Characteristics and natural history of early-stage cardiac transthyretin amyloidosis. (24th May 2022)

• Record Type: Journal Article
• Authors: Law, Steven; Bezard, Melanie; Petrie, Aviva; Chacko, Liza; Cohen, Oliver C; Ravichandran, Sriram; Ogunbiyi, Olabisi; Kharoubi, Mounira; Ganeshananthan, Sashiananthan; Ganeshananthan, Sharmananthan; Gilbertson, Janet A; Rowczenio, Dorota; Wechalekar, Ashutosh; Martinez-Naharro, Ana; Lachmann, Helen J; Whelan, Carol J; Hutt, David F; Hawkins, Philip N; Damy, Thibaud; Fontana, Marianna; Gillmore, Julian D
• Is Part Of: European heart journal. Volume 43:Number 27(2022)
• Page Start: 2622
• Page End: 2632
• Publication Date: 2022-05-24
• Subjects: Amyloidosis -- Amyloid -- Transthyretin -- TTR -- Staging -- Cardiomyopathy; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehac259
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: 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. Structured Graphical Abstract: Structured Graphical Abstract Patients diagnosed with NAC ATTR Stage Ia amyloidosis have an estimated median survival in excess of 100 months in the absence of disease-modifying therapy despite significant cardiovascular morbidity which increases further during follow up.