for the in vitro quantitative measurement of type natriuretic … · 2020. 5. 7. · ended us riage...

Triage BNP

A symbols g

INTThe Quidel TSystems for tusing EDTA a as an aid as an aid for the ri for the ri

SUMMARIt is estimatecases occurriamount of blSymptoms ofoften vague a B‐type natriuis the main soincreased hein early stageQuidel Triagestratification

PRINCIPLEThe Quidel Tvessel with mparticles coatimmobilized BNP. After inunbound ma

Systems fopeptide (B

for BCIS

glossary can

TENDED USriage BNP testhe In Vitro quas the anticoa in the diagno in the assesssk stratificatisk stratificati

Y AND EXPed that 5.8 miing each yearood to the bof CHF includeand nonspeci

uretic peptideource of circuart pressure. es of CHF. Thee BNP test off in patients w

ES OF THE riage BNP tesmouse monocted with mouanti‐BNP on tcubation in aterials are wa

or the In VitroNP) in plasm

be found at

SE st is intendeduantitative mgulant. The tosis of congessment of seveon of patienton of patient

PLANATIOllion people i.1 Congestiveody.2 This con shortness ofific for detect

e (BNP) is a mulating BNP inVarious stude level of BNPfers an objectwith acute cor

PROCEDUst is a two‐siteclonal anti‐huuse Omniclonthe solid phaa reaction vesashed away. A

o quantitativma specimens

t quidel.com

for use with measurement est is intendestive heart faerity of congets with acute ts with heart f

N n the United e heart failurendition can ocf breath, fluidting early stag

ember of a cn humans.5,6 Ties have demP in the bloodtive, noninvasronary syndro

RE e immunoenzman BNP antal anti‐humase, while the ssel, materialsA chemilumin

ve measurems using EDTA

m/glossary.

the Beckmanof B‐type nated to be usedilure (also refestive heart facoronary synfailure

States have he (CHF) occurccur at any ag retention, anges of CHF.2

lass of hormoThe moleculemonstrated thd continues tosive measureomes (ACS).7,8

zymatic (“santibody‐alkalinn BNP antibomouse anti‐Bs bound to thnescent subst

ment of B‐typA as the antic

n Coulter Accetriuretic pept for the followferred to as hailure ndromes

heart failure wrs when the hge but is mosnd respirator

ones that rege is released inhat increased o increase as ment for asse8

ndwich”) assane phosphataody. BNP in huBNP conjugathe solid phasetrate, Lumi‐Ph

pe natriuretcoagulant.

ess Family of tide (BNP) in pwing indicatioheart failure)

with approximheart cannot dst prevalent iny distress. Th

ulate blood pnto the bloodlevels of circuthe CHF diseaessing patien

ay. A sample ise conjugate uman plasmate reacts spece are held in ahos* 530, is a

ic

Page

Immunoassaplasma specimons:

mately 670,0deliver a suffin an aged pophese symptom

pressure.3,4 Thd in response ulating BNP aase advancests for CHF an

s added to a and paramag

a binds to the cifically with ba magnetic fieadded to the

e 1 of 25

ay mens

00 new icient pulation. ms are

he heart to

are found s.7 The d risk

reaction gnetic

bound eld while reaction

Triage BNP

vessel and ligproportional from a stored

PRODUCTQuidel TriCat. No. 9820 Provided Store up Refrigera Stable un Stable at Signs of p If the rea All antise R1a: Pa

Taz

R1b: PP

R1c: Mb

WARNING For In Vit Patient s

procedurprecautiocertificatand their

Sodium aof liquids

The Quidinterpret

Blood cothat are c

GHS HazarGXM/MXLH P

for BCIS

ght generatedto the conced, multi‐point

T INFORMAage BNP R00: 100 deterd ready to useright and refrate at 2°C to 1ntil the expirat 2°C to 10°C fpossible deteagent pack is era are polycl

aramagnetic RIS buffered szide.

urified mouseroClin 300 an

Mouse monocuffered saline

GS AND PRtro Diagnosticamples and bre described. ons and goodtion. Use an ar containers iazide may reas, flush with adel Triage BNPted along withncentrations candidates fo

rd ClassificPMP WARN

H302 H315 H317 H319 P264

d by the reactentration of Bt calibration c

ATION Reagents rminations, 2e. rigerate at 2°C10°C for a mination date stafor 28 days afrioration are damaged (i.eonal unless o

particles coatsaline, with b

e and goat IgGnd < 0.1% sod

clonal anti‐hue with BSA, 0

RECAUTIONc Use. blood‐derivedHowever, ha

d clinical laborappropriate dn accordanceact with lead a large volumP test should h clinical findof BNP may bor renal dialys

cation NING

tion is measuNP in the samcurve.

2 packs, 50 te

C to 10°C. nimum of twoated on the lafter initial usea broken ela., broken elasotherwise indi

ted with moubovine serum

G in TRIS buffium azide.

man BNP ant.1% ProClin 3

NS

d products maandle these prratory practicisinfectant foe with local, stand copper pe of water tonot be used aings and othebe elevated insis, and patien

Harmful if sCauses skinMay cause Causes seriWash hand

red with a lummple. The amo

ests/pack

o hours beforbel when stoe. stomeric layestomer), discaicated.

use Omniclonalbumin (BSA

fered saline, w

tibody‐alkalin300, and < 0.1

ay be routineroducts as poces, regardlesor decontamintate and fedeplumbing to fo prevent azidas absolute eer laboratory n patients whnts that have

swallowed n irritation an allergic skous eye irritas thoroughly

minometer. Tount of analy

re use on the ored at 2°C to

er on the packard the pack.

al anti‐humaA), 0.1% ProC

with bovine s

ne phosphatas1% sodium az

ely processed otentially infess of their orignation. Store eral regulatioorm highly exde build‐up.9

evidence for Ctest results.ho are experie had renal dia

kin reaction ation after handlin

The light prodyte in the sam

instrument. 10°C.

k or control v.

n BNP antiboClin** 300, an

serum albumi

se bovine conide.

with minimuectious accordgin, treatmenand dispose ns and guidelxplosive meta

CHF. The resu

encing a hearalysis.

ng

Page

duction is diremple is determ

values out of r

ody suspendend < 0.1% sod

in (BSA), 0.1%

njugate in PBS

um risk using tding to univernt, or prior of these matlines. al azides. On d

ults should be

rt attack, pati

e 2 of 25

ectly mined

range.

d in dium

%

S

the rsal

erials

disposal

e

ients

Triage BNP for BCIS of 25

P270 Do not eat, drink or smoke when using this product P272 Contaminated work clothing should not be allowed out of the

workplace P301+P312 IF SWALLOWED: Call a POISON CENTER or doctor/physician if you

feel unwell P302+P352 IF ON SKIN: Wash with plenty of soap and water P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove

contact lenses, if present and easy to do. Continue rinsing. P321 Specific treatment: Seek medical attention if ill effect develops P330 Rinse mouth P332+P313 If skin irritation occurs: Get medical advice/attention P333+P313 If skin irritation or rash occurs: Get medical advice/attention. P337+P313 If eye irritation persists: Get medical advice/attention P501 Dispose of contents/container to: Dispose in a safe manner in

accordance with local/national regulations

European Hazard Classification GXM/MXLH PMP WARNING Xi;R43 R43 May cause sensitization by skin contact. The Safety Data Sheet (SDS) is available upon request.

