Monitoring Tafamidis Response in ATTR — EECC MCQ

Correct answer: D — Disease progression despite tafamidis can occur — tafamidis slows but does not halt progression; worsening GLS and rising NT-proBNP indicate advancing disease despite stabilisation of wall thickness; supportive care optimisation and consideration of emerging therapies (TTR gene silencers) should be discussed

Tafamidis stabilises the TTR tetramer, reducing new amyloid fibril formation, but does NOT remove existing deposits. Therefore: (1) disease may continue to progress (albeit more slowly) if amyloid burden is already substantial at treatment initiation; (2) monitoring should include: serial echocardiography (wall thickness, GLS — apical sparing pattern is characteristic and worsening GLS indicates progression), NT-proBNP/BNP, functional capacity (6MWT), and NYHA class; (3) GLS may be a more sensitive marker of disease activity than wall thickness (which may remain stable while myocardial function deteriorates); (4) emerging therapies: TTR gene silencers (patisiran — siRNA, inotersen — antisense oligonucleotide) reduce TTR production by 80-90% and may provide additional benefit; CRISPR-based TTR gene editing (NTLA-2001) is in clinical trials. The ESC 2023 Cardiomyopathy Guidelines recommend early tafamidis initiation (NYHA I-II) for best outcomes.

Reference: ESC (2023): Cardiomyopathies; ATTR-ACT Trial