Iron Deficiency Prevalent, Linked to Adverse Outcomes in Patients with HFrEF

Published on: 

Iron deficiency marks more than a comorbidity in heart failure, with adverse manifestations, including anemia and a higher risk of mortality, influencing the clinical trajectory of patients with HFrEF.

A recent analysis evaluated the clinical profile of iron deficiency and its prevalence among a cohort of patients with heart failure with reduced ejection fraction (HFrEF).1

Across the population of nearly 400 patients in India, more than half of patients with HFrEF and three-quarters of patients with iron deficiency exhibited anemia, demonstrating a significant association between iron deficiency and anemia in heart failure (P <.05).

“The pervasive prevalence of iron deficiency in patients with HFrEF makes it a noteworthy concern,” wrote the investigative team, led by Alhad Mulkalway, MBBS, department of pharmacology, Dr. D.Y. Patil Medical College, Hospital & Research Centre. “This condition is not only significantly associated with increased mortality in HFrEF patients, but also stands out as a common comorbidity, independent of the presence of anemia.”

Definitions of iron deficiency in heart failure are different than the general population given its chronic inflammation—the definition is marked by a ferritin level of <100 ng/mL (absolute iron deficiency) or 100-299 ng/mL and transferrin saturation (TSAT) of <20% (functional iron deficiency).

Iron deficiency was once thought to only have clinical consequences in the presence of anemia but iron deficiency without anemia is now understood to be a significant contributor to increased mortality and hospitalization for heart failure. Iron deficiency in HFrEF has been extensively studied—these data suggest non-anemic iron-deficient patients experience worse clinical outcomes than anemic iron-replaced patients.

However, despite this identified association between iron deficiency and HFrEF, the prevalence of iron deficiency remains misunderstood, owing to infrequent screening for iron deficiency in non-anemic patients. Iron deficiency’s impact on outcomes, mortality, and various psychological parameters continues to be investigated—these study results could provide new insights into the management and prognosis of patients with HFrEF.

The prospective cohort study was conducted at King Edward Memorial Hospital in India and spanned 1.5 years, including 371 participants with HFreF. Each participant underwent comprehensive clinical and laboratory assessments, assessing iron deficiency with various hematological and biochemical parameters.

Among the 371 patients analyzed, 44 (12%) exhibited absolute iron deficiency and 141 (38%) exhibited functional iron deficiency, for a total of 185 (50%) participants presenting with iron deficiency. Among these 185 patients (mean age, 57 years; 42.5% female), 148 (80%) presented with anemia, and 43% (n = 81) anemics were in iron repletes (n = 186).

Based on these data, investigators noted there was a statistically significant association of anemia with iron deficiency, including absolute and functional deficiency (P <.05). Further analysis revealed iron deficiency was significantly associated with increased mortality in patients with HFrEF (x2, 3.88; P = .048). Those with iron deficiency were 1.9 times more likely to die than iron-replete patients (relative risk [RR], 1.9; 95% CI, 0.9884 to 3.7570; P = .0541).

Moreover, the analysis identified a significant correlation between absolute iron deficiency and dyspnea severity (r2 = .949; P = .026). However, no statistically significant relationship between functional or total iron deficiency and dyspnea severity was observed. Mean left ventricular ejection fraction (LVEF) measures were lower in iron-deficient patients than in non-deficient, but the difference was also not statistically significant (P = .299).

A comprehensive analysis of complete blood count (CBC), serum iron studies, blood glucose tests, lipid profiles, and serum C-reactive protein. The analysis revealed statistically significant differences between patients with and without iron deficiency in hemoglobin, serum iron, serum ferritin, TSAT, and total iron-binding capacity.

Mulkalway and colleagues suggested further research is required to refine optimal identification and management strategies for iron deficiency in heart failure. They noted the potential need for awareness campaigns to educate patients and providers on its significant implications.

“Further research is imperative to refine strategies for optimal identification and management of iron deficiency in HFrEF patients, elucidating the intricate mechanisms that underlie its association with adverse outcomes in this population,” they wrote.


Sarate N, Sonawane R, Pai V, Karatela S, Mulkalwar A. Iron Deficiency: A Silent Threat in Patients With Heart Failure With Reduced Ejection Fraction. Cureus. 2024;16(2):e53542. Published 2024 Feb 4. doi:10.7759/cureus.53542