Triage NT-proBNP Product Insert

Rapid quantitative tests for N-terminal pro Brain Natriuretic Peptide (NT-proBNP)
A symbols glossary can be found at quidel.com/glossary.

For Export Only. Not for sale in the United States.

INTENDED USE
The Quidel Triage NT-proBNP Test is a fluorescence immunoassay to be used with the Quidel Triage
Meter for the quantitative determination of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP)
in EDTA anticoagulated whole blood and plasma specimens. The test is to be used as an aid in
the diagnosis of individuals suspected of having congestive heart failure (also referred to as heart
failure). The test is also to be used as an aid for the risk stratification of patients with heart failure and
the risk stratification of patients with acute coronary syndromes (ACS). The test may also serve as an
aid in the assessment of increased risk for cardiovascular events and mortality in patients at risk for
heart failure who have stable coronary artery disease.

SUMMARY AND EXPLANATION OF THE TEST

It is estimated that 5.8 million people in the United States have heart failure with approximately
670,000 new cases occurring each year.1 Congestive heart failure (CHF) occurs when the heart
cannot deliver a sufficient amount of blood to the body.2 This condition can occur at any age but is
most prevalent in an aged population. Symptoms of CHF include shortness of breath, fluid retention
and respiratory distress. These symptoms are often vague and nonspecific for detecting early stages
of CHF.2
The heart is the main source of circulating NT-proBNP in humans.5,6 The molecule is released into the
blood in response to increased heart pressure. NT-proBNP is released after the cardiomyocytes are
stimulated to produce the precursor molecule preproBNP. Through a cleavage cascade proBNP is
cleaved into BNP and NT-proBNP which are both released into circulation.7,8 Elevated plasma NT-
proBNP is a sensitive and specific biomarker for heart failure and allows physicians to differentiate
between heart failure and lung disorders with similar symptoms. Various studies have demonstrated
that increased levels of circulating NT-proBNP are found in early stages of CHF. The level of NT-
proBNP in the blood continues to increase as the CHF disease advances.9 Furthermore, NT-proBNP
has been demonstrated to have prognostic utility.10,11,12 Studies show that NT-proBNP is a strong
independent predictor of one year mortality in patients with acute coronary syndromes (ACS).13,14
Multiple studies involving patients with stable coronary artery disease (CAD) have demonstrated
that elevated NT-proBNP levels lead to a greater risk of future adverse cardiovascular events.15,16,17
The Quidel Triage NT-proBNP Test offers an objective, noninvasive measurement for assessing
patients for CHF, for risk stratification in patients with CHF and patients with ACS, and for assessing
increased risk of cardiac mortality in patients with stable CAD.

PRINCIPLES OF THE PROCEDURE

The Quidel Triage NT-proBNP Test is a single use fluorescence immunoassay device designed
to determine the concentration of NT-proBNP in EDTA anticoagulated whole blood or plasma
specimens.
The test procedure involves the addition of several drops of an EDTA anticoagulated whole blood or
plasma specimen to the sample port on the Test Device. After addition of the specimen, the whole
blood cells are separated from the plasma using a filter contained in the Test Device. The specimen
reacts with fluorescent antibody conjugates and flows through the Test Device by capillary action.
Complexes of fluorescent antibody conjugate are captured on discrete zone specific to that analyte.

