Early cardiovascular autonomic failure in ATTRv predicts poor prognosis and may respond to disease-modifying therapy.

Background: Hereditary transthyretin amyloidosis (ATTRv) is a life-threatening, but treatable disease presenting with autonomic dysfunction. This study investigates the progression of autonomic failure, response to treatment, and the impact of autonomic failure in ATTRv.

Methods: Clinical features and autonomic function test (AFT) results were evaluated in 126 patients (40 had treatment) and 12 asymptomatic TTR variant carriers. A subgroup had follow-up (FU) AFT. Kaplan-Meier estimates compared survival time between participants with and without neurogenic orthostatic hypotension (nOH), and logistic regression assessed its impact on mortality.

Results: Patients treated early with disease modifying therapies (DMT) had slower progression and did not develop nOH. In 59 individuals with repeat AFT, autonomic dysfunction worsened, with a decline in the Valsalva ratio (p = 0.002), even in early-stage disease (p = 0.019; median disease duration at FU 4 years). nOH at first assessment predicted worse outcome (mean survival time in individuals with nOH 7.0 vs. 14.9 years without nOH, p < 0.001) and death (OR = 5.27; 95%CI: 1.94 - 14.31; p = 0.001).

Conclusions: The early development of autonomic dysfunction and nOH is an independent predictive factor for shorter survival in ATTRv. Autonomic testing is a valuable biomarker to capture disease progression. Prospective studies need to confirm the benefit of DMT on autonomic dysfunction.