High-Sensitivity Troponin I (TnIH)

Current Revision and Datea Rev. 10, 2024-08

Product Name Atellica IM High‑Sensitivity Troponin I (TnIH) 10997840

(100 tests)

10997841
(500 tests)

Abbreviated Product Name Atellica IM TnIH

Test Name/ID TnIH

Systems Atellica IM Analyzer

Materials Required but Not Provided Atellica IM APW3 10998580

Optional Materials Atellica IM Multi‑Diluent 11 10995642

(2‑pack)

Atellica IM TnIH MCM 10997842

Specimen Types Serum, lithium-heparin plasma

Sample Volume 100 µL

Measuring Interval 2.50–25,000.00 pg/mL (ng/L)

a A vertical bar in the page margin indicates technical content that differs from the previous version.

Intended Use
The Atellica® IM High‑Sensitivity Troponin I (TnIH) assay is for in vitro diagnostic use in the
quantitative measurement of cardiac troponin I in human serum or plasma (lithium heparin)
using the Atellica® IM Analyzer. The assay can be used to aid in the detection of myocardial
injury and in the diagnosis of acute myocardial infarction (AMI).
The Atellica IM TnIH assay can be used in the detection of myocardial injury and can aid in risk
stratification for 30-, 90-, and 365-day all-cause mortality (ACM) and major adverse cardiac
events (MACE) in patients presenting with signs and symptoms suggestive of acute coronary
syndrome (ACS). MACE consists of myocardial infarction, urgent revascularization, cardiac
death, or heart failure hospitalization.

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Summary and Explanation

Troponin I (TnI) exists in 3 distinct isoforms: cardiac muscle, slow-twitch skeletal muscle, and
fast-twitch skeletal muscle.1 Each isoform is encoded by a distinct gene, each with a unique
amino acid sequence, leading to an approximately 40% dissimilarity between cardiac
troponin I (cTnI) and the two skeletal muscle isoforms.1–4
cTnI is an inhibitory protein of the troponin-tropomyosin complex. cTnI is the only TnI isotype
present in the myocardium and is not expressed during any developmental stage in skeletal
muscle.2,5,6 cTnI has a molecular weight of 24,000 daltons.7
The cardiac form of TnI is further unique in that it has 31 additional amino acid residues on its
N-terminus, not present in the skeletal forms, which allows for specific monoclonal antibody
development.7 The cardiac specificity of this isoform improves the accuracy of detection of
myocardial injury in patients with acute or chronic skeletal muscle injury; this is the basis for
its selection as a cardiac marker in the detection of myocardial injury and consequently, in the
diagnosis of AMI.1,2,4,5,7-9
The 2018 Fourth Universal Definition of Myocardial Infarction Consensus Document provides
definitions to differentiate myocardial injury from myocardial infarction. According to the
consensus document, myocardial injury is defined as an elevation in cardiac troponin (cTn)
above the 99th percentile upper reference limit (URL). The myocardial injury is acute if there is
a rising and/or falling pattern of cTn values, or chronic in the setting of persistently, but not
changing, elevated cTn levels.9
Acute myocardial infarction is defined as an acute myocardial injury with clinical evidence of
myocardial ischemia and with the detection of a rising and/or falling pattern of cTn values,
with at least one value above the 99th percentile URL and at least one of the following:9
• Symptoms of myocardial ischemia.
• New ischemic ECG changes.
• Development of pathological Q waves.
• Imaging evidence of new loss of viable myocardium or new regional wall motion
abnormality in a pattern consistent with an ischemic etiology.
• Identification of an acute coronary atherothrombosis by angiography or autopsy (not for
type 2 or 3 MIs).
The 2020 European Society of Cardiology (ESC) guidelines for the management of suspected
non‑ST‑segment elevation acute coronary syndrome (NSTE‑ACS) have proposed the use of
shorter serial sampling time intervals (0–1 hour [h] and 0–2 h). This type of approach allows
rule-out of myocardial injury, as well as rule-in of myocardial injury which is highly suggestive
of non-ST-segment elevation myocardial infarction (NSTEMI).10 A shortened strategy requires a
high-sensitivity cTn assay that employs validated rule-out and rule-in algorithms using assay-
specific cut-offs and changes over time.10 These algorithms may help facilitate early discharge
and outpatient management during triage of suspected NSTE‑ACS patients.
In patients presenting with signs and symptoms of ACS, elevated cTn levels indicative of
myocardial injury (including in those with stable coronary artery disease, chronic kidney
disease, and heart failure) provide useful prognostic information relative to the short and long-
term risk of cardiovascular death and MACE.11-14 It has been reported that elevated cTn may be
associated with adverse prognosis (e.g., death and MACE) even in the general population.15-17
The assessment of prognosis can be useful in identifying patients most likely to benefit from
therapeutic interventions or lifestyle changes.11,18-23

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Definition of a High-Sensitivity Assay

The International Federation of Clinical Chemistry (IFCC) Task Force on Clinical Applications of
Cardiac Bio-Markers defines a cTn assay as a high-sensitivity assay if it meets the following
criteria:24,25
• Total imprecision (CV) at the 99th percentile value should be at or below 10%.
• At least 50% of measurable concentrations should be attainable above the limit of
detection (LoD) for healthy males and healthy females, separately.
cTn values must be used in the context of the patient clinical presentation. Serial sampling is
recommended to detect the temporal rise and fall of cTn levels characteristic of AMI. The
demonstration of a temporal rise and fall in cTn, along with clinical assessment, is needed to
distinguish AMI from cTn elevations associated with non-AMI conditions, such as renal failure,
arrhythmias, pulmonary embolism, chronic renal disease, myocarditis, and cardiotoxicity.9,26–29

Principles of the Procedure

The Atellica IM TnIH is a 3-site sandwich immunoassay using direct chemiluminometric
technology. The Solid Phase reagent is magnetic particles conjugated with streptavidin with 2
bound biotinylated capture monoclonal antibodies each recognizing a unique cTnI epitope.
The Lite Reagent comprises a conjugate whose architecture consists of a proprietary
acridinium ester and a recombinant anti-human cTnI sheep Fab covalently attached to bovine
serum albumin (BSA) for chemiluminescent detection.
A direct relationship exists between the amount of cTnI present in the patient sample and the
amount of relative light units (RLUs) detected by the system.

Reagents
Material Description Storage Stabilitya

Atellica IM TnIH ReadyPack® primary reagent pack Unopened at 2–8°C Until expiration date on
Lite Reagent product
8.0 mL/reagent pack
Bovine serum albumin (BSA) conjugated to a Onboard 28 days
recombinant monoclonal (sheep) Fab anti-human cTnI
(~0.2–0.4 µg/mL) labeled with acridinium ester in
HEPES buffer; stabilizers; preservatives
Solid Phase
13.0 mL/reagent pack
Streptavidin-coated magnetic particles (0.45 mg/mL)
with 2 biotinylated (mouse and sheep) monoclonal
anti-troponin I antibodies in buffer; stabilizers;
preservatives

Atellica IM TnIH CAL L Unopened at 2–8°C Until expiration date on

1.0 mL/vial product
HEPES buffer; bovine serum albumin (BSA);
surfactants; preservatives Opened at 2–8°C 4 hours

Opened at ≤ -20°C 30 days; thaw 1 time

Onboard at room 4 hours

temperature

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Material Description Storage Stabilitya

Atellica IM TnIH CAL H Lyophilized at 2–8°C Until expiration date on

1.0 mL/vial; lyophilized product
After reconstitution, human serum; human cTnI;
preservatives Reconstituted at 2–8°C 4 hours

Reconstituted at ≤ -20°C 30 days; thaw 1 time

Onboard at room 4 hours

temperature

Atellica IM APW3 ReadyPack ancillary reagent packb Unopened at 2–8°C Until expiration date on
25.0 mL/pack product
Phosphate-buffered saline; sodium azide (< 0.1%);
surfactant Onboard 28 days

Atellica IM Multi‑Diluent 11 ReadyPack ancillary Unopened at 2–8°C Until expiration date on

reagent packc product
5.0 mL/pack
Tris buffer; goat serum; protein stabilizers; Onboard 28 days
preservatives
a Refer to Storage and Stability.
b Refer to Materials Required but Not Provided.
c Refer to Optional Materials.

Warnings and Precautions

For in vitro diagnostic use.
For Professional Use.

CAUTION
Federal (USA) law restricts this device to sale by or on the order of a licensed healthcare
professional.

Safety data sheets (SDS) available on siemens-healthineers.com.

The summary of safety and performance for this in vitro diagnostic medical device is available
to the public in the European database on medical devices (EUDAMED) when this database is
available and the information has been uploaded by the Notified Body. The web address of the
EUDAMED public website is: https://ec.europa.eu/tools/eudamed.

Warning! Potential Biohazard

Contains human source material.
No known test method can ensure that products derived from human source materials will not
transmit infection. These materials should be handled using good laboratory practices and
universal precautions.30‑32

CAUTION
This device contains material of animal origin and should be handled as a potential carrier and
transmitter of disease.

Contains sodium azide as a preservative. Sodium azide can react with copper or lead plumbing
to form explosive metal azides. On disposal, flush reagents with a large volume of water to
prevent buildup of azides. Disposal into drain systems must be in compliance with prevailing
regulatory requirements.

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Dispose of hazardous or biologically contaminated materials according to the practices of your

institution. Discard all materials in a safe and acceptable manner and in compliance with
prevailing regulatory requirements.
Note For information about reagent preparation, refer to Preparing the Reagents in the
Procedure section.
Note For information about calibrator preparation, refer to Preparing the Calibrators.

Storage and Stability

Store reagents in an upright position. Protect the product from heat and light sources.
Unopened reagents are stable until the expiration date on the product when stored at 2–8°C.
Store Atellica IM TnIH CAL L in an upright position. Unopened calibrator is stable until the
expiration date on the product when stored at 2–8°C. Opened calibrator is stable for 4 hours at
2–8°C. Freeze opened product at ≤ -20°C for up to 30 days; thaw 1 time. Calibrators are stable
for 4 hours at room temperature.
Store Atellica IM TnIH CAL H in an upright position. Lyophilized calibrator is stable until the
expiration date on the product when stored at 2–8°C. Reconstituted calibrator is stable for
4 hours at 2–8°C. Freeze reconstituted product at ≤ -20°C for up to 30 days; thaw 1 time.
Reconstituted calibrators are stable for 4 hours at room temperature.
Store Atellica IM APW3 in an upright position. Unopened Atellica IM APW3 is stable until the
expiration date on the product when stored at 2–8°C.
Store Atellica IM Multi‑Diluent 11 in an upright position. Unopened Atellica IM Multi‑Diluent 11
is stable until the expiration date on the product when stored at 2–8°C.
Do not use products beyond the expiration date printed on the product labeling.

Onboard Stability
Reagents are stable onboard the system for 28 days. Discard reagents at the end of the
onboard stability interval.
Atellica IM APW3 is stable onboard the system for 28 days.
Atellica IM Multi‑Diluent 11 is stable onboard the system for 28 days.
Do not use products beyond the expiration date printed on the product labeling.

Specimen Collection and Handling

Serum and plasma (lithium heparin) are the recommended sample types for this assay.

Collecting the Specimen

• Observe universal precautions when collecting specimens. Handle all specimens as if they
are capable of transmitting disease.32
• Follow recommended procedures for collection of diagnostic blood specimens by
venipuncture.33
• Follow the instructions provided with your specimen collection device for use and
processing.34
• Allow blood specimens to clot completely before centrifugation.35
• Keep tubes capped at all times.35
• The use of a single sample type (either lithium-heparin plasma or serum) is recommended
for cTnI analysis when collecting serial samples from the same patient.