Triage NT-proBNP 1
The Test Device is inserted into the Quidel Triage Meter (hereafter referred to as Meter). The Meter WARNINGS AND PRECAUTIONS
is programmed to perform the analysis after the specimen has reacted with the reagents within
 For In Vitro Diagnostic Use.
the Test Device. The analysis is based on the amount of fluorescence the Meter detects within a
measurement zone on the Test Device. The concentration of the analyte in the specimen is directly  For use by healthcare professionals.
proportional to the fluorescence detected. The results are displayed on the Meter screen in  Do not use the kit beyond the expiration date printed on the outside of the box.
approximately 20 minutes from the addition of specimen. All results are stored in the Meter memory  Carefully follow the instructions and procedures described in this insert.
to display or print when needed. If connected, the Meter can transmit results to the lab or hospital  Optimal results will be achieved by performing testing at temperatures between 20°C to 24°C
information system (68°F to 75°F).
 If results from multiple samples within the same patient will be compared, it is recommended to
REAGENTS AND MATERIALS PROVIDED maintain a consistent sample type (whole blood or plasma).
The Quidel Triage NT-proBNP Test contains all the reagents necessary for the quantification of  Sample dilution is not recommended.
NT-proBNP in EDTA anticoagulated whole blood or plasma specimens.
 The use of non-Quidel Controls and Calibration Verification materials is not recommended.
The Test Device Contains:
 Keep the Test Device in the sealed pouch until ready for immediate use. Discard after single use.
 Murine monoclonal and sheep monoclonal antibodies against NT-proBNP
 The transfer pipette should be used for one patient specimen only. Discard after single use.
 Fluorescent dye
 Patient specimens, used Test Devices and used transfer pipettes are potentially infectious. Proper
 Stabilizers handling and disposal methods should be followed in accordance with local, state and federal
regulations.
Kit contains:
 Proper laboratory safety techniques should be followed at all times when working with patient
specimens because they are potentially infectious.
Component Quantity Description
 The Quidel Triage NT-proBNP Test should not be used as absolute evidence for CHF. The results
25 Test Devices should be interpreted along with clinical findings and other laboratory test results.
 Blood concentrations of NT-proBNP may be elevated in patients who are experiencing a heart
attack, patients that are candidates for renal dialysis, and patients that have had renal dialysis.
25 Transfer Pipettes
STORAGE AND HANDLING REQUIREMENTS
1 Reagent CODE CHIP Module™  Store the Test Devices in a refrigerator at 2°C to 8°C (35°F to 46°F).
 Once removed from refrigeration, the pouched Test Device is stable for up to 14 days at room
temperature, but not beyond the expiration date printed on the pouch. With a soft, felt tip marker,
gently write the date and time of removal from the refrigerator on the pouch and cross out the
1 Printer Paper Roll manufacturer expiration date printed on the pouch. Care must be taken to document the time the
product is at room temperature. Once equilibrated to room temperature, do not return the Test
Device to refrigeration.
Materials Required but Not Provided  Before using refrigerated Test Devices, allow individual foil pouches to reach operating
Quidel Triage MeterPro Cat. # 55070 or 55071 – software version 05.03.034 or greater temperature (20°C to 24°C or 68°F to 75°F). This will take a minimum of 15 minutes. If a kit
Triage MeterPlus Cat. # 55040 or 55041 – software version 04.07.061 or greater containing multiple Test Devices is removed from refrigeration, allow the kit to reach room
temperature before use. This will take a minimum of 60 minutes.
NOTE: Please ensure meter software has been upgraded, as indicated above.
 Do not remove the Test Device from the pouch until prepared for immediate use.
Quidel Triage NT-proBNP Control 1 Cat. # 98713EU
Quidel Triage NT-proBNP Control 2 Cat. # 98714EU

2 Triage NT-proBNP Triage NT-proBNP 3

SPECIMEN COLLECTION AND PREPARATION TESTING PATIENT SPECIMENS
 A venous whole blood or plasma specimen using K2 or K3 EDTA as the anticoagulant is Procedural Notes
acceptable for testing with this product. Other blood specimen types have not been evaluated.
 For each day of patient testing, perform QC Device testing. Refer to the Quality Control
 For specimen collection, follow the sample tube manufacturer’s recommended procedure.
Considerations section.
 Test blood or plasma specimens immediately or within 24 hours of sample collection. If testing
 Frozen plasma and refrigerated whole blood or plasma specimens must be allowed to reach
cannot be completed within 24 hours, the plasma should be separated and stored frozen at room temperature and be mixed thoroughly before testing.
≤ −20 ºC until it can be tested.
 Mix whole blood specimens by gently inverting the tube several times.
 No more than a single freeze/thaw cycle is recommended.
 Mix plasma specimens by vortexing or inverting the tube several times.
 Transport specimens at room temperature or chilled and avoid extreme temperatures.
 Avoid using severely hemolyzed specimens whenever possible. If a specimen appears to be Step 1 – Add Patient Specimen
severely hemolyzed, another specimen should be obtained and tested. 1. Open the pouch and label the Test Device with the patient identification number.
NOTE: Do not use fluorescent or brightly colored ink, or write outside of the blank area as this
TEST PROCEDURE
may interfere with the test.
Lot Calibration Using the Reagent CODE CHIP Module 2. Place the Test Device on a level, horizontal surface.
When a new lot of Test Devices is opened, the calibration and expiration data for that lot of Test 3. Using the transfer pipette, squeeze the larger (top) bulb completely and insert the tip into the
Devices must be transferred to the Meter before patient testing. Use the Reagent CODE CHIP specimen.
module supplied with the new lot of Test Devices to transfer the data to the Meter.
4. Release the bulb slowly. The transfer pipette barrel should fill completely with some fluid flowing
into the smaller (lower) bulb.
NOTE: Ensure that the pipette is not under filled or over filled. An under filled pipette is one
where the barrel is not filled completely with specimen and there is no specimen in the lower
bulb. An over filled pipette is one where there is some specimen in the top bulb. Ideally the
Reagent CODE CHIP Module lower bulb should contain a small amount of specimen (less than one quarter the volume of the
lower bulb).
5. Place the tip of the transfer pipette into the sample port of the Test Device and squeeze the
Perform one time for each new lot of Test Devices larger bulb completely. The entire volume of fluid in the transfer pipette barrel must flow into the
1. From the main screen, select Install New Code Chip. Press Enter. sample port. The specimen in the smaller (lower) bulb should not be expelled.
2. Place the Reagent CODE CHIP module into the lower left front corner of the Meter and follow NOTE: Too much specimen has been added to the device if the specimen has migrated outside
the prompts on the screen. of the sample port and on to the label.
6. Remove the transfer pipette tip from the sample port and then release the larger (top) bulb.
7. Discard the transfer pipette.
8. Allow specimen to absorb completely before moving the Test Device. At a minimum the sample
should be below the sample port opening to be considered fully absorbed.
Step 2 – Run Test
1. From the main screen, select Run Test and press Enter.
2. Select Patient Sample and press Enter.
3. Remove the Reagent CODE CHIP module from the Meter when data transfer is complete.
3. Enter the patient identification number and press Enter.
4. Place the Reagent CODE CHIP module back into its original container for storage.
4. Confirm that the number was entered correctly by selecting Confirm Patient ID and pressing
Enter. If the number was not entered correctly, select Correct Patient ID, press Enter and repeat
the previous step.

