The frequency of cardiac amyloidosis in 182 patients receiving carpal tunnel release surgery
Authors: Hansen F.G , Bastkjaer R , Nielsen S.K , Petersen A.S , Moeller H.E.H , Jensen K.P , Tromborg H , Kejlaa G , Beck H.C , Rojek A.S , Hansen C.T , Marcussen N , Overgaard S , Abildgaard N , Mogensen J 
Published: November 2020

Abstract

Introduction
Retrospective studies have suggested that a significant proportion of patients with cardiac amyloidosis received surgical treatment for carpal tunnel syndrome (CTS) 5–10 years before diagnosis of their cardiac condition. So far, one cross-sectional study has investigated the presence of localized and systemic amyloidosis in 98 patients undergoing carpal tunnel release surgery (CTRS). Ten percent were shown to have amyloid deposits in the carpal tunnel while two had cardiac involvement caused by either AL amyloidosis or wild-type transthyretin amyloidosis (ATTR).

Purpose
To investigate the prevalence of cardiac amyloidosis among unselected and consecutive patients undergoing CTRS.

Methods
Tissue samples from the carpal tunnel of 182 CTRS patients were stained with Congo Red. Amyloid positive samples were subtyped by immunoelectron microscopy and mass spectrometry.
Amyloid positive patients underwent investigations for cardiac amyloidosis including ECG-recording, echocardiography and strain imaging, cardiac magnetic resonance imaging and whole-body scintigraphy (99m-tc-DPD). Genetic investigation of the gene for TTR was performed in patients with ATTR amyloidosis or an undetermined subtype. Patients were also investigated by measurements of NT-proBNP, troponins, immunoglobulins, M-protein in serum and urine, and free light kappa and lambda chains in serum.

Results
In total, 16% (29/182) of the patients had amyloid positive biopsies. They were significantly older than amyloid negative patients (73 years vs 53 years, p&lt;0.001). The prevalence of males was significantly higher in the amyloid positive group (66% vs 25%, p&lt;0.001). The presence of bilateral CTS was not associated with amyloid deposits.
The subtype of amyloid was shown to be (a) ATTR in 86% (n=25) of patients, (b) localized light-chain amyloidosis in 3% (n=1), and (c) fibrinogen alpha amyloidosis in 3% (n=1), while the amount of tissue did not allow subtyping in 7% (n=2). All ATTR patients had a normal genetic investigation.
So far, 24 of the 29 amyloid positive patients have completed all clinical investigations and no one fulfilled diagnostic criteria of cardiac amyloidosis.

Conclusion
A significant number of CTRS patients, (14%), had wild-type ATTR amyloidosis confined to the carpal tunnel. None of these had cardiac involvement. These findings were different from the results in the previous prospective study and were likely to be explained by differences in the patient cohorts investigated. We investigated unselected patients in contrast to the highly selected cohort in the previous study.
Based on the findings in the current study the proportion of CTRS patients with localized amyloidosis who may develop systemic disease is unknown. Therefore, it is necessary to perform long term follow-up of these patients before routine investigations for amyloidosis may be recommended.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Financial support was obtained by an unrestricted research grant from Alnylam Pharmaceuticals