hsTnI Risk Strat

en
08P13
STAT High Sensitive Troponin-I Reagent Kit H05938R03
B8P1D0
Revised October 2020.

08P1327
08P1337
Instructions must be carefully followed. Reliability of assay results cannot be (ECG) changes, development of pathological Q waves, imaging evidence of
guaranteed if there are any deviations from these instructions. new loss of viable myocardium or new regional wall motion abnormality in

ll
NAME
a pattern consistent with an ischemic etiology, identification of a coronary
thrombus by angiography or autopsy.14, 17 A gender difference in 99th
Alinity i STAT High Sensitive Troponin-I Reagent Kit (also referred to as hsTnI percentile has been reported, indicating the benefit of using gender-specific
Risk Strat) 99th percentile cutoff values.16
ll
INTENDED USE Several major studies have shown that cTnI is also useful as a predictor of
cardiac risk in patients with unstable angina.18, 19 Additional studies have
The Alinity i STAT High Sensitive Troponin-I assay is a chemiluminescent
shown that during a 30-day follow-up, patients with acute coronary syndromes
microparticle immunoassay (CMIA) used for the quantitative determination of
(including unstable angina) were at greater risk of progressing to MI if cTnI
cardiac troponin I (cTnI) in human plasma and serum on the Alinity i analyzer.
was elevated.20, 21 Results from the PRISM trial showed that elevated cTnI
The Alinity i STAT High Sensitive Troponin-I assay is to be used as an aid in levels could help to identify patients with unstable angina who had additional
the diagnosis of myocardial infarction (MI) and to aid in the assessment of cardiac risk (especially within the first 72 hours after onset of symptoms)
30-day and 90-day prognosis relative to all-cause mortality and major adverse and who could benefit from treatment with a glycoprotein IIb/IIIa receptor
cardiac events (MACE) consisting of myocardial infarction, revascularization, antagonist.20 Thus, cTnI can play an important role in identifying patients with
and cardiac death in patients who present with symptoms suggestive of acute acute coronary syndromes who are at greater risk for cardiac events. The
coronary syndrome (ACS). ESC, ACCF, AHA, and National Academy of Clinical Biochemistry (NACB) also
The cTnI values may also be used, in conjunction with clinical and diagnostic recommend using cTnI results when making treatment decisions regarding
findings, to aid in stratifying the risk of cardiovascular disease, including unstable angina and non-ST segment elevation MI (NSTEMI).10, 22
cardiovascular death, MI, coronary revascularization, heart failure, or ischemic Studies employing sensitive troponin assays, capable of measuring troponin
stroke in asymptomatic individuals. levels in the general population or in patients with stable cardiovascular
ll
SUMMARY AND EXPLANATION OF THE TEST disease, have shown that elevated troponin levels are associated with
structural heart disease, risk of future cardiovascular events, and
Cardiac troponin I is a regulatory subunit of the troponin complex associated
mortality.23-26 Other research has shown that elevated troponin is indicative of
with the actin thin filament within cardiac muscle cells.1 Troponin I, in
future risk in patients undergoing chemotherapy, following non-cardiac surgery,
conjunction with troponin C and troponin T, plays an integral role in the
or with heart failure.27-29
regulation of muscle contraction. Three distinct tissue-specific isoforms
of troponin I have been identified from skeletal and cardiac muscles. The Also, studies have demonstrated that troponin values generated using the
cardiac isoform exhibits only 60% similarity with the skeletal muscle isoform Alinity i STAT High Sensitive Troponin-I assay can be incorporated into
and contains additional amino acids at the N-terminus; cTnI has a molecular cardiovascular risk prediction models and risk scores to stratify the risk (low/
weight of approximately 24 000 daltons.2, 3 moderate/elevated) of future cardiac events in asymptomatic individuals.30-38
High sensitivity troponin assays have been defined by the International
Federation of Clinical Chemistry (IFCC) as those which can achieve precision
ll
BIOLOGICAL PRINCIPLES OF THE PROCEDURE
This assay is a two-step immunoassay for the determination of cTnl in human
of less than or equal to 10% CV at the 99th percentile of a healthy population plasma and serum using chemiluminescent microparticle immunoassay
and are capable of detecting troponin in greater than 50% of both men and (CMIA) technology.
women individually.4-7
Sample and anti-troponin I coated paramagnetic microparticles are combined
Clinical studies have demonstrated the release of cTnI into the blood and incubated. The cardiac troponin I present in the sample binds to the
stream within hours following myocardial infarction (MI) or ischemic injury. anti-troponin I coated microparticles. The mixture is washed. Anti-troponin
High sensitivity assays can detect elevated levels of cTnI (above the 99th I acridinium-labeled conjugate is added to create a reaction mixture and
percentile of an apparently healthy reference population) within 3 hours after incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are
the onset of chest pain. Cardiac troponin I reaches peak concentrations in added.
approximately 8 to 28 hours and remains elevated for 3 to 10 days following
The resulting chemiluminescent reaction is measured as relative light units
MI.2, 8 Cardiac troponin is the preferred biomarker for the detection of
(RLUs). There is a direct relationship between the amount of cTnl in the
myocardial injury based on improved sensitivity and superior tissue specificity
sample and the RLUs detected by the system optics.
compared to other available biomarkers of necrosis, including CK-MB,
myoglobin, lactate dehydrogenase, and others.9, 10 The high tissue specificity For additional information on system and assay technology, refer to the Alinity
of cTnI measurements is beneficial for identifying cardiac injury in clinical ci-series Operations Manual, Section 3.
conditions involving skeletal muscle injury resulting from surgery, trauma,
extensive exercise, or muscular disease.11-13 High tissue specificity of cTnI,
ll
REAGENTS
however, should not be confused with the specificity for the mechanism Kit Contents
of injury (e.g., MI versus myocarditis). When an increased value for cTnI Alinity i STAT High Sensitive Troponin-I Reagent Kit 08P13
is encountered (e.g., exceeding the 99th percentile of a reference control NOTE: Some kit sizes are not available in all countries. Please contact your
population) in the absence of evidence of myocardial ischemia, a careful local distributor.
search of other possible etiologies for cardiac damage should be taken.9 Volumes (mL) listed in the table below indicate the volume per cartridge.
Elevated troponin levels may be indicative of myocardial injury associated with
heart failure, renal failure, chronic renal disease, myocarditis, arrhythmias, 08P1327 08P1337
pulmonary embolism, or other clinical conditions.14-16 Tests per cartridge 100 600
Per the fourth universal definition of MI,17 the term myocardial injury should Number of cartridges
be used when there is evidence of elevated cardiac troponin (cTn) values, 2 2
per kit
with at least one value above the 99th percentile upper reference limit (URL). Tests per kit 200 1200
The myocardial injury is considered acute if there is a rise and/or fall of
6.6 mL 33.8 mL
cTn values. The term acute myocardial infarction should be used in specific
situations when there is acute myocardial injury with clinical evidence of acute 6.1 mL 33.8 mL
myocardial ischemia and with detection of a rise and/or fall of cTn values
with at least one value above the 99th percentile URL and at least one of the Anti-troponin I (mouse, monoclonal) coated microparticles
following symptoms of myocardial ischemia: new ischemic electrocardiogram in TRIS buffer with protein (bovine) stabilizer. Minimum concentration: 0.035%
solids. Preservative: ProClin 300.

