Doctor pushes for early diagnosis and insurance benefit for rare heart disease ATTR-CM

Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a progressive, rare disease in which the protein transthyretin (TTR), which is normally produced in the body, becomes unstable and accumulates abnormally in the heart, causing dysfunction of the heart muscle. If not treated promptly, the disease can lead to heart failure and sudden cardiac death due to amyloid buildup.

The problem is that although ATTR-CM can be diagnosed through nuclear medicine tests, low awareness of the disease and non-specific symptoms make early diagnosis difficult and push misdiagnosis rates high.

Recently, ATTR-CM was designated as a "rare disease subject to national management," allowing patients to receive special benefits for its treatment.

However, there is still much room for improvement, as Vyndamax (tafamidis), the only drug licensed for the treatment of ATTR-CM, has remained a non-reimbursed drug for four years.

Korea Biomedical Review interviewed Professor Son Jung-woo of the Department of Cardiology at Wonju Severance Christian Hospital, a member of the Insurance Committee of the Korean Society of Heart Failure, to listen to the recent changes in the ATTR-CM treatment landscape and the challenges faced to improve the treatment environment.

Question: We are curious to know how the diagnosis and treatment of ATTR-CM have changed before and after the rare disease designation.

Answer: To answer this, it's important to understand how it differs from traditional amyloidosis. Traditional cardiac amyloidosis or amyloidosis can be diagnosed through a biopsy, and this diagnosis is subject to a special calculation (for insurance benefits). ATTR-CM, on the other hand, is the only type of amyloidosis that can be diagnosed through a bone scan (nuclear scintigraphy). ATTR-CM can be suspected if the bone scan shows strong uptake in the heart. However, this excludes patients diagnosed by blood tests with primary (AL or Amyloid Light chain) amyloidosis.

At the time, ATTR-CM was not eligible for reimbursement; patients had to be diagnosed with amyloidosis through biopsy. In particular, there are two types of ATTR-CM: "genotypic" and "normal. Genotypic can be diagnosed through genetic testing, but the normal type must be biopsied. In addition to the limited number of hospitals that can perform cardiac biopsies, ATTR-CM patients are usually elderly, and it is difficult to get a diagnosis because elderly patients may not be comfortable with cardiac biopsies.

However, criteria have recently been established to diagnose ATTR-CM without biopsy, meaning that patients suspected of having ATTR-CM can receive a special exception to the calculation even if they are diagnosed with ATTR-CM through a bone scan test rather than a biopsy. However, only a rare disease center can assign a special calculation code because ATTR-CM is included in rare diseases.

Q: Is there any reason why ATTR-CM is difficult to diagnose early?

A: ATTR-CM is less likely to be diagnosed through biopsy than primary (AL) amyloidosis. A biopsy mostly confirms AL amyloidosis because a large amount of amyloid causes it. However, structural changes cause ATTR (transthyretin amyloid), so symptoms take a long time to appear. In addition, because ATTR-CM is a disease with systemic symptoms, it is difficult to diagnose in the early stages because it has "non-specific" symptoms, including heart failure, spinal stenosis, and carpal tunnel syndrome, even after it has progressed.

Therefore, it is important for healthcare providers to always consider this condition. Because ATTR-CM mainly affects older adults, it was often dismissed as a symptom of aging until there was a cure. However, after a cure occurred, doctors began actively seeking out patients. The Korean Society of Heart Failure is also promoting ATTR-CM and sharing diagnosis cases.

Q: Why is the early diagnosis and treatment of ATTR-CM so important?

A: ATTR-CM patients usually die two to three years after diagnosis. Since 2019, Wonju Severance Christian Hospital has been working to find ATTR-CM patients after introducing equipment for bone scans, genetic tests, and heart tests, and has diagnosed 10 patients so far. Unfortunately, 75 percent of these patients have died. If these patients had been identified earlier and treated sooner, their symptoms would have been less severe, and their mortality rate would have been much lower.

Q: The ATTR-CM has indeed become eligible for special calculation for insurance benefits, alleviating some of the burden on patients. However, it will likely be of little actual help for patients as long as the drug remains non-reimbursed, isn’t it?

A: Right. Although treatments with different mechanisms are being developed, tafamidis, which prevents amyloid accumulation, is currently the best option for treating ATTR-CM. Not only is tafamidis recommended for treating ATTR-CM in national and international heart failure guidelines, but the guidelines also recommend that patients with heart failure with preserved ejection fraction (HFpEF) be screened for ATTR-CM so that the drug can be used early and appropriately.

Currently, therapies using gene-scissoring technology, siRNA therapies to prevent the protein from being produced, and antibodies to remove deposited amyloid are being developed in clinical trials. Still, they are expected to be at least four to five years away from commercialization, making treatment with tafamidis important. The heart failure society has submitted its opinion to the government to inform its discussions on reimbursement of tafamidis. It is organizing a separate session at a related society event to communicate the need for reimbursement for patients with ATTR-CM.

In the real world, patients with ATTR-CM are often hospitalized repeatedly for shortness of breath or leg swelling and often die. It is heartbreaking to think that these patients could have lived longer and more comfortably if the treatment was available. As the government expands innovative new drug recognition and economic evaluation special system, I hope it will flexibly apply the criteria for treatment. Pharmaceutical companies also need to work with the government to find a compromise.

Unlike in the past, we have advanced diagnostic technology, and it is very sad to see patients dying without receiving the correct treatment, even though there are approved drugs in Korea. I hope the treatment will be covered as soon as possible so that patients can receive treatment, improve their quality of life, and live longer.