Feasibility of the cardiac output response to stress test in suspected heart failure patients.

BACKGROUND: Diagnostic tools available to support general practitioners diagnose heart failure (HF) are limited. OBJECTIVES: (i) Determine the feasibility of the novel cardiac output response to stress (CORS) test in suspected HF patients, and (ii) Identify differences in the CORS results between (a) confirmed HF patients from non-HF patients, and (b) HF reduced (HFrEF) vs HF preserved (HFpEF) ejection fraction. METHODS: Single centre, prospective, observational, feasibility study. Consecutive patients with suspected HF (N = 105; mean age: 72 ± 10 years) were recruited from specialized HF diagnostic clinics in secondary care. The consultant cardiologist confirmed or refuted a HF diagnosis. The patient completed the CORS but the researcher administering the test was blinded from the diagnosis. The CORS assessed cardiac function (stroke volume index, SVI) noninvasively using the bioreactance technology at rest-supine, challenge-standing, and stress-step exercise phases. RESULTS: A total of 38 patients were newly diagnosed with HF (HFrEF, n = 21) with 79% being able to complete all phases of the CORS (91% of non-HF patients). A 17% lower SVI was found in HF compared with non-HF patients at rest-supine (43 ± 15 vs 51 ± 16 mL/beat/m2, P = 0.02) and stress-step exercise phase (49 ± 16 vs 58 ± 17 mL/beat/m2, P = 0.02). HFrEF patients demonstrated a lower SVI at rest (39 ± 15 vs 48 ± 13 mL/beat/m2, P = 0.02) and challenge-standing phase (34 ± 9 vs 42 ± 12 mL/beat/m2, P = 0.03) than HFpEF patients. CONCLUSION: The CORS is feasible and patients with HF responded differently to non-HF, and HFrEF from HFpEF. These findings provide further evidence for the potential use of the CORS to improve HF diagnostic and referral accuracy in primary care.

Heart failure (HF) is a global pandemic affecting 26 million people worldwide with an estimated 1 million people in the United Kingdom. Accurate early diagnosis of HF and the initiation of evidence-based treatment is essential to reduce morbidity and mortality and the associated burden on healthcare. As there are no state-of-the-art approaches, early diagnosis is challenging and often inaccurate, as initial signs and symptoms are nonspecific. We have developed an innovative test, named CORS (cardiac output response to stress test), to help general practitioners identify HF, which uses a method similar to an electrocardiogram and measures heart function at rest and during short step exercise. We recruited suspected HF patients from specialist HF diagnostic clinics in secondary care to complete the CORS test. We successfully demonstrated that 79% of patients with newly diagnosed HF (n = 38) and 91% of non-HF patients (n = 67) were able to complete all phases of the CORS test. Our findings demonstrate that newly diagnosed HF patients are able to complete this test, which provides further evidence for the potential use of the CORS test to improve HF diagnostic and referral accuracy in primary care.

Long term trends in natriuretic peptide testing for heart failure in UK primary care: a cohort study.

AIMS: Heart failure (HF) is a malignant condition with poor outcomes and is often diagnosed on emergency hospital admission. Natriuretic peptide (NP) testing in primary care is recommended in international guidelines to facilitate timely diagnosis. We aimed to report contemporary trends in NP testing and subsequent HF diagnosis rates over time. METHODS AND RESULTS: Cohort study using linked primary and secondary care data of adult (≥45 years) patients in England 2004-18 (n = 7 212 013, 48% male) to report trends in NP testing (over time, by age, sex, ethnicity, and socioeconomic status) and HF diagnosis rates. NP test rates increased from 0.25 per 1000 person-years [95% confidence interval (CI) 0.23-0.26] in 2004 to 16.88 per 1000 person-years (95% CI 16.73-17.03) in 2018, with a significant upward trend in 2010 following publication of national HF guidance. Women and different ethnic groups had similar test rates, and there was more NP testing in older and more socially deprived groups as expected. The HF detection rate was constant over the study period (around 10%) and the proportion of patients without NP testing prior to diagnosis remained high [99.6% (n = 13 484) in 2004 vs. 76.7% (n = 12 978) in 2017]. CONCLUSION: NP testing in primary care has increased over time, with no evidence of significant inequalities, but most patients with HF still do not have an NP test recorded prior to diagnosis. More NP testing in primary care may be needed to prevent hospitalization and facilitate HF diagnosis at an earlier, more treatable stage.

