Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology.

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice.

Optimizing outcomes in heart failure: 2022 and beyond.

Although the development of therapies and tools for the improved management of heart failure (HF) continues apace, day-to-day management in clinical practice is often far from ideal. A Cardiovascular Round Table workshop was convened by the European Society of Cardiology (ESC) to identify barriers to the optimal implementation of therapies and guidelines and to consider mitigation strategies to improve patient outcomes in the future. Key challenges identified included the complexity of HF itself and its treatment, financial constraints and the perception of HF treatments as costly, failure to meet the needs of patients, suboptimal outpatient management, and the fragmented nature of healthcare systems. It was discussed that ongoing initiatives may help to address some of these barriers, such as changes incorporated into the 2021 ESC HF guideline, ESC Heart Failure Association quality indicators, quality improvement registries (e.g. EuroHeart), new ESC guidelines for patients, and the universal definition of HF. Additional priority action points discussed to promote further improvements included revised definitions of HF 'phenotypes' based on trial data, the development of implementation strategies, improved affordability, greater regulator/payer involvement, increased patient education, further development of patient-reported outcomes, better incorporation of guidelines into primary care systems, and targeted education for primary care practitioners. Finally, it was concluded that overarching changes are needed to improve current HF care models, such as the development of a standardized pathway, with a common adaptable digital backbone, decision-making support, and data integration, to ensure that the model 'learns' as the management of HF continues to evolve.

A cost effectiveness study establishing the impact and accuracy of implementing the NICE guidelines lowering plasma NTproBNP threshold in patients with clinically suspected heart failure at our institution.

AIMS: The 2014 National Institute of Clinical Excellence (NICE) guidelines on the management of acute heart failure recommended using a plasma NT-proBNP threshold of 300pg/ml to assist in ruling out the diagnosis of heart failure (HF), updating previous guidelines recommending using a threshold of 400pg/ml. NICE based their recommendations on 6 studies performed in other countries. This study sought to determine the diagnostic and economic implications of using these thresholds in a large unselected UK population. METHODS: Patient and clinical demographics were recorded for all consecutive suspected HF patients over 12months, as well as clinical outcomes including time to HF hospitalisation and time to death (follow up 15.8months). RESULTS: Of 1995 unselected patients admitted with clinically suspected HF, 1683 (84%) had a NTproBNP over the current NICE recommended threshold, of which 35% received a final diagnosis of HF. Lowering the threshold from 400 to 300pg/ml would have involved screening an additional 61 patients and only would have identified one new patient with HF (sensitivity 0.985, NPV 0.976, area under the curve (AUC) at 300pg/ml 0.67; sensitivity 0.983, NPV 0.977, AUC 0.65 at 400pg/ml). The economic implications of lowering the threshold would have involved additional costs of £42,842.04 (£702.33 per patient screened, or £ 42,824.04 per new HF patient). CONCLUSION: Applying the recent updated NICE guidelines to an unselected real world population increases the AUC but would have a significant economic impact and only identified one new patient with heart failure.

Effectiveness and cost-effectiveness of serum B-type natriuretic peptide testing and monitoring in patients with heart failure in primary and secondary care: an evidence synthesis, cohort study and cost-effectiveness model.

