Introduction

Acute myocardial infarction (AMI) is a critical cardiovascular event that demands immediate medical attention and medical intervention.1 Recognizing the symptoms, seeking prompt medical attention, running confirmatory tests and treating accurately all play a crucial role when the clock is ticking at a faster rate in this emergency situation. Despite the latest advancements, mortality rates still remain high in AMI patients.2 Early diagnosis strategies can help rule out non-cardiac causes of chest pain and also help in cases presenting with non-ST elevation myocardial infarction (NSTEMI), whereby physicians have to keep a continuous watch on the troponin levels of the patients.3 Lifestyle changes and adherence to post-AMI treatment can all lead to better outcomes and improve quality of life (QOL) in patients suffering from coronary artery disease (CAD); however, early diagnosis remains crucial for treating this devastating disease.4

The diagnosis of AMI is currently based on clinical and paraclinical findings. Ischemic changes lead to symptoms of typical chest pain, for which patients usually approaches the emergency services. Electrocardiogram (ECG) results show ST–elevation or depression and/or pathological Q-waves or they can be normal. A typical increase in cardiac troponin T or I levels and a rapid rise in creatine kinase isoenzyme myocardial band (CK-MB) levels usually confirms diagnosis. Coronary angiography can be used as a confirmatory test and as a therapeutic procedure but, in many instances, healthcare facilities lack these units or specialized teams for interventional cardiology, which further increases the difficulty of treating this life-threatening condition.5,6

Troponin is a widely used cardiac biomarker for the diagnosis and risk stratification of CAD, a condition characterized by narrowing or blockage of coronary arteries, thus compromising blood supply to the myocardium. Troponins are a group of proteins found in cardiac myocytes, which play a crucial role in regulating muscle contraction. During myocardial injury due to decreased perfusion of the muscle wall, such as in the case of myocardial infarction (heart attack) or unstable angina, troponins are released into the bloodstream, leading to elevated levels of this biomarker.7

The use of troponin as a diagnostic marker for CAD has revolutionized the field of cardiovascular medicine. Traditionally, the diagnosis of CAD relied on clinical symptoms, electrocardiogram findings, and imaging techniques, which were limited in their sensitivity and specificity. Lately, troponins, particularly cardiac troponin I (cTnI) and cardiac troponin T (cTnT), have emerged as highly sensitive and specific biomarkers for detecting myocardial injury associated with CAD. Troponin levels are measured upon admission to the hospital and at subsequent time points to assess the extent of myocardial injury and guide clinical decision-making.8

The development of high-sensitivity troponin assays (Hs-T) has further improved the detection and risk stratification of CAD. These high-sensitivity assays can measure troponin levels with greater precision at lower concentrations, enabling the detection of even minor myocardial damage. Hence, it can be said that the high-sensitivity troponin assays have improved the early diagnosis of CAD, allowing prompt initiation of appropriate treatment strategies and thus achieving better patient outcomes. However, a means of diagnosing myocardial infarction as quickly as possible, given the fact that the time elapsed from the occurrence of the infarction to the opening of the coronary artery is directly proportional to the amount of necrotic myocardium, remains elusive. Unfortunately, the detection of cardiac troponins is done a few hours after the occurrence of myocardial necrosis.9,10 In addition to these markers, the neutrophil to albumin ratio can be considered as a predictor of severity of CAD in NSTEMI patients.11 Global longitudinal strain (GLS) value is now used for prediction of mortality rates in STEMI patients.12

Hence, it can be said that troponin, specifically cTnI and cTnT, is a valuable biomarker for the diagnosis and risk stratification of CAD. Its high sensitivity and specificity, along with the advent of high-sensitivity troponin assays, have transformed the approach to CAD diagnosis, enabling earlier detection of myocardial injury and improved risk assessment.13

The timeline for troponin may vary from individual to individual and is based on the severity of the myocardial infarction. A general timeline of troponin levels in myocardial infarction calculated from the appearance of symptoms is illustrated in Table 1. (Table 1)

Table 1 Timelines Concerning Troponin Levels in Myocardial Infarction from the Appearance of Symptoms

Another cardiac marker routinely used is CK-MB, an enzyme found predominantly in the heart muscle. It is a subtype of the creatine kinase isoenzyme, which is responsible for catalyzing the conversion of creatine to phosphocreatine, playing a role in energy metabolism within cells. CK-MB is commonly used as a diagnostic marker for myocardial infarction. It is released in the bloodstream, indicating damage to the myocytes. Therefore, elevated levels of CK-MB in the blood can indicate acute myocardial infarction (AMI) or other heart-related conditions.14,15

Traditionally, CK-MB was measured through laboratory blood tests. However, in recent years, the use of other cardiac biomarkers, such as troponin, has become more prevalent due to their higher specificity and sensitivity in diagnosing myocardial injury.15

Lactate dehydrogenase (LDH) is an enzyme found in various tissues of the body, including the heart. LDH exists in different forms, or isoenzymes, which are designated LDH-1 to LDH-5. LDH-1 is mainly found in the heart, and LDH-2 is found in lesser amounts in the heart as well as in other tissues.

Karakayalı et al demonstrated that the white blood cell count to mean platelet volume ratio is associated with early risk stratification in patients with ST-segment elevation myocardial infarction.16 Similarly, the authors also stated that the prognostic value of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, which indicates the nutritional and inflammatory status of the body, can be helpful in predicting in-hospital mortality in patients with ST-elevation myocardial infarction undergoing coronary intervention.17

During an AMI, due to the adverse effect of reduced perfusion on the myocardial cells, LDH-1 levels in the bloodstream can increase (Table 2). However, LDH is not considered a specific marker for myocardial infarction, as LDH is also present in other tissues, such as the liver, kidneys, and red blood cells. Therefore, LDH alone is not commonly used as a definitive diagnostic tool for MI. Heart fatty acid binding protein (H-FABP) is a cardiac biomarker that has gained attention over recent years for its potential role in the diagnosis and management of myocardial infarction, commonly known as a heart attack. H-FABP is a small protein primarily found in cardiac muscle cells and is involved in the transport of fatty acids within the heart. During a myocardial infarction, damaged heart cells release H-FABP into the bloodstream, leading to elevated levels of this biomarker.18–20 Measurement of this biomarker is accurate, non-invasive, easy to perform, reveals infarct-related artery patency, and can be used to check if thrombolysis is adequate or not.21 The urine and plasma levels of H-FABP can also be loyal indicators of myocardial perfusion injury in patients undergoing cardiac surgery, according to a study conducted on ten patients by Hayashida et al22

Table 2 Timeline Comparison of Different Cardiac Markers in Relation to Acute Myocardial Infarction

The use of H-FABP as a cardiac marker has been investigated recently to determine its diagnostic value and potential clinical applications. Early detection of myocardial infarction is crucial for prompt intervention and optimal patient outcomes. Traditional cardiac biomarkers, such as troponin, have been widely used for the diagnosis of myocardial infarction, but they may take several hours to become elevated after the onset of symptoms. It can also be used a prognostic tool for determining a 30-day risk evaluation for patients suffering from acute coronary syndrome.23 In a study conducted by O’Donoghue et al involving 2287 patients suffering from ACS, the clinical importance of prognostic evaluation with H-FABP was proven.24 The study demonstrated how H-FABP can be considered superior to other cardiac biomarkers in terms of mortality risk prediction.

The unique characteristic of H-FABP is its rapid release into the bloodstream following cardiac injury, making it a promising candidate for early detection of myocardial infarction. Studies have shown that H-FABP can be detected in the blood as early as 1–3 hours after the onset of symptoms, providing a potential advantage over other cardiac biomarkers.25,26

However, the clinical utility of H-FABP as a stand-alone marker for myocardial infarction diagnosis is still under investigation. Its specificity to myocardial infarction has been questioned, as elevated H-FABP levels can also occur in other conditions that cause damage to the heart muscle, such as myocarditis or congestive heart failure. Therefore, H-FABP is often used in combination with other markers, clinical symptoms, and diagnostic tools to improve the accuracy of myocardial infarction diagnosis.