Screening for atrial fibrillation: a call for evidence.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and prevalence is predicted to double over the next 30 years due to changing demographics and the rise in prevalence of risk factors such as hypertension and diabetes. Atrial fibrillation is associated with a five-fold increased stroke risk, but anticoagulation in eligible patients can reduce this risk by around 65%. Many people with AF currently go undetected and therefore untreated, either because they are asymptomatic or because they have paroxysmal AF. Screening has been suggested as one approach to increase AF detection rates and reduce the incidence of ischaemic stroke by earlier initiation of anticoagulation therapy. However, international taskforces currently recommend against screening, citing the cost implications and uncertainty over the benefits of a systematic screening programme compared to usual care. A number of large randomized controlled trials have commenced to determine the cost-effectiveness and clinical benefit of screening using a range of devices and across different populations. The recent AppleWatch study demonstrates how advances in technology are providing the public with self-screening devices that are increasingly affordable and accessible. Health care professionals should be aware of the implications of these emerging data for diagnostic pathways and treatment. This review provides an overview of the gaps in the current evidence and a summary of the arguments for and against screening.

Obesity, self-reported symptom severity, and quality of life in people with atrial fibrillation: A community-based cross-sectional survey.

BACKGROUND AND AIMS: Intentional weight loss may reduce symptom severity of atrial fibrillation (AF) in relatively young AF patients with overweight. We examined whether symptom severity and quality of life (QoL) are associated with weight status in the general population with AF. METHODS AND RESULTS: Patients with electrocardiogram-confirmed AF completed validated questionnaires: the EuroQol 5 Dimensions QoL questionnaire and the Toronto Atrial Fibrillation Severity Scale (AFSS). The AFSS assessed the AF burden scoring on AF-related symptoms and the total AF burden measured as a combination of duration, frequency, and severity of an irregular heartbeat. Generalized liner models examined the association of body mass index (BMI) with AF severity and QoL adjusting for confounders. Between 2018 and 2019, 882 of 1901 (46%) mailed questionnaires were returned completed. Participants had a mean (SD) age of 74 (10) years old and a BMI of 27.4 (5.6) kg/m2. Sixteen percent reported having never experienced an irregular heartbeat. A 5 kg/m2 higher BMI was associated with a 0.65 (95%CI: 0.25 to 1.06) higher symptom score, where 3 points represent a clinically relevant change in state. A 5 kg/m2 higher BMI was associated with a -1.61 (95%CI: -2.72 to -0.50) lower QoL score. The coefficient of the total AF burden for a 5 kg/m2 higher BMI was 0.17 (95% CI: -0.01 to 0.68). CONCLUSION: BMI was positively associated with symptoms and negatively associated with one of the two measures of QoL, but not with the total AF burden. However, the strength of association was small and not clinically meaningful.

The role of informal carers in the diagnostic process of heart failure: a secondary qualitative analysis.

BACKGROUND: Heart failure (HF) is a common clinical syndrome, particularly in older people, and symptoms can develop gradually. The aim of this study was to explore the role of informal carers in the HF diagnostic process. METHODS: Secondary analysis of qualitative interviews with 16 participants with a new diagnosis of HF. Original interviews were conducted in the participant's home, with carers present in some cases. Interview transcripts were re-analysed using the Framework Method for themes pertaining to informal carers and how they were involved in the diagnostic process. RESULTS: Informal carers often noticed symptoms, such as breathlessness, before participants. In some cases, carers colluded with participants in normalising symptoms but over time, when symptoms failed to resolve or got worse, they encouraged participants to seek medical help. Adult children of participants commonly initiated help-seeking behaviour. During the diagnostic process, carers coordinated participants' healthcare through advocacy and organisation. Carers were keen to be informed about the diagnosis, but both participants and carers struggled to understand some aspects of the term 'heart failure'. CONCLUSIONS: Carers play a crucial role in HF diagnosis, particularly in initiating contact with healthcare services, and should be empowered to encourage people with HF symptoms to seek medical help. Improving public awareness of HF could mean informal carers are more likely to notice symptoms. The important role of carers in supporting the patient's route to diagnosis should be incorporated into future care pathways and explored in further research.