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• For serum specimens, complete clot formation should take place before centrifugation.
Serum should be physically separated from cells as soon as possible from the time of
collection.35
• Samples must be free of fibrin or other particulate matter. The presence of fibrin, red blood
cells, or suspended particles may lead to inaccurate results. Serum samples that contain
suspended fibrin particles or erythrocyte stroma must be re-centrifuged before testing.
• If clotting time is increased due to thrombolytic or anticoagulant therapy, the use of
plasma specimens will allow for faster sample processing and reduce the risk of micro-
clots, fibrin or particulate matter.
• For plasma specimens, avoid transferring white blood cells or platelets from the layer
located just above the red blood cells.
• If a fixed angle rotor is used for centrifugation, care should be taken to avoid re-
suspending cellular material (platelets) upon removal from the centrifuge.

Storing the Specimen

• Samples are stable up to 8 hours when tightly capped and stored at room temperature.
• Samples are stable up to 24 hours when tightly capped and stored at 2–8°C.
• Samples can be frozen at ≤ -20°C for up to 40 days. Do not store in a frost-free freezer.
• Samples can be frozen at ≤ -70°C for up to 1 year.
• Freeze samples only once and mix thoroughly after thawing.

CAUTION
Thoroughly mix thawed samples and centrifuge them before using.35 Collect the supernatant
into a clean vial.

The handling and storage information provided here is based on data or references
maintained by the manufacturer. It is the responsibility of the individual laboratory to use all
available references and/or its own studies when establishing alternate stability criteria to
meet specific needs.

Transporting the Specimen

Ship samples frozen.
Package and label specimens for shipment in compliance with applicable federal and
international regulations covering the transport of clinical specimens and etiological agents.

Preparing the Samples

This assay requires 100 µL of sample for a single determination. This volume does not include
the unusable volume in the sample container or the additional volume required when
performing duplicates or other tests on the same sample. For information about determining
the minimum required volume, refer to the online help.
The sample volume required to perform onboard dilution differs from the sample volume
required to perform a single determination. Refer to Dilutions.
Note Do not use specimens with apparent contamination.
Before placing samples on the system, ensure that samples are free of:
• Bubbles or foam.
• Fibrin or other particulate matter.
Note Remove particulates by centrifugation according to CLSI guidance and the collection
device manufacturer’s recommendations.35

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Note For a complete list of appropriate sample containers, refer to the online help.

Procedure
Materials Provided
The following materials are provided:

Number of
Contents Tests

10997840 1 ReadyPack primary reagent pack containing Atellica IM TnIH Lite Reagent and Solid 100
Phase
Atellica IM TnIH master curve and test definition
1 vial Atellica IM TnIH CAL low calibrator
1 vial Atellica IM TnIH CAL high calibrator
Atellica IM TnIH CAL calibrator lot-specific value sheet

10997841 5 ReadyPack primary reagent packs containing Atellica IM TnIH Lite Reagent and 500
Solid Phase
Atellica IM TnIH master curve and test definition
2 vials Atellica IM TnIH CAL low calibrator
2 vials Atellica IM TnIH CAL high calibrator
Atellica IM TnIH CAL calibrator lot-specific value sheet

Materials Required but Not Provided

The following materials are required to perform this assay, but are not provided:

Description

Atellica IM Analyzera

10998580 Atellica IM APW3 (probe wash) 2 ReadyPack ancillary reagent packs containing 25.0 mL/pack

a Additional system fluids are required to operate the system: Atellica IM Wash, Atellica IM Acid, Atellica IM Base,
and Atellica IM Cleaner. For system fluid instructions for use, refer to the Document Library.

Optional Materials
The following materials may be used to perform this assay, but are not provided:

Description

10995642 Atellica IM Multi‑Diluent 11 (diluent) 2 ReadyPack ancillary reagent packs containing

5.0 mL/pack

10997842 Atellica IM TnIH MCM (master curve 5 x 1.0 mL levels of master curve material
material)

Assay Procedure
The system automatically performs the following steps:
1. Dispenses 100 µL of sample into a cuvette.
2. Dispenses 130 µL of Solid Phase and 80 µL of Lite Reagent, then incubates for 8 minutes at
37°C.
3. Separates, aspirates, then washes the cuvette with Atellica IM Wash.

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4. Dispenses 300 μL each of Atellica IM Acid and Atellica IM Base to initiate the
chemiluminescent reaction.
5. Reports results.

Preparing the Reagents

All reagents are liquid and ready to use. Before loading primary reagent packs onto the system,
mix them by hand and visually inspect the bottom of the reagent pack to ensure that all
particles are resuspended. For information about preparing the reagents for use, refer to the
online help.

Preparing the System

Ensure that the system has sufficient reagent packs loaded in the reagent compartment. The
system automatically mixes reagent packs to maintain homogeneous suspension of the
reagents. For information about loading reagent packs, refer to the online help.
For automated dilutions, ensure that Atellica IM Multi‑Diluent 11 is loaded on the system.

Master Curve Definition

Before initiating calibration on each new lot of reagent, load the assay master curve and test
definition values by scanning the 2D barcodes. For loading instructions, refer to the
online help.

Performing Calibration
For calibration of the Atellica IM TnIH assay, use the calibrators provided with each kit.

Calibration Frequency
Perform a calibration if one or more of the following conditions exist:
• When changing lot numbers of primary reagent packs.
• At the end of the lot calibration interval, for a specified lot of calibrated reagent on the
system.
• At the end of the pack calibration interval, for calibrated reagent packs on the system.
• When indicated by quality control results.
• After major maintenance or service, if indicated by quality control results.
At the end of the onboard stability interval, replace the reagent pack on the system with a new
reagent pack. Recalibration is not required, unless the lot calibration interval is exceeded.

Stability Interval Days

Lot Calibration 47

Pack Calibration 31

Reagent Onboard Stability 28

For information about lot calibration and pack calibration intervals, refer to the online help.
Follow government regulations or accreditation requirements for calibration frequency.
Individual laboratory quality control programs and procedures may require more frequent
calibration.

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Preparing the Calibrators

Low Calibrator
The Atellica IM TnIH CAL L is liquid and ready to use. Gently mix and invert the vials to ensure
homogeneity of the material.

DO NOT ADD WATER TO THE LOW CALIBRATOR.

High Calibrator
Prepare the Atellica IM TnIH CAL H using the following steps:
1. Add 1.00 mL of special reagent water into the vial using a class A volumetric pipet or an
equivalent pipet. Replace cap.
Note For information about special reagent water requirements, refer to the online help.
2. Let the vial stand for 15–20 minutes at room temperature to allow the lyophilized material
to dissolve.
3. Gently mix and invert the vial to ensure homogeneity of the material.
Note For extended storage, aliquot the low and high calibrators into cryovials and seal tightly.
Store material according to stability limits specified in Storage and Stability. Do not store in a
frost-free freezer.
Before using frozen calibrators, allow the material to completely thaw. Gently mix and invert
the vials to ensure homogeneity of the material. Use immediately and discard any remaining
material.
Note Use calibrators within the stability limits specified in Storage and Stability and discard
any remaining material.

Calibration Procedure
The required sample volume for testing depends on several factors. For information about
sample volume requirements, refer to the online help.
Use the following lot‑specific materials to perform calibration:
• For the master curve and assay test definitions, refer to the lot‑specific master curve and
test definition sheet provided with the assay reagents.
• Calibrators provided in an assay kit must only be used with reagents from that assay kit lot.
Do not use calibrators from one assay kit with reagents from a different assay kit lot.
• For the calibrator definitions, refer to the lot‑specific value sheet provided with
the calibrator materials.
• Generate lot‑specific barcode labels to use with the calibrator samples.
For instructions about how to perform the calibration procedure, refer to the online help.

Performing Quality Control

For quality control of the Atellica IM TnIH assay, use an appropriate quality control material of
known analyte concentration with at least 2 levels at least once during each day that samples
are analyzed. For assistance in identifying a quality control material, refer to Atellica® IM
Quality Control Material Supplement available on siemens-healthineers.com.
Additional quality control material can be used at the discretion of the laboratory. Use the
quality control material in accordance with the quality control instructions for use.

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In addition, perform quality control:

• Following a valid calibration
• With use of a new lot of reagent
• When troubleshooting test results that do not match clinical conditions or symptoms
Follow government regulations or accreditation requirements for quality control frequency.
Individual laboratory quality control programs and procedures may require more frequent
quality control testing.
Acceptable performance is achieved when the analyte values obtained are within the expected
control interval for the system, as indicated by the manufacturer of the control material or
within the interval determined by an internal laboratory quality control procedure.
Follow your laboratory’s quality control procedures if the results obtained do not fall within the
acceptable limits. For information about entering quality control definitions, refer to the
system online help.

Taking Corrective Action

If the quality control results do not fall within the assigned values, do not report results.
Perform corrective actions in accordance with established laboratory protocol. For suggested
protocol, refer to the online help.

Results
Calculation of Results
The system determines the result using the calculation scheme described in the online help.
The system reports results in pg/mL (common units) or ng/L (SI units), depending on the units
defined when setting up the assay.
Conversion formula: 1.0 pg/mL (common units) = 1.0 ng/L (SI units)
For information about results outside the specified measuring interval, refer to Measuring
Interval.

Dilutions
The measuring interval for serum and plasma is 2.50–25,000.00 pg/mL (ng/L). For information
about dilution options, refer to the online help.
Patient samples with cTnI levels > 25,000.00 pg/mL (ng/L) can be diluted and retested to
obtain quantitative results. Patient samples with cTnI levels ≤ 25,000.00 pg/mL (ng/L) should
not be diluted.
For automated dilutions, ensure that Atellica IM Multi‑Diluent 11 is loaded in the reagent
compartment. Ensure that sufficient sample volume is available to perform the dilution and
that the appropriate dilution factor is selected when scheduling the test, as indicated in the
table below.
For automatic dilutions, enter a dilution setpoint ≤ 25,000.00 pg/mL (ng/L).

Sample Dilution Sample Volume (µL)

Serum and plasma 1:2 100

Serum and plasma 1:5 60

Interpretation of Results
Results of this assay should always be interpreted in conjunction with the patient’s medical
history, clinical presentation, and other findings.

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Limitations
The following information pertains to limitations of the assay:
• The use of a single sample type (either lithium heparin or serum) is recommended for cTnI
analysis when collecting serial samples from the same patient.
• Values obtained with different assay methods cannot be used interchangeably.
Interpretations using serial measurements should be based on results obtained with the
same assay method. The measured concentration of cTnI in a given specimen can vary
between assays due to differences in assay design and methodology.
• If clotting time is increased due to thrombolytic or anticoagulant therapy, using serum
samples may increase the risk of micro-clots, fibrin, or particulate matter. Lithium-heparin
plasma is the preferred sample type for patients undergoing anticoagulant therapy.
• Samples from patients receiving preparations of mouse monoclonal antibodies for therapy
or diagnosis may contain human anti-mouse antibodies (HAMA). Such samples may show
either falsely elevated or falsely depressed values when tested with this method.36
• Specimens from some individuals with pathologically high gamma globulin levels may
demonstrate depressed cTnI values. This may be due to the presence of cTnI-specific
autoantibodies.37 Additional information may be required for diagnosis.
• Patient samples may contain heterophilic antibodies that could react in immunoassays to
give falsely elevated or depressed results. This assay is designed to minimize interference
from heterophilic antibodies.38,39

Expected Values
A reference interval for apparently healthy adults was established in accordance with CLSI
Document EP28‑A3c40 on the Atellica IM Analyzer.
Serum and lithium-heparin plasma specimens were collected from 2007 apparently healthy
individuals from the United States who ranged in age from 22–91 years of age. Each specimen
was frozen, thawed, and assayed once. The 99th percentile values were determined using the
non-parametric statistical method described in CLSI Document EP28‑A3c.40 Two female
subjects had cTnI values of approximately 300 pg/mL (ng/L) and 5000 pg/mL (ng/L), and were
considered to be outliers. These results were not included in the 99th percentile
determination.
The 99th percentile values determined for lithium-heparin plasma (female, male, and
combined), and for serum (female, male, and combined) are shown in the following table. The
90% confidence intervals demonstrate that there is no statistical basis for using separate 99th
percentile values based on gender or sample type.
The combined gender and the more commonly used sample type of lithium-heparin plasma
were used to determine the overall observed 99th percentile of 45.20 pg/mL (ng/L). In the
IFCC-recommended reporting format (whole numbers), the 99th percentile is 45 pg/mL (ng/L).