The study aims to explore iwhether H-FABP can be beneficial in the context of early diagnosis of acute myocardial infarction compared to other standard cardiac markers, to evaluate its diagnostic value, potential use in risk stratification, and limitations.

Materials and Methods

We evaluated 83 consecutive COVID-negative myocardial infarction patients admitted between August 2020 to June 2021 in the intensive coronary care unit of the County Hospital, Baia Mare, Romania, out of the total of 485 coronary patients addressed in that period. The patients were tested for H-FABP levels along with standard cardiac markers at the time of presentation to the hospital with symptoms indicating an ongoing coronary event. The patients were divided into two groups. Patients presenting to the hospital between 0 to 4 hours of the onset of chest pain were labelled group 1 and those presenting later than 4 hours were termed group 2. Patients were also divided according to having STEMI or not having STEMI. Statistical analysis of the results was performed to identify the specificity and sensitivity of testing the H-FABP and whether it contributes to early diagnosis and can be relied upon.

Before initiating the study, approval from the relevant ethical committees was obtained, according to the tenets of the Declaration of Helsinki. The study was approved by the Comisia de Etică a Cercetării Stiintifice (Ethics Committee for Scientific Research) of the Dr. Constantin Opriș County Emergency Baia Mare Hospital, Baia Mare (24406, 27.08.2021) and by the ethics committee of the Victor Babes University of Medicine and Pharmacy, Timisoara (approval reg. no. 74/2020, 22/2020 rev. 01.04.2024).

The inclusion criteria in the study were represented by the presence of the diagnosis of MI established in the following cumulative conditions: patients being diagnosed based on the European Society of Cardiology guidelines27 for acute myocardial infarction andpresenting at the hospital up to a maximum of 24 hours after the onset of pain. Those with thrombotic occlusion or stenotic lesion in the left coronary artery, circumflex coronary artery, and/or right coronary artery were included.

The exclusion criteria were as follows: a diagnosis of neoplasm, degenerative disease, atrial fibrillation, or COVID-19 infection; presenting at the hospital more than 24 hours after the onset of pain; participation in any clinical study in the previous month; or having hematological, hepatic, or renal pathologies.

The patients’ written informed consent was obtained before enrollment in our study.

There were no exclusion criteria based on sex, age, political or religious affiliation, socio-economic status, place of origin (city or village), or means of transport to hospital.

After expressing voluntary agreement to participate in the study based on the inclusion and exclusion criteria, 83 patients were selected.

To establish the diagnosis of acute myocardial infarction, at the time of presentation to the emergency department of the hospital the patients biological samples were sent for the determination of enzymes of myocardial necrosis (high-sensitivity troponin I, total CK, CK-MB), blood count, serum creatinine, serum urea, serum glucose, ASAT, ALAT, and coagulation levels. For H-FABP evaluation, blood collection was also carried out, but its determination required a special regime.

The plasma, obtained by blood centrifugation, was stored at −40°C until the number of patients required to open the H-FABP determination kit was reached. For the determination of H-FABP, the Human FABP3 (cardiac) ELISA Kit was used, which had a maximum possible number of 96 samples.

In the shortest possible time from the first medical contact, the patients were transferred to the cardiac catheterization laboratory for emergency coronary angiography to detect the culprit lesion, as well as for interventional de-blockage through the percutaneous intravascular placement of pharmacologically active stents in accordance with the current recommendations of the practice guidelines of the European Society of Cardiology.27 The drug treatment instituted after the coronary revascularization procedures was according to the recommendations of good practice guidelines.27 The data were centralized using Microsoft Excel and their statistical processing was carried out using MedCalc v20.023, considering statistical significance values of p <0.05. We use descriptive statistics, figures, and tables to summarize our findings. Results for targeted variables are presented using descriptive statistics (mean, standard deviation, range, median, and associated interquartile range) for continuous data, and counts with associated percentages for categorical data.

