Tenosynovial and Transverse Carpal Ligament Biopsy for Early Transthyretin Amyloidosis Cardiomyopathy Detection: A Systematic Review and African American Retrospective Cohort Study

Purpose Performing tenosynovial biopsy during carpal tunnel release (CTR) has emerged as a promising diagnostic tool for systemic transthyretin amyloidosis cardiomyopathy (ATTR-CM). Early detection is critical because therapies, such as Tafamidis, have been shown to significantly improve outcomes when initiated prior to heart failure. The Val122Ile mutation (V122I) of the transthyretin (TTR) gene causes hereditary ATTR amyloidosis (hATTR), is found almost exclusively in people of African descent, and is underdiagnosed. The importance of diagnostic feasibility of transverse carpal ligament (TCL) biopsy is critical in the African American population, who often have poorer outcomes from delayed treatment. Methods We reviewed 22 studies published between 2017 and 2025 and conducted a retrospective cohort study of patients who underwent CTR at our institution between 2021 and 2025. Intraoperative TCL or A1 pulley specimens were routinely biopsied. All samples were analyzed for the presence of amyloid using Congo Red staining. Demographic data were extracted from the medical record. Results Our literature review found that 10% to 30% of CTR specimens contained amyloid deposits, mass spectrometry was the superior analytic modality, and biopsying the TCL in high-risk patients had greater diagnostic yield. At our institution, 89 patients (61.8% African American and 38.2% Caucasian) underwent CTR with concurrent tenosynovial biopsy between 2021 and 2025. The mean age was 55.36 ± 12 years and 32.6% were men. All specimens were analyzed with Congo Red staining. Amyloid deposits were not identified in any specimens. Conclusions Our negative findings with the largest studied African American population to date underscore the importance of further investigation to refine selection criteria, standardize sampling, and clarify the role of TCL biopsy in early detection of ATTR-CM. Type of study/level of evidence Therapeutic III.