(504 days)
Not Found
No
The device description details a standard immunometric assay based on chemical reactions and light detection. There is no mention of AI/ML in the device description, intended use, or performance studies. The performance studies focus on traditional statistical metrics like sensitivity, specificity, and AUC, not metrics typically associated with AI/ML model evaluation.
No
Explanation: This device is for in vitro diagnostic use, specifically for the quantitative measurement of NT-proBNP to aid in the diagnosis and assessment of heart failure. It does not provide any therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states, "For in vitro diagnostic use only," and "to aid in the diagnosis of heart failure." The device measures a biomarker to assist in identifying a medical condition.
No
The device description clearly outlines a chemical assay performed on a physical instrument (VITROS Systems) using reagents and calibrators. This involves hardware components and chemical reactions, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states: "# Intended Use / Indications for Use For in vitro diagnostic use only." This statement directly identifies the device as an in vitro diagnostic product.
N/A
Intended Use / Indications for Use
For in vitro diagnostic use only.
For the quantitative measurement of N-terminal pro Brain Natriuretic Peptide (NT-proBNP) in human serum and plasma (K2 EDTA or Lithium Heparin) using the VITROS 3600 Immunodiagnostic System to aid in the diagnosis of heart failure. The test can also be used in the assessment of heart failure severity in patients diagnosed with heart failure.
Product codes
NBC
Device Description
The VITROS NT-proBNP II test is performed using the VITROS VITROS NT-proBNP II Reagent Pack and the VITROS NT-proBNP II Calibrators on the VITROS Systems.
The VITROS NT-proBNP II test utilizes a one-step immunometric bridging assay design. A well is pushed from the pack and patient sample is dispensed into the antibody coated well. The assay reagent and the conjugate reagent are then dispensed into the well with the patient sample. NT-proBNP present in the sample binds with horseradish peroxidase (HRP)-labeled antibody conjugate which is captured by biotinylated anti-NT-proBNP capture antibody which is bound to Streptavidin coated microwells. The well is incubated for 8 minutes, before unbound materials are removed by washing.
The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrate (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the System. The amount of HRP conjugate bound is directly proportional to the concentration of NT-proBNP present.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
22 years and older
Intended User / Care Setting
Emergency Department (ED), Cardiology Clinics and other outpatient facilities.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Emergency Department Setting: A multi-center prospective study including 20 collection sites across the United States was conducted. Subjects 22 years and older presenting to the Emergency Department (ED) with dyspnea (acute or worsening) and clinical suspicion of heart failure (HF) were enrolled into the study. Subjects with terminal kidney failure on chronic dialysis and subjects with dyspnea clearly not secondary to HF were excluded from the study. The final clinical diagnosis was adjudicated by independent cardiologists or ED physicians experienced in diagnosing HF. Individuals in the population were African American (36.55%) and Caucasian (59.59%), with the remaining 3.86% represented by other races. Dyspnea was acute in 44.09%, worsening in 55.45% and not specified in 0.45% of subjects. The VITROS NT-proBNP II test results were determined from 2200 ED subjects, 1016 (46.18%) females and 1184 (53.82%) males, ranging in age from 22 to 106 years.
Outpatient Setting: The VITROS NT-proBNP II test results were also determined from 777 subjects, 391 females and 386 males ranging in age from 23 to 94 years presenting to Cardiology Clinics and other outpatient facilities with a clinical suspicion of HF (not previously diagnosed) and at least one HF sign, symptom or risk factor at 10 collection sites across the United States. Subjects with terminal kidney failure on chronic dialysis and subjects with dyspnea clearly not secondary to HF were excluded from the study. The final clinical diagnosis was adjudicated by independent cardiologists or ED physicians experienced in diagnosing HF. The prevalence of HF in the population was 6.18% (48/777). Individuals in the population were African American (31.66%) and Caucasian (64.74%), with the remaining 3.60% represented by other races.
Correlation with NYHA Functional Classification: The VITROS NT-proBNP II test results were determined from samples from 1143 subjects with heart failure ranging in age from 22 to 106 years. The population consisted of 475/1143 (41.56%) females and 668/1143 (58.44%) males.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance - Aid in Diagnosis of Heart Failure (Emergency Department Setting)
- Study Type: Multi-center prospective study
- Sample Size: 2200 ED subjects
- AUC: Ranged from 0.904 to 0.954 within and across gender. Overall AUC was 0.920 (95% CI 0.909-0.931). For relevant clinical subgroups, AUC was greater than or equal to 0.899.