Results

We analyzed 83 patients diagnosed with MI, who underwent angio coronagraphy and were divided according to the time elapsed from the onset of pain to the first medical contact into two groups. Group 1 patients had their first medical contact at 0–4 hours after the onset of pain (36 patients) and the second group at 4–24 hours after (47 patients). Further, they were divided according to the number of arteries causing the vascular disease, monovascular, bivascular or trivascular, and the type of myocardial infarction, that is, whether STEMI or non-STEMI (Figure 1). The basal demographic data are shown in Table 3. (Table 3)

Table 3 Characteristics of the Study Population

Figure 1 Patient distribution according to the moment of first medical contact, type of myocardial infarction, and number of vessels involved.

Among these patients, three in group 1 were suffering from multi-vessel disease and 12 from group 2. There were 33 patients with monovascular disease in group 1 and 35 in group 2. Regardless of when the patient presented, the presence of non-STEMI myocardial infarction was statistically significant (chi-square test, p-value = 0.0029). It can also be observed that the probability of presenting with a STEMI increases significantly if the duration from the onset of pain to the first medical contact is over 4 hours (two-sample z-test for proportions, p-value = <0.0001). Even in this situation, the number of non-STEMI coronary events is significantly higher during the same time interval (two-sample z-test for proportions, p-value = <0.0001). It is also observed that the incidence of non-STEMI type events predominates regardless of time interval until the moment of first medical contact.

To analyze the usefulness of H-FABP compared to already used enzyme markers (CK-MB respectively hsTnI) in the diagnosis of patients with acute coronary syndromes to confirm the diagnosis of myocardial infarction, an ROC curve was used. An ROC curve (receiver operating characteristic curve) is a graph showing the performance of a classification model at all classification thresholds. The statistical test used was a comparison of ROC curves and areas under the curve (AUC) for several classification variables of MI.

Based on the data analyzed in this study, it can be said that, despite intense efforts via social media to highlight the possibility of experiencing a myocardial infarction in the case of chest pain, the presentation of patients to the emergency room is still quite delayed. Further, a significant number of patients who could benefit from interventional myocardial reperfusion methods fail to present themselves during the optimal therapeutic window. In the situation of patients presented in the first 4 hours from the onset of pain, a comparison of ROC curves is presented in Table 4, the variables used being CK-MB, H-FABP, and hsTni for patients who presented with MI. (Table 4) As can be seen from Table 5 and Figure 2, (Table 5) (Figure 2) there are statistical differences between the AUC for the three elements under discussion, between CK-MB and hsTni, registering a p-value of 0.035, and for the comparison between H-FABP and hsTni, registering a p-value of 0.039. In other words, hsTni is a weaker discriminating element than H-FABP and CK-MB in the case of patients presenting at the hospital up to a maximum of 4 hours after the onset of chest pain.

Table 4 Comparison of AUC for Patients Presenting in Less than 4 Hours from the Onset of Chest Pain

Table 5 Pairwise Comparison of ROC Curves for Patients Presenting in Less than 4 Hours from the Onset of Chest Pain

Figure 2 Pairwise comparison of ROC curves for patients included in group 1.

Regarding group 2, the analyzed parameters were the same (CK-MB, hsTni, H-FABP). The comparison of AOC is presented in Tables 6 and 7 and Figure 3 shows the pairwise comparison of ROC curves. (Tables 6 and 7)

Table 6 Comparison of AUC for Patients Presenting After 4 Hours from the Onset of Chest Pain

Table 7 Pairwise Comparison of ROC Curves for Patients Presenting After 4 Hours from the Onset of Chest Pain

Figure 3 Pairwise comparison of ROC curves for patients included in group 2.

As results from the data show, there are statistical differences between the AUC of H-FABP and hsTni (p-value = 0.035) and, in this situation, H-FABP proves to be a significantly better discriminator in detecting acute myocardial infarction at an early stage (Figure 3).

