Temporal Trends of Wild-Type Transthyretin Amyloid Cardiomyopathy in the Transthyretin Amyloidosis Outcomes Survey

Abstract

Background Transthyretin amyloid cardiomyopathy results from the accumulation of wild-type (ATTRwt) or variant (ATTRv) transthyretin amyloid fibrils in the myocardium. THAOS (Transthyretin Amyloidosis Outcomes Survey) is a global, longitudinal, observational survey of patients with ATTRv and ATTRwt amyloidosis and asymptomatic patients with transthyretin mutations. Objectives This study explored temporal trends in ATTRwt amyloidosis diagnoses using data from THAOS. Methods Using THAOS data from December 2007 to January 2020, the following comparisons were made according to year: ATTRwt amyloidosis diagnoses in the United States versus rest of the world, ATTRwt versus ATTRv amyloidosis with cardiac-associated mutations diagnoses, and ATTRwt amyloidosis diagnoses by tissue biopsy versus bone scintigraphy. Results There were 1,069 patients with ATTRwt amyloidosis and 525 with ATTRv amyloidosis with cardiac mutations enrolled in THAOS. The median time from symptom onset to ATTRwt amyloidosis diagnosis did not change over the past 5 years (>60 months from 2015–2019). ATTRwt amyloidosis diagnoses increased from 2 in 2005 to >100 per year from 2016, with a more pronounced increase in the United States compared with the rest of the world. Diagnoses of ATTRwt amyloidosis by tissue biopsy increased yearly and peaked in 2014 before declining, whereas diagnoses by bone scintigraphy increased markedly since 2011. ATTRv amyloidosis with cardiac mutation diagnoses increased from 3 in 2005 to 37 in 2011, then plateaued. The proportion of patients with ATTRwt amyloidosis diagnosed with New York Heart Association functional class III/IV heart failure decreased from 2012 (46.4%) to 2019 (16.0%). Conclusions In the past decade, ATTRwt amyloidosis diagnoses increased worldwide. Despite the growing utilization of bone scintigraphy, patients are diagnosed several years after symptom onset. (Transthyretin Amyloidosis Outcomes Survey [THAOS]; NCT00628745 )

Evaluation of the cardiac amyloidosis clinical pathway implementation: a real-world experience

“… 6 An analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS) found that despite the rising use of scintigraphy in diagnosis, half of ATTR wild-type CA patients experienced diagnostic delay >4.7 years. 24 The observed improvement in diagnostic delay in our study, may partly be explained by the new drug treatment in ATTR-CA launched in 2018, leading to an increase in scientific papers, presentations on (inter)national congresses, revision of diagnostic algorithms and the help of pharmaceutical industry with flyers and symposia. 23 , 25 As CA in general, including AL-CA, was in the spotlights, this probably also contributed to an improvement in the diagnostic delay.…”

Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update

“…Diagnosing ATTRwt amyloidosis can be particularly challenging because cardiac symptoms are often consistent with more common types of heart failure, and historically a diagnosis has been obtained through endomyocardial biopsy, an invasive and expensive technique [ 6 , 25 ]. It is expected that increased use of bone scintigraphy, a minimally invasive and less expensive diagnostic tool, would decrease the time to diagnosis among these patients [ 3 , 6 ], although this effect has not yet been reflected in THAOS [ 26 ]. Patients with early-onset Val30Met disease had the shortest time to diagnosis, but there was still an average 2 years from symptom onset to obtain a diagnosis despite most of these patients being from countries with endemic foci.…”

Annual Cardiovascular-Related Hospitalization Days Avoided with Tafamidis in Patients with Transthyretin Amyloid Cardiomyopathy

“…Clinicians should consider the early identification of affected individuals with widely available non-invasive diagnostic techniques. Real-world observations suggest that the increased awareness and availability of minimally invasive diagnostic tools, such as bone scintigraphy in the absence of a monoclonal protein, have contributed to a greater proportion of patients being diagnosed in NYHA class I or II over time, highlighting a shift to earlier diagnosis and the growing importance of these patients [ 16 , 17 ].…”

“…The effect of tafamidis on the frequency and duration of CV-related hospitalizations was numerically more favorable in patients with wild-type ATTR-CM. Considering that a recent publication reported that wild-type patients made up the vast majority of diagnoses over the past decade, particularly in the USA, the results of our study could be considered a conservative estimate of the reduction in hospitalization burden for the real-world ATTR-CM population [ 16 ]. Likewise, there was a similar effect in frequency and duration of CV-related hospitalizations in both tafamidis doses (80 mg and 20 mg).…”