- Key Results:
- Pretest Probability of HF (Overall): 49.8% (1095/2200)
- Posttest Probability of HF for Positive results (Overall): 82.9% (949/1145) (95% CI 80.6-85.0)
- Posttest Probability of non-HF for Negative results (Overall): 97.9% (599/612) (95% CI 96.4-98.8)
- Likelihood Ratio Positive (overall): 4.89 (95% CI 4.29-5.56)
- Likelihood Ratio Negative (overall): 0.02 (95% CI 0.01-0.04)
Clinical Performance - Aid in Diagnosis of Heart Failure (Outpatient Setting)
- Study Type: Clinical study at 10 collection sites.
- Sample Size: 777 subjects (with clinical suspicion of HF, not previously diagnosed, and at least one HF sign, symptom or risk factor).
- AUC: 0.880 (CI 0.822 to 0.937) for all subjects. For relevant clinical subgroups, AUC was greater than or equal to 0.838.
- Key Results (using 125 pg/mL cutoff):
- Sensitivity: 91.7% (44/48) (95% CI 80.0-97.7)
- Specificity: 67.2% (490/729) (95% CI 63.7-70.6)
- NPV: 99.2% (490/494) (95% CI 97.9-99.8)
- PPV: 15.6% (44/283) (95% CI 11.5-20.3)
- LR-: 0.12 (95% CI 0.05-0.31)
- LR+: 2.80 (95% CI 2.44-3.20)
Correlation with New York Heart Association (NYHA) Functional Classification
- Study Type: Correlation study
- Sample Size: 1143 subjects with heart failure
- Key Results: The Jonckheere-Terpstra test of trend showed a statistically significant relationship (p
§ 862.1117 B-type natriuretic peptide test system.
(a)
Identification. The B-type natriuretic peptide (BNP) test system is an in vitro diagnostic device intended to measure BNP in whole blood and plasma. Measurements of BNP are used as an aid in the diagnosis of patients with congestive heart failure.(b)
Classification. Class II (special controls). The special control is “Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers.”
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
October 4, 2021
Ortho Clinical Diagnostics Ann Quinn Director, Regulatory Affairs 100 Indigo Creek Drive Rochester, New York 14626
Re: K201312
Trade/Device Name: VITROS® Immunodiagnostic Products NT-proBNP II Reagent Pack Regulation Number: 21 CFR 862.1117 Regulation Name: B-Type Natriuretic Peptide Test System Regulatory Class: Class II Product Code: NBC Dated: November 6, 2020 Received: November 9, 2020
Dear Ann Quinn:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
1
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Marianela Perez-Torres. Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
2
Indications for Use
510(k) Number (if known) K201312
Device Name
VITROS® Immunodiagnostic Products NT-proBNP II Reagent Pack
Indications for Use (Describe) For in vitro diagnostic use only.
For the quantitative measurement of N-terminal pro Brain Natriuretic Peptide (NT-proBNP) in human serum and plasma (K2 EDTA or Lithium Heparin) using the VITROS 3600 Immunodiagnostic System to aid in the diagnosis of heart failure. The test can also be used in the assessment of heart failure severity in patients diagnosed with heart failure.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K201312
-
- Submitter Ortho-Clinical Diagnostics, Inc. name, 100 Indigo Creek Drive Rochester, NY 14626 address, contact P: (585) 453-4152 F: (585) 453-3113 Contact Person: Ann Quinn, Director, Regulatory Affairs
- September 23, 2021 2. Preparation Date
-
- Device Trade or Proprietary Names: VITROS® Immunodiagnostic Products NT-proBNP II Reagent Pack name Common Name: VITROS NT-proBNP II Classification: B-Type natriuretic peptide test system (862.1117) Class II Product Code: NBC
- Roche Elecsys® proBNP II Immunoassay, K072437 4. Predicate Device
- Device 5. The VITROS NT-proBNP II test is performed using the VITROS description VITROS NT-proBNP II Reagent Pack and the VITROS NT-proBNP II Calibrators on the VITROS Systems.
The VITROS NT-proBNP II test utilizes a one-step immunometric bridging assay design. A well is pushed from the pack and patient sample is dispensed into the antibody coated well. The assay reagent and the conjugate reagent are then dispensed into the well with the patient sample. NT-proBNP present in the sample binds with horseradish peroxidase (HRP)-labeled antibody conjugate which is captured by biotinylated anti-NT-proBNP capture antibody which is bound to Streptavidin coated
4
| | microwells. The well is incubated for 8 minutes, before unbound
materials are removed by washing. |
|------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | The bound HRP conjugate is measured by a luminescent reaction. A
reagent containing luminogenic substrate (a luminol derivative and a
peracid salt) and an electron transfer agent, is added to the wells. The HRP
in the bound conjugate catalyzes the oxidation of the luminol derivative,
producing light. The electron transfer agent (a substituted acetanilide)
increases the level of light produced and prolongs its emission. The light
signals are read by the System. The amount of HRP conjugate bound is
directly proportional to the concentration of NT-proBNP present. |
| 6. Device
intended
use | Rx ONLY
For in vitro diagnostic use only. |
| | For the quantitative measurement of N-terminal pro Brain Natriuretic
Peptide (NT-proBNP) in human serum and plasma (K2 EDTA or Lithium
Heparin) using the VITROS 3600 Immunodiagnostic System to aid in the
diagnosis of heart failure. The test can also be used in the assessment of
heart failure severity in patients diagnosed with heart failure. |
-
- Compari-The following tables provide a summary of the key features of the new son to device assessed against the predicate. predicate device:
| Device
Characteristic | New Device
VITROS NT-proBNP II | Predicate Device
Roche Elecsys proBNP
II Immunoassay,
K072437 | |
|--------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------|
| Intended Use | Rx ONLY
For in vitro diagnostic use only.
For the quantitative measurement of N-terminal pro Brain
Natriuretic Peptide (NT-proBNP) in human serum and
plasma (K2 EDTA or Lithium Heparin) using the VITROS
3600 Immunodiagnostic System to aid in the diagnosis of
heart failure. The test can also be used in the assessment of
heart failure severity in patients diagnosed with heart
failure. | For the quantitative
determination of N-
terminal pro-Brain
natriuretic peptide in
human serum and
plasma. Elecsys proBNP
II assay is used as an aid
in the diagnosis of
individuals suspected of
having congestive heart
failure. The test is
further indicated for the
risk stratification of
patients with acute
coronary syndrome and
congestive heart failure.
The test may also serve | |
| Device
Characteristic | New Device
VITROS NT-proBNP II | Predicate Device
Roche Elecsys proBNP
II Immunoassay,
K072437 | |
| Intended Use | See above | as an aid in the
assessment of increased
risk of cardiovascular
events and mortality in
patients at risk for heart
failure who have stable
coronary artery disease.
The electro-
chemiluminescense
immunoassay "ECLIA"
is intended for use on
Elecsys and cobas e
immunoassay analyzers. | |
| Basic Principle | Sandwich immunoassay | Same | |
| Antibody | Monoclonal anti-NT-proBNP | Same | |
| Sample Type | Serum and plasma | Same | |
| Measuring
Range | 20-30,000 pg/mL | 5-35,000 pg/mL | |
| Traceability | Standardized against the Elecsys proBNP II assay. | Standardized against the
Elecsys proBNP assay.
10% with the test at the concentrations indicated at nominal NT-proBNP concentrations of 125 pg/mL (14.8 pmol/L) and 2000 pg/mL (236 pmol/L).