The sensitivity and specificity of all three biomarkers studied, in both groups based on time of presentation, are shown in Table 8. (Table 8)

Table 8 Sensitivity and Specificity of CK-MB, hsTnI, and H-FABP in Myocardial Infarction Patients

Discussion

The data presented in our research clearly demonstrates that H-FABP can be a useful tool for diagnosing acute myocardial infarction at an early stage, especially when clinical and paraclinical evaluations are not clear or require time. A simple cardiac biomarker like H-FABP can help clinicians save time and reach accurate diagnoses both in STEMI and non-STEMI cases.

Serial troponin levels are required to rule out the chance of having a myocardial injury if their level at the time of the first determination does not fall within the diagnostic limits for acute myocardial infarction.

During COVID-19, many doctors struggled to differentiate between the most common symptom, myalgia, and chest pain due to a cardiac cause or entirely due to COVID-19. Indeed, some researchers described myocardial issues post-COVID-19 infectionas increasing the complexity involved in diagnosing and managing already complex entities.28,29 Various studies reported the presence of chest pain mimicking myocardial infarction and a rise in new-onset rhythm disturbances, in previously healthy individuals,30 especially when anxiety levels were high due to the devastating nature of coronavirus. In such instances, tests to rapidly exclude a cardiac cause, such as myocardial infarction or a thromboembolic event causing coronary blockage, which result in myocardial injury, can help physicians to a great extent. Rosca et al reported cases of rhythm disturbance without previous cardiac pathologies in healthy young men who presented with chest pain and syncopal episodes.31 Although the culprit was coronavirus infection leading to arrhythmias, a test like H-FABP can make it easier for the physician to work in critical periods such as the pandemic and rule out the need for the patient to be transferred toa cardiac catheterization lab immediately. Moreover, the use of bioassays with increased sensitivity for myocardial injury will decrease the need for invasive coronary investigations, thus limiting the iatrogenic risk in these patients. Multimerin-2 levels and a rise in interim blood pressure difference are shown to indicate the presence of collateral coronary circulation in MI patients and post-interventions,32,33 but they are not commonly taken into consideration and standard biomarkers are used extensively. The rise in troponin levels and CK-MB due to noncardiac causes increase the difficulty of diagnosis, especially when the patient is presenting with nonspecific chest pain and stroke.34 One rare association, but which is burdened by increased mortality, is that of the overlap between myocardial infarction and stroke.35 This clinical situation is all the more therapeutically exciting because the two ischemic events have different therapeutic windows.9,10,36 The limitations of cardiac markers of myocardial necrosis are mainly represented by the time elapsed from the occurrence of the acute coronary event to their increase, as well as their existence from non-cardiac sources.10,36 It should also not be forgotten that there are non-cardiac conditions that can induce electrocardiographic changes that can mimic acute myocardial infarction, including stroke.37 In these situations, the existence of markers of myocardial necrosis that have an increase in plasma concentration as close as possible to the moment of its installation is mandatory. One of the possible variants is the dosage of H-FABP whose origin is predominantly cardiac.38 With the improvement in laboratory methods for H-FABP dosage, their sensitivity and specificity has increased.38,39

Conclusion

H-FABP can be considered an important tool due to its accuracy and early rise in patients suffering from myocardial injury. Standard procedure protocols for all patients presenting to the emergency units with a suspicion of acute myocardial infarction should be evaluated for H-FABP, in addition to the pre-existing testing plans, as it can save time and the financial burden of performing serial tests, especially in the case of NSTEMI. Ruling out the possibility of myocardial infarction by performing a single test like H-FABP can reduce not only the financial burden of a series of investigations but also the anxiety levels of the patient and their relatives. Upon ruling out the possibility of a heart attack, the physicians can search for the underlying cause that mimicked the symptoms of a possible MI. This study also reiterates the importance of prompt recognition of non-STEMI myocardial infarction, knowing that “time is myocardium” and the more prompt and correct the therapeutic sanctions are, the greater is the amount of saved myocardium.

Data Sharing Statement

All data and materials will be made available on written request to the corresponding author.