4 Triage NT-proBNP Triage NT-proBNP 5

5. Holding the Test Device by the edges, insert the Test Device into the Meter and press Enter. The Performing Quidel Triage System Quality Control – QC Device
results will be displayed when the analysis is complete.
Use the QC Device to ensure proper function of the Quidel Triage Meter. Perform QC Device testing
NOTE: The Test Device must be inserted into the Meter within 30 minutes from the time the patient for the following conditions:
specimen was added. A delay longer than 30 minutes may cause the results to be invalid and
 Upon initial setup of the Meter.
blocked out on the printout.
 Each day of patient testing.
Step 3 – Read the Results  When the Meter has been transported or moved.
1. Results may be printed by pressing the Print button.  Whenever there is uncertainty about the performance of the Meter.
2. Discard the Test Device after release from the Meter.  Whenever required by your laboratory’s quality control requirements.
3. A blocked out result indicates the result was invalid and the test should be repeated. Do not discard the Quidel Triage QC Device and associated CODE CHIP module. Store them in the
QC Device Box.
RESULTS Refer to the Quidel Triage Meter User Manual for complete instructions for use of the QC Device.
The Meter measures the target analyte automatically. The results are displayed on the screen. 1. The first time a new QC Device is run in the Meter, install the QC Device CODE CHIP module. The
A number in pg/mL represents the amount of NT-proBNP present in the specimen. The operator has QC Device CODE CHIP module data is stored in the Meter memory. The QC Device CODE CHIP
the option to print the results. module does not need to be reinstalled after the first time.
For additional information, refer to the Quidel Triage Meter User Manual.

STANDARDIZATION
The Quidel Triage NT-proBNP Test has been standardized using a purified protein preparation of
NT-proBNP based on the mass (concentration) of the analyte present in EDTA anticoagulated plasma.
QC DEVICE CODE CHIP MODULE
QUALITY CONTROL CONSIDERATIONS
a. From the main screen, select Install New Code Chip and press Enter.
Every Quidel Triage NT-proBNP Test is a quantitative test that includes two control materials of
different concentrations that are run automatically with every patient specimen, external liquid b. Place the QC Device CODE CHIP module into the lower left front corner of the Meter.
control solution, or proficiency testing sample. If the automatic check of these built-in controls Follow the prompts on the screen.
shows that the control value results are within the limits set during manufacturing, the Meter will
report a result for the specimen or sample being tested. If the automatic check of these built-in
controls shows that the control value results are not within the limits set during manufacturing, a
test result will not be reported. Instead, the Meter will display a warning or error message that is
described in the Quidel Triage Meter User Manual.
Good Laboratory Practice suggests that external controls should be tested with each new lot of test
materials, or every 30 days, and as otherwise required by your laboratory’s standard quality control
procedures. Controls should be tested in the same manner as if testing patient samples. When
running patient specimens or external controls, if an analyte fails for any reason (built-in control c. Remove the QC Device CODE CHIP module from the Meter when data transfer is complete.
failure or an external control out of range) no patient results will be reported.
d. Place the QC Device CODE CHIP module back into the QC Device Box for storage.
Users should follow government guidelines (for example, federal, state or local) and/or
2. From the main screen, select Run Test and press Enter.
accreditation requirements for quality control.
3. If User ID is enabled enter your User ID number and press Enter.
4. Select QC Device and press Enter.
5. Insert QC Device into the Meter and press Enter.

