The following are key points to remember from this state-of-the-art review about iron deficiency in patients with cardiovascular disease:

1. Iron deficiency is typically defined as a ferritin <100 ng/mL (absolute iron deficiency) or ferritin 100-299 ng/mL and a transferrin saturation (TSAT) <20% (functional iron deficiency). These definitions have been validated in the heart failure (HF) population with 82% sensitivity and 72% specificity compared to bone marrow iron staining. Alternative definitions of iron deficiency use transferrin receptor or TSAT ≤19.8% with serum iron ≤13 μmoL/L.
2. Approximately one-half of patients with HF have iron deficiency with or without anemia, with a slightly higher prevalence in HF with preserved ejection fraction (HFpEF) compared to HF with mildly reduced EF (HFmrEF) or HF with reduced EF (HFrEF). Women, older patients, and those with increased disease severity or symptoms are more likely to have iron deficiency.
3. Iron deficiency has been associated with higher 5-year mortality, increased risk of all-cause death and all-cause hospitalizations in patients with HF, with higher risk of death or HF hospitalization associated with persistent iron deficiency. In patients with acute decompensated HF, iron deficiency was similar in HFrEF (54%) and HFpEF (56%); however, only associated with longer hospital stay in patients with HFrEF.
4. Oral iron supplementation has not been shown in randomized controlled trials to improve outcomes in patients with HF, potentially due to limited absorption and lack of tolerance due to side effects such as nausea, diarrhea, constipation, and flatulence.
5. Intravenous (IV) iron supplementation in HF patients has been shown to improve functional status and quality of life, and reduce HF hospitalizations; however, data on mortality benefit have been conflicting. Most randomized controlled trials have included patients with acute or chronic HF with left ventricular EF (LVEF) <45-50% with or without anemia (hemoglobin <13.5-15 g/dL) with ferric carboxymaltose being the most studied iron formulation to date.
6. Iron deficiency is associated with higher risk of ischemic heart events and cardiovascular mortality (with or without pre-existing coronary artery disease [CAD]). Iron deficiency has been found in 43% of patients presenting with acute coronary syndrome and up to 60% of patients with CAD. Iron deficiency in CAD is associated with increased risk of cardiovascular mortality and myocardial infarction; however, treatment with IV iron has not been studied in this population.
7. Around 45% of patients with cerebrovascular disease are iron deficient and this may be associated with decreased functional status, inflammation, and anemia. There are no data for treatment of iron deficiency in the absence of anemia in patients with cerebrovascular disease.
8. Aortic stenosis is associated with iron deficiency in approximately 50% of patients with sparse and inconclusive data on outcomes. IV iron did not show benefit in 6-minute walk distance (6MWD), New York Heart Association (NYHA) class, or health-related quality of life in patients with aortic stenosis after transcatheter aortic valve implantation (TAVI) and is not currently recommended in the absence of anemia.
9. Approximately 50% of patients with atrial fibrillation (AF) have iron deficiency, although there are not conclusive data on outcomes or use of iron supplementation in this disease state. The IRON-AF trial is currently underway, which will assess the effect of iron repletion with IV ferric carboxymaltose in patients with AF and iron deficiency on outcomes including peak oxygen uptake, quality of life, 6MWD, AF burden, health resource utilization, and mortality.
10. Iron deficiency can be found in up to 75% of patients with pulmonary hypertension (PH) with a range in prevalence depending on the type of PH (e.g., highest in precapillary PH [75%], and lowest in chronic thromboembolism [20%]). Data on outcomes and treatment response are limited and suggest no indication to treat iron deficiency in the absence of anemia in PH.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Valvular Heart Disease, Atherosclerotic Disease (CAD/PAD), Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Lipid Metabolism, Nonstatins, Acute Heart Failure, Pulmonary Hypertension, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Structural Heart Disease, Interventions and Vascular Medicine, Diet, Hypertension

Keywords: Acute Coronary Syndrome, Anemia, Anemia, Iron-Deficiency, Aortic Valve Stenosis, Atrial Fibrillation, Cardiovascular Diseases, Cerebrovascular Disorders, Coronary Artery Disease, Dietary Supplements, Ferritins, Heart Failure, Hemoglobins, Hypertension, Pulmonary, Inflammation, Myocardial Infarction, Patient Care Team, Primary Prevention, Quality of Life, Receptors, Transferrin, Stroke Volume, Thromboembolism, Transcatheter Aortic Valve Replacement, Transferrins

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