Studies Reporting on Survival in ATTR in Japan

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Notes: COD = cause of death; dx = diagnosis; LT = liver transplant
  • 6-minute walk test (6MWT), a performance-based test that evaluates an individual’s functional exercise capacity by measuring the distance walked in 6 minutes over a flat, hard surface​
ALXN: ATTR Amyloidosis: Epidemiology Dossier. Elissa Wilker & Shona Fang. September 2021. 18_ATTR Amyloidosis Epi Dossier. Citing:
  1. Yamada T, Takashio S, Arima Y, Nishi M, Morioka M, Hirakawa K, et al. Clinical characteristics and natural history of wild-type transthyretin amyloid cardiomyopathy in Japan. ESC Heart Fail. 2020;7(5):2829-37.
  2. Yamashita T, Ueda M, Nomura T, Okazaki T, Okada M, Tsuda Y, et al. Natural history and long-term effects of variant protein reduction in non-V30M ATTR amyloidosis. Neurology. 2019;93(16):714-6.
  3. Ohya Y, Okamoto S, Tasaki M, Ueda M, Jono H, Obayashi K, et al. Manifestations of transthyretin-related familial amyloidotic polyneuropathy: long-term follow-up of Japanese patients after liver transplantation. Surg Today. 2011;41(9):1211-8.

Tracking Disease Progression: Impact of Atrial Fibrillation

Prevalence and survival impact of atrial fibrillation in patients with transthyretin cardiac amyloidosis; analysis from a large cohort
  • Patients are living longer with treatment and an increased risk of A-fib due to age
  • Impact on survival has not been analyzed but should have an impact
  • A-fib was most frequently treated with beta blockers, calcium antagonists, amiodarone; anticoagulants are used but thrombotic events still occur so patients may be at increased risk due to amyloids
Multivariant analysis
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Variables independently associated with death: diabetes, higher age or Nt-proBNP, lower LVEF or eGFR
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Baseline characteristics:
  • N = 1157 patients
  • 87.4% male, mean age 75.7 years, 83% wild-type
  • Median follow-up 23.2 months
  • AF at baseline: 574 (49.6%)
  • No AF at baseline: 583 (51.4%)
    • 187 (16.1% developed AF during follow-up
    • 396 (34.2%) remained in sinus rhythm
  • A-fib is very common in patients with ATTR cardiac amyloidosis (49.7% at diagnosis)
  • 1 in 3 ATTR-CM patients will develop A-fib during a median follow-up of 4 years
  • Patients with A-fib have worst prognosis, but A-fib is not an independent predictor of mortality
  • Most frequent strategy to control A-fib is rate control; rhythm control seems to have low success
*Very low numbers, both limits above 1

Notes: A-fib = atrial fibrillation; eGFR = estimated glomerular filtration rate; LVEF = left ventricular ejection fraction; NT-proBNP = N-terminal pro b-type natriuretic peptide
  1. ALXN: ISA 2020 Clinical Report_ATTR. Presentation: Adrian Rivas Perez- Prevalence and survival impact of atrial fibrillation in patients with transthyretin cardiac amyloidosis. Analysis from a large cohort.

Tracking Disease Progression: Changes in Amyloid Load

In addition to specific cardiac biomarkers, modern non-invasive imaging techniques such as CMR are available today [1]; CMR is the most sensitive tool to quantify and track changes in amyloid load over time [2]
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Notes: AUC = area under the curve; ECV = extracellular volume fraction; eGFR = estimated glomerular filtration rate; NAC = National Amyloidosis Centre (UK); NT-proBNP = N-terminal pro b-type natriuretic peptide; NYHA = New York Heart Association
1 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).

2 ALXN: 14_Differentiation workshop Pre-reads.

Tracking Disease Progression: Serum TTR Levels

  • Robust biomarker to explore the in vivo effects of increased TTR stability, based on:
    • Destabilizing mutations are often associated with below‐normal serum TTR concentrations in ATTRv patients;
    • ATTRwt patients tend to have low‐normal to below‐normal levels as well;
    • In ATTRwt‐CM patients, below‐normal TTR levels (<3.2 μM or 18 mg/dL) are associated with a worse prognosis than normal levels;
    • Heterozygous T119M (super‐stabilizing mutation) carriers have 20% higher TTR concentrations compared to the general healthy adult population;
    • Treatment with a TTR stabilizer increases circulating TTR concentrations in patients with ATTR amyloidosis
  • However, TTR concentrations are affected by several factors, including age, gender nutritional status, infections, inflammation—not to be used in isolation
  • Need of a validation in the general population and better characterization in affected patients (RBP4 and other biomarkers to be investigated)
  • While TTR stabilizers aim at maintaining / increasing serum TTR levels, TTR Knock-down agents aim at suppressing them, with good results in ATTR-PN
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In a review of patients with biopsy-proven ATTRwt (n=101), one study showed that each rise of 1 mg/dL in serum TTR is associated with an up to 11% reduced risk of mortality [2]
Notes: 6MWT = 6-minute walk test, a performance-based test that evaluates an individual’s functional exercise capacity by measuring the distance walked in 6 minutes over a flat, hard surface; RBP4 = retinol binding protein-4
  1. ALXN: 14_Differentiation workshop Pre-reads. Citing: Lane T, et al. Circulation 2019;140:16–26.
  2. Hanson JLS, et al. Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin. Circ Heart Fail. 2018 Feb;11(2):e004000. doi: 10.1161/CIRCHEARTFAILURE.117.004000. PMID: 29449366; PMCID: PMC5819619 & TTR Matters. bridgebio. Available at Accessed January 13, 2022.