Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR

Abstract

Patients with transthyretin amyloidosis (ATTR) polyneuropathy, a hereditary fatal disease, often report defects in both thermal perception and autonomic nervous system function as their first clinical symptoms. While elevated thermal perception thresholds (TPT) for cold and warmth only recently have been shown as an early marker of small nerve fiber dysfunction in these patients, heart rate variability (HRV) has frequently been used to quantify autonomic neuropathy. The main purpose with this report was to elucidate a possible relationship between estimates of HRV and TPT in a selected group of early and late-onset Swedish Val30Met ATTR patients. The results show significantly more pronounced elevation of TPT in early compared to late-onset patients. Significant correlations between HRV and TPT were found among late-onset cases, indicating a possible relationship between loss of thin nerve fibers in somatic and autonomic nerves, while generally no such relationships were found among early-onset cases. This observation emphasizes the importance of testing both HRV and TPT to ensure optimal early detection of neuropathic changes in an as wide as possible range of small nerve fibers in suspected ATTR patients. This is of particular importance as the phenotype of the ATTR disease varies between groups with different age of onset.

Cardiac transthyretin amyloidosis

“…Reduced heart rate variability on 24 h Holter monitoring is associated with autonomic nerve involvement and correlates with late onset disease in ATTR V30M amyloidosis 35. Reduced heart rate variability has been shown to predict short-term mortality in AA- and AL-type amyloid36 but the prognostic implications in ATTR type are not known, and are unlikely to be clinically relevant in SSA and V122I amyloid which are not reported to cause autonomic neuropathy.…”