Primary care REFerral for EchocaRdiogram (REFER) in heart failure: a diagnostic accuracy study

BackgroundSymptoms of breathlessness, fatigue, and ankle swelling are common in general practice but deciding which patients are likely to have heart failure is challenging.AimTo evaluate the performance of a clinical decision rule (CDR), with or without N-Terminal pro-B type natriuretic peptide (NT-proBNP) assay, for identifying heart failure.Design and settingProspective, observational, diagnostic validation study of patients aged >55 years, presenting with shortness of breath, lethargy, or ankle oedema, from 28 general practices in England.MethodThe outcome was test performance of the CDR and natriuretic peptide test in determining a diagnosis of heart failure. The reference standard was an expert consensus panel of three cardiologists.ResultsThree hundred and four participants were recruited, with 104 (34.2%; 95% confidence interval [CI] = 28.9 to 39.8) having a confirmed diagnosis of heart failure. The CDR+NT-proBNP had a sensitivity of 90.4% (95% CI = 83.0 to 95.3) and specificity 45.5% (95% CI = 38.5 to 52.7). NT-proBNP level alone with a cut-off <400 pg/ml had sensitivity 76.9% (95% CI = 67.6 to 84.6) and specificity 91.5% (95% CI = 86.7 to 95.0). At the lower cut-off of NT-proBNP <125 pg/ml, sensitivity was 94.2% (95% CI = 87.9 to 97.9) and specificity 49.0% (95% CI = 41.9 to 56.1).ConclusionAt the low threshold of NT-proBNP <125 pg/ml, natriuretic peptide testing alone was better than a validated CDR+NT-proBNP in determining which patients presenting with symptoms went on to have a diagnosis of heart failure. The higher NT-proBNP threshold of 400 pg/ml may mean more than one in five patients with heart failure are not appropriately referred. Guideline natriuretic peptide thresholds may need to be revised.

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The REFER (REFer for EchocaRdiogram) study: a prospective validation and health economic analysis of a clinical decision rule, NT-proBNP or their combination in the diagnosis of heart failure in primary care

Efficacy and Mechanism Evaluation ◽

10.3310/eme04030 ◽

2017 ◽

Vol 4 (3) ◽

pp. 1-56 ◽

Cited By ~ 1

Author(s):

Clare J Taylor ◽

Mark Monahan ◽

Andrea K Roalfe ◽

Pelham Barton ◽

Rachel Iles ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Primary Care ◽

Natriuretic Peptide ◽

Outcome Measure ◽

Cost Effective ◽

Clinical Decision ◽

Clinical Decision Rule ◽

Main Outcome Measure ◽

Patients With Heart Failure

Background Heart failure is a treatable condition but making a diagnosis can be challenging. Objective To evaluate the performance of a clinical decision rule (CDR) with or without a natriuretic peptide assay for identifying heart failure in symptomatic patients presenting to primary care. Design Prospective, observational, diagnostic validation study and economic evaluation. Setting Twenty-eight general practices in central England, UK. Participants Primary care patients aged ≥ 55 years presenting with recent new-onset shortness of breath, lethargy or peripheral ankle oedema of > 48 hours’ duration. Instrument The CDR included a clinical element (male, history of myocardial infarction, crepitations at the lung bases and oedema) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) blood test. The reference standard was an expert consensus panel of three cardiology specialists. Main outcome measure The main outcome measure was test performance of the CDR and the natriuretic peptide test alone, and in combination, in estimating sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) for a diagnosis of heart failure. Economic evaluation of a decision tree with a NHS/Personal Social Services perspective determined the cost per quality-adjusted life-year (QALY) gained. Results In total, 304 participants were recruited to the validation cohort. The mean age was 73.9 years (standard deviation 8.8 years) and 124 (40.8%) participants were male. In total, 104 [34.2%, 95% confidence interval (CI) 28.9% to 39.8%] had a confirmed diagnosis of heart failure. The CDR had a sensitivity of 90% (95% CI 83% to 95%), specificity of 46% (95% CI 39% to 53%), PPV of 46% (95% CI 39% to 53%) and NPV of 90% (95% CI 83% to 95%). NT-proBNP level alone with a cut-off point of < 400 pg/ml had a sensitivity of 77% (95% CI 68% to 85%) and specificity of 92% (95% CI 87% to 95%). At the lower cut-off point of 125 pg/ml, sensitivity was 94% (95% CI 88% to 98%) and specificity was 49% (95% CI 42% to 56%). The economic model results suggest that referring a patient for a confirmatory diagnosis if they have had a previous myocardial infarction or have a NT-proBNP level that is greater than a 400 pg/ml threshold (current practice in England) is the most cost-effective option, with a cost of £4400 per QALY gained compared with a do nothing strategy. The base-case results were robust to deterministic and probabilistic sensitivity analyses. Conclusions Natriuretic peptide testing alone performed as well as the validated CDR in determining which patients presenting with symptoms went on to have a diagnosis of heart failure. The current NT-proBNP cut-off point of 400 pg/ml used in the UK is too high and means that one in five patients with heart failure may not be appropriately referred for further investigation and diagnosis, but this threshold was cost-effective in the REFer for EchocaRdiogram (REFER) trial. The study found only three patients with heart failure with reduced ejection fraction (HFREF), which might limit the benefits of early detection. The other diagnostic strategies with lower NT-proBNP referral levels become more cost-effective as the proportion of HFREF patients increases. International consensus on the optimal cut-off point for natriuretic peptide testing in patients with symptoms suggestive of heart failure should be sought. Trial registration Current Controlled Trials ISRCTN17635379. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

