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Abstract
Introduction Iron deficiency anaemia (IDA) is common in patients with heart failure (HF) and is associated with advanced HF and increased mortality. Intravenous iron supplementation increases exercise tolerance, improves quality of life, and decreases symptoms among patients with HF with reduced ejection fraction (HFrEF) and iron deficiency. Despite this, many patients are not screened or treated for IDA. We aimed to increase rates of screening and treatment of IDA among HF patients through the introduction of curated materials to aid HF clinicians with appropriate screening and treatment.
Methods We conducted a retrospective chart review to identify the baseline number of HFrEF patients screened and treated for IDA at two ambulatory cardiology clinics in Toronto, Ontario. A quality improvement initiative was then introduced, which consisted of education and curated materials to aid clinicians in the screening and treatment of IDA among HFrEF patients. The proportion of patients screened and treated for IDA preintervention and postintervention were compared using χ2 tests of Independence.
Results In the preintervention cohort, 36.3% (n=45) of patients with anaemia were screened for IDA. Among those screened, 64.4% (n=29) had IDA. Only 17.2% (n=5) of these were treated with IV iron. After implementation of the quality improvement initiative, 90.9% (n=60) of patients with anaemia were screened for IDA (p<0.001) and 90.3% (n=28) of those with IDA were treated with IV iron (p<0.001).
Conclusion The introduction of curated materials to aid clinicians was associated with increased rates of screening and treatment of IDA among ambulatory HFrEF patients. Further work is required to identify barriers and implement strategies to increase screening and treatment rates of IDA among HFrEF patients.
- Ambulatory care
- Chronic disease management
- Quality improvement
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Iron deficiency is common in patients with heart failure and is associated with worse symptoms and increased mortality.
Intravenous iron supplementation increases exercise tolerance, improves quality of life, decreases fatigue, and decreases heart failure symptoms in patients with reduced ejection fraction and iron deficiency.
WHAT THIS STUDY ADDS
We identified that rates of screening and treatment of iron deficiency in ambulatory patients with heart failure at our centre are low.
The implementation of curated materials to aid heart failure clinicians was associated with significantly increased rates of screening and treatment of iron deficiency in ambulatory patients with heart failure.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Future work is required to identify barriers to screening and treatment of iron deficiency among heart failure patients, and to implement strategies to increase rates in both ambulatory and inpatient settings.
Introduction
Iron deficiency (ID) is common in patients with heart failure (HF), affecting up to 60% of those with and 40% of those without anaemia.1–4 In patients with HF, iron deficiency anaemia (IDA) is defined as a haemoglobin <130 g/L and either ferritin <100 ng/mL or ferritin 100–300 ng/mL with transferrin saturation <20%.5–7
In patients with HF, anaemia is associated with reduced exercise capacity, adverse left ventricular (LV) remodelling, advanced HF, decreased renal function, and increased mortality.8–10 Independent of anaemia, ID is associated with reduced exercise capacity and quality of life, as well as increased mortality among those with HF.1 2 11 12
The CONFIRM-HF (Ferric Carboxymaltose Evaluation on Performance in Patients with Iron Deficiency in Combination with Chronic Heart Failure)13 and FAIR-HF (Ferinject Assessment in Patients with Iron Deficiency and Chronic Heart Failure)14 trials demonstrated that intravenous (IV) iron supplementation can abate certain negative sequelae associated with ID. Specifically, these studies demonstrated that IV iron can increase exercise tolerance, improve quality of life, decrease fatigue, and decrease HF symptoms among patients with reduced ejection fraction and ID.13 14 Meta-analyses have shown that IV iron in patients with HF and ID also decreases cardiovascular and HF hospitalisations and all-cause mortality, without an increase in adverse effects.15–17
IV iron is preferred over oral iron for the treatment of ID in patients with HF due to poor absorption and inadequacy of oral iron to replete stores.6 18 Furthermore, oral iron supplementation has not been shown to have benefit on exercise capacity or quality of life in HF patients.19 20
The European Society of Cardiology, Canadian Cardiovascular Society, American College of Cardiology, and American Heart Association recommend that patients with heart failure with reduced ejection fraction (HFrEF) are screened and treated for ID with IV iron, regardless of haemoglobin level.5 21 22 Despite recommendations from clinical guidelines, many barriers prevent the screening and treatment of ID in patients with HF. These barriers include (1) the lack of understanding of appropriate screening tests and interpretation of iron studies, (2) the organisation and provision of IV infusions within the clinical setting, (3) the cost of IV iron, (4) the lack of experience by healthcare providers regarding the counselling and management of adverse effects, (5) provider time constraints, and (6) the appropriate follow-up of biochemical and clinical response to IV iron therapy.
