Gastric emptying in hereditary transthyretin amyloidosis: the impact of autonomic neuropathy

Abstract

Background: Gastrointestinal (GI) complications are common in hereditary transthyretin amyloidosis and an autonomic dysfunction has been considered to explain these symptoms. The aim of this study was to investigate the impact of autonomic neuropathy on gastric emptying in hereditary transthyretin amyloidosis and to relate these findings to nutritional status, GI symptoms, gender, and age at disease onset.

Methods: Gastric emptying was evaluated with gastric emptying scintigraphy. Spectral analysis of the heart rate variability and cardiovascular responses after tilt test were used to assess the autonomic function. The nutritional status was evaluated with the modified body mass index (s-albumine × BMI).

Key results: Gastric retention was found in about one-third of the patients. A weak correlation was found between the scintigraphic gastric emptying rate and both the sympathetic (rs = -0.397, P < 0.001) and parasympathetic function (rs = -0.282, P = 0.002). The gastric emptying rate was slower in those with lower or both upper and lower GI symptoms compared with those without symptoms (median T(50) 123 vs 113 min, P = 0.042 and 192 vs 113 min, P = 0.003, respectively). Multiple logistic regression analysis showed that age of onset (OR 0.10, CI 0.02-0.52) and sympathetic dysfunction (OR 0.23, CI 0.10-0.51), but not gender (OR 0.76, CI 0.31-1.84) and parasympathetic dysfunction (OR 1.81, CI 0.72-4.56), contributed to gastric retention.

Conclusions and inferences: Gastric retention is common in hereditary transthyretin amyloidosis early after onset. Autonomic neuropathy only weakly correlates with gastric retention and therefore additional factors must be involved.

Figure 1

Gastric emptying scintigraphy. Graph showing the result from a slightly delayed gastric emptying scintigraphy (136 min) in a 54-year-old female patient with hereditary transthyretin amyloidosis. Lag phase from 0 to 20 min.

Figure 2

Heart rate variability (HRV). Heart rate and spectral analysis of the HRV in two patients with hereditary transthyretin amyloidosis. To the left an early onset case with an almost normal HRV and to the right a late onset case with a low HRV. The heart rate was measured in both the supine and the upright position. The high-frequency component in the supine position (HF_sup) was used as an indirect estimate of the parasympathetic function and the low-frequency component in an upright position (LF_tilt) as an estimate of the sympathetic function.

Figure 3

Gastrointestinal symptoms and gastric emptying. Box plot showing the differences in the scintigraphic gastric emptying rate related to gastrointestinal (GI) symptoms (P = 0.004). Upper GI symptoms = nausea/vomiting. Lower GI symptoms = diarrhea/constipation.

Figure 4

Autonomic function and gastric emptying. Scatterplot showing the relationship between (A) the scintigraphic gastric emptying rate and the parasympathetic function (rs = −0.282, P = 0.002) and (B) the relationship between the scintigraphic gastric emptying rate and the sympathetic function (rs = −0.397, P < 0.001). HRV = heart rate variability.