Early Diagnosis of ATTR-CM Using Carpal Tunnel Biopsy Examination

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized but still underdiagnosed cause of heart failure in older people, typically causing substantial and irreversible cardiac damage before diagnosis. Specific therapies have lately become available that slow disease progression, early diagnosis now being a major priority to improving outcomes. Amyloid-associated carpal tunnel syndrome commonly precedes symptomatic cardiomyopathy, but histological examination at surgical decompression is seldom sought. This multicenter prospective study was conducted to determine whether biopsy at carpal tunnel decompression can aid early diagnosis of ATTR-CM. OBJECTIVES: This study sought to determine whether carpal tunnel biopsies obtained at routine surgical decompression can aid early diagnosis of ATTR-CM. METHODS: This prospective, multicenter, cross-sectional United Kingdom study included unselected patients >50 years of age who were undergoing carpal tunnel decompression and who provided biopsies for amyloid histological examination. Exclusion criteria included the inability to consent and an existing diagnosis of amyloidosis. Patients with biopsy-proven amyloid deposition were invited to undergo repurposed bone scintigraphy, echocardiography, and clinical assessments for systemic amyloidosis. RESULTS: A total of 555 patients, including 315 women, were studied with a mean ± SD age of 68.7 ± 11.0 years. The majority (60.3%), had bilateral symptoms, and the biopsy procedure proved safe. Amyloid was identified in 216 (39%) cases (51% of male and 30% of female patients), more frequently in tenosynovial than transverse carpal ligament biopsies (82.6% vs 70.2%; P < 0.001). Of 216 biopsy-positive patients, 116 assented to cardiac assessment. This assessment identified myocardial amyloid by using technetium-3,3-diphosphono-1,2-propanodicarboxlyic acid (Tc-DPD) scintigraphy in 32 of 116 (28%) patients: 26 were male, 10 had Perugini grade 2 uptake, and the remainder had grade 1 uptake. Echocardiography and serum biomarkers identified significant ATTR-CM in patients with Perugini grade 2 DPD scans, prompting commencement of disease-modifying therapy. Two further patients received a diagnosis of unsuspected systemic light-chain (AL) amyloidosis, thus enabling timely chemotherapy. CONCLUSIONS: Transthyretin amyloid (ATTR) is commonly present in the tenosynovium and transverse carpal ligaments of older people with carpal tunnel syndrome, and more than one quarter of whom have ATTR cardiac amyloid infiltration that is readily identifiable using bone scintigraphy. Biopsies of samples taken at carpal tunnel decompression present a practicable pathway to enable early diagnosis and treatment of ATTR-CM.