SPECIMEN COLLECTION AND PREPARATION Plasma (EDTA) is the required sample. Use of plastic blood draw tubes containing K2 EDTA as an anticoagulant for sample collection permits an accurate measurement of plasma BNP concentrations for sample collection (Davidson et al., Circulation 91: 1276, 1995). Other specimen types have not been evaluated. Observe the following recommendations for handling, processing, and storing blood samples:10 Collect all blood samples observing routine precautions for venipuncture. Mix the blood specimen by gently inverting the tube several times. Keep tubes stoppered at all times. Samples should be tested as soon as possible after collection. However, if it is not possible to test the

samples immediately, the following is recommended: Blood and plasma specimens may be stored at room temperature (or chilled) for testing within 7 hours

of collection. Plasma specimens may be stored chilled for testing within 24 hours of collection. Transport specimens at room temperature or chilled and avoid extreme temperatures.

For longer storage, transfer at least 500 μL of cell‐free sample to a storage tube. Tightly stopper the tube

immediately and freeze at –20C or colder in a non‐defrosting freezer. When thawing, allow samples to equilibrate to room temperature for a minimum of 30 minutes prior to testing.

Thaw samples only once. It is recommended to avoid using severely hemolyzed specimens whenever possible. If a specimen appears

to be severely hemolyzed, another specimen should be obtained and tested. Use the following guidelines when preparing specimens, unless instructed otherwise in the product insert: Ensure residual fibrin and cellular matter has been removed prior to analysis. Follow blood collection tube manufacturer’s recommendations for centrifugation.


Each laboratory should determine the acceptability of its own blood collection tubes. Variations in these products may exist between manufacturers and, at times, from lot to lot.

MATERIALS PROVIDED R1: Quidel Triage BNP Reagent Packs

MATERIALS REQUIRED BUT NOT PROVIDED Quidel Triage BNP Calibrators: Provided at zero, and approximately 25, 100, 500, 2500, and 5000 pg/mL

(Cat. #98202). Quidel Triage BNP QC Controls: Provided at approximately 80, 400, and 2200 pg/mL (Cat. #98201). Access*** Substrate (Cat. #81906) Access Wash Buffer II

NOTE: The required wash buffer II catalog number is dependent upon your current instrument status. Please contact Beckman Coulter technical support if you are unsure of which buffer to order. Cat. No. A16792 (Access, Access 2, SYNCHRON LXi, UniCel DxC600i) Cat. No. A16793 (UniCel DxX 660i, UniCel DxC 680i, UniCel DxC 860i, UniCel DxC 880i, UniCel DxI 600, UniCel DxI 800)

One of the following immunoassay systems: Access, Access 2, Synchron LXi 725, UniCel DxC 660i, UniCel DxC 680i, UniCel DxC 860i, UniCel DxC 880i, UniCel DxI 600, UniCel DxI 800 or UniCel DxC600i

PROCEDURAL COMMENTS Refer to the appropriate system manuals and/or help system for a specific description of installation, start‐

up, principles of operation, system performance characteristics, operating instructions, calibration procedures, operational limitations and precautions, hazards, maintenance, and troubleshooting.

Mix contents of new (unpunctured) reagent packs by gently inverting pack several times before loading on the instrument. Do not invert open (punctured) packs.

Use 55 µL of sample for each determination in addition to the sample container and system dead volumes. Use one hundred fifty‐five (155) µL of sample in addition to the sample container and system dead volumes for each determination run with the DxI system onboard dilution feature. Refer to the appropriate system manuals and/ or Help system for the minimum sample volume required.

The unit of measure for sample results is pg/mL.

PROCEDURE Refer to the appropriate system manuals and/ or Help system for information on managing samples, configuring tests, requesting tests, and reviewing test results.

Calibration Details An active calibration curve is required for all tests. For the Quidel Triage BNP test, calibration is required every 28 days. Refer to the appropriate system manuals and/ or Help system for information on calibration theory, configuring calibrators, calibrator test request entry, and reviewing calibration data.

QUALITY CONTROL Quality control materials simulate the characteristics of patient samples and are essential for monitoring the system performance of immunochemical assays. Because samples can be processed at any time in a “random access” format rather than a “batch” format, quality control materials should be included in each 24‐hour time period.11 Include Quidel Triage BNP QC Controls for the Beckman Coulter Access Family of Immunoassay


Systems that cover at least two levels of the analyte. The use of non‐Quidel Control materials is not recommended. More frequent use of controls or the use of additional controls is left to the discretion of the user based on good laboratory practices or laboratory accreditation requirements and applicable laws. Follow manufacturer's instructions for reconstitution and storage. Each laboratory should establish mean values and acceptable ranges to assure proper performance. Quality control results that do not fall within acceptable ranges may indicate invalid test results. Examine all test results generated since obtaining the last acceptable quality control test point for this analyte. Refer to the appropriate system manuals and/ or Help system for information about reviewing quality control results.

RESULTS Patient test results are determined automatically by the system software using a smoothing spline math model. The amount of analyte in the sample is determined from the measured light production by means of the stored calibration data. Patient test results can be reviewed using the appropriate screen. Refer to the appropriate system manuals and/or Help system for complete instructions on reviewing sample results.

Interpretation of the Results The Beckman Coulter Access Family of Immunoassay Systems calculates the test results automatically. A number in pg/mL represents the amount of BNP present in the sample. BNP results less than or equal to 100 pg/mL are representative of normal values in patients without CHF. BNP results greater than 100 pg/mL are considered abnormal and suggestive of patients with CHF. BNP results of > 5000 pg/mL are considered very high values for BNP and exceed the upper limits of the

BNP test. Higher BNP concentrations measured in the first 72 hours after an acute coronary syndrome are

associated with an increased risk of death, myocardial infarction, and CHF. Higher BNP concentrations or the lack of a decrease in the BNP concentration from hospital admission to

discharge indicate an increased risk of hospitalization or death in patients with heart failure.

LIMITATIONS OF THE PROCEDURE The results of the Quidel Triage BNP test should be evaluated with all clinical and laboratory data available.

If Quidel Triage BNP test results do not agree with the clinical evaluation, additional tests should be performed.

This test has been evaluated with plasma using EDTA as the anticoagulant. Serum and blood or plasma specimens obtained using other anticoagulants (e.g., heparin or citrate) have not been evaluated and should not be used.

Other factors may interfere with the Quidel Triage BNP test and may cause erroneous results. These include technical or procedural errors, as well as additional substances in blood specimens that are not listed or exceed the concentrations listed in the Interfering Substances and the Analytical Specificity sections.

1. Samples can be accurately measured within the analytic range of the lower limit of detection and the highest calibrator value [approximately 1–5000 pg/mL]. When the DxI system onboard dilution feature is used, the system will report results approximately 4250‐10,000 pg/mL.

If a sample contains more than the stated value of the highest Quidel Triage BNP Calibrator (S5), report the result as greater than that value [i.e. > 5000 pg/mL]. Alternatively, dilute one volume of sample with one volume of Access Wash Buffer. Refer to the appropriate system manuals and/ or Help system for instructions on entering a sample dilution in a test request. The system reports the results adjusted for the


dilution. The DxI system onboard dilution feature automates the dilution process, using one volume of sample with one volume of UniCel DxI Access Immunoassay Systems Wash Buffer II, allowing samples to be quantitated up to approximately 10,000 pg/mL. The system reports the results adjusted for the dilution.

2. Human anti‐mouse antibodies (HAMA) may be present in samples from patients who have received immunotherapy utilizing monoclonal antibodies.12 Additionally, other heterophile antibodies such as human anti‐goat antibodies, may be present in patient samples.13 This test has been specifically formulated to minimize the effects of these antibodies on the assay. However, carefully evaluate results from patients suspected of having such antibodies.

3. The Quidel Triage BNP test does not demonstrate any “hook” effect when tested up to BNP concentrations of 150,000 pg/mL.

