Change in N-terminal pro-B-type natriuretic peptide at 1 year predicts mortality in wild-type transthyretin amyloid cardiomyopathy

Abstract

ObjectivesWild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is a progressive and fatal condition. Although prognosis can be determined at the time of diagnosis according to National Amyloidosis Centre (NAC) transthyretin amyloidosis (ATTR) stage, the clinical course varies substantially between individuals. There are currently no established measures of rate of disease progression. Through systematic analysis of functional, biochemical and echocardiographic disease-related variables we aimed to identify prognostic markers of disease progression in wtATTR-CM.MethodsThis is a retrospective observational study of 432 patients with wtATTR-CM diagnosed at the UK NAC, none of whom received disease-modifying therapy. The association between mortality from the 12-month timepoint and change from diagnosis to 12 months in a variety of disease-related variables was explored using Cox regression.ResultsChange in N-terminal pro-B-type natriuretic peptide concentration (∆ NT-proBNP) at 12 months from diagnosis was the strongest predictor of ongoing mortality and was independent of both change in other disease-related variables (HR 1.04 per 500 ng/L increase (95% CI 1.01 to 1.07); p=0.003) and a range of known prognostic variables at the time of diagnosis (HR 1.07 per 500 ng/L increase (95% CI 1.02 to 1.13); p=0.007). An increase in NT-proBNP of >500 ng/L, >1000 ng/L and >2000 ng/L during the first year of follow-up occurred in 45%, 35% and 16% of patients, respectively.ConclusionChange in NT-proBNP concentration during the first year of follow-up is a powerful independent predictor of mortality in wtATTR-CM.

Circulating biomarkers in diagnosis and management of cardiac amyloidosis: a review for internist

“…Similar results, in term of reduction of TTR levels, were reported in patients receiving Inotersen in the NEURO TTR study [76]. Recently, Law et al [77] reported that change in NT-proBNP concentration, during the first year of follow-up, is a powerful independent predictor of mortality in a large cohort of patients with untreated wtATTR-CM. The authors emphasize that the prognostic relevance of the NT-proBNP changing was independent of NAC ATTR stage, troponin T, age, NYHA class, 6MWT distance, presence of atrial fibrillation and interventricular septal thickness at echocardiography.…”

Prevalence and clinical outcomes of transthyretin amyloidosis: a systematic review and meta‐analysis

“…A formal bias assessment of identified studies is provided in online supplementary Table . The individual studies and the extracted aggregate data are summarized in Table 2 2,3,10,11,13,26,27,29,30,52,54,65,71,78–158 . An exponential growth in the annual publication of studies on clinical outcomes of ATTR was observed over the recent years ( Figure ).…”

Progression of echocardiographic parameters and prognosis in transthyretin cardiac amyloidosis

“…Blood biomarker studies to date have mainly focused on wtATTR-CM. 2 Echocardiography typically offers the first clues to diagnosis of ATTR-CM and its prognosis. [3][4][5][6][7] However, whilst its value for diagnosis and prognosis at patients' initial presentation has been established, 8 the role of serial echocardiography to ascertain and elucidate the basis for disease progression within individuals has been little studied.…”

“…However, the natural history remains poorly understood as are the most clinically meaningful parameters acquired by serial echocardiography, which is nevertheless performed routinely to monitor disease progression. Blood biomarker studies to date have mainly focused on wtATTR‐CM 2 …”