The aim of our study was to implement a quality improvement initiative consisting of education and curated materials to support HF clinicians in the appropriate screening and treatment of IDA among ambulatory patients with HFrEF. The objective of the project was to determine the change in proportion of HFrEF patients who were screened and treated for IDA after the implementation of this quality improvement initiative.
Methods
Study context and design
This was a quality improvement project conducted at a tertiary care hospital (Sunnybrook Health Sciences Centre (SHSC)) in Toronto, Canada between 1 January 2018 and 27 October 2021. The study included patients from two ambulatory clinics at SHSC: the HF Clinic and Rapid Cardiology Assessment Clinic (RCAC). The objective of the study was to determine the change in proportion of patients with HFrEF who were screened and treated for IDA after implementation of a quality improvement initiative. The project focused on patients with IDA only, and not patients with ID without anaemia, given the logistical barriers to screening and treating a greater number of patients during the COVID-19 pandemic.
The first part of the study consisted of a retrospective chart review to identify the baseline number of HFrEF patients screened and treated for IDA at the HF Clinic and RCAC between 1 January 2018 and 1 January 2020. A quality improvement initiative was then implemented starting 27 October 2020, to aid clinicians in the screening and treatment of IDA in HF patients. The second part of the study aimed to determine the change in proportion of HF patients screened and treated for IDA at the HF Clinic and RCAC between 27 October 2020 and 27 October 2021, after implementation of this quality improvement initiative. The postintervention period was shorter due to resource limitations during the COVID-19 pandemic (ie, reduced access to the outpatient infusion suit).
Preintervention cohort
The preintervention cohort included patients identified by retrospective chart review who attended the HF Clinic or RCAC at SHSC between 1 January 2018 through 1 January 2020. This was completed using the hospital patient record, including patient data from the electronic medical record (SunnyCare; SOVERA, CGI), and the blood bank information system (WellSky, Kansas, USA). Patients were included in the preintervention cohort if they had HFrEF, defined as ejection fraction ≤40%. Patients were excluded if they did not have a valid Ontario Health Insurance Plan health card or if they had an active bacterial or viral infection, due to concerns for increased pathogen growth with IV iron. Patients were also excluded if they had hypotension, defined as systolic blood pressure ≤90 mm Hg, due to the potential risk of aggravating hypotension with IV iron (figure 1).
Flow chart describing the patient selection and exclusion process for the preintervention and postintervention cohort.
For each patient included in the preintervention cohort, the following data were extracted from their chart: (1) baseline demographics: age, sex, New York Heart Association (NYHA) class, left ventricular ejection fraction at the first visit within the study timeline, aetiology of HF (ischaemic or non-ischaemic), and body weight; (2) pre-existing medical comorbidities: hypertension, dyslipidaemia, diabetes mellitus, atrial fibrillation, past or active smoking, family history of cardiovascular disease, prior myocardial infarction, prior coronary revascularisation, angina pectoris, and stroke; (3) active medications and devices, including diuretics, angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), angiotensin receptor-neprilysin inhibitors (ARNi), beta blockers, mineralocorticoid receptor antagonists, antiplatelet agents, anticoagulants, lipid-lowering therapy, oral hypoglycaemic agents, insulin, implantable cardioverter-defibrillators, and cardiac resynchronisation therapy devices; (4) most recently documented pre-IV and post-IV iron treatment complete blood count, mean corpuscular volume, ferritin, transferrin saturation, total iron binding capacity (TIBC), creatinine, electrolytes, and N-terminal pro-hormone brain natriuretic peptide (NT-proBNP); (5) and adverse events: emergency department visits for HF management, hospitalisation for any cardiovascular cause, hospitalisation for worsening HF, death due to cardiovascular cause, death due to worsening HF, and adverse reactions to IV iron.