Survival following a diagnosis of heart failure in primary care.

Background: Heart failure is a common long term condition affecting around 900 000 people in the UK and patients commonly present to primary care. The prognosis of patients with a code of heart failure in their primary care record is unknown. Objective: The study sought to determine the overall survival rates for patients with heart failure in a primary care population from the time of diagnosis. Methods: Survival analysis was carried out using UK primary care records from The Health Improvement Network (THIN) between 1 January 1998 and 31 December 2012. Patients age 45 or over with a first diagnostic label of heart failure were matched by age, sex and practice to people without heart failure. Outcome was death in the heart failure and no heart failure cohorts. Kaplan-Meier curves were used to compare survival. Age-specific survival rates at 1, 5 and 10 years were determined for men and women with heart failure. Survival rates by year of diagnosis and case definition were also calculated. Results: During the study period, 54313 patients had a first diagnostic code of heart failure. Overall survival rates for the heart failure group were 81.3% (95%CI 80.9-81.6), 51.5% (95%CI 51.0-52.0) and 29.5% (95%CI 28.9-30.2) at 1, 5 and 10 years respectively and did not change over time. Conclusions: In a primary care population, the survival of patients diagnosed with heart failure did not improved over time. Further research is needed to explain these trends and to find strategies to improve outlook.

Heart failure and major haemorrhage in people with atrial fibrillation.

BACKGROUND: Heart failure (HF) is not included in atrial fibrillation (AF) bleeding risk prediction scores, reflecting uncertainty regarding its importance as a risk factor for major haemorrhage. We aimed to report the relative risk of first major haemorrhage in people with HF and AF compared with people with AF without HF ('AF only'). METHODS: English primary care cohort study of 2 178 162 people aged ≥45 years in the Clinical Practice Research Datalink from January 2000 to December 2018, linked to secondary care and mortality databases. We used traditional survival analysis and competing risks methods, accounting for all-cause mortality and anticoagulation. RESULTS: Over 7.56 years median follow-up, 60 270 people were diagnosed with HF and AF of whom 4996 (8.3%) had a major haemorrhage and 36 170 died (60.0%), compared with 8256 (6.4%) and 34 375 (27.2%), respectively, among 126 251 people with AF only. Less than half those with AF were prescribed an anticoagulant (45.6% from 2014 onwards), although 75.7% were prescribed an antiplatelet or anticoagulant. In a fully adjusted Cox model, the HR for major haemorrhage was higher among people with HF and AF (2.52, 95% CI 2.44 to 2.61) than AF only (1.87, 95% CI 1.82 to 1.92), even in a subgroup analysis of people prescribed anticoagulation. However, in a Fine and Gray competing risk model, the HR of major haemorrhage was similar for people with AF only (1.82, 95% CI 1.77 to 1.87) or HF and AF (1.71, 95% CI 1.66 to 1.78). CONCLUSIONS: People with HF and AF are at increased risk of major haemorrhage compared with those with AF only and current prediction scores may underestimate the risk of haemorrhage in HF and AF. However, people with HF and AF are more likely to die than have a major haemorrhage and therefore an individual's expected prognosis should be carefully considered when predicting future bleeding risk.

Outcomes for older people with screening detected versus existing chronic kidney disease: Cohort study with data linkage.

