Current & Future Treatment

  • Liver transplant is not an option for ATTRwt, and heart transplant is uncommon for ATTRwt due to generally advanced age of the patients—however, successful outcomes have been reported in selected younger patients [1]
  • ATTRwt-CM Tx involves both (i) disease modifying agents to treat the underlying condition and (ii) supportive care to manage cardiovascular complications [1,2]
Disease-modifying agents:
  • TTR stabilizers provide kinetic stabilization of TTR tetramer and inhibit the initiation of amyloid formation by preventing dissociation of the TTR tetramer into monomers; preventing TTR tetramer dissociation results in slowing progression of disease and preservation of function, which is also expected to translate to improved QoL
    • Pfizer’s Vyndaqel (tafamidis, approved 2019), a TTR stabilizer, is the first approved disease-modifying treatment for ATTRwt-CM in Japan [1]
    • TTR silencer Acoramidis (Eidos / Alexion) is currently being evaluated in a phase 3 randomized controlled studies in ATTR-CM and ATTR-PN
  • TTR Silencers are RNA molecules that inhibit the liver production of TTR by binding to the TTR mRNA, preventing its translation
    • TTR silencers (e.g., Vutrisiran and AKCEA-TTR-LRx [next-generation inotersen]) are currently being evaluated in phase 3 randomized controlled studies in patients with ATTRwt and ATTRv cardiac amyloidosis (CA)
Supportive care:
  • CA initially exhibits a clinical phenotype akin to heart failure with preserved ejection fraction due to other causes, but most well‐recognized anti‐HF drugs may be harmful due to CA’s unique pathology; therefore, HF therapy for CA is primarily based on correct titration of diuretics [3,4]
  • CA patients have various supraventricular and/or ventricular arrhythmia; HCPs should choose the therapy individually based on CA characteristics
  • Many ATTR‐CA patients at a high risk of conduction system disorders requiring cardiac pacing for symptomatic atrioventricular block or bradycardia
  • Common causes of death in patients with cardiac amyloidosis are a (rapidly) progressive heart failure and sudden cardiac death [3]
  • However, recent emergence of effective therapies that slow disease progression and improve clinical outcomes promises to render ATTR-CM a treatable disease [5]
  • Receiving a diagnosis of ATTR-CM does not guarantee that the patient will receive appropriate treatment, e.g., “[HCPs] prescribed Metoprolol and Lisinopril, and those are not appropriate drugs for amyloidosis”
  • Patients and caregivers feel frustrated by a lack of information from their HCPs, e.g., “his cardiologist admitted he didn’t know anything about it, either”
  • Patients and caregivers often feel helpless, which can also cause feelings of resignation and depression; “My husband is suffering. Much difficulty breathing and can’t walk. Coughing is extremely painful. I need help and feel hopeless. How do I change this endless situation of hospital admissions for everything?”
  • “There is nothing I can do.” Being told that you have a condition that will worsen and for which there is no cure available is extremely difficult to accept
  • A change in perspective; a positive outlook. Each patient must come to terms with how to live with their disease, which may be a resolution to make the most of what they have with the realization that although there is no cure, there are still things that patients can do to improve the way they live
  • This is beyond me. Local HCP refers patient to amyloidosis center of excellence 
  1. Kitaoka, et al. JCS 2020 Guidelines Dx Tx Cardiac Amyloidosis. Circ. J. 2020.
  2. Muchtar E, et al. J Intern Med. 2021;289:268-292.
  3. Yilmaz, A., Bauersachs, J., Bengel, F. et al. Diagnosis and treatment of cardiac amyloidosis: position statement of the German Cardiac Society (DGK). Clin Res Cardiol 110, 479–506 (2021).
  4. Yamamoto H, Yokochi T. Transthyretin cardiac amyloidosis: an update on diagnosis and treatment. ESC Heart Fail. 2019;6(6):1128-1139. doi:10.1002/ehf2.12518.
  5. Ruberg FL, et al. J Am Coll Cardiol. 2019;73:2872-2891.