6 Triage NT-proBNP Triage NT-proBNP 7

6. A Pass or Fail result will be displayed when complete. Each parameter should pass before patient The LoD was determined based on the limit of blank and the standard deviation of low concentration
testing is performed. whole blood and plasma samples. The limit of detection corresponds to the lowest analyte
7. Remove the QC Device from the Meter and place in the QC Device Box. DO NOT DISCARD THE concentration which can be detected above the limit of blank with 95% confidence. The LoD was
QC DEVICE. determined to be 20 pg/mL.
NOTE: If the QC Device or external controls do not perform as expected, review the above The limit of quantitation was determined by measurement of low concentration whole blood and
instructions to see if the test was performed correctly, repeat the test, then contact Quidel or your plasma samples on three lots of test devices across multiple replicates and test runs. The LoQ is
local Quidel representative (refer to the Assistance section). Refer to the Quidel Triage Meter User defined as the NT-proBNP level at which the test displays a 20% coefficient of variation (%CV). The
Manual for a complete description of the quality control system. LoQ was determined to be 48 pg/mL.
Measurable Ranges
LIMITATIONS OF THE PROCEDURE The measureable range of the NT-proBNP assay is 20 pg/mL to 35,000 pg/mL. Values below
 The results should be evaluated in the context of all the clinical and laboratory data available. In 20 pg/mL are reported as < 20 pg/mL and values above 35,000 pg/mL are reported as
those instances where test results do not agree with the clinical evaluation, additional tests should > 35,000 pg/mL.
be performed accordingly.
 Severely hemolyzed specimens should be avoided. When a sample appears to be severely Hook Effect
hemolyzed, another specimen should be obtained and tested. Hook effect was evaluated using samples containing NT-proBNP concentrations significantly
 Patients with renal failure may have elevated NT-proBNP. higher than the upper limit of the measurable range. No hook effect was observed up to
350,000 pg/mL.
 This test has been evaluated with venous whole blood and plasma using K2 or K3 EDTA as the
anticoagulant. Other specimen types, draw methods, or anticoagulants have not been evaluated. Reproducibility
Use standard veni-puncture techniques. Follow the sample collection recommendations of the Within run and total precision were determined by testing three lots of test devices with plasma
sample tube manufacturer. control samples containing various levels of NT-proBNP. Each control sample was tested in
 There is the possibility that factors such as technical or procedural errors, as well as additional duplicate twice a day for 20 days. Data were analyzed using methods provided in CLSI-EP5A2.
substances in blood specimens that are not listed below, may interfere with the test and cause Representative results form this study are in the following table.
erroneous results.
 As with any assay employing mouse antibodies, the possibility exists for interference by human
anti-mouse antibodies (HAMA) in the sample. The test has been formulated to minimize this Mean Within Run Precision Total Precision
interference; however, specimens from patients who have been routinely exposed to animals or Concentration SD (pg/mL) CV SD (pg/mL) CV
to animal serum products may contain heterophile antibodies which may cause erroneous results.
 This assay is a fluorescence immunoassay, and may be affected by environmental conditions. 121 pg/mL 18 15.0 % 20 16.4 %
Therefore, it is important for each laboratory to establish its own reference range, based on the 992 pg/mL 82 8.2 % 86 8.7 %
laboratory conditions and procedures.
2844 pg/mL 238 8.4 % 263 9.3 %
PERFORMANCE CHARACTERISTICS 22,844 pg/mL 2547 11.1 % 2675 11.7 %
Representative Data: results in individual laboratories may vary from these data. Individual
laboratory results may differ from these studies due to differences in the testing protocol, and
between instruments, calibrations, reagents and replicates.
QUALITY CONTROL SPECIFICATIONS ALLOW RELEASE OF PRODUCT
Analytical Sensitivity THAT HAS THE FOLLOWING RANGE OF PRECISION (%CV):
The Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) were determined
using the methods provided in CLSI EP17-A. NT-proBNP
The LoB was evaluated by running 20 replicates per day of a whole blood and plasma blank (analyte- 7.4 – 15.4
free) sample for five days on three lots of test devices. The LoB corresponds to the lowest detectable
concentration that is distinguishable from zero with 95% confidence. The LoB was determined to
be 8 pg/mL.

