Clinical Epidemiology and Ageing

Characteristics and natural history of early-stage cardiac transthyretin amyloidosis.

Law S, Bezard M, Petrie A, Chacko L, Cohen OC, Ravichandran S, Ogunbiyi O, Kharoubi M, Ganeshananthan S, Ganeshananthan S, Gilbertson JA, Rowczenio D, Wechalekar A, Martinez-Naharro A, Lachmann HJ, Whelan CJ, Hutt DF, Hawkins PN, Damy T, Fontana M, Gillmore JD Eur Heart J. 2022;43(27):2622-2632.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly diagnosed at an early stage of the disease natural history, defined as National Amyloidosis Centre (NAC) ATTR Stage I. The natural history of early-stage ATTR-CM remains poorly characterized.

METHODS AND RESULTS: A retrospective multi-centre observational study of 879 patients with ATTR-CM, either wild-type TTR genotype or carrying the p.V142I TTR variant, and NAC ATTR Stage I biomarkers at the time of diagnosis who did not receive disease-modifying therapy for amyloidosis. Disease characteristics at diagnosis that were independently associated with mortality by Cox regression analysis were N-terminal pro-B-type natriuretic peptide (NT-proBNP), TTR genotype, and troponin T. Patients were categorized into NAC ATTR Stage Ia, defined as a furosemide equivalent diuretic requirement of <0.75 mg/kg and an NT-proBNP ≤500 ng/L or ≤1000 ng/L in the presence of atrial fibrillation, and NAC ATTR Stage Ib comprising all remaining Stage I patients. Median estimated survival among the 88% NAC ATTR Stage Ib patients was 75 (95% CI 57-93) months compared with >100 months in the 12% with Stage Ia disease [hazard ratio for death 5.06 (95% confidence interval 1.23-20.87); P = 0.025] despite significant cardiovascular morbidity at the time of diagnosis which increased during follow-up, including among patients diagnosed in NAC ATTR Stage Ia. Estimated survival among UK NAC ATTR Stage Ia patients was comparable to UK general population controls (P = 0.297).

CONCLUSION: Patients with NAC ATTR Stage I ATTR-CM can be further stratified according to NT-proBNP concentration and diuretic requirement at diagnosis. Patients with Stage Ia ATTR-CM have significant cardiovascular morbidity despite good short- and mid-term survival.

MeSH terms: Amyloid Neuropathies, Familial; Cardiomyopathies; Cardiovascular Diseases; Disease Progression; Diuretics; Humans; Prealbumin
DOI: 10.1093/eurheartj/ehac259