4. The Quidel Triage BNP test results should be interpreted in light of the total clinical presentation of the patient, including: clinical history, data from additional tests and other appropriate information.

SPECIFIC PERFORMANCE CHARACTERISTICS Performance characteristics were determined using the Access immunoassay platform.

Methods Comparison A comparison of 412 EDTA plasma samples measured values using the Quidel Triage BNP test on the Access Immunoassay System and the Quidel Triage BNP test gave the following statistical data using Passing‐Bablok regression analysis:

n

Range of Observations

(pg/mL)

Intercept (pg/mL)

Slope

Correlation Coefficient

(r)

412 5–4970 ‐0.15 1.00 0.950

The results indicate that Quidel Triage BNP test results can be used interchangeably.

Dilution Recovery (Linearity) Multiple dilutions of 4 plasma samples spiked with purified BNP to final concentrations of approximately 5000 pg/mL using unspiked plasma as the diluent resulted in the following data:

Percent Recovery

Donor 1 Donor 2 Donor 3 Donor 4 Level 1 102.2% 103.4% 106.0% 100.3% Level 2 101.1% 101.5% 97.1% 98.4% Level 3 97.0% 98.7% 94.8% 96.1% Level 4 93.3% 93.3% 90.1% 91.5% Level 5 89.9% 92.2% 88.0% 88.2% Level 6 92.1% 91.2% 83.3% 89.5% Level 7 91.6% 90.6% 87.8% 90.0% Level 8 91.0% 88.2% 87.9% 87.9% Level 9 88.1% 89.4% 86.6% 85.0%


Imprecision Reproducibility of the Quidel Triage BNP test was determined in a study using commercially available and in‐house human control material with two lots of reagents. The study included a total of 20 assays, 2 replicates per assay, over 20 days. Representative data were calculated based on NCCLS EP5‐A guidelines and are presented in the following table.14,15

Control Mean (pg/mL)

Within Run SD

Within Run % CV

Between Run SD

Between Run % CV

Total %

EDTA Plasma 1 40.8 1.24 3.1 1.82 4.5 5.4

EDTA Plasma 2 1343.6 12.89 1.0 89.05 6.6 6.7

Control Level 1 24.5 0.65 2.7 1.29 5.3 5.9

Control Level 2 77.2 1.97 2.6 2.49 3.2 4.1

Control Level 3 3966.2 45.04 1.1 70.90 1.8 2.1

Interfering Substances Hemoglobin (up to 500 mg/dL), triglycerides (triolein up to 3000 mg/dL), bilirubin (conjugated up to 20 mg/dL), fibrinogen (up to 800 mg/dL), or human serum albumin (up to 1500 mg/dL) added to plasma specimens containing BNP did not interfere with the recovery of BNP.

Analytical Specificity Pharmaceuticals The following drugs were evaluated for potential cross‐reactivity and interference in the Quidel Triage BNP test. All drugs were tested at concentrations representing the blood concentrations that would result from a maximal therapeutic dose and at least twice the maximal therapeutic dose. None of the drugs interfered with the recovery of BNP. Additionally, these drugs did not produce a significant response when tested in a specimen not containing BNP. There was no significant interference with the BNP measurement, nor was there any assay cross‐reactivity.

Acetaminophen Cocaine Nitrofurantoin

Allopurinol Diclofenac Nystatin

Ambroxol Digoxin Oxytetracycline

Ampicillin Dopamine Phenytoin

Ascorbic Acid Erythromycin Propranolol

Aspirin Furosemide Quinidine

Atenol Heparin Theophylline

Caffeine Ibuprofen Trimethoprim

Captopril Methyldopa Verapamil

Cinnarizine Nifedipine Nesiritide is a synthetic form of BNP; BNP measurements should not be performed during Nesiritide Infusion.


Proteins and Peptides The following proteins and peptides were evaluated for potential cross‐reactivity and interference in the Quidel Triage BNP test at the concentrations indicated below. There was no significant interference with the BNP measurement, nor was there any significant assay cross‐reactivity. Reactivity with Related Proteins and Peptides

Concentration Substance of Substance % Recovery

Adrenomedullin 1000 pg/mL 101.4%

Atrial Natriuretic polypeptide 1‐28 1000 pg/mL 99.2%

Angiotensin I 600 pg/mL 97.9%

Angiotensin II 600 pg/mL 96.5%

Angiotensin III 1000 pg/mL 95.1%

Arg Vasopressin 1000 pg/mL 95.7%

C type Natriuretic Peptide 53 1000 pg/mL 96.8%

Endothelin I 20 pg/mL 99.2%

Prepro ANF 104‐123 1000 pg/mL 96.7%

Prepro ANF 26‐55 1000 pg/mL 94.2%

Prepro ANF 56‐92 1000 pg/mL 95.6%

Prepro BNP 1‐21 1000 pg/mL 98.5%

Prepro BNP 22‐46 1000 pg/mL 97.7%

Renin 50 ng/mL 95.8%

Urodilatin 95‐126 1000 pg/mL 91.6%

Analytical Sensitivity The lowest detectable level of BNP distinguishable from zero (Quidel Triage BNP Calibrator S0) with 95% confidence is 1 pg/mL. This value is determined by processing a complete six‐point calibration curve, controls, and 10 replicates of the zero calibrator in multiple assays. The analytical sensitivity value is calculated from the curve at the point that is two standard deviations from the mean zero calibrator signal.

Data from Clinical Studies Individuals Without CHF The circulating BNP concentration was determined from 1286 individuals without CHF (676 women and 610 men). This population included individuals with hypertension, diabetes, renal insufficiency, and chronic obstructive pulmonary disease. There are no statistically significant changes in BNP concentration associated with hypertension, diabetes, renal insufficiency, and chronic obstructive pulmonary disease. The descriptive statistics for BNP concentrations in individuals without CHF are shown in the table below. The values are representative of the values obtained from clinical studies. The decision threshold was determined by the 95% confidence limit of BNP concentration in the non‐CHF population age 55 and older. The most appropriate decision threshold apparent from these distributions is 100 pg/mL. This value translates into a general specificity of the test of 98%, i.e. less than 2% expected false positives in individuals without CHF. Each laboratory should establish a reference range that represents the patient population that is to be evaluated.


Descriptive Statistics – BNP Concentration (pg/mL) Non‐CHF Population

All

All Age < 45 Age 45–54 Age 55–64 Age 65–74 Age 75+

Median 12.3 7.7 11.1 17.9 19.8 53.9

95th Percentile 73.5 39.6 64.5 76.1 84.7 179.4

Percent < 100 pg/mL

98.0% 99.5% 99.2% 97.4% 96.9% 84.2%

Minimum 5.0 5.0 5.0 5.0 5.0 5.0

Maximum 252.0 251.3 252.0 207.7 197.9 218.5

N 1286 423 385 229 192 57

Males


Median 7.1 5.0 7.2 9.0 15.7 39.0

95th Percentile 56.9 23.8 39.0 72.4 62.7 77.9

Percent < 100 pg/mL

98.9% 98.9% 99.5% 98.3% 98.9% 95.8%

Minimum 5.0 5.0 5.0 5.0 5.0 5.0

Maximum 252.0 251.3 252.0 207.7 127.3 218.5

N 610 183 196 118 89 24

Females


Median 18.5 11.6 17.7 28.2 27.6 67.1

95th Percentile 84.2 47.4 71.7 80.5 95.4 179.5

Percent < 100 pg/mL

97.2% 100.0% 98.9% 96.4% 95.1% 75.8%

Minimum 5.0 5.0 5.0 5.0 5.0 5.0

Maximum 197.9 92.6 142.8 143.2 197.9 194.1

N 676 240 189 111 103 33 Individuals with CHF Blood samples were obtained from 804 patients diagnosed with CHF (246 women and 558 men). The descriptive statistics for BNP concentrations in patients with CHF are presented in the table below. These values are representative of the values obtained from clinical studies. Each laboratory should establish a reference range that represents the patient population that is to be evaluated. In addition, laboratories should be aware of their respective institutions’ current practice for the evaluation of patients with CHF.