1
 08P1327 08P1337 P333+P313 If skin irritation or rash occurs: Get medical
advice / attention.
Anti-troponin I (mouse-human chimeric, monoclonal) P362+P364 Take off contaminated clothing and wash it
acridinium-labeled conjugate in MES buffer with protein (bovine) stabilizer before reuse.
and human IgG. Minimum concentration: 0.1 mg/L. Preservative: ProClin 300. Disposal
P501 Dispose of contents / container in accordance
Warnings and Precautions with local regulations.
•
• For In Vitro Diagnostic Use * Not applicable where regulation EC 1272/2008 (CLP) or OSHA Hazard
Communication 29 CFR 1910.1200 (HCS) 2012 have been implemented.
Safety Precautions
Follow local chemical disposal regulations based on your location along with
recommendations and content in the Safety Data Sheet to determine the safe
disposal of this product.
CAUTION: This product contains human-sourced and/or potentially For the most current hazard information, see the product Safety Data Sheet.
infectious components. Refer to the REAGENTS section of this package Safety Data Sheets are available at www.corelaboratory.abbott or contact your
insert. No known test method can offer complete assurance that products local representative.
derived from human sources or inactivated microorganisms will not transmit For a detailed discussion of safety precautions during system operation, refer
infection. Therefore, all human-sourced materials should be considered to the Alinity ci-series Operations Manual, Section 8.
potentially infectious. It is recommended that these reagents and human Reagent Handling
specimens be handled in accordance with the OSHA Standard on Bloodborne
Pathogens. Biosafety Level 2 or other appropriate biosafety practices should • Upon receipt, gently invert the unopened reagent kit by rotating it over
be used for materials that contain or are suspected of containing infectious and back for a full 180 degrees, 5 times with green label stripe facing up
agents.39-42 and then 5 times with green label stripe facing down. This ensures that
liquid covers all sides of the bottles within the cartridges. During reagent
The human-sourced materials used in the conjugate are nonreactive for
shipment, microparticles can settle on the reagent septum.
HBsAg, HCV, and anti-HIV-1/HIV-2.
–– Place a check in the square on the reagent kit to indicate to others
The following warnings and precautions apply to: that the inversions have been completed.
• After mixing, place reagent cartridges in an upright position for 1 hour
before use to allow bubbles that may have formed to dissipate.
• If a reagent cartridge is dropped, place in an upright position for 1 hour
before use to allow bubbles that may have formed to dissipate.
WARNING Contains methylisothiazolones. • Reagents are susceptible to the formation of foam and bubbles. Bubbles
H317 May cause an allergic skin reaction. may interfere with the detection of the reagent level in the cartridge and
Prevention cause insufficient reagent aspiration that may adversely affect results.
P261 Avoid breathing mist / vapors / spray. For a detailed discussion of reagent handling precautions during system
operation, refer to the Alinity ci-series Operations Manual, Section 7.
P272 Contaminated work clothing should not be
allowed out of the workplace. Reagent Storage
P280 Wear protective gloves / protective clothing / Storage Maximum Additional Storage
eye protection. Temperature Storage Time Instructions
Response Unopened 2 to 8°C Until expiration Store in upright position.
P302+P352 IF ON SKIN: Wash with plenty of water. date If cartridge does not remain
P333+P313 If skin irritation or rash occurs: Get medical upright, gently invert the
advice / attention. cartridge 10 times and place
P362+P364 Take off contaminated clothing and wash it in an upright position for 1
before reuse. hour before use.
Disposal Onboard System 30 days
P501 Dispose of contents / container in accordance Temperature
with local regulations. Opened 2 to 8°C Until expiration Store in upright position.
date If cartridge does not remain
The following warnings and precautions apply to: upright during storage, discard
the cartridge.
Do not reuse original
reagent caps or replacement
caps due to the risk of
WARNING Contains methylisothiazolones and polyethylene contamination and potential
glycol octylphenyl ether. to compromise reagent
H317 May cause an allergic skin reaction. performance.
H319 Causes serious eye irritation. Reagents may be stored on or off the system. If removed from the system,
H316* Causes mild skin irritation. store reagents with new replacement caps in an upright position at 2 to 8°C.
Prevention For reagents stored off the system, it is recommended that they be stored in
P261 Avoid breathing mist / vapors / spray. their original trays or boxes to ensure they remain upright.
P264 Wash hands thoroughly after handling. For information on unloading reagents, refer to the Alinity ci-series Operations
Manual, Section 5.
P272 Contaminated work clothing should not be
allowed out of the workplace. Indications of Reagent Deterioration
P280 Wear protective gloves / protective clothing / Deterioration of the reagents may be indicated when a calibration error occurs
eye protection. or a control value is out of the specified range. Associated test results are
Response invalid, and samples must be retested. Assay recalibration may be necessary.
P305+P351+P338 IF IN EYES: Rinse cautiously with water for For troubleshooting information, refer to the Alinity ci-series Operations
several minutes. Remove contact lenses, if Manual, Section 10.

P337+P313
present and easy to do. Continue rinsing.
If eye irritation persists: Get medical advice /
ll
INSTRUMENT PROCEDURE
The Alinity i STAT High Sensitive Troponin-I assay file must be installed on the
attention. Alinity i analyzer prior to performing the assay.
P302+P352 IF ON SKIN: Wash with plenty of water.

2
For detailed information on assay file installation and viewing and editing • If the specimens:
assay parameters, refer to the Alinity ci-series Operations Manual, Section 2. –– contain fibrin, red blood cells, or other particulate matter, including
For information on printing assay parameters, refer to the Alinity ci-series cryoprecipitate, or
Operations Manual, Section 5. –– have been stored at 2 to 8°C for more than 24 hours, centrifuge at a
For a detailed description of system procedures, refer to the Alinity ci-series Relative Centrifugal Force (RCF) of 3000 to 3500 x g for 30 minutes
Operations Manual. before testing to ensure consistency in results.
• Centrifuged specimens with a lipid layer on the top must be transferred to
Alternate Result Units
a sample cup or secondary tube. Care must be taken to transfer only the
Edit assay parameter "Result Units" to select an alternate unit.
clarified specimen without the lipemic material.
Conversion formula:
Prepare frozen specimens as follows:
(Concentration in Default result unit) x (Conversion factor) = (Concentration in
• Frozen specimens must be completely thawed before mixing.
Alternate result unit)
• Mix thawed specimens thoroughly by gentle inversion or low speed
Default Result Unit Conversion Factor Alternate Result Unit vortex.
ng/L 0.001 ng/mL • Visually inspect the specimens. If layering or stratification is observed,
0.001 μg/L mix until specimens are visibly homogeneous.
1.0 pg/mL • If specimens are not mixed thoroughly, inconsistent results may be
obtained.
ll
SPECIMEN COLLECTION AND PREPARATION • Recentrifuge specimens.
FOR ANALYSIS • Process specimens as follows before testing:
–– Serum specimens:
Specimen Types
◦◦ centrifuge at an RCF of 3000 to 3500 x g for 30 minutes.
The specimen types listed below were verified for use with this assay.
–– Plasma specimens:
Other specimen types and collection tube types have not been verified with
this assay. ◦◦ centrifuge at an RCF of 13 000 to 13 500 x g for 30 minutes.
Specimen Types Collection Tubes OR
Serum Serum with and without separator ◦◦ centrifuge at an RCF of 3000 to 3500 x g for 10 minutes, transfer
Serum with thrombin-based clot the supernatant into a new centrifuge tube, taking care to avoid
activator transfer of any pellet, and spin again at an RCF of 3000 to 3500
Plasma Lithium heparin with and without x g for an additional 10 minutes.
separator • Transfer the supernatant to a sample cup or secondary tube for testing.
K2 EDTA Care must be taken to avoid transfer of any pellet or lipid layer, if present.
K3 EDTA
Specimen Storage
• When serial specimens are being evaluated, use the same specimen type Maximum
throughout the evaluation. Specimen Storage
• Performance has not been established for the use of cadaveric Type Temperature Time Special Instructions
specimens or the use of bodily fluids other than human serum/plasma.
Serum/Plasma Room 8 hours* Specimens may be stored
• Liquid anticoagulants may have a dilution effect resulting in lower temperature on or off the clot, red
concentration values for individual specimens. blood cells, or separator
• The instrument does not provide the capability to verify specimen types. gel.
It is the responsibility of the operator to verify that the correct specimen
types are used in the assay. 2 to 8°C 24 hours* Specimens may be stored
on or off the clot, red
Specimen Conditions blood cells, or separator
• Do not use: gel.
–– heat-inactivated specimens
If testing will be delayed more than 72 hours, plasma or serum should be
–– pooled specimens
removed from the red blood cells, clot, or separator gel and stored frozen
–– specimens with obvious microbial contamination (-10°C or colder).
• For accurate results, serum and plasma specimens should be free Serum with thrombin-based clot activator: after 24 hours at 2 to 8°C, serum
of fibrin, red blood cells, and other particulate matter, including should be stored at -10°C or colder.
cryoprecipitate.
Freeze specimens only once.
–– Ensure that complete clot formation in serum specimens has taken
*Limitations
place prior to centrifugation.
• If testing is delayed by more than 2 hours from specimen collection,
–– Some specimens, especially those from patients receiving
studies demonstrated a mean difference of ≤ 10% (within the range of 10
anticoagulant or thrombolytic therapy, may exhibit increased clotting
to 50 000 ng/L) and ± 1 ng/L (within the range of 3.2 to 10 ng/L) under
time. If the specimen is centrifuged before a complete clot forms,
the following conditions:
the presence of fibrin may cause erroneous results.
–– On or Off the clot, red blood cells, or separator gel at room
• To prevent cross contamination, use of disposable pipettes or pipette tips
temperature for up to 8 hours.
is recommended.
–– On or Off the clot, red blood cells, or separator gel at 2 to 8°C for up
Preparation for Analysis to 24 hours.
• Follow the tube manufacturer’s processing instructions for collection • If testing is delayed by more than 2 hours from specimen collection for
tubes. Gravity separation is not sufficient for specimen preparation. refrigerated or frozen specimens, studies demonstrated a mean difference
• Specimens should be free of bubbles. Remove bubbles with an applicator of < 20% in concentration under the following conditions:
stick before analysis. Use a new applicator stick for each specimen to –– On or Off the clot, red blood cells, or separator gel at 2 to 8°C for 24
prevent cross contamination. to 72 hours.
• Limitations –– Off the clot, red blood cells, or separator gel frozen at -10°C or
–– For serum collection tubes, allow for proper clotting prior to analysis. colder for up to 31 days.
Note: Serum specimens from individuals on anticoagulant therapy • Plasma specimens stored at -70°C or colder were reported to be stable
for up to 5 years.43
may show inconsistent results due to incomplete clotting. Abbott
recommends the use of plasma for rapid turnaround of results. Specimen Shipping
–– Serum with thrombin-based clot activator showed acceptable results Package and label specimens in compliance with applicable state, federal,
when centrifuged 30 minutes after blood draw. Other clotting times and international regulations covering the transport of clinical specimens and
were not evaluated. infectious substances.
Do not exceed the storage limitations listed above.

