Diagnosis & Staging

  • A diagnosis of ATTRwt-CM requires 3 key steps:
    1. Suspicion of cardiac amyloidosis (clinical finding, ultrasonic cardiogram, cardiac MRI)
    2. Diagnosis of cardiac amyloidosis (PYP, M protein, Congo red staining)
    3. Confirmation of the type of cardiac amyloidosis (immunostaining, genetic test, bone-marrow examination)
  • Endocardial biopsy has been the gold standard for diagnosing ATTR-CM because of its high sensitivity and specificity—it is currently a standard for diagnosis through the Japan Cardiology Society guidelines but may become less common due to advances in imaging [1]
  • Bone scintigraphy has revolutionized the diagnosis and recognition of ATTR-CM, being extremely sensitive to detect TTR amyloid deposits in the heart, even prior to clinical manifestations or abnormal findings on CMR or ECHO [2]
  • Currently, there is no universal system of staging ATTR amyloidosis; the following are both used [3,4]:
    • Mayo Clinic model: soluble cardiac biomarkers are used to stratify ATTRwt patients into three distinct risk groups based on troponin T and NT-proBNP
    • NAC (UK) model: replaces troponin T with eGFR, while keeping NT-proBNP at the same Mayo Clinic model threshold
      • The NAC criteria are based on biomarkers of cardiomyopathy (NT-proBNP) and nephropathy (eGFR) and can determine disease severity
  • Many HCP specialties may be involved in diagnosis of ATTRwt, but cardiologists are primarily the (confirming) diagnosing physicians
  • Upon diagnosis, patients (and caregivers) are oftentimes in shock and overwhelmed by the severity of the diagnosis
  • Some patients are relieved to finally have received a diagnosis and to know what they are dealing with
  • Some patients feel like they are not given enough information about the disease and don’t really understand the implications.  If they have no symptoms, they may not be too worried about it at first.
  • Shock, devastation, and fear. Upon diagnosis, patients research ATTR and learn about poor survival rates and are in complete shock, and sometimes in despair about their outlook
  • “What is going to happen to me?” After receiving a diagnosis, some patients may be confused about what to expect and what to do, especially if their HCP does not provide enough information for them to fully understand the condition and how it progresses. When they hear that there is no cure, patients may worry that they could die the next day, or they may feel that they don’t need to think about it at all. 
  1. ALXN: 210201_ALXN2060_Diagnostic summary.​​
  2. Kitaoka H, et al. JCS 2020 guideline on diagnosis and treatment of cardiac amyloidosis. Circ J. 2020. 84(9), 1610-1671. https://doi.org/10.1253/circj.CJ-20-0110.​
  3. ALXN: ALXN2060 Differentiation workshop. Citing: Rapezzi, JACC Imaging. 2011:659-70 & Hutt, Eur Heart J. 2014;15:1289-1298.​
  4. ALXN: Acoramidis ​for the Treatment of ATTR-CM: Training Deck. November 22, 2021. 34_Acoradmidis Training Deck_22Nov21 FINAL. Citing: Gillmore JD, Damy T, Fontana M, Hutchinson M, Lachmann HJ, Martinez-Naharro A, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018;39(30):2799-806.​
  5. Garcia-Pavia P, et al. Diagnosis and Treatment of Cardiac Amyloidosis: A Position Statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42(16):1554-1568. DOI: https://doi.org/10.1093/eurheartj/ehab072.​
  6. Lousada, et al. Amyloidosis Research Consortium Cardiac Amyloidosis Survey: Results from Patients with AL and ATTR Amyloidosis and Their Caregivers. Presented at the XVIth International Symposium on Amyloidosis. 2018. Kumamoto, Japan.