CHF Population – All

NYHA Functional Class

All CHF* I II III IV

Median 359.5 95.4 221.5 459.1 1006.3

5th Percentile 22.3 14.8 9.9 37.6 147.2

Percent > 100 pg/mL 80.6% 48.3% 76.6% 86.0% 96.3%

Minimum 5.0 5.0 5.0 5.2 5.0

Maximum > 5000 904.6 4435.8 > 5000 > 5000

N 804 118 197 300 187

CHF Population – Males



Median 317.8 87.8 232.6 458.9 1060.3

5th Percentile 21.9 16.8 10.7 25.0 196.5

Percent > 100 pg/mL 78.9% 46.5% 78.8% 85.2% 97.2%


Minimum 5.0 5.0 5.0 5.2 5.0

Maximum > 5000 904.6 2710.6 > 5000 > 5000

N 558 101 146 203 106

CHF Population – Females



Median 499.7 114.7 191.2 469.2 996.5

5th Percentile 30.7 6.8 9.7 45.6 121.0

Percent > 100 pg/mL 84.6% 58.8% 70.6% 87.6% 95.1%

Minimum 5.0 5.0 5.0 11.7 15.5

Maximum > 5000 519.6 4435.8 4582.0 4706.5

N 246 17 51 97 81

*2 CHF with unknown NYHA class (male) The New York Heart Association (NYHA) developed a four‐stage functional classification system for CHF that is based on a subjective interpretation of the severity of a patient’s clinical signs and symptoms. Class I patients have no limitations of physical activity and have no symptoms with ordinary physical activity. Class II patients have a slight limitation of physical activity and have symptoms with ordinary physical activity. Class III patients have a marked limitation of physical activity and have symptoms with less than ordinary physical activity, but not at rest. Class IV patients are unable to perform any physical activity without discomfort. Reports in the scientific literature have indicated that there is a relationship between BNP and the severity of CHF.2,7,16‐18 An analysis of NYHA classification and BNP concentrations from the clinical study data indicate that there is a relationship between the severity of the clinical signs and symptoms of CHF and BNP concentration. These data are consistent with the previous reports in the literature, and further demonstrate that BNP measurements, along with NYHA classification, can provide additional objective information to the physician about the patient’s CHF severity.

Diagnostic Utility Various studies have demonstrated that circulating BNP concentrations increase with the severity of CHF based on the NYHA classification. BNP concentrations are much lower than ANP concentrations normally, but as the severity of CHF advances according to the NYHA classification, plasma BNP increases progressively more than respective ANP values.6 Therefore, BNP is a more useful marker than ANP to distinguish between normal subjects and patients in the earlier stages of CHF. BNP is more sensitive and specific than ANP for detecting


decreases in LVEF.7,16 Additionally, there is a positive correlation between blood BNP concentrations and left ventricular end diastolic pressure and inverse correlation to left ventricular function following acute myocardial infarction.16 Blood BNP concentrations represent an independent assessment of ventricular function without the use of other invasive or expensive diagnostic tests.16 There is an association with elevated BNP concentrations and alterations in hemodynamic parameters including raised atrial and pulmonary wedge pressures, reduced ventricular systolic and diastolic function, left ventricular hypertrophy, and myocardial infarction.19 Numerous reports in the scientific literature have described the utility of BNP as a diagnostic marker for CHF and left ventricular dysfunction.1,2,7,16‐23 These observations are supported by an analysis of the clinical study data. The Receiver Operating Characteristic (ROC) Curve of BNP cut‐offs versus clinical sensitivity and specificity from the clinical study data is provided below. The area under the curve is 0.955 ± 0.005. The clinical utility of the Quidel Triage BNP test also has been confirmed and described in detail in the scientific literature.24,25

A box and whiskers plot for the clinical study population is provided below, with a horizontal dashed line representing the suggested cutoff of 100 pg/mL.


The clinical sensitivity and specificity of the Quidel Triage BNP test using a cutoff of 100 pg/mL for various age groups within each gender is described in the table below.

Males

Age < 45 Age 45–54 Age 55–64 Age 65–74 Age 75+

Sensitivity 81.6% 76.0% 75.6% 79.3% 82.4%

95% Confidence Interval

70.8% – 92.5% 67.5% – 84.6% 68.2% – 82.9% 72.6% – 86% 76.1% – 88.7%

Specificity 98.9% 99.5% 98.3% 98.9% 95.8%


97.4% – 100.0% 98.5% – 100.0% 97.7% – 98.9% 98.4% – 99.4% 94.7% – 96.9%

Females

Age < 45 Age 45–54 Age 55–64 Age 65–74 Age 75+

Sensitivity 82.1% 69.0% 82.4% 97.9% 91.9%


68.0% – 96.3% 57.1% – 80.9% 71.9% – 92.8% 93.7% – 100.0% 85.2% – 98.7%

Specificity 100.0% 98.9% 96.4% 95.0% 75.7%


100.0% – 100.0% 97.5% – 100.0% 95.5% – 97.4% 93.4% – 96.7% 72.2% – 79.2%

It has been reported that BNP has excellent utility as an aid in the diagnosis of patients with CHF and preserved systolic function (CHF–PSF), generally referred to as diastolic dysfunction.19,26‐28 The diagnostic utility of BNP in CHF‐PSF patients was determined from the clinical study data by determining the area under the ROC curve for individuals without CHF versus 155 individuals with CHF that had ejection fractions ≥50%. The area under the curve is 0.934 ± 0.012, which indicates that the test is effective as an aid in the diagnosis of CHF in patients with preserved systolic function.


An age‐matched analysis of the clinical data was performed with the following common age distribution in the groups of individuals with and without CHF: individuals less than 35 years old comprise 3% of the total number of observations, individuals age 35–44 comprise 6% of the total, individuals age 45–54 comprise 11% of the total, individuals 55–64 years old comprise 22% of the total, individuals 65–74 years old comprise 26% of the total, and individuals 75 years and older comprise 32% of the total. This age distribution reflects the prevalence of CHF within the age groups and genders, according to data published by the American Heart Association in the 2000 Heart and Stroke Statistical Update, and also reflects the age structure of the United States population, according to data published by the National Center for Health Statistics in Health, United States, 2000. The resulting area under the ROC curve is 0.930 with a 95% confidence interval of 0.902–0.958.

Prognostic Utility in Patients with Acute Coronary Syndromes BNP concentrations measured in patients with acute coronary syndromes (ACS) or cardiovascular disease provide prognostic information about the patient's risk for death and the development of CHF.19,29‐33 Statistically significant increases in death, future myocardial infarction, and CHF have been associated with higher BNP concentrations measured within the first 72 hours after the onset of ACS symptoms. In a recent clinical study, BNP concentrations were evaluated in an observational, retrospective manner in patients with ACS (consisting of unstable angina, myocardial infarction with ST‐segment elevation, or myocardial infarction without ST‐segment elevation). BNP measurements were performed on specimens obtained within 72 hours after the onset of ischemic discomfort from a population of 2525 high‐risk ACS patients that met standard diagnostic criteria for ACS. Patients whose BNP concentration was at least 80 pg/mL had higher rates of death, myocardial infarction, and CHF both at 30 days and at 10 months after presentation than patients whose BNP concentration was below 80 pg/mL.8 In this population of patients with ACS, BNP measurements within the first 72 hours after the onset of symptoms provide useful predictive information to aid in the risk stratification of patients with ACS.