9
| Compound | Concentration | Compound | Concentration | ||
|---|---|---|---|---|---|
| Acetaminophen | 156 µg/mL | 1030 µmol/L | Ibuprofen | 21.9 mg/dL | 1.06 mmol/L |
| Acetylcysteine | 15.0 mg/dL | 920 µmol/L | Insulin | 3.12 µg/dL | 5.37 nmol/L |
| Adrenaline (Epinephrine) | 20.0 µg/dL | 1.09 µmol/L | Intralipid | 2.00 g/dL | NA |
| Alprazolam | 25.8 µg/dL | 836 nmol/L | L-dopa (Levodopa) | 750 µg/dL | 38.0 µmol/L |
| Amlodipine besylate | 10.5 µg/dL | 184 nmol/L | Levothyroxine | 42.9 µg/dL | 552 nmol/L |
| Amoxicillin | 5.40 mg/dL | 148 µmol/L | Lidocaine | 1.50 mg/dL | 64.0 µmol/L |
| Ascorbic acid | 5.25 mg/dL | 298 µmol/L | Methyldopa sesquihydrate | 2.25 mg/dL | 94.4 µmol/L |
| Atorvastatin | |||||
| calciumtrihydrate | 162 µg/dL | 1.34 µmol/L | Methylprednisolone | 783 µg/dL | 20.9 µmol/L |
| Benazepril HCl | 44.0 µg/dL | 955 nmol/L | Metoprolol hemitartrate | 150 µg/dL | 2.19 µmol/L |
| Bilirubin, conjugated | 40.0 mg/dL | 474 µmol/L | Metronidazole | 12.3 mg/dL | 718 µmol/L |
| Bilirubin, unconjugated | 40.0 mg/dL | 684 µmol/L | Molsidomine | 18.0 µg/dL | 743 nmol/L |
| Biotin | 3510 ng/mL | 14.4 µmol/L | Naproxen sodium | 39.3 mg/dL | 1.56 mmol/L |
| Caffeine | 10.8 mg/dL | 556 µmol/L | Nicardipine HCL | 46.5 µg/dL | 901 nmol/L |
| Carvedilol | 43.2 µg/dL | 1.06 µmol/L | Nifedipine | 58.8 µg/dL | 1.70 µmol/L |
| Ceftriaxone | |||||
| disodium | |||||
| hemi(heptahydrate) | 100 mg/dL | 1510 µmol/L | Omeprazole | 840 µg/dL | 24.3 µmol/L |
| Cholesterol | 400 mg/dL | 10.3 mmol/L | Oxycodone HCl | 32.4 µg/dL | 0.92 µmol/L |
| Clopidogrel | |||||
| hydrogensulfate | 2.40 µg/dL | 57.2 nmol/L | Phenobarbital | 69.0 mg/dL | 2.97 mmol/L |
| Cotinine | 240 µg/dL | 13.6 µmol/L | Phenprocoumo | ||
| n(Marcumar) | 1.50 mg/dL | 53.5 µmol/L | |||
| Creatinine | 15.0 mg/dL | 1.33 mmol/L | Propafenone HCL | 72.0 µg/dL | 1.91 µmol/L |
| Cyclosporine | 180 µg/dL | 1.50 µmol/L | Pseudoephedrine HCl | 330 µg/dL | 16.4 µmol/L |
| Dextran | 2.40 g/dL | 600 µmol/L | Rheumatoid Factor | 1500 IU/mL | NA |
| Digitoxin | 7.50 µg/dL | 98.0 nmol/L | Rifampicin (Rifampin) | 4.80 mg/dL | 58.3 µmol/L |
| Digoxin | 3.90 µg/dL | 49.9 nmol/L | Salicylic acid | 2.86 mg/dL | 207 µmol/L |
| Diphenhydramine HCl | 77.4 µg/dL | 2.65 µmol/L | Salmeterol | 1.65 µg/dL | 39.7 nmol/L |
| Dipyrone (as 4- | |||||
| methylaminoantipyrine | |||||
| Hydrochloride) | 3.30 mg/dL | 130 µmol/L | Sotalol hydrochloride | 510 µg/dL | 16.5 µmol/L |
| Dypyridamole | 1.00 mg/dL | 19.8 µmol/L | Spironolactone | 55.5 µg/dL | 1.33 µmol/L |
| Doxycycline hyclate | 1.80 mg/dL | 35.1 µmol/L | Streptokinase | 150,000 U/dL | NA |
| Enalaprilat dihydrate | 81.9 µg/dL | 2.13 µmol/L | Theophylline | 6.00 mg/dL | 333 µmol/L |
| Ethanol | 600 mg/dL | 130 mmol/L | Tolbutamide | 54.9 mg/dL | 2.03 mmol/L |
| Fibrinogen | 1000 mg/dL | NA | Total Protein | 15.0 g/dL | NA |
| Furosemide | 1.59 mg/dL | 48.1 µmol/L | tPA (Alteplase) | 1.20 mg/dL | NA |
| Gentamicin Sulfate | 3.51 mg/dL | 61.0 µmol/L | Triglyceride | 1500 mg/dL | 16.9 mmol/L |
| Glycerylnitrate | |||||
| (Nitroglycerin) | 1.20 µg/dL | 52.8 nmol/L | Valproic Acid | 31.8 mg/dL | 2.21 mmol/L |
| HAMA (Human Anti- | |||||
| MouseAntibody | 800 µg/L | NA | Vancomycin Hydrochloride | 12.3 mg/dL | 82.8 µmol/L |
| Hemoglobin | 1000 mg/dL | 155 µmol/L | Verapamil Hydrochloride | 160 µg/dL | 3.26 µmol/L |
| Heparin (Sodium), UFH | 330 U/dL | NA | Warfarin | 8.00 mg/dL | 260 µmol/L |
The substances shown to interfere with the VITROS NT-proBNP II test are provided in the table below. These results are representative. The degree of interference at concentrations other than those listed might not be predictable from these results. Other interfering substances may be encountered in the patient population.
