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Will BNP or NT pro-BNP prove useful in identifying patients with heart failure in  Primary Care ? Dr Ahmet Fuat Darlington & The Dales PCTs Darlington Memorial Hospital Bishop Auckland General Hospital
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Natriuretic Peptides
Natriuretic Peptides: Origin and  Stimulus of Release Adapted from Burnett JC,  J Hypertens  2000;17(Suppl 1):S37-S43 ANP = Atrial Natriuretic Peptide BNP = B-type Natriuretic Peptide CNP = C-type Natriuretic Peptide Peptide Primary Origin Stimulus of Release ANP Cardiac atria Atrial distension BNP Ventricular myocardium Ventricular overload CNP Endothelium  Endothelial stress
Release of BNP from  Cardiac Myocytes myocyte preproBNP (134 aa) proBNP (108 aa) signal peptide (26 aa) secretion NT-proBNP (1-76) BNP (77-108)
B-Type Natriuretic Peptide (BNP) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Clinical Potential of BNP / NT-proBNP Has already been extensively studied! Diagnosis- raised in those with LVSD/AF/ LVH Normal BNP makes LVSD very unlikely NEGATIVE PREDICTIVE VALUE Prognosis- of patients with heart failure  Therapy-   monitor efficacy Treatment-   ?
WHY IS IT NOT BEING USED? 1.   Previous studies used “in-house” assays - Two now commercially available - BNP + NT proBNP.  Which to use? 2.   What cut off should be used (Bayesian model)? Companies report 97.5 percentile in volunteers up to 65! 3.   Can medication “normalize” the level? 4.   Where does it fit with other tests etc? 5.   Will we be swamped? 6.   Will it be cost effective?
A Comparison of the Two Commercially available Assays for B-Type Natriuretic Peptide when Selecting Patients with Suspected Heart Failure in Primary Care. Which should we choose? ,[object Object],[object Object],[object Object],[object Object]
Aims & Methodology Aims To compare the 2 assays directly in comparison to the “gold standard”: assessment of LV function by echo criteria To identify appropriate “cut-off” point for assays To plan “rollout” of BNP in primary care Methods & Setting Patients from primary care with suspected HF are referred to one-stop clinics at DMH & BAGH – all have bloods, ECG, CXR, BNP, NT pro-BNP & Echo  S can performed by BSE accredited senior technician LV function assessed by “eye-ball”, Simpson’s rule, wall motion score  Sensitivity, specificity and ROC used to calculate AUC, NPV and PPV for each assay
Preliminary data 280   consecutive  patients have been seen  and  studied Data has been assessed for 120 Age: Me a n 74 yrs  (Range 39-93)  Sex: 44 Males  76 Females LVSD present in 44 / 120 (37%)
BNP (Biosite) Negative predictive value at: pg/ml NPV % false / all negatives 20 78.9   4/19 40 88.2   6/51 50 87.7   7/57 60 86.9   8/61 80 86.3   10/73 100 82.2   14/79
NT pro-BNP (Roche) Negative predictive value at: pg/ml NPV %   fa lse/all negatives 50  87.5   1/8 100  95.5   1/22 125  96.7   1/30 150   97.3   1/37 175  93.0   3/43 200  91.5   4/47
Predictive Value ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
CONCLUSIONS Only a minority of patients referred to HF clinic had LVSD. In the real-life setting, NT pro-BNP performed better than BNP. A satisfactory cut-off has been identified (needs validating). NT pro-BNP could be used to select referrals to a HF clinic or for echocardiography.  This hypothesis needs testing  in real life GP
Suspected Heart Failure in Primary Care – the Utility of B-Type Natriuretic Peptide ( NT pro-BNP) as a Pre-screening Test for Secondary Care Referral – a Real Life Study Darlington & Bishop Auckland
Study Design & Aims ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Costing ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Methodology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Cost Analysis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Proposed outcome/evaluation measures ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
How research findings will be disseminated and implemented   ,[object Object],[object Object],[object Object]

