Physicians' Academy for Cardiovascular Education

Natural history study of early-stage transthyretin amyloid cardiomyopathy

Characteristics and natural history of early-stage cardiac transthyretin amyloidosis

Literature - Law S, Bezard M, Petrie A, et al. - Eur Heart J. 2022 May 24;ehac259. doi: 10.1093/eurheartj/ehac259

Introduction and methods


Transthyretin amyloid cardiomyopathy (ATTR-CM) is a challenging diagnosis. Due to recent improvements in diagnostic imaging techniques coupled with increased awareness of the disease among cardiologists, >50% of patients are now diagnosed with early-stage ATTR-CM [1-8]. However, the natural history of early-stage disease remains poorly characterized.

Aim of the study

The authors aimed to characterize the natural disease course and clinical outcome among patients with early-stage ATTR-CM (National Amyloidosis Centre (NAC) ATTR Stage I).


In this retrospective, multicenter, observational study, 879 patients with ATTR-CM who visited one of two large amyloidosis centers in the UK and France between August 2009 and July 2020 were included. Inclusion criteria were: (1) wild-type TTR gene sequence or TTR mutation encoding the known pathogenic p.V142I variant; (2) NAC ATTR Stage I biomarkers at time of diagnosis (NT-proBNP ≤3000 ng/L and eGFR ≥45 mL/min per 1.73 m2); and (3) no disease-modifying therapy during clinical follow-up.

Patients were systemically evaluated at diagnosis and thereafter at a 6–12-month intervals as clinically indicated up to 100 months, if possible.

Main results


Cardiovascular morbidity in Stage Ia


In this natural history study, ATTR-CM patients with NAC ATTR Stage I could be further stratified according to NT-proBNP level and diuretic requirement at diagnosis. Despite good short- and mid-term survival, patients with Stage Ia showed significant CV morbidity.

The authors believe their “findings lend strong support to the argument for considering disease-modifying therapy with TTR stabilisers or TTR gene silencers at the time of identification of ATTR amyloid in patients with cardiac uptake by radionuclide imaging, even in patients without a primary cardiovascular presentation or overt heart failure symptoms.” However, they add, it remains to be determined whether this will reduce CV morbidity and prolong survival.


Show references

Find this article online at Eur Heart J.

Share this page with your colleagues and friends: