A Scoping Review on Troponin as a Diagnostic Marker in Myocardial infarction.

1. Running Head: SCOPING REVIEW
Title: A Scoping Review on Troponin as a Diagnostic Marker in Myocardial infarction.
Student Name:
Student ID:

2. Table of Contents
Abstract ........................................................................................................................................... 4
Introduction..................................................................................................................................... 5
Background ................................................................................................................................. 5
Rationale ..................................................................................................................................... 5
Research Aim.............................................................................................................................. 6
Research Question....................................................................................................................... 6
Methods........................................................................................................................................... 6
Search Strategy ........................................................................................................................... 6
Inclusion and Exclusion Criteria................................................................................................. 6
Reviewing Process ...................................................................................................................... 7
Data Charting.............................................................................................................................. 7
Data Extraction from Included Studies....................................................................................... 7
Outcomes and How They Will be Presented .............................................................................. 7
Results............................................................................................................................................. 8
Discussion..................................................................................................................................... 11
Diagnostic Characteristics of the Analyte (Troponin) .............................................................. 11
Modern Cardiovascular Prophylaxis and Use of Highly Sensitive Troponin-I........................ 11
Highly Sensitive Cardiac Troponins......................................................................................... 13
Highly Sensitive Troponin-I Determining the Risk of Developing CVS Events ..................... 13
What is the purpose of determining the level of Troponin-I in the blood?............................... 13
Highly Sensitive Troponin in Cardiac Stratification of Stable Outpatients.............................. 14
Conclusion .................................................................................................................................... 14
References..................................................................................................................................... 15
Appendix 1: Search Strategy and Keywords ................................................................................ 20

3. PubMed Search Strategy Performed 5th September’21 ............................................................ 20
Cochrane Library Search Strategy Performed 5th September’21.............................................. 20
Appendix 2: PRISMA................................................................................................................... 21
Appendix 2: Critical Appraisal of Selected Articles..................................................................... 22
Appendix 3: Summary of Selected Articles.................................................................................. 24

4. Abstract
Troponins are highly myocardial specific regulatory proteins associated with the
contractile element of myofilaments of cardiomyocytes. Cardiac troponins are the main
biomarkers for the diagnosis of acute myocardial infarction, complementing clinical (symptoms
of chest pain, shortness of breath, palpitations, sweating, loss of consciousness, etc.) and
functional data (electrocardiography, echocardiography). This research is merely based in the
validity of Troponin as a diagnostic marker, it is a protein, a specific marker of heart muscle
damage, used in the diagnosis of myocardial infarction. A scoping review of the literature on
Troponin as a diagnostic marker in myocardial infarction was performed. In-depth search uses a
broader search strategy, taking into account the reproducibility, transparency and credibility of
the current state of the literature. scoping review a descriptive description of the accompanying
studies was prepared to demonstrate the use of Troponin as a diagnostic marker in myocardial
infarction. The numerical analysis shows the number, geographical distribution and types of
higher education institutions involved in the research. Due to the wide range of results, in some
cases they are pooled by subject to record the overall effect of Troponin on positive, negative,
neutral, or mixed quantitative or mixed methods. For this scoping research a total 10 research
papers were collected (5 from Cochrane Library and 5 from PubMed).

5. Introduction
Background
Cardiovascular diseases are one of the leading causes of death and disability in the
population (Duplyakov & Chaulin, 2019). Laboratory diagnostics of cardiovascular diseases is
an important direction, since it is one of the key methods of diagnosis verification (Chaulin et al.
2019a; Chaulin, 2020). In recent years, many clinical studies have been conducted on recently
discovered biomarkers of cardiovascular diseases (Chaulin et al. 2019b), among which catestatin,
highly sensitive cardiac troponins, and proprotein-convertase subtilisin/Kexin type 9 are
particularly noteworthy (Chaulin, & Duplyakov, 2019). Troponin complex is part of the
contractile system of the muscle cell. It is formed by three proteins: troponin T, which forms a
bond with tropomyosin, troponin I, which can inhibit ATPase activity, and troponin C, which has
a significant affinity for Ca2 + (Januzzi Jr et al. 2012). The content of troponin T in
myocardiocytes is approximately 2 times higher than the level of troponin I (Solecki et al. 2015).
About 93% of troponin T is contained in the contractile apparatus of myocytes; this fraction can
be a precursor for the synthesis of the troponin complex and 7% in cytolysis (Rains et al., 2014).
Troponin T from the heart muscle differs in amino acid composition and immune properties from
troponin T of other muscles. In the blood of healthy people, even after excessive physical
exertion, the level of troponin T does not exceed 0.2-0.5 ng / ml, therefore, an increase in it
above the specified limit indicates damage to the heart muscle (Daubert & Jeremias, 2010).
Rationale
This research is merely based in the validity of Troponin as a diagnostic marker, it is a
protein, a specific marker of heart muscle damage, used in the diagnosis of myocardial
infarction. An increase in troponin I is noted within 4 - 6 hours after an attack. This test allows
healthcare professionals to diagnose even microscopic areas of myocardial damage. As per
Aldous et al. (2011) myoglobin is a hemoprotein that is found in large amounts in skeletal
muscles and in small amounts in the heart muscle and takes part in tissue respiration. With
myocardial infarction, the concentration of myoglobin in the blood increases after 2 hours, but
this is a nonspecific marker of myocardial infarction, since the heart muscle contains a small
amount of myoglobin. This marker is used in the diagnosis of myocardial infarction in
combination with other biochemical tests (Tricco et al. 2018).

6. ResearchAim
The following research aims is discussed throughout this scoping review: “To Analyse the
Role of Troponin as a Diagnostic Marker in Myocardial infarction.”
ResearchQuestion
The following research question is answered throughout this this scoping review: “What
is the Role of Troponin as a Diagnostic Marker in Myocardial infarction.”
Methods
Search Strategy
A scoping review of the literature on Troponin as a diagnostic marker in myocardial
infarction was performed. The main determinants of myocardial infarction, methods and results
used in the Troponin study were evaluated by Tricco et al. (2018). In-depth search uses a broader
search strategy, taking into account the reproducibility, transparency and credibility of the
current state of the literature. The detailed structure of this scope study, including the steps of the
search strategy and the systematic review process, has been published elsewhere. In short, the
search strategy includes a set of keywords related to Troponin and myocardial infarction health
determinants identified by experts from the e-book search library. The keywords search strategy
are detailed in the appendix 1.
Original previously peer-reviewed articles published in English journals from January
2010 till date were systematically searched in seven electronic bibliographic databases,
including: PubMed and Cochrane Library. All articles found in the search were imported into the
reference management system and all titles and duplicates in other languages were removed
Inclusion and Exclusion Criteria
The “PICOS framework (participants, intervention, context, outcomes, and study
design)” is used to set eligibility criteria. In order to include in this scoping review the reviewed
must meet five inclusion criteria. First, the study views the Troponin as a diagnostic marker in
myocardial infarction in which participant study is involved. Studies on other diagnostic marker
in myocardial infarction that do not specifically assess the Troponin are excluded. Second, the
aim of the research is to define Troponin as clinical marker for diagnosis of myocardial
infarction. Studies that combined other interventions and diagnostic markers with Troponin were
also excluded because we were unable to determine the independent impact of Troponin as
clinical marker for diagnosis of myocardial infarction. Third, the study was conducted in urban

7. areas. All studies that explicitly focused on rural, suburban, or peri-urban areas were excluded,
unless the results were derived from apartheid for comparison with urban areas. Fourth, the
results of at least one measurement or study report are determinants of Troponin. Fifth, for this
research we considered only peer-reviewed articles in English that describe the original
combination of quantitative, qualitative, or methodological studies. Grey literature, reviews,
narratives or other material (such as reports and essays) are excluded. Systematic reviews were
also included, but all relevant references have been carefully considered and can be used for
further relevant work.
Reviewing Process
The collected papers were manually reviewed in 3 stages: (1) Title and Year of
Publication; (2) Abstract and Methods; and (3) a thorough study and reading of selected papers.
Data Charting
To assess the quality of the included articles a standardized and modified scoring system
was designed inspired from Wallace et al. (2004) and Ohly et al. (2016) criteria. Given the
combination of test methods found in the quantitative study (cross-sectional, randomized
controlled trials, pre- and post-control, risk assessment), it is not appropriate to consider only one
existing quality assessment tool for quality assessment. For this scoping review the authors
selected a 12-point checklist based on criteria and questions from the following three sources of
quality assessment tools: (i) assessment tools used in studies, cross-sectional and observational
cohort studies, as well as preliminary and controlled studies, (ii) tools for quantitative evaluation
of EPHPP research quality and (iii) research limits and ethical standards.
Data Extraction from Included Studies
When an article was selected, the following data is entered in the spreadsheet comprising
of following columns: “complete reference, title of the study, author(s), year of publication,
country of focus, source, relevant used chapters, aimresearch question, and research
method(s)”. The appendix 3 presents table of critical apparels of selected articles and appendix 4
presents summary of selected articles.
Outcomes and How They Will be Presented
For scoping review a descriptive description of the accompanying studies was prepared to
demonstrate the use of Troponin as a diagnostic marker in myocardial infarction. The numerical
analysis shows the number, geographical distribution and types of higher education institutions

8. involved in the research. Due to the wide range of results, in some cases they are pooled by
subject to record the overall effect of Troponin on positive, negative, neutral, or mixed
quantitative or mixed methods. Neutral effects are attributed to studies that provide quantitative
measurement tools but do not use significant results because positive or negative measurement
effects lead to these results. Mixing effects are used to classify studies that show positive and
negative effects of measurement results. On the other hand, use terms such as perceived benefit,
difficulty, or motivation to classify the results of qualitative research and other mixed surveys.
The findings and conclusions of the report are summarized and grouped under specific titles
designated by the author to facilitate the explanation of the story.
Results
For this scoping research a total 10 research papers were collected (5 from Cochrane
Library and 5 from PubMed), the selected of these research papers has been laid out in the
PRISMA Flowchart as provided in appendix 2. Whereas, following is the graphical
representation of presented for overall selected quantitative studies.
0 0.5 1 1.5 2 2.5
Randomised control trial
Cross sections studies
Prospective cohoret study
retrospective cohoret studies
case control
Animal studies
Cell culture models
0
200
400
600
800
1000
total no of
studies
<18 18-40 40-60 <70
Males Females

9. The kinetics of troponin T in myocardial infarction differs from the kinetics of other
enzymes. On the first day of an increase in troponin T, it depends on the blood flow in the
infarction zone (Alexandrov & Mazaev, 2019; Aldous, 2013). With myocardial infarction,
troponin T rises in the blood already 3-4 hours after the onset of a pain attack, its peak
concentration falls on 3-4 days, a plateau is observed within 5-7 days, then the level of troponin
T gradually decreases, but remains elevated to 10 -20th day (Aydin et al. 2014). Successful
thrombolysis reveals two peaks: the first one - 14 hours after the onset of myocardial infarction,
its value is significantly higher than the level of the second peak, which corresponds to the 4th
day of acute myocardial infarction (Mythili & Malathi, 2015). Rapid detection of an increase in
serum troponin T is observed in patients with early recanalization of the occluded artery due to
fibrinolysis, i.e. the concentration of troponin T in the blood on the first day of myocardial
infarction depends on the duration of occlusion; the sooner the vessel "opens", the more
pronounced the increase in troponin T will be (Voicu et al. 2012; Negahdary et al. 2017). An
increase in troponin T concentration (second peak) indicates progressive proteolytic degradation
of the contractile apparatus and, accordingly, irreversible myocardial necrosis (Nenakhova,
2018). With prolonged occlusion, the high level of troponin T in the blood, observed within 10
days, is explained by its prolonged release from the infarction zone (the half-life of troponin T is
12 minutes) (Carroll et al. 2013).
With an uncomplicated course of myocardial infarction, the troponin T concentration
decreases by the 5-6th day, and by the 7th day, increased troponin T values are detected in 60%
of patients (Chaulin et al. 2020a). The specificity of methods for determining troponin T in the
blood in myocardial infarction is 90-100% and exceeds the specificity for creatine kinase, lactate
dehydrogenase and myoglobin. In the first 2 hours from the onset of a pain attack, the sensitivity
of troponin T determination methods is 33%, after 4 hours - 50%, after 10 hours - 100%, on the
7th day - 84% (Chaulin et al. 2019).
The concentration of troponin T increases after the onset of myocardial infarction
significantly more than creatine kinase and lactate dehydrogenase. In some patients with
successful recanalization, the troponin T concentration may increase more than 300-fold (Chen
et al. 2019). The concentration of troponin T in the blood depends on the size of the focus of
myocardial infarction. With large-focal or transmural myocardial infarction after thrombolysis,
the level of troponin T can increase by a maximum of 400 times, and in patients with myocardial

10. infarction without a Q wave - only 37 times. The "diagnostic window" (the time to detect an
increase in an enzyme or protein in pathological changes) for troponin T increases 4 times
compared with creatine kinase and 2 times compared with lactate dehydrogenase (Daubert &
Jeremias, 2010). The interval of absolute diagnostic sensitivity in acute myocardial infarction for
troponin T is 125-129 hours. For creatine kinase and lactate dehydrogenase - 22 and 70 hours,
respectively (Wang et al. 2020).
The level of troponin T in the blood can be used to assess the magnitude of myocardial
necrosis. Its peak level is strictly inversely proportional to the wall mobility index, left
ventricular ejection fraction, measured using two-dimensional echocardiography and contrast
ventriculography (Keller et al. 2011).
An increase in troponin T is detected in 40% of patients with unstable angina. Its level
increases only in patients with unstable class III angina pectoris according to E. Braunwald, and
this increase occurs in the range of 0.55-3.1 ng / ml and can be short-term or long-term (Rains et
al. 2014). Most often, the content of troponin T increases in patients with changes in the terminal
part of the gastric complex on the ECG, especially transient changes in the ST segment, which
are precursors of an unfavorable outcome in patients with unstable angina. Stably increased
values of troponin T in patients with unstable angina pectoris indicates that the patient had
microinfarctions (Keller et al. 2010).
The concentration of troponin T in the blood serum on the first day after the onset of pain
clearly depends on the blood flow in the infarction zone. This early washout of troponin T
usually ceases 32 hours after the onset of pain (Januzzi Jr et al. 2012). The dependence of its
release from the focus of myocardial damage on perfusion can be quite clearly determined by the
ratio of the maximum concentration of troponin T in serum on the first day of myocardial
infarction to its concentration after 72 hours (Long et al. 2020). This ratio does not depend on the
size of the infarction and allows all patients in whom successful recanalization occurred less than
6 hours from the onset of pain, to be regarded as patients with successful reperfusion. Instead of
measuring the individual maximum increase in troponin T on the first day of myocardial
infarction, it can be conventionally taken as the maximum increase in its level 14 hours after the
onset of pain (Solecki et al. 2015). If the ratio of troponin T concentration after 14 hours of its
concentration after 32 hours after the onset of pain is greater than 1. This is reliable evidence that
early recanalization of the occluded artery was successful (Body et al. 2011). The ratio of

11. troponin T concentration at 14 hours after a painful attack to its concentration at 32 hours is a
reliable indicator of successful thrombolytic therapy. With effective thrombolytic therapy, this
ratio is greater than 1 (Aldous et al. 2011).
Discussion
Diagnostic Characteristics of the Analyte (Troponin)
Troponins are small proteins involved in the regulation of muscle contraction. Two types
of troponins, cTn-I and cTn-T, found in cardiac muscle, are structurally different from cTn-I and
cTn-T of skeletal muscles; therefore, their cardiospecific forms can be isolated by immunoassay
methods (Alexandrov & Mazaev, 2019). The difference in concentrations in myocardial cells and
blood plasma for troponin is much higher than for enzymes and myoglobin, which makes it a
highly sensitive marker of myocardial damage (Reichlin et al. 2012). About 5% of troponin
inside muscle cells is in free form in the cytoplasm, which explains the early increase in its level
in blood plasma after damage to the heart muscle, which is possible within 1-3 hours, and after 6
hours, the troponin concentration increases in 95% of patients (Nenakhova, 2018). The main
amount of troponin in the cell is associated with muscle filaments and, when the heart cell is
damaged, is released at a later stage, corresponding to the degradation of myofibrils with
irreversible cell damage, as a result of which an increased concentration of troponin in the blood
persists for 1-2 weeks after myocardial injury (Chaulin et al. 2020a). The period of increased
troponin release thus overlaps the "diagnostic windows" of both creatine kinase-MB and LDH
(Meder et al. 2012).
Modern Cardiovascular Prophylaxis and Use of Highly Sensitive Troponin-I
A new clinical use of highly sensitive troponin-I is to determine the risk of cardiovascular
events (CVD) in the general population. Troponins are highly myocardial specific regulatory
proteins associated with the contractile element of myofilaments of cardiomyocytes (Negahdary
et al. 2017). Cardiac troponins are the main biomarkers for the diagnosis of acute myocardial
infarction, complementing clinical (symptoms of chest pain, shortness of breath, palpitations,
sweating, loss of consciousness, etc.) and functional data (electrocardiography,
echocardiography) (Negahdary et al. 2017). An increase in cardiac troponins in the blood serum,
along with symptoms and ischemic signs of electrocardiography, is the basis for the diagnosis of
myocardial infarction and the initiation of appropriate therapy. Highly sensitive troponin assays

12. approved for clinical use have significantly accelerated the early diagnosis of myocardial
infarction (Gerede et al. 2015).
Currently, a new clinical use of highly sensitive troponin-I has become possible - to
determine the risk of developing cardiovascular events (CVS) in the general population (Chaulin
et al. 2019). This additional diagnostic value of the marker appeared due to the high sensitivity of
the High Sensitivity Troponin-I test system, which allows the determination of very low
concentrations of cardiac troponin-I in the blood, including in healthy people (Daubert &
Jeremias, 2010). According to the WHO, diseases of the heart and blood vessels are the leading
cause of death worldwide. 17.5 million people die from cardiovascular disease (CVD) every
year. In Russia, mortality from CVD, including due to the influence of the new coronavirus
infection, increased from January to October by 25% (Laugaudin et al. 2016).
According to recent studies, the level of Troponin-I in the absence of clinical
manifestations is an independent predictor of the development of CVS, such as myocardial
infarction, heart failure, ischemic stroke, coronary revascularisation and cardiovascular death
(Rains et al. 2014). In addition, there was an increased risk of MI and stroke in apparently
healthy people in whom the level of troponin-I in the body is approaching the upper reference
limit (Raskovalova et al. 2014).
At the heart of modern cardiovascular prophylaxis is the prediction of the risk of CVD.
The study of highly sensitive troponin-I in blood can be used to examine apparently healthy
people in order to identify risk groups long before the first symptoms of CVD appear, which will
allow doctors to determine the tactics of patient management and prevent adverse outcomes
(Januzzi Jr et al. 2012). Depending on the level of troponin-I in the blood, the cardiovascular risk
can be low, moderate, or increased (Omran et al. 2018).
The test is a more sensitive marker than ultrasensitive c-reactive protein in the diagnosis
of myocardial infarction, cardiovascular failure, or cardiovascular death (Solecki et al. 2015).
Supplementing existing models for predicting cardiovascular risk, including traditional tests
(European SCORE scale, Framingham scale, etc.) with high-sensitivity troponin-I, will help
improve patient re-classification (Parikh et al. 2015). Improving the accuracy of predicting
cardiovascular risk is an important strategy for the prevention of cardiovascular diseases, the
successful implementation of which will reduce the number of cardiovascular events, thereby

13. increasing the duration of active life and reducing the cost of resources of the healthcare system
(Omland, 2010)
Highly Sensitive Cardiac Troponins
Cardiac troponins are released when the myocardium is damaged by several mechanisms
(Chaulin, 2019; Alexandrov & Mazaev, 2019; Nenakhova, 2018) With reversible damage, the
integrity of the cardiomyocyte membrane is violated, and there is a partial breakdown of the
cytosolic troponin pool into smaller fragments and their exit into the bloodstream (Chaulin et al.
2020a). With irreversible damage, intracellular acidosis increases and proteolytic enzymes are
activated, which destroy the contractile apparatus of cardiomyocytes (Chaulin et al. 2020b). The
introduction of highly sensitive test systems into clinical practice allowed detecting cardiac
troponins in almost all healthy people in low concentrations (below 99-percentile) (Chaulin et al.
2019).
Troponins are also found in other biological fluids: serous cavity fluids, liquor, urine, and
oral fluid (Chaulin et al. 2020c). The study of troponins in pericardial fluid is used in forensic
medical examination, and the determination in urine and oral fluid is of significant interest for
non- invasive diagnostics and monitoring of cardiovascular diseases (Nenakhova, 2018). An
increase in cardiac troponins (cTn) in biological fluids indicates reversible or irreversible damage
to cardiomyocytes, but does not explain the etiology and pathogenesis of this damage (Chaulin et
al. 2020b). Highly sensitive cardiac troponins are valuable diagnostic biomarkers of
cardiovascular diseases and are often used in modern research (Chaulin et al. 2020a).
Highly Sensitive Troponin-I Determining the Risk of Developing CVS Events
The term "highly sensitive" in relation to troponin does not imply the determination of its
special form, but refers to the analytical characteristics of modern highly sensitive test systems
for the determination of cardiac troponin, which, unlike the previous ones, allow with sufficient
accuracy to quantitatively measure even an extremely low level of troponin in blood serum part
of healthy people, the analytical variation in the range of the upper limit of the norm does not
exceed 10% (Aldous et al. 2011). The 99th percentile of the distribution of its values in
practically healthy individuals, which is separate for men and women, is used as the upper limit
of the reference values of highly sensitive troponin. The use of such methods has significantly
increased the clinical sensitivity of the test (Irfan et al. 2013).
What is the purpose of determining the level of Troponin-I in the blood?

14. Highly sensitive troponin is the recommended test for the diagnosis of acute myocardial
infarction. The leading symptom in patients with suspected acute coronary syndrome (ACS) is
chest pain (Reichlin et al. 2011). To make a diagnosis of acute myocardial infarction, it is
necessary to confirm the presence of acute myocardial damage (characteristic dynamics of
troponin levels with growth and / or fall, the result goes beyond the upper limit of the norm in at
least one dimension) in combination with clinical evidence of myocardial ischemia (instrumental
examination methods include ECG , Echocardiography, angiography, etc.) (Aldous et al. 2011).
Highly Sensitive Troponin in Cardiac Stratification of Stable Outpatients
The introduction of highly sensitive troponin testing methods has made it possible to
investigate the potential role of this cardiospecific marker in further refining cardiac risk in stable
outpatients, in addition to taking into account standard factors (Alexandrov & Mazaev, 2019). It
has been shown that relatively higher values of cardiospecific troponin, even within the limits of
reference values, can potentially be used as an auxiliary factor in stratification of cardiac risks
(Negahdary et al. 2017).
Conclusion
In conclusion, it seems advisable to give a typical algorithm for the diagnosis of acute
myocardial infarction, recommended by specialists from the British Heart Foundation. First of
all, an increase with a subsequent decrease in the level of troponin T, or troponin I, or creatinine
phosphokinase in combination with at least one of the following pathological conditions is
determined: 1) a clinic suspicious of acute myocardial infarction; 2) the development of
pathological Q waves on the ECG; 3) ischemic ECG changes; 4) the transferred interventions on
the coronary vessels. The study of the concentration of highly sensitive troponin-I can be used to
assess the effectiveness of statin treatment in people with coronary heart disease, diabetes, and
stroke. According to recent studies, troponin-I is predictively more favourable regardless of LDL
cholesterol lowering. Increases and / or decreases in troponin levels, indicative of myocardial
damage, are common in patients with acute respiratory infections, including COVID-19, and
correlate with disease severity.

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Januzzi Jr, J. L., Filippatos, G., Nieminen, M., & Gheorghiade, M. (2012). Troponin elevation in
patients with heart failure: on behalf of the third Universal Definition of Myocardial
Infarction Global Task Force: Heart Failure Section. European heart journal, 33(18),
2265-2271.
Keller, T., Tzikas, S., Zeller, T., Czyz, E., Lillpopp, L., Ojeda, F. M., ... & Blankenberg, S.
(2010). Copeptin improves early diagnosis of acute myocardial infarction. Journal of the
American College of Cardiology, 55(19), 2096-2106.
Keller, T., Zeller, T., Ojeda, F., Tzikas, S., Lillpopp, L., Sinning, C., ... & Blankenberg, S.
(2011). Serial changes in highly sensitive troponin I assay and early diagnosis of
myocardial infarction. Jama, 306(24), 2684-2693.
Laugaudin, G., Kuster, N., Petiton, A., Leclercq, F., Gervasoni, R., Macia, J. C., ... & Roubille,
F. (2016). Kinetics of high-sensitivity cardiac troponin T and I differ in patients with ST-
segment elevation myocardial infarction treated by primary coronary
intervention. European heart journal: acute cardiovascular care, 5(4), 354-363.
Long, B., Long, D. A., Tannenbaum, L., & Koyfman, A. (2020). An emergency medicine
approach to troponin elevation due to causes other than occlusion myocardial
infarction. The American journal of emergency medicine, 38(5), 998-1006.
Meder, B., Keller, A., Vogel, B., Haas, J., Sedaghat-Hamedani, F., Kayvanpour, E., ... &
Rottbauer, W. (2011). MicroRNA signatures in total peripheral blood as novel
biomarkers for acute myocardial infarction. Basic research in cardiology, 106(1), 13-23.
Mueller, C. (2012). Counterpoint: detection of myocardial infarction—is it all troponin? Role of
new markers. Clinical chemistry, 58(1), 162-164.
Mythili, S., & Malathi, N. (2015). Diagnostic markers of acute myocardial
infarction. Biomedical reports, 3(6), 743-748.
Negahdary, M., Behjati-Ardakani, M., Sattarahmady, N., Yadegari, H., & Heli, H. (2017).
Electrochemical aptasensing of human cardiac troponin I based on an array of gold

18. nanodumbbells-Applied to early detection of myocardial infarction. Sensors and
Actuators B: Chemical, 252, 62-71.
Nenakhova, E. A. (2018). Highly Sensitive troponin I in the early diagnosis of ACS.
In Proceedings of the III Interregional scientific and practical conference with
international participation.-Samara: OOO" etch.
Ohly, H., Gentry, S., Wigglesworth, R., Bethel, A., Lovell, R., & Garside, R. (2016). A
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quantitative and qualitative evidence. BMC Public Health, 16(1), 1-36.
Omland, T. (2010). New features of troponin testing in different clinical settings. Journal of
internal medicine, 268(3), 207-217.
Omran, M. M., Zahran, F. M., Kadry, M., Belal, A. A., & Emran, T. M. (2018). Role of
myeloperoxidase in early diagnosis of acute myocardial infarction in patients admitted
with chest pain. Journal of Immunoassay and Immunochemistry, 39(3), 337-347.
Parikh, R. H., Seliger, S. L., & deFilippi, C. R. (2015). Use and interpretation of high sensitivity
cardiac troponins in patients with chronic kidney disease with and without acute
myocardial infarction. Clinical biochemistry, 48(4-5), 247-253.
Rains, M. G., Laney, C. A., Bailey, A. L., & Campbell, C. L. (2014). Biomarkers of acute
myocardial infarction in the elderly: troponin and beyond. Clinical interventions in
aging, 9, 1081.
Raskovalova, T., Twerenbold, R., Collinson, P. O., Keller, T., Bouvaist, H., Folli, C., ... &
Labarère, J. (2014). Diagnostic accuracy of combined cardiac troponin and copeptin
assessment for early rule-out of myocardial infarction: a systematic review and meta-
analysis. European Heart Journal: Acute Cardiovascular Care, 3(1), 18-27.
Reichlin, T., Irfan, A., Twerenbold, R., Reiter, M., Hochholzer, W., Burkhalter, H., ... &
Mueller, C. (2011). Utility of absolute and relative changes in cardiac troponin
concentrations in the early diagnosis of acute myocardial infarction. Circulation, 124(2),
136-145.
Reichlin, T., Schindler, C., Drexler, B., Twerenbold, R., Reiter, M., Zellweger, C., ... & Mueller,
C. (2012). One-hour rule-out and rule-in of acute myocardial infarction using high-
sensitivity cardiac troponin T. Archives of internal medicine, 172(16), 1211-1218.

19. Solecki, K., Dupuy, A. M., Kuster, N., Leclercq, F., Gervasoni, R., Macia, J. C., ... & Roubille,
F. (2015). Kinetics of high-sensitivity cardiac troponin T or troponin I compared to
creatine kinase in patients with revascularized acute myocardial infarction. Clinical
Chemistry and Laboratory Medicine (CCLM), 53(5), 707-714.
Tricco, A. C., Lillie, E., Zarin, W., O'Brien, K. K., Colquhoun, H., Levac, D., ... & Straus, S. E.
(2018). PRISMA extension for scoping reviews (PRISMA-ScR): checklist and
explanation. Annals of internal medicine, 169(7), 467-473.
Voicu, S., Sideris, G., Deye, N., Dillinger, J. G., Logeart, D., Broche, C., ... & Henry, P. (2012).
Role of cardiac troponin in the diagnosis of acute myocardial infarction in comatose
patients resuscitated from out-of-hospital cardiac arrest. Resuscitation, 83(4), 452-458.
Wallace, A., Croucher, K., Quilgars, D., & Baldwin, S. (2004). Meeting the challenge:
developing systematic reviewing in social policy. Policy & politics, 32(4), 455-470.
Wang, X. Y., Zhang, F., Zhang, C., Zheng, L. R., & Yang, J. (2020). The biomarkers for acute
myocardial infarction and heart failure. BioMed research international, 2020.

20. Appendix 1: Search Strategy and Keywords
PubMed Search Strategy Performed 5th September’21
“Troponin” [Mesh] OR “Troponin T” [Mesh:NoExp] OR “Cardiac Regulatory Proteins”
[Mesh:NoExp] OR “Troponin I” [Mesh] OR “Troponin Elevation” [Mesh:NoExp] OR “Cardiac
Troponin T (cTnT)” [Mesh] OR “Troponin I (cTnI)” [tiab] OR “Troponin Tests” [Mesh:NoExp]
OR “Cardiac-Specific Troponin” [tiab] OR “High Troponin Levels” [Mesh]
AND
“Diagnostic Marker” [Mesh:NoExp] OR “Cardiac Arrest” [tiab] OR “Diagnosis” OR “Heart
Injury” [Mesh:NoExp] “Muscular Contraction” [Mesh:NoExp] OR “Symptoms” [tiab] OR
“Troponin Tests” [Mesh]
AND
“Myocardial Infarction” [Mesh:NoExp] OR “Muscular Contraction” [Mesh] OR “Cardiac
Arrest” [tiab] OR “Cardiac-Specific Troponin” [Mesh]
Cochrane Library Search Strategy Performed 5th September’21
“Troponin”
“Cardiac Regulatory Proteins”
“Troponin Elevation”
“Cardiac Troponin T (cTnT)”
“Troponin I (cTnI)”
“Diagnostic Marker”
“Myocardial Infarction”
“Muscular Contraction”
“Cardiac Arrest”
“Cardiac-Specific Troponin”