99th Percentilea 90% CIb

Sample Type Gender N (pg/mL; ng/L) (pg/mL; ng/L)

Lithium heparin plasma Female 1007 34.11 27.36–66.23

Male 1000 53.48 38.73–80.22

Combined 2007 45.20 33.21–64.30

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99th Percentilea 90% CIb

Sample Type Gender N (pg/mL; ng/L) (pg/mL; ng/L)

Serum Female 1007 38.64 28.58–72.36

Male 994 53.53 33.77–78.03

Combined 2001 45.43 35.47–63.63

a IFCC Task Force on Clinical Applications of Cardiac Bio-Markers recommends that cTn values be reported as
whole numbers.24
b Confidence interval.
As with all in vitro diagnostic assays, each laboratory should establish its own diagnostic cutoff
value, which reflects criteria for AMI diagnosis at their institution and is representative of
specific populations.

Performance Characteristics
Measuring Interval
The Atellica IM TnIH assay provides results from 2.50–25,000.00 pg/mL (ng/L). The lower end
of the measuring interval is defined by the LoQ. Report patient results below the measuring
interval as < 2.50 pg/mL (ng/L). When sample results exceed the measuring interval, refer to
Dilutions.

Specificity
The Atellica IM TnIH assay shows high specificity for cTnI. The following compounds were
added at the concentrations indicated to a serum or lithium-heparin plasma sample with a
known cTnI concentration. Atellica IM TnIH assay results from the spiked samples were
compared with those of unspiked control samples. Percent cross-reactivity was determined in
accordance with CLSI Document EP07‑A241 and is calculated as:
(concentration of spiked sample - concentration of unspiked sample)
% cross-reactivity = x 100
concentration of compound

Amount Cross-reactivity
Cross-reactant (ng/mL) (%)

Cardiac troponin Ta 1000 NDb

Skeletal troponin I 1000 ND

Tropomyosin 1000 ND

Actin 1000 ND

Troponin C 1000 ND

Myosin light chain 1000 ND

Myoglobin 1000 ND

CK-MB 1000 ND
a Human recombinant.
b Not detectable (< 0.01%).
Assay results obtained at individual laboratories may vary from the data presented.

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Detection Capability
Detection capability was determined in accordance with CLSI Document EP17‑A2.42 The assay
is designed to have a limit of detection (LoD) ≤ 1.6 pg/mL (ng/L), and a limit of quantitation
(LoQ) ≤ 3.0 pg/mL (ng/L).
Representative detection capability data are shown below. Assay results obtained at individual
laboratories may vary from the data presented.
The LoB corresponds to the highest measurement result that is likely to be observed for a
blank sample. The LoB of the Atellica IM TnIH assay is 0.50 pg/mL (ng/L).
The LoD corresponds to the lowest concentration of cTnI that can be detected with a
probability of 95%. The LoD for the Atellica IM TnIH assay is 1.60 pg/mL (ng/L).
The observed LoD ranged from 1.13–1.53 pg/mL (ng/L) across 3 reagent lots and 2 matrices
(serum and lithium-heparin plasma).
The LoQ corresponds to the lowest amount of analyte in a sample at which the within-
laboratory precision is 20%. The LoQ of the Atellica IM TnIH assay is 2.50 pg/mL (ng/L).
Report results below the LoQ as < 2.50 pg/mL (ng/L).
The upper cTnI value for a CV of < 10% for the Atellica IM TnIH assay is 6.00 pg/mL (ng/L).
Actual results will vary depending on the study design and on the samples used. Results
obtained at individual laboratories may vary from the data provided.

High-Sensitivity Determination
The Atellica IM TnIH assay meets the IFCC Task Force on Clinical Applications of Cardiac Bio-
Markers' definition of a high-sensitivity cTn assay.24
1. Total imprecision (CV) at the 99th percentile value of 45.20 pg/mL (ng/L) is below 10%.
2. Greater than 50% of measurements from both male and female subjects in a healthy
population (AACC Universal Sample Bank) were above the LoD of 1.60 pg/mL (ng/L).43,44

Clinical Performance
A prospective study was performed to assess diagnostic accuracy for subjects in both serum
and lithium-heparin plasma sample types. Specimens were collected at 29 emergency
departments across the United States, from subjects presenting with symptoms consistent
with acute coronary syndrome (ACS).
All subject diagnoses were adjudicated by panels of certified cardiologists and emergency
physicians according to the Third Universal Definition Of Myocardial Infarction - consensus
guideline45 endorsed by the European Society of Cardiology (ESC), the American College of
Cardiology Foundation (ACCF), the American Heart Association (AHA), and the World Heart
Federation (WHF). The observed AMI prevalence in this study was 13%.
The results from the study are presented using serial time intervals analyzed according to:
• the time from baseline blood draw
• the time of presentation to the emergency department
The cutoff value, and sensitivity and specificity information should only be used as a guide
when determining the appropriate cutoff value for your institution. Because sensitivity and
specificity are influenced by the cutoff value, laboratories should select a cutoff value based on
their specific sensitivity and specificity requirements.

Analysis 1: Time from baseline blood draw

The results were analyzed using serial time intervals subsequent to a baseline blood draw
collected for the study during the emergency department visit. The baseline blood draw for
the study was collected 45 minutes (median) after the emergency department blood draw.

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TnIH Atellica IM Analyzer

Note The initial emergency department blood draw occurred at a median of 44 minutes
(interquartile range of 26–70 minutes) following patient admission.
The pooled gender results that are summarized in table 1 are based on time from the study
baseline blood draw, calculated using the overall 99th percentile of 45.20 pg/mL (ng/L).
Gender-specific data are presented in tables 2 and 3:
Table 1: Pooled gender results based on time from study baseline blood draw

Positive Predictive Negative Predictive

Sensitivity Specificity Value Value
Time-Point
(hours) Na % 95% CIb N % 95% CI N % 95% CI N % 95% CI

Lithium-heparin plasma

Baseline 299 84.3 79.7–88.0 2003 90.8 89.4–92.0 437 57.7 53.0–62.2 1865 97.5 96.7–98.1

≥ 0.75– < 1.5 255 90.6 86.4–93.6 1871 90.8 89.4–92.0 403 57.3 52.4–62.1 1723 98.6 97.9–99.1

≥ 1.5– < 2.5 138 92.8 87.2–96.0 1042 89.8 87.8–91.5 234 54.7 48.3–61.0 946 98.9 98.1–99.4

≥ 2.5– < 3.5 118 93.2 87.2–96.5 682 90.0 87.6–92.1 178 61.8 54.5–68.6 622 98.7 97.5–99.3

≥ 3.5– < 9 251 94.0 90.4–96.3 1120 86.9 84.8–88.7 383 61.6 56.7–66.4 988 98.5 97.5–99.1

≥ 9–24 224 92.4 88.2–95.2 885 86.6 84.1–88.6 326 63.5 58.1–68.5 783 97.8 96.6–98.6

Serum

Baseline 294 84.7 80.1–88.4 2035 91.0 89.7–92.2 432 57.6 52.9–62.2 1897 97.6 96.8–98.2

≥ 0.75– < 1.5 252 88.1 83.5–91.5 1881 91.1 89.8–92.3 389 57.1 52.1–61.9 1744 98.3 97.6–98.8

≥ 1.5– < 2.5 134 91.8 85.9–95.4 1048 90.0 88.0–91.7 228 53.9 47.5–60.3 954 98.8 97.9–99.4

≥ 2.5– < 3.5 113 92.0 85.6–95.8 680 90.4 88.0–92.4 169 61.5 54.0–68.5 624 98.6 97.3–99.2

≥ 3.5– < 9 245 94.7 91.1–96.9 1124 87.7 85.7–89.5 370 62.7 57.7–67.5 999 98.7 97.8–99.2

≥ 9–24 225 91.6 87.2–94.5 895 87.4 85.0–89.4 319 64.6 59.2–69.6 801 97.6 96.3–98.5

a Number of samples.
b Confidence interval.

Results for females based on time from study baseline blood draw, calculated using the
female-specific 99th percentile values of 34.11 pg/mL (ng/L) for plasma and
38.64 pg/mL (ng/L) for serum are summarized in table 2.
Table 2: Results for females based on time from study baseline blood draw

Positive Predictive Negative Predictive

Sensitivity Specificity Value Value
Time-Point
(hours) Na % 95% CIb N % 95% CI N % 95% CI N % 95% CI

Lithium-heparin plasma

Baseline 106 87.7 80.1–92.7 903 91.4 89.4–93.0 171 54.4 46.9–61.7 838 98.4 97.4–99.1

≥ 0.75– < 1.5 92 90.2 82.4–94.8 835 91.5 89.4–93.2 154 53.9 46.0–61.6 773 98.8 97.8–99.4

≥ 1.5– < 2.5 43 97.7 87.9–99.6 435 91.7 88.8–94.0 78 53.8 42.9–64.5 400 99.8 98.6–100.0

≥ 2.5– < 3.5 41 95.1 83.9–98.7 318 87.7 83.7–90.9 78 50.0 39.2–60.8 281 99.3 97.4–99.8

≥ 3.5– < 9 92 94.6 87.9–97.7 468 88.2 85.0–90.9 142 61.3 53.1–68.9 418 98.8 97.2–99.5

≥ 9–24 77 93.5 85.7–97.2 360 86.1 82.2–89.3 122 59.0 50.1–67.3 315 98.4 96.3–99.3

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Positive Predictive Negative Predictive

Sensitivity Specificity Value Value
Time-Point
(hours) Na % 95% CIb N % 95% CI N % 95% CI N % 95% CI

Serum

Baseline 101 86.1 78.1–91.6 911 91.7 89.7–93.3 163 53.4 45.7–60.9 849 98.4 97.3–99.0

≥ 0.75– < 1.5 88 88.6 80.3–93.7 830 91.7 89.6–93.4 147 53.1 45.0–60.9 771 98.7 97.6–99.3

≥ 1.5– < 2.5 40 95.0 83.5–98.6 431 92.3 89.4–94.5 71 53.5 42.0–64.6 400 99.5 98.2–99.9

≥ 2.5– < 3.5 38 94.7 82.7–98.5 322 88.8 84.9–91.8 72 50.0 38.7–61.3 288 99.3 97.5–99.8

≥ 3.5– < 9 87 95.4 88.8–98.2 476 89.1 86.0–91.6 135 61.5 53.1–69.3 428 99.1 97.6–99.6

≥ 9–24 76 93.4 85.5–97.2 360 88.6 84.9–91.5 112 63.4 54.2–71.7 324 98.5 96.4–99.3

a Number of samples.
b Confidence interval.