8 Triage NT-proBNP Triage NT-proBNP 9

Whole Blood/Plasma Method Comparison Proteins
Results in whole blood and plasma were compared by testing matching whole blood and plasma The following proteins were evaluated for cross reactivity and interference with the
specimens in singlet with a single lot of test devices. Study data were analyzed with Passing-Bablok NT-proBNP assay using the methods provided in CLSI EP7-A. Each protein was added to a plasma
regression analysis and Bland-Altman bias plots. The results of these analyses are presented below. pool containing approximately 125 pg/mL NT-proBNP and did not show any significant cross
reactivity:
Correlation
Slope Intercept Mean Bias Adrenomedullin (1 ng/mL), aldosterone (0.6 ng/mL), angiotensin I (0.6 ng/mL), angiotensin II
coefficient (r)
(95% CI) (95% CI) (%) (0.6 ng/mL), angiotensin III (1 ng/mL), ANP28 (3.1 ug/mL), Arg-vasopressin (1 ng/mL), BNP32
(95% CI)
(3.5 ug/mL), CNP22 (2.2 ug/mL), Endothelin 1 (500 pg/mL), NT-proANP1-30 (3.5 ug/mL),
0.92 −9.29 0.99
−11.2 % NT-proANP31-67 (1 ng/mL), NT-proANP79-98 (1 ng/mL), renin (50 ng/mL), urodilatin (3.5 ug/mL).
(0.88 to 0.96) (-37.67 to 2.15) (0.98 to 0.99)
Method Comparison to Predicate
NOTE: A negative bias indicates higher results with plasma.
Method comparison to the Roche Elecsys 2010 proBNP II assay was performed using samples
A bias can exist between whole blood and plasma specimens. It is recommended to use a consistent from apparently healthy individuals (N = 252) and patients with confirmed heart failure (N = 257).
sample type when comparing results from multiple tests. Of the 509 patients evaluated in a clinical study it was determined that 464 samples contained an
Interfering Substances NT-proBNP concentration between 20 pg/mL and 35000 pg/mL. A comparison of 464 NT-proBNP
measurements on the Quidel Triage NT-proBNP assay to the Roche Elecsys proBNP II assay were
Samples containing up to 500 mg/dL hemoglobin, 280 mg/dL cholesterol, 1.5 g/dL triglycerides or
analyzed with Passing-Bablok regression and Spearman correlation analysis. The results of these
25 mg/dL bilirubin (conjugated) were evaluated for potential cross-reactivity and interference using
analyses are presented in the following table.
the methods provided in CLSI EP7-A. These substances did not impact NT-proBNP results.
Pharmaceuticals Quidel Triage Assay Slope Intercept Correlation coefficient (r)
The following drugs were evaluated for potential cross-reactivity and interference using the Range [pg/mL] (95% CI) (95% CI) (95% CI)
methods provided in CLSI EP7-A. Each drug was added to a plasma pool containing approximately 20 – 3,000 0.99 −9.53 0.96
125 pg/mL NT-proBNP. Each drug was tested at the concentration recommended by CLSI EP7-A or (N=361) (0.95, 1.03) (−13.37, −4.22) (0.95, 0.97)
at a concentration at least equivalent to the maximum therapeutic level. None of the drugs impacted
NT-proBNP results. 20 – 7,000 0.95 −5.55 0.97
(N=413) (0.91, 0.98) (−10.40, −0.93) (0.96, 0.98)
Acetaminophen Dextromethorphan Lisinopril
Activase Digoxin Loratadine 20 – 35,000 0.89 −1.23 0.98
(N=464) (0.86, 0.92) (−5.58, 2.93) (0.97, 0.98)
Albuterol Diphenhydramine Metoprolol
Alprazolam Dopamine Nicotine
Amlodipine Doxycycline Nicotinic Acid EXPECTED VALUES
Amoxicillin Erythromycin Nitroglycerin NT-proBNP results greater than 125 pg/mL for patients younger than 75 years old and greater than
Ascorbic acid Furosemide Prednisone 450 pg/mL for patients 75 years and older are considered abnormal and suggestive of patients
with CHF.
Aspirin Heparin Prochlorperazine
Each laboratory should establish a reference range that is representative of the patient population
Atenolol Hydrochlorothiazide Sertraline
to be evaluated. Additionally, each laboratory should consider the current practice in the evaluation
Atorvastatin Hydrocodone Verapamil of patients experiencing symptoms at each institution.
Caffeine Ibuprofen Warfarin
Cephalexin Levothyroxine Zolpidem