3
ll
PROCEDURE Once a calibration is accepted and stored, all subsequent samples may be
tested without further calibration unless:
Materials Provided • A reagent kit with a new lot number is used.
08P13 Alinity i STAT High Sensitive Troponin-I Reagent Kit • Daily quality control results are outside of statistically-based quality
Materials Required but not Provided control limits used to monitor and control system performance, as
• Alinity i STAT High Sensitive Troponin-I assay file described in the Quality Control Procedures section of this package
insert.
• 08P1301 Alinity i STAT High Sensitive Troponin-I Calibrators
–– If statistically-based quality control limits are not available, then
• 08P1310 Alinity i STAT High Sensitive Troponin-I Controls or other
the calibration should not exceed a 30-day limit for recalibration
commercially available controls
frequency.
• 09P1540 Alinity i Multi-Assay Manual Diluent
This assay may require recalibration after maintenance to critical parts or
• Alinity Trigger Solution
subsystems or after service procedures have been performed.
• Alinity Pre-Trigger Solution
• Alinity i-series Concentrated Wash Buffer Quality Control Procedures
For information on materials required for operation of the instrument, refer to The recommended control requirement for the Alinity i STAT High Sensitive
the Alinity ci-series Operations Manual, Section 1. Troponin-I assay is that a single sample of each control level be tested once
For information on materials required for maintenance procedures, refer to the every 24 hours each day of use.
Alinity ci-series Operations Manual, Section 9. Additional controls may be tested in accordance with local, state, and/or
federal regulations or accreditation requirements and your laboratory’s quality
Assay Procedure control policy.
For a detailed description of how to run an assay, refer to the Alinity ci-series To establish statistically-based control limits, each laboratory should establish
Operations Manual, Section 5. its own concentration target and ranges for new control lots at each clinically
• If using primary or aliquot tubes, refer to the Alinity ci-series Operations relevant control level. This can be accomplished by assaying a minimum of 20
Manual, Section 4 to ensure sufficient specimen is present. replicates over several (3-5) days and using the reported results to establish
• To minimize the effects of evaporation, verify adequate sample cup the expected average (target) and variability about this average (range) for the
volume is present prior to running the test. laboratory. Sources of variation that should be included in this study in order
• Maximum number of replicates sampled from the same sample cup: 8 to be representative of future system performance include:
–– Priority: • Multiple stored calibrations
◦◦ Sample volume for first test: 210 µL • Multiple reagent lots
• Multiple calibrator lots
◦◦ Sample volume for each additional test from same sample cup:
• Multiple processing modules (if applicable)
160 µL
• Data points collected at different times of the day
–– ≤ 3 hours on the reagent and sample manager:
Refer to published guidelines for information or general control
◦◦ Sample volume for first test: 210 µL recommendation, for example Clinical and Laboratory Standards Institute
◦◦ Sample volume for each additional test from same sample cup: (CLSI) Document C24-A3 or other published guidelines, for general quality
160 µL control recommendations.44
–– > 3 hours on the reagent and sample manager: • If more frequent control monitoring is required, follow the established
quality control procedures for your laboratory.
◦◦ Replace with a fresh aliquot of sample. • If quality control results do not meet the acceptance criteria defined by
• Refer to the Alinity i STAT High Sensitive Troponin-I calibrator package your laboratory, sample results may be suspect. Follow the established
insert and/or Alinity i STAT High Sensitive Troponin-I control package quality control procedures for your laboratory. Recalibration may be
insert for preparation and usage. necessary. For troubleshooting information, refer to the Alinity ci-series
• For general operating procedures, refer to the Alinity ci-series Operations Operations Manual, Section 10.
Manual, Section 5. • Review quality control results and acceptance criteria following a change
• For optimal performance, it is important to perform routine maintenance of reagent or calibrator lot.
as described in the Alinity ci-series Operations Manual, Section 9. Commercial controls should be used according to the guidelines and
Perform maintenance more frequently when required by laboratory recommendations of the control manufacturer. Concentration ranges provided
procedures. in the control package insert should be used only for guidance.
Sample Dilution Procedures For any control material in use, the laboratory should ensure that the matrix
Samples with an analyte value exceeding 50 000.0 ng/L (50 ng/mL) are of the control material is suitable for use in the assay per the assay package
flagged with the code "> 50 000.0 ng/L" (> 50 ng/mL) and may be diluted with insert.
either the Automated Dilution Protocol or the Manual Dilution Procedure. Quality Control Guidance
Automated Dilution Protocol Refer to “Basic QC Practices” by James O Westgard, Ph.D. for guidance on
The system performs a 1:10 dilution of the sample and automatically laboratory quality control practices.45
calculates the concentration by multiplying the result by the dilution factor. Verification of Assay Claims
Manual Dilution Procedure For protocols to verify package insert claims, refer to Verification of Assay
Suggested dilution: 1:10 Claims in the Alinity ci-series Operations Manual.
Add 25 μL of the sample to 225 μL of Alinity i Multi-Assay Manual Diluent.
The operator must enter the dilution factor in the Specimen or Control
ll
RESULTS
tab of the Create Order screen. The system will use this dilution factor to Calculation
automatically calculate the concentration of the sample and report the result. The Alinity i STAT High Sensitive Troponin-I assay utilizes a 4 Parameter
The result should be ≥ 10 ng/L (0.01 ng/mL) before the dilution factor is Logistic Curve fit data reduction method (4PLC, Y-weighted) to generate a
applied. calibration and results.
If the operator does not enter the dilution factor, the result must be manually For information on alternate result units, refer to the INSTRUMENT
multiplied by the appropriate dilution factor before reporting the result. If a PROCEDURE, Alternate Result Units section of this package insert.
diluted sample result is less than 10 ng/L (0.01 ng/mL), do not report the Flags
result. Rerun using an appropriate dilution. Some results may contain information in the Flags field. For a description of
For detailed information on ordering dilutions, refer to the Alinity ci-series the flags that may appear in this field, refer to the Alinity ci-series Operations
Operations Manual, Section 5. Manual, Section 5.
Calibration Measuring Interval
For instructions on performing a calibration, refer to the Alinity ci-series Measuring interval is defined as the range of values in ng/L (ng/mL) which
Operations Manual, Section 5. meets the limits of acceptable performance for linearity, imprecision, and bias.
Each assay control must be tested to evaluate the assay calibration. The analytical measuring interval of the Alinity i STAT High Sensitive Troponin-I
assay is 3.2 to 50 000 ng/L (0.0032 to 50 ng/mL).

