Intravenous Iron Therapy in Heart Failure With Reduced Ejection Fraction: Tackling the Deficiency.
Ontology highlight
ABSTRACT:
SUBMITTER: Sawicki KT
PROVIDER: S-EPMC8323966 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Intravenous Iron Therapy in Heart Failure With Reduced Ejection Fraction: Tackling the Deficiency.
Sawicki Konrad Teodor KT Ardehali Hossein H
Circulation 20210726 4
Similar Datasets
Project description:AimsA budget impact analysis compared treating patients with heart failure (HF) and reduced ejection fraction (HFrEF) and iron deficiency (ID) in Switzerland with intravenous ferric carboxymaltose (FCM) or placebo.MethodsClinical data from four international randomized trials showed that FCM versus placebo treatment was associated with a reduced hospitalization rate due to HF. The budget impact of this was modelled over 1 year. Hospital treatment costs for HFrEF, FCM drug costs, and estimated patient numbers were based on published data, official tariffs, specially commissioned analyses of SwissDRG data, and clinical and diagnosis-related groups (DRG) coding expert opinion. The original cost year was 2015. Sensitivity analyses were conducted including updated unit costs from 2019/2020.ResultsFCM treatment was associated with average cost savings of Swiss Francs (SFr) 503 per patient per year from the perspective of the Swiss mandatory health insurance system. Extrapolating across all eligible HFrEF patients with ID in Switzerland, this amounted to estimated savings of SFr 23,336,873. Sensitivity analyses showed these results to be robust in the face of changes to input parameters like treatment costs, different hospital settings, updated unit costs, and including outpatient treatment and patient co-payments in the analysis.ConclusionsThe present analysis shows that using FCM to treat HFrEF patients with ID in line with current guideline recommendations resulted not only in medical benefits but also in significant cost savings. The analysis also provides an example of the pitfalls of transferring economic evaluation results, even between countries with similar hospital reimbursement systems.
| S-EPMC9440178 | biostudies-literature
Project description:AimIntravenous ferric carboxymaltose (FCM) has been shown to improve overall quality of life in iron-deficient heart failure with reduced ejection fraction (HFrEF) patients at a trial population level. This FAIR-HF and CONFIRM-HF pooled analysis explored the likelihood of individual improvement or deterioration in Kansas City Cardiomyopathy Questionnaire (KCCQ) domains with FCM versus placebo and evaluated the stability of this response over time.Methods and resultsChanges versus baseline in KCCQ overall summary score (OSS), clinical summary score (CSS) and total symptom score (TSS) were assessed at weeks 12 and 24 in FCM and placebo groups. Mean between-group differences were estimated and individual responder analyses and analyses of response stability were performed. Overall, 760 (FCM, n = 454) patients were studied. At week 12, the mean improvement in KCCQ OSS was 10.6 points with FCM versus 4.8 points with placebo (least-square mean difference [95% confidence interval, CI] 4.36 [2.14; 6.59] points). A higher proportion of patients on FCM versus placebo experienced a KCCQ OSS improvement of ≥5 (58.3% vs. 43.5%; odds ratio [95% CI] 1.81 [1.30; 2.51]), ≥10 (42.4% vs. 29.3%; 1.73 [1.23; 2.43]) or ≥15 (32.1% vs. 22.6%; 1.46 [1.02; 2.11]) points. Differences were similar at week 24 and for CSS and TSS domains. Of FCM patients with a ≥5-, ≥10- or ≥15-point improvement in KCCQ OSS at week 12, >75% sustained this improvement at week 24.ConclusionTreatment of iron-deficient HFrEF patients with intravenous FCM conveyed clinically relevant improvements in health status at an individual-patient level; benefits were sustained over time in most patients.
| S-EPMC9313582 | biostudies-literature
Project description:Over the past decade, the detrimental impact of iron deficiency in heart failure with reduced ejection fraction has become abundantly clear, showing a negative impact on functional status, quality of life, cardiac function and structure, exercise capacity and an increased risk of hospitalisation due to heart failure. Mechanistic studies have shown the impact of iron deficiency in altering mitochondrial function and negatively affecting the already altered cardiac energetics in heart failure with reduced ejection fraction. Such failing energetics form the basis of the alterations to cellular myocyte shortening, culminating in reduced systolic function and cardiac performance. The IRON-CRT trials show that ferric carboxymaltose is capable of improving cardiac structure and cardiac performance. This article discusses the effect of iron deficiency on cardiac function and structure and how it can be alleviated.
