Performance analysis considering endpoints for three accelerated diagnostic protocols for chest pain.

INTRODUCTION: The modified accelerated diagnostic protocol (ADP) to assess patients with chest pain symptoms using troponin as the only biomarker (mADAPT), the History, ECG, Age, Risk factors, and Troponin (HEART) pathway, and the Emergency Department Assessment of Chest Pain Rule (EDACS)-ADP, are the three most well-known ADPs for patients with chest pain. These ADPs define major adverse cardiac event (MACE) as components of acute myocardial infarction, revascularization, and death; unstable angina is not included as an endpoint. METHODS: We performed a single-center prospective observational study comparing the performance of these 3 ADPs for patients with 30-day MACE with and without unstable angina. We hypothesized that these ADPs will have high sensitivities for MACE without unstable angina, a definition used for score derivation studies. However, when unstable angina is included in the MACE, their performances would be lower than the acceptable rate of >99% sensitivity. RESULTS: A total of 1,214 patients were included in the analysis. When unstable angina was not included in the endpoint, sensitivities for MACE were 99.1% (95% confidence interval [CI]: 96.7-99.9%), 99.5% (95% CI: 97.4-100%), and 100% (95% CI: 98.3-100%) for mADAPT, EDACS-ADP, and HEART pathway, respectively. The HEART pathway had the highest proportion of patients classified as low risk (39.2%, 95% CI: 35.8-42.9%), followed by EDACS-ADP (31.3%, 95% CI: 28.2-34.6%) and mADAPT (29.3%, 95% CI: 26.4-32.5%). However, when unstable angina was included in the MACE, sensitivities were 96.6% (95% CI: 94.4-98.1%) for mADAPT, 97.3% (95% CI: 95.3-98.6%) for EDACS-ADP, and 97.3% (95% CI: 95.3-98.6%) for the HEART pathway, respectively. There were 15 false-negative cases with mADAPT, and 12 false-negative cases each for EDACS-ADP and HEART pathway. CONCLUSION: All three ADPs-mADAPT, EDACS-ADP, and HEART pathway-were similarly accurate in their discriminatory performance for the risk stratification of ED patients presenting with possible ACS when unstable angina was not included in the endpoint. The HEART pathway showed the best combination of sensitivity and proportion of patients that can be classified as safe for early discharge. However, when unstable angina was added to the endpoint, all three ADPs did not show appropriate safety levels and their performances were lower than the acceptable risk of MACE.

Development of a prehospital prediction model for risk stratification of patients with chest pain.

INTRODUCTION: Chest pain is one of the most common reasons for contacting the emergency medical services (EMS). About 15% of these chest pain patients have a high-risk condition, while many of them have a low-risk condition with no need for acute hospital care. It is challenging to at an early stage distinguish whether patients have a low- or high-risk condition. The objective of this study has been to develop prediction models for optimising the identification of patients with low- respectively high-risk conditions in acute chest pain early in the EMS work flow. METHODS: This prospective observational cohort study included 2578 EMS missions concerning patients who contacted the EMS in a Swedish region due to chest pain in 2018. All the patients were assessed as having a low-, intermediate- or high-risk condition, i.e. occurrence of a time-sensitive diagnosis at discharge from hospital. Multivariate regression analyses using data on symptoms and symptom onset, clinical findings including ECG, previous medical history and Troponin T were carried out to develop models for identification of patients with low- respectively high-risk conditions. Developed models where then tested hold-out data set for internal validation and assessing their accuracy. RESULTS: Prediction models for risk-stratification based on variables mutual for both low- and high-risk prediction were developed. The variables included were: age, sex, previous medical history of kidney disease, atrial fibrillation or heart failure, Troponin T, ST-depression on ECG, paleness, pain debut during activity, constant pain, pain in right arm and pressuring pain quality. The high-risk model had an area under the receiving operating characteristic curve of 0.85 and the corresponding figure for the low-risk model was 0.78. CONCLUSIONS: Models based on readily available information in the EMS setting can identify high- and low-risk conditions with acceptable accuracy. A clinical decision support tool based on developed models may provide valuable clinical guidance and facilitate referral to less resource-intensive venues.