BACKGROUND: Chronic Kidney Disease (CKD) is a common health problem, associated with increased risk of cardiovascular disease (CVD), end stage kidney disease (ESKD), and premature death. A third of people aged≥70 years have CKD, many of whom are undiagnosed, but little is known about the value of screening. AIM: To compare the risk of adverse health outcomes between people with an existing diagnosis of CKD and those identified on screening. To identify factors associated with mortality in CKD. DESIGN & SETTING: Prospective cohort study of 892 primary care patients aged≥60 years with CKD (existing and screening detected) in Oxfordshire, with data linkage to civil death registry and secondary care. METHOD: Hazard Ratios (HR) and 95% Confidence Intervals (CI) were estimated using Cox proportional-hazard models to compare the risk of all-cause mortality, hospitalisation, CVD, ESKD separately, and as a composite between CKD groups, as well as to identify factors associated with mortality. RESULTS: After a median follow-up of 3-5 years, 49 people died, 493 were hospitalised, 57 had an incident CVD event, and 0 had an ESKD event. There was no difference in the composite outcome between those existing CKD and those identified on screening (HR 0.94, CI 0.67-1.33). Older age (HR 1.10, CI 1.06-1.15), male sex (HR 2.31, CI 1.26-4.24), and heart failure (HR 5.18, CI 2.45-10.97) were associated with increased risk of death. CONCLUSION: Screening older people for CKD may be of value, as their risk of short-term mortality, hospitalisation, and CVD is comparable to people routinely diagnosed. Larger studies with longer follow-up in more diverse and representative populations of older adults are needed to corroborate these findings.

Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial.

Chronic kidney disease (CKD) is associated with a substantial risk of progression to end-stage renal disease and vascular events. The nonsteroidal mineralocorticoid receptor antagonist (MRA), finerenone, offers cardiorenal protection for people with CKD and diabetes, but there is uncertainty if the steroidal MRA, spironolactone, provides the same protection. In this prospective, randomized, open, blinded endpoint trial, we assessed the effectiveness of 25 mg spironolactone in addition to usual care or usual care alone for reducing cardiovascular outcomes in stage 3b CKD among an older community cohort (mean age = 74.8 years and s.d. = 8.1). We recruited 1,434 adults from English primary care, of whom 1,372 (96%) were included in the primary analysis. The primary outcome was time from randomization until the first occurrence of death, hospitalization for heart disease, stroke, heart failure, transient ischemic attack or peripheral arterial disease, or first onset of any condition listed not present at baseline. Across 3 years of follow-up, the primary endpoint occurred in 113 of 677 participants randomized to spironolactone (16.7%) and 111 of 695 participants randomized to usual care (16.0%) with no significant difference between groups (hazard ratio = 1.05, 95% confidence interval: 0.81-1.37). Two-thirds of participants randomized to spironolactone stopped treatment within 6 months, predominantly because they met prespecified safety stop criteria. The most common reason for stopping spironolactone was a decrease in the estimated glomerular filtration rate that met prespecified stop criteria (n = 239, 35.4%), followed by participants being withdrawn due to treatment side effects (n = 128, 18.9%) and hyperkalemia (n = 54, 8.0%). In conclusion, we found that spironolactone was frequently discontinued due to safety concerns, with no evidence that it reduced cardiovascular outcomes in people with stage 3b CKD. Spironolactone should not be used for people with stage 3b CKD without another explicit treatment indication. ClinicalTrials.gov registration: ISRCTN44522369 .

Multiprofessional heart failure self-development framework.