| S-EPMC8977990 | biostudies-literature
Project description:BackgroundGuidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) have medical therapy titrated to target doses derived from clinical trials, as tolerated. The degree to which titration occurs in contemporary U.S. practice is unknown.ObjectivesThis study sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and to identify associated factors and reasons for medication changes.MethodsAmong 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry with complete medication data and no contraindications to medical therapy, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) were examined at baseline and at 12-month follow-up.ResultsAt baseline, 658 (25%), 525 (20%), 287 (11%), and 45 (2%) patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI therapy, respectively. At 12 months, proportions of patients with medication initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation or dose decrease were 4%, 7%, 11%, and 3%, respectively. Over 12 months, <1% of patients were simultaneously treated with target doses of ACEI/ARB/ARNI, beta-blocker, and MRA. In multivariate analysis, across the classes of medications, multiple patient characteristics were associated with a higher likelihood of initiation or dose increase (e.g., previous HF hospitalization, higher blood pressure, lower ejection fraction) and discontinuation or dose decrease (e.g., previous HF hospitalization, impaired quality of life, more severe functional class). Medical reasons were the most common reasons for discontinuations and dose decreases of each therapy, but the relative contributions from patient preference, health team, and systems-based reasons varied by medication.ConclusionsIn this contemporary U.S. registry, most eligible HFrEF patients did not receive target doses of medical therapy at any point during follow-up, and few patients had doses increased over time. Although most patients had no alterations in medical therapy, multiple clinical factors were independently associated with medication changes. Further quality improvement efforts are urgently needed to improve guideline-directed medication titration for HFrEF.
| S-EPMC7197490 | biostudies-literature
Project description:: Iron deficiency is present in ≈50% of patients with heart failure and is an independent predictor of mortality. Despite growing recognition of the functional and prognostic significance of iron deficiency, randomized multicenter trials exploring the use of oral iron supplementation in heart failure, a therapy that is inexpensive, readily available, and safe, have not been performed. Moreover, patient characteristics that influence responsiveness to oral iron in patients with heart failure have not been defined. Although results of intravenous iron repletion trials have been promising, regularly treating patients with intravenous iron products is both expensive and poses logistical challenges for outpatients. Herein, we describe the rationale for the Oral Iron Repletion effects on Oxygen Uptake in Heart Failure (IRONOUT HF) trial. This National Institute of Health-sponsored trial will investigate oral iron polysaccharide compared with matching placebo with the primary end point of change in exercise capacity as measured by peak oxygen consumption at baseline and at 16 weeks. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02188784.
| S-EPMC6078413 | biostudies-literature
Project description:AimsHeart failure (HF) is a proinflammatory disease often associated with the onset of iron deficiency (ID). ID alters mitochondrial function, reducing the generation of cellular energy in skeletal muscle and cardiomyocytes. This study aimed to analyse the response of patients with HF to intravenous iron administration according to the type of HF: preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF).Methods and resultsWe conducted a retrospective, single-centre study of 565 consecutive outpatients diagnosed with HF, recruited over 5 years, who were given intravenous ferric carboxymaltose (FCM) for the treatment of ID [defined as ferritin < 100 μg/L or ferritin 100-300 μg/L with transferrin saturation (TSAT) < 20%]. Clinical, laboratory, and echocardiographic parameters were analysed before and after administration. After FCM administration, overall ferritin, TSAT, and haemoglobin levels increased up to 5-fold, 1.6-fold, and 1.1-fold, respectively, relative to baseline values in HF patients with reduced and preserved ejection fraction (P < 0.0001), with a greater increase in ferritin and TSAT in HFpEF patients. The left ventricular ejection fraction of the overall series improved by 8 percentage points in both types of HF (from 40% to 48%, P < 0.0001). The percentage of patients with normalization of right ventricular function increased by 6.9 points (from 74.1% to 81%) in HFpEF patients and by 6.4 points (from 53% to 59.4%) in the HFrEF subgroup (P < 0.0001). New York Heart Association functional status slightly improved, from a median of 2.4 (interquartile range, IQR: 2-2.7) to 1.9 (IQR: 1.5-2.5; P < 0.0001) after FCM in both types of HF. No changes were noted in plasma levels of liver enzymes, creatinine, or natriuretic peptide (P > 0.05).ConclusionsIntravenous iron administration appeared to improve ejection fraction and cardiac functional status in outpatients with ID and HF with both preserved and reduced ejection fraction.