Prognostic Utility in Patients with Heart Failure BNP concentrations measured at admission and/or discharge in patients with heart failure provide prognostic information about the patient's risk for death or rehospitalization. A systematic review of studies investigating BNP for prognostic utility in patients with heart failure concluded that every 100 pg/mL increase in BNP concentration was associated with a 35% increase in the relative risk of death, and that admitted heart failure patients whose BNP values did not decrease over the course of their treatment are at a particularly high risk of death or a cardiovascular event.39 The authors also found that higher BNP concentrations in asymptomatic patients were prognostic for future death or cardiovascular events. Vrtovec et al and Harrison et al studied heart failure patients at the time of presentation and found that patients with higher BNP concentrations (> 1,000 pg/mL and > 480 pg/mL, respectively) had a significantly higher risk of all‐cause, cardiac, and pump‐failure death and cardiac‐related readmissions.40,41 Cheng et al and Bettencourt et al studied admitted heart failure patients receiving treatment and found that patients who did not experience death or readmission within 30 days or 6 months exhibited a decrease in BNP concentrations from admission to discharge, while patients whose BNP concentration did not decrease from admission to discharge were at significantly higher risk for adverse events.42,43 Logeart et al found that admitted heart failure patients with pre‐discharge BNP concentrations of 350‐700 pg/mL had a hazard ratio of 5.1 for death or readmission for heart failure within 6 months and patients with a pre‐discharge BNP concentration greater than 700 pg/mL had a hazard ratio of 15.2 for the same endpoint compared to patients with a pre‐discharge BNP concentration less than 350 pg/mL.44 Taken together, these studies indicate that higher BNP concentrations or the lack of a decrease in the BNP concentration from hospital admission to discharge indicate an increased risk of hospitalization or death in patients with heart failure.

Triage BNP

A symbols g

INTThe Quidel Tusing the Bec

SUMMARQuality contrsystem perfopractices.11,34

integrity of thproperly.

PRODUCTQuidel TriCat. No. 9820 Provided Mix cont Stable un

freezer a Vial is sta Signs of p Refer to QC 1, QC 2,

QCC Value C



for BCIS

glossary can

TENDED USriage BNP QCckman Coulte

Y AND EXProl materials sormance of th4‐38 When perhe assays. Th

T INFORMAage BNP Q01: 2.5 mL/vid ready to useents by gentlntil the expiraway from theable at 2°C topossible detethe QC value

QC 3: Re(ng0.1

Card: 1

GS AND PRtro Diagnosticamples and bre described. ons and goodtion. Use an ar containers i

be found at

SE C Controls areer Access Fam

PLANATIOsimulate the he Quidel Triarforming the Qe assayed val

ATION QC Controlial, 2 vials eace. y inverting beation date stae freezer doo 10°C for 30 drioration are card for mea

ecombinant hg/L), respecti1% ProClin**


d clinical laborappropriate dn accordance

t quidel.com

e intended formily of Immun

N characteristicage BNP test. Quidel Triagelues should fa

s ch level

efore use. Avated on the lar. days after initcontrol valuean values and

uman BNP covely, in buffer300.

NS

d products maandle these prratory practicisinfectant foe with local, st

m/glossary.

r monitoring noassay Syste

cs of patient sIn addition, te BNP test, incall within the

oid bubble fobel when sto

tial use or whes out of rang standard dev

omplex at levred BSA matr

ay be routineroducts as poces, regardlesor decontamintate and fede

the performams.

samples and they are an include quality acceptable r

ormation. ored at –20°C

hen removed ge. viations (SD).

vels of approxrix with surfac

ely processed otentially infess of their orignation. Store eral regulatio

ance of the Q

are essentialntegral part ocontrol mateange if the te

or colder in a

from frozen s

.

ximately 80, 4ctant, < 0.1%

with minimuectious accordgin, treatmenand dispose ns and guidel

Page 1

Quidel Triage B

for monitorif good laboraerials to validaest system is w

a non‐defrost

storage.

400, and 2200sodium azide

um risk using tding to univernt, or prior of these matlines.

14 of 25

BNP test

ng the atory ate the working

ting

0 pg/mL e, and

the rsal

erials

Triage BNP

Sodium aof liquids

GHS HazarGXM/MXLH P

European GXM/MXLH P The Safet

PROCEDUDetermine thAccess Familyprocessed atshould be inccontrols is lefrequirementinformation oreviewing qu

LIMITATIOIf there is evi

EXPECTEDFor the valueentire lot, arestandard devmay result invalues and st

for BCIS

azide may reas, flush with a


H315 H317 H319 P261 P272 P280

P302+P321 P333+P362+P501

Hazard ClPMP WARN

Xi;R43R43

ty Data Sheet

RE he concentraty of Immunoa any time in acluded in eachft to the discrs and applicaon quality couality control

ONS OF THidence of mic

D VALUES e assignment e selected anviations are lisn values differtandard devia

act with lead a large volum

cation NING

CaMCaAvCoWpr

+P352 IF Sp

+P313 If s+P364 Ta

Diswi

assificatioNING 3

M

t (SDS) is avai

tion of BNP inassay Systema “random ach 24‐hour timretion of the ble laws. Refentrol theory, data.

E PROCEDcrobial contam

of the Quided assayed to sted on the Qrent from thoations (SD).

and copper pe of water to

auses skin irritay cause an aauses serious void breathingontaminated wear protectivotection ON SKIN: Wapecific treatmskin irritationke off contamspose of contth local/natio

n

ay cause sens

ilable upon re

n the Quidel Ts in the samecess” format

me period.11 Muser based oer to the appconfiguring c

DURE mination or e

l Triage BNP Qprovide a rel

QC value cardose listed. The

plumbing to fo prevent azid

tation allergic skin reeye irritationg dust/fume/work clothinge gloves/prot

ash with plentent: Seek men or rash occuminated clothtents/containonal regulatio

sitization by s

equest.

Triage BNP tee manner as arather than a

More frequenn good laboraropriate systecontrols, qual

xcessive turb

QC Controls, iable estimat. Variations, serefore, each

orm highly exde build‐up.9

eaction. n /gas/mist/vapg should not btective clothi

ty of soap andedical attentiours: Get mediching and washner: Dispose ions

skin contact.

est QC Controa patient sama “batch” formnt use of contatory practiceem manuals aity control sa

bidity in a reag

a number of te of the measuch as in teclaboratory sh

xplosive meta

pors/spray be allowed oung/eye prote

d water on if ill effect cal advice/atth it before reun a safe man

ols using the Bmple. Becausemat, quality crols or the uses or laboratoand/or Help sample test req

gent, discard

samples, repn value. The chnique, equihould establis

Page 1

al azides. On d

ut of the worection/face

develops tention. use ner in accord

Beckman Cou samples cancontrol materse of additionory accreditatsystem for quest entry, a

the vial.

resentative omean values pment, or reash its own me

15 of 25

disposal

rkplace

ance

lter be rials nal tion

and

of the and agents ean

Triage BNP

A symbols g

INTEThe Quidel TdeterminatioSystems.

