Path to Diagnosis/Misdiagnosis

Delayed Diagnosis:​

  • The diagnostic process for ATTRwt-CM may be long and difficult, ranging from months to 10(+) years​.
    • In a targeted literature review, the weighted means of reported mean and median diagnostic delays were 6.1 and 3.4 years for ATTRwt-CM. [2]​
  • ATTRwt-CM is now diagnosed more than twice as frequently as hereditary ATTR-CM—presumably reflecting the remarkable sensitivity and increasingly widespread use of cardiac magnetic resonance imaging and bone scintigraphy, which in turn have fueled increased awareness of the condition among cardiologists. [6​]
    • However, a recent report (n=1,069 ATTRwt patients) shows that median time from symptom onset to ATTRwt diagnosis did not change over the past 5 years (>60 months from 2015-2019). [8]​
    • For comparison: a smaller study (n=122 ATTRwt patients) in France found significantly shorter delays after 2012, averaging ~5-12 months between when cardiac amyloidosis was first suspected and diagnosis. [3]​

Misdiagnosis:​

  • Patients are also often misdiagnosed, and may even be given inappropriate or even counter-indicated treatments​.
  • Up to ~40% of ATTRwt patients reported initially being misdiagnosed, and 75% of misdiagnosed patients received treatment for the misdiagnosed condition. [4]​
  • In a larger US cohort, 63% of patients also reported having to see 2 or more cardiologists before diagnosis. [5]
  • >99% of US cardiologists believe that patients with cardiac amyloidosis (CA) experience diagnostic delays primarily due to low awareness of CA and diagnostic algorithm / tests[1]
  • Patients with gradual symptom onset may initially dismiss symptoms but will eventually get to a point where they recognize that something may be wrong and seek medical attention
  • Patients and caregivers may become frustrated and fearful due to their long search for answers and perceived “missed” opportunities for earlier intervention
  • Is something wrong with me? Patients may attribute ATTRwt symptoms to the “regular” aging process
  • What is wrong with me? Patients get no answers that seem right about what’s wrong with them and why they are getting worse
  • Poisoned by the wrong therapy. Before correct diagnosis, patients (esp. with cardiac involvement) may receive therapies counter-indicated for ATTRwt
  • Time to Diagnosis = Time to Live! Early diagnosis significantly enhances outcomes
 
  1. Castano, et al. Cardiac Amyloidosis: Current Insights from Patients and Cardiologists Journeying Together. Journal of Cardiac Failure Vol. 25 No. 8S August 2019.
  2. Rozenbaum MH, Large S, Bhambri R, et al. Impact of Delayed Diagnosis and Misdiagnosis for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM): A Targeted Literature Review. Cardiol Ther. 2021;10(1):141-159. doi:10.1007/s40119-021-00219-5.
  3. Dang D, et al. Gateway and journey of patients with cardiac amyloidosis. ESC Heart Failure. Volume: 7, Issue: 5, Pages: 2418-2430, First published: 26 June 2020, DOI: (10.1002/ehf2.12793).
  4. Lousada, et al. Amyloidosis Research Consortium Cardiac Amyloidosis Survey: Results from Patients with AL and ATTR Amyloidosis and Their Caregivers. Poster presented at the XVIth International Symposium on Amyloidosis; March 26-29, 2018; Kumamoto, Japan; Lousada, et al. Amyloidosis Research Consortium Cardiac Amyloidosis Survey: Results from Patients with AL and ATTR Amyloidosis and Their Caregivers. Poster presented at the 23rd annual Heart Failure Society of America; September 13-16, 2019; Philadelphia, PA.
  5. Unavailable
  6. Rozenbaum MH, Large S, Bhambri R, et al. Impact of Delayed Diagnosis and Misdiagnosis for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM): A Targeted Literature Review. Cardiol Ther. 2021;10(1):141-159. doi:10.1007/s40119-021-00219-5.
  7. Lane, T, et al. May 21, 2019. Natural History, Quality of Life, and Outcome in Cardiac Transthyretin Amyloidosis. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.038169.
  8. Nativi-Nicolau J, et al. Temporal Trends of Wild-Type Transthyretin Amyloid Cardiomyopathy in the Transthyretin Amyloidosis Outcomes Survey. J Am Coll Cardiol CardioOnc. 2021 Oct, 3 (4) 537–546. DOI: https://www.jacc.org/doi/10.1016/j.jaccao.2021.08.009.