Results for males based on time from study baseline blood draw, calculated using the male-
specific 99th percentile values of 53.48 pg/mL (ng/L) for plasma and 53.53 pg/mL (ng/L) for
serum are summarized in table 3.
Table 3: Results for males based on time from study baseline blood draw

Positive Predictive Negative Predictive

Sensitivity Specificity Value Value
Time-Point
(hours) Na % 95% CIb N % 95% CI N % 95% CI N % 95% CI

Lithium-heparin plasma

Baseline 193 81.9 75.8–86.7 1100 91.1 89.3–92.6 256 61.7 55.6–67.5 1037 96.6 95.3–97.6

≥ 0.75– < 1.5 163 89.0 83.2–92.9 1036 91.0 89.1–92.6 238 60.9 54.6–66.9 961 98.1 97.1–98.8

≥ 1.5– < 2.5 95 88.4 80.4–93.4 607 89.8 87.1–92.0 146 57.5 49.4–65.3 556 98.0 96.5–98.9

≥ 2.5– < 3.5 77 90.9 82.4–95.5 364 91.2 87.9–93.7 102 68.6 59.1–76.8 339 97.9 95.8–99.0

≥ 3.5– < 9 159 93.1 88.0–96.1 652 86.8 84.0–89.2 234 63.2 56.9–69.2 577 98.1 96.6–98.9

≥ 9–24 147 91.2 85.5–94.8 525 87.4 84.3–90.0 200 67.0 60.2–73.1 472 97.2 95.3–98.4

Serum

Baseline 193 82.9 77.0–87.6 1124 91.2 89.4–92.7 259 61.8 55.7–67.5 1058 96.9 95.7–97.8

≥ 0.75– < 1.5 164 87.2 81.2–91.5 1051 91.2 89.4–92.8 235 60.9 54.5–66.9 980 97.9 96.7–98.6

≥ 1.5– < 2.5 94 87.2 79.0–92.5 617 89.8 87.1–91.9 145 56.6 48.4–64.3 566 97.9 96.3–98.8

≥ 2.5– < 3.5 75 90.7 82.0–95.4 358 91.3 88.0–93.8 99 68.7 59.0–77.0 334 97.9 95.7–99.0

≥ 3.5– < 9 158 93.0 88.0–96.1 648 87.8 85.1–90.1 226 65.0 58.6–71.0 580 98.1 96.6–98.9

≥ 9–24 149 89.9 84.1–93.8 535 87.9 84.8–90.4 199 67.3 60.5–73.5 485 96.9 95.0–98.1

a Number of samples.
b Confidence interval.

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Analysis 2: Time of presentation to the emergency department

The pooled gender results based on time of presentation to the emergency department,
calculated using the overall 99th percentile of 45.20 pg/mL (ng/L), are summarized in table 4.
Gender-specific data are presented in tables 5 and 6.
Table 4: Pooled gender results based on time from presentation to the emergency department

Positive Predictive Negative Predictive

Sensitivity Specificity Value Value
Time-Point
(hours) Na % 95% CIb N % 95% CI N % 95% CI N % 95% CI

Lithium-heparin plasma

0– < 1.5 145 77.2 69.8–83.3 964 91.9 90.0–93.5 190 58.9 51.8–65.7 919 96.4 95.0–97.4

≥ 1.5– < 2.5 240 90.0 85.6–93.2 1625 90.6 89.1–92.0 368 58.7 53.6–63.6 1497 98.4 97.6–98.9

≥ 2.5– < 3.5 201 92.0 87.5–95.0 1369 90.6 88.9–92.0 314 58.9 53.4–64.2 1256 98.7 97.9–99.2

≥ 3.5– < 4.5 149 92.6 87.3–95.8 1080 90.8 89.0–92.4 237 58.2 51.9–64.3 992 98.9 98.0–99.4

≥ 4.5– < 6 66 97.0 89.6–99.2 461 89.2 86.0–91.7 114 56.1 47.0–64.9 413 99.5 98.3–99.9

≥ 6– < 9 193 92.7 88.2–95.6 905 87.6 85.3–89.6 291 61.5 55.8–66.9 807 98.3 97.1–99.0

≥ 9– < 24 215 94.0 89.9–96.4 835 86.6 84.1–88.7 314 64.3 58.9–69.4 736 98.2 97.0–99.0

≥ 24 62 93.5 84.6–97.5 253 83.4 78.3–87.5 100 58.0 48.2–67.2 215 98.1 95.3–99.3

Serum

0– < 1.5 140 78.6 71.1–84.6 980 92.2 90.4–93.8 186 59.1 52.0–65.9 934 96.8 95.5–97.7

≥ 1.5– < 2.5 239 87.9 83.1–91.4 1646 91.0 89.5–92.3 358 58.7 53.5–63.6 1527 98.1 97.3–98.7

≥ 2.5– < 3.5 195 90.8 85.9–94.1 1384 90.8 89.1–92.2 305 58.0 52.4–63.4 1274 98.6 97.8–99.1

≥ 3.5– < 4.5 147 91.2 85.5–94.8 1083 91.0 89.1–92.5 232 57.8 51.3–63.9 998 98.7 97.8–99.2

≥ 4.5– < 6 64 96.9 89.3–99.1 454 89.6 86.5–92.1 109 56.9 47.5–65.8 409 99.5 98.2–99.9

≥ 6– < 9 185 93.5 89.0–96.3 904 88.7 86.5–90.6 275 62.9 57.1–68.4 814 98.5 97.4–99.2

≥ 9– < 24 213 93.9 89.8–96.4 841 86.7 84.2–88.8 312 64.1 58.6–69.2 742 98.2 97.0–99.0

≥ 24 63 90.5 80.7–95.6 255 85.5 80.6–89.3 94 60.6 50.5–69.9 224 97.3 94.3–98.8

a Number of samples.
b Confidence interval.

Results for females based on time of presentation to the emergency department, calculated
using the female-specific 99th percentile of 34.11 pg/mL (ng/L) for plasma and
38.64 pg/mL (ng/L) for serum are summarized in table 5.
Table 5: Results for females based on time of presentation to the emergency department

Positive Predictive Negative Predictive

Sensitivity Specificity Value Value
Time-Point
(hours) Na % 95% CIb N % 95% CI N % 95% CI N % 95% CI

Lithium-heparin plasma

0– < 1.5 45 84.4 71.2–92.3 401 93.5 90.7–95.5 64 59.4 47.1–70.5 382 98.2 96.3–99.1

≥ 1.5– < 2.5 79 89.9 81.3–94.8 720 91.8 89.6–93.6 130 54.6 46.0–62.9 669 98.8 97.7–99.4

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Positive Predictive Negative Predictive

Sensitivity Specificity Value Value
Time-Point
(hours) Na % 95% CIb N % 95% CI N % 95% CI N % 95% CI

≥ 2.5– < 3.5 73 94.5 86.7–97.8 622 91.6 89.2–93.6 121 57.0 48.1–65.5 574 99.3 98.2–99.7

≥ 3.5– < 4.5 50 94.0 83.8–97.9 488 89.5 86.5–92.0 98 48.0 38.3–57.7 440 99.3 98.0–99.8

≥ 4.5– < 6 26 96.2 81.1–99.3 239 87.0 82.2–90.7 56 44.6 32.4–57.6 209 99.5 97.3–99.9

≥ 6– < 9 69 94.2 86.0–97.7 374 88.0 84.3–90.9 110 59.1 49.7–67.8 333 98.8 97.0–99.5

≥ 9– < 24 74 94.6 86.9–97.9 342 87.4 83.5–90.5 113 61.9 52.7–70.4 303 98.7 96.7–99.5

≥ 24 27 96.3 81.7–99.3 110 80.9 72.6–87.2 47 55.3 41.2–68.6 90 98.9 94.0–99.8

Serum

0– < 1.5 42 81.0 66.7–90.0 407 93.6 90.8–95.6 60 56.7 44.1–68.4 389 97.9 96.0–99.0

≥ 1.5– < 2.5 77 89.6 80.8–94.6 721 92.0 89.7–93.7 127 54.3 45.7–62.7 671 98.8 97.7–99.4

≥ 2.5– < 3.5 67 92.5 83.7–96.8 620 92.4 90.1–94.3 109 56.9 47.5–65.8 578 99.1 98.0–99.6

≥ 3.5– < 4.5 48 93.8 83.2–97.9 485 90.3 87.4–92.6 92 48.9 38.9–59.0 441 99.3 98.0–99.8

≥ 4.5– < 6 26 96.2 81.1–99.3 237 87.8 83.0–91.3 54 46.3 33.7–59.4 209 99.5 97.3–99.9

≥ 6– < 9 63 95.2 86.9–98.4 378 88.6 85.0–91.4 103 58.3 48.6–67.3 338 99.1 97.4–99.7

≥ 9– < 24 73 94.5 86.7–97.8 342 89.5 85.8–92.3 105 65.7 56.2–74.1 310 98.7 96.7–99.5

≥ 24 26 96.2 81.1–99.3 111 82.9 74.8–88.8 44 56.8 42.2–70.3 93 98.9 94.2–99.8

a Number of samples.
b Confidence interval.

Results for males based on time of presentation to the emergency department, calculated
using the male-specific 99th percentile of 53.48 pg/mL (ng/L) for plasma and
53.53 pg/mL (ng/L) for serum, are summarized in table 6.
Table 6: Results for males based on time of presentation to the emergency department

Positive Predictive Negative Predictive

Sensitivity Specificity Value Value
Time-Point
(hours) Na % 95% CIb N % 95% CI N % 95% CI N % 95% CI

Lithium-heparin plasma

0– < 1.5 100 75.0 65.7–82.5 563 91.5 88.9–93.5 123 61.0 52.1–69.1 540 95.4 93.3–96.8

≥ 1.5– < 2.5 161 87.6 81.6–91.8 905 91.2 89.1–92.8 221 63.8 57.3–69.9 845 97.6 96.4–98.5

≥ 2.5– < 3.5 128 89.8 83.4–94.0 747 90.0 87.6–91.9 190 60.5 53.4–67.2 685 98.1 96.8–98.9

≥ 3.5– < 4.5 99 90.9 83.6–95.1 592 92.2 89.8–94.1 136 66.2 57.9–73.6 555 98.4 96.9–99.1

≥ 4.5– < 6 40 92.5 80.1–97.4 222 90.5 86.0–93.7 58 63.8 50.9–74.9 204 98.5 95.8–99.5

≥ 6– < 9 124 91.1 84.8–95.0 531 88.5 85.5–91.0 174 64.9 57.6–71.6 481 97.7 96.0–98.7

≥ 9– < 24 141 93.6 88.3–96.6 493 85.6 82.2–88.4 203 65.0 58.2–71.3 431 97.9 96.1–98.9

≥ 24 35 91.4 77.6–97.0 143 88.1 81.8–92.4 49 65.3 51.3–77.1 129 97.7 93.4–99.2

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Positive Predictive Negative Predictive

Sensitivity Specificity Value Value
Time-Point
(hours) Na % 95% CIb N % 95% CI N % 95% CI N % 95% CI

Serum

0– < 1.5 98 77.6 68.3–84.7 573 91.6 89.1–93.6 124 61.3 52.5–69.4 547 96.0 94.0–97.3

≥ 1.5– < 2.5 162 86.4 80.3–90.9 925 91.5 89.5–93.1 219 63.9 57.4–70.0 868 97.5 96.2–98.3

≥ 2.5– < 3.5 128 87.5 80.7–92.2 764 89.9 87.6–91.9 189 59.3 52.1–66.0 703 97.7 96.3–98.6

≥ 3.5– < 4.5 99 88.9 81.2–93.7 598 92.5 90.1–94.3 133 66.2 57.8–73.7 564 98.0 96.5–98.9

≥ 4.5– < 6 38 94.7 82.7–98.5 217 90.8 86.2–94.0 56 64.3 51.2–75.5 199 99.0 96.4–99.7

≥ 6– < 9 122 91.0 84.6–94.9 526 89.9 87.1–92.2 164 67.7 60.2–74.4 484 97.7 96.0–98.7

≥ 9– < 24 140 93.6 88.2–96.6 499 85.6 82.2–88.4 203 64.5 57.7–70.8 436 97.9 96.1–98.9

≥ 24 37 86.5 72.0–94.1 144 88.9 82.7–93.0 48 66.7 52.5–78.3 133 96.2 91.5–98.4

a Number of samples.
b Confidence interval.

