Cleveland Clinic researchers identified amyloid deposits in 10.2 percent of patients undergoing carpal tunnel release surgery, suggesting biopsies of hand tissue could be an early signal of life-threatening cardiac amyloidosis.
The study, published online in the Journal of American College of Cardiology, contained wide inclusion criteria; all men in their 50s or older and all women in their 60s or older were eligible unless they had known amyloidosis or carpal tunnel syndrome considered to be from trauma or arthritis.
As the authors of an accompanying editorial noted, cardiac amyloidosis is being recognized as a more common form of cardiomyopathy than previously thought, and one that is now treatable given recent innovations. That has changed the attitude surrounding it from “therapeutic nihilism”—“Why diagnose what you can’t treat?”—to a more optimistic approach, according to Matthew S. Maurer, MD, and Frederick L. Ruberg, MD.
“Recent advances have dramatically altered the therapeutic landscape, rendering systemic amyloidosis with cardiac involvement a treatable disease, affording patients an array of therapeutic options,” they wrote. “It is clear that early recognition of amyloidosis is critical because current treatment strategies suppress precursor protein production or stabilize the protein preventing misfolding, but do not directly target existing amyloid deposits.”
Observing that carpal tunnel syndrome often precedes cardiac disease, lead author Brett W. Sperry, MD, and colleagues performed biopsies of tenosynovial tissue taken from 98 patients who underwent the hand surgery.
Upon Congo red staining, amyloid deposits were found in 10.2 percent of the patients, who were 68 years old on average and 51 percent male in the overall cohort. Mass spectrometry in the amyloid patients identified seven of them as having transthyretin amyloidosis (ATTR), two as having light-chain amyloidosis (AL) and one as having an unspecified subtype, although ATTR was suspected.
After sending these patients for further cardiac evaluation, clinicians found two of them already had cardiac amyloidosis, leading to changes in their medications.
“A third patient had a mutation in the TTR gene, which leads to a progressive polyneuropathy, and was also treated with disease-modifying therapy,” Sperry et al. noted. “… These findings point to the importance of recognizing idiopathic carpal tunnel syndrome as a possible predictor for amyloid heart disease, and the opportunity for incorporating tenosynovial tissue biopsy for early detection and diagnosis of amyloidosis in the perioperative workflow.”
The researchers said AL progresses much more rapidly than ATTR once it affects the heart, making it even more important to catch that disease subtype early and initiate proper therapy.
In fact, the results of this study and other emerging evidence around cardiac amyloidosis led to a change in protocol at the Cleveland Clinic surgery centers for carpal tunnel release patients, according to Sperry and colleagues.
If a man older than 50 or a woman older than 60 has bilateral carpal tunnel symptoms or a prior carpal tunnel release, the protocol suggests they receive a tissue biopsy with Congo red (Thioflavin-S). Similarly, a tissue biopsy should be performed if a patient either meets the age criteria or has bilateral symptoms/prior release surgery, plus at least one of the following: spinal stenosis, biceps tendon rupture, history of atrial fibrillation or flutter, a pacemaker, congestive heart failure or a family history of ATTR.
“If Congo red staining is positive, prompt typing with mass spectrometry and referral to an amyloidosis specialist is recommended,” Sperry and coauthors recommended. “We believe that the low cost of screening patients for amyloidosis at the time of carpal tunnel release surgery may avert the expense of progressive heart failure care in patients diagnosed early.”
One limitation of the study is its low number of black participants—important considering that “3 percent to 4 percent of African Americans in the United States carry the V122I TTR gene mutation, which is a known cause of hereditary cardiac amyloidosis,” according to the authors.
Maurer and Ruberg said the study justifies larger screening efforts for cardiac amyloidosis.
“It remains to be determined which screening methodology will prove the best approach, but given the emerging nature of amyloidosis, a screening algorithm will likely be incorporated into everyday clinical practice in the near future,” they wrote.
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.