| S-EPMC8788053 | biostudies-literature
Project description:AimsThis study aimed to investigate the prognostic value of dynamic changes in left ventricular ejection fraction (EF) for cardiovascular (CV) outcomes in an all-comer heart failure (HF) population with reduced EF (HFrEF, EF < 40%). We sought to identify independent factors related to improvement in EF and to identify risk factors for increased risk of CV events in the subgroups of improved EF (iEF) and non-improved EF (niEF), respecively.Methods and resultsThis is a retrospective sub-analysis from the REDEAL HF trial, which included consecutive patients with chronic HF who were hospitalized from July 2009 to December 2017. Baseline and follow-up echocardiography data (interval ≥12 months) of 573 consecutive patients with HFrEF were analysed. iEF was defined as absolute improvement in EF ≥ 10% and follow-up EF over 40%. The primary endpoint was defined as a composite endpoint of cardiovascular (CV) death, CV hospitalization, or appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular arrhythmia. EF improved in 37.2% of patients with HFrEF during follow-up (median period of 17 months). iEF was independently associated with shorter HF duration (>4 vs. ≤4 years, odd ratio [OR] = 0.477, 95% CI 0.305-0.745), no coronary artery disease (CAD vs. no CAD, OR = 0.583, 95% CI 0.396-0.858), and no ICD implantation (ICD vs. no ICD, OR = 0.341, 95% CI 0.228-0.511). Compared with niEF, iEF was significantly and independently associated with lower all-cause mortality (22.1% vs. 31.1%, P = 0.019; hazard ratio [HR] = 0.674, 95% CI 0.469-0.968), lower CV mortality (8.9% vs. 16.1%, P = 0.015; HR = 0.539, 95% CI 0.317-0.916), and lower CV events risk (27.2% vs. 49.2%, P < 0.001; HR 0.519, 95% CI 0.381-0.708), after adjustment for age, sex, duration of HF, and other clinical risk factors. Hypertension (HR = 2.452, P = 0.032) and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP >1153 pg/mL, HR = 4.372, P < 0.001) were identified as independent risk factors for CV events in the iEF subgroup. ICD implantation (HR = 1.533, P = 0.011), elevated NT-proBNP (HR = 1.626, P = 0.018), increased left atrial volume index (HR = 1.461, P = 0.021), reduced lateral mitral annular plane systolic excursion (HR = 1.478, P = 0.025), and reduced tricuspid plane systolic excursion (HR = 1.491, P = 0.039) were identified as risk factors for CV events in the niEF subgroup.ConclusionsImprovement in EF is independently related to the longer survival and lower CV related mortality and hospitalization rate of HFrEF. Elevated baseline NT-proBNP is identified as the strongest prognostic factor associated with increased CV events risk in HFrEF patients both with and without improved EF, regardless of age, sex, duration of HF, and other clinical risk factors.
| S-EPMC10053299 | biostudies-literature
Project description:AimsHeart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging.Methods and resultsPatients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40-49% on the second study. Patients were classified as HFmrEF-Increasing if LVEF had increased ≥10% (n = 450), HFmrEF-Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF-Stable if they did not meet other criteria (n = 389). The primary outcome was all-cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co-morbidities, and medications. In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow-up of 15.3 months, the composite outcome occurred in 811 patients. During follow-up, patients with HFmrEF-Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60-0.88, P < 0.001] compared with HFmrEF-Stable. Patients with HFmrEF-Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01-1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98-1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF-Increasing: adjusted HR 0.72, 95% CI 0.59-0.88, P = 0.005; HFmrEF-Decreasing: adjusted HR 1.20, 95% CI 1.01-1.44, P = 0.044). Patients with HFmrEF-Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89-1.20, P = 0.670). Patients with HFmrEF-Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62-0.87, P < 0.001).ConclusionsAmongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions.
| S-EPMC9065872 | biostudies-literature
Project description:Heart failure with reduced ejection fraction (HFrEF) is a common, incompletely treatable, complex, progressive, and severe medical problem despite guideline-directed medical therapy. HFrEF is associated with sympathetic activation and parasympathetic inhibition; these reflexive processes may ultimately be maladaptive and exacerbate or even perpetuate the problem. Attempts to regulate autonomic tone during HFrEF in animal models and in humans has shown promise with beneficial effects that include improvement in symptoms, mitigation of arrhythmic events, reduction in mortality, and correction in hemodynamics. Several modalities to regulate autonomic tone such as unilateral parasympathetic nerve activation, baroreceptor activation, renal nerve ablation and spinal cord stimulation have been investigated. Although they demonstrated some benefit, the long-term efficacy in HFrEF has not been proven. Considering specific limitations of each modality, to draw definitive conclusions is impossible at this time. Here, we review the present state-of-the-art hiterature? of device of autonomic regulation therapy to affect outcomes in HFrEF.
| S-EPMC7533145 | biostudies-literature
Project description:BackgroundChronic congestive heart failure is a common condition that, if untreated, markedly impairs the quality of life and is associated with a high risk of recurrent hospitalization and death.MethodsThis review is based on articles retrieved by a selective search in PubMed, as well as on relevant guidelines.ResultsEvidence-based treatment options are available only for congestive heart failure with a low ejection fraction. Pharma - cotherapy is based on neurohumoral inhibition of the renin-angiotensin-aldosterone system and the adrenergic system. The prognosis of patients with this condition has been further improved recently through the introduction of combined angiotensin receptor antagonists and neprilysin inhibitors. Modern implantable devices are a further component of treatment. Implantable defibrillators and special pacemakers for cardiac resynchronization are well established; the utility of alternative devices (baroreflex modulation or cardiac contractility modulation) needs to be investigated in further studies. It was recently shown that the catheter-based treatment of secondary mitral regurgitation with a MitraClip improves the outcome of selected patients.ConclusionThe treatment of chronic systolic heart failure as recommended in the relevant guidelines, with drugs and implanted devices if indicated, can significantly improve the clinical outcome.
| S-EPMC7643567 | biostudies-literature