Amyloidosis Screening by Biopsy During Carpal Tunnel Release: A Systematic Review and Meta-analysis

Background: Cardiac amyloidosis (CA) is an underdiagnosed cause of heart failure with newly available effective therapies. Carpal tunnel syndrome is a common early manifestation of amyloidosis, and tissue obtained during carpal tunnel release (CTR) can be screened for amyloid, allowing for early CA diagnosis and treatment. However, neither screening criteria nor diagnostic yield are well defined. We estimated the prevalence of amyloid within the tenosynovium or transverse carpal ligament and occult CA among patients undergoing screening biopsy during CTR based on the results of published studies. Methods: We conducted a systematic review and meta-analysis of studies that analyzed screening biopsies obtained at the time of CTR for the presence of amyloid. Results: Of 21 articles meeting inclusion criteria, 14 included biopsies from a general population undergoing CTR, 5 reported biopsies from a prescreened population at elevated risk for amyloidosis undergoing CTR, and 2 included patients undergoing CTR with suspected amyloidosis. The pooled prevalence of amyloid within the tenosynovium/transverse carpal ligament was 11% (95% confidence interval: 5%-18%) in American and European studies without prescreening, 20% (95% confidence interval: 13%-29%) in studies of screened patients, and 88%-100% in studies of patients suspected of having amyloidosis preoperatively. Overall, 5%-20% of patients with amyloid-positive biopsies who underwent cardiac screening were eventually diagnosed with CA, of whom 33% were started on transthyretin tetramer stabilizers. Conclusions: Biopsies for amyloid during CTR demonstrate a high rate of positivity among at-risk populations and an opportunity for early detection of occult CA. Future studies should further refine diagnostic criteria to optimize cost-effectiveness of widespread screening.