Carpal tunnel biopsy may fall short for spotting heart amyloidosis

Collecting and analyzing wrist tissue for the presence of hallmark toxic protein clumps may not be sufficient as a stand-alone strategy for early detection of transthyretin cardiac amyloidosis (ATTR-CM) in African Americans undergoing surgery to ease carpal tunnel syndrome.

That’s according to a study that found no such clumps in carpal tunnel biopsy samples obtained from African Americans with carpal tunnel syndrome — which is increasingly recognized as an early marker of transthyretin amyloidosis (ATTR).

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ATTR is a group of conditions, including ATTR-CM, that are marked by toxic aggregates of the transthyretin protein, called amyloid deposits, that accumulate in tissues, causing damage.

While previous studies support biopsy of wrist tissues during carpal tunnel surgery as a possible tool for early ATTR-CM detection, “data for African American populations remain scarce,” the researchers wrote. “In our [study] containing the largest sample of African American individuals to date, [carpal tunnel] biopsy during [carpal tunnel surgery] did not identify amyloid, despite known high genetic risk.”

The findings highlight the importance of further studies to clarify the diagnostic potential of carpal tunnel biopsy for early ATTR-CM detection, especially in underrepresented at-risk populations such as African Americans.

The study, “Tenosynovial and Transverse Carpal Ligament Biopsy for Early Transthyretin Amyloidosis Cardiomyopathy Detection: A Systematic Review and African American Retrospective Cohort Study,” was published in the Journal of Hand Surgery Global Online.

ATTR can be caused by mutations in the TTR gene, which encodes the transthyretin protein, or occur due to aging-associated processes. ATTR-CM is a form of ATTR marked by accumulation of transthyretin clumps mainly in the heart, which can lead to heart failure, abnormal heart rhythms, and electrical conduction problems.

ATTR can also involve tissues outside the heart, including nerves outside the brain and spinal cord.

ATTR-CM disproportionately affects African Americans, particularly those who carry the V122I mutation in the TTR gene — reported in about 3% to 4% of African Americans.

“Despite this strong genetic predisposition, the disease is underdiagnosed, leading to worse clinical outcomes for African Americans,” the researchers wrote.

Carpal tunnel tissue may aid screening

Carpal tunnel syndrome is a condition characterized by abnormal pressure on the median nerve in the wrist and can cause numbness and tingling in the affected hand. It frequently precedes an ATTR diagnosis by several years.

Tissue collected during carpal tunnel release, a surgery meant to ease carpal tunnel syndrome, “has been proposed as a potential site for early detection of amyloid [deposits],” the researchers wrote.

To know more, a team of researchers in the U.S. first systematically reviewed studies published between 2017 and 2025 that examined tissue collected during carpal tunnel surgery.

In the studies reviewed, the proportion of samples containing amyloid deposits varied from 0% to about 10%. Detection rates were generally higher among older patients and those already diagnosed with ATTR-CM.

Some studies examined tenosynovial tissue, which surrounds tendons in the wrist, while others analyzed the transverse carpal ligament (TCL), a band of tissue forming part of the carpal tunnel. Some studies collected both.

The reviewed studies suggested that tenosynovial tissue may be more reliable for detecting amyloid deposits, and that collecting both tissue types may improve detection chances.

The reviewed studies generally supported targeted screening of people at higher risk rather than routine biopsy for everyone undergoing carpal tunnel release.

“However, most studies underrepresented African Americans, providing limited conclusions about population-specific screening,” the researchers wrote.

To address this knowledge gap, the team retrospectively analyzed carpal tunnel biopsy samples from 55 African Americans and 34 Caucasians who underwent carpal tunnel release at their institution between 2021 and 2025. Their mean age was about 55, and 67.4% were women. A total of 88 TCL specimens and 41 tenosynovial specimens were analyzed.

No amyloid found in biopsy samples

Despite high rates of cardiovascular risk factors in the study population, none of the tissue specimens from either African American or Caucasian participants tested positive for amyloid deposits.

The absence of amyloid deposits does not mean that tissue biopsy during carpal tunnel surgery has no diagnostic value, the researchers emphasized. Instead, the findings highlight the need to better identify which patients are most likely to benefit from biopsy and which tissue should be collected.

Most analyzed specimens came from the TCL, which may not be as reliable as tenosynovial tissue for amyloid deposit detection. Also, amyloid deposits in wrist tissue may not fully reflect the amount of amyloid deposits in the heart, the team noted.

For African American patients at risk of ATTR-CM, genetic testing for the V122I variant, cardiac imaging, biomarkers, and clinical evaluation may be useful alongside selected tissue biopsy.

Larger, multicenter studies, including studies that follow people over time, are needed to determine how well carpal tunnel biopsy may help detect ATTR-CM early across diverse populations and to develop more reliable screening criteria.

“Our negative findings with the largest studied African American population to date underscore the importance of further investigation to refine selection criteria, standardize sampling, and clarify the role of [carpal tunnel] biopsy in early detection of ATTR-CM,” the researchers wrote.