Most ATTR patients in China have symptoms of 2 amyloidosis types
Analysis finds diagnostic delays – and both nerve and heart problems
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Most people with transthyretin amyloidosis (ATTR) in China have a hereditary form of the rare disease and experience symptoms of both ATTR with polyneuropathy (ATTR-PN) — marked by nerve problems and muscle weakness — and ATTR cardiomyopathy (ATTR-CM), characterized by heart damage that can lead to heart failure.
Those are among the key findings of a large real-world study in the Asian nation, which showed that nearly three-quarters of patients with the genetic form of the disease had a “mixed” profile, with signs of both types, according to the researchers.
Moreover, the team found that most ATTR patients had waited, on average, more than three years from their first disease manifestation for a diagnosis. About half then received ATTR-targeted treatment, generally starting within about a month and a half, the data showed. However, the team noted that many individuals remained untreated despite having a diagnosis.
“Chinese patients with ATTR amyloidosis demonstrated high clinical [variability], delays in diagnosis and treatment initiation, poor disease outcomes, and considerable clinical burden,” the researchers wrote.
Their analysis further “reveals a critical pattern” in terms of delayed diagnoses, the scientists noted: Most patients first experienced nerve-related symptoms, but then also showed heart problems at diagnosis.
“This finding indicates disease progression before diagnosis and underscores the urgent need for multidisciplinary cooperation, notably between neurologists and cardiologists, in early disease identification and intervention,” the team wrote.
The study, “Characteristics, treatment patterns, and outcomes of patients with transthyretin amyloidosis: a large-scale, observational, retrospective study in China (OverTTuRe China),” was published in the Orphanet Journal of Rare Diseases.
ATTR develops when the transthyretin (TTR) protein — which acts like a delivery truck in the bloodstream — misfolds and forms toxic clumps, called amyloid deposits, that accumulate in tissues, causing damage. The disease can be hereditary (hATTR), caused by mutations in the TTR gene, or wild-type (wATTR), which develops with aging.
When amyloid deposits build up mainly in the nerves outside the brain and spinal cord, the disease is called ATTR-PN, a form that is usually hereditary. When these clumps accumulate mainly in the heart, it is called ATTR-CM, which is most often wild-type.
Increasing evidence shows that many people around the world have a mixed form of ATTR, with both nerve and heart involvement.
Because ATTR can affect different parts of the body and cause symptoms that overlap with other conditions, getting the right diagnosis can be difficult. Treatment options have also historically been limited, although therapies that stabilize TTR or reduce its production can now slow disease progression and improve outcomes.
Most Chinese patients wait over 3 years for ATTR diagnosis
Now, a team led by researchers at the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing sought to better understand the clinical characteristics, diagnosis, treatment, and disease burden of ATTR in the country.
To that end, the team analyzed 2013-2024 data from 218 Chinese patients who participated in OverTTuRe (NCT06355934), an international observational study of adults with ATTR. Of the participants from China, about 45% had a family history of ATTR and slightly more than 70% were men.
Nearly all of these patients (96%) had hATTR; one individual had confirmed wtATTR. The remaining participants had no genetic results available.
A mixed profile was the most common presentation among patients, seen in 72%, the researchers noted. About 19% had ATTR-CM and approximately 9% had ATTR-PN. Among those with hATTR, 73% had a mixed profile, 18% had ATTR-CM, and 9% had ATTR-PN.
The mean age at disease onset was 53.7 years, but was lowest among those with hATTR-PN, averaging 42.8 years. Numbness was the most common initial manifestation, seen in more than one-quarter of patients, followed by muscle weakness and chronic diarrhea, each affecting about 14%.
The researchers noted that patients waited a mean of 3.4 years from the onset of their first symptom to diagnosis. The diagnostic delay rose to 3.8 years for those with hereditary mixed disease. At the time of diagnosis, leg swelling and muscle weakness were the most common symptoms, affecting 31%, while shortness of breath was seen among 23%.
Because leg swelling and shortness of breath can be symptoms of heart disease, these results indicate that “while most patients started with [nerve damage-related] symptoms, the majority presented with [heart damage] at diagnosis,” the team wrote. According to the scientists, that finding suggests the disease progressed during the diagnostic lag.
Main ATTR type diagnosed in a single person in this study
The researchers pointed to several possible reasons for delayed or missed diagnoses, including early nerve-related symptoms being mistaken for more common conditions. Low disease awareness and limited access to specialized testing were other likely factors cited by the team.
wtATTR appeared especially likely to be missed in China: Although it accounts for an estimated 70%-90% of ATTR-CM in certain regions, it was diagnosed here in a single person — 0.5% of patients, the researchers noted.
Just about one-half of participants had data from an echocardiogram, an ultrasound of the heart, available at diagnosis, the researchers also noted. Fewer than 45% of patients had undergone a biopsy, in which a small tissue sample is examined under a microscope for amyloid deposits. About 25% underwent PYP scintigraphy, an imaging test that can detect amyloid deposits in the heart.
Altogether, nearly 60% of patients received an ATTR treatment — given at a median of 45 days, or about 1.5 months, after diagnosis. Vyndamax (tafamidis), an approved ATTR-CM therapy, was the most commonly used treatment, given to 83% of participants. Diflunisal, an oral anti-inflammatory medication shown to stabilize TTR, was used off-label in 8% of patients. At the time of the study, Wainua (eplontersen) had recently been approved for hATTR-PN but was not yet commercially available.
Our findings highlight the urgent need to enhance [ATTR] awareness, streamline the diagnostic pathway, and improve access to treatment in China to alleviate the considerable burden imposed by the disease on patients.
Despite treatment, however, disease burden remained “substantial,” the researchers noted, especially when compared with data from the U.S. and other international patient groups.
Over more than 1.5 years, available follow-up data showed that slightly more than half of participants developed a new disease manifestation, and 39% were hospitalized at least once. About 8% of patients died, the data showed.
Those with hereditary mixed disease tended to have worse outcomes than those with hATTR-PN and hATTR-CM, the researchers noted.
“This is the largest real-world study of Chinese patients with ATTR amyloidosis conducted to date,” the team wrote. “Our findings highlight the urgent need to enhance [ATTR] awareness, streamline the diagnostic pathway, and improve access to treatment in China to alleviate the considerable burden imposed by the disease on patients.”
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