In the retrospective chart review, a patient was considered to have been screened for IDA if values for CBC and ferritin plus or minus transferrin saturation were available within the laboratory system or had been documented in the note (for external laboratory testing). A patient was considered to have IDA if they had a haemoglobin <130 g/L and either ferritin <100 ng/mL or ferritin 100–300 ng/mL with transferrin saturation <20%, as per the most widely accepted definition of IDA by the Canadian Cardiovascular Society, European Cardiovascular Society, and American College of Cardiology.5–7 In this study, a patient was considered to have been treated for IDA if they had received either two doses of iron sucrose 300 mg (Venofer) or ferric derisomaltose 1000 mg (Monoferric). Iron sucrose and ferric derisomaltose are the only non-iron dextran formulations used in outpatients in our jurisdiction.
Intervention
The intervention was a quality improvement initiative, consisting of education and curated materials to aid HF clinicians in the screening and treatment of IDA between 27 October 2020 and 27 October 2021. These curated materials were referred to as the Pumping Iron Bundle, which consisted of: (1) an IV iron replacement protocol (online supplemental appendix I); (2) a prefilled IV iron order set for outpatient hospital infusion (online supplemental appendix II); (3) a prefilled hospital laboratory requisition form that requested CBC, ferritin, TIBC (which includes iron and transferrin saturation), creatinine, electrolytes, and NT-proBNP; (4) a prefilled laboratory requisition form for outpatient laboratories that requested CBC, ferritin, TIBC, creatinine, electrolytes, and NT-proBNP; (5) a patient information handout about iron supplementation for IDA (online supplemental appendix III); and (6) a prefilled Exceptional Access Programme form for government reimbursement for IV iron for patients without private insurance. These materials were introduced through a rounds-style live seminar for the clinic staff, which consisted of a Cardiologist and Nurse Practitioner. Content of the educational sessions included: ID as it relates to HF, guidelines related to ID and HF, treatment modalities for ID, benefit of IV iron, laboratory testing and interpretation of iron studies, and recommended follow-up for patients with ID. The authors also conducted monthly check-ins with the clinic staff to address any questions and review the diagnostic and treatment algorithms.
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Postintervention cohort
The postintervention cohort consisted of patients identified through retrospective chart review from 27 October 2020 to 27 October 2021, who attended the HF Clinic or RCAC, after implementation of the Pumping Iron Bundle along with educational sessions. The same inclusion and exclusion criteria were used in the postintervention cohort as in the preintervention cohort. In addition, the same criteria were used to define screening and treatment of IDA in the postintervention cohort as in the pre-intervention cohort.
Outcome measures
Primary outcomes measured were as follows: (1) the proportion of HFrEF patients screened for IDA preintervention and postintervention, (2) the proportion of HFrEF patients diagnosed for IDA preintervention and postintervention, and (3) the proportion of HFrEF patients with IDA who were eligible for iron therapy (excluding those with allergy, other confounding comorbidities, or personal preference to decline therapy) treated preintervention and postintervention. The primary aim of the quality improvement initiative was to have at least 75% of HFrEF patients screened and treated for IDA after implementation of the Pumping Iron Bundle.
Secondary outcomes of the study included: (1) preintervention to postintervention emergency department visits for HF management, (2) 12 month hospitalisation for any cardiovascular cause, (3) 12 month hospitalisation for HF, (4) death due to any cause, and (5) adverse effects from IV iron.
Statistical analysis
The proportion of patients with IDA and the proportion of patients treated with IV iron preintervention and postintervention were compared using χ2 Tests of Independence. Results are reported as a percentage of total for categorical variables. A p value<0.05 was deemed significant. All analyses were completed using the R statistical software package (V.4.1.2, R Core Team 2021).23
Ethical considerations
The study was approved by the hospital Research Ethics Board (Project Identification Number 1528) in line with the Declaration of Helsinki. Patients and the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.
