Diagnostic utility of red cell indices in relation to serum iron indices for evaluation of iron deficiency in heart failure

Background: Iron deficiency (ID) in heart failure (HF) causes poorer outcomes, and evaluation using ferritin and transferrin saturation (TSAT) in our setting is hampered by cost and availability. Though the red cell indices (RCIs), routinely used for assessment of ID anaemia, have shown utility in predicting outcomes in HF, they have not been evaluated in this population for prediction of ID relative to the iron indices. A combination of the RCIs, the combined cell index (CCI), may be more accurate. Validating the diagnostic accuracy of the RCIs would improve evaluation of ID in low-resource settings and improve uptake of iron supplementation as adjunctive HF treatment. Objective: To evaluate the sensitivity and specificity of the RCIs and CCI relative to TSAT and ferritin for ID in HF patients, the prevalence of ID, and clinical differences between ID and iron-replete HF patients. Methods: This was a diagnostic cross-sectional prospective study set in Aga Khan University Hospital. Patients above 18 years old with HF were sampled consecutively. A sample size of 143 was calculated using the specificity formula. Data collected included demographics and functional status. RCIs were obtained from a haemogram, and the ferritin and TSAT were measured. Sensitivity and specificity analysis, and receiver operating characteristics (ROC) curves, were performed for the RCIs and CCI. Medians and interquartile ranges were calculated for continuous variables and prevalence was reported as percentages or odds ratios (ORs) and their confidence intervals (95%CI). Results:One hundred and forty-five patients met eligibility criteria. Male-to-female ratio was 1.2:1. Median age was 67.0 (range 20.0-96.0 years). The prevalence of ID was 61.4% (95%CI 53.0-69.4%). ID was more common in females (OR 2.3 [95%CI 1.1-4.7]), non-heart failure with reduced ejection fraction (non-HFrEF) forms (OR 3.0 [95%CI 1.3-6.7]), more symptomatic patients (OR 4.0 (95%CI 1.8-8.9 for NYHA II-IV vs. NYHA I patients), and overweight/obese patients (OR 1.1 [95%CI 1.0-1.2] per unit increase in body-mass index). The RCIs had areas-under-the-curve (AUCs) of 0.59-0.69 on ROC analysis. The best predictors were MCHC and MCH. CCI performed no better than the individual RCIs. RDW had specificity of 96.4% (95%CI 87.7-99.6%). A combination of RDW ≥18% then TSAT Conclusion: ID is common in HF patients, mainly affecting women, non-HFrEF, overweight/obese and more symptomatic patients. RCIs provided moderate diagnostic capability in HF. RDW screening for overt ID prior to TSAT testing may reduce the need to test all patients with TSAT and ferritin, hence reducing cost burden to HF patients