Development of a Three-Source Convergent Risk Assessment Tool for Amyloidosis Screening in Carpal Tunnel Syndrome Patients.

Authors

Komatsu David Edward, Badalamente Marie Anne, Grabowski Kathryn, Paulus Megan, Muhlrad Samantha, Meo Ann Marie, Gorevic Peter Dov, Vlay Stephen, Hurst Lawrence Colwyn

Published in

Journal of hand surgery global online. Volume 8. Issue 6. Pages 101102. Epub Aug 07, 2026.

Abstract

Amyloid transthyretin cardiomyopathy (ATTR-CM) is a progressive and frequently fatal disease that is under-recognized. A diagnosis of carpal tunnel syndrome (CTS) elevates the risk of receiving a diagnosis of ATTR-CM, with a diagnosis of CTS often recognized 5-10 years before ATTR-CM is clinically diagnosed. The recent development of the availability of disease-modifying therapies, which appear to be most effective during the early deposition phase of amyloidogenesis, has underscored the need to define the "red flags" that may signal the diagnosis of ATTR-CM. This study sought to develop a risk assessment tool to identify CTS patients at elevated risk for amyloidosis.
We developed a 34-item questionnaire and administered it to three cohorts: (1) cardiac amyloid patients; (2) CTS patients; and (3) general orthopedic patients. Demographics, symptoms, and diagnoses were compared using chi-squared tests. Subsequently, three independent evidence streams were prespecified for weight assignment: (1) absolute prevalence differences from the primary cohort; 2) risk differences from an 800,662-subject TriNetX study; and 3) prospective tenosynovial biopsy data. Prespecified tier criteria were applied to assign point weights, with concordance across streams assessed as the primary methodological validity metric. A five-tier weighted scoring system was developed, comprising four progressively higher risk categories and a highest risk category that unequivocally recommends tenosynovial biopsy.
Eighteen risk factors demonstrated statistically significant prevalence differences between the amyloidosis and CTS cohorts (P < .05). The highest were irregular heartbeat/arrhythmia, chronic fatigue, and shortness of breath. Concordance between the questionnaire-derived risk hierarchy and the TriNetX study was 95%, and a four-tier scoring system was established.
We developed an evidence-based, weighted risk assessment tool to identify CTS patients at elevated risk for amyloidosis and guide tenosynovial biopsy decisions during carpal tunnel release.
This tool has the potential to identify CTS patient at risk for cardiac amyloidosis that could benefit from biopsy at the time of surgery.

PMID:
42604118
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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