'With Vyndamax reimbursed, Korea moves toward better ATTR-CM management'

“Early diagnosis is crucial for treating transthyretin amyloid cardiomyopathy (ATTR-CM). The longer treatment is delayed, the harder it becomes to reverse the amyloid already deposited in the heart. That’s why early detection and timely intervention are essential.”

ATTR-CM is caused by the destabilization of the transthyretin (TTR) protein, which is normally produced in the body. When TTR becomes unstable, it accumulates abnormally in the heart, leading to impaired heart function. If not treated early, it can progress to heart failure and sudden cardiac death.

For a long time, ATTR-CM went largely undiagnosed because even when doctors identified it, treatment options were limited. Although Vyndamax (tafamidis), a treatment for ATTR-CM, was introduced in Korea in 2020, it remained unreimbursed for nearly four years, making it financially inaccessible to most patients.

In March, Vyndamax was finally included under insurance coverage, significantly improving treatment access. Korea Biomedical Review spoke with Professor Kim Da-rae from the Department of Cardiology at Samsung Medical Center about how the reimbursement will impact patient care and what steps are still needed to enhance the treatment environment.

Q: Although Vyndamax was approved more than four years ago, ATTR-CM remains relatively unknown. How is it diagnosed?

A: ATTR-CM presents with symptoms similar to common heart failure and often overlaps with other chronic conditions frequently seen in older adults. Because of this, the disease often goes unrecognized—so clinical suspicion is the first and most important step toward diagnosis.

Diagnosis requires several stages of testing, but in recent years, noninvasive techniques have made it possible to confirm the disease without biopsies. If electrocardiograms or echocardiograms suggest ATTR-CM and primary (AL) amyloidosis is ruled out, nuclear medicine imaging can be used for confirmation. If monoclonal immunoglobulin abnormalities appear in blood tests, a biopsy may be required to identify the subtype.

The most critical step is to suspect the disease in the first place. Signs such as unexplained left ventricular thickening, heart failure with preserved ejection fraction (HFpEF), arrhythmias like atrial fibrillation, or red flags like bilateral carpal tunnel syndrome, spinal stenosis, or autonomic dysfunction in elderly patients should raise suspicion.

Q: What makes diagnosis particularly difficult?

A: Many patients with ATTR-CM are over 70 and already have chronic conditions like hypertension, diabetes, or atherosclerosis. As a result, symptoms like fatigue or shortness of breath can be misattributed to those pre-existing conditions.

Nuclear imaging is also relatively new, and there’s a delay in getting a diagnosis through this route. Studies show patients often see five or more doctors before receiving a correct diagnosis, and fewer than half are diagnosed within six months of symptom onset. Even when echocardiography shows heart wall thickening, it can be mistaken for other conditions like hypertensive cardiomyopathy, aortic stenosis, or hypertrophic cardiomyopathy.

The disease may also affect organs beyond the heart, including the kidneys, nerves, GI tract, and musculoskeletal system, which complicates diagnosis without a multidisciplinary approach.

That’s why more hospitals are establishing specialized amyloid centers that bring together cardiology, nuclear medicine, pathology, neurology, and genetics. ATTR-CM diagnosis and care can't be managed by one department alone—collaborative care is essential.

As a progressive disease, ATTR-CM requires long-term management. Establishing comprehensive amyloid centers is key to maintaining patients' quality of life.

Q: Vyndamax was approved but largely unused due to its high cost. What’s changed since reimbursement?

A: Patients who have consistently taken Vyndamax show slower disease progression. Those who began treatment early—particularly in NYHA class II or below—have shown better quality of life and preserved functional status.

The approval of Vyndamax was a turning point—it was the first meaningful treatment for ATTR-CM. Before insurance coverage, patients and their families were often forced to abandon treatment due to its unaffordable cost.

Since March, insurance reimbursement has greatly improved access. Patient organizations welcomed the news, and this has also motivated healthcare providers to identify undiagnosed cases more proactively.

Q: Are there still limitations despite reimbursement?

A: Unfortunately, Korea’s reimbursement criteria still require a left ventricular wall thickness of at least 12 mm, as used in the ATTR-ACT clinical trial. This threshold was necessary for the study design but doesn't reflect the full range of patients who could benefit from treatment.

In real-world clinical settings, patients diagnosed early often have wall thickness below 12 mm, and starting treatment earlier may result in better outcomes. It’s frustrating that these patients are excluded based on arbitrary numbers.

In East Asian populations, especially among Korean women who tend to be smaller, even pathologic thickening might not reach the 12 mm threshold. Interpretation should consider body size rather than relying solely on absolute measurements.

What we urgently need is a national patient database. Right now, ATTR-CM cases are managed sporadically at university hospitals, making it difficult to coordinate registries, follow-ups, trials, or genetic studies.

A national amyloidosis center of excellence and a standardized Korean ATTR-CM cohort would enable better research and policy development—including more appropriate reimbursement standards, support for early diagnosis, and better access to treatment.

Q: In the end, early diagnosis seems to be the key to optimizing treatment. What message would you share with healthcare providers?

A: Primary care physicians are the first line of defense. When heart failure symptoms or lab abnormalities appear, even subtle clues should raise suspicion for ATTR-CM.

Instead of seeing it as a rare disease, doctors should look closely at older patients with unexplained heart issues. Recognizing the signs early can dramatically alter the course of the disease. If ATTR-CM is suspected, referral to a specialized amyloid center is strongly recommended.