10 Triage NT-proBNP Triage NT-proBNP 11

Clinical Sensitivity and Specificity ROC Analysis
Clinical sensitivity and specificity were calculated using data collected from approximately 509 The ROC analyses for both the Quidel Triage NT-proBNP Test and the Roche Elecsys NT-proBNP
subjects. Of these subjects, 257 (120 women and 137 men) individuals were diagnosed with CHF assays for the clinical study population are shown below. The area under the curve (AUC) for both
and 252 (139 women and 113 men) were without CHF. Those subjects without CHF included the Quidel Triage NT-proBNP assay and Elecsys NT-proBNP assay is 0.93.
individuals with common co-morbidities to CHF such as hypertension, hyperlipidemia, chronic
obstructive pulmonary disease (COPD), diabetes, and renal disease. The use of the cut-offs of
125 pg/mL for individuals younger than 75 years of age and 450 pg/mL for individuals 75 years
of age or older was evaluated across all patients. Sensitivity and specificity are presented in the
following table:
No discrimination

Age Stratified Sensitivity and Specificity:

True positive rate (Sensitivity)

125 pg/mL for age < 75 , 450 pg/mL for age ≥ 75 Roche NT-proBNP

CHF Patients Triage NT-proBNP

Age (years) < 75 ≥ 75

N 184 73
Sensitivity (95% CI) 88% (82% – 92%) 92% (83% – 97%)
All Non-CHF
Age (years) < 75 ≥ 75
N 188 64
False positive rate (1-Sensitivity)
Specificity (95% CI) 87% (81% – 91%) 77% (64% – 86%)
Non-CHF Without Co-morbidity
Clinical Agreement Analysis
The positive and negative agreement between the Quidel Triage NT-proBNP assay and the Roche
Age (years) < 75 ≥ 75 Elecsys NT-proBNP assay were calculated using data collected from 509 subjects, 257 individuals
N 74 7 diagnosed with CHF and 252 without CHF. The positive and negative agreements are presented in
the table below:
Specificity (95% CI) 89% (80% – 95%) 57% (18% – 90%)
Roche Positive Roche Negative All Subjects
(N=291) (N=218) (N=509)
Quidel Triage Positive 266 2 268
Quidel Triage Negative 25 216 241
Positive Agreement 91.4%
Negative Agreement 99.1%

12 Triage NT-proBNP Triage NT-proBNP 13

CHF Population by NYHA Classification Descriptive Statistics – NT-proBNP Concentration (pg/mL) in Non-CHF
257 subjects diagnosed with heart failure were evaluated using the Quidel Triage NT-proBNP Test. Population
The descriptive statistics for the resulting NT-proBNP concentrations are presented according to
the New York Heart Association (NYHA) Functional Classification in the table below. Non-CHF
All Non-CHF
Without Co-morbidity
NYHA Class ALL CHF I II III IV
Age (years) ≥ 75 < 75 All ≥ 75 < 75 All
ALL
N 64 188 252 7 74 81
N 257 28 113 82 34
Mean 450 71 168 593 64 110
Mean 4653 1916 3751 5662 7475
SD 906 70 487 622 57 233
SD 6439 2205 5983 7115 7212
Median 177 51 59 369 50 54
Median 2210 1345 1840 2690 4845
95th Percentile 1810 199 557 1810 170 344
95th percentile 22100 6780 16300 22500 24300
% < 125 pg/mL 86.7% 89.2%
MALE
% < 450 pg/mL 76.6% 57.1%
N 137 21 62 38 16
Mean 5148 2142 4236 6948 8353 Descriptive Statistics – NT-proBNP Concentration (pg/mL) in CHF Population
SD 6853 2411 6309 7920 8134 CHF Patients
Median 2420 1510 1990 3500 4845 Age (years) ≥ 75 < 75 All
95th percentile 23000 6780 18200 26700 25300 N 73 184 257
FEMALE Mean 5187 4442 4653
N 120 7 51 44 18 SD 5968 6620 6439
Mean 4089 1235 3162 4551 6695 Median 3190 2015 2210
SD 5908 1334 5565 6217 6420 95th Percentile 20600 22500 22100
Median 2060 866 1470 2250 5305 % < 125 pg/mL 12.5%
95th percentile 15600 4070 10200 14900 22900 % < 450 pg/mL 8.2%

Non-CHF and CHF Group Descriptive Statistics

The overall incidence of disease in the evaluated population (n=509) included 62% (315) with
hypertension, 32% (162) with diabetes, 8% (40) with chronic obstructive pulmonary disease, 41%
(208) with shortness of breath, 54% (277) with coronary artery disease, 8% (39) with valvular heart
disease, 7% (34) with atrial fibrillation, 23% (115) with hyperlipidemia, and 4 % (22) with renal disease.
The circulating NT-proBNP concentration was determined in 509 individuals with and without CHF.
The evaluated CHF population excluded patients with a recent history (within 30 days) of myocardial
infarction, renal failure requiring dialysis, or cardiovascular surgery. The descriptive statistics for
the total Non-CHF group, Non-CHF without co-morbidities and CHF group are presented in the
following tables:

