ABSTRACT: AIMS:Anaemia and iron deficiency (ferritin level < 100 or 100-300 ?g/L with transferrin saturation < 20%) are prevalent in heart failure. Mechanistically, iron deficiency is linked to poor intestinal uptake, increased intestinal loss, and chronic inflammation. However, the prevalence of underlying gastrointestinal malignancies is not established in iron-deficient heart failure with or without anaemia. METHODS AND RESULTS:Patients followed up in a single-centre, heart failure database with baseline registration of haemoglobin and iron status were retrospectively evaluated. The proportion of patients undergoing upper and lower gastrointestinal endoscopy between inclusion and censoring was determined. Afterwards, the prevalence of biopsy that confirmed intestinal malignancies in relation to baseline iron and haemoglobin status was determined. Anaemia was defined as a haemoglobin level <12 g/dL, and iron deficiency according to the aforementioned criteria. Of the 1197 patients in the database, 699 (59%) patients underwent full endoscopic workup over a mean follow-up of 50 ± 27 months. A total of 50 intestinal malignancies were identified (n = 42, 84%, in iron-deficient vs. n = 8, 16%, non-iron-deficient patients; P < 0.001). The prevalence of intestinal malignancies was non-statistically different in iron-deficient patients with anaemia (n = 12/129, 9.3%) or without anaemia (n = 30/287, 10.5%; P = 0.551). The prevalence was much lower in patients without iron deficiency with anaemia (n = 5/83, 6%) or without anaemia (n = 3/200, 1.5%). In patients with iron deficiency but without anaemia (a group in which the role of endoscopic workup is less established), ferritin levels carried an inverse diagnostic capacity in detecting patients with an underlying malignancy (area under the curve = 0.741, P < 0.001). A ferritin level < 56 ?g/L had the best acuity, detecting malignancies with a sensitivity of 80% and a specificity of 71%. CONCLUSIONS:Endoscopic evaluation is warranted in heart failure patients with iron-deficient anaemia given the high prevalence of underlying intestinal malignancies, as advised by gastroenterology guidelines. However, additional research is needed assessing the best approach to patients with iron deficiency without anaemia, given the high occurrence of intestinal malignancies in these patients. A lower ferritin level could potentially help stratify the need for an endoscopic workup in these patients.