Factors affecting serum neurofilament light chain in transthyretin amyloid cardiomyopathy

While serum neurofilament light chain (sNfL) has shown promise as a biomarker for the development of peripheral neuropathy (PN) in hereditary transthyretin (TTR) amyloidosis (vATTR), its role in all-comers with ATTR cardiomyopathy (ATTR-CM) is less well defined, and it is unknown how CM severity and TTR stabilizer therapy affect sNfL.

Study participants included those with ATTR-CM not on gene-silencer therapy referred to Oregon Health & Science University. The association between sNfL and baseline patient characteristics, including age, sex, body mass index (BMI), presence of PN, ATTR subtype, N-terminal pro b-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR) and tafamidis treatment, were evaluated utilizing linear regression.

66 patients (age: 78.5 ± 6.9 years, 6.1% female, 16.7% with diabetes mellitus, 10.6% vATTR-CM, 43.9% with PN symptoms, 30.3% receiving tafamidis at baseline) were included. There was no difference in sNfL levels when stratified by ATTR subtype (p = 0.168), PN symptoms (p = 0.881), or tafamidis treatment measured categorically (p = 0.418). In 17 patients (17.6% vATTR-CM) with available paired pre-tafamidis and on-tafamidis samples, there was no difference in sNfL level. In our univariable and multivariable analysis, NT-proBNP and eGFR were associated with sNfL.

In ATTR-CM, cardiomyopathy severity and renal dysfunction impact sNfL more than presence of PN or other clinical factors.