Prevalence and prognostic value of different iron deficiency definitions in light chain cardiac amyloidosis patients

Research on iron deficiency (ID) in patients with light chain cardiac amyloidosis (AL-CM) has been limited in previous studies. The purpose of this study was to investigate the prevalence and its association with prognosis of ID based on different definitions in patients with AL-CM.

Three different ID definitions were applied: (1) serum ferritin concentration of <100 ng/mL, or 100-299 ng/mL with transferrin saturation (TSAT) < 20% (according to guidelines on heart failure), (2) TSAT < 20% and (3) serum iron <13 μmol/L. The primary outcome measure was all-cause mortality. Prevalence and outcomes of various ID definitions were evaluated among patients diagnosed with AL-CM at Heart Failure Center, Fuwai Hospital between September 2017 and October 2023. Overall, 149 patients were included with a mean age of 60.71 ± 10.11 years, of whom 60 (40.3%) patients were female, 127 (85.2%) patients were in New York Heart Association (NYHA) class III-IV and 136 (91.3%) patients were in the revised Mayo 2012 stage III-IV. Assessments of iron biomarkers revealed the following results: median ferritin levels were 183.68 ng/mL (interquartile range [IQR] 95.48, 339.01), median TSAT was 21.80% (IQR 16.34, 29.48), and median serum iron was 10.87 μmol/L (IQR 7.38, 13.71). Serum iron were highly correlated with TSAT (r = 0.85, P < 0.0001). Depending on the definition used, 63 (42.3%) patients, 61 (40.9%) patients and 105 (70.5%) patients were defined as ID, respectively (P < 0.0001). ID defined by TSAT and serum iron was associated with the primary outcome [hazard ratio (HR) 2.14, 95% confidence interval (CI) 1.36-3.37, P < 0.001, and HR 2.16, 95% CI (1.23-3.80), P < 0.01], but the same association was not seen with the guideline definition of ID [HR 1.39, 95% CI (0.88-2.18), P = 0.158]. In the multivariable model adjusting for age, gender, haemoglobin, and revised 2012 Mayo staging, the predictive value of TSAT < 20% [adjusted HR 2.49, 95% CI (1.54-4.05), P < 0.001] and serum iron < 13 μmol/L [adjusted HR 2.24, 95% CI (1.23-4.09), P < 0.01] remained.

Different definitions of ID yield inconsistent results in terms of prevalence and prognosis. ID, as defined by TSAT < 20% or serum iron < 13 μmol/L, rather than the guideline definition, emerged as an independent predictor of all-cause mortality in patients with AL-CM.