Contents

Search

transthyretin cardiac amyloidosis; amyloid transthyretin cardiomyopathy (ATTR-CM)

Epidemiology: - occurs primarily in men > 60 years of age - may be > 10% in elderly men with preserved LVEF - hereditary cardiac amyloidosis with Val122Ile mutation in transthyretin gene present in 3.5% of blacks [2] Pathology: - occurs when misfolded transthyretin protein accumulates as amyloid fibrils in the heart, leading to heart failure & cardiac arrhythmias - in hereditary cardiac amyloidosis with Val122Ile mutation in transthyretin gene, end-organ damage other than cardiac is uncommon [2] Genetics: - can be inherited as an autosomal dominant trait - hereditary cardiac amyloidosis due to Val122Ile mutation in the transthyretin gene - deposition of wild-type transthyretin protein can occur Laboratory: 1) also see cardiac amyloidosis 2) biopsy - aspiration of abdominal fat pad (first line) - myocardial biopsy (last resort) 3) amyloid amyloid typing - Val122Ile mutation in transthyretin gene is most common variant in hereditary cardiac amyloidosis* * MGUS may co-occur with transthyretin cardiac amyloidosis [2] Special laboratory: - electrocardiography - echocardiography - see cardiac amyloidosis Radiology: - cardiac technetium-99m pyrophosphate scintigraphy diagnostic [2] Differential diagnosis: - AL amyloidosis Management: - tafamidis meglumine (Vyndaqel) [1] - subcutaneous inotersen (Tegsedi) 300 mg weekly - subcutaneous eplontersen (Wainua) 45 mg every 4 weeks (FDA-approved) - prior to tafamidis, treatment has been supportive - liver transplantation for severe disease [2]

Interactions

disease interactions

General

transthyretin amyloidosis; ATTR amyloidosis cardiac amyloidosis

References

  1. Maurer MS, Schwartz JH, Gundapaneni B et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 2018 Aug 27; PMID: 30145929 Free full text https://www.nejm.org/doi/10.1056/NEJMoa1805689 - Quarta CC, Solomon SD. Stabilizing transthyretin to treat ATTR cardiomyopathy. N Engl J Med 2018 Aug 27 PMID: 30145933 Free Article https://www.nejm.org/doi/10.1056/NEJMe18100
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 17. 18, 19. American College of Physicians, Philadelphia 1998, 2015, 2018, 2022.
  3. Shah KB, Mankad AK, Castano A et al Transthyretin Cardiac Amyloidosis in Black Americans. Circ Heart Fail. 2016 Jun;9(6):e002558. Review. PMID: 27188913 Free PMC Article
  4. Coelho T, Marques Jr W, Dasgupta NR et al Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. Published online September 28, 2023. PMID: 37768671 https://jamanetwork.com/journals/jama/fullarticle/2810248 - George J FDA Approves New Agent for Nerve Pain From Rare Inherited Disease. Eplontersen gets a nod for polyneuropathy from hereditary transthyretin-mediated amyloidosis. MedPage Today December 22, 2023 https://www.medpagetoday.com/neurology/generalneurology/108020