Tafamidis treatment in transthyretin cardiac amyloidosis: A retrospective cohort analysis of outcomes and associated factors.

BACKGROUND

Transthyretin cardiac amyloidosis is an important cause of heart failure. Tafamidis, the only specific treatment for cardiac amyloidosis currently widely available in France, has been shown to reduce mortality efficiently.

AIM: The purpose of this study was to describe time to cardiovascular events (death or hospitalization) in patients with transthyretin cardiac amyloidosis treated with tafamidis, and to investigate associated factors.

METHODS

We retrospectively included consecutive patients with a new diagnosis of transthyretin cardiac amyloidosis and an indication for tafamidis in a tertiary centre from August 2012 to July 2022. We collected time-to-event data, and associated clinical, biological, ultrasound and therapeutic factors.

RESULTS

We included 128 patients, with visits every 6 months and a median follow-up of 15 months. A total of 42 patients (33%) died or were hospitalized for cardiovascular causes, with a median time-to-event of 1050 days (95% confidence interval 897 - not available). The mean time between diagnosis and start of treatment was 127±361 days. Several factors were associated with cardiovascular outcomes: older age at diagnosis correlated with reduced frequency of death or hospitalization (hazard ratio 0.93, 95% confidence interval 0.89-0.97; P<0.01), whereas obesity correlated with increased occurrence of death or hospitalization (hazard ratio 3.95, 95% confidence interval 1.45-10.76; P=0.01). More importantly, N-terminal prohormone of B-type natriuretic peptide>1000ng/L at diagnosis was a major risk factor in the multivariable analysis (hazard ratio 4.10, 95% confidence interval 1.64-10.25; P<0.01). After the initiation of treatment, New York Heart Association class and weight decreased significantly.

CONCLUSIONS

Patients with transthyretin cardiac amyloidosis have a poor prognosis in the short term, despite the use of tafamidis. Important prognostic factors, including clinical features and biomarkers (especially N-terminal prohormone of B-type natriuretic peptide) are essential for risk stratification. As these surrogate endpoints show significant improvement after starting tafamidis, initiating therapy promptly appears mandatory in the most severe patients.