10
| Interferent | Interferent Concentration | Measured NT-proBNP Concentration* | % Bias** | |
|---|---|---|---|---|
| pg/mL | pmol/L | |||
| Cefoxitin sodium | 697 mg/dL | 84.3 | 9.95 | -24.1 |
| 15.5 mmol/L | 922 | 109 | -19.1 | |
| 311 mg/dL | 105 | 12.4 | -10.0 | |
| 306 mg/dL | 806 | 95.1 | -10.0 | |
| Sodium Azide | 100 mg/dL | 91.4 | 10.8 | -12.1 |
| 85.9 mg/dL | 93.6 | 11.0 | -10.0 | |
| 15.4 mmol/L | ||||
| 13.2 mmol/L |
- Average test replicate determinations.
** Estimate of the maximum difference observed as a percentage.
The cross-reactivity of the VITROS NT-proBNP II test was evaluated by adding the following substances to a human serum sample containing no NT-proBNP.
| Cross-Reactant | Concentration | Mean Result of Control Sample | Mean Result of Cross-Reactant Sample | % Cross- Reactivity | |||
|---|---|---|---|---|---|---|---|
| pg/mL | pmol/L | pg/mL | pmol/L | ||||
| ANP28 | 3.10 µg/mL | 1.01 nmol/L | * | * | * | * | * |
| proBNP (glycosylated) | 3000 pg/mL | N/A | -0.14 | -0.02 | 57.6 | 6.80 | 1.9 |
| proBNP (nonglycosylated) | 3000 pg/mL | 0.249 nmol/L | -0.48 | -0.06 | 863 | 102 | 28.8 |
| NT-proANP1-30 | |||||||
| (preproANP25-55) | 3.50 µg/mL | 0.998 µmol/L | * | * | * | * | * |
| NT-proANP31-67 | |||||||
| (preproANP56-92) | 1.00 ng/mL | 0.258 nmol/L | * | * | * | * | * |
| NT-proANP79-98 | |||||||
| (preproANP 104-123) | 1.00 ng/mL | 0.458 nmol/L | * | * | * | * | * |
| BNP32 (Natrecor®) | 3.50 µg/mL | 1.01 µmol/L | * | * | * | * | * |
| CNP22 | 2.20 µg/mL | 1.00 µmol/L | * | * | * | * | * |
| Adrenomedullin | 1.00 ng/mL | 0.166 nmol/L | * | * | * | * | * |
| Aldosterone | 0.600 ng/mL | 1.66 nmol/L | * | * | * | * | * |
| Angiotensin I | 0.600 ng/mL | 0.463 nmol/L | * | * | * | * | * |
| Angiotensin II | 0.600 ng/mL | 0.574 nmol/L | * | * | * | * | * |
| Angiotensin III | 1.00 ng/mL | 1.07 nmol/L | * | * | * | * | * |
| Endothelin | 20.0 pg/mL | 8.03 pmol/L | * | * | * | * | * |
| Urodilatin | 3.50 µg/mL | 0.998 µmol/L | * | * | * | * | * |
| Arg-Vasopressin | 1.00 µg/mL | 0.922 µmol/L | * | * | * | * | * |
| Renin | 50.0 ng/mL | 28.4 nmol/L | * | * | * | * | * |
*Not Detectable (ND). Concentration was below the measuring range of the test, 20.0-30,000 pg/mL (2.36-3,540 pmol/L).
