Project description: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.
Project description:AimsIntravenous ferric carboxymaltose (FCM) has been shown to improve functional capacity and quality of life in iron deficient heart failure patients. However, FCM's effect on hospitalizations and mortality remains unclear as previous randomized controlled trials (RCTs) and their meta-analyses have been underpowered to detect significant differences. We sought to conduct an updated meta-analysis using recently published RCT data.Methods and resultsOnline databases were searched from inception until November 2020 for RCTs evaluating the effects of FCM on clinical outcomes in iron-deficient heart failure patients. Outcomes of interest included heart failure hospitalizations, all-cause mortality, and cardiovascular mortality. Meta-analysis was performed using a fixed-effect model and estimates were reported as odds ratios (ORs), hazard ratios, or rate ratios (RRs) along with corresponding 95% confidence intervals (CIs). A total of 1947 patients (n = 1062 in the FCM group; n = 885 in the placebo group) were included. FCM, compared with placebo, significantly reduced the risk of the composite endpoint of time to first heart failure hospitalization or cardiovascular death (hazard ratio = 0.76; 95% CI = 0.63-0.90; I2 = 55%). FCM also significantly reduced the risk of recurrent heart failure hospitalizations (RR = 0.68; 95% CI = 0.54-0.85; I2 = 71%) and recurrent cardiovascular hospitalizations (RR = 0.71; 95% CI = 0.59-0.86; I2 = 56%). However, FCM had no significant effect on the risk of all-cause (OR = 0.97; 95% CI = 0.73-1.28; I2 = 0%) or cardiovascular mortality (OR = 0.93; 95% CI = 0.69-1.27; I2 = 0%).ConclusionsFerric carboxymaltose reduces heart failure hospitalizations and cardiovascular hospitalizations with no beneficial effect on all-cause and cardiovascular mortality in iron-deficient heart failure patients. These findings reinforce the role of FCM as a therapeutic option in heart failure patients.
Project description:Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1-year all-cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: -0.13 to 9.21). Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1-year all-cause mortality, first HHF, and improved LVEF with IV iron therapy.
Project description:There is an increasing awareness of the prevalence of iron deficiency (ID) in patients with heart failure (HF) and its contributory role in the morbidity and mortality of HF. It is important to note that many HF patients have ID without being anaemic, hence it is vital to screen for ID even in patients with haemoglobin within the normal laboratory range. This review summarises the pathophysiology and epidemiology of ID in HF before discussing the evidence for iron replacement therapy in HF patients. Finally, it discusses the ongoing large outcome trials evaluating iron replacement in HF.
Project description:BackgroundRandomized clinical trials (RCTs) evaluating the role of intravenous (IV) iron administration in patients with heart failure (HF) and iron deficiency (ID) have yielded inconsistent results.MethodsElectronic search of MEDLINE, EMBASE and OVID databases was performed until November 2022 for RCTs that evaluated the role of IV iron administration in patients with HF and ID. The main study outcomes were the composite of HF hospitalization or cardiovascular mortality, and individual outcome of HF hospitalization. Summary estimates were evaluated using random effects model.ResultsThe final analysis included 12 RCTs with 3,492 patients (1,831 patients in the IV iron group and 1,661 patients in the control group). The mean follow-up was 8.3 months. IV iron was associated with a lower incidence in the composite of HF hospitalization or cardiovascular mortality (31.9% vs. 45.3%; relative risk [RR] 0.72; 95% confidence interval [CI] 0.59-0.88) and individual outcome of HF hospitalization (28.4% vs. 42.2; RR 0.69; 95% CI 0.57-0.85). There was no significant difference between both groups in cardiovascular mortality (RR 0.88; 95% CI 0.75-1.04) and all-cause mortality (RR 0.95; 95% CI 0.83-1.09). IV iron was associated with lower New York Heart Association class and higher left ventricular ejection fraction (LVEF). Meta-regression analyses showed no effect modification for the main outcomes based on age, hemoglobin level, ferritin level or LVEF.ConclusionAmong patients with HF and ID, IV iron administration was associated with reduction in the composite of HF hospitalization or cardiovascular mortality and driven by a reduction in HF hospitalization.
Project description:BackgroundHeart failure (HF) is a major global challenge, emphasised by its designation as the leading cause of hospitalisation in those aged 65 and above. Approximately half of all patients with HF have concurrent iron deficiency (ID) regardless of anaemia status. In HF, iron deficiency is independently associated with higher rates of hospitalisation and death, lower exercise capacity, and poorer quality-of-life than in patients without iron deficiency. With such consequences, several studies have investigated whether correcting ID can improve HF outcomes. Main body. As of 1st June 2021, seven randomised controlled trials have explored the use of intravenous (IV) iron in patients with HF and ID, along with various meta-analyses including an individual patient data meta-analysis, all of which are discussed in this review. IV iron was well tolerated, with a comparable frequency of adverse events to placebo. In the context of heart failure with reduced ejection fraction (HFrEF), IV iron reduces the risk of hospitalisation for HF, and improves New York Heart Association (NYHA) functional class, quality-of-life, and exercise capacity (as measured by 6-min walk test (6MWT)) distance and peak oxygen consumption. However, the effect of IV iron on mortality is uncertain. Finally, the evidence for IV iron in patients with acute decompensated heart failure, or heart failure with preserved ejection fraction (HFpEF) is limited.ConclusionsIV iron improves some outcomes in patients with HFrEF and ID. Patients with HFrEF should be screened for ID, defined as ferritin < 100 µg/L, or ferritin 100-299 µg/L if transferrin saturation < 20%. If ID is found, IV iron should be considered, although causes of ID other than HF must not be overlooked.