4
Based on representative data for the Limit of Quantitation (LoQ) and the Age Range 99th Percentile 90% CI
Limit of Detection (LoD), the ranges over which results can be reported are
Population n (years) (ng/L) (ng/L)
provided below.
Overall 1531 21 - 75 26.2 (23.3, 29.7)
ng/L (pg/mL)
Analytical Measuring Interval (AMI)a 3.2 - 50 000.0 CI - Confidence Interval
a During the gender-specific analysis, the 3 tube type results from one female
Extended Measuring Interval (EMI)b 50 000.0 - 500 000.0
subject were identified as outliers using the Dixon method. The subject and
Reportable Intervalc 1.3 - 500 000.0
results were excluded from the gender-specific analysis, the subject and
a AMI: The AMI extends from the LoQ to the upper limit of quantitation results were included in the overall analysis.
(ULoQ). This is determined by the range of values in ng/L (pg/mL) that Guidance from the IFCC states that, for high sensitivity cTn assays, the 99th
demonstrated acceptable performance for linearity, imprecision and bias. percentile URL of a healthy population should be measured with an analytical
b EMI: The EMI extends from the ULoQ to the ULoQ x dilution factor. The precision of ≤ 10% CV. The overall precision at the 99th percentile for the
value reflects a 1:10 dilution factor. Alinity i STAT High Sensitive Troponin-I assay is 4.6%.
c The reportable interval extends from the LoD to the upper limit of the EMI.46 The IFCC guidelines also state that high sensitivity cTn assays should
NOTE: The default low linearity value in the assay file corresponds to the measure cTn above the limit of detection in ≥ 50% of healthy subjects.
lower limit of the reportable interval. Data generated using the ARCHITECT STAT High Sensitive Troponin-I assay
has demonstrated detection of cTnI in subjects above the observed limit of
ll
LIMITATIONS OF THE PROCEDURE detection (LoD) of greater than 50%.
• Any condition resulting in myocardial injury can potentially increase It is recommended that each laboratory verifies that the 99th percentile is
cardiac troponin I levels.14, 15, 17 For MI diagnostic purposes, the Alinity i transferable to its own population or establish its own 99th percentile.
STAT High Sensitive Troponin-I results should be used in conjunction with
other information such as ECG, clinical observations, and symptoms, etc. ll
Risk Stratification
• A single cTnI result may not be sufficient to evaluate MI. Serial blood This study was performed on the ARCHITECT i System.
draws are recommended for evaluation of acute coronary syndrome Gender-specific risk stratification cutoffs were derived from selected
(ACS) patients.9, 10, 14, 17 peer-reviewed published data30-38 and validated in a prospective study.
• Specimens from patients who have received preparations of mouse The following cutoff points may be used to aid in stratifying the risk of
monoclonal antibodies for diagnosis or therapy may contain human cardiovascular disease in asymptomatic individuals.
anti-mouse antibodies (HAMA).47, 48 Such specimens may show either Troponin Level
falsely elevated or depressed values when tested with assay kits such as Risk Male (ng/L) Female (ng/L)
Alinity i STAT High Sensitive Troponin-I that employ mouse monoclonal Low <6 <4
antibodies.47 Additional clinical or diagnostic information may be required
Moderate ≥ 6 - ≤ 12 ≥ 4 - ≤ 10
to determine patient status.
• Heterophilic antibodies and rheumatoid factor (RF) in human serum Elevated > 12 > 10
can react with reagent immunoglobulins, interfering with in vitro Asymptomatic individuals with elevated troponin levels are associated with a
immunoassays.49 The presence of heterophilic antibodies or RF in higher risk of developing cardiovascular related diseases in the future. Refer
a patient specimen may demonstrate anomalous values. Additional to the SPECIFIC PERFORMANCE CHARACTERISTICS, Clinical Performance,
information may be required for diagnosis. Risk Stratification Data section of this package insert for further details.
• Although the Alinity i STAT High Sensitive Troponin-I assay is specifically
designed to minimize the effects of HAMA, heterophilic antibodies, and ll
SPECIFIC PERFORMANCE CHARACTERISTICS
RF, assay results that are not consistent with other clinical observations Representative performance data are provided in this section. Results obtained
may require additional information for diagnosis. in individual laboratories may vary.
• Autoantibodies may react with troponin I or T 50-54 with a prevalence The Alinity i analyzer and the ARCHITECT i System utilize the same reagents
dependent on the cohort tested.50, 55, 56 The presence of autoantibodies and sample/reagent ratios.
may result in the observation of depressed or elevated troponin values Unless otherwise specified, all studies were performed on the Alinity i
(e.g. ‘macrotroponin’).57, 58 The clinical impact of autoantibodies is analyzer.
not fully defined but research has demonstrated an association with
conditions such as cardiomyopathy, myocarditis, cardiotoxicity and Precision
remodeling.51, 59-62 Troponin results should always be used in conjunction Within-Laboratory Precision
with other patient information. Refer to the SPECIFIC PERFORMANCE A study was performed based on guidance from CLSI EP05-A2. Testing was
CHARACTERISTICS, Clinical Performance section of this package insert conducted using 1 lot of the Alinity i STAT High Sensitive Troponin-I Reagent
for further details. Kit, 1 lot of the Alinity i STAT High Sensitive Troponin-I Calibrators, and 1
• Specimens from individuals with pathologically high total protein may lot of the Alinity i STAT High Sensitive Troponin-I Controls and 1 instrument.
demonstrate anomalous values. Additional information may be required for Three controls and 6 panels were assayed in a minimum of 2 replicates at 2
diagnosis. separate times per day on 20 different days.64
Refer to the SPECIMEN COLLECTION AND PREPARATION FOR ANALYSIS Within-Run Within-Laboratory
section of this package insert for specimen limitations. Mean (Repeatability) (Total)a