SUMMARQuantitative calibrators) athe measuremathematicapatient samp

TRACEABIThe measuracalibrators. T The assignedto the assay may be differ

PRODUCTQuidel TriCat. No. 982 Provided Stable un

freezer a Vial is sta Signs of p S0:

S1, S2, S3, S4, S5:

Calibration

for BCIS

glossary can

ENDED USriage BNP Caon of BNP leve

Y AND EXPassay calibraare tested liked responses aal relationshipples to specifi

LITY and (analyte) Traceability pr

d values were methodologierent. Such dif

T INFORMAage BNP C

202: S0–S5, 1d ready to usentil the expiraway from theable at 2°C topossible dete

Buf< 0

Rec500Pro

Card: 1

be found at

E librators are els in human

PLANATIOation is the pre patient samand the knowp, or calibratic quantitative

in the Quidelrocess is base

established ues of the Quidfferences, if p

ATION

Calibrators.5 mL/vial e. ation date stae freezer doo 10°C for 30 drioration are

ffered bovine.1% sodium a

combinant hu00 pg/mL in boClin 300.

t quidel.com

intended to cEDTA plasma

N ocess by whic

mples to measwn analyte conon curve, is ue analyte con

Triage BNP Ced on prEN IS

using represedel Triage BNpresent, may

s

ated on the lar. days after initcontrol value

serum albumazide, and 0.1

uman BNP combuffered BSA

m/glossary.

calibrate the Qa using the Be

ch samples wure the responcentrations used to convencentrations.

Calibrators is O 17511.

entative sampNP test reagenbe caused by

bel when sto

tial use or whes out of rang

min (BSA) mat1% ProClin**

mplex at levematrix with s

Quidel Triageeckman Coult

with known anonse. The maestablishes tert RLU (Relat

traceable to

ples from thisnts. Values asy inter‐metho

ored at –20°C

hen removed ge.

trix with surfa300.

els of approxiurfactant, < 0

e BNP test forter Access Fam

nalyte concenthematical rehe calibrationtive Light Unit

the manufact

s lot of calibrassigned by othod bias.

or colder in a

from frozen s

actant,

mately 25, 100.1% sodium

Page 1

r the quantitamily of Immu

ntrations (i.e.elationship ben curve. This t) measureme

turer’s worki

ator and are sher methodo

a non‐defrost

storage.

00, 500, 2500azide, and 0.

16 of 25

ative noassay

, assay etween

ents of

ng

specific logies

ting

0 and 1%

Triage BNP



Sodium aof liquids

GHS HazarGXM/MXLH P

European GXM/MXLH P The Safet

PROCEDURefer to the acalibrators, c

CALIBRATThe Quidel T5000 pg/mL. Run Calibrato

for BCIS

GS AND PRtro Diagnosticamples and bre described. ons and goodtion. Use an ar containers iazide may reas, flush with a


H315 H317 H319 P264 P272

P302+P305+

P321 P332+P333+P337+P362+P501

Hazard ClPMP WARN

Xi;R43R43

ty Data Sheet

RE appropriate scalibrator test

ION DETAriage BNP CaAssay calibra

ors in duplica


d clinical laborappropriate dn accordanceact with lead a large volum

cation NING

+P352 +P351+P338

+P313 +P313 +P313 +P364

assificatioNING 3

M

t (SDS) is avai

system manut request entr

ILS librators are ation data are

te.

NS

d products maandle these prratory practicisinfectant foe with local, stand copper pe of water to

Causes skinMay cause Causes seriWash handContaminatworkplaceIF ON SKIN:IF IN EYES: contact lenSpecific treaIf skin irritaIf skin irritaIf eye irritatTake off conDispose of caccordance

n

ay cause sens

ilable upon re

als and/or Hery, and review

provided at 6e valid up to 2

ay be routineroducts as poces, regardlesor decontamintate and fedeplumbing to fo prevent azid

n irritation an allergic skous eye irritas thoroughly ted work clot

Wash skin thRinse cautiouses, if presenatment: Seektion occurs: Gtion or rash otion persists: ntaminated ccontents/cone with local/na

sitization by s

equest.

elp system fowing calibratio

6 levels – zero28 days.

ely processed otentially infess of their orignation. Store eral regulatioorm highly exde build‐up 9.

kin reaction. ation after handlinthing should n

horoughly witusly with watent and easy tok medical atteGet medical aoccurs: Get mGet medical clothing and wntainer: Dispoational regula

skin contact.

r informationon data.

o and approxi

with minimuectious accordgin, treatmenand dispose ns and guidelxplosive meta

ng not be allowe

th mild soap er for severalo do. Continueention if ill effadvice/attentmedical adviceadvice/attenwash it beforeose in a safe mations

n on calibratio

imately 25, 10

Page 1

um risk using tding to univernt, or prior of these matlines. al azides. On d

ed out of the

and water l minutes. Ree rinsing fect developstion e/attention. tion e reuse manner in

on theory, co

00, 500, 2500

17 of 25

the rsal

erials

disposal

move

s

nfiguring

0 and


LIMITATIONS OF THE PROCEDURE If there is evidence of microbial contamination or excessive turbidity in a reagent, discard the vial.

Limited Warranty. FOR THE APPLICABLE WARRANTY PERIOD, QUIDEL WARRANTS THAT EACH PRODUCT SHALL BE (I) OF GOOD QUALITY AND FREE OF MATERIAL DEFECTS, (II) FUNCTION IN ACCORDANCE WITH THE MATERIAL SPECIFICATIONS REFERENCED IN THE PRODUCT MANUAL, AND (III) APPROVED BY THE PROPER GOVERNMENTAL AGENCIES REQUIRED FOR THE SALE OF PRODUCTS FOR THEIR INTENDED USE (the “LIMITED WARRANTY”). IF THE PRODUCT FAILS TO MEET THE REQUIREMENTS OF THE LIMITED WARRANTY, THEN AS CUSTOMER’S SOLE REMEDY, QUIDEL SHALL EITHER REPAIR OR REPLACE, AT QUIDEL'S DISCRETION, THE PRODUCT. EXCEPT FOR THE LIMITED WARRANTY STATED IN THIS SECTION, QUIDEL DISCLAIMS ANY AND ALL WARRANTIES, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO, ANY WARRANTY OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON‐INFRINGEMENT REGARDING THE PRODUCT. QUIDEL'S MAXIMUM LIABILITY WITH ANY CUSTOMER CLAIM SHALL NOT EXCEED THE NET PRODUCT PRICE PAID BY CUSTOMER. NEITHER PARTY SHALL BE LIABLE TO THE OTHER PARTY FOR SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES, INCLUDING, WITHOUT LIMITATION, LOSS OF BUSINESS, PROFITS, DATA OR REVENUE, EVEN IF A PARTY RECEIVES NOTICE IN ADVANCE THAT THESE KINDS OF DAMAGES MIGHT RESULT. The Limited Warranty above shall not apply if the Customer has subjected the Product to physical abuse, misuse, abnormal use, use inconsistent with the Product Manual or Insert, fraud, tampering, unusual physical stress, negligence or accidents. Any warranty claim by Customer pursuant to the Limited Warranty shall be made in writing within the applicable Limited Warranty period.

*Lumi‐Phos is a trademark of Lumigen, Inc., a subsidiary of Beckman Coulter, Inc.

**ProClin is a trademark of Rohm and Haas Company.

***Beckman Coulter, Access, UniCel, DxI, and SYNCHRON LX are trademarks of Beckman Coulter, Inc., and are registered in the USPTO.

ASSISTANCE If you have any questions regarding the use of this product, please contact Quidel Technical Support at 1.800.874.1517 (in the U.S.) or [email protected]. If outside the U.S., contact your local distributor or one of the Technical Support Centers listed below. You may also contact us at quidel.com.