14 Triage NT-proBNP Triage NT-proBNP 15

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2. Remme WJ, et al. The European Society of Cardiology Task Force Report: Guidelines for the cardiology. J Lab Clin Med 1999;134:437-444.
diagnosis and treatment of chronic heart failure. European Heart Journal 2001;22:1527-1560. Yeo KT, et al. Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite
3. Bonow, R. O., New insights into the cardiac natriuretic peptides. Circulation 93:1946-1950, 1996. Triage BNP assay. Clin Chim Acta 2003;338:107-115.
4. McDowell, G., Shaw, C., Buchanan, K., and Nicholls, D., The natriuretic peptide family. Eur. J. Clin. Bernstein L, et al. Renal Insufficiency in Predicting NT-ProBNP Level Elevation (RIPPLE): A TriHospital
Invest. 25:291-298, 1995. Study. American Society for Clinical Pathology 2007 Annual Meeting: Abstract 6. Presented October
5. Yandle, T., Biochemistry of natriuretic peptides. J. Internal Med. 235:561-576, 1994. 18, 2007.
6. Mukoyama, M., Nakao, K., Hosoda, K., Suga, S., Saito, Y., Ogawa, Y., Shirakami, G., Jougaski, M., Apple, F.S., Panteghini, M., Ravkilde, J., Mair, J., Wu, A.H., Tate, J., Pagani, F., Christenson, R.H.,
Obata, K., Yasue, H., Kambayashi, Y., Inouye, K., and Imura, H., Brain natriuretic peptide as a novel Jaffe, A.S.; Committee on Standardization of Markers of Cardiac Damage of the IFCC. Quality
cardiac hormone in humans: Evidence for an exquisite dual natriuretic peptide system, atrial specifications for B-type natriuretic peptide assays. Clin. Chem. 51:486-496, 1995.
natriuretic peptide and brain natriuretic peptide. J. Clin Invest. 87:1402-1412, 1991. Wilkins, M., Redondo, J., and Brown, L., The natriuretic-peptide family. Lancet 349:1307-1310, 1997.
7. Pfister R, et al. Use of NT-proBNP in routine testing and comparison to BNP. Eur J Heart Fail Stein, B., and Levin, R., Natriuretic peptides: physiology, therapeutic potential, and risk stratification
2004;6(3):289-293. in ischemic heart disease. Am. Heart J. 135:914-923, 1998.
8. Seino Y, et al. Application of NT-proBNP and BNP measurements in cardiac care: a more discerning
Espiner, E.A., Richards, M., Yandle, T. G., Nicholls, M. G., Natriuretic Hormones. Clinical Disorders of
marker for the detection and evaluation of heart failure. Eur J Heart Fail 2004;6(3):295-300.
Fluid and Electrolyte Metabolism 24:481-509, 1995.
9. Clerico, A., Iervasi, G., Del Chicca, M.G., Emdin, M., Maffei, S., Nannipieri, M., Sabatino, L., Forini,
Guyton, Arthur C. Textbook of Medical Physiology. Philadelphia: W.B. Saunders Co., 1991, pp.205-
F., Manfredi, C., and Donato, L., Circulating levels of cardiac natriuretic peptides (ANP and BNP)
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measured by highly sensitive and specific immunoradiometric assays in normal subjects and in
patients with different degrees of heart failure. J. Endocrinol. Invest. 21:170-179, 1998. Espiner, E.A., Physiology of natriuretic peptides. J. Internal Med. 235:527-541, 199
10. The European Society of cardiology, Struthers AD. How to use natriuretic peptide levels for
Limited Warranty. FOR THE APPLICABLE WARRANTY PERIOD, QUIDEL WARRANTS THAT EACH
diagnosis and prognosis. Eur Heart J 1999;20:1374-1375.
PRODUCT SHALL BE (I) OF GOOD QUALITY AND FREE OF MATERIAL DEFECTS, (II) FUNCTION
11. Hunt PJ, Richards AM, Nicholls MG, Yandle TG, Doughty RN, Espiner EA. Immunoreactive IN ACCORDANCE WITH THE MATERIAL SPECIFICATIONS REFERENCED IN THE PRODUCT
aminoterminal pro-brain natriuretic peptide (NT-PROBNP): a new marker for cardiac impairment. MANUAL, AND (III) APPROVED BY THE PROPER GOVERNMENTAL AGENCIES REQUIRED FOR THE
Clin Endocrinol 1997;47:287-296. SALE OF PRODUCTS FOR THEIR INTENDED USE (the “LIMITED WARRANTY”). IF THE PRODUCT
12. Talwar S, Squire IB, Davies JE, Barnett DB, Ng LL. Plasma N-terminal pro-brain natriuretic peptide FAILS TO MEET THE REQUIREMENTS OF THE LIMITED WARRANTY, THEN AS CUSTOMER’S SOLE
and the ECG in the assessment of left-ventricular systolic dysfunction in a high risk population. Eur REMEDY, QUIDEL SHALL EITHER REPAIR OR REPLACE, AT QUIDEL’S DISCRETION, THE PRODUCT.
Heart J 1999;20:1736-1744. EXCEPT FOR THE LIMITED WARRANTY STATED IN THIS SECTION, QUIDEL DISCLAIMS ANY AND
13. DeLemos, J.A., Morrow, D.A., Bentley, J.H., Omland, T., Sabatine, M.S., McCabe, C.H., Hall, C., ALL WARRANTIES, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO, ANY WARRANTY
Cannon, C.P., and Braunwald, E., The prognostic value of B-type natriuretic peptide in patients OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT
with acute coronary syndromes. New Engl. J. Med. 345:1014-1021, 2001. REGARDING THE PRODUCT. QUIDEL’S MAXIMUM LIABILITY WITH ANY CUSTOMER CLAIM SHALL
14. James SK, et al. NT proBNP and other Risk Markers for the Separate Prediction of Mortality and NOT EXCEED THE NET PRODUCT PRICE PAID BY CUSTOMER. NEITHER PARTY SHALL BE LIABLE
Subsequent Myocardial Infarction in Patients with Unstable Coronary Artery Disease. GUSTO IV TO THE OTHER PARTY FOR SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES, INCLUDING,
Substudy. Circulation 2003,108:275-281. WITHOUT LIMITATION, LOSS OF BUSINESS, PROFITS, DATA OR REVENUE, EVEN IF A PARTY
RECEIVES NOTICE IN ADVANCE THAT THESE KINDS OF DAMAGES MIGHT RESULT.
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Pro-Brain Natriuretic Peptide and C-Reactive Protein for Risk Stratification in Stable and The Limited Warranty above shall not apply if the Customer has subjected the Product to physical
Unstable Coronary Artery Disease: results from the AtheroGene study. European Heart Journal abuse, misuse, abnormal use, use inconsistent with the Product Manual or Insert, fraud, tampering,
2005;26:241-249. 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.
16. Kragelund C, Gronning B, Kober L, Hildebrandt P and Steffensen R. N-terminal pro-B-Type
Natriuretic Peptide and Long-Term Mortality in Stable Coronary Heart Disease. New England
Journal of Medicine 2005;352:666-675. Manufactured under license from Roche Diagnostics GmbH.
17. Ndrepepa G, Braun S, Niemoller K, Mehilli J, von Beckerath N, von Beckerath O, et al. Prognostic
Value of NTerminal Pro-Brain Natiuretic Peptide in Patients with Chronic Stable Angina. Circulation
2005;112:2102-2107. Peptide as an Independent Predictor of Mortality in Diabetic Nephropathy.
Diabetologia 2005;48:149-155.