Ethics Approval

Before the commencement of the study, ethical approval and written consent was obtained from all patients/individuals and both ethical committees based on the tenets of the Declaration of Helsinki. The study was approved by the “Comisia de Etică a Cercetării Stiintifice” (Ethics Committee for Scientific Research) of the Dr. Constantin Opriș County Emergency Baia Mare Hospital, Romania (24406, 27.08.2021) and the ethics committee of Victor Babes University of Medicine and Pharmacy, Timisoara (approval reg. nr. 74/2020, 22/2020 rev. 01.04.2024).

Approval Statement

All authors have read and approved the final version of the manuscript.

Acknowledgments

The work was carried out in the Department of Cardiology, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania and Dr. Constantin Opriș County Emergency Baia Mare Hospital, Romania.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

We would like to acknowledge Victor Babes University of Medicine and Pharmacy Timisoara, Romania for its support in covering the costs of publication for this research paper.

Disclosure

The authors declare that there is no conflict of interest.

References

1. Dauerman HL, Ibanez B. The Edge of Time in Acute Myocardial Infarction. J Am Coll Cardiol. 2021;77(15):1871–1874. doi:10.1016/j.jacc.2021.03.003 PubMed PMID: 33858623.

2. Aso S, Imamura H, Sekiguchi Y, et al. Incidence and mortality of acute myocardial infarction. A population-based study including patients with out-of-hospital cardiac arrest. Int Heart J. 2011;52(4):197–202. doi:10.1536/ihj.52.197 PubMed PMID: 21828943.

3. Stengaard C, Sørensen JT, Rasmussen MB, Bøtker MT, Pedersen CK, Terkelsen CJ. Prehospital diagnosis of patients with acute myocardial infarction. Diagnosis. 2016;3(4):155–166. doi:10.1515/dx-2016-0021 PubMed PMID: 29536903.

4. Lee YM, Kim RB, Lee HJ, et al. Relationships among medication adherence, lifestyle modification, and health-related quality of life in patients with acute myocardial infarction: a cross-sectional study. Health Qual Life Outcomes. 2018. 16(1):100. 10.1186/s12955-018-0921-z. Epub 20180522. PubMed PMID: 29788961; PubMed Central PMCID: PMC5964665.

5. Zeymer U. Diagnosis and initial management of acute myocardial infarction. MMW Fortschr Med. 2019;161(4):34–36. doi:10.1007/s15006-019-0223-3 PubMed PMID: 30830611.

6. Rozenman Y, Gotsman MS. The earliest diagnosis of acute myocardial infarction. Annu Rev Med. 1994;45(1):31–44. doi:10.1146/annurev.med.45.1.31 PubMed PMID: 8198386.

7. Parikh RH, Seliger SL, de Lemos J, et al. Prognostic Significance of High-Sensitivity Cardiac Troponin T Concentrations between the Limit of Blank and Limit of Detection in Community-Dwelling Adults: a Metaanalysis. Clin Chem. 2015. 61(12):1524–1531. 10.1373/clinchem.2015.244160. Epub 20151027. PubMed PMID: 26506994.

8. Morrow DA. Clinical application of sensitive troponin assays. N Engl J Med. 2009;361(9):913–915. doi:10.1056/NEJMe0905790 PubMed PMID: 19710490.

9. Collet J-P, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2020;42:1289–1367. doi:10.1093/eurheartj/ehaa575

10. Thygesen K. ‘Ten Commandments’ for the Fourth Universal Definition of Myocardial Infarction 2018. Eur Heart J. 2019;40(3):226. doi:10.1093/eurheartj/ehy856 PubMed PMID: 30649367.

11. Karasu M, Karaca Y, Yıldırım E, Kobat MA, Er F. Neutrophil-to-albumin ratio: a promising tool for CAD assessment in non-ST elevation AMI. Eur Rev Med Pharmacol Sci. 2023;27(24):11832–11839. doi:10.26355/eurrev_202312_34781 PubMed PMID: 38164846.

12. Ravenna E, Locorotondo G, Manfredonia L, et al. Global longitudinal strain for prediction of mortality in ST-segment elevation myocardial infarction and aortic stenosis patients: two sides of the same coin. Eur Rev Med Pharmacol Sci. 2023;27(21):10736–10748. doi:10.26355/eurrev_202311_34354 PubMed PMID: 37975399.