OBJECTIVE: Heart failure remains a key public health priority across the globe. The median age of people with heart failure admitted to hospital in the UK is 81 years old. Many such patients transcend the standard interventions that are well characterised and evidenced in guidelines, into holistic aspects surrounding frailty, rehabilitation and social care. Previous published competency frameworks in heart failure have focused on the value of doctors, nurses and pharmacists. We aimed to provide an expert consensus on the minimum heart failure-specific competencies necessary for multiple different healthcare professionals, including physiotherapists, occupational therapists, dietitians and cardiac physiologists. METHODS: The document has been developed focussing on four main parts, (1) establishing a project working group of expert professionals, (2) a literature review of previously existing published curricula and competency frameworks, (3) consensus building, which included developing a structure to the framework with ongoing review of the contents to adapt and be inclusive for each specialty and (4) write up and dissemination to widen the impact of the project. RESULTS: The final competency framework displays competencies across seven sections; knowledge (including subheadings on heart failure syndrome, diagnosis and clinical management); general skills; heart failure-specific skills; clinical autonomy; multidisciplinary team working; teaching and education; and research and development. CONCLUSION: People with heart failure can be complex and have needs that require input from a broad range of specialties. This publication focuses on the vital impact of wider multidisciplinary groups and should help define the generic core heart failure-specific competencies needed to support future pipelines of professionals, who regularly interact with and deliver care for patients with heart failure.

Long term changes in health-related quality of life for people with heart failure: the ECHOES study.

AIMS: Heart failure (HF) impairs all aspects of health-related quality of life (HRQoL), but little is known about the effect of developing HF on HRQoL over time. We aimed to report changes in HRQoL over a 13-year period. METHODS AND RESULTS: HRQoL was measured in the Echocardiographic Heart of England Screening (ECHOES) study and the ECHOES-X follow-up study (N = 1618) using the SF-36 questionnaire (Version 1). Mixed modelling compared changes in HRQoL across diagnostic groups, adjusting for potential predictors and design variables. Patients who had developed HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF) at rescreening had significantly greater reduction in physical functioning (PF) and role physical (RP) scores compared with those without HF; adjusted mean difference in PF: HFrEF -16.1, [95% confidence interval (CI) -22.2 to -10.1]; HFpEF -14.6, (95% CI -21.2 to -8.1); in RP: HFrEF -20.7, (95% CI -31.8 to -9.7); HFpEF -19.3, (95% CI -31.0 to -7.6). Changes in HRQoL of those with a HF diagnosis at baseline and rescreen, with exception of role emotion, were similar to those without HF but started from a much lower baseline score. CONCLUSIONS: People with a new diagnosis of HF at rescreening had a significant reduction in HRQoL. Conversely, for those with HF detected on initial screening, little change was observed in HRQoL scores on rescreening. Further research is required to understand the development of HF over time and to test interventions designed to prevent decline in HRQoL, potentially through earlier diagnosis and treatment optimization.

Body mass index and survival in people with heart failure.

AIMS: In people with heart failure (HF), a high body mass index (BMI) has been linked with better outcomes ('obesity paradox'), but there is limited evidence in community populations across long-term follow-up. We aimed to examine the association between BMI and long-term survival in patients with HF in a large primary care cohort. METHODS: We included patients with incident HF aged ≥45 years from the Clinical Practice Research Datalink (2000-2017). We used Kaplan-Meier curves, Cox regression and penalised spline methods to assess the association of pre-diagnostic BMI, based on WHO classification, with all-cause mortality. RESULTS: There were 47 531 participants with HF (median age 78.0 years (IQR 70-84), 45.8% female, 79.0% white ethnicity, median BMI 27.1 (IQR 23.9-31.0)) and 25 013 (52.6%) died during follow-up. Compared with healthy weight, people with overweight (HR 0.78, 95% CI 0.75 to 0.81, risk difference (RD) -4.1%), obesity class I (HR 0.76, 95% CI 0.73 to 0.80, RD -4.5%) and class II (HR 0.76, 95% CI 0.71 to 0.81, RD -4.5%) were at decreased risk of death, whereas people with underweight were at increased risk (HR 1.59, 95% CI 1.45 to 1.75, RD 11.2%). In those underweight, this risk was greater among men than women (p value for interaction=0.02). Class III obesity was associated with increased risk of all-cause mortality compared with overweight (HR 1.23, 95% CI 1.17 to 1.29). CONCLUSION: The U-shaped relationship between BMI and long-term all-cause mortality suggests a personalised approach to identifying optimal weight may be needed for patients with HF in primary care. Underweight people have the poorest prognosis and should be recognised as high-risk.

Natriuretic peptide testing and heart failure diagnosis in primary care: diagnostic accuracy study.