The cross-reactivity of the VITROS NT-proBNP II test was evaluated by adding the following substances to a human serum sample containing NT-proBNP at a concentration of 125 pg/mL (14.8 pmol/L).
| Cross-Reactant | Concentration | Mean NT-proBNP
Result of Control
Sample | | Mean NT-proBNP
Result of Cross-
Reactant Sample | | % Cross-
Reactivity |
|--------------------------|---------------|-----------------------------------------------|--------|-------------------------------------------------------|--------|------------------------|
| | | pg/mL | pmol/L | pg/mL | pmol/L | |
| ANP28 | 3.10 µg/mL | 112 | 13.2 | 113 | 13.3 | 99th percentile (> 0.034 ng/mL VITROS Troponin I ES assay) .
- HbA1c > 6.5% .
- Creatinine (eGFR ≤ 60 mL/min) ●
12
| Age | Gender | n | RI Lower
Limit
(pg/mL) | RI Upper
Limit
(pg/mL) |
|-----------|--------|-----|------------------------------|------------------------------|
| 22 - Total | 114 | 141 | 255 |
| 50-Total | 538 | 630 | 1168 |
| ≥75 | VITROS NT-proBNP II Test
Result Interpretation | Positive | 372 | 62 | 434 |
| | | Gray Zone | 69 | 153 | 222 |
| | | Negative | 2 | 119 | 121 |
| | | Total | 443 | 334 | 777 |
| All Subjects | VITROS NT-proBNP II Test
Result Interpretation | Positive | 949 | 196 | 1145 |
| | | Gray Zone | 133 | 310 | 443 |
| | | Negative | 13 | 599 | 612 |
| | | Total | 1095 | 1105 | 2200 |
15
The following analyses were conducted to determine clinical performance:
| VITROS NT-proBNP II Test
| Results Classification | Adjudicated Diagnosis | Total | |
|---|---|---|---|
| HF | Non-HF | ||
| Positive: Heart Failure Likely | A | B | A+B |
| Gray Zone: Result | |||
| Indeterminate | C | D | C+D |
| Negative: Heart Failure | |||
| Unlikely | E | F | E+F |
| Total | A+C+E | B+D+F | A+B+C+D+E+F |
Pretest Probability of HF (prevalence of HF in the study) = (A+C+E)(A+B+C+D+E+F)
Posttest Probability of HF
Posttest probability of HF for positive test results = A/(A+B)
Posttest probability of HF for Gray zone test results = C/(C+D)
Posttest Probability of non-HF
Posttest probability of non-HF for Gray zone test results = D/(C+D)
Posttest probability of non-HF for negative test results = F/(E+F)
Likelihood ratios (LR) of HF given VITROS NT-proBNP II test result category
LR positive = (A/(A+C+E))/(B/(B+D+F))
LR gray zone = (C/(A+C+E))/(D/(B+D+F))
LR negative = (E/(A+C+E))/(F/(B+D+F))
The pretest probability of HF (prevalence of HF in the study), posttest probabilities, likelihood ratios and the two-tailed 95% CIs of the VITROS NT-proBNP II test result versus adjudicated diagnosis were determined across and within gender using the agedependent rule-in (450 pg/mL for subjects 22-75 years old) and age-independent rule-out (300 pg/mL) cutoffs and are summarized in the following tables:
| Age Group (Years) | Pretest Probability of HF (Prevalence of HF in Study) (n/N) | VITROS NT-proBNP II Test Result Interpretation | Posttest Probability of HF (n/N) | Posttest Probability of non-HF (n/N) | Likelihood Ratio Positive (HF) | 95% CI** | ||
|---|---|---|---|---|---|---|---|---|
| Estimate (%) | 95% CI* (%) | Estimate (%) | 95% CI* (%) | |||||
| 22- |