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My stuff

  • 1. Will BNP or NT pro-BNP prove useful in identifying patients with heart failure in Primary Care ? Dr Ahmet Fuat Darlington & The Dales PCTs Darlington Memorial Hospital Bishop Auckland General Hospital
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  • 5. Natriuretic Peptides: Origin and Stimulus of Release Adapted from Burnett JC, J Hypertens 2000;17(Suppl 1):S37-S43 ANP = Atrial Natriuretic Peptide BNP = B-type Natriuretic Peptide CNP = C-type Natriuretic Peptide Peptide Primary Origin Stimulus of Release ANP Cardiac atria Atrial distension BNP Ventricular myocardium Ventricular overload CNP Endothelium Endothelial stress
  • 6. Release of BNP from Cardiac Myocytes myocyte preproBNP (134 aa) proBNP (108 aa) signal peptide (26 aa) secretion NT-proBNP (1-76) BNP (77-108)
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  • 8. Clinical Potential of BNP / NT-proBNP Has already been extensively studied! Diagnosis- raised in those with LVSD/AF/ LVH Normal BNP makes LVSD very unlikely NEGATIVE PREDICTIVE VALUE Prognosis- of patients with heart failure Therapy- monitor efficacy Treatment- ?
  • 9. WHY IS IT NOT BEING USED? 1. Previous studies used “in-house” assays - Two now commercially available - BNP + NT proBNP. Which to use? 2. What cut off should be used (Bayesian model)? Companies report 97.5 percentile in volunteers up to 65! 3. Can medication “normalize” the level? 4. Where does it fit with other tests etc? 5. Will we be swamped? 6. Will it be cost effective?
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  • 11. Aims & Methodology Aims To compare the 2 assays directly in comparison to the “gold standard”: assessment of LV function by echo criteria To identify appropriate “cut-off” point for assays To plan “rollout” of BNP in primary care Methods & Setting Patients from primary care with suspected HF are referred to one-stop clinics at DMH & BAGH – all have bloods, ECG, CXR, BNP, NT pro-BNP & Echo S can performed by BSE accredited senior technician LV function assessed by “eye-ball”, Simpson’s rule, wall motion score Sensitivity, specificity and ROC used to calculate AUC, NPV and PPV for each assay
  • 12. Preliminary data 280 consecutive patients have been seen and studied Data has been assessed for 120 Age: Me a n 74 yrs (Range 39-93) Sex: 44 Males 76 Females LVSD present in 44 / 120 (37%)
  • 13. BNP (Biosite) Negative predictive value at: pg/ml NPV % false / all negatives 20 78.9 4/19 40 88.2 6/51 50 87.7 7/57 60 86.9 8/61 80 86.3 10/73 100 82.2 14/79
  • 14. NT pro-BNP (Roche) Negative predictive value at: pg/ml NPV % fa lse/all negatives 50 87.5 1/8 100 95.5 1/22 125 96.7 1/30 150 97.3 1/37 175 93.0 3/43 200 91.5 4/47
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  • 16. CONCLUSIONS Only a minority of patients referred to HF clinic had LVSD. In the real-life setting, NT pro-BNP performed better than BNP. A satisfactory cut-off has been identified (needs validating). NT pro-BNP could be used to select referrals to a HF clinic or for echocardiography. This hypothesis needs testing in real life GP
  • 17. Suspected Heart Failure in Primary Care – the Utility of B-Type Natriuretic Peptide ( NT pro-BNP) as a Pre-screening Test for Secondary Care Referral – a Real Life Study Darlington & Bishop Auckland
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Editor's Notes

  1. Listed here are the three common natriuretic peptides. Structurally, the natriuretic peptides are similar. All have a 17 AA ring structure with 11 identical AA. This ring structure is essential for receptor binding (Guanylate cyclase linked receptor). The first natriuretic peptide that was identified in the late 1960s was the Atrial Natriuretic Peptide , a 28-amino acid hormone found predominantly in the atrium of the heart. ANP is increased in volume overload conditions in normal patients, as well as patients with CHF. The B-type, or formerly called Brain Natriuretic Peptide, has been found to be a more useful marker for congestive heart failure because the hormone is elevated in patients with congestive heart failure. BNP is secreted from the ventricles of the heart in response to ventricular stretch and volume overload. BNP has been synthesized and developed as a therapeutic tool for use in congestive heart failure. The C-type natriuretic peptide is found in the endothelium of the heart, has a very low concentration in plasma, and is not elevated in CHF. Other members of the natriuretic peptide family such as Urodilatin are still being identified and characterized. This family of hormonally active peptides clearly has a regulatory role in cardiovascular disease. The Triage® BNP Test is indicated for use as an aid in the diagnosis of congestive heart failure.
  2. This slide lists the origin and stimulus for the release of the natriuretic peptides. Note that BNP is specifically released from the ventricles of the heart in response to ventricular stretch and volume overload. The Triage® BNP Test is indicated for use as an aid in the diagnosis of congestive heart failure.
  3. BNP is produced from the cardiac myocytes as a prepro hormone of 134 amino acids, which is clipped into a proBNP hormone. Upon stimulus for secretion, it is released into the blood as the fragment protein N-terminal Pro BNP and the BNP molecule itself. The N-terminal portion is made of 77 amino acids and is a biologically inactive protein. BNP holds the biological activity primarily responsible for counteracting the RAA system. BNP is the hormonally active natriuretic peptide that is represented in the literature we will be reviewing. The Triage® BNP Test is indicated for use as an aid in the diagnosis of congestive heart failure.
  4. BNP is found in the cardiac ventricles and is released in direct response to stretch and increased volume in the ventricle. The utility of BNP in staging the severity of disease has been documented through its relationship to left ventricular end-diastolic pressure and New York Heart Association Classification. This information will now be reviewed. The Triage® BNP Test is indicated for use as an aid in the diagnosis of congestive heart failure.