ll
EXPECTED VALUES Sample
Low Control
n
119
(ng/L)
20.5
SD
0.50
%CV
2.5
SD
0.80
%CV
3.9
This study was performed on the ARCHITECT i System.
Representative performance data are provided in this section. Results
Medium Control 119 191.5 3.28 1.7 4.67 2.4
obtained in individual laboratories may vary. High Control 120 15 965.2 244.37 1.5 306.69 1.9
Any condition resulting in myocardial injury can potentially increase cardiac Panel 1 (Native 120 10.5 0.41 3.9 0.76 7.2
troponin I levels.14, 15, 17 cTnl)
A reference range study was conducted based on guidance from Clinical Panel 2 (Bio-Rad 120 42.4 1.05 2.5 1.40 3.3
and Laboratory Standards Institute (CLSI) document C28‑A3c.63 Specimens Level Low)
were collected in 3 tube types (serum separator, lithium heparin separator, K2 Panel 3 (Native 119 173.7 3.30 1.9 4.90 2.8
EDTA) from 1531 apparently healthy individuals in a US population with normal cTnl)
levels of BNP, HbA1c, and estimated GFR values. Each specimen was frozen, Panel 4 (Bio-Rad 119 2014.3 27.57 1.4 36.10 1.8
thawed, and evaluated in replicates of one using the ARCHITECT STAT High Level 2)
Sensitive Troponin-I assay. The 4593 results were used to establish the 99th Panel 5 (Bio-Rad 120 6391.3 94.44 1.5 115.19 1.8
percentiles below. The observed 99th percentiles described below for this Level 3)
population were determined using the robust statistical method described in
Panel 6 119 43 256.2 614.16 1.4 716.20 1.7
CLSI document C28-A3c. (Recombinant
Age Range 99th Percentile 90% CI cTnl)
Population n (years) (ng/L) (ng/L)
Female 764a 21 - 75 15.6 (13.8, 17.5)
Male 766 21 - 73 34.2 (28.9, 39.2)
5
 Within-Run Within-Laboratory Specificity was determined by studying the cross-reactivity of 1000 ng/mL
(Repeatability) (Total)a skeletal troponin I, 1000 ng/mL cardiac troponin T, and 1000 ng/mL troponin C
Mean in samples prepared with cTnI across the range of ≤ 3.2 to 45 000 ng/L. The
Sample n (ng/mL) SD %CV SD %CV
observed percent cross-reactivity for each potential cross-reactant at each
Low Control 119 0.021 0.0006 2.8 0.0008 4.1 cTnI concentration was ≤ 0.1%.
Medium Control 119 0.192 0.0033 1.7 0.0047 2.5
Interference
High Control 120 15.965 0.2444 1.5 0.3067 1.9
Potentially Interfering Endogenous Substances and Potentially Interfering Drugs
Panel 1 (Native 120 0.011 0.0005 5.0 0.0008 7.7
These studies were performed on the ARCHITECT i System.
cTnl)
The studies were performed based on guidance from CLSI EP7-A2.67
Panel 2 (Bio-Rad 120 0.043 0.0011 2.6 0.0015 3.4
Level Low) Potentially interfering endogenous substances were evaluated to determine
the impact on cTnI results. Samples with cTnI concentrations of 15 ng/L and
Panel 3 (Native 119 0.174 0.0033 1.9 0.0049 2.8
500 ng/L demonstrated interference within ± 10% for the potentially interfering
cTnl)
substances listed below.
Panel 4 (Bio-Rad 119 2.014 0.0276 1.4 0.0361 1.8
Level 2) Potentially Interfering Substance Concentration
Panel 5 (Bio-Rad 120 6.391 0.0944 1.5 0.1152 1.8 Unconjugated Bilirubin ≤ 20.0 mg/dL
Level 3) Conjugated Bilirubin ≤ 20.0 mg/dL
Panel 6 119 43.256 0.6141 1.4 0.7162 1.7 Hemoglobin ≤ 500.0 mg/dL
(Recombinant Triglycerides ≤ 3000 mg/dL
cTnl)
Total protein was evaluated using human serum albumin (HSA) and
a Includes within-run, between-run, and between-day variability. concentrated normal specimens. Samples supplemented with HSA to total
Precision Profile protein ≤ 12 g/dL demonstrated interference within ± 10%. Specimens
Data from the 20-day precision and limit of quantitation (LoQ) studies were were concentrated to produce elevated total protein concentrations. The
evaluated together to estimate the following parameters: concentrated specimens were supplemented with cTnI to target concentrations
of 15 and 500 ng/L. The results are presented in the following table.
Precision Below LoQ
15 ng/L cTnI 500 ng/L cTnI
10% CV = 3.7 ng/L
Total Protein Observed Total Protein Observed
20% CV = 2.1 ng/L Concentration Interference Concentration Interference
Precision at 99th Percentiles 9.9 g/dL -7.3% 9.6 g/dL -8.5%
Female 15.6 ng/L = 5.0% CV 12.6 g/dL -7.5% 12.2 g/dL -16.6%
Male 34.2 ng/L = 4.5% CV The potentially interfering drugs listed below were tested in samples with
Overall 26.2 ng/L = 4.6% CV cTnI concentrations of 15 ng/L and 500 ng/L. Each cTnI level was tested
with potentially interfering drugs at therapeutic and high concentrations. The
Lower Limits of Measurement observed percent differences ranged from -3.1% to 4.3% at the therapeutic
Studies were performed based on guidance from CLSI EP17-A2. Testing was concentrations and -5.5% to 4.1% at the high concentrations.
conducted using a minimum of 4 lots of the Alinity i STAT High Sensitive Potentially
Troponin-I Reagent Kit on a minimum of 3 instruments over a minimum of 3 Interfering Therapeutic Potentially Therapeutic
days. Drug Conc. High Conc Interfering Drug Conc. High Conc
The observed pooled Limit of Blank (LoB) and Limit of Detection (LoD) values Abciximab 4 μg/mL 20 μg/mL Low MW Heparin 1.8 U/mL 5 U/mL
are summarized below.65
Acetaminophen 20 μg/mL 250 μg/mL Levodopa 1.8 μg/mL 20 μg/mL
ng/L ng/mL Acetylsalicylic 260 μg/mL 1000 μg/mL Methyldopa 4 μg/mL 25 μg/mL
LoBa 0.7 0.0007 Acid
LoDb 1.3 0.0013 Adrenaline 60 ng/mL 0.37 μg/mL Methylprednisolone 8 μg/mL 80 μg/mL
Studies were performed based on guidance from CLSI EP17-A2. Testing was Allopurinol 12 μg/mL 400 μg/mL Metronidazole 23 μg/mL 200 μg/mL
conducted using 2 lots of the Alinity i STAT High Sensitive Troponin-I Reagent Ambroxol 0.1 μg/mL 400 μg/mL Nicotine 37 ng/mL 2 mg/dL
Kit on each of 2 instruments over a minimum of 3 days. Ampicillin 10 μg/mL 1000 μg/mL Nifedipine 125 ng/mL 60 μg/mL
The observed range of Limit of Quantitation (LoQ) values are summarized Ascorbic Acid 12 μg/mL 300 μg/mL Nitrofurantoin 2.0 μg/mL 64 μg/mL
below.65 Atenolol 1 μg/mL 10 μg/mL Nystatin 2 μg/mL 7.5 μg/mL
ng/L ng/mL Bivalirudin 11 μg/mL 42 μg/mL Oxytetracycline 2 μg/mL 5 μg/mL
LoQc 2.2 - 2.7 0.0022 - 0.0027 Caffeine 12 μg/mL 100 μg/mL Phenobarbital 25 μg/mL 15 mg/dL
a The LoB represents the 95th percentile from n ≥ 60 replicates of zero- Captopril 1.0 μg/mL 50 μg/mL Phenytoin 12 μg/mL 100 μg/mL
analyte samples. Carvedilol 5 μg/mL 150 μg/mL Phenylbutazone 30 μg/mL 400 μg/mL
b The LoD represents the lowest concentration at which the analyte can be Cefoxitin 120 μg/mL 2500 μg/mL Propranolol 1 μg/mL 5 μg/mL
detected with 95% probability based on n ≥ 60 replicates of low-analyte level Cinnarizine 4 μg/mL 400 μg/mL Primidone 10 μg/mL 10 mg/dL
samples.
c The LoQ was determined from n ≥ 60 replicates of low-analyte level
Clopidogrel 15 μg/mL 75 μg/mL Quinidine 4 μg/mL 20 μg/mL
Cocaine 0.1 μg/mL 10 μg/mL Rifampicin 7 μg/mL 60 μg/mL
samples and is defined as the lowest concentration at which a maximum
allowable precision of 20 %CV was met. Cyclosporine 0.8 μg/mL 5 μg/mL Salicylic Acid 199 μg/mL 600 μg/mL
Diclofenac 2.5 μg/mL 50 μg/mL Simvastatin 4 μg/mL 20 μg/mL
Linearity
Digoxin 1 ng/mL 7.5 μg/mL Sodium Heparin 2 U/mL 8 U/mL
A study was performed based on guidance from CLSI EP06-A.66
Dopamine 0.3 μg/mL 900 μg/mL Streptokinase 4 U/mL 31.3 U/mL
This assay is linear across the analytical measuring interval of 3.2 to
50 000 ng/L (0.0032 to 50 ng/mL). Doxycycline 10 μg/mL 50 μg/mL Theophylline 12 μg/mL 75 μg/mL
Eptifibatide 2 μg/mL 7 μg/mL TPA 0.52 μg/mL 2.3 μg/mL
Analytical Specificity
Erythromycin 11 μg/mL 200 μg/mL Trimethoprim 12 μg/mL 75 μg/mL
This study was performed on the ARCHITECT i System.
Fondaparinux 1.2 μg/mL 4 μg/mL Verapamil 325 ng/mL 160 μg/mL
The Alinity i STAT High Sensitive Troponin-I assay has an analytical specificity
of ≤ 0.1% cross-reactivity with skeletal troponin I and ≤ 1% cross-reactivity Furosemide 20 μg/mL 400 μg/mL Warfarin 2 μg/mL 30 μg/mL
with cardiac troponin T and troponin C. Ibuprofen 40 μg/mL 500 μg/mL
Conc. = Concentration
TPA = Tissue plasminogen activator