Elevated cTnI Values in Patients Without AMI

There are conditions other than AMI that are known to cause myocardial injury and elevated
cTnI values.9,26–29,46‑53
The Atellica IM TnIH clinical trial enrolled all patients presenting to the emergency department
with symptoms consistent with ACS. Some of these patients had an acute or chronic condition
other than AMI.
In the clinical trial, 11% of patients without an AMI diagnosis had at least 1 Atellica IM TnIH
test result above the 99th percentile (> 45.20 pg/mL (ng/L)) on 1 or more serial draws. 88% of
these patients were found to have 1 or more of the following conditions:
Cardiac conditions
• Angina
• Atrial fibrillation
• Cardiomyopathy
• Coronary artery disease
• Heart failure
• Hypertensive urgency
• Pericarditis
• Recent cardiac intervention
• Severe valvular heart disease
• Tachycardia
Non-cardiac conditions
• Chronic lung disease
• Cardiac contusion related to a traumatic injury
• Renal failure
• Pneumonia
• Pulmonary embolism

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• Shock
• Systemic sclerosis

AMI Rule-Out and Rule-In Diagnostic Algorithms

The 2020 ESC guidelines for the management of NSTE‑ACS have recommended the use of
shortened 0–1 hour (h) or 0–2 h serial sampling time intervals for assessment of rule-out or
rule-in of suspected NSTEMI.10 A shortened strategy requires a high-sensitivity cTn assay that
employs validated rule-out and rule-in algorithms using assay-specific cut-offs and changes
over time, and must be used along with ECG and clinical assessment.10 The 0 h/1 h and 0 h/2 h
algorithms were developed in large derivation cohorts and then confirmed in large
independent validation cohorts.

The 0 h/1 h and 0 h/2 h algorithms to triage patients as rule-out or rule-in of suspected NSTEMI
were derived and validated on the ADVIA Centaur® system using the Advantageous Predictors
of Acute Coronary Syndrome Evaluation (APACE) cohort and published in the 2020 ESC
guidelines.10,54 The algorithms were subsequently validated on the Atellica IM Analyzer.55–57
The algorithms presented in table 7 are not intended to be used with cTn results generated
with different assays or systems. Confounders affecting cTn concentration in suspected
NSTE‑ACS patients like age, renal function, time from chest pain to emergency department
presentation, and sex are not considered in these algorithms.
Table 7: 0 h/1 h and 0 h/2 h algorithms derived on the ADVIA Centaur system and validated on the
Atellica IM Analyzer for AMI rule-out and rule-in of suspected NSTEMI

Algorithm Rule-Out Observe Rule-In

cTnI 0 h/1 h 0 h < 3 ng/La or 0 h < 6 ng/L Other 0 h > 120 ng/L
(pg/mL; ng/L) and or
Δ 0 h/1 h < 3 ng/L Δ 0 h/1 h ≥ 12 ng/L

cTnI 0 h/2 h 0 h < 3 ng/La or 0 h < 8 ng/L Other 0 h > 120 ng/L
(pg/mL; ng/L) and or
Δ 0 h/2 h < 7 ng/L Δ 0 h/2 h ≥ 20 ng/L
a For chest pain onset > 3 hours

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A separate validation study for the Atellica IM TnIH assay was performed by Siemens
Healthineers to assess the clinical performance of the 0 h/1 h and 0 h/2 h algorithms for a
population of US patients presenting to the emergency department with signs and symptoms
of NSTE-ACS. This study was performed after the exclusion of subjects having an ST-segment
elevation myocardial infarction (STEMI) at study presentation, or NSTEMI subjects with a
history of recent cardiac intervention, recent AMI, end stage renal disease, or traumatic injury.
The performance of the 2 algorithms applied to lithium heparin plasma specimen data
obtained on the Atellica IM TnIH assay is summarized in table 8. Similar results were obtained
from analysis of the serum specimen data.
Table 8: Validation of the performance of the 0 h/1 h and 0 h/2 h algorithms for AMI rule-out and rule-in of
suspected NSTEMI, after exclusions, using the Atellica IM TnIH assay

Algorithm Na Rule-Out (%) Observe (%) Rule-In (%)

0 h/1 h 1817 Ruled-out: 55.6 Observed: 33.7 Ruled-in: 10.6

NPV: 99.7 (CI: 99.1–99.9)b PPV: 75.1 (CI: 68.6–80.7)

Sensitivity: 98.4 (CI: 95.3–99.4) Specificity: 97.1 (CI: 96.1–97.8)

0 h/2 h 995 Ruled-out: 62.1 Observed: 27.3 Ruled-in: 10.7

NPV: 99.8 (CI: 99.1–99.9) PPV: 72.6 (CI: 63.5–80.2)

Sensitivity: 99.0 (CI: 94.6–99.8) Specificity: 96.8 (CI: 95.4–97.7)

a Number of samples tested.
b CI = 95% Confidence Interval

A summary of published literature on the validation of the 0 h/1 h algorithm for the Atellica IM
Analyzer in various populations is presented in table 9. The reagent formulations used on the
Atellica IM Analyzer are the same as those used on the ADVIA Centaur systems. Some rule-out
and rule-in algorithm studies were performed with the ADVIA Centaur system using identical
algorithms to those of the Atellica IM Analyzer. The HIGH-US study presents a reanalysis of the
data presented in table 8 using all NSTEMI subjects, including those with a history of recent
cardiac intervention, recent AMI, end stage renal disease, and traumatic injury. A subset of
these publications include additional performance analyses using the 0 h/2 h algorithm.54,56
Table 9: Published validation studies supporting the 0 h/1 h algorithm for AMI rule-out and rule-in of
suspected NSTEMI using the ADVIA Centaur TNIH assay or the Atellica IM TnIH assay in patients presenting
to the emergency department

Study / Trial Na Region Assay Rule-Out (%) Observe (%) Rule-In (%)

APACE54 b 1755 Europe ADVIA Centaur TNIH assay Ruled-out: 46.0 Observed: 36.0 Ruled-in: 18.0

NPV: 99.7 NSTEMI PPV: 72.5

prevalence: 11.0
Sensitivity: 99.1 Specificity: 94.1

BACC55 1800 Europe Atellica IM TnIH assay Ruled-out: 48.3 Observed: 36.5 Ruled-in: 15.1

NPV: 99.8 NSTEMI PPV: 68.0

prevalence: 7.4
Sensitivity: 99.1 Specificity: 94.4

HIGH-US56 b, c 2113 United Atellica IM TnIH assay Ruled-out: 50.4 Observed: 37.1 Ruled-in: 12.5
States
NPV: 99.7 NSTEMI PPV: 69.4
prevalence: 5.6
Sensitivity: 98.7 Specificity: 95.7

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Study / Trial Na Region Assay Rule-Out (%) Observe (%) Rule-In (%)

High-STEACS57 1920 Europe Atellica IM TnIH assay Ruled-out: 64.5 Observed: 28.6 Ruled-in: 6.9

NPV: 99.0 PPV: 77.6

Sensitivity: 92.2 Specificity: 98.2

RACING-MI58 1370 Europe ADVIA Centaur TNIH assay Ruled-out: 52.4 Observed: 39.1 Ruled-in: 8.5

NPV: 100 NSTEMI PPV: 83.8

prevalence: 3.5
Sensitivity: 100 Specificity: 97.4

Ishii et al.59 754 Japan ADVIA Centaur TNIH assay Ruled-out: 28 Observed: 52 Ruled-in: 28

NPV: 100 NSTEMI PPV: 37.1

prevalence: 0.9
Sensitivity: 100 Specificity: 79.6

a Number of patients enrolled.

b Publications include additional performance analyses using the 0 h/2 h algorithm.
c Blood collection times are presented in the Clinical Performance section above.

Risk Stratification
A study was conducted in which patients presenting to the emergency department with signs
and symptoms suggestive of ACS were followed up for 30-, 90-, and 365‑day progression to
ACM and MACE (consisting of myocardial infarction, urgent revascularization, cardiac death, or
heart failure hospitalization). At each time point, the risk (cumulative incidence) and hazard
ratios were calculated for populations with baseline cTnI levels ≤ or > the 99th percentile value
(overall and gender-specific). For these analyses, baseline blood draw occurred 93 minutes
(median) after presentation to emergency department. Kaplan-Meier curves were generated
to display the absolute risk (cumulative incidence) of ACM and MACE outcomes. Analyses were
performed for all enrolled patients (entire population) and separately for the entire population
excluding those with an adjudicated AMI at presentation. Type 1 and Type 2 myocardial
infarctions were not separated. Analyses were performed separately for both serum and
lithium heparin plasma sample types.
Table 10: ACM and MACE outcomes for all enrolled patients with baseline cTnI levels ≤ or > the overall 99th
percentile value

Baseline ≤ 99th Percentile Baseline > 99th Percentile

(No myocardial injury) (Myocardial injury)

ACM/MACE ACM/MACE
Incidence % Absolute Risk Incidence % Absolute Risk Risk Difference Hazard Ratioa
Nb (N) (95% CI)c, d N (N) (95% CI) (%)a (95% CI)

Lithium heparin plasma

30 1922 54 2.82 452 41 9.09 6.27 3.35

Days (2.16, 3.66) (6.78, 12.14) (2.23, 5.03)

90 1922 114 5.96 452 87 19.34 13.38 3.49

Days (4.98, 7.11) (15.98, 23.30) (2.64, 4.62)

365 1922 257 13.54 452 148 33.16 19.62 2.81

Days (12.08, 15.17) (28.99, 37.75) (2.30, 3.45)

Serum

30 1956 58 2.97 446 41 9.21 6.24 3.22

Days (2.31, 3.83) (6.87, 12.30) (2.16, 4.80)

11208873_EN Rev. 10, 2024-08 21 / 36

TnIH Atellica IM Analyzer

Baseline ≤ 99th Percentile Baseline > 99th Percentile

(No myocardial injury) (Myocardial injury)

ACM/MACE ACM/MACE
Incidence % Absolute Risk Incidence % Absolute Risk Risk Difference Hazard Ratioa
Nb (N) (95% CI)c, d N (N) (95% CI) (%)a (95% CI)

90 1956 119 6.11 446 83 18.70 12.59 3.28

Days (5.13, 7.27) (15.37, 22.65) (2.48, 4.34)

365 1956 266 13.77 446 143 32.48 18.71 2.69

Days (12.31, 15.39) (28.32, 37.09) (2.20, 3.30)

a p values were < 0.0001 when comparing the populations (≤ and > 99th percentile) within each time point.
b Number of patient samples tested.
c Kaplan-Meier estimate of the cumulative incidence of ACM and MACE.
d CI = Confidence Interval.
Kaplan-Meier curves for absolute risk of ACM/MACE (cumulative incidence) are shown in the
figure below for all enrolled patients with baseline cTnI levels ≤ or > the overall 99th percentile
value. Results shown are for lithium heparin plasma samples. Results for serum samples are
comparable (refer to table 10).


