Epidemiology of transthyretin (ATTR) amyloidosis: a systematic literature review

Abstract

Introduction: Significant advances in the treatment of transthyretin (ATTR) amyloidosis has led to an evolving understanding of the epidemiology of this condition. This systematic literature review (SLR) aims to synthesize current evidence on epidemiology and mortality outcomes in ATTR amyloidosis, addressing the need for a comprehensive understanding of its current global impact.

Methods: An SLR of the literature from January 2018 to April 2023 was conducted using the Medline and Embase databases. The review followed the PRISMA guidelines. Studies evaluating populations with genotypes and phenotypes of ATTR amyloidosis (variant and wild-type cardiomyopathy, polyneuropathy, and mixed) were included. Observational studies, systematic reviews, and meta-analyses were eligible, while reports, commentaries, clinical trials, and non-ATTR amyloidosis studies were excluded. Extracted data included prevalence, incidence, and mortality rates.

Results: Of the 1,458 studies identified, 113 met the inclusion criteria. Forty-nine studies reported on epidemiology, while 64 focused on mortality rates in cohorts of patients with ATTR amyloidosis from Europe (n = 16), North America (n = 26), Asia (n = 5), and Australia (n = 2). No studies were found that exclusively focused on ATTR amyloidosis in Africa or South America. ATTR prevalence ranged from 6.1/million in the US to 232/million in Portugal with very limited data on ATTR-PN. The 2-year mortality risk ranged from 10 to 30% among wild-type ATTR-CM and from 10 to 50% for variant type of ATTR-CM.

Conclusions: This SLR demonstrated heterogeneity in ATTR epidemiology and mortality rates across global regions. Further investigation is needed to address knowledge gaps of the epidemiology and burden of ATTR, which may improve early diagnosis and management.

Fig. 1

PRISMA flow chart summarizing the selection process of articles included in this systematic review. Abbreviations: ATTR = transthyretin amyloidosis; CM = cardiomyopathy; NYHA = Ner York Heart Association classification; PN = polyneuropathy; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Fig. 2

Prevalence of ATTR amyloidosis in the General Population. Except for the data from Japan and Portugal, all other prevalence and incidence rates depicted in this figure pertain to unspecified ATTR-CM. Abbreviations: ATTR-PN = amyloid transthyretin polyneuropathy; PMPY = Per Million Per Year; ATTRwt-CM = wild-type amyloid transthyretin cardiomyopathy

Fig. 3

Clinical Studies Reporting the Number Per Million of ATTR amyloidosis in Patients with (A) Heart Failure and (B) other high-risk conditions. ^a Observed prevalence may be related to the small sample size (n = 87) and the specialized diagnostic criteria used. ^b observed prevalence was among patients suspected of ATTR amyloidosis, selected based on specific cardiac amyloidosis indicators and imaging results. *History of (CTS, LSS, etc.)/echocardiographic red flags/hs-troponin T higher than the upper reference limit. †Sensory-motor idiopathic PN and 2 + red-flag (e.g., Family history of PN or CM, CTS, etc.). Abbreviations: AF = Atrial Fibrillation; AS = Aortic Stenosis; ATTR-CM = Transthyretin Amyloid Cardiomyopathy; ATTRv-CM = Variant Transthyretin Amyloid Cardiomyopathy; ATTRv-PN = Variant Transthyretin Polyneuropathy; CTS = Carpal Tunnel Syndrome; DLT = Domino Liver Transplant; HDP = hydroxymethylene diphosphonate; HF = heart failure; LVH = Left Ventricular Hypertrophy; LVH + AF = Left Ventricular Hypertrophy plus Atrial Fibrillation; ATTRwt-CM = Wild-Type Transthyretin Amyloid Cardiomyopathy