Key Information
Study Questions:
What is the prognostic importance of an increase in N-terminal pro–B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a cohort of patients with transthyretin cardiac amyloidosis (ATTR-CA)?
Methods:
The investigators evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from seven specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n = 1,598) and validated in the external cohort from the remaining centers (n = 677).
Results:
Between baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase >700 ng/L and >30%), which was associated with mortality (NAC cohort: hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.57-2.10; p < 0.001; validation cohort: HR, 1.75; 95% CI, 1.32-2.33; p < 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR, 1.88; 95% CI, 1.62-2.18; p < 0.001; validation cohort: HR, 2.05; 95% CI, 1.53-2.74; p < 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR, 1.93; 95% CI, 1.65-2.27; p < 0.001; validation cohort: HR, 1.94; 95% CI, 1.36-2.77; p < 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR, 2.98; 95% CI, 2.42-3.67; p < 0.001; validation cohort: HR, 3.23; 95% CI, 2.17-4.79; p < 0.001).
Conclusions:
The authors report that NT-proBNP progression and ODI are frequent and consistently associated with an increased risk of mortality in ATTR-CA.
Perspective:
This large cohort of patients with ATTR-CA reports that NT-proBNP progression and ODI were frequent and consistently associated with an increased risk of mortality. Combining both variables produces a simple, universally applicable model that detects disease progression. These data suggest that inclusion of NT-proBNP progression and ODI as outcomes in clinical studies could facilitate earlier recognition of clinically meaningful and potentially modifiable events in patients with cardiac ATTR amyloidosis.