6
Note: As the Alinity i STAT High Sensitive Troponin-I assay does not utilize
Positive Negative
a biotinylated antibody complex, there is no risk of potential interference to Predictive Predictive
troponin I values reported by the assay when analyzing samples containing Sensitivitya Specificityb Valuec Valued
Biotin.
Tube Time 95% 95% 95% 95%
Potentially Interfering Other Conditions Type Point n (%) CI (%) CI (%) CI (%) CI
This study was performed on the ARCHITECT i System. K2 EDTA Baseline 931 84.44 75.28, 85.49 82.93, 38.38 31.58, 98.09 96.82,
Twenty-two specimens positive for human anti-mouse antibodies (HAMA) and 91.23 87.81 45.54 98.95
22 specimens positive for rheumatoid factor (RF) were evaluated. The results 2 - 4 942 90.91 82.16, 84.74 82.17, 34.65 28.11, 99.05 98.06,
are summarized in the following table. Hours 96.27 87.07 41.65 99.62
Mean (Range) Native cTnl Concentration 4 - 9 862 93.90 86.34, 83.33 80.53, 37.20 30.60, 99.24 98.23,
Clinical Condition % Interference Range (ng/L) Hours 97.99 85.88 44.17 99.75
HAMA -2.8% (-11.7% to 3.3%) 10.1 to 370.3 Lithium Baseline 951 81.05 71.72, 83.18 80.50, 34.84 28.58, 97.53 96.13,
RF -3.4% (-21.2% to 9.5%) 11.9 to 386.0 Heparin 88.37 85.62 41.52 98.53
Separator 2 - 4 958 90.70 82.49, 83.03 80.37, 34.51 28.33, 98.91 97.86,
Method Comparison Hours 95.90 85.46 41.10 99.53
A study was performed based on guidance from CLSI EP09-A3 using the 4 - 9 903 93.94 87.27, 79.98 77.04, 36.61 30.68, 99.08 98.00,
Deming regression method.68 Hours 97.74 82.69 42.86 99.66
Alinity i STAT High Sensitive Troponin-I vs ARCHITECT STAT High Sensitive Troponin-I Serum Baseline 884 87.32 77.30, 85.85 83.27, 35.03 28.02, 98.73 97.60,
Separator 94.04 88.18 42.54 99.42
Correlation Concentration
Units n Coefficient Intercept Slope Range 2 - 4 942 90.67 81.71, 84.54 81.96, 33.66 27.18, 99.05 98.06,
Hours 96.16 86.89 40.63 99.62
Plasma ng/L 115 1.00 1.39 1.00 10.5 - 47 065.9
(ng/mL) (0.00) (0.011 - 47.066) 4 - 9 863 93.15 84.74, 82.03 79.17, 32.38 26.10, 99.23 98.22,
Hours 97.74 84.64 39.16 99.75
Carryover CI = Confidence Interval
The Alinity i STAT High Sensitive Troponin-I assay has a within assay carryover The results using the overall 99th percentile cutoff (26.2 ng/L) are
of less than or equal to 1.9 ng/L of troponin-I from a sample greater than or summarized in the table below.
equal to 500 000 ng/L to a sample with less than or equal to 3.2 ng/L.
Positive Negative
Clinical Performance Predictive Predictive
These studies were performed on the ARCHITECT i System. Sensitivitya Specificityb Valuec Valued
Diagnosis Tube Time 95% 95% 95% 95%
Serial sampling to detect the temporal rise and fall of cTnI levels is Type Point n (%) CI (%) CI (%) CI (%) CI
recommended for the differentiation of acute cardiac events from chronic K2 EDTA Baseline 931 84.44 75.28, 85.73 83.18, 38.78 31.92, 98.10 96.82,
cardiac disease.10, 14 91.23 88.03 45.98 98.95
A prospective study was performed to assess diagnostic accuracy of 2 - 4 942 92.21 83.81, 85.20 82.66, 35.68 29.03, 99.19 98.25,
the ARCHITECT STAT High Sensitive Troponin-I assay. Specimens were Hours 97.09 87.50 42.76 99.70
collected at 11 emergency departments from 1101 subjects presenting to 4 - 9 862 93.90 86.34, 82.82 79.99, 36.49 29.99, 99.23 98.22,
the emergency department with symptoms consistent with acute coronary Hours 97.99 85.40 43.38 99.75
syndrome (ACS). All subject diagnoses were adjudicated by three board Lithium Baseline 951 85.26 76.51, 83.76 81.12, 36.82 30.43, 98.08 96.81,
certified cardiologists according to current standard of care.69 The observed Heparin 91.70 86.17 43.56 98.95
MI prevalence in this study was 11.81%. Separator 2 - 4 958 91.86 83.95, 83.72 81.09, 35.75 29.43, 99.05 98.05,
• 748 specimens with serial sampling from 130 MI subjects Hours 96.66 86.11 42.45 99.62
• 7488 specimens with serial sampling from 971 non-MI subjects 4 - 9 903 94.95 88.61, 80.72 77.82, 37.75 31.71, 99.24 98.22,
The specimens were collected in three tube types (lithium heparin separator, Hours 98.34 83.39 44.09 99.75
K2 EDTA, serum separator) and frozen. The specimens were thawed and Serum Baseline 884 87.32 77.30, 86.35 83.79, 35.84 28.70, 98.73 97.61,
evaluated using the ARCHITECT STAT High Sensitive Troponin-I assay. The Separator 94.04 88.63 43.47 99.42
Area Under the Curve (AUC) results70 are summarized in the following table.
2 - 4 942 92.00 83.40, 85.81 83.31, 35.94 29.16, 99.20 98.27,
Tube Type Time Point n AUC 95% CI Hours 97.01 88.07 43.16 99.71
K2 EDTA Baseline 931 0.9326 0.9048, 0.9604 4 - 9 863 93.15 84.74, 84.05 81.31, 35.05 28.36, 99.25 98.26,
2 - 4 Hours 942 0.9431 0.9081, 0.9782 Hours 97.74 86.54 42.21 99.76
4 - 9 Hours 862 0.9503 0.9149, 0.9857 CI = Confidence Interval
Lithium Heparin Baseline 951 0.9197 0.8914, 0.9480 a Sensitivity = 100 × A ÷ (A + C)
Separator 2 - 4 Hours 958 0.9349 0.8986, 0.9712 b Specificity = 100 × D ÷ (B + D)

4 - 9 Hours 903 0.9498 0.9190, 0.9805 c Positive Predictive Value = 100 × A ÷ (A + B)

Serum Separator Baseline 884 0.9412 0.9102, 0.9722 d Negative Predictive Value = 100 × D ÷ (C + D)

2 - 4 Hours 942 0.9419 0.9041, 0.9796 ARCHITECT STAT High Diagnosis

4 - 9 Hours 863 0.9449 0.9046, 0.9852 Sensitive Troponin-I MI Non-MI
CI = Confidence Interval cTnI Value > cutpoint A B
The results were further analyzed using the serial sampling time points cTnI Value ≤ cutpoint C D
collected during the emergency department visit. The use of delta values (difference of cTnI levels between two test points)
The results using the gender-specific 99th percentile cutoffs (female may have the potential to improve the clinical specificity for acute coronary
15.6 ng/L; male 34.2 ng/L) are summarized in the table below. syndrome (ACS). An analysis of delta values was performed based on
analyses described in the literature.71, 72 The absolute percent difference
(delta value) was calculated between each of the three time points (Baseline,
2-4 Hours, 4-9 Hours) for each subject. The following two groups of subjects
were compared:
• Subjects who had an absolute percent difference greater than the given
cutoff and at least one value greater than the 99th percentile
• Subjects who had an absolute percent difference less than or equal to
the given cutoff or did not have any value greater than the 99th percentile

7
The sensitivity, specificity, positive predictive value, and negative predictive Positive Negative
Cutoff
value were calculated for the given cutoffs for each tube type. The absolute Predictive Predictive
(Absolute
percent change for lithium heparin separator tubes using the gender-specific Percent Time Sensitivitya Specificityb Valuec Valued
99th percentile cutoffs (female 15.6 ng/L; male 34.2 ng/L) are summarized in Change) Point n (%) (%) (%) (%)
the table below. The K2 EDTA and serum separator results were comparable.
250% Baseline 836 29.23 98.83 67.86 94.31
Cutoff Positive Negative vs. 2 - 4
(Absolute Predictive Predictive Hours
Percent Sensitivitya Specificityb Valuec Valued Baseline 772 55.56 96.86 64.52 95.49
Change) Time Point n (%) (%) (%) (%) vs. 4 - 9
20% Baseline vs. 836 70.77 93.26 46.94 97.43 Hours
2 - 4 Hours 2-4 819 19.12 98.80 59.09 93.10
Baseline vs. 772 79.17 90.57 46.34 97.69 Hours
4 - 9 Hours vs. 4 - 9
2 - 4 Hours 819 63.24 94.81 52.44 96.61 Hours
vs. 4 - 9 a Sensitivity = 100 × A ÷ (A + C)
Hours b Specificity = 100 × D ÷ (B + D)
50% Baseline vs. 836 56.92 95.20 50.00 96.33 c Positive Predictive Value = 100 × A ÷ (A + B)
2 - 4 Hours
d Negative Predictive Value = 100 × D ÷ (C + D)
Baseline vs. 772 73.61 93.29 53.00 97.17
4 - 9 Hours ARCHITECT STAT High Diagnosis
2 - 4 Hours 819 50.00 97.34 62.96 95.56 Sensitive Troponin-I MI Non-MI
vs. 4 - 9 cTnI Value > cutpoint A B
Hours
cTnI Value ≤ cutpoint C D
100% Baseline vs. 836 36.92 97.80 58.54 94.84
2 - 4 Hours Risk Stratification Data
Baseline vs. 772 61.11 95.00 55.70 95.96 To demonstrate the ability of the ARCHITECT STAT High Sensitive Troponin-I
4 - 9 Hours assay for risk stratification of asymptomatic individuals into risk categories
2 - 4 Hours 819 42.65 98.40 70.73 94.99 for cardiovascular disease including cardiovascular death, MI, coronary
vs. 4 - 9 revascularization, heart failure, or ischemic stroke, specimen testing was
Hours performed with prospectively collected clinical specimens from two cohorts.
250% Baseline vs. 836 29.23 98.83 67.86 94.31 The purpose of the studies was to investigate determinants of heart disease
2 - 4 Hours in relation to traditional cardiovascular risk factors.
Baseline vs. 772 55.56 96.86 64.52 95.49 Subjects from the study above were followed-up for subsequent events by
4 - 9 Hours medical record review and follow-up visits to assess for correlation between
cardiovascular outcome and troponin values in prospectively collected
2 - 4 Hours 819 19.12 98.80 59.09 93.10
samples. The hazard ratios for the gender-specific Risk Stratification cutoffs
vs. 4 - 9
Hours (female < 4, ≥ 4 to ≤ 10 and > 10 ng/L; male < 6, ≥ 6 to ≤ 12 and > 12 ng/L)
are summarized in the tables below. In addition, the prospectively collected
The absolute percent change for the lithium heparin separator tubes using the samples were evaluated against ARCHITECT CRP Vario (6K26) and using the
overall 99th percentile cutoff (26.2 ng/L) are summarized in the table below. Framingham model.
The K2 EDTA and serum separator results were comparable. Published studies also show that cTnI elevations above the risk categories
Cutoff Positive Negative stated are associated with increased risk of MI, heart failure or cardiovascular
(Absolute Predictive Predictive death. cTnI values determined using the ARCHITECT STAT High Sensitive
Percent Time Sensitivitya Specificityb Valuec Valued Troponin-I assay provide superior predictive information to cCRP (cardiac CRP
Change) Point n (%) (%) (%) (%) High Sensitive) values determined using ARCHITECT CRP Vario. Study results
20% Baseline 836 70.77 93.51 47.92 97.43 suggest that cTnI measurement is a better risk stratification tool than cCRP
vs. 2 - 4 to identify individuals at high CVD (cardiovascular disease) risk and may
Hours represent the preferred biomarker for targeted prevention.36
Baseline 772 79.17 90.71 46.72 97.69 Published studies also show that a change in cTnI is associated with a
vs. 4 - 9 modification in risk for CVD.70 Additionally, studies show that statin therapy
Hours use where cTnI concentrations were above 6 ng/L had the most benefit or risk
reduction for CVD.30, 72
2-4 819 63.24 94.67 51.81 96.60
Hours Baseline characteristics for the cohorts used to validate ARCHITECT
vs. 4 - 9 STAT High Sensitive Troponin-I for risk stratification of CVD
Hours Summary
50% Baseline 836 56.92 95.46 51.39 96.34 Age 59.0 [18.0 to 75.0]
vs. 2 - 4
Gender (Female) 6632 / 11 529 (57.5%)
Hours
Race/ethnicity
Baseline 772 73.61 93.71 54.64 97.19
vs. 4 - 9 Black 3431 / 11 529 (29.8%)
Hours Non-black 8098 / 11 529 (70.2%)
2-4 819 50.00 97.20 61.82 95.55 Hypertension Treatment 3787 / 11 429 (33.1%)
Hours Diabetes 1600 / 11 490 (13.9%)
vs. 4 - 9
Hours Current Smoker 2155 / 11 487 (18.8%)
100% Baseline 836 36.92 97.80 58.54 94.84 Blood Pressure
vs. 2 - 4 Systolic 124.0 [113.0 to 137.0]
Hours Diastolic 73.0 [66.0 to 80.0]
Baseline 772 61.11 95.14 56.41 95.97 Cholesterol (mg/dL)
vs. 4 - 9 Total Cholesterol 194.0 [170.0 to 219.0]
Hours
HDL 48.0 [39.0 to 59.0]
2-4 819 42.65 98.40 70.73 94.99
Hours Body Mass Index 28.2 [24.9 to 32.2]
vs. 4 - 9 Family History of Congenital Heart Defect
Hours Mother Side 1237 / 7711 (16.0%)
Father Side 2375 / 7380 (32.2%)