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Number at Risk

≤ 99th percentile value 1922 1863 1829 1795 1772 1756 1724 1711 1697 1684 1672 1660 1128

> 99th percentile value 452 410 387 363 352 345 333 326 323 319 309 307 198

22 / 36 11208873_EN Rev. 10, 2024-08

Atellica IM Analyzer TnIH

Table 11: ACM and MACE outcomes for all enrolled patients with baseline cTnI levels ≤ or > the gender-
specific 99th percentile value

Baseline ≤ 99th Percentile Baseline > 99th Percentile

(No myocardial injury) (Myocardial injury)

ACM/MACE ACM/MACE
Incidence % Absolute Risk Incidence % Absolute Risk Risk Difference Hazard Ratioa
N (N) (95% CI)b, c N (N) (95% CI) (%)a (95% CI)

Lithium heparin plasma

30 1931 58 3.01 443 37 8.37 5.36 2.87

Days (2.34, 3.88) (6.14, 11.37) (1.90, 4.33)

90 1931 120 6.24 443 81 18.37 12.13 3.14

Days (5.25, 7.42) (15.06, 22.32) (2.37, 4.16)

365 1931 265 13.91 443 140 31.94 18.03 2.62

Days (12.43, 15.55) (27.80, 36.54) (2.13, 3.21)

Serum

30 1965 60 3.06 437 39 8.94 5.88 3.03

Days (2.39, 3.93) (6.62, 12.04) (2.02, 4.53)

90 1965 122 6.23 437 80 18.40 12.17 3.15

Days (5.25, 7.40) (15.06, 22.37) (2.38, 4.18)

365 1965 271 13.98 437 138 31.92 17.94 2.60

Days (12.51, 15.60) (27.75, 36.55) (2.12, 3.19)

a p values were < 0.0001 when comparing the populations (≤ and > 99th percentile) within each time point.
b Kaplan-Meier estimate of the cumulative incidence of ACM and MACE.
c CI = Confidence Interval.

11208873_EN Rev. 10, 2024-08 23 / 36

TnIH Atellica IM Analyzer

Kaplan-Meier curves for absolute risk of ACM/MACE (cumulative incidence) are shown in the
figure below for all enrolled patients with baseline cTnI levels ≤ or > the gender-specific 99th
percentile value. Results shown are for lithium heparin plasma samples. Results for serum
samples are comparable (refer to table 11).


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Number at Risk

≤ 99th percentile value 1931 1868 1833 1798 1776 1759 1728 1715 1700 1687 1674 1662 1130

> 99th percentile value 443 405 383 360 348 342 329 322 320 316 307 305 196

Tables 12 and 13 present a reanalysis of tables 10 and 11 excluding patients with an

adjudicated AMI at the time of presentation. Increased cTn levels indicative of myocardial
injury provide useful prognostic information relative to the short and long-term risk of
cardiovascular death and MACE, regardless of AMI diagnosis.11-14 Analyses were performed for
absolute risk (cumulative incidence) and hazard ratios of ACM/MACE outcomes associated with
non-AMI myocardial injury.
Table 12: ACM and MACE outcomes for all enrolled patients with baseline cTnI levels ≤ or > the overall 99th
percentile value, excluding patients with an adjudicated AMI at presentation

Baseline ≤ 99th Percentile Baseline > 99th Percentile

(No myocardial injury) (Myocardial injury)

ACM/MACE ACM/MACE
Incidence % Absolute Risk Incidence % Absolute Risk Risk Difference Hazard Ratioa
N (N) (95% CI)b, c N (N) (95% CI) (%)a (95% CI)

Lithium heparin plasma

30 1874 51 2.73 190 16 8.46 5.73 3.21

Days (2.08, 3.57) (5.27, 13.44) (1.83, 5.64)

24 / 36 11208873_EN Rev. 10, 2024-08

Atellica IM Analyzer TnIH

Baseline ≤ 99th Percentile Baseline > 99th Percentile

(No myocardial injury) (Myocardial injury)

ACM/MACE ACM/MACE
Incidence % Absolute Risk Incidence % Absolute Risk Risk Difference Hazard Ratioa
N (N) (95% CI)b, c N (N) (95% CI) (%)a (95% CI)

90 1874 106 5.68 190 40 21.16 15.48 4.03

Days (4.72, 6.83) (15.99, 27.70) (2.80, 5.80)

365 1874 242 13.08 190 75 40.13 27.05 3.64

Days (11.62, 14.70) (33.47, 47.58) (2.81, 4.72)

Serum

30 1909 54 2.84 188 16 8.55 5.71 3.13

Days (2.18, 3.69) (5.33, 13.58) (1.79, 5.47)

90 1909 110 5.79 188 38 20.32 14.53 3.79

Days (4.82, 6.93) (15.22, 26.83) (2.62, 5.48)

365 1909 251 13.31 188 72 38.96 25.65 3.44

Days (11.85, 14.93) (32.31, 46.43) (2.65, 4.47)

a p values were < 0.0001 when comparing the populations (≤ and > 99th percentile) within each time point.
b Kaplan-Meier estimate of the cumulative incidence of ACM and MACE.
c CI = Confidence Interval.

11208873_EN Rev. 10, 2024-08 25 / 36

TnIH Atellica IM Analyzer

Kaplan-Meier curves for absolute risk of ACM/MACE (cumulative incidence) are shown in the
figure below for all enrolled patients with baseline cTnI levels ≤ or > the overall 99th percentile
value, excluding patients with an adjudicated AMI at presentation. Results shown are for
lithium heparin plasma samples. Results for serum samples are comparable (refer to table 12).


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Number at Risk

≤ 99th percentile value 1874 1818 1788 1754 1732 1717 1685 1672 1660 1647 1638 1626 1107

> 99th percentile value 190 173 160 150 145 140 133 129 126 125 120 119 74

Table 13: ACM and MACE outcomes for all enrolled patients with baseline cTnI levels ≤ or > the gender-
specific 99th percentile value excluding patients with an adjudicated AMI at presentation

Baseline ≤ 99th Percentile Baseline > 99th Percentile

(No myocardial injury) (Myocardial injury)

ACM/MACE ACM/MACE
Incidence % Absolute Risk Incidence % Absolute Risk Risk Difference Hazard Ratioa
N (N) (95% CI)b, c N (N) (95% CI) (%)a (95% CI)

Lithium heparin plasma

30 1882 55 2.93 182 12 6.63 3.70 2.31

Days (2.26, 3.80) (3.82, 11.38) (1.24, 4.32)

90 1882 112 5.98 182 34 18.78 12.80 3.33

Days (4.99, 7.15) (13.81, 25.28) (2.27, 4.89)

365 1882 249 13.41 182 68 37.85 24.44 3.29

Days (11.94, 15.05) (31.19, 45.40) (2.51, 4.30)

Serum

26 / 36 11208873_EN Rev. 10, 2024-08

Atellica IM Analyzer TnIH

Baseline ≤ 99th Percentile Baseline > 99th Percentile

(No myocardial injury) (Myocardial injury)

ACM/MACE ACM/MACE
Incidence % Absolute Risk Incidence % Absolute Risk Risk Difference Hazard Ratioa
N (N) (95% CI)b, c N (N) (95% CI) (%)a (95% CI)

30 1917 56 2.93 180 14 7.82 4.89 2.75

Days (2.26, 3.79) (4.71, 12.85) (1.53, 4.95)

90 1917 113 5.92 180 35 19.55 13.63 3.54

Days (4.95, 7.08) (14.45, 26.16) (2.42, 5.17)

365 1917 255 13.48 180 68 38.29 24.81 3.32

Days (12.02, 15.11) (31.57, 45.89) (2.54, 4.34)

a p values were < 0.01 when comparing the populations (≤ and > 99th percentile) within each time point.
b Kaplan-Meier estimate of the cumulative incidence of ACM and MACE.
c CI = Confidence Interval.
Kaplan-Meier curves for absolute risk of ACM/MACE (cumulative incidence) are shown in the
figure below for all enrolled patients with baseline cTnI levels ≤ or > the gender-specific 99th
percentile value, excluding patients with an adjudicated AMI at presentation. Results shown
are for lithium heparin plasma samples. Results for serum samples are comparable (refer to
table 13).


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Number at Risk

≤ 99th percentile value 1882 1822 1791 1756 1735 1719 1688 1675 1662 1649 1640 1628 1109

> 99th percentile value 182 169 157 148 142 138 130 126 124 123 118 117 72

11208873_EN Rev. 10, 2024-08 27 / 36

TnIH Atellica IM Analyzer

Precision
Precision was determined in accordance with CLSI Document EP05‑A3.60 Samples were
assayed on an Atellica IM Analyzer in duplicate in 2 runs per day for 20 days. The assay was
designed to have within-laboratory precision of ≤ 12% CV for samples from 9–20 pg/mL (ng/L)
and ≤ 10% CV for samples > 20 pg/mL (ng/L). The following results were obtained:

Repeatability Within-Laboratory Precision

Mean SDb CVc SD CV

Sample Type Na (pg/mL; ng/L) (pg/mL; ng/L) (%) (pg/mL; ng/L) (%)

Serum 1 80 9.54 0.48 5.0 0.71 7.5

Serum 2 80 18.90 0.57 3.0 1.02 5.4

Serum 3 80 39.10 0.92 2.4 1.52 3.9

Serum 4 80 147.37 2.56 1.7 4.39 3.0

Serum 5 80 1610.40 28.61 1.8 50.95 3.2

Serum 6 80 21,392.14 411.79 1.9 534.59 2.5

Plasma 1 80 27.50 0.77 2.8 1.38 5.0

Plasma 2 80 144.81 2.64 1.8 3.27 2.3

Plasma 3 80 1131.65 22.38 1.7 28.45 2.1

Plasma 4 80 15,822.86 200.07 1.3 395.37 2.5

a Number of samples tested.
b Standard deviation.
c Coefficient of variation.
Based on internal testing on the Atellica IM Analyzer, the overall reproducibility is estimated to
be ≤ 13% CV for samples tested and includes multiple reagent lots, instruments, days, and
replicates. Performance of the assay at individual laboratories may vary.

Interferences
Interference testing was performed in accordance with CLSI Document EP07‑A2.41
Testing was performed with both human serum and lithium-heparin plasma samples, with
cTnI concentrations in the ranges of 20–60 pg/mL (ng/L) and 1000–2000 pg/mL (ng/L). The
following drugs were added to the samples at the concentrations indicated, and were
evaluated for potential interference using the Atellica IM TnIH assay. The results demonstrated
a ≤ 10% interference from each drug.