16 Triage NT-proBNP Triage NT-proBNP 17

ASSISTANCE 98700EU – Quidel Triage NT-proBNP Test
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 technicalsupport@quidel.com. 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 EMEproductsupport@alere.com
Asia Pacific + 61.7.3363.7711 APproductsupport@alere.com
Africa, Russia and CIS + 972.8.9429.683 ARCISproductsupport@alere.com
Latin America + 57.2.6618797 LAproductsupport@alere.com
Canada + 1.613.271.1144 CANproductsupport@alere.com
MDSS GmbH
Schiffgraben 41
30175 Hannover,
Germany

Quidel Cardiovascular Inc.

9975 Summers Ridge Drive
San Diego, CA 92121 USA ENSRC26592enEUA
quidel.com PN: 26592enEU Rev. A 2018/04

Revision Changes:
Initial release for Quidel Cardiovascular Inc.

18 Triage NT-proBNP Triage NT-proBNP 19

GLOSSARY

Catalogue number CE mark Authorized representative in

the European Community

Batch code Use-by date Manufacturer

Date of manufacture Temperature limit Intended use

Consult instructions In vitro diagnostic Test device

for use medical device

Do not re-use Contents/Contains Patient number

Transfer pipette CODE CHIP module Printer paper

Peel open here Add sample immediately Use EDTA whole blood or
after opening foil pouch plasma sample only

Add sample here

20 Triage NT-proBNP Triage NT-proBNP 21