Ronald Witteles, MD, is a professor of cardiovascular medicine at Stanford University and co-director of the Stanford Amyloid Center and the Stanford Multidisciplinary Sarcoidosis Program

Ronald Witteles, MD

Approaches to Treatment Selection in ATTR-CM

The panel discusses how clinicians approach selecting disease-modifying therapy once ATTR-CM is confirmed. They emphasize that treatment choice is individualized and begins with assessing disease stage and overall cardiac function. If a patient is extremely advanced and unlikely to benefit, the conversation may shift toward goals of care. For most patients, the next consideration is whether neuropathy is present, particularly in hereditary variants, where a silencer such as vutrisiran may be preferred because it addresses both cardiac and neurologic manifestations.

Cost and access are also significant factors, and the panel notes that insurance coverage may determine which agent is feasible. Finally, patient preference plays an important role: some prefer a daily oral therapy, while others favor a less frequent injection to avoid managing multiple medications. The experts emphasize shared decision-making, stating that the key principle is to initiate approved therapy, as the only clearly wrong choice is receiving no treatment.

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The panel discusses how clinicians approach selecting disease-modifying therapy once ATTR-CM is confirmed. They emphasize that treatment choice is individualized and begins with assessing disease stage and overall cardiac function. If a patient is extremely advanced and unlikely to benefit, the conversation may shift toward goals of care. For most patients, the next consideration is whether neuropathy is present, particularly in hereditary variants, where a silencer such as vutrisiran may be preferred because it addresses both cardiac and neurologic manifestations.
Cost and access are also significant factors, and the panel notes that insurance coverage may determine which agent is feasible. Finally, patient preference plays an important role: some prefer a daily oral therapy, while others favor a less frequent injection to avoid managing multiple medications. The experts emphasize shared decision-making, stating that the key principle is to initiate approved therapy, as the only clearly wrong choice is receiving no treatment.


Key Takeaways from AHA 2025 Scientific Sessions

The panel reviews key insights related to transthyretin amyloidosis therapies discussed at the AHA 2025 Scientific Sessions. They emphasize that the new data presented are largely “on the margins,” reinforcing findings already established in pivotal trials: the major disease-modifying therapies for ATTR-CM are effective and safe, and the most important mistake is not initiating any therapy once the diagnosis is confirmed. One topic highlighted from recent analyses is atrial arrhythmias in ATTR-CM. The panel notes that while patients with atrial arrhythmias often represent more advanced disease, the presence of arrhythmias does not diminish the efficacy of available treatments. The discussion also touches on renal function data, where improvements are believed to reflect better heart failure status and reduced diuretic need, rather than a direct renal effect of therapy. Overall, the panel emphasizes individualized management and careful clinical interpretation rather than one-size-fits-all assumptions.

The Role of Vitamin Supplementation in Patients Receiving ATTR-CM Therapies

The panel discusses the importance of monitoring and supporting vitamin status in patients receiving ATTR-CM therapies, particularly those on transthyretin silencers that reduce hepatic production of TTR. Because TTR transports retinol-binding protein, lowering TTR levels can affect vitamin A transport. The clinicians explain that when silencing therapy is used, patients should receive vitamin A supplementation, but at the appropriate physiologic dose, not excess replacement. They caution that high-dose vitamin A can be harmful and stress the need to avoid overcorrection, particularly in older adults.

The panel also notes that education is essential, as patients may assume all supplements are beneficial or may take additional over-the-counter vitamins without disclosing them. Clear counseling helps ensure patients understand what to take, what to avoid, and why. Overall, the discussion emphasizes thoughtful, monitored supplementation as part of comprehensive care, rather than a standalone intervention.

The panel discusses the importance of monitoring and supporting vitamin status in patients receiving ATTR-CM therapies, particularly those on transthyretin silencers that reduce hepatic production of TTR. Because TTR transports retinol-binding protein, lowering TTR levels can affect vitamin A transport. The clinicians explain that when silencing therapy is used, patients should receive vitamin A supplementation, but at the appropriate physiologic dose, not excess replacement. They caution that high-dose vitamin A can be harmful and stress the need to avoid overcorrection, particularly in older adults.
The panel also notes that education is essential, as patients may assume all supplements are beneficial or may take additional over-the-counter vitamins without disclosing them. Clear counseling helps ensure patients understand what to take, what to avoid, and why. Overall, the discussion emphasizes thoughtful, monitored supplementation as part of comprehensive care, rather than a standalone intervention.


Efficacy and Safety of Transthyretin Stabilizers in ATTR-CM

The panel discusses the role of transthyretin (TTR) stabilizers in the management of ATTR-CM, focusing on tafamidis and acoramidis. They explain that both agents work by stabilizing the TTR tetramer to prevent dissociation and subsequent amyloid fibril formation. Tafamidis is highlighted as the first approved stabilizer with demonstrated benefit in reducing morbidity and mortality in ATTR-CM. Clinicians note that many patients experience stable disease over time with tafamidis, and its favorable tolerability profile, with minimal need for laboratory monitoring, is especially helpful for older adults seeking consistent, manageable treatment.

The discussion then shifts to acoramidis, which is designed to strongly stabilize the TTR protein. The panel describes clinical impressions that acoramidis has shown promising results in trials and represents an important emerging option. They emphasize that having multiple stabilizers broadens therapeutic choice and may help align treatment selection with patient needs and disease characteristics, reinforcing the importance of earlier diagnosis and appropriate therapy initiation.

The panel discusses the role of transthyretin (TTR) stabilizers in the management of ATTR-CM, focusing on tafamidis and acoramidis. They explain that both agents work by stabilizing the TTR tetramer to prevent dissociation and subsequent amyloid fibril formation. Tafamidis is highlighted as the first approved stabilizer with demonstrated benefit in reducing morbidity and mortality in ATTR-CM. Clinicians note that many patients experience stable disease over time with tafamidis, and its favorable tolerability profile, with minimal need for laboratory monitoring, is especially helpful for older adults seeking consistent, manageable treatment.
The discussion then shifts to acoramidis, which is designed to strongly stabilize the TTR protein. The panel describes clinical impressions that acoramidis has shown promising results in trials and represents an important emerging option. They emphasize that having multiple stabilizers broadens therapeutic choice and may help align treatment selection with patient needs and disease characteristics, reinforcing the importance of earlier diagnosis and appropriate therapy initiation.


Ronald Witteles, MD

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