Region Phone E‐mail Address

Europe and Middle East + 44.161.483.9032 [email protected]

Asia Pacific + 61.7.3363.7711 [email protected]

Africa, Russia and CIS + 972.8.9429.683 [email protected]

Latin America + 57.2.6618797 [email protected]

Canada + 1.613.271.1144 [email protected]

Triage BNP

REFERENC1. Lloyd‐Jon

from theCirculatio

2. Wu A. B‐Observer

3. Bonow R4. McDowe

25:291‐25. Yandle T6. Mukoyam

KambayaEvidencepeptide.

7. Clerico ADonato Lspecific ifailure. J.

8. deLemosThe progMed. 200

9. Manual GAzide Sal

10. ApprovedCommitt

11. Cembrow12. Hansen H

Immunoa13. Levinson

Immunoa14. Approved

Committ15. Krouwer 16. Maeda K

marker odysfunct

17. Dao Q, KMaisel Asetting. J

18. Mukoyamhuman b

19. Sagnella Clin. Scie

20. McDonagDargie HJ

21. Mair J, Frdysfunct

22. Muders Fnatriuret

for BCIS

CES nes D, Adams American Heon. 2010;121Type natriurer 2001; 10: 10RO. New insigell G, Shaw C, 298. . Biochemistrma M, Nakao ashi Y, Inouyee for an exquiJ. Clin Invest.

A, Iervasi G, DeL. Circulating mmunoradio. Endocrinol. s JA, Morrow gnostic value o01; 345: 1014Guide – Safetlts. April 30, 1d Guideline –ee for Clinicawski GS, CareyHJ, et al. HAMassay 1993; 1 SS. The natuassay 1992; 1d Guideline Eee for ClinicaJS, Rabinowi

K, Tsutamoto Tof high left veion. Am. Hearishnaswamy. Utility of B‐t. Am. Coll. Cama M, Nakao brain natriuretGA. Measureence 1998; 95gh TA, Robb SJ. Biochemicariedl W, Thomion. Scand. J. F, Kromer EP,tic peptides a

s RJ, Brown TMeart Associati:e1‐e170. etic peptide a0‐14. hts into the cBuchanan K,

ry of natriuretK, Hosoda K,

e K, Imura H. Bsite dual natr. 1991; 87:14el Chicca MGlevels of cardmetric assaysInvest. 1998;DA, Bentley Jof B‐type nat4‐1021. y Manageme1976. Atlanta – Procedures fal Standards. y RN. Laborat

MA interferen16: 294‐299. re of heterop15: 108‐115. Evaluation of al Laboratory tz R. How to T, Wada A, Hntricular endrt J. 1998; 13y P, Kazanegratype natriuretardiol. 2001; 3K, Saito Y, Ogtic peptide inement and sig5: 519‐529. SD, Murdoch al detection omas S, PuscheClin. Lab. Inv, Griese DP, Ps markers for

M, et al. Hearon Statistics

and its clinica

cardiac natriuNicholls D. T

tic peptides. J, Suga S, SaitoBrain natriureriuretic peptid02‐1412. , Emdin M, Mdiac natriuretis in normal su 21:170‐179.JH, Omland Triuretic pepti

ent, No. CDC‐2GA: Centers for Handling

tory Quality Mce with murin

philic antibod

precision perStandards, Vimprove estimisanaga T, Kin‐diastolic pre5: 825‐832. a R, Harrison tic peptide in37: 379‐385.gawa Y, Hoson congestive hgnificance of c

DR, Morton Jof left‐ventricendorf B. Natrvest. 1999; 59Pfeifer M, Henr left ventricu

rt Disease andCommittee a

l utility in pat

retic peptidehe natriuretic

J. Internal Meo Y, Ogawa Y, etic peptide ade system, at

Maffei S, Nannic peptides (Aubjects and in

, Sabatine MSide in patient

22, Decontamfor Disease Cand Processin

Managementne monoclon

ies and the ro

rformance of 19, N2. mates of impnoshita M. Plaessure in patie

A, Amirnovin the diagnosi

oda K, Suga S, heart failure. circulating na

JJ, Ford I, Moular systolic driuretic Peptid9: 132‐142. nse HW, Rieggular dysfunctio

d Stroke Statind Stroke Sta

tients with he

s. Circulationc peptide fam

ed. 1994; 235 Shirakami G,as a novel cartrial natriuret

nipieri M, SabANP and BNP)n patients wit

S, McCabe CHts with acute

mination of LaControl. ng of Blood S

: QC & QA. ASal antibody‐b

ole in immun

clinical chem

recision. Clinasma brain nents with sym

n R, Lenert L, is of congestiv

Shirakami G,New Engl. J. Matriuretic pep

rrison CE, Tundysfunction. Ldes in assess

ger GAJ, Elsneon. Am. Hear

istics—2010 Uatistics Subco

eart failure. M

n 1996; 93: 19mily. Eur. J. Cli

5:561‐576. , Jougaski M, rdiac hormontic peptide an

batino L, Forin) measured bth different d

H, Hall C, Cancoronary syn

aboratory Sin

pecimens, H1

SCP Press, Chbased immun

oassay interf

mistry device,

ical Chemistratriuretic pepmptomatic lef

Clopton P, Alve heart failu

, Jougasaki MMed. 1990; 3tides in cardi

nstall‐Pedoe Lancet 1998; ment of left‐v

er D. Evaluatirt J.1997; 134

Page 1

Update. A Reommittee .

Medical Labor

946‐1950. in. Invest. 199

Obata K, Yase in humans: nd brain natriu

ni F, Manfredby highly sensegrees of hea

non CP, Braudromes. New

k Drains to R

18‐A2. 1999.

hicago, IL, 198oassays. J Cli

ference. J Clin

EP5‐A. 1999.

ry 1984; 30: 2ptide as a bioft ventricular

berto J, Hlaviure in an urge

M, Imura H. Inc323: 757‐758.ovascular dis

H, McMurray351: 9‐13. ventricular

ion of plasma4: 442‐449.

19 of 25

port

ratory

95;

ue H, uretic

i C, itive and art

nwald E. w Engl. J.

emove

National

89. n

n

National

90‐292. chemical

in P, ent‐care

creased sease.

y JJV,

a


23. Cowie MR, Struthers AD, Wood DA, Coats AJS, Thompson SG, Poole‐Wilson PA, Sutton GC. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet 1997; 350: 1347‐1351.

24. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A. Knudsen CW. Perez A. Kazanegra R. Herrmann HC. McCullough PA. Breathing Not Properly Multinational Study Investigators. Rapid measurement of B‐type natriuretic peptide in the emergency diagnosis of heart failure. N. Engl. J. Med. 2002; 347: 161‐167.

25. McCullough PA, Nowak RM, McCord J, Hollander JE, Herrmann HC, Steg PG, Duc P, Westheim A, Omland T, Knudsen CW, Storrow AB, Abraham WT, Lamba S, Wu AH, Perez A, Clopton P, Krishnaswamy P, Kazanegra R, Maisel AS. B‐type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation 2002; 106: 416‐422.

26. Maisel AS, Koon J, Krishnaswamy P, Kazanegra R, Clopton P, Gardetto N, Morrisey R, Garcia A, Chiu A, De Maria A. Utility of B‐natriuretic peptide as a rapid, point‐of‐care test for screening patients undergoing echocardiography to determine left ventricular dysfunction. Am. Heart J. 2001; 141: 367‐374.

27. Lubien E, DeMaria A, Krishnaswamy P, Clopton P, Koon J, Kazanegra R, Gardetto N, Wanner E, Maisel AS. Utility of B‐natriuretic peptide in detecting diastolic dysfunction. Circulation 2002; 105: 595‐601.

