Anemia and outcome in cardiac amyloidosis

Abstract Background Anemia is a common comorbidity in patients with cardiac amyloidosis, yet its prognostic significance remains poorly understood. This study aims to evaluate the impact of anemia on survival in patients with either transthyretin (TTR) or light chain (AL) cardiac amyloidosis. Purpose The purpose of this study is to assess the impact of anemia on survival in patients with AL or ATTR cardiac amyloidosis. The study aims to determine whether anemia serves as an independent prognostic factor in this population, thereby enhancing our understanding of its role in the clinical course of the disease. Methods Consecutive patients diagnosed with cardiac amyloidosis at a single tertiary centre were enrolled from 2002 to 2024. Patients received a full clinical and biohumoral characterization and were then followed up for the endpoint of all-cause mortality. Anemia was defined as a hemoglobin level <13 g/dL in men and <12 g/dL in women. Multivariate analyses were adjusted for age, sex, amyloidosis type, and follow-up time. Subgroup analyses by age, sex, and amyloidosis subtype (AL, ATTR, and others) were performed. Sensitivity analyses, with exclusion of early mortality cases, and multiple imputation for missing data, were conducted to validate the robustness of the findings. Results We enrolled 514 patients (mean age 70.1 ± 25.7 years; 69% ATTR, 22% with AL amyloidosis). Anemia was identified in 30.4% of patients (28.0% in ATTR, 50.4% in AL). After a median follow-up of 30.6 months (interquartile range 18.0-48.0 months), 211 patients (41%) died. Anemia emerged as an independent prognostic factor (HR = 1.32, 95% CI: 1.10-1.58, p = 0.003), particularly in patients with AL amyloidosis (HR = 1.51, 95% CI: 1.09-2.10, p = 0.015). The association was stronger in patients with AL amyloidosis aged ≥70 years (HR = 1.30, 95% CI: 1.04-1.62, p = 0.021) and in women (HR = 1.29, 95% CI: 1.02-1.64, p = 0.033). In patients with ATTR amyloidosis, analyses shown a statistically significant difference (HR = 1.28, 95% CI: 1.01–1.67, p = 0.039). Cox regression analyses and sensitivity analyses confirmed the consistency of these findings across different hemoglobin thresholds. Conclusion Anemia is an independent predictor of survival in cardiac amyloidosis, particularly in AL amyloidosis. These findings highlight the need for early detection and management of anemia in this patient population. Further research is warranted to explore potential biomarkers and alternative hemoglobin cutoffs to refine anemia’s prognostic value.Kaplan-Meier Survival Curves