Exploring Cardiac Sympathetic Denervation in Transthyretin-Mediated Hereditary Amyloidosis (ATTRv): Insights from 123I-mIBG Scintigraphy

Abstract

Background/Objectives: Hereditary transthyretin-mediated amyloidosis (ATTRv) is a rare disease characterized by the deposition of amyloid in the heart and peripheral nerves, particularly affecting small fibers. This study aims to evaluate autonomic cardiac involvement in ATTRv. Methods: Twelve patients with ATTRv and twelve sex- and age-matched healthy subjects underwent ¹²³I-mIBG scintigraphy to evaluate the early and late heart-to-mediastinum ratio (eH/M and lH/M), ^99mTc-HDP bone scan scintigraphy, and neurophysiological assessments. Data were analyzed in relation to functional cardiac and neurologic scales (NYHA and FAP scales). Results: Patients with ATTRv exhibited significant cardiac denervation, as demonstrated by the reduction in early and late H/M ratios compared to the control group (eH/M: 1.48 ± 0.08 vs. 1.89 ± 0.05, p < 0.001; lH/M: 1.39 ± 0.08 vs. 2.01 ± 0.05, p < 0.001). Values of eH/M and lH/M < 1.6 effectively differentiated patients with ATTRv from the healthy controls. Cardiac denervation correlated with interventricular septal thickness and the Perugini score but was not related to neurophysiological assessments or NYHA and FAP scales. Conclusions: Ultimately, ¹²³I-mIBG scintigraphy is an effective tool for assessing cardiac denervation in patients with ATTRv.

Keywords: 123I-mIBG scintigraphy; ATTRv; amyloidosis; heart denervation; transthyretin.

Figure 1

(A) ^99mTc-HDP planar chest image. Application of the semi-quantitative method with the calculation of the heart-to-contralateral ratio (H/CL ratio): the circle of the region of interest being studied is in blue (ROI 2), and the contralateral comparison circle is shown in white (ROI 1). (B) ¹²³I-mIBG planar anterior chest image of a patient with lH/M:1.88. A manually drawn ROI is placed on the heart (ROI 1) and a fixed ROI is placed in the mediastinum (ROI 0).

Figure 2

(A) ^99mTc-HDP planar chest image of the patient with a Perugini score of 0 and a Phe84Leu mutation. (B) ¹²³I-mIBG planar anterior chest image of the patient with the Phe84Leu mutation. lH/M:1.31. A manually drawn ROI is placed on the heart (ROI 0) and a fixed ROI is placed in the mediastinum (ROI 1).

Figure 3

(A). Early H/M ratio in healthy controls and patients with ATTRv. (B). Late H/M ratio in healthy controls and patients with ATTRv. * p < 0.05. The boxes indicate the upper and lower quartiles, and the whiskers indicate the minimum to the maximum value.

Figure 4

Early H/M ratio in patients with Perugini scores 2 and 3. * p < 0.05. The boxes indicate the upper and lower quartiles, and the whiskers indicate the minimum to the maximum value.