8
Continuous variables except for age are presented as median [25-75% Inter Quartile Range]. Age is reported as median [min-max].
Categorical variables are presented as number / total (percent)
Unadjusted Cox Proportional Hazards Model, ARCHITECT STAT High Sensitive Troponin-I
ARCHITECT STAT High Sensitive
Population Cohort n Troponin-I category (ng/L) Estimate Standard Error Hazard Ratio 95% CI P value
Overall Pooled Cohort 11 035 Moderate Risk: Male 6 - 12 ng/L, 0.67 0.062 1.95 1.72,2.19 <0.0001
Female 4 - 10 ng/L
Elevated Risk: Male >12 ng/L, 0.43 0.070 1.54 1.34,1.77 <0.0001
Female >10 ng/L
Female Pooled Cohort 6386 Moderate Risk: 4 - 10 ng/L 0.86 0.084 2.37 2.00,2.78 <0.0001
Elevated Risk: >10 ng/L 0.51 0.104 1.67 1.35,2.04 <0.0001
Male Pooled Cohort 4649 Moderate Risk: 6 - 12 ng/L 0.52 0.092 1.68 1.40,2.01 <0.0001
Elevated Risk: >12 ng/L 0.36 0.095 1.43 1.18,1.72 0.0002

Unadjusted Cox Proportional Hazards Model, ARCHITECT CRP Vario

Moderate
ARCHITECT Low Risk: Risk: 10% - High Risk: P value for
CRP Vario Female Total < 10 % 20% >20% Trend
category Standard Hazard P
MI 177 / 6301 147 / 5856 25 / 406 5 / 39 < 0.0001
Population Cohort n (mg/L) Estimate Error Ratio 95% CI value
(2.8%) (2.5%) (6.2%) (12.8%)
Overall Pooled 10 725 Average 0.12 0.066 1.13 0.99,1.28 0.0683
Stroke 139 / 6301 105 / 5856 31 / 406 3 / 39 < 0.0001
Cohort Risk: 1.0 -
(2.2%) (1.8%) (7.6%) (7.7%)
3.0 mg/L
Revascularization 204 / 6301 166 / 5856 35 / 406 3 / 39 < 0.0001
High Risk: 0.09 0.060 1.09 0.97,1.23 0.1375
(3.2%) (2.8%) (8.6%) (7.7%)
>3.0 mg/L
Cardiac Death 59 / 6301 39 / 5856 16 / 406 4 / 39 < 0.0001
Event Summary by ARCHITECT STAT High Sensitive Troponin-I Risk (0.9%) (0.7%) (3.9%) (10.3%)
Category for Pooled Cohort Data
Moderate
Low Risk: Moderate Elevated Low Risk: Risk: 10% - High Risk: P value for
< 4 ng/L Risk: 4 - 10 Risk: >10 P value for Male Total < 10 % 20% >20% Trend
Female Total (%) ng/L (%) ng/L (%) Trend Global CVD 1157 / 4594 166 / 1571 832 / 2686 159 / 337 < 0.0001
Global CVD 984 / 6387 697 / 5238 181 / 635 106 / 514 < 0.0001 (25.2%) (10.6%) (31.0%) (47.2%)
(15.4%) (13.3%) (28.5%) (20.6%) All Death 580 / 4594 96 / 1571 407 / 2686 77 / 337 < 0.0001
All Death 501 / 6387 352 / 5238 94 / 635 55 / 514 < 0.0001 (12.6%) (6.1%) (15.2%) (22.8%)
(7.8%) (6.7%) (14.8%) (10.7%) CHF 280 / 4594 33 / 1571 190 / 2686 57 / 337 < 0.0001
CHF 360 / 6387 213 / 5238 91 / 635 56 / 514 < 0.0001 (6.1%) (2.1%) (7.1%) (16.9%)
(5.6%) (4.1%) (14.3%) (10.9%) MI 232 / 4594 23 / 1571 167 / 2686 42 / 337 < 0.0001
MI 180 / 6387 119 / 5238 29 / 635 32 / 514 < 0.0001 (5.1%) (1.5%) (6.2%) (12.5%)
(2.8%) (2.3%) (4.6%) (6.2%) Stroke 113 / 4594 11 / 1571 81 / 2686 21 / 337 < 0.0001
Stroke 141 / 6387 92 / 5238 30 / 635 19 / 514 < 0.0001 (2.5%) (0.7%) (3.0%) (6.2%)
(2.2%) (1.8%) (4.7%) (3.7%) Revascularization 418 / 4594 35 / 1571 315 / 2686 68 / 337 < 0.0001
Revascularization 205 / 6387 170 / 5238 22 / 635 13 / 514 0.3323 (9.1%) (2.2%) (11.7%) (20.2%)
(3.2%) (3.2%) (3.5%) (2.5%) Cardiac Death 79 / 4594 17 / 1571 52 / 2686 10 / 337 0.0033
Cardiac Death 59 / 6387 33 / 5238 10 / 635 16 / 514 < 0.0001 (1.7%) (1.1%) (1.9%) (3.0%)
(0.9%) (0.6%) (1.6%) (3.1%)
Event Summary by cTnI Additive Values to Framingham Risk Score
Low Risk: Moderate Elevated
Group for Pooled Cohort Data
< 6 ng/L Risk: 6 - 12 Risk: >12 P value for
Male Total (%) ng/L (%) ng/L (%) Trend High Risk: Male
Global CVD 1171 / 4651 908 / 3865 136 / 379 127 / 407 < 0.0001 Elevated Risk: cTnI > 12 ng/L
(25.2%) (23.5%) (35.9%) (31.2%) Male cTnI > 12 Female cTnI
ng/L High Risk: >10 ng/L or
All Death 591 / 4651 446 / 3865 73 / 379 72 / 407 < 0.0001 Female cTnI Framingham Framingham P value for
(12.7%) (11.5%) (19.3%) (17.7%) Overall >10 ng/L (%) > 20% (%) >20% (%) Trenda
CHF 281 / 4651 172 / 3865 57 / 379 52 / 407 < 0.0001 Global CVD 233 / 921 175 / 376 369 / 1233 < 0.0001
(6.0%) (4.5%) (15.0%) (12.8%)
(25.3%) (46.5%) (29.9%)
MI 236 / 4651 175 / 3865 29 / 379 32 / 407 < 0.0001
All Death 127 / 921 88 / 376 189 / 1233 < 0.0001
(5.1%) (4.5%) (7.7%) (7.9%)
(13.8%) (23.4%) (15.3%)
Stroke 114 / 4651 84 / 3865 13 / 379 17 / 407 0.0028
(2.5%) (2.2%) (3.4%) (4.2%) CHF 108 / 921 64 / 376 155 / 1233 < 0.0001
(11.7%) (17.0%) (12.6%)
Revascularization 419 / 4651 336 / 3865 47 / 379 36 / 407 0.0670
(9.0%) (8.7%) (12.4%) (8.8%) MI 64 / 921 47 / 376 102 / 1233 < 0.0001
Cardiac Death 84 / 4651 51 / 3865 9 / 379 24 / 407 < 0.0001 (6.9%) (12.5%) (8.3%)
(1.8%) (1.3%) (2.4%) (5.9%) Stroke 36 / 921 24 / 376 50 / 1233 < 0.0001
(3.9%) (6.4%) (4.1%)
Event Summary by Framingham Risk Score Group for Pooled Cohort
Revascularization 49 / 921 71 / 376 109 / 1233 < 0.0001
Data
(5.3%) (18.9%) (8.8%)
Moderate Cardiac Death 40 / 921 14 / 376 46 / 1233 < 0.0001
Low Risk: Risk: 10% - High Risk: P value for
Female Total < 10 % 20% >20% Trend (4.3%) (3.7%) (3.7%)
Global CVD 976 / 6301 820 / 5856 140 / 406 16 / 39 < 0.0001
(15.5%) (14.0%) (34.5%) (41.0%)
All Death 497 / 6301 415 / 5856 71 / 406 11 / 39 < 0.0001
(7.9%) (7.1%) (17.5%) (28.2%)
CHF 356 / 6301 289 / 5856 60 / 406 7 / 39 < 0.0001
(5.6%) (4.9%) (14.8%) (17.9%)

