Temporal Trends of Wild-type Attr Amyloidosis in the Transthyretin Amyloidosis Outcomes Survey

Abstract

Introduction Wild-type transthyretin amyloidosis (ATTRwt) is an infiltrative cardiomyopathy (CM) underdiagnosed in older adults. The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, observational survey of patients with inherited (ATTRv) and ATTRwt amyloidosis, and asymptomatic gene carriers. Temporal trends in ATTRwt diagnosis were explored in this analysis. Hypothesis ATTRwt CM diagnosis has trended up since introducing scintigraphy. Methods Demographic and diagnostic data of CM patients enrolled in THAOS up to the 06January2020 data cut-off were analyzed. Diagnosis frequency between ATTRwt and ATTRv with cardiac phenotype (p.Val142Ile, p.Leu131Met, p.Thr60Ala, p.Ile88Leu), and ATTRwt diagnostic modality, were compared by year. Results A total of 1,069 ATTRwt patients (94.6% male) from 15 countries were identified. Symptoms were reported at a mean (SD) age of 68.8 (11.1) years and diagnosis made at 76.1 (7.1) years. Median (Q1, Q3) time to diagnosis from symptom onset was 4.7 (1.0, 10.9) years. ATTRwt diagnoses increased from single digits to >100 per year, whereas ATTRv with cardiac phenotype increased after 2007 then plateaued after 2011 (Panel A). ATTRwt diagnosis with biopsies increased and peaked in 2014 with a subsequent decline, compared to an increase in diagnosis with scintigraphy since 2012 (Panel B). Conclusions In the last decade, ATTRwt CM amyloidosis diagnoses increased with a concomitant shift from using biopsy to scintigraphy. Despite rising use of scintigraphy, half of the patients experienced diagnosis delays of >4.7 years.