13. Filusch A, Giannitsis E, Katus HA, Meyer FJ. High-sensitive troponin T: a novel biomarker for prognosis and disease severity in patients with pulmonary arterial hypertension. Clin Sci. 2010. 119(5):207–213. 10.1042/cs20100014. Epub 20100602. PubMed PMID: 20412051.

14. Ternant D, Ivanes F, Prunier F, et al. Revisiting myocardial necrosis biomarkers: assessment of the effect of conditioning therapies on infarct size by kinetic modelling. Sci Rep. 2017. 7(1):10709. 10.1038/s41598-017-11352-4. Epub 20170906. PubMed PMID: 28878319; PubMed Central PMCID: PMC5587689.

15. Fan J, Ma J, Xia N, Sun L, Li B, Liu H. Clinical Value of Combined Detection of CK-MB, MYO, cTnI and Plasma NT-proBNP in Diagnosis of Acute Myocardial Infarction. Clin Lab. 2017;63(03/2017):427–433. doi:10.7754/Clin.Lab.2016.160533 PubMed PMID: 28271683.

16. Karakayalı M, Omar T, Artac I, et al. The white blood cell count to Mean Platelet Volume Ratio (WMR) is associated with syntax score in patients with ST-segment elevation myocardial infarction. Kafkas J Med Sci. 2023;13(2):173–178. doi:10.5505/kjms.2023.98512

17. Karakayali M, Omar T, Artac I, et al. The prognostic value of HALP score in predicting in-hospital mortality in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Coron Artery Dis. 2023. 34(7):483–488. 10.1097/mca.0000000000001271. Epub 20230728. PubMed PMID: 37799045.

18. Jaffe AS, Ravkilde J, Roberts R, et al. It’s time for a change to a troponin standard. Circulation. 2000;102(11):1216–1220. doi:10.1161/01.cir.102.11.1216 PubMed PMID: 10982533.

19. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J. 2019;40(3):237–269. doi:10.1093/eurheartj/ehy462 PubMed PMID: 30165617.

20. Das DK, Barua PK, Jones RM. Release of fatty acid-binding protein from ischemic-reperfused rat heart and its prevention by mepacrine. Biochim Biophys Acta. 1991;1073(2):394–401. doi:10.1016/0304-4165(91)90148-a PubMed PMID: 2009286.

21. de Lemos JA, Antman EM, Morrow DA, et al. Heart-type fatty acid binding protein as a marker of reperfusion after thrombolytic therapy. Clin Chim Acta. 2000;298(1–2):85–97. doi:10.1016/s0009-8981(00)00259-x PubMed PMID: 10876006.

22. Hayashida N, Chihara S, Akasu K, et al. Plasma and urinary levels of heart fatty acid-binding protein in patients undergoing cardiac surgery. Jpn Circ J. 2000;64(1):18–22. doi:10.1253/jcj.64.18 PubMed PMID: 10651201.

23. Suzuki M, Hori S, Noma S, Kobayashi K. Prognostic value of a qualitative test for heart-type fatty acid-binding protein in patients with acute coronary syndrome. Int Heart J. 2005;46(4):601–606. doi:10.1536/ihj.46.601 PubMed PMID: 16157951.

24. O’Donoghue M, de Lemos JA, Morrow DA, et al. Prognostic utility of heart-type fatty acid binding protein in patients with acute coronary syndromes. Circulation. 2006. 114(6):550–557. 10.1161/circulationaha.106.641936. Epub 20060731. PubMed PMID: 16880323.

25. Apple FS, Collinson PO. Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem. 2012. 58(1):54–61. 10.1373/clinchem.2011.165795. Epub 20110930. PubMed PMID: 21965555.

26. Rosalki SB, Roberts R, Katus HA, Giannitsis E, Ladenson JH, Apple FS. Cardiac biomarkers for detection of myocardial infarction: perspectives from past to present. Clin Chem. 2004. 50(11):2205–2213. 10.1373/clinchem.2004.041749. Epub 20041001. PubMed PMID: 15502101.

27. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720–3826. doi:10.1093/eurheartj/ehad191 PubMed PMID: 37622654.

28. Poletaev V, Antonelli D, Rozner E, Turgeman Y. [ACUTE MYOCARDIAL INFARCTION FOLLOWING COVID-19]. Harefuah. 2022;161(7):416–418. PubMed PMID: 35833426.

29. Duda-Seiman D, Kundnani NR, Dugaci D, Man DE, Velimirovici D, Dragan SR. COVID-19 Related Myocarditis and Myositis in a Patient with Undiagnosed Antisynthetase Syndrome. Biomedicines. 2022. 11(1):11. 10.3390/biomedicines11010095. Epub 20221230. PubMed PMID: 36672603; PubMed Central PMCID: PMC9856070.

30. Cabrera Martimbianco AL, Pacheco RL, Bagattini ÂM, Riera R. Frequency, signs and symptoms, and criteria adopted for long COVID-19: a systematic review. Int J Clin Pract. 2021. 75(10):e14357. 10.1111/ijcp.14357. Epub 20210602. PubMed PMID: 33977626; PubMed Central PMCID: PMC8236920.

31. Rosca CI, Branea HS, Sharma A, et al. Rhythm Disturbances in Post-Acute COVID-19 Syndrome in Young Men without Pre-Existing Known Cardiovascular Disease-A Case Series. Biomedicines. 2023;11(4):11. doi:10.3390/biomedicines11041146 PubMed PMID: 37189764; PubMed Central PMCID: PMC10136152.

32. Demirkıran A, Aydın C, Yılmaz A, et al. A new marker of coronary collateral flow in patients presenting with acute myocardial infarction. Eur Rev Med Pharmacol Sci. 2023;27(13):6256–6263. doi:10.26355/eurrev_202307_32985 PubMed PMID: 37458637.

33. Zehir R, Güvendi Şengör B, Yılmaz C. The effect of interarm blood pressure difference on coronary collateral flow in patients with ST-segment elevation myocardial infarction who had undergone primary percutaneous coronary intervention. Eur Rev Med Pharmacol Sci. 2023;27(12):5515–5521. doi:10.26355/eurrev_202306_32788 PubMed PMID: 37401287.

34. Rosca CI, Sharma A, Nisulescu DD, et al. Prevalence of Cardio-Embolic Brain Complications in Permanent and Paroxysmal Atrial Fibrillation Patients. Healthcare. 2023;11(2). Epub 20230106. doi: 10.3390/healthcare11020175. PubMed PMID: 36673543; PubMed Central PMCID: PMC9858915

35. Yeo LLL, Andersson T, Yee KW, et al. Synchronous cardiocerebral infarction in the era of endovascular therapy: which to treat first? J Thromb Thrombolysis. 2017;44(1):104–111. doi:10.1007/s11239-017-1484-2 PubMed PMID: 28220330.

36. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: a Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019. 50(12):e344–e418. 10.1161/str.0000000000000211. Epub 20191030. PubMed PMID: 31662037.

37. Fure B, Bruun Wyller T, Thommessen B. Electrocardiographic and troponin T changes in acute ischaemic stroke. J Intern Med. 2006;259(6):592–597. doi:10.1111/j.1365-2796.2006.01639.x PubMed PMID: 16704560.

38. Moon M-G, Yoon C-H, Lee K, Kang S-H, Youn T-J, Chae I-H. Evaluation of Heart-type Fatty Acid-binding Protein in Early Diagnosis of Acute Myocardial Infarction. J Korean Med Sci. 2021;36(8). doi:10.3346/jkms.2021.36.e61

39. Carroll C, Al Khalaf M, Stevens JW, et al. Heart-type fatty acid binding protein as an early marker for myocardial infarction: systematic review and meta-analysis. Emerg Med J. 2013. 30(4):280–286. 10.1136/emermed-2012-201174. Epub 20120516. PubMed PMID: 22593266.