BACKGROUND: Natriuretic peptide (NP) testing is recommended for patients presenting to primary care with symptoms of chronic heart failure (HF) to prioritise referral for diagnosis. AIM: To report NP test performance at European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guideline referral thresholds. DESIGN AND SETTING: Diagnostic accuracy study using linked primary and secondary care data (2004 to 2018). METHOD: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NP testing for HF diagnosis was assessed. RESULTS: In total, 229 580 patients had an NP test and 21 102 (9.2%) were diagnosed with HF within 6 months. The ESC NT-proBNP threshold ≥125 pg/mL had a sensitivity of 94.6% (95% confidence interval [CI] = 94.2 to 95.0) and specificity of 50.0% (95% CI = 49.7 to 50.3), compared with sensitivity of 81.7% (95% CI = 81.0 to 82.3) and specificity of 80.3% (95% CI = 80.0 to 80.5) for the NICE NT-proBNP ≥400 pg/mL threshold. PPVs for an NT-proBNP test were 16.4% (95% CI = 16.1 to 16.6) and 30.0% (95% CI = 29.6 to 30.5) for ESC and NICE thresholds, respectively. For both guidelines, nearly all patients with an NT-proBNP level below the threshold did not have HF (NPV: ESC 98.9%, 95% CI = 98.8 to 99.0 and NICE 97.7%, 95% CI = 97.6 to 97.8). CONCLUSION: At the higher NICE chronic HF guideline NP thresholds, one in five cases are initially missed in primary care but the lower ESC thresholds require more diagnostic assessments. NP is a reliable 'rule-out' test at both cut-points. The optimal NP threshold will depend on the priorities and capacity of the healthcare system.

Diagnostic accuracy of natriuretic peptide screening for left ventricular systolic dysfunction in the community: systematic review and meta-analysis.

AIMS: Heart failure (HF) is a global health burden and new strategies to achieve timely diagnosis and early intervention are urgently needed. Natriuretic peptide (NP) testing can be used to screen for left ventricular systolic dysfunction (LVSD), but evidence on test performance is mixed, and international HF guidelines differ in their recommendations. Our aim was to summarize the evidence on diagnostic accuracy of NP screening for LVSD in general and high-risk community populations and estimate optimal screening thresholds. METHODS: We searched relevant databases up to August 2020 for studies with a screened community population of over 100 adults reporting NP performance to diagnose LVSD. Study inclusion, quality assessment, and data extraction were conducted independently and in duplicate. Diagnostic test meta-analysis used hierarchical summary receiver operating characteristic curves to obtain estimates of pooled accuracy to detect LVSD, with optimal thresholds obtained to maximize the sum of sensitivity and specificity. RESULTS: Twenty-four studies were identified, involving 26 565 participants: eight studies in high-risk populations (at least one cardiovascular risk factor), 12 studies in general populations, and four in both high-risk and general populations combined. For detecting LVSD in screened high-risk populations with N-terminal prohormone brain natriuretic peptide (NT-proBNP), the pooled sensitivity was 0.87 [95% confidence interval (CI) 0.73-0.94] and specificity 0.84 (95% CI 0.55-0.96); for BNP, sensitivity was 0.75 (95% CI 0.65-0.83) and specificity 0.78 (95% CI 0.72-0.84). Heterogeneity between studies was high with variations in positivity threshold. Due to a paucity of high-risk studies that assessed NP performance at multiple thresholds, it was not possible to calculate optimal thresholds for LVSD screening in high-risk populations alone. To provide an indication of where the positivity threshold might lie, the pooled accuracy for LVSD screening in high-risk and general community populations were combined and gave an optimal cut-off of 311 pg/mL [sensitivity 0.74 (95% CI 0.53-0.88), specificity 0.85 (95% CI 0.68-0.93)] for NT-proBNP and 49 pg/mL [sensitivity 0.68 (95% CI 0.45-0.85), specificity 0.81 (0.67-0.90)] for BNP. CONCLUSIONS: Our findings suggest that in high-risk community populations NP screening may accurately detect LVSD, potentially providing an important opportunity for diagnosis and early intervention. Our study highlights an urgent need for further prospective studies, as well as an individual participant data meta-analysis, to more precisely evaluate diagnostic accuracy and identify optimal screening thresholds in specifically defined community-based populations to inform future guideline recommendations.

