Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure diagnosis in primary care

Wright, Samson; Doughty, Robert N.; Pearl, Ann; Gamble, Greg; Whalley, Gillian A.; Walsh, Helen; Gordon, Gary; Bagg, Warwick; Oxenham, Helen; Yandle, Tim G.; Richards, Mark; Sharpe, Norman

doi:10.1016/j.jacc.2003.05.011

Cited by 216 publications

(43 citation statements)

References 31 publications

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“…A commonly used biochemical marker for severity of HF is pro-BNP, which has been shown to correlate with the severity of HF [24,25]. In the present study, the VO 2 peak/THV ratio was shown to correlate with pro-BNP, indicating that the ratio can potentially serve as a measure for severity of HF.…”

Section: Discussionsupporting

confidence: 60%

Peak oxygen uptake in relation to total heart volume discriminates heart failure patients from healthy volunteers and athletes

Engblom

Steding

Carlsson

et al. 2010

Journal of Cardiovascular Magnetic Resonance

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BackgroundAn early sign of heart failure (HF) is a decreased cardiac reserve or inability to adequately increase cardiac output during exercise. Under normal circumstances maximal cardiac output is closely related to peak oxygen uptake (VO2peak) which has previously been shown to be closely related to total heart volume (THV). Thus, the aim of this study was to derive a VO2peak/THV ratio and to test the hypothesis that this ratio can be used to distinguish patients with HF from healthy volunteers and endurance athletes. Thirty-one patients with HF of different etiologies were retrospectively included and 131 control subjects (60 healthy volunteers and 71 athletes) were prospectively enrolled. Peak oxygen uptake was determined by maximal exercise test and THV was determined by cardiovascular magnetic resonance. The VO2peak/THV ratio was then derived and tested.ResultsPeak oxygen uptake was strongly correlated to THV (r2 = 0.74, p < 0.001) in the control subjects, but not for the patients (r2 = 0.0002, p = 0.95). The VO2peak/THV ratio differed significantly between control subjects and patients, even in patients with normal ejection fraction and after normalizing for hemoglobin levels (p < 0.001). In a multivariate analysis the VO2peak/THV ratio was the only independent predictor of presence of HF (p < 0.001).ConclusionsThe VO2peak/THV ratio can be used to distinguish patients with clinically diagnosed HF from healthy volunteers and athletes, even in patients with preserved systolic left ventricular function and after normalizing for hemoglobin levels.

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Section: Discussionsupporting

confidence: 60%

Peak oxygen uptake in relation to total heart volume discriminates heart failure patients from healthy volunteers and athletes

Engblom

Steding

Carlsson

et al. 2010

Journal of Cardiovascular Magnetic Resonance

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“…A normal level of N-terminal pro-brain natriuretic peptide (NT-proBNP) effectively rules out left ventricular systolic dysfunction in outpatients presenting with symptoms possibly due to heart failure who are referred from primary care to hospital-based cardiology services [1,2,3,4]. Dyspnea is the leading symptom of heart and lung disease.…”

Section: Introductionmentioning

confidence: 99%

NT-proBNP for Pulmonologists: Not Only a Rule-Out Test for Systolic Heart Failure but Also a Global Marker of Heart Disease

Wieshammer

Dreyhaupt²,

Basler³

et al. 2009

Respiration

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Background: Recognizing heart disease is relevant to pulmonologists because many patients suspected to have dyspnea of pulmonary origin harbor heart disease. Objectives: To investigate the role of N-terminal pro-brain natriuretric peptide (NT-proBNP) in identifying heart disease and cardiac causes of dyspnea among patients referred for evaluation by a pulmonologist. Methods: 697 consecutive outpatients (aged 57.5 ± 16.4 years) with chronic dyspnea prospectively underwent a diagnostic work-up for heart and lung diseases. Results: The prevalence of patients with heart disease was 25.3%. The cardiac findings were placed into 6 groups which were associated with an increase in NT-proBNP in the following order: (1) left ventricular hypertrophy [regression coefficient (β) = 0.33, p = 0.03]; (2) exercise-induced myocardial ischemia (β = 0.73, p = 0.02);(3) valvular or congenital heart disease or pericardial effusion (β = 0.93, p < 0.0001); (4) pulmonary hypertension (β = 1.14, p < 0.0001); (5) atrial fibrillation or left bundle branch block (β = 1.22, p < 0.0001), and (6) left ventricular systolic dysfunction (β = 1.94, p < 0.0001). Using predefined cut-off values of 93 pg/ml (men) and 144 pg/ml (women), sensitivity was 0.75 and specificity was 0.79 for identifying heart disease. The negative predictive value was 0.90. If heart disease had to be considered as a cause of the dyspnea, sensitivity and the negative predictive value went up to 0.90 and 0.97, respectively. Conclusions: NT-proBNP performs well as a test for ruling out cardiac dyspnea. It is also useful as a rule-in test for heart disease, which enables the pulmonologist to appropriately select candidates for in-depth evaluation by cardiology.

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“…The decision rule was derived from an individual patient data set from one of these studies (Zaphiriou et al 17 ) and externally validated on four others that included relevant variables. [18][19][20][21] The MICE rule comprised four clinical elements -Male, history of myocardial Infarction, Crepitations at the lung bases and oEdema -and was combined with natriuretic peptide levels to identify those likely to have heart failure and who should be referred for further diagnostic testing. The elements of the CDR are shown in Box 1.…”

Section: Clinical Decision Rulesmentioning

confidence: 99%

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

et al. 2017

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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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Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure diagnosis in primary care

Abstract: This study demonstrates that N-BNP measurement significantly improves the diagnostic accuracy of HF by GPs over and above customary clinical review.

Cited by 216 publications

References 31 publications

Peak oxygen uptake in relation to total heart volume discriminates heart failure patients from healthy volunteers and athletes

Peak oxygen uptake in relation to total heart volume discriminates heart failure patients from healthy volunteers and athletes

NT-proBNP for Pulmonologists: Not Only a Rule-Out Test for Systolic Heart Failure but Also a Global Marker of Heart Disease

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

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