This activity was funded by Alnylam Pharmaceuticals. The medical content was developed independently by M3 and Professor Violaine Planté-Bordeneuve.

Highlights from

AAN 2021, EAN 2021, ESC-HF 2021 & PNS 2021

VIRTUAL, APRIL - JULY 2021

Amyloidosis Conference Highlights

Tafamidis treatment in patients with ATTR-CM

Take-home messages
  • Tafamidis 61 mg delays progression of myocardial amyloid deposition in ATTR-CM
  • Tafamidis 61 mg has beneficial outcomes for cardiac structure and function in ATTR-CM
  • Serial CMR with MOLLI-ECV may be appropriate disease-specific therapy monitoring in patients with ATTR-CM

At Heart Failure & World Congress on Acute Heart Failure 2021, PhD candidate Renne Rettl shared his findings on the use of tafamidis treatment in patients with transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy (ATTR-CM), as part of the 'Young Investigator Award: clinical research' session.

ATTR-CM is an increasingly diagnosed infiltrative cardiomyopathy characterised by the accumulation of transthyretin (TTR) monomers (dissociated from the TTR tetramer) as amyloid fibrils in the myocardium. This causes progressive heart failure, with a fatal prognosis, that has few effective treatment options.1,2

Recent evidence suggests that tafamidis, a kinetic stabiliser of TTR that prevents tetramer dissociation (the rate-limiting step in the amyloidogenic process),3 may halt the progress of myocardial disease in patients with ATTR-CM. In the ATTR-ACT study, tafamidis reduced all-cause mortality and cardiovascular hospitalisations, and improved exercise capacity and quality of life, versus placebo in patients with ATTR-CM.4

These results show that tafamidis can improve clinical status of patients with ATTR-CM; Renne’s work looked to build upon this. Firstly, by determining the disease-modifying effects of tafamidis on myocardial amyloid deposition and how it effects cardiac structure and function. Secondly, by evaluating the utility of imaging parameters that could be applied for specific therapy monitoring (serial cardiac magnetic resonance (CMR) imaging with T1 mapping using modified look-locker inversion sequence to derive extracellular volume (MOLLI-ECV)).

Renne's analysis was carried out in a group of patients with wild-type ATTR-CM recruited as part of a heart failure registry at the Medical University of Vienna. 116 patients were screened between 2015 and 2020, of whom 75 underwent CMR imaging. The final analysis was conducted in 19 untreated patients (median follow-up 12 months), 15 patients treated with tafamidis 20 mg once-daily (median follow-up 11 months) and 35 patients treated with tafamidis 61 mg once-daily (median follow-up 9 months).

In agreement with results from ATTR-ACT, Renne found evidence of beneficial effects of tafamidis on exercise capacity (improved mean 6-minute walking distance) and cardiac biomarkers (reduction in median serum NT-proBNP levels), that were not observed in untreated patients (comparisons between tafamidis 61 mg once-daily and untreated patients: p=0.005 and p=0.002, respectively).

In terms of cardiac structure, there was evidence of stabilisation in left ventricular (LV) mass for patients treated with tafamidis (61 mg: baseline 110.2 g/m2 vs follow-up 106.2 g/m2, p=0.304), while untreated patients showed a significant increase in LV mass (baseline 98.9 g/m2 vs follow-up 106.9 g/m2, p=0.027). Similarly, stabilisation of MOLLI-ECV was observed in patients treated with tafamidis (61 mg: baseline 47.5% vs follow-up 47.7%, p=0.861), that was not observed in untreated patients (baseline 49.3% vs 54.6%; p=0.023). Comparison of the changes in patients treated with 61 mg tafamidis versus untreated patients showed a significant difference for both parameters (LV mass p=0.036; MOLLI-ECV p=0.03), but the difference between patients treated with 20 mg tafamidis and untreated patients was not significant.

Cardiac function was also found to improve with tafamidis treatment; LV ejection fraction stabilised with treatment (61 mg: baseline 47.6% vs follow-up 47.5%, p=0.935) but decreased without treatment (baseline 53.3% vs follow-up 45.7%, p=0.031). These changes were significantly different between the 61 mg tafamidis group and untreated patients (p=0.035) but again, not significant for the 20 mg group versus the untreated group.

A correlation between longitudinal changes in NT-proBNP levels and MOLLI-ECV was observed (Pearson correlation: 0.254, p=0.034), suggesting that MOLLI-ECV is a suitable measure of myocardial amyloid deposition in ATTR-CM.

Renne’s results show that tafamidis 61 mg once-daily delays progression of myocardial amyloid deposition in patients with ATTR-CM and that this results in significant benefits in cardiac structure and function, and in clinical status, compared with the untreated course of disease. The lack of significant difference in outcomes between untreated patients and patients treated with 20 mg tafamidis supports the use of 61 mg tafamidis for patients with ATTR amyloidosis and cardiomyopathy, in contrast to the 20 mg dose licensed for use in patients with ATTR amyloidosis and polyneuropathy.5,6 Renne concludes by suggesting that serial CMR imaging with MOLLI-ECV could be an appropriate technique for monitoring the effects of specific therapies in patients with ATTR-CM.

NT-proBNP: N-terminal pro B-type natriuretic peptide

Based on: Rettl R, Mann C et al. Tafamidis treatment in patients with transthyretin amyloid cardiomyopathy. Presented at Heart Failure & World Congress on Acute Heart Failure 2021, 29 June-1 July 2021

  1. Ruberg F L, Berk J L. Transthyretin (TTR) cardiac amyloidosis. Circulation 2012;126(10):1286-1300
  2. Yamamoto H, Yokochi T. Transthyretin cardiac amyloidosis: an update on diagnosis and treatment. ESC Heart Fail 2019;6(6):1128-1139
  3. Gertz M A, Benson M D et al. Diagnosis, prognosis, and therapy of transthyretin amyloidosis. J Am Coll Cardiol 2015;66(21):2451-2466
  4. Maurer M S, Schwartz J H et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 2018;379(11):1007-1016
  5. Tafamidis 20 mg Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/2837/smpc. Accessed July 2021
  6. Tafamidis 61 mg Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/11141/smpc. Accessed July 2021

Top image: Eraxion

Article image: mr.suphachai praserdumrongchai

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.

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