The REFER (REFer for EchocaRdiogram) protocol: a prospective validation of a clinical decision rule, NT-proBNP, or their combination, in the diagnosis of heart failure in primary care. Rationale and design.

BACKGROUND: Heart failure is a major cause of mortality and morbidity. As mortality rates are high, it is important that patients seen by general practitioners with symptoms suggestive of heart failure are identified quickly and treated appropriately. Identifying patients with heart failure or deciding which patients need further tests is a challenge. All patients with suspected heart failure should be diagnosed using objective tests such as echocardiography, but it is expensive, often delayed, and limited by the significant skill shortage of trained echocardiographers. Alternative approaches for diagnosing heart failure are currently limited. Clinical decision tools that combine clinical signs, symptoms or patient characteristics are designed to be used to support clinical decision-making and validated according to strict methodological procedures. The REFER Study aims to determine the accuracy and cost-effectiveness of our previously derived novel, simple clinical decision rule, a natriuretic peptide assay, or their combination, in the triage for referral for echocardiography of symptomatic adult patients who present in general practice with symptoms suggestive of heart failure. METHODS/DESIGN: This is a prospective, Phase II observational, diagnostic validation study of a clinical decision rule, natriuretic peptides or their combination, for diagnosing heart failure in primary care. Consecutive adult primary care patients 55 years of age or over presenting to their general practitioner with a chief complaint of recent new onset shortness of breath, lethargy or peripheral ankle oedema of over 48 hours duration, with no obvious recurrent, acute or self-limiting cause will be enrolled. Our reference standard is based upon a three step expert specialist consensus using echocardiography and clinical variables and tests. DISCUSSION: Our clinical decision rule offers a potential solution to the diagnostic challenge of providing a timely and accurate diagnosis of heart failure in primary care. Study results will provide an evidence-base from which to develop heart failure care pathway recommendations and may be useful in standardising care. If demonstrated to be effective, the clinical decision rule will be of interest to researchers, policy makers and general practitioners worldwide. TRIAL REGISTRATION: ISRCTN17635379.

A Systematic Review of Economic Aspects of Service Interventions to Increase Anticoagulation Use in Atrial Fibrillation.

OBJECTIVE: To systematically identify and appraise existing evidence surrounding economic aspects of anticoagulation service interventions for patients with atrial fibrillation. METHODS: We searched the published and grey literature up to October 2019 to identify relevant economic evidence in any health care setting. A narrative-synthesis approach was taken to summarise evidence by economic design and type of service intervention, with costs expressed in pound sterling and valued at 2017 to 2018 prices. RESULTS: A total of 13 studies met our inclusion criteria from 1,168 papers originally identified. Categories of interventions included anticoagulation clinics (n = 4), complex interventions (n = 4), decision support tools (n = 3) and patient-centred approaches (n = 2). Anticoagulation clinics were cost-saving compared with usual care (range for mean cost difference: £188-£691 per-patient per-year) with equivalent health outcomes. Only one economic evaluation of a complex intervention was conducted; case management was more expensive than usual care (mean cost difference: £255 per-patient per-year) and the probability of its cost-effectiveness did not exceed 70%. There was limited economic evidence surrounding decision support tools or patient-centred approaches. Targeting service interventions at high-risk groups and those with suboptimal treatment was most likely to result in cost savings. CONCLUSION: This review revealed some evidence to support the cost-effectiveness of anticoagulation clinics. However, summative conclusions are constrained by a paucity of economic evidence, a lack of direct comparisons between interventions, and study heterogeneity in terms of intervention, comparator and study year. Further research is urgently needed to inform commissioning and service development. Data from this review can inform future economic evaluations of anticoagulation service interventions.