21. Appendix 2: PRISMA
PRISMA 2009 Flow Diagram
Records identified through
database searching
(n = 100)
Screening
Included
Eligibility
Identification
Additional records identified
through other sources
(n = 20)
Records after duplicates removed
(n = 90)
Records screened
(n = 30)
Records excluded
(n = 60 )
Full-text articles assessed
for eligibility
(n = 10 )
Full-textarticlesexcluded,
with reasons
(n = 20 )
Studies included in
qualitative synthesis
(n = 5 )
Studies included in
quantitative synthesis
(meta-analysis)
(n = 5 )

22. Appendix 2: Critical Appraisal of Selected Articles
Additional file. Quality appraisal for qualitative, quantitative and mixed methods studies
First
Author,
Year,
Referen
ce
Study
design
1. Are
the
researc
h
questio
n and
or
objecti
ves
clear?
2. Is the
theoretic
al or
ideologic
al
perspecti
ve of
author
explicit,
andHas
this
influence
d the
study
design,
methods
or
research
findings?
3. Is the
study
design
appropri
ate to
answer
the
question
?
4. Is the
context
or
setting
adequat
ely
describe
d?
5. Is the
sample
adequate
to
explore
the
range of
subjects
and
settings,
andhas
it been
drawn
from an
appropri
ate
populati
on?
6. Was
the data
collecti
on
adequat
ely
describe
d?
7. Was
the data
collecti
on
rigorous
ly
conduct
ed to
ensure
confide
nce in
the
findings
?
8. Was
there
evidenc
e that
the data
analysis
was
rigorous
ly
conduct
ed to
ensure
confide
nce in
the
findings
?
9. Are the
findings
substantia
tedby the
data?
10. Has
considerat
ion been
given to
any
limitation
s of the
methods
or data
that may
have
affected
the
results?
11. Do any
claims to
generalisab
ility follow
logically
and
theoreticall
y from the
data?
12. Have
ethical
issues
been
addressed
and
confidentia
lity
respected?
Total
# Yes
ratin
g
Overall
quality…
STRONG:
12-10Y,
MODERA
TE: 6-9Y,
Weak:1-5
Y
Alexand
rov &
Mazaev
(2019)
Qualitati
ve
Y P Y Y Y P P P P N NA CT 4 Weak
Nenakho
va
(2018)
Qualitati
ve
Y Y Y Y P P P N Y P Y CT 6
MODERA
TE
Chaulin
et al.
(2020a)
Qualitati
ve
N P P Y N N N N P P P CT 1 Weak
Chaulin
et al.
(2019)
Qualitati
ve
Y Y Y Y P P N N Y Y NA CT 6
MODERA
TE
Daubert
&
Jeremias
(2010)
Qualitati
ve
N N N Y N Y N N P P NA N 2 Weak
Negahda
ry et al.
(2017)
Quantita
ive
Y Y Y Y Y Y Y P Y Y NA N 9
MODERA
TE
Rains et
al.
(2014)
Quantita
ive
Y Y Y Y Y Y Y Y Y Y P Y 11 STRONG
Januzzi
Jr et al.
(2012)
Quantita
ive
Y Y Y Y Y Y Y Y Y P NA CT 9
MODERA
TE

23. Solecki
et al.
(2015)
Quantita
ive
Y Y Y P N P P P Y N NA N 4 WEAK
Aldous
et al.
(2011)
Quantita
ive
Y N Y Y Y Y Y Y Y N NA N 8
MODERA
TE
Answers: Y:YES, P:PARTIAL, N:NO,
NA: Not Applicable,CT:Can't tell

24. Appendix 3: Summary of Selected Articles
Retrived Articles
S.No Pro Forma Article 1 Article 2 Article 3 Article 4 Article 5
1 Reference(s) Negahdary, M., Behjati-Ardakani,M., Sattarahmady, N., Yadegari,
H., & Heli, H. (2017). Electrochemical aptasensingof humancardiac
troponinI basedon an arrayof gold nanodumbbells-Appliedtoearly
detectionof myocardial infarction. Sensors andActuators B:
Chemical, 252, 62-71.
Rains, M. G.,
Laney, C. A.,
Bailey, A. L., &
Campbell, C. L.
(2014). Biomarkers
of acute myocardial
infarctionin the
elderly: troponin
andbeyond.
Clinical
interventions in
aging, 9, 1081.
Januzzi Jr, J. L.,
Filippatos,G.,
Nieminen, M.,&
Gheorghiade, M.
(2012). Troponin
elevationin
patients with heart
failure: on behalf
of the third
Universal
Definitionof
Myocardial
InfarctionGlobal
Task Force: Heart
Failure Section.
European heart
journal, 33(18),
2265-2271.
Solecki, K., Dupuy,
A. M., Kuster, N.,
Leclercq, F.,
Gervasoni, R.,
Macia, J. C., ... &
Roubille, F. (2015).
Kinetics of high-
sensitivitycardiac
troponinT or
troponinI
comparedto
creatine kinase in
patients with
revascularized
acute myocardial
infarction. Clinical
Chemistryand
Laboratory
Medicine (CCLM),
53(5), 707-714.
Aldous, S. J.,
Florkowski, C. M.,
Crozier, I. G.,
Elliott,J., George,
P., Lainchbury, J.
G., ... & Than, M.
(2011).
Comparisonof
high sensitivity
andcontemporary
troponinassays for
the early detection
of acute
myocardial
infarctionin the
emergency
department. Annals
of clinical
biochemistry,
48(3), 241-248.