BACKGROUND: Heart failure (HF) affects around 500,000 people in the UK. HF medications are frequently underprescribed and B-type natriuretic peptide (BNP)-guided therapy may help to optimise treatment. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of BNP-guided therapy compared with symptom-guided therapy in HF patients. DESIGN: Systematic review, cohort study and cost-effectiveness model. SETTING: A literature review and usual care in the NHS. PARTICIPANTS: (a) HF patients in randomised controlled trials (RCTs) of BNP-guided therapy; and (b) patients having usual care for HF in the NHS. INTERVENTIONS: Systematic review: BNP-guided therapy or symptom-guided therapy in primary or secondary care. Cohort study: BNP monitored (≥ 6 months' follow-up and three or more BNP tests and two or more tests per year), BNP tested (≥ 1 tests but not BNP monitored) or never tested. Cost-effectiveness model: BNP-guided therapy in specialist clinics. MAIN OUTCOME MEASURES: Mortality, hospital admission (all cause and HF related) and adverse events; and quality-adjusted life-years (QALYs) for the cost-effectiveness model. DATA SOURCES: Systematic review: Individual participant or aggregate data from eligible RCTs. Cohort study: The Clinical Practice Research Datalink, Hospital Episode Statistics and National Heart Failure Audit (NHFA). REVIEW METHODS: A systematic literature search (five databases, trial registries, grey literature and reference lists of publications) for published and unpublished RCTs. RESULTS: Five RCTs contributed individual participant data (IPD) and eight RCTs contributed aggregate data (1536 participants were randomised to BNP-guided therapy and 1538 participants were randomised to symptom-guided therapy). For all-cause mortality, the hazard ratio (HR) for BNP-guided therapy was 0.87 [95% confidence interval (CI) 0.73 to 1.04]. Patients who were aged < 75 years or who had heart failure with a reduced ejection fraction (HFrEF) received the most benefit [interactions (p = 0.03): < 75 years vs. ≥ 75 years: HR 0.70 (95% CI 0.53 to 0.92) vs. 1.07 (95% CI 0.84 to 1.37); HFrEF vs. heart failure with a preserved ejection fraction (HFpEF): HR 0.83 (95% CI 0.68 to 1.01) vs. 1.33 (95% CI 0.83 to 2.11)]. In the cohort study, incident HF patients (1 April 2005-31 March 2013) were never tested (n = 13,632), BNP tested (n = 3392) or BNP monitored (n = 71). Median survival was 5 years; all-cause mortality was 141.5 out of 1000 person-years (95% CI 138.5 to 144.6 person-years). All-cause mortality and hospital admission rate were highest in the BNP-monitored group, and median survival among 130,433 NHFA patients (1 January 2007-1 March 2013) was 2.2 years. The admission rate was 1.1 patients per year (interquartile range 0.5-3.5 patients). In the cost-effectiveness model, in patients aged < 75 years with HFrEF or HFpEF, BNP-guided therapy improves median survival (7.98 vs. 6.46 years) with a small QALY gain (5.68 vs. 5.02) but higher lifetime costs (£64,777 vs. £58,139). BNP-guided therapy is cost-effective at a threshold of £20,000 per QALY. LIMITATIONS: The limitations of the trial were a lack of IPD for most RCTs and heterogeneous interventions; the inability to identify BNP monitoring confidently, to determine medication doses or to distinguish between HFrEF and HFpEF; the use of a simplified two-state Markov model; a focus on health service costs and a paucity of data on HFpEF patients aged < 75 years and HFrEF patients aged ≥ 75 years. CONCLUSIONS: The efficacy of BNP-guided therapy in specialist HF clinics is uncertain. If efficacious, it would be cost-effective for patients aged < 75 years with HFrEF. The evidence reviewed may not apply in the UK because care is delivered differently. FUTURE WORK: Identify an optimal BNP-monitoring strategy and how to optimise HF management in accordance with guidelines; update the IPD meta-analysis to include the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) RCT; collect routine long-term outcome data for completed and ongoing RCTs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37248047 and PROSPERO CRD42013005335. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 40. See the NIHR Journals Library website for further project information. The British Heart Foundation paid for Chris A Rogers' and Maria Pufulete's time contributing to the study. Syed Mohiuddin's time is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West at University Hospitals Bristol NHS Foundation Trust. Rachel Maishman contributed to the study when she was in receipt of a NIHR Methodology Research Fellowship.

MICE or NICE? An economic evaluation of clinical decision rules in the diagnosis of heart failure in primary care.

BACKGROUND: Detection and treatment of heart failure (HF) can improve quality of life and reduce premature mortality. However, symptoms such as breathlessness are common in primary care, have a variety of causes and not all patients require cardiac imaging. In systems where healthcare resources are limited, ensuring those patients who are likely to have HF undergo appropriate and timely investigation is vital. DESIGN: A decision tree was developed to assess the cost-effectiveness of using the MICE (Male, Infarction, Crepitations, Edema) decision rule compared to other diagnostic strategies to identify HF patients presenting to primary care. METHODS: Data from REFER (REFer for EchocaRdiogram), a HF diagnostic accuracy study, was used to determine which patients received the correct diagnosis decision. The model adopted a UK National Health Service (NHS) perspective. RESULTS: The current recommended National Institute for Health and Care Excellence (NICE) guidelines for identifying patients with HF was the most cost-effective option with a cost of £4400 per quality adjusted life year (QALY) gained compared to a "do nothing" strategy. That is, patients presenting with symptoms suggestive of HF should be referred straight for echocardiography if they had a history of myocardial infarction or if their NT-proBNP level was ≥400pg/ml. The MICE rule was more expensive and less effective than the other comparators. Base-case results were robust to sensitivity analyses. CONCLUSIONS: This represents the first cost-utility analysis comparing HF diagnostic strategies for symptomatic patients. Current guidelines in England were the most cost-effective option for identifying patients for confirmatory HF diagnosis. The low number of HF with Reduced Ejection Fraction patients (12%) in the REFER patient population limited the benefits of early detection.

Model-based cost-effectiveness analysis of B-type natriuretic peptide-guided care in patients with heart failure.

