Abstract
BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is frequently preceded by carpal tunnel syndrome (CTS). The value of age- and biopsy-guided screening during CTS surgery for early detection of ATTR-CM remains uncertain. OBJECTIVES: We aimed to determine the proportion of amyloid deposition in tenosynovial biopsies, the proportion of ATTR-CM among biopsy-positive patients, and to compare disease severity between screening-detected and clinically diagnosed ATTR-CM patients. METHODS: This prospective, multicenter cohort study enrolled men ≥65 and women ≥75 years undergoing surgery for idiopathic CTS and analyzed tenosynovial biopsies for amyloid deposition. Patients with amyloid-positive biopsies underwent cardiac workup, including echocardiography, bone scintigraphy, biomarker testing, and genetic testing to confirm ATTR-CM. A control cohort of contemporary clinically diagnosed wildtype ATTR-CM patients was included for comparison. RESULTS: In total, 109 CTS patients were included (median age 79 years [IQR: 75-82]). Tenosynovial amyloid deposition was detected in 61/109 patients (56.0%; 95% CI: 46.1-65.5), of whom 52/61 patients completed cardiac evaluation. ATTR-CM was diagnosed in 9/52 patients (17.3%; 95% CI: 8.2-30.3; median age 83 years [IQR: 80-84]; male-to-female ratio 3.5:1; n = 7/2). Patients identified through screening had milder disease, 8/9 (89%) were in the National Amyloidosis Centre stage I compared to 26/47 (55%) among clinically diagnosed patients. CONCLUSIONS: Systematic age- and biopsy-guided screening during CTS surgery identified a high proportion of carpal amyloid deposition. Among amyloid-positive CTS patients, 1 in 6 was diagnosed with early-stage ATTR-CM. This approach demonstrated a higher yield in identifying ATTR-CM with mild disease burden and may serve as a tool for earlier diagnosis.