Prevalence and prognostic value of autonomic neuropathy assessed by Sudoscan® in transthyretin wild-type cardiac amyloidosis

Mounira Kharoubi, Fréderic Roche, Mélanie Bézard, David Hupin, Sidney Silva, Silvia Oghina, Coraline Chalard, Amira Zaroui, Arnault Galat, Soulef Guendouz, Florence Canoui-Poitrine, Luc Hittinger, Emmanuel Teiger, Jean-Pascal Lefaucheur, Thibaud Damy, Mounira Kharoubi, Fréderic Roche, Mélanie Bézard, David Hupin, Sidney Silva, Silvia Oghina, Coraline Chalard, Amira Zaroui, Arnault Galat, Soulef Guendouz, Florence Canoui-Poitrine, Luc Hittinger, Emmanuel Teiger, Jean-Pascal Lefaucheur, Thibaud Damy

Abstract

Aims: The prevalence of autonomic neuropathy (AN) is high in patients with hereditary transthyretin amyloidosis but remains unknown in transthyretin wild-type cardiac amyloidosis (ATTRwt-CA). This study aimed to determine the prevalence of AN in patients with ATTRwt-CA using Sudoscan®, a non-invasive method used to provide evidence of AN in clinical practice and based on measurement of electrochemical skin conductance at the hands and feet (fESC).

Methods and results: A series of 62 non-diabetic patients with ATTRwt-CA was prospectively included over 2 years and compared with healthy elderly subjects, matched by age, gender, and body mass index. The presence of AN was defined as electrochemical skin conductance at the hands <60 μS and/or fESC <70 μS, and conductances were analysed according to clinical, biological, and echocardiographic data. Mean fESC was significantly lower in patients with ATTRwt-CA compared with elderly controls: 68.3 (64.1-72.5) vs. 76.9 (75.6-78.1) μS (P < 0.0001), respectively. Prevalence of fESC <70 μS was higher in ATTRwt-CA patients than in controls: 48.4% vs. 19.9%, P < 0.05. Univariate analysis showed that fESC, N-terminal pro-B-type natriuretic peptide, creatinine plasma levels, and echocardiographic global longitudinal strain were associated with decompensated cardiac failure and death. Multivariate analysis revealed that fESC was an independent prognostic factor, and Kaplan-Meier estimator evidenced a greater occurrence of cardiac decompensation and death in patients with fESC <70 μS, P = 0.046.

Conclusions: Reduced fESC was observed in almost 50% of patients with ATTRwt-CA and was associated with a worse prognosis. Sudoscan® could easily be used to screen ATTRwt-CA patients for the presence of AN and identify patients at higher risk for a poor outcome.

Keywords: Aging; Cardiac amyloidosis; Heart failure; Neuropathy; Prognosis; Sudoscan.

Conflict of interest statement

M.K., M.B., S.S., C.C., A.Z., A.G., S.F., F.C.P., L.H., and J.P.L. have no conflict of interest to declare for this study. T.D. has received research grant and honorarium from Pfizer, Akcea, and Novartis and honorarium from Alnylam and Prothena. F.R. has no conflict of interest to declare for this study. The PROOF study was supported by two national PHRC (1998 and 2001; DGOS, URCIP CHU Saint Etienne).

© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Figures

Figure 1
Figure 1
Percentage of healthy elderly controls and transthyretin wild‐type cardiac amyloidosis (ATTRwt‐CA) patients with reduced electrochemical skin conductance at the hands (hESC) (

Figure 2

Correlation between right and left…

Figure 2

Correlation between right and left electrochemical skin conductance at the hands (hESC) or…

Figure 2
Correlation between right and left electrochemical skin conductance at the hands (hESC) or feet (fESC) in healthy elderly controls and transthyretin wild‐type cardiac amyloidosis (ATTRwt‐CA) patients.

Figure 3

Correlation between right and left…

Figure 3

Correlation between right and left electrochemical skin conductance at the hands (hESC) or…

Figure 3
Correlation between right and left electrochemical skin conductance at the hands (hESC) or feet (fESC) in transthyretin wild‐type cardiac amyloidosis (ATTRwt‐CA) patients with or without carpal tunnel syndrome, diffuse neuropathy, or lumbar spinal stenosis.

Figure 4

Kaplan–Meier curves for cardiac decompensation…

Figure 4

Kaplan–Meier curves for cardiac decompensation or death in transthyretin wild‐type cardiac amyloidosis (ATTRwt‐CA)…

Figure 4
Kaplan–Meier curves for cardiac decompensation or death in transthyretin wild‐type cardiac amyloidosis (ATTRwt‐CA) patients with electrochemical skin conductance at the feet (fESC) ≥70 μS or
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References
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Figure 2
Figure 2
Correlation between right and left electrochemical skin conductance at the hands (hESC) or feet (fESC) in healthy elderly controls and transthyretin wild‐type cardiac amyloidosis (ATTRwt‐CA) patients.
Figure 3
Figure 3
Correlation between right and left electrochemical skin conductance at the hands (hESC) or feet (fESC) in transthyretin wild‐type cardiac amyloidosis (ATTRwt‐CA) patients with or without carpal tunnel syndrome, diffuse neuropathy, or lumbar spinal stenosis.
Figure 4
Figure 4
Kaplan–Meier curves for cardiac decompensation or death in transthyretin wild‐type cardiac amyloidosis (ATTRwt‐CA) patients with electrochemical skin conductance at the feet (fESC) ≥70 μS or

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