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

Background

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).

Methods

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

Survival

Cardiovascular morbidity in Stage Ia

Conclusion

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.

References

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Find this article online at Eur Heart J.

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