9
 High Risk: cTnI High Risk: cTnI
Elevated Risk: High Risk: > 10 ng/L or Elevated Risk: High Risk: > 12 ng/L or
cTnI > 10 ng/L Framingham Framingham P value for cTnI > 12 ng/L Framingham Framingham P value for
Female (%) >20% (%) >20% (%) Trenda Male (%) > 20% (%) >20% (%) Trenda
Global CVD 106 / 514 16 / 39 115 / 532 < 0.0001 Global CVD 127 / 407 159 / 337 254 / 701 < 0.0001
(20.6%) (41.0%) (21.6%) (31.2%) (47.2%) (36.2%)
All Death 55 / 514 11 / 39 60 / 532 < 0.0001 All Death 72 / 407 77 / 337 129 / 701 < 0.0001
(10.7%) (28.2%) (11.3%) (17.7%) (22.8%) (18.4%)
CHF 56 / 514 7 / 39 58 / 532 < 0.0001 CHF 52 / 407 57 / 337 97 / 701 < 0.0001
(10.9%) (17.9%) (10.9%) (12.8%) (16.9%) (13.8%)
MI 32 / 514 5 / 39 35 / 532 < 0.0001 MI 32 / 407 42 / 337 67 / 701 < 0.0001
(6.2%) (12.8%) (6.6%) (7.9%) (12.5%) (9.6%)
Stroke 19 / 514 3 / 39 19 / 532 < 0.0001 Stroke 17 / 407 21 / 337 31 / 701 < 0.0001
(3.7%) (7.7%) (3.6%) (4.2%) (6.2%) (4.4%)
Revascularization 13 / 514 3 / 39 16 / 532 0.0034 Revascularization 36 / 407 68 / 337 93 / 701 < 0.0001
(2.5%) (7.7%) (3.0%) (8.8%) (20.2%) (13.3%)
Cardiac Death 16 / 514 4 / 39 18 / 532 < 0.0001 Cardiac Death 24 / 407 10 / 337 28 / 701 < 0.0001
(3.1%) (10.3%) (3.4%) (5.9%) (3.0%) (4.0%)
a Trend test p-value for cTnI and Framingham Risk Score combined

Prognosis
The ARCHITECT STAT High Sensitive Troponin-I assay was evaluated for use as an aid in the assessment of 30-day and 90‑day prognosis relative to all-cause
mortality (ACM) and major adverse cardiac events (MACE) consisting of myocardial infarction, urgent revascularization, and cardiac death in subjects who
present with symptoms suggestive of acute coronary syndrome (ACS).
Subjects from the diagnostic study above were followed-up for subsequent events by medical record review and/or subject/caregiver contact.
The 30-day and 90-day prognosis (Kaplan-Meier analysis) and hazard ratios (Cox regression) for the gender-specific 99th percentiles (female, 15.6 ng/L; male,
34.2 ng/L) are summarized in the tables below.
≤ Cutoff > Cutoff
No MACE/ACM No MACE/ACM
Tube Type Time Point MACE/ACM (Censoreda) Proportion MACE/ACM (Censoreda) Proportion Log-Rank p-value
K2 EDTA 30 Days 18 802 2.20% 18 226 7.38% < 0.0001
90 Days 28 792 3.41% 33 211 13.52% < 0.0001
Lithium Heparin 30 Days 17 802 2.08% 19 247 7.14% < 0.0001
Separator 90 Days 29 790 3.54% 35 231 13.16% < 0.0001
Serum Separator 30 Days 16 791 1.98% 14 206 6.36% 0.0006
90 Days 27 780 3.35% 28 192 12.73% < 0.0001
ACM = all cause mortality
a Censored = subject has not experienced MACE at the indicated follow-up time point.

Follow-up Likelihood
Tube Type Time Point n Hazard Ratio 95% CI Ratio p-value
K2 EDTA 30 Days 1064 3.45 1.79, 6.68 0.0003
90 Days 1064 4.17 2.52, 6.94 < 0.0001
Lithium Heparin 30 Days 1085 3.53 1.83, 6.86 0.0002
Separator 90 Days 1085 3.91 2.39, 6.44 < 0.0001
Serum Separator 30 Days 1027 3.28 1.58, 6.73 0.0018
90 Days 1027 3.98 2.34, 6.79 < 0.0001
CI = Confidence Interval
The 30-day and 90-day prognosis (Kaplan-Meier analysis) and hazard ratios (Cox regression) for the overall 99th percentile cutoff (26.2 ng/L) are summarized in
the tables below.
≤ Cutoff > Cutoff
No MACE/ACM No MACE/ACM
Tube Type Time Point MACE/ACM (Censoreda) Proportion MACE/ACM (Censoreda) Proportion Log-Rank p-value
K2 EDTA 30 Days 19 802 2.31% 17 226 7.00% 0.0004
90 Days 30 791 3.65% 31 212 12.76% < 0.0001
Lithium Heparin 30 Days 17 803 2.07% 19 246 7.17% < 0.0001
Separator 90 Days 30 790 3.66% 34 231 12.83% < 0.0001
Serum Separator 30 Days 17 796 2.09% 13 201 6.07% 0.0020
90 Days 29 784 3.57% 26 188 12.15% < 0.0001
ACM = all cause mortality
a Censored = subject has not experienced MACE at the indicated follow-up time point.

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 Follow-up Likelihood 22. Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA focused
Tube Type Time Point n Hazard Ratio 95% CI Ratio p-value update of the guideline for the management of patients with
unstable angina/non–ST-elevation myocardial infarction (updating
K2 EDTA 30 Days 1064 3.09 1.59, 5.95 0.0011
the 2007 guideline and replacing the 2011 focused update). JACC
90 Days 1064 3.65 2.21, 6.05 < 0.0001 2012;60(7):645-681.
Lithium Heparin 30 Days 1085 3.54 1.84, 6.87 0.0002 23. de Lemos JA, Drazner MH, Omland T, et al. Association of troponin
Separator 90 Days 1085 3.68 2.25, 6.05 < 0.0001 T detected with a highly sensitive assay and cardiac structure and
Serum Separator 30 Days 1027 2.95 1.41, 6.05 0.0050 mortality risk in the general population. JAMA 2010;304(22):2503-
2512.
90 Days 1027 3.55 2.08, 6.03 < 0.0001
24. deFilippi CR, de Lemos JA, Christenson RH, et al. Association of
CI = Confidence Interval serial measures of cardiac troponin T using a sensitive assay with
incident heart failure and cardiovascular mortality in older adults.
ll
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Approved Guideline—Second Edition. CLSI Document EP17-A2. Revised October 2020.
Wayne, PA: CLSI; 2012. ©2019, 2020 Abbott Laboratories

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