Study suggests doctors test hATTR patients for nerve damage
Researchers say gaps show need for standardized assessment
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People with hereditary transthyretin amyloidosis (hATTR) should be checked for polyneuropathy (damage to multiple nerves) in addition to cardiomyopathy (heart damage), a study in the U.S. suggested.
While all hATTR patients in the study had a diagnosis code for polyneuropathy, only about one-third had undergone specialized testing that confirmed nerve damage. The researchers said the findings “highlight the gap between administrative coding and clinical documentation and support standardized neurological assessment in hATTR.”
The study, “Polyneuropathy Assessment and Treatment Patterns in Patients with Hereditary Transthyretin Amyloidosis,” was published in Cardiology and Therapy.
In hATTR, mutations in the TTR gene cause transthyretin to misfold and accumulate as toxic amyloid deposits in tissues. When these accumulate mainly in the nerves outside the brain and spinal cord, the disease is classified as hATTR with polyneuropathy (hATTR-PN); when they tend to build in the heart, it is called hATTR with cardiomyopathy (hATTR-CM).
A particular TTR mutation, V142I, is commonly linked to cardiomyopathy, which weakens the heart muscles and their ability to pump blood throughout the body. It is the most common mutation causing hATTR in the U.S., particularly among African Americans. Yet while people carrying V142I may have both cardiomyopathy and polyneuropathy, the latter may be overlooked.
Diagnosis codes vs. medical records
The researchers wanted to determine how often a diagnosis code for polyneuropathy in hATTR patients was supported by medical records and whether the strength of that evidence guided treatment.
They reviewed the medical records of 54 people seen at Medstar Georgetown University Hospital in Washington who had international diagnosis codes for both hATTR and polyneuropathy. Their median age was 77, and more than half (64.8%) were men. Most were non-Hispanic Black (90.7%) and carried the V142I mutation (87%).
Heart involvement was confirmed in 51 patients (94.4%), “consistent with the expected cardiac-predominant [clinical profile] of V142I,” the researchers wrote.
In contrast, 18 patients (33%) had polyneuropathy confirmed by electromyogram, a test that measures the electrical activity in muscles and nerve cells. About one-quarter (25.9%) had a doctor document polyneuropathy without an electromyogram; 20.4% had symptoms suggesting nerve damage but no confirmation, and the remaining 20.4% had too little information in their medical records to determine whether they had polyneuropathy.
Most patients (79.6%) had confirmed or suspected polyneuropathy based on available documentation.
“In this [group] of patients with hereditary ATTR, primarily V142I, selected for a coded diagnosis of polyneuropathy, most had documented clinical support for that diagnosis, though the strength and quality of that support varied widely,” the researchers wrote. However, they noted, “concern for polyneuropathy marks where clinical reasoning should begin and calls for a standardized assessment protocol.”
Of the 42 patients eligible for a TTR stabilizer therapy, which prevents TTR from becoming unstable, 40 (95.2%) received one. Most of these received tafamidis, approved as Vyndamax in the U.S. for ATTR-CM, both hereditary or not (wild-type).
Sixteen patients (29.6%) received a gene silencer therapy, which reduces production of abnormal TTR. This type of therapy includes Onpattro (patisiran), Amvuttra (vutrisiran), and Wainua (eplontersen). Eleven patients (20.4%) received both.
Treatment with gene silencers was more common when the polyneuropathy diagnosis was better documented. Half of the patients with abnormal electromyogram results received a gene silencer, compared with 18.2% of those with symptoms alone. Neurology consultations and electromyograms were also more common among patients whose records supported polyneuropathy.
Three patients had no confirmed heart involvement. All received gene silencers rather than TTR stabilizers, which was consistent with their disease mainly affecting the nerves rather than the heart. The study period predated the 2025 approval of Amvuttra for ATTR-CM, so the gene silencers used in this study were intended specifically for polyneuropathy, the researchers noted.
The study shows that a diagnosis code alone does not necessarily prove that a patient has polyneuropathy.
“As gene silencers become approved for cardiomyopathy and no longer require neurological documentation for access, the incentive to perform that assessment may fall, although its clinical relevance remains,” the researchers wrote. “Recognizing the full neurological burden of transthyretin amyloidosis, across hereditary variants and in wild-type disease as well, will require that assessment continue on clinical grounds.”
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