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

Abstract

AimsThere 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 resultsConsecutive 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.ConclusionsIron 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.

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“…4,[36][37][38] Three different definitions of ID are available: (i) serum ferritin concentration of <100 ng/ml, or 100-299 ng/ml with transferrin saturation <20% (guideline definition), (ii) serum iron concentration ≤13 μmol/L, or (iii) transferrin saturation <20%. Papadopoulou et al 39 evaluated these definitions of ID in 801 consecutive patients referred for heart transplantation at a single UK centre between January 2010 and May 2022. The prevalence of ID varied from 39% to 55% according to the definition.…”

Striving for the ‘perfect’ definition of iron deficiency in heart failure

“…[2][3][4][5] Based on this assumption, in this issue of the Journal, Papadopoulou and co-authors have provided the data on the prevalence and prognostic importance of ID among patients referred for heart transplantation; moreover the authors also studied the clinical consequences of different ID definitions in their study group. 6 Iron deficiency is important and unique in HF not only because it is involved in the pathophysiology of disease progression or clinical manifestation but primarily because unlike other HF malfunctions it is correctable, which translates into improvement in the clinical course of the disease. 7 While the mechanisms behind the development of ID and its consequences in HF are undeniably highly complex, involving numerous biochemical and molecular pathways that are still under intense investigation by basic scientists, the primary unknown from clinical perspective is: How can we define most accurately ID in HF 8 ?…”

“…In this issue of Journal, Papadopoulou et al 6 aimed to compare different ID definitions among patients referred for heart transplantation. The authors defined the ID in the study in three different ways: (i) serum ferritin concentration of <100 ng/ml, or 100-299 ng/ml with TSAT <20% (so-called 'guideline definition'); (ii) serum iron concentration ≤13 μmol/L; and (iii) TSAT <20%.…”

“…Moreover, many of these previously mentioned pathological changes are typically exacerbated in patients with advanced or acute HF, rendering them a special cohort for research studies 2–5 . Based on this assumption, in this issue of the Journal, Papadopoulou and co‐authors have provided the data on the prevalence and prognostic importance of ID among patients referred for heart transplantation; moreover the authors also studied the clinical consequences of different ID definitions in their study group 6 …”

“…In this issue of Journal, Papadopoulou et al 6 . aimed to compare different ID definitions among patients referred for heart transplantation.…”