28. Krishnaswamy P, Lubien E, Clopton P, Koon J, Kazanegra R, Wanner E, Gardetto N, Garcia A, DeMaria A, Maisel AS. Utility of B‐natriuretic peptide in identifying patients with left ventricular systolic or diastolic dysfunction. Am. J. Med. 2001; 111: 274‐279.

29. Omland T, Aakvaag A, Bonarjee VVS, Caidahl K, Lie RT, Nilsen DWT, Sundsfjord JA, Dickstein K. Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long‐term survival after acute myocardial infarction. Circulation 1996; 93: 1963‐1969.

30. Richards AM, Nicholls MG, Yandle TG, Ikram H, Espiner EA, Turner JG, Buttimore RC. Lainchbury JG. Elliott JM. Frampton C. Crozier IG. Smyth DW. Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction. Heart 1999; 81: 114‐120.

31. Stein BC, Levin RI. Natriuretic peptides: physiology, therapeutic potential, and risk stratification in ischemic heart disease. Am. Heart J. 1998; 135: 914‐923.

32. Wallen T, Landahl S, Hedner T, Nakao K, Saito Y. Brain natriuretic peptide predicts mortality in the elderly. Heart 1997; 77: 264‐267.

33. Darbar D, Davidson NC, Gillespie N, Choy AMJ, Lang CC, Shyr Y, McNeill GP, Pringle TH, and Struthers AD. Diagnostic value of B‐type natriuretic peptide concentrations in patients with acute myocardial infarction. Am. J. Cardiol. 1996; 78: 284‐287.

34. Broome HE, Cembrowski GS, Kahn SN, Martin PL, Patrick CA. Implementation and use of a manual multi‐rule quality control procedure. Lab Med 1985; 16: 533‐537.

35. Westgard JO, Barry PL, Hunt MR, Groth T. A multi‐rule Shewhart chart for quality control in clinical chemistry. Clin Chem 1981; 27: 493‐501.

36. Koch DD, Oryall JJ, Quam EF, Feldbruegger DH, et al. Selection of medically useful QC procedures for individual tests done in a multitest analytical system. Clin Chem 1990; 36:230‐233.

37. Mugan K, Carlson IH, Westgard JO. Planning QC procedures for immunoassays. J Clin Immunoassay 1994;17:216‐222.

38. Approved Guidelines – Statistical Quality Control for Quantitative Measurements: Principles and Definitions, C24‐A2. February 1999. National Committee for Clinical Standards.

39. Doust, J.A., Pietrzak, E., Dobson, A., and Glasziou, P., How well does B‐type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. BMJ 330:625‐633, 2005.

40. Vrtovec, B., Delgado, R., Zewail, A., Thomas, C.D., Richartz, B.M., and Radovancevic, B., Prolonged QTc interval and high B‐type natriuretic peptide levels together predict mortality in patients with advanced heart failure. Circulation 107:1764‐1769, 2003.

41. Harrison, A., Morrison, L.K., Krishnaswamy, P., Kazanegra, R., Clopton, P., Dao, Q., Hlavin, P., and Maisel, A.S.., B‐type natriuretic peptide predicts future cardiac events in patients presenting to the emergency department with dyspnea. Ann. Emerg. Med. 39:131‐138, 2002.


42. Cheng, V., Kazanegra, r., Garcia, A., Lenert, L., Krishnaswamy, P., Gardetto, N., Clopton, P., and Maisel, A., A rapid bedside test for B‐type natriuretic peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study. J. Am. Coll. Cardiol. 37:386‐391, 2001.

43. Bettencourt, P., Ferreira, S., Azevedo, A., and Ferreira, A.., Preliminary data on the potential usefulness of B‐type natriuretic peptide levels in predicting outcome after hospital discharge in patients with heart failure. Am. J. Med. 2002 113:215‐219, 2002.

44. Logeart, D., Thabut, G., Jourdain, P., Chavelas, C., Beyne, P., Beauvais, F., Bouvier, E., and Solal, A.C., Predischarge B‐type natriuretic peptide assay for identifying patients at high risk of re‐admission after decompensated heart failure. J. Am. Coll. Cardiol. 43:635‐41, 2004.

Other Suggested Reading Apple, F.S., Panteghini, M., Ravkilde, J., Mair, J., Wu, A.H., Tate, J., Pagani, F., Christenson, R.H., Jaffe, A.S.; Committee on Standardization of Markers of Cardiac Damage of the IFCC. Quality specifications for B‐type natriuretic peptide assays. Clin. Chem. 51:486‐496, 1995.

Wilkins M, Redondo J, and Brown L. The natriuretic‐peptide family. Lancet 1997; 349:1307‐1310.

Stein B, and Levin R. Natriuretic peptides: physiology, therapeutic potential, and risk stratification in ischemic heart disease. Am. Heart J. 1998; 135:914‐923.

Davidson NC, Struthers AD. Brain natriuretic peptide. J. Hypertension 1994; 12: No. 4: 329‐336.

Espiner EA, Richards M. Yandle TG. Nicholls, M. G., Natriuretic Hormones. Clinical Disorders of Fluid and Electrolyte Metabolism 1995; 24: 481‐509.

Guyton Arthur C. Textbook of Medical Physiology. Philadelphia: W.B. Saunders Co., 1991, pp.205‐219.

Espiner EA. Physiology of natriuretic peptides. J. Internal Med. 1994; 235:527‐541.

98200 – Quidel Triage BNP Reagents 98201 – Quidel Triage BNP QC Controls 98202 – Quidel Triage BNP Calibrators

MDSS GmBH Schiffgraben 41 30175 Hannover, Germany


Manufactured for: Quidel Cardiovascular Inc. 9975 Summers Ridge Drive San Diego, CA 92121 USA quidel.com

ENSRC26608enAPN: 26608en Rev. A 2018/05

Manufactured by: Beckman Coulter, Inc. 250 S. Kraemer Blvd. Brea, CA 92821 USA Distributed by: Quidel Second Floor Merchants Square Merchants Road Galway, Ireland +353 (0) 91 412474 Revision Changes: Initial release for Quidel Cardiovascular Inc. Additional hazard codes added.

Triage BNP

GLOSSARY

Catalogue nu

Authorized rein the Europe

Prescription

Use‐by date

Date of manu

Temperature

Caution, cons

Causes skin iMay cause anCauses seriou

Contains suff

for BCIS

Y

umber

epresentativeean Commun

Use Only

ufacture

e limit

sult accompa

rritation n allergic skinus eye irritati

ficient for < n

e ity

anying docum

n reaction on

> tests

CE

In

In

Ba

M

U

ments Co

HCaMCa

Bi

E mark

n vitro diagno

ntended use

atch code

Manufacturer

pper limit of

onsult instruc

armful if swaauses skin irr

May cause an aauses serious

iological risks

stic medical d

temperature

ctions for use

llowed itation allergic skin rs eye irritation

s

device

e

e

reaction n

Page 223 of 25

Triage BNP

Mean

This way up

Contents/con

Control 1

Control 3

Calibrator S0

Calibrator S2

Calibrator S4

Reagent

for BCIS

ntains

0

2

4

St

Re

Co

Co

Ca

Ca

Ca

Ca

Re

tandard devia

ecyclable

ontrol

ontrol 2

alibrator

alibrator S1

alibrator S3

alibrator S5

eagent 1a

ation

Page 224 of 25


Reagent 1a

Reagent 1c

Calibration card

Quality control card

Buffer

Origin: mouse

Origin: human

Origin: goat

Antibody BNP

Antigen B‐Type natriuretic peptide (BNP)

Antibody BNP – alkaline phosphatase conjugate

for the in vitro quantitative measurement of type natriuretic … · 2020. 5. 7. · ended us riage...

Documents