Cardiac disease monitoring measures in patients with transthyretin amyloid cardiomyopathy treated with tafamidis.

Background: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience worsening cardiac disease (WCD) despite disease-modifying treatment. However, a strict definition is lacking. Recent studies have shown that N-terminal pro-B-natriuretic peptide (NT-proBNP increase), or intensification of oral diuretics, is associated with increased mortality risk.

Aim: To describe the pattern of WCD at 1 year in patients with ATTR-CM on tafamidis and explore the association with mortality and cardiovascular (CV) hospitalisation.

Methods: Patients diagnosed with ATTR-CM at Columbia University after 2018 who were treated with tafamidis were enrolled in the study. WCD was defined as: increase in NT-proBNP >700 pg/mL and >30% from baseline or oral diuretic intensification (ODI) or both. Survival and CV hospitalisation risk analysis was performed using Kaplan-Meier curves, Cox regression and competing risk regression adjusted for age, genotype and disease severity by the National Amyloidosis Centre (NAC) stage.

Results: A total of 238 patients were enrolled, 100 (42%) of whom showed WCD at 1 year. WCD was associated with increased mortality risk (log rank, p<0.0001, HR=1.91 (1.10-3.32), p=0.023, after adjustment for age, genotype and baseline NAC stage). In competing risk analysis, WCD was associated with increased risk for CV-related hospitalisation (HR=1.8 (1.17-2.99, p=0.009)) after adjustment for age, genotype and baseline NAC stage.

Conclusions: NT-proBNP increase and ODI can serve as markers of WCD and predict mortality and CV hospitalisations in a cohort of patients taking tafamidis.