) µV and 50.7 (41.0, 57.9) m/s; peroneal conduction was 13.0 (4.4, 27.0) µV and 51.0 (41.7, 59.7) m/s, respectively. Median (10th, 90th percentile) percentage change from baseline in sural nerve amplitude was variable, but generally decreased over time from -7.4 (-43.2, 52.4) at year 1 to -14.4 (-76.9, 46.7) at year 8. Percent change from baseline in sural nerve velocity declined similarly: -0.1 (-14.5, 15.3) at year 1 and - 6.4 (-21.3, 10.5) at year 8. The decline was more pronounced in patients with greater disability at baseline. Similar patterns were observed for the peroneal nerve. These data show an association between nerve amplitudes and velocities and disease severity, suggesting progressive deterioration in nerve conduction may be an indicator of ATTRv amyloidosis disease progression.