OBJECTIVE: Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction. METHODS: We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients <75 years; (2) HFpEF patients <75 years; and (3) HFrEF patients ≥75 years. There is no evidence of benefit in patients with HFpEF aged ≥75 years. We used individual patient data meta-analyses and linked primary care, hospital and mortality data to inform the key model parameters. We performed probabilistic analysis to assess the uncertainty in model results. RESULTS: In younger patients (<75 years) with HFrEF, the mean QALYs (5.57 vs 5.02) and costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (-£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (-£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect. CONCLUSIONS: We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older patients with HFrEF, but more evidence is required, particularly with respect to the frequency, duration and BNP target for monitoring. Cost-effectiveness results from trials in specialist settings cannot be generalised to primary care.

The healthcare costs of heart failure during the last five years of life: A retrospective cohort study.

BACKGROUND: Evidence on the economic impact of heart failure (HF) is vital in order to predict the cost-effectiveness of novel interventions. We estimate the health system costs of HF during the last five years of life. METHODS: We used linked primary care and mortality data accessed through the Clinical Practice Research Datalink (CPRD) to identify 1555 adults in England who died with HF in 2012/13. We used CPRD and linked Hospital Episode Statistics to estimate the cost of medications, primary and hospital healthcare. Using GLS regression we estimated the relationship between costs, HF diagnosis, proximity to death and patient characteristics. RESULTS: In the last 3months of life, healthcare costs were £8827 (95% CI £8357 to £9296) per patient, more than 90% of which were for inpatient or critical care. In the last 3months, patients spent on average 17.8 (95% CI 16.8 to 18.8) days in hospital and had 8.8 (95% CI 8.4 to 9.1) primary care consultations. Most (931/1555; 59.9%) patients were in hospital on the day of death. Mean quarterly healthcare costs in quarters after HF diagnosis were higher (£1439; [95% CI £1260 to £1619]) than in quarters preceding diagnosis. Older patients and patients with lower comorbidity scores had lower costs. CONCLUSIONS: Healthcare costs increase sharply at the end of life and are dominated by hospital care. There is potential to save money by implementation and evaluation of interventions that are known to reduce hospitalisations for HF, particularly at the end of life.

UK guidelines for referral and assessment of adults for heart transplantation.

Patients with advanced heart failure have a dismal prognosis and poor quality of life. Heart transplantation provides an effective treatment for a subset of these patients. This article provides cardiologists with up-to-date information about referral for transplantation, the role of left ventricular assist devices prior to transplant, patient selection, waiting-list management and donor heart availability. Timing is of central importance; patients should be referred before complications (eg, cardiorenal syndrome or secondary pulmonary hypertension) have developed that will increase the risk of, or potentially contraindicate, transplantation. Issues related to heart failure aetiology, comorbidity and adherence to medical treatment are reviewed. Finally, the positive role that cardiologists can play in promoting and facilitating organ donation is discussed.

Retrospective analysis of the cost-effectiveness of using plasma brain natriuretic peptide in screening for left ventricular systolic dysfunction in the general population.

OBJECTIVES: We sought to assess the cost-effectiveness of using plasma brain natriuretic peptide (BNP) as a pre-echocardiographic screening test for left ventricular systolic dysfunction (LVSD) in the general population. BACKGROUND: We hypothesized that plasma BNP and simple clinical parameters would reduce the number of echocardiograms needed and cost when screening for LVSD in the general population. METHODS: A random sample of 1,257 community subjects (age 25 to 74 years) was examined. Three risk groups were formed: one group with symptomatic ischemic heart disease (IHD); a second group with blood pressure >160/95 mm Hg and/or an abnormal electrocardiogram (high risk); and a group with none of these risk factors (low risk). The BNP assay was adjusted to give a high sensitivity. RESULTS: Left ventricular systolic dysfunction was prevalent in 0.7% (6/823), 6% (16/269), and 19% (26/140) of low-risk and high-risk subjects and IHD subjects, respectively. Raised BNP concentrations (>8 pg/ml) occurred in 41%, 64%, and 71%. Sensitivities of BNP for detecting LVSD were 83% (5/6), 94% (15/16), and 92% (24/26); and the negative predictive values were 99.8%, 99.0%, and 95.1%. Brain natriuretic peptide was not associated with LVSD in low-risk subjects (p = 0.087), but in IHD subjects (p = 0.015) and high-risk subjects (p = 0.023). Screening high-risk subjects by BNP before echocardiography could have reduced the cost per detected case of LVSD by 26% for the cost ratio of 1/20 (BNP/echocardiogram). CONCLUSIONS: Subjects at low and high risk of LVSD can be identified by simple clinical parameters, and BNP testing further reduces the number of echocardiograms needed and the costs of screening in subjects at risk <75 years of age in the general population.