Low or Therapeutic Concentration High or Toxic Concentration

Potential Interferents Common units SI units Common units SI units

Abciximab 5 µg/mL N/Aa 40 µg/mL N/A

Acetaminophen 20 µg/mL 133 µmol/L 200 µg/mL 1324 µmol/L

Acetylsalicylic acid 261 µg/mL 1.45 mmol/L 652 µg/mL 3.62 mmol/L

Allopurinol 13 µg/mL 92 µmol/L 40 µg/mL 294 µmol/L

Amiodarone 1.8 µg/mL 2.6 µmol/L 6.1 µg/mL 8.92 µmol/L

Ampicilin 10 µg/mL 29.1 µmol/L 53 µg/mL 152 µmol/L

28 / 36 11208873_EN Rev. 10, 2024-08

Atellica IM Analyzer TnIH

Low or Therapeutic Concentration High or Toxic Concentration

Potential Interferents Common units SI units Common units SI units

Ascorbic acid 12 µg/mL 68.5 µmol/L 60 µg/mL 342 µmol/L

Atenolol 1.1 µg/mL 4.14 µmol/L 10 µg/mL 37.6 µmol/L

Caffeine 12 µg/mL 64.4 µmol/L 60 µg/mL 308 µmol/L

Captropril 1.0 µg/mL 4.6 µmol/L 5.0 µg/mL 23 µmol/L

Cefoxitin 120 µg/mL 281 µmol/L 660 µg/mL 1546 µmol/L

Cinnarizine 200 ng/mL 542 nmol/L 400 ng/mL 1084 nmol/L

Clopidogrel 37.5 µg/mL 116 µmol/L 75 µg/mL 233 µmol/L

Cocaine 0.1 µg/mL 0.33 µmol/L 10 µg/mL 33 µmol/L

Digoxin 1.4 ng/mL 1.8 nmol/L 6.1 ng/mL 7.8 nmol/L

Digitoxin 30 ng/mL 39 nmol/L 60 ng/mL 78 nmol/L

Diltiazem 0.2 µg/mL 0.55 µmol/L 6.2 µg/mL 15 µmol/L

Disopyramide 3.5 µg/mL 10.4 µmol/L 10 µg/mL 29.5 µmol/L

Dopamine 0.3 µg/mL 1.96 µmol/L 0.9 µg/mL 5.87 µmol/L

Doxycycline 10.0 µg/mL 22.5 µmol/L 30 µg/mL 67.5 µmol/L

Erythromycin 11 µg/mL 14.96 µmol/L 60 µg/mL 81.6 µmol/L

Furosemide 20 µg/mL 60.4 µmol/L 60 µg/mL 181 µmol/L

Ibuprofen 40 µg/mL 194.3 µmol/L 500 µg/mL 2425 µmol/L

Isosorbide dinitrate 50 ng/mL 212 nmol/L 150 ng/mL 636 nmol/L

Lisinopril 0.10 µg/mL 0.25 µmol/L 0.30 µg/mL 0.74 µmol/L

Lovastatin 40 ng/mL 95 nmol/L 80 ng/mL 191 nmol/L

Low MW heparin 6.75 U/mL N/A 30 U/mL N/A

Methotrexate 546 µg/mL 1.2 mmol/L 910 µg/mL 2.0 mmol/L

Methyldopa 4.2 µg/mL 20.12 µmol/L 15 µg/mL 71 µmol/L

Methylprednisolone N/A N/A 40 µg/mL 107 µmol/L

Mexiletine 1.3 µg/mL 7 µmol/L 4.0 µg/mL 22.3 µmol/L

Nicotine 37 ng/mL 0.23 µmol/L 1000 ng/mL 6.2 µmol/L

Nifedipine 125 ng/mL 362 nmol/L 400 ng/mL 1156 nmol/L

Nitrofurantoin 2.0 µg/mL 8.4 µmol/L 4.0 µg/mL 16.8 µmol/L

Nitroglycerine 7.5 ng/mL 33 nmol/L 160 ng/mL 704 nmol/L

Phenobarbital 24 µg/mL 107.6 µmol/L 97 µg/mL 431 µmol/L

Phenytoin 12 µg/mL 49.5 µmol/L 50 µg/mL 198 µmol/L

Primidone 10.5 µg/mL 48.2 µmol/L 40 µg/mL 183 µmol/L

Propranolol 0.50 µg/mL 1.94 µmol/L 2.0 µg/mL 7.71 µmol/L

11208873_EN Rev. 10, 2024-08 29 / 36

TnIH Atellica IM Analyzer

Low or Therapeutic Concentration High or Toxic Concentration

Potential Interferents Common units SI units Common units SI units

Quinidine 3.7 µg/mL 11.56 µmol/L 12 µg/mL 37 µmol/L

Simvastatin 16 µg/mL 38 µmol/L 32 µg/mL 76 µmol/L

Theophylline 12 µg/mL 69.4 µmol/L 40 µg/mL 222 µmol/L

Thyroxine 0.08 µg/mL 0.11 µmol/L 1.01 µg/mL 1.30 µmol/L

Tissue plasminogen activator (TPA) 1.15 µg/mL N/A 2.3 µg/mL N/A

Trimethoprim 12 µg/mL 43 µmol/L 40 µg/mL 138 µmol/L

Verapamil 0.33 µg/mL 0.72 µmol/L 2.0 µg/mL 4.4 µmol/L

Warfarin 2.0 µg/mL 6.6 µmol/L 10 µg/mL 32.5 µmol/L

a Not applicable.
Assay results obtained at individual laboratories may vary from the data presented.

Hemolysis, Icterus, Lipemia (HIL), and Other Interferences

Potential interference in the Atellica IM TnIH assay from the compounds listed below is
designed to be ≤ 10%.

Specimens that are... Demonstrate ≤ 10% change in results up to...

Hemolyzed 500 mg/dL of hemoglobin

Lipemic 2000 mg/dL of triglycerides

Icteric 40 mg/dL of conjugated bilirubin

Icteric 60 mg/dL of unconjugated bilirubin

Specimens that contain... Demonstrate ≤ 10% change in results up to...

Biotin 3500 ng/mL of biotin

Cholesterol 500 mg/dL of cholesterol

Protein Albumin 6 g/dL

Protein Gamma Globulin 2.5 g/dL

Total Protein 12 g/dL

Assay results obtained at individual laboratories may vary from the data presented.

Linearity
The Atellica IM TnIH assay is linear from 2.50–25,000.00 pg/mL (ng/L). Linearity was evaluated
according to the CLSI Document EP06‑A.61 Serum and lithium-heparin plasma samples were
used to make pools at 3 different cTNI ranges. The dilution series were made by mixing high
and low dose samples. The resulting sample mixtures were tested with the Atellica IM TnIH
assay.

30 / 36 11208873_EN Rev. 10, 2024-08

Atellica IM Analyzer TnIH

High-Dose Hook Effect

High cTnI concentrations can cause a paradoxical decrease in the RLUs (high-dose hook
effect). In this assay, patient samples with cTnI concentrations as high as
500,000 pg/mL (ng/L) will report > 25,000.00 pg/mL (ng/L).

Standardization
The Atellica IM TnIH assay standardization is traceable to an internal standard manufactured
using human heart homogenate. Assigned values for calibrators are traceable to this
standardization.

Technical Assistance
According to EU regulation 2017/746, any serious incident that has occurred in relation to the
device shall be reported to the manufacturer and the competent authority of the EU Member
State in which the user and/or patient is established.
For customer support, contact your local technical support provider or distributor.
siemens-healthineers.com

References
1. Mair J, Wagner I, Puschendorf B, et al. Cardiac troponin I to diagnose myocardial injury.
Lancet. 1993;341(8848):838–839.
2. Adams JE 3rd, Bodor GS, Davila-Romain VG, et al. Cardiac troponin I. A marker for cardiac
injury. Circulation. 1993;88(1):101–106.
3. Corin SJ, Juhasz O, Zhu L, et al. Structure and expression of the human slow twitch skeletal
muscle troponin I gene. J Biol Chem. 1994;269(14):10651–10659.
4. Mair J, Larue C, Mair P, et al. Use of cardiac troponin I to diagnose perioperative myocardial
infarction in coronary artery bypass grafting. Clin Chem. 1994;40(11, pt 1):2066–2070.
5. Adams JE 3rd, Sicard GA, Allen BT, et al. Diagnosis of perioperative myocardial infarction
with measurement of cardiac troponin I. N Engl J Med. 1994;330(10):670-674.
6. Adams JE 3rd, Schechtman KB, Landt Y, et al. Comparable detection of acute myocardial
infarction by creatine kinase MB isoenzyme and cardiac troponin I. Clin Chem. 1994;40(7,
pt 1):1291–1295.
7. Bodor GS, Porter S, Landt Y, Ladenson JH. Development of monoclonal antibodies for an
assay of cardiac troponin-I and preliminary results in suspected cases of myocardial
infarction. Clin Chem. 1992;38(11):2203–2214.
8. Apple FS. Acute myocardial infarction and coronary reperfusion. Serum cardiac markers for
the 1990s. Am J Clin Pathol. 1992;97(2):217–226.
9. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth Universal Definition of Myocardial Infarction
(2018). Circulation. 2018 Nov 13;138(20):e618–e651.
10. Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute
coronary syndromes in patients presenting without persistent ST-segment elevation. Eur
Heart J 2021;42(14):1289–1367.
11. Raber I, McCarthy CP, Januzzi JL, Jr. A Test in Context: Interpretation of High-Sensitivity
Cardiac Troponin Assays in Different Clinical Settings. J Am Coll Cardiol.
2021;77(10):1357-1367.
12. Roos A, Bandstein N, Lundback M, Hammarsten O, Ljung R, Holzmann MJ. Stable High-
Sensitivity Cardiac Troponin T Levels and Outcomes in Patients With Chest Pain. J Am Coll
Cardiol. 2017;70(18):2226-2236.

11208873_EN Rev. 10, 2024-08 31 / 36

TnIH Atellica IM Analyzer

13. Roos A, Sartipy U, Ljung R, Holzmann MJ. Relation of Chronic Myocardial Injury and Non-
ST-Segment Elevation Myocardial Infarction to Mortality. Am J Cardiol.
2018;122(12):1989-1995.
14. Sörensen NA, Ludwig S, Makarova N, et al. Prognostic Value of a Novel and Established
High-Sensitivity Troponin I Assay in Patients Presenting with Suspected Myocardial
Infarction. Biomolecules. 2019;9(9):469.
15. McEvoy JW, Chen Y, Ndumele CE, et al. Six-Year Change in High-Sensitivity Cardiac
Troponin T and Risk of Subsequent Coronary Heart Disease, Heart Failure, and Death.
JAMA Cardiol. 2016;1(5):519-528.
16. de Lemos JA, Drazner MH, Omland T, et al. Association of troponin T detected with a
highly sensitive assay and cardiac structure and mortality risk in the general population.
JAMA. 2010;304(22):2503-2512.
17. Januzzi JL Jr, Suchindran S, Hoffmann U, et al. Single-Molecule hsTnI and Short-Term Risk
in Stable Patients With Chest Pain. J Am Coll Cardiol. 2019;73(3):251-260.
18. Pandey A, Keshvani N, Ayers C, et al. Association of Cardiac Injury and Malignant Left
Ventricular Hypertrophy With Risk of Heart Failure in African Americans: The Jackson Heart
Study. JAMA Cardiol. 2019;4(1):51-58.
19. Pandey A, Patel KV, Vongpatanasin W, et al. Incorporation of Biomarkers Into Risk
Assessment for Allocation of Antihypertensive Medication According to the 2017 ACC/AHA
High Blood Pressure Guideline: A Pooled Cohort Analysis. Circulation.
2019;140(25):2076-2088.
20. Sandoval Y, Bielinski SJ, Daniels LB, et al. Atherosclerotic Cardiovascular Disease Risk
Stratification Based on Measurements of Troponin and Coronary Artery Calcium. J Am Coll
Cardiol. 2020;76(4):357-370.
21. Marston NA, Bonaca MP, Jarolim P, et al. Clinical Application of High-Sensitivity Troponin
Testing in the Atherosclerotic Cardiovascular Disease Framework of the Current Cholesterol
Guidelines. JAMA Cardiol. 2020;5(11):1255-1262.
22. Eggers KM, Lindahl B. Application of Cardiac Troponin in Cardiovascular Diseases Other
Than Acute Coronary Syndrome. Clin Chem. 2017;63(1):223-235.
23. McCarthy CP, Raber I, Chapman AR, et al. Myocardial Injury in the Era of High-Sensitivity in
Assays: A Practical Approach for Clinicians. JAMA Cardiol. 2019;4(10):1034-1042.
24. Apple FS, Sandoval Y, Jaffe AS, Ordonez-Llanos J. IFCC Task Force on Clinical Applications
of Cardiac Bio-Markers. Cardiac troponin assays: Guide to understanding analytical
characteristics and their impact on clinical care. Clin Chem. 2017;63(1):73–81.
25. Wu AHB, Christenson R, Greene D, et al. Clinical Laboratory Practice Recommendations for
the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the
Academy of the American Association for Clinical Chemistry and the Task Force on Clinical
Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry
and Laboratory Medicine. Clin Chem. 2018; 64(4):645–655.
26. Wildi K, Twerenbold R, Mueller C. How acute changes in cardiac troponin concentrations
help to handle the challenges posed by troponin elevations in non-ACS-patients. Clin
Biochem. 2015 Mar;48(4-5):218–222.
27. IFCC Task Force on Clinical Applications of Cardiac Biomarkers (June 2014). Analytical
characteristics of high-sensitivity cardiac troponin assays. Clin Chem. 2012;58:1,54–61.
28. Amsterdam EA, Wenger NK, Brindis RG, Casey DE, et al. 2014 AHA/ACC Guideline for the
Management of Patients With Non-ST-Elevation Acute Coronary Syndromes. Circulation.
2014;130:e344–e426. https://doi.org/10.1161/CIR.0000000000000134. Accessed
12/15/2016.

