Prognostic value of three iron deficiency definitions in patients with advanced heart failure

• Published in: European journal of heart failure Vol. 25; no. 11; pp. 2067 - 2074
• Main Authors: Papadopoulou, Charikleia, Reinhold, Johannes, Grüner‐Hegge, Nicolai, Kydd, Anna, Bhagra, Sai, Parameshwar, K. Jayan, Lewis, Clive, Martinez, Luis, Pettit, Stephen J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK John Wiley & Sons, Ltd 01-11-2023
• Subjects: Advanced heart failure; Anemia, Iron-Deficiency - diagnosis; Anemia, Iron-Deficiency - epidemiology; Heart Failure - diagnosis; Heart Failure - epidemiology; Heart Failure - etiology; Heart transplant; Humans; Iron; Iron Deficiencies; Iron deficiency; Prognosis; Transferrins; Heart transplant; Iron deficiency; Advanced heart failure
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1002/ejhf.2949

Aims
There is uncertainty about the definition of iron deficiency (ID) and the association between ID and prognosis in patients with advanced heart failure. We evaluated three definitions of ID in patients referred for heart transplantation.
Methods and results
Consecutive patients assessed for heart transplantation at a single UK centre between January 2010 and May 2022 were included. ID was defined as (1) serum ferritin concentration of <100 ng/ml, or 100–299 ng/ml with transferrin saturation <20% (guideline definition), (2) serum iron concentration ≤13 μmol/L, or (3) transferrin saturation <20%. The primary outcome measure was a composite of all‐cause mortality, urgent heart transplantation or need for mechanical circulatory support. Overall, 801 patients were included, and the prevalence of ID was 39–55% depending on the definition used. ID, defined by either serum iron or transferrin saturation, was an independent predictor of the primary outcome measure (hazard ratio [HR] 1.532, 95% confidence interval [CI] 1.264–1.944, and HR 1.595, 95% CI 1.323–2.033, respectively), but the same association was not seen with the guideline definition of ID (HR 1.085, 95% CI 0.8827–1.333). These findings were robust in multivariable Cox regression analysis. ID, by all definitions, was associated with lower 6‐min walk distance, lower peak oxygen consumption, higher intra‐cardiac filling pressures and lower cardiac output.
Conclusions
Iron deficiency, when defined by serum iron concentration or transferrin saturation, was associated with increased frequency of adverse clinical outcomes in patients with advanced heart failure. The same association was not seen with guideline definition of ID.
Venn diagram of iron deficiency (ID) according to various definitions and associated outcomes. Non‐scaled VENN diagram. Data for hazard ratio (HR) is mean (95% confidence interval). Red circles indicate worst prognosis, yellow intermediate prognosis and green best prognosis. 6MWD, 6‐min walk distance; CI, cardiac index; CPI, cardiac power index; LVEF, left ventricular ejection fraction; PA, pulmonary artery; PCW, pulmonary capillary wedge; RA, right atrial; TAPSE, tricuspid annular plane systolic excursion; TSAT, transferrin saturation; VO2, oxygen consumption.