A prospective multicenter cohort study suggests that biopsy-guided screening during surgery for idiopathic carpal tunnel syndrome may identify transthyretin amyloid cardiomyopathy (ATTR-CM) at an earlier stage in selected older patients. Among 52 patients with amyloid-positive tenosynovial biopsies who completed cardiac evaluation, nine (17%) were diagnosed with ATTR-CM, most with mild, asymptomatic disease at presentation.
The study enrolled 109 patients undergoing surgery for idiopathic carpal tunnel syndrome, including men aged 65 years or older and women aged 75 years or older. During surgery, researchers obtained two to three tenosynovial biopsies and assessed amyloid deposition using Congo red staining. Patients with amyloid-positive biopsies were referred for cardiac evaluation within a median of 5 weeks, including echocardiography, technetium-labeled bone scintigraphy, biomarker testing, and genetic testing. A comparison cohort included 47 patients with clinically diagnosed wild-type ATTR-CM.
Tenosynovial amyloid deposition was identified in 61 of 109 patients (56%). Of these, 52 completed cardiac evaluation, and nine were diagnosed with ATTR-CM. Among amyloid-positive male patients older than 75 years, ATTR-CM was identified in seven of 26 (27%).
Patients identified through screening had less advanced disease than those diagnosed through usual clinical pathways. Eight of the nine screening-detected patients (89%) were classified as National Amyloidosis Centre stage I, compared with 26 of 47 (55%) in the clinically diagnosed cohort. Most screening-detected patients were asymptomatic, with seven of nine (78%) in New York Heart Association class I.
Screening also identified a higher proportion of women compared with usual clinical pathways. Two of nine screening-detected patients (22%) were women, compared with two of 47 (4%) in the clinically diagnosed cohort. The researchers noted this difference may reflect underrecognition of ATTRwt-CM in women in routine practice.
Biomarker levels were lower in screening-detected patients, and structural cardiac involvement was less pronounced. These patients had lower interventricular septal thickness and left ventricular mass index and less impairment in systolic and diastolic function compared with clinically diagnosed patients. Notably, two of nine patients (22%) had normal N-terminal pro–B-type natriuretic peptide levels, and eight of nine (89%) had normal troponin I levels at diagnosis.
Genetic testing showed that eight patients had wild-type ATTR-CM and one patient had hereditary ATTR-CM.
During a mean follow-up of 2.3 years among 43 patients with amyloid-positive biopsies without cardiomyopathy, no cases of ATTR-CM were identified.
The findings suggest that age- and biopsy-guided screening during carpal tunnel surgery may provide an opportunity to detect ATTR-CM earlier in its disease course, particularly in high-risk surgical populations. However, the study was not designed to assess clinical outcomes, and earlier detection should not be interpreted as evidence of improved prognosis.
Limitations included the absence of a screening log, which limits assessment of selection bias, and the lack of long-term follow-up to determine progression to cardiomyopathy. All patients were White, limiting generalizability.
“Systematic age- and biopsy-guided screening during CTS surgery identified a high proportion of carpal amyloid deposition and enabled detection of predominantly early-stage ATTR-CM,” wrote lead researcher Sie Kronborg Fensman, MD, of Aarhus University Hospital, Aarhus, Denmark, and colleagues.
Disclosures: The study was supported by Novo Nordisk. The researchers reported relationships with Novo Nordisk, Pfizer, AstraZeneca, Bayer, Alnylam, Cytokinetics, and BridgeBio; other researchers reported no relevant conflicts.
Source: JACC: Advances