32 / 36 11208873_EN Rev. 10, 2024-08

Atellica IM Analyzer TnIH

29. Roffi M, Patrono C, Collet JP, Mueller C, et al. 2015 ESC Guidelines for the management of
acute coronary syndromes in patients presenting without persistent ST-segment elevation.
European Heart Journal. 2016;37: 267–315.
30. US Department of Health and Human Services. Biosafety in Microbiological and
Biomedical Laboratories. 5th ed. Washington, DC: US Government Printing Office;
December 2009.
31. World Health Organization. Laboratory Biosafety Manual. 3rd ed. Geneva: World Health
Organization; 2004.
32. Clinical and Laboratory Standards Institute. Protection of Laboratory Workers From
Occupationally Acquired Infections; Approved Guideline—Fourth Edition. Wayne, PA:
Clinical and Laboratory Standards Institute; 2014. CLSI Document M29‑A4.
33. Clinical and Laboratory Standards Institute. Procedures for the Collection of Diagnostic
Blood Specimens by Venipuncture; Approved Standard—Sixth Edition. Wayne, PA: Clinical
and Laboratory Standards Institute; 2007. CLSI Document GP41‑A6.
34. Clinical and Laboratory Standards Institute. Tubes and Additives for Venous and Capillary
Blood Specimen Collection; Approved Standard—Sixth Edition. Wayne, PA: Clinical and
Laboratory Standards Institute; 2010. CLSI Document GP39‑A6.
35. Clinical and Laboratory Standards Institute. Procedures for the Handling and Processing of
Blood Specimens for Common Laboratory Tests; Approved Guideline—Fourth Edition.
Wayne, PA: Clinical and Laboratory Standards Institute; 2010. CLSI Document GP44‑A4.
36. Schroff RW, Foon KA, Beatty SM, et al. Human anti-murine immunoglobulin responses in
patients receiving monoclonal antibody therapy. Clin Chem 1988;34:261–264.
37. Savukoski T, Engström E, Engblom J, et al. Troponin-specific autoantibody interference in
different cardiac troponin I assay configurations. Clin Chem. 2012;58(6):1040–1048.
38. Kricka LJ. Human anti-animal antibody interferences in immunological assays. Clin Chem.
1999;45(7):942–956.
39. Vaidya HC, Beatty BG. Eliminating interference from heterophilic antibodies in a two-site
immunoassay for creatine kinase MB by using F(ab’)2 conjugate and polyclonal mouse
IgG. Clin Chem. 1992;38(9):1737–1742.
40. Clinical and Laboratory Standards Institute. Defining, Establishing, and Verifying Reference
Intervals in the Clinical Laboratory; Approved Guideline—Third Edition. Wayne, PA:
Clinical and Laboratory Standards Institute; 2010. CLSI Document EP28‑A3c (formerly C28-
A3c).
41. Clinical and Laboratory Standards Institute. Interference Testing in Clinical Chemistry;
Approved Guideline—Second Edition. Wayne, PA: Clinical and Laboratory Standards
Institute; 2005. CLSI Document EP07‑A2.
42. Clinical and Laboratory Standards Institute. Evaluation of Detection Capability for Clinical
Laboratory Measurement Procedures; Approved Guideline—Second Edition. Wayne, PA:
Clinical and Laboratory Standards Institute; 2012. CLSI Document EP17‑A2.
43. Wu AHB, Apple F, Love SA, Koch D, et al. Creation of a Universal Sample Bank for
Determining the 99th Percentile for Cardiac Troponin Assays. J Appl Lab Med. 2017 May
1;1(6):711–719.
44. Apple FS, Wu AHB, Sandoval Y, et al. Sex-Specific 99th Percentile Upper Reference Limits
for High Sensitivity Cardiac Troponin Assays Derived Using a Universal Sample Bank. Clin
Chem. 2020 Mar 1;66(3):434–444.
45. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, et al. Third universal definition of myocardial
infarction. Circulation. 2012;126:2020–35.

11208873_EN Rev. 10, 2024-08 33 / 36

TnIH Atellica IM Analyzer

46. Antman EM, Tanasijevic MJ, Thompson B, et al. Cardiac-specific troponin I levels to predict
the risk of mortality in patients with acute coronary syndromes. N Engl J Med.
1996;335(18):1342–1349.
47. Chin C, Shah A, McAllister D, Cowell S, et al. High-sensitivity troponin I concentrations are
a marker of an advanced hypertrophic response and adverse outcomes in patients with
aortic stenosis. Eur Heart J. 2014 Sep 7;35:2312–2321.
48. Youssef A, Hassan A, El-Ghamry R, Ahmed A. Serum troponin-I as a prognostic marker in
acute exacerbated chronic obstructive pulmonary disease patients. Egypt J Chest Dis
Tuberc. 2013;62:549–555.
49. Hijazi Z, Siegbahn A, Andersson U, Granger C, et al. High-sensitivity troponin I for risk
assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in
Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.
Circulation. 2014;Feb 11;129(6):625-34.
50. Omland T, Cardiac Troponins: a tool for a personalized medicine strategy in stable
coronary artery disease? J Am Coll Cardiol. 2014;63(4):355–357.
51. Avouac J, Meune C, Chenevier-Gobeaux C, Borderie D, et al. Cardiac biomarkers in
systemic sclerosis: contribution of high-sensitivity cardiac troponin in addition to N-
terminal pro-brain natriuretic peptide. Arthritis Care & Res. 2015;67(7):1022–1030.
52. White HD, Tonkin A, Simes J, Stewart R, et al. Association of Contemporary Sensitive
Troponin I Levels at Baseline and Change at 1 Year With Long-Term Coronary Events
Following Myocardial Infarction or Unstable Angina: Results from the LIPID Study (Long-
Term Intervention With Pravastatin in Ischaemic Disease). J Am Coll Cardiol.
2014;63(4):345–354.
53. Yeon JL, Lee H, Park JS, Kim SJ, et al. Cardiac troponin I as a prognostic factor in critically ill
pneumonia patients in the absence of acute coronary syndrome. J Crit Care.
2015;30(2):390–394.
54. Boeddinghaus J, Twerenbold R, Nestelberger T, et al. Clinical Validation of a Novel High-
Sensitivity Cardiac Troponin I Assay for Early Diagnosis of Acute Myocardial Infarction. Clin
Chem 2018;64(9):1347–60.
55. Sörensen NA, Goßling A, Neumann JT, et al. Diagnostic Validation of a High-Sensitivity
Cardiac Troponin I Assay. Clin Chem. 2021;67(9):1230–1239.
56. Nowak RM, Christenson RH, Jacobsen G, et al. Performance of Novel High-Sensitivity
Cardiac Troponin I Assays for 0/1-Hour and 0/2- to 3-Hour Evaluations for Acute Myocardial
Infarction: Results from the HIGH-US study. Ann Emerg Med; 2020;76(1):1–13.
57. Chapman AR, Fujisawa T, Lee KK, et al. Novel high-sensitivity cardiac troponin I assay in
patients with suspected acute coronary syndrome. Heart 2019;105(8):616–22.
58. Andersen CF, Bang C, Lauridsen KG, et al. External validation of a high-sensitive troponin I
algorithm for rapid evaluation of acute myocardial infarction in a Danish cohort. Eur Heart
J Acute Cardiovasc Care. 2021, doi:10.1093/ehjacc/zuab062.
59. Ishii J. First clinical validation of the 0-hour/1-hour algorithm using high-sensitivity cardiac
troponin I for the diagnosis of acute myocardial infarction in Japanese patients. EMJ
Cardiol. 2020;8(1):42–44.
60. Clinical and Laboratory Standards Institute. Evaluation of Precision of Quantitative
Measurement Procedures; Approved Guideline—Third Edition. Wayne, PA: Clinical and
Laboratory Standards Institute; 2014. CLSI Document EP05‑A3.
61. Clinical and Laboratory Standards Institute. Evaluation of the Linearity of Qualitative
Measurement Procedures: A Statistical Approach; Approved Guideline. Wayne, PA: Clinical
and Laboratory Standards Institute; 2003. CLSI Document EP06-A.

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Definition of Symbols
The following symbols may appear on the product labeling:

Symbol Symbol Title Source Symbol Symbol Title Source

Manufacturer 5.1.1a Authorized representative 5.1.2a

in the European
Community

Use-by date 5.1.4a Authorized representative Proprietary

in Switzerland

Catalog number 5.1.6a Batch code 5.1.5a

Consult Instructions for 5.4.3a Contains sufficient for <n> 5.5.5a

Use tests

Internet URL address to Proprietary Version of Instructions for Proprietary

access the electronic Use
instructions for use

In vitro diagnostic medical 5.5.1a Revision Proprietary

device

Prescription device (US FDAb Unique Device Identifier 5.7.10c

only)

CE Marking with Notified EU IVDRd CE Marking EU IVDRd

Body

Temperature limit 5.3.7a Keep away from sunlight 5.3.2a

Upper limit of tempera- 5.3.6a Lower limit of temperature 5.3.5a

ture

Do not re-use 5.4.2a Do not freeze Proprietary

Recycle 1135e This way up 0623e

Biological risks 5.4.1a Caution 5.4.4a

Common Units Proprietary International System of Proprietary

Units

YYYY-MM-DD Date format (year-month- N/A YYYY-MM Date format (year-month) N/A
day)

Document face upf 1952e Handheld barcode scanner Proprietary

Target Proprietary Mixing of substances 5657g

11208873_EN Rev. 10, 2024-08 35 / 36

TnIH Atellica IM Analyzer

Symbol Symbol Title Source Symbol Symbol Title Source

Variable hexadecimal Proprietary Interval Proprietary

number that ensures the
Master Curve and Cali-
brator definition values
entered are valid.

Unique material identifica- Proprietary Material Proprietary

tion number

Type of control Proprietary Name of control Proprietary

Quality control lot value Proprietary Calibrator lot value Proprietary

a International Standard Organization (ISO). ISO 15223-1 Medical Devices- Symbols to be used with medical
device labels, labelling and information to be supplied.
b Federal Register. Vol. 81, No 115. Wednesday, June 15, 2016. Rules and Regulations: 38911.
c ISO 15223-1:2020-04
d IVDR REGULATION (EU) 2017/746
e International Standard Organization (ISO). ISO 7000 Graphical symbols for use on equipment.
f Indicates Assay-eNote
g International Electrotechnical Commission (IEC). IEC 60417-1 Graphical symbols for use on equipment – Part 1:
Overview and Application

Legal Information
Atellica and ReadyPack are trademarks of Siemens Healthineers.
All other trademarks and brands are the property of their respective owners.
© 2017–2024 Siemens Healthineers. All rights reserved.

Siemens Healthcare Diagnostics Inc.

511 Benedict Avenue
Tarrytown, NY 10591 USA

Siemens Healthineers Headquarters

Siemens Healthcare GmbH
Henkestraße 127
91052 Erlangen
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Phone: +49 9131 84-0
siemens-healthineers.com

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