Results
A total of 379 patients were included in the study; 249 were included in the preintervention cohort (spanning 24 months) and 130 were included in the postintervention cohort (spanning 12 months). Of these, 124 (49.8%) patients and 66 (50.8%) patients were found to have anaemia (haemoglobin <130 g/L) in the preintervention and postintervention cohorts, respectively. Among those with anaemia, the mean baseline haemoglobin level was 112 g/L in the preintervention cohort and 108 g/L in the postintervention cohort. Preintervention and postintervention cohort baseline characteristics were similar (tables 1 and 2).
Demographic and clinical baseline characteristics of all participants in the preintervention and postintervention cohorts
Demographic and clinical baseline characteristics of participants with anaemia in the preintervention and postintervention cohorts
In the preintervention cohort, 36.3% (n=45) of patients with anaemia were screened for IDA and 29 patients (64.4% of those screened) were identified as having IDA over the 24 month period. After implementation of the Pumping Iron Bundle, a significantly greater proportion of HFrEF patients were screened for IDA (90.9%; n=60; p<0.001; figure 2). In the postintervention cohort, which spanned 12 months, 31 patients (51.7% of those screened) were identified as having IDA.
Comparison of the proportion of patients with HFrEF screened for IDA in the preintervention and postintervention groups. (A) Comparison as a per cent of total of HFrEF patients screened for IDA across the preintervention and postintervention groups. (B) Run chart of preintervention IDA screening rates. Data are demonstrated in 2 month blocks (J/F=January/February, etc). X represents COVID-19 pandemic. (C) Run chart postintervention IDA screening rates. IDA, iron deficiency anaemia; HFrEF, heart failure with reduced ejection fraction.
Among HFrEF patients with IDA in the preintervention cohort, 17.2% (n=5) of those eligible were treated for IDA with IV iron. After implementation of the Pumping Iron Bundle, 90.3% (n=28) of patients with IDA in the postintervention cohort were treated (p<0.001; figure 3).
Comparison of the proportion of patients with HFrEF treated for IDA in the preintervention and postintervention groups. (A) Comparison as a per cent of total of HFrEF patients treated for IDA across the preintervention and postintervention groups. (B) Run chart of preintervention treatment rates for patients with IDA. Data are demonstrated in 2 month blocks (J/F=January/February, etc). X represents peak in COVID-19. (C) Run chart of postintervention treatment rates for patients with IDA. IDA, iron deficiency anaemia; HFrEF, heart failure with reduced ejection fraction.
There were no statistically significant differences in secondary outcomes between the preintervention and postintervention cohorts (table 3). No patients experienced adverse effects from IV iron.
Comparison of secondary outcomes in the preintervention and postintervention cohorts
Discussion
Consistent with our findings, previous studies suggest that rates of screening for ID in patients with HF are low. In a 2016 study of ambulatory HF patients in England, only 50% of patients with symptomatic HF and an ejection fraction ≤45% had iron levels checked in the prior 6 months; none of the patients found to have IDA were treated with IV iron.24 Rates of screening may be similarly low in the inpatient population. In retrospective studies, only 20%–39% of patients admitted to hospital with HF are screened for ID.25 26 No significant differences in screening rates have been observed with respect to age, however, men are more likely to be screened than women.25 Our results and previous studies suggest that patients with HF are underscreened and undertreated for IDA. The FAIF-HF trial was published in the New England Journal of Medicine in 2009, over 25 years ago, calling for greater efforts in knowledge translation and implementation science to shorten time from scientific discovery to implementation.14
After implementation of the Pumping Iron Bundle, 90.3% of patients were treated for IDA. Factors that enabled successful implementation of the intervention included a small number of involved clinicians at a single-tertiary centre. In addition, clinicians had access to an already established outpatient infusion clinic where IV iron could be provided. Prefilled laboratory requisition forms and IV iron order sets minimised administrative time for clinicians. Monthly check-ins with clinicians ensured questions were addressed and served as reminders about the intervention.
