Deep screening unveils hidden cardiac amyloidosis: carpal tunnel syndrome as a gateway to early transthyretin cardiac amyloidosis diagnosis

Background Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive disease where early diagnosis and treatment can significantly improve prognosis. Carpal tunnel syndrome (CTS) often precedes cardiac involvement by 5–10 years, making it a potential early red flag for ATTR-CM. Previous studies have reported stepwise screening for cardiac involvement in cases where amyloid deposits were detected in tenosynovium during carpal tunnel release (CTR). However, comprehensive screening, including cardiac MRI, Technetium-99m pyrophosphate scintigraphy (99mTc-PYP scintigraphy), and genetic testing in all cases, has not been reported. Objective To perform detailed cardiac screening in patients with tenosynovial ATTR amyloid deposits found during CTR, evaluating the prevalence of ATTR-CM and identifying its predictive factors. Methods & Results This prospective study included 81 consecutive patients who underwent CTR for CTS between October 2022 and December 2024. Tenosynovial amyloid deposits were detected in 27 cases (33.3%), all confirmed as ATTR-positive. Among them, 24 patients (mean age 74.1±8.1 years, 11 males) consented to undergo blood tests, echocardiography, cardiac MRI, 99mTc-PYP scintigraphy, and genetic testing. All cases were wild-type ATTR, and 6 cases (28.9%) met the Japanese Cardiac Society 2020 Guideline criteria for probable or definite ATTR-CM (CTS-ATTR-CM). All CTS-ATTR-CM cases exhibited elevated troponin T beyond the normal range (0.028 ng/ml [0.017-0.034]); however, septal wall thickness remained within normal limits in four out of six cases (10.8±2.5 mm). Univariate logistic regression analysis identified extracellular volume fraction (ECV) increase by 1% (p=0.04, OR 1.38) and troponin T increase by 0.01 ng/mL (p=0.032, OR 9.39) as significant predictors of CTS-ATTR-CM, whereas echocardiographic markers such as wall thickness and ejection fraction were not predictive. Conclusion Comprehensive cardiac screening in patients with tenosynovial ATTR amyloid deposits identified ATTR-CM in 7.4% of all CTR cases. While ECV and troponin T emerged as potential predictors, echocardiographic findings proved insufficient in detecting early-stage ATTR-CM in CTS patients. Proactive screening in this population may facilitate early diagnosis and timely intervention.