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).

Keywords: ATTR amyloidosis, transthyretin amyloidosis; ATTR-CM, transthyretin amyloid cardiomyopathy; ATTRv amyloidosis, variant transthyretin amyloidosis; ATTRwt amyloidosis, wild-type transthyretin amyloidosis; NYHA, New York Heart Association; Q, quartile; TTR, transthyretin; bone scintigraphy; registry; wild-type transthyretin amyloidosis.

Conflict of interest statement

The THAOS registry and this analysis were sponsored by Pfizer. Dr Nativi-Nicolau has received research grants from Akcea/Ionis, Eidos, and Pfizer; has received consulting fees from Akcea, Alnylam, Eidos, and Pfizer; and has received educational grants from Pfizer. Dr Siu has received funding from Pfizer for meeting expenses (travel). Dr Dispenzieri has received research grants from Celgene, Millennium, Pfizer, Janssen, and Alnylam; and has received funding from Pfizer for meeting expenses (travel) and attended advisory boards for Akcea and Intellia. Dr Maurer has received grants from Pfizer during the conduct of the study; has received grants and personal fees from Pfizer, Eidos, Prothena, and Ionis; has received grants from Alnylam; and has received personal fees from GlaxoSmithKline and Akcea outside the submitted work. Dr Rapezzi has received research grants from Pfizer; and has received consultancy fees from Pfizer, Alnylam, and Prothena. Dr Kristen has received reimbursement for study visits from Pfizer during the conduct of the study. Dr Garcia-Pavia has received speaking fees from Pfizer, Eidos, Alnylam, and Akcea; has received consulting fees from Pfizer, Eidos, Neurimmune, Alnylam, Prothena, and Akcea; and has received research/educational support to his institution from Pfizer, Eidos, and Alnylam. Dr LoRusso has received support to her institution from Pfizer and Alnylam. Dr Waddington-Cruz has received research funding, consulting fees, and travel support for advisory boards and meetings from FoldRx Pharmaceuticals and Pfizer. Dr Lairez has received research grants from Pfizer; and has received consultancy fees from Pfizer and Alnylam. Dr Witteles has received honoraria for advisory board participation and funding for clinical trials from Pfizer, Alnylam, Eidos, and Ionis/Akcea. Drs Amass and Chapman are full-time employees of Pfizer and hold stock and/or stock options with Pfizer. Dr Grogan has received grants, and advisory board and consultancy fees paid to her institution from Alnylam, Eidos, Prothena, and Pfizer.

© 2021 The Authors.

Figures

Graphical abstract

Figure 1

ATTRwt Amyloidosis Patient Enrollment and Participating Centers per Year Participating centers in THAOS (the Transthyretin Amyloidosis Outcomes Survey) were centers with data available for patients with wild-type transthyretin amyloidosis (ATTRwt amyloidosis) in any given year. The number of participating centers with patients with ATTRwt amyloidosis grew from 3 in 2007 to 31 in 2019, and the number of new patient enrollments per year grew from 4 to 230. The average number of patients with ATTRwt amyloidosis enrolled per year per participating center has increased from 7 in 2018 and 2019.

Central Illustration

Diagnoses of Wild-Type Transthyretin Amyloidosis Versus Variant Transthyretin Amyloidosis With Cardiac Mutations Diagnoses in THAOS (the Transthyretin Amyloidosis Outcomes Survey) are shown by year. Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) diagnoses increased from 2 in 2005 to >100 per year starting in 2016. Diagnoses of variant transthyretin amyloidosis (ATTRv amyloidosis) with cardiac mutations increased from 3 in 2005 to 37 in 2011, after which they plateaued. ∗Year of diagnosis missing for 87 patients with ATTRwt amyloidosis and 116 patients with ATTRv amyloidosis with cardiac mutations.

Figure 2

Diagnoses of ATTRwt Amyloidosis by Region Diagnoses in the United States versus the rest of the world in THAOS (the Transthyretin Amyloidosis Outcomes Survey) are shown by year. Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) diagnoses in the United States in THAOS increased steadily from 2005 to 2017, after which diagnoses appeared to decrease. In the rest of the world, ATTRwt amyloidosis diagnoses increased less steadily, but continued upward in 2018 and 2019. ∗Year of diagnosis missing for 45 patients in the United States and 42 in the rest of the world.

Figure 3

Diagnoses of ATTRwt Amyloidosis by Tissue Biopsy Versus Bone Scintigraphy Diagnoses in THAOS (the Transthyretin Amyloidosis Outcomes Survey) are shown by year. The number of patients with wild-type transthyretin amyloidosis (ATTRwt amyloidosis) diagnosed by tissue biopsy increased yearly and peaked in 2014 before declining. The number of patients with ATTRwt amyloidosis diagnosed by bone scintigraphy increased steadily from 2011 to 2017, with more patients diagnosed by bone scintigraphy than tissue biopsy every year from 2016. ∗Year of diagnosis missing for 66 patients diagnosed by biopsy and 18 patients diagnosed by scintigraphy.