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448 Prognostic value of brain natriuretic peptide and an enhanced ventilatory response during cardiopulmonary exercise test in patients with heart failure

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(06)80310-3 ◽

2006 ◽

Vol 5 (1) ◽

pp. 107-107

Author(s):

A SCARDOVI ◽

R DEMARIA ◽

C COLETTA ◽

S PERNA ◽

N ASPROMONTE ◽

...

Keyword(s):

Heart Failure ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Exercise Test ◽

Prognostic Value ◽

Ventilatory Response ◽

Cardiopulmonary Exercise Test ◽

Cardiopulmonary Exercise ◽

Patients With Heart Failure

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1338 What proportion of patients with heart failure and preserved left-ventricular systolic dysfunction has an elevated brain natriuretic peptide?

European Heart Journal ◽

10.1016/s0195-668x(03)94592-1 ◽

2003 ◽

Vol 24 (5) ◽

pp. 255

Author(s):

K HOGG

Keyword(s):

Heart Failure ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Left Ventricular Systolic Dysfunction ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Ventricular Systolic Dysfunction ◽

Patients With Heart Failure

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The Use of Clinical Decision Support in Reducing Readmissions for Patients with Heart Failure: A Quasi-experimental Study

Contemporary Nurse ◽

10.1080/10376178.2021.1919161 ◽

2021 ◽

pp. 1-21

Author(s):

Susan R. Giscombe ◽

Diana-Lyn Baptiste ◽

Binu Koirala ◽

Reiko Asano ◽

Yvonne Commodore-Mensah

Keyword(s):

Heart Failure ◽

Experimental Study ◽

Decision Support ◽

Clinical Decision Support ◽

Clinical Decision ◽

Patients With Heart Failure ◽

Quasi Experimental

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GW25-e3320 Clinical research of the change of cardiac ankyrin repeat protein and brain natriuretic peptide in patients with heart failure

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2014.06.770 ◽

2014 ◽

Vol 64 (16) ◽

pp. C167

Author(s):

Chen Moshui

Keyword(s):

Heart Failure ◽

Clinical Research ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Ankyrin Repeat ◽

Repeat Protein ◽

Ankyrin Repeat Protein ◽

Cardiac Ankyrin Repeat Protein ◽

Patients With Heart Failure

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Diversity of Molecular Forms of Plasma Brain Natriuretic Peptide (BNP) in Patients with Heart Failure (HF)

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2008.07.198 ◽

2008 ◽

Vol 14 (7) ◽

pp. S171-S172

Author(s):

Kazuyoshi Tadokoro ◽

Toshio Nishikimi ◽

Kimihiko Ishimura ◽

Chikako Iemura ◽

Hiroaki Matsuoka ◽

...

Keyword(s):

Heart Failure ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Molecular Forms ◽

Plasma Brain Natriuretic Peptide ◽

Patients With Heart Failure

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Effects of high-urgency ambulance transportation on pro-B-type natriuretic peptide levels in patients with heart failure

The American Journal of Emergency Medicine ◽

10.1016/j.ajem.2008.12.041 ◽

2010 ◽

Vol 28 (5) ◽

pp. 568-576 ◽

Cited By ~ 2

Author(s):

Ulrike Weber ◽

Agnes Reitinger ◽

Tomasz Erdeii ◽

Christian Hellmich ◽

Barbara Steinlechner ◽

...

Keyword(s):

Heart Failure ◽

Natriuretic Peptide ◽

High Urgency ◽

Patients With Heart Failure

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Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽

10.1161/circ.132.suppl_3.12849 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Gianluigi Savarese ◽

Camilla Hage ◽

Ulf Dahlström ◽

Pasquale Perrone-Filardi ◽

Lars H Lund

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Total Mortality ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

The Impact

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.

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