Treatment with tafamidis showed potential to reduce amyloid accumulation in the hearts of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) but revealed no corresponding improvements in clinical symptoms, functional capacity or biomarker levels, according to a study published recently in the Journal of Nuclear Cardiology.
The results highlighted the complexity of managing ATTR-CM and suggested that tafamidis may stabilize disease progression rather than reverse its effects.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
‘We assessed 99mTc-PYP scintigraphy with SPECT/CT in ATTR-CM patients before and after tafamidis therapy,” study authors said. “Although no clinical benefits were observed, there was a significant reduction in myocardial accumulation of 99mTc-PYP after tafamidis administration.”
Read more about ATTR-CM therapies
The result was not statistically significant because of the study’s small sample size, the authors said, adding that larger studies involving a greater number of cases across multiple institutions are needed.
In the single-center prospective study, 14 patients with ATTR-CM were treated with 80 mg per day of tafamidis and underwent 99mTc-PYP scintigraphy before and one year after therapy. Imaging revealed a significant reduction in the left ventricle-to-whole chest ratio, a key measure of amyloid burden. The reduction was visually confirmed in representative cases, with high interrater reliability for imaging interpretation, underscoring the accuracy of SPECT/CT in tracking changes in deposition of myocardial amyloid.
Despite the imaging improvements, clinical outcomes remained unchanged. Five patients who underwent cardiopulmonary exercise testing showed no improvement in peak VO2, a measure of exercise capacity. Similarly, levels of NT-proBNP, a biomarker associated with the severity of heart failure, did not decrease during the study period.
The results aligned with earlier studies suggesting that while tafamidis stabilizes amyloid deposits, it may not reverse existing damage to cardiac tissues. The evidence pointed to tafamidis’s role in halting disease progression, although its effect on improving patients’ daily lives and cardiac function remains uncertain.
The study’s limitations, including its small sample size, single-center design and lack of a control group, prevented definitive conclusions about tafamidis’s therapeutic effects. The absence of statistically significant changes in clinical measures highlighted the need for larger multicenter trials to explore the relationship between imaging findings and functional outcomes.
The results underlined the importance of continued research to better understand the mechanisms by which tafamidis interacts with amyloid deposition in the heart. For patients, the study emphasized the need for ongoing monitoring and a multifaceted approach to managing ATTR-CM, addressing both the underlying disease and its broader effect on quality of life.