25. 2 Title Electrochemical aptasensingof humancardiac troponinI basedon
an array of goldnanodumbbells-Appliedto early detectionof
myocardial infarction.
Biomarkers of
acute myocardial
infarctionin the
elderly: troponin
andbeyond.
Troponin elevation
in patients with
heart failure: on
behalf of the third
Universal
Definitionof
Myocardial
InfarctionGlobal
Task Force:
Kinetics of high-
sensitivitycardiac
troponinT or
troponinI
comparedto
creatine kinase in
patients with
revascularized
acute myocardial
infarction.
Comparisonof
high sensitivity
andcontemporary
troponinassays for
the early detection
of acute
myocardial
infarctionin the
emergency
department.
3 Author (s) Negahdary, M., Behjati-Ardakani,M., Sattarahmady, N., Yadegari,
H., & Heli, H.
Rains, M. G.,
Laney, C. A.,
Bailey, A. L., &
Campbell, C. L.
Januzzi Jr, J. L.,
Filippatos,G.,
Nieminen, M.,&
Gheorghiade, M.
Solecki, K., Dupuy,
A. M., Kuster, N.,
Leclercq, F.,
Gervasoni, R.,
Macia, J. C., ... &
Roubille, F.
Aldous, S. J.,
Florkowski, C. M.,
Crozier, I. G.,
Elliott,J., George,
P., Lainchbury, J.
G., ... & Than, M.
4 Year of Publication 2017 2014 2012 2015 2011
5 Country of Focus None None None None None
6 Source PubMed PubMed PubMed PubMed PubMed
7 Relevent/Used
Chapters
Intro,LR, Results, Discussion Intro,LR, Results,
Discussion
Intro,LR, Results,
Discussion
Intro,LR, Results,
Discussion
Intro,LR, Results,
Discussion
8 Aim/Research Question To study early detectionof myocardial infarction through human
cardiac troponin I basedon an arrayof goldnanodumbbells.
To reviewacute
myocardial
infarctionin the
elderly.
To determine
troponinelevation
in patients with
heart failure.
To analyse kinetics
of high-sensitivity
cardiac troponin T
or troponin I.
To comparehigh
sensitivityand
contemporary
troponinassays for
the early detection
of acute
myocardial
infarctionin the
emergency
department

26. 10 Research Method(s) Quamtitave Quamtitave Quamtitave Quamtitave Quamtitave

27. S.No Pro Forma Article 6 Article 7 Article 8 Article 9 Article 10
1 Reference(s) Alexandrov, A. G., &
Mazaev, A. Y. (2019).
Chaulin am, Alexandrova
OS Cardiac troponins:
biochemical andclinical
features. Journal of
science, 8, 32.
Nenakhova,E. A. (2018).
highly Sensitive troponin
I in the early diagnosis of
ACS. In Proceedings of
the III Interregional
scientific andpractical
conference with
international
participation.-Samara:
OOO" etch.
Chaulin, A. M., Karslian,L. S.,
Alexandrov, A. G., & Duplyakov,
D. V. (2020a). Increasingthe
concentrationof cardiospecific
troponins in the absenceof
myocardial infarction. Part 1.
Doctor,31(3), 22-27. DOI:
https://doi.org/10.29296/25877305-
2020-03-04
Chaulin, A. M., Karslian,
L. S., Nurbaltaeva, D. A.,
Grigorieva, E. V., &
Duplyakov, D. V. (2019).
Metabolism of cardiac
troponins in normal and
pathological conditions.
Siberian medical review,
6, 5-14. DOI:
10.20333/2500136-2019-
6-5-14
Daubert, M. A., &
Jeremias, A. (2010).
The utility oftroponin
measurement todetect
myocardial infarction:
reviewof the current
findings. Vascular
health andrisk
management,6, 691.
2 Title Chaulin am, Alexandrova
OS Cardiac troponins:
biochemical andclinical
features.
Highly Sensitive troponin
I in the early diagnosis of
ACS. In Proceedings of
the III Interregional
scientific andpractical
conference with
international
participation.
Chaulin, A. M., Karslian,L. S.,
Alexandrov, A. G., & Increasing
the concentration ofcardiospecific
troponins in the absenceof
myocardial infarction. Part 1.
Metabolism ofcardiac
troponins in normal and
pathological conditions.
The utility oftroponin
measurement todetect
myocardial infarction:
reviewof the current
findings.

28. 3 Author (s) Alexandrov, A. G., &
Mazaev, A. Y. .
Nenakhova,E. A. Duplyakov, D. V. Chaulin, A. M., Karslian,
L. S., Nurbaltaeva, D. A.,
Grigorieva, E. V., &
Duplyakov, D. V.
Daubert, M. A., &
Jeremias, A.
4 Year of Publication 2019 2018 2020 2019 2010
5 Country of Focus None None None None None
6 Source Cochrane Library Cochrane Library Cochrane Library Cochrane Library Cochrane Library
7 Relevent/UsedChapters Intro,LR, Results,
Discussion
Intro,LR, Results,
Discussion
Intro,LR, Results, Discussion Intro,LR, Results,
Discussion
Intro,LR, Results,
Discussion
8 Aim/Research Question To determine biochemical
andclinical features of
Troponins
To study highly Sensitive
troponinI in the early
diagnosis of ACS.
To analyse cardiospecific troponins
in the absence of myocardial
infarction.
To review metabolism of
cardiac troponins.
To discuss the utilityof
troponinmeasurement
to detect myocardial
infarction.
10 Research Method(s) Qualitative Qualitaive Qualitaive Qualitaive Qualitaive