Iron and the heart: understanding anemia in cardiac amyloidosis

Abstract Introduction Anemia and iron deficiency (ID) are common comorbidities in patients with heart failure (HF) and have been associated with adverse clinical outcomes. However, their prevalence, clinical impact, and prognostic implications in cardiac amyloidosis (CA), particularly in transthyretin (ATTR) and light-chain (AL) subtypes, remain insufficiently explored. Given the frequent overlap between CA and HF, understanding the role of anemia and ID in CA is essential for optimizing patient management and identifying potential therapeutic targets. Aim We aimed to assess the prevalence of anemia and ID in CA subtypes and evaluate their association with clinical outcomes. Methods Patients with CA, including AL and ATTR types, were enrolled in a prospective registry. Clinical characteristics, medical history, laboratory and echocardiographic parameters were assessed at baseline. Anemia was defined as hemoglobin 13 g/dL in males and 12 g/dL in females, while ID was defined as transferrin saturation (TSAT) 20%. The primary endpoint was a composite of cardiac death and heart failure hospitalization. Results Anemia was present in 56.7% of CA patients, with higher prevalence in AL (69.6%) than ATTR (51.9%, p=0.007). ID was identified in 50.7% of the total cohort (AL: 43.0%, ATTR: 53.1%) (Figure 1). AL patients exhibited significantly lower hemoglobin levels than ATTR (AL: 12.3g/dL, ATTR: 13.4g/dL, p0.001), but within ATTR, ID was associated with reduced hemoglobin and hematocrit (p0.001 for both). TSAT 20% was independently predictive of adverse outcomes in both AL and ATTR subgroups (p0.001). In both CA subgroups, patients with ID had significantly higher levels of NT-pro BNP at baseline (3836.0pg/ml versus 2455.0pg/ml, p=0.010 in AL and 2972.0pg/ml versus 1656.0pg/ml, p=0.001 in ATTR). Kaplan-Meier analysis demonstrated an association between ID and increased risk of cardiac death or HF hospitalization, irrespective of left ventricular ejection fraction (LVEF) (Figure 2). Conclusion Anemia and ID are prevalent in patients with CA and are associated with worse clinical outcomes. A transferrin saturation (TSAT) level below 20% correlates with elevated NT-pro BNP levels, independently predicting poor outcomes in CA. These findings highlight the importance of screening for anemia and ID to identify patients at risk of adverse clinical outcomes. Additionally, they suggest that addressing ID may serve as a potential therapeutic target in both AL and ATTR subtypes of CA, warranting further investigation.Figure 1 Figure 2