Project description:ObjectiveThis study aimed to assess the cost-effectiveness of telehealthcare in heart failure patients as add-on to usual care.DesignA cost-utility analysis was conducted from a public payer perspective alongside the randomised controlled TeleCare North trial.SettingThe North Denmark Region, Denmark.ParticipantsThe study included 274 heart failure patients with self-reported New York Heart Association class II-IV.InterventionsPatients in the intervention group were provided with a Telekit consisting of a tablet, a digital blood pressure monitor, and a scale and were instructed to perform measurements one to two times a week. The responsibility of the education, instructions and monitoring of the heart failure (HF) patients was placed on municipality nurses trained in HF and telemonitoring. Both groups received usual care.Outcome measuresCost-effectiveness was reported as incremental net monetary benefit (NMB). A micro-costing approach was applied to evaluate the derived savings in the first year in the public health sector. Quality-adjusted life-years (QALY) gained were estimated using the EuroQol 5-Dimensions 5-Levels questionnaire at baseline and at a 1-year follow-up.ResultsData for 274 patients were included in the main analysis. The telehealthcare solution provided a positive incremental NMB of £5164. The 1-year adjusted QALY difference between the telehealthcare solution and the usual care group was 0.0034 (95% CI: -0.0711 to 0.0780). The adjusted difference in costs was -£5096 (95% CI: -8736 to -1456) corresponding to a reduction in total healthcare costs by 35%. All sensitivity analyses showed the main results were robust.ConclusionsThe TeleCare North solution for monitoring HF was highly cost-effective. There were significant cost savings on hospitalisations, primary care contacts and total costs.Trial registration numberClinicalTrials.gov: NCT02860013.
Project description:IntroductionHeart failure (HF) presents a significant health challenge, with intravenous (IV) iron therapy considered a potential treatment avenue.MethodWe assessed IV iron therapy's efficacy in HF patients with concurrent iron deficiency versus standard of care. Primary outcomes included the composite of HF hospitalizations or cardiovascular-related mortality, HF hospitalizations, and all-cause, HF, and cardiovascular mortality rates. Secondary measures encompassed improvements in New York Heart Association functional classification, quality of life, 6-minute walk test, left ventricular ejection fraction, and adverse events. We used a random-effects model to compute relative risk (RR) or mean difference (MD) with 95% confidence intervals (CIs).ResultsBased on an analysis of 14 randomized controlled trials involving 6614 patients, IV iron therapy significantly reduced composite outcome (RR: 0.84, 95% CI: 0.73, 0.96; P = 0.01) and HF hospitalizations (RR: 0.74, 95% CI: 0.61, 0.89; P = 0.002) compared to standard of care. Mortality rates showed no significant difference. IV iron therapy improved New York Heart Association functional classification, quality of life, and 6-minute walk test, with no major impact on left ventricular ejection fraction. Adverse events remained stable.ConclusionsIV iron therapy holds promise for diminishing HF hospitalizations and enhancing quality of life and 6-minute walk test in HF patients. Yet, its effect on all-cause or cardiovascular mortalities appears limited.
Project description:In patients with heart failure (HF), iron deficiency (ID) correlates with decreased exercise capacity and poor health-related quality of life, and predicts worse outcomes. Both absolute (depleted iron stores) and functional (where iron is unavailable for dedicated tissues) ID can be easily evaluated in patients with HF using standard laboratory tests (assessment of serum ferritin and transferrin saturation). Intravenous iron therapy in iron-deficient patients with HF and reduced ejection fraction has been shown to alleviate HF symptoms and improve exercise capacity and quality of life. In this paper, we provide information on how to diagnose ID in HF. Further we discuss pros and cons of different iron preparations and discuss the results of major trials implementing iron supplementation in HF patients, in order to provide practical guidance for clinicians on how to manage ID in patients with HF.
Project description:AimsFor patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta-analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF.Methods and resultsWe identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all-cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61-0.93; p < 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53-0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70-1.05; p = 0.14) and all-cause mortality (OR 0.93, 95% CI 0.78-1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow-up, which was less disrupted by the COVID-19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49-0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74-1.30) (heterogeneity p = 0.07).ConclusionIn patients with HF and ID, this meta-analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all-cause mortality remains inconclusive.