Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction

Martens, Pieter; Nijst, Petra; Verbrugge, Frederik H.; Smeets, Kevin; Dupont, Matthias; Mullens, Wilfried

doi:10.1080/00015385.2017.1351239

Cited by 140 publications

(190 citation statements)

References 15 publications

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“…The decrease in maximum oxygen consumption in iron deficiency seems to be independent of LVEF . Iron deficiency seems to have greater clinical repercussions than anemia per se, and the associations with worsened exercise capacity, oxygen consumption, hospitalization, and mortality are stronger in patients with HF who have iron deficiency than in those with anemia without iron deficiency …”

Section: Epidemiology and Pathophysiology Of Anemia And Iron Deficienmentioning

confidence: 92%

“…Regardless of whether it is accompanied by anemia, iron deficiency affects patient prognosis, being associated with adverse clinical events, reduced oxygen consumption in exercise testing, worsening of functional class, increase in hospitalizations for HF, and increases in mortality in patients with HF . The decrease in maximum oxygen consumption in iron deficiency seems to be independent of LVEF .…”

Section: Epidemiology and Pathophysiology Of Anemia And Iron Deficienmentioning

confidence: 99%

“…This bias can help explain the disparate results among studies. Several studies found no differences in systolic function between patients with and without anemia, but others found worse systolic function in patients with anemia . Moreover, different studies used different techniques to measure myocardial contractility (eg, left ventricular systolic time interval ratio or left ventricular pre‐ejection period in impedance cardiography), further confounding efforts to compare results …”

Section: Echocardiography In Anemia and Iron Deficiencymentioning

confidence: 99%

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Anemia and iron deficiency in heart failure: a review of echocardiographic features

2019

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Anemia and iron deficiency are often associated with heart failure, influencing the symptoms and prognosis. Correction of anemia and iron deficiency improves functional capacity and decreases hospitalizations. Many studies have analyzed echocardiographic parameters in iron deficiency and anemia and their evolution after iron treatment; however, the heterogeneity of the results makes it difficult to draw conclusions. The aim of this paper is to review the echocardiographic parameters during anemia and iron deficiency, and their evolution after treatment. Available data suggest that they lead to ventricular and atrial remodeling, a decrease in ventricular contractility, and an alteration of ventricular relaxation, although in heart failure with preserved ejection fraction these changes are not significant. Anemia and iron deficiency also increase systolic pulmonary artery pressure. There is consistent evidence that correction of these comorbidities leads to a reduction in preload and left ventricular cavity dimensions, an improvement in diastolic and load‐independent ventricular systolic function parameters, and a decrease in systolic pulmonary artery pressure. However, the evidence is less consistent about the changes produced in ventricular hypertrophy, load‐dependent systolic function parameters, and E‐wave. Generally, anemia and iron deficiency affect the echocardiographic findings, and correcting these conditions often results in improvement in the affected echocardiographic parameters.

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Section: Epidemiology and Pathophysiology Of Anemia And Iron Deficienmentioning

confidence: 92%

Section: Epidemiology and Pathophysiology Of Anemia And Iron Deficienmentioning

confidence: 99%

Section: Echocardiography In Anemia and Iron Deficiencymentioning

confidence: 99%

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Anemia and iron deficiency in heart failure: a review of echocardiographic features

2019

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“…5 Briefly, the study cohort is the result of a pooled analysis of five different investigator-initiated prospective studies all performed at the ZOL Genk hospital, with overlapping design in terms of collection of baseline and clinical outcome data. The design and results of the heart failure database have previously been published.…”

Section: Study Populationmentioning

confidence: 99%

Prevalence of underlying gastrointestinal malignancies in iron‐deficient heart failure

et al. 2018

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AimsAnaemia and iron deficiency (ferritin level < 100 or 100–300 μg/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 resultsPatients 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 μg/L had the best acuity, detecting malignancies with a sensitivity of 80% and a specificity of 71%.ConclusionsEndoscopic 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.

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“…1,2 Iron deficiency is associated with a reduced functional status, poor exercise performance, and increased risk for heart failure hospitalization and cardiovascular mortality. 1,2 Iron deficiency is associated with a reduced functional status, poor exercise performance, and increased risk for heart failure hospitalization and cardiovascular mortality.…”

Section: Introductionmentioning

confidence: 99%

Rationale and design of the IRON‐CRT trial: effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy

et al. 2019

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Aims Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF). In patients with cardiac resynchronization therapy (CRT), it is associated with a diminished reverse remodelling response and poor functional improvement. The latter is partially related to a loss in contractile force at higher heart rates (negative force-frequency relationship). Methods and resultsThe effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy (IRON-CRT) trial is a multicentre, prospective, randomized, double-blind controlled trial in HFrEF patients who experienced incomplete reverse remodelling (defined as a left ventricular ejection fraction below <45%) at least 6 months after CRT. Additionally, patients need to have iron deficiency defined as a ferritin below 100 μg/L irrespective of transferrin saturation or a ferritin between 100 and 300 μg/L with a transferrin saturation <20%. Patients will be randomized to either intravenous ferric carboxymaltose (dose based according to Summary of Product Characteristics) or intravenous placebo. The primary objective is to evaluate the effect of ferric carboxymaltose on metrics of cardiac reverse remodelling and contractility, measured by the primary endpoint, change in left ventricular ejection fraction assessed by three-dimensional (3D) echo from baseline to 3 month follow-up and the secondary endpoints change in left ventricular end-systolic and enddiastolic volume. The secondary objective is to determine if ferric carboxymaltose is capable of improving cardiac contractility in vivo, by assessing the force-frequency relationship through incremental biventricular pacing. A total of 100 patients will be randomized in a 1:1 fashion. Conclusions The IRON-CRT trial will determine the effect of ferric carboxymaltose on cardiac reverse remodelling and ratedependent cardiac contractility in HFrEF patients.

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Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction

Abstract: Iron deficiency is common in patients with HFrEF, HFmrEF and HFpEF, and negatively affects VO and clinical-outcome. Progression of iron deficiency parallels an increased risk for worsening of heart failure.

Cited by 140 publications

References 15 publications

Anemia and iron deficiency in heart failure: a review of echocardiographic features

Anemia and iron deficiency in heart failure: a review of echocardiographic features

Prevalence of underlying gastrointestinal malignancies in iron‐deficient heart failure

Rationale and design of the IRON‐CRT trial: effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy

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