Although 90.3% of patients were treated for IDA after implementation of the Pumping Iron Bundle, 9.1% were not screened and 9.7% of those with IDA were not treated. Most unscreened patients were already being followed by another physician for anaemia (eg, a Nephrologist associated with the Dialysis Day Unit). However, in some cases, screening was simply not performed. Clinicians and patients included in the study were not interviewed on specific barriers to screening or treatment; however, barriers could include cost of IV iron, organisation of transfusions, the impact of the COVID-19 pandemic, provider time constraints, and time for infusions.
In our study, there were no statistically significant differences in secondary outcomes between the preintervention and postintervention cohorts, however, the rate of emergency department visits for HF did decrease from 9.7% to 3.0%. It is likely that the statistical power and duration of the study were not sufficient to demonstrate a relationship between IV iron supplementation and these secondary outcomes.
In addition to improving symptoms and mortality, IV iron may be cost-effective for healthcare systems. In the USA and Europe, an estimated 1%–2% of all healthcare costs are devoted towards HF.27 The most significant cost element in most studies is hospital admissions.28 IV iron therapy for HF patients may reduce overall costs to healthcare systems. A budget impact analysis performed by Brock et al showed that treatment of HF patients with ID with IV iron resulted in overall average cost savings of Swiss Francs 503 per patient per year, an equivalent of approximately 750 dollars Canadian.29 Further work could be done to evaluate the cost-effectiveness of implementing strategies to treat ID in HF patients in the Canadian setting.
The results of this study should be interpreted with consideration of certain limitations. The project spanned peak COVID months. During this time, healthcare resources were strained and interaction with patients was significantly reduced; the rates of screening and treatment of IDA during this time may have been lower—and therefore underestimated—compared with pre-COVID and post-COVID eras. This study was conducted in an ambulatory clinic at a single-tertiary centre and, therefore, results may not be generalisable to other centres or inpatient populations. There were no statistically significant differences between the preintervention cohort and postintervention cohort for secondary outcomes; however, it is likely that the sample size was not large enough to show significance. The percentage of patients taking an ACEi/ARB was higher in the preintervention cohort and the percentage taking an ARNi was higher in the postintervention cohort, likely because of changes in guideline recommendations for HF. In addition, there were fewer men and fewer patients with NYHA class I HF in the postintervention cohort. It is possible that differences in baseline characteristics between preintervention and postintervention cohorts affected study outcomes, particularly secondary outcomes. We screened for and treated ID among patients with anaemia. Further work could be conducted to determine the impact of a similar quality improvement initiative among HF patients with ID without anaemia.
Conclusion
The introduction of curated materials, such as an IV iron replacement protocol, a prefilled IV iron order set, and a prefilled laboratory requisition form, along with education, can aid clinicians to increase rates of screening and treatment of IDA among ambulatory HF patients. Further work is required to identify barriers to screening and treating ID among HF patients, and to implement strategies to increase rates in both ambulatory and inpatient settings.
Supplemental material
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Patient consent for publication
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Twitter @jeanniecallum
Contributors MG contributed to the study design, data collection, and manuscript writing. RM contributed to manuscript writing. KW contributed to data collection. JS contributed to data analysis and manuscript writing. AG contributed to study design and patient recruitment. BM, OIH, MW, SL, RP, and SP contributed to study design. JC contributed to study design and manuscript writing, and acts as the study guarantor. All authors contributed to manuscript review.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests YL and JC have received research funding from Octapharma and the Canadian Blood Services. SP has received research funding from Boehringer-Ingelheim and has participated in a clinical trial with Abbott within the past two years. SP is a member of a speakers’ bureau for Agence L.I.V., University of Toronto, and University Health Network. YL has acted as a consultant for Choosing Wisely Canada. SP is a member of a national heart failure advisory board that works with AstraZeneca, Boehringer-Ingelheim, Novartis, and Servier.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.