Progression of autonomic failure in patients with transthyretin amyloidosis and asymptomatic carriers – a Follow-up study

<h3>Introduction</h3> Hereditary or variant transthyretin amyloidosis (ATTRv) is a progressive disease with disabling autonomic symptoms. With effective disease modifying treatments (DMT) markers of disease progression are required. This study describes progression of autonomic failure (AuF) in ATTRv patients and carriers using autonomic function testing (AFT) and ambulatory blood pressure (BP) monitoring (ABPM). <h3>Methods</h3> 53 patients and 6 <i>TTR</i> mutation carriers had AFT (31% F, mean age 54 years, 37% T60A mutation) at baseline (BL) and at follow-up (FU; range 7-133 months, median 23 months). 45 subjects (6 carriers) had ABPM with FU. We defined three AuF stages: normal AFT (0), mild parasympathetic and/or sympathetic impairment (I), neurogenic orthostatic hypotension (II). BP dipping profile was defined according to the consensus criteria. <h3>Results</h3> All six subjects (2 carriers) with initial stage 0 developed stage I within 4 years. Progression from stage I to II was detected in 4/27 patients within 2 years, one patient on DMT improved to stage 0. 8/24 patients improved from stage II to I. ABPM showed normal dipping profile in 15 subjects (one carrier) at BL, 7/15 developed pathologic dipping at FU. <h3>Conclusion</h3> Cardiovascular autonomic failure and impaired BP profile are frequent, early features with progression over time. Carriers showed subclinical autonomic dysfunction. AuF improvement can occur with DMT.