Impact of iron deficiency on adverse outcomes in transthyretin cardiac amyloidosis
A Martins, A Vazao, J Pereira, M Amado, C Domingues, C Ruivo, D DuraoAbstract
Introduction
Transthyretin cardiac amyloidosis (ATTR-CA) is a restrictive cardiomyopathy associated with symptomatic heart failure (HF) and an increased risk of cardiovascular events. Iron deficiency (ID), a common comorbidity in HF, may also influence outcomes in ATTR-CA, but its prognostic impact remains insufficiently defined.
Objectives
This study aimed to assess the prevalence of ID and evaluate its association with clinical outcomes in patients with ATTR-CA followed at a Cardiomyopathy Clinic in a regional hospital in Portugal.
Methods
Retrospective, single-center study including patients diagnosed with ATTR-CA between 2018 and 2024. Baseline clinical and laboratory data were collected (table 1). ID was defined using either the conventional criteria [ferritin <100 µg/L, or 100–300 µg/L with transferrin saturation (TSAT) <20%] and the TSAT-based criteria (TSAT <20%). The primary endpoint, a composite of cardiac death and HF hospitalization, was assessed at 18 months. Patients who experienced the primary endpoint (group 1) were compared with those who did not (group 2).
Results
61 patients were included (81 ± 6 years, 93% male), of whom 30 (49%) experienced the primary endpoint (group 1). ID was observed in 79% of patients by conventional criteria and in 44% by the TSAT-based criteria, with a higher prevalence in group 1 only under the TSAT-based definition (60 vs 29%, p=0.015). Group 1 patients also had a higher prevalence of atrial fibrillation (AF) (90 vs 52%, p=0.001), chronic kidney disease (CKD) (83 vs 32%, p<0.001) and significant valvular heart disease (33 vs 19%, p<0.001). In multivariate analysis, AF (OR 8.02, 95% CI 1.53–41.91, p=0.014), CKD (OR 10.63, 95% CI 2.33–48.38, p=0.002) and TSAT <20% (OR 6.29, 95% CI 1.32–19.32, p=0.041) were associated with the occurrence of the primary endpoint. Kaplan-Meier curves showed lower event-free survival in patients with TSAT <20% (Figure 1). Patients with TSAT <20% had higher levels of NTproBNP at baseline (4870.0 vs. 3810.0 pg/mL, p=0.047). The primary driver of 18-month MACE was HF hospitalizations (60%), followed by cardiac death (40%).
Conclusions
In this cohort of patients with ATTR-CA, ID was highly prevalent, particularly when defined by conventional criteria. However, only the TSAT-based definition demonstrated prognostic relevance, being associated with worse outcomes. These findings highlight the importance of screening for ID, especially TSAT <20%, to identify patients at increased risk.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.