Warning system improve the clinical outcomes in transfer patients with ST-segment elevation myocardial infarction.

ABSTRACT: A warning system included directly faxing electrocardiography information to the mobile phone immediately after an ST-segment elevation myocardial infarction (STEMI) diagnosis was made at a non-percutaneous coronary intervention (PCI) capable hospital. This study aimed to explore the outcomes after using a warning system in transfer STEMI patients.From October 2013 to December 2016, 667 patients experienced a STEMI event and received primary PCI at our institution. 274 patients who were divided into transfer group were transferred from non-PCI capable hospitals and connected to a first-line cardiovascular doctor by the warning system. Other 393 patients were divided into the non-transfer group.The transfer group still had a longer pain-to-reperfusion time and presented higher troponin-I level when compared with non-transfer group. There was no significant difference in the use of drug-eluting stent and procedural devices between non-transfer and transfer groups. The prevalence of different anti-platelet agents loading did not differ between non-transfer and transfer groups. Non-significant trend about higher prevalence of statin use was noted in transfer group (78.9% vs 86.1%, P = .058). The transfer group presented similar clinical short-term results regarding both cardiovascular and all-cause mortality when comparing with non-transfer group. The transfer group provided non-significant trend about lower one-year cardiovascular mortality (10.7% vs 6.2%, P = .052) and lower all-cause mortality (12.2% vs 6.9%, P = .026) when compared with non-transfer group. There was a significant difference in the Kaplan-Meier curve of 1-year cardiovascular mortality between the transfer group and the non-transfer group (P = .049).After using the warning system, the inter-facility transfer group had comparable outcomes even though a longer pain-to-reperfusion time and a higher peak troponin-I level when comparing with non-transfer group.

Downstream Cascades of Care Following High-Sensitivity Troponin Test Implementation.

BACKGROUND: Patients with chest pain are often evaluated for acute myocardial infarction through troponin testing, which may prompt downstream services (cascades) of uncertain value. OBJECTIVES: This study sought to determine the association of high-sensitivity cardiac troponin (hs-cTn) assay implementation with cascade events. METHODS: Using electronic health record and billing data, this study examined patient-visits to 5 emergency departments from April 1, 2017, to April 1, 2019. Difference-in-differences analysis compared patient-visits for chest pain (n = 7,564) to patient-visits for other symptoms (n = 100,415) (irrespective of troponin testing) before and after hs-cTn assay implementation. Outcomes included presence of any cascade event potentially associated with an initial hs-cTn test (primary), individual cascade events, length of stay, and spending on cardiac services. RESULTS: Following hs-cTn implementation, patients with chest pain had a 2.8% (95% confidence interval [CI]: 0.72% to 4.9%) net increase in experiencing any cascade event. They were more likely to have multiple troponin tests (10.5%; 95% CI: 9.0% to 12.0%) and electrocardiograms (7.1 per 100 patient-visits; 95% CI: 1.8 to 12.4). However, they received net fewer computed tomography scans (-1.5 per 100 patient-visits; 95% CI: -1.8 to -1.1), stress tests (-5.9 per 100 patient-visits; 95% CI: -6.5 to -5.3), and percutaneous coronary intervention (PCI) (-0.65 per 100 patient-visits; 95% CI: -1.01 to -0.30) and were less likely to receive cardiac medications, undergo cardiology evaluation (-3.5%; 95% CI: -4.5% to 2.6%), or be hospitalized (-5.8%; 95% CI: -7.7% to -3.8%). Patients with chest pain had lower net mean length of stay (-0.24 days; 95% CI: -0.32 to -0.16) but no net change in spending. CONCLUSIONS: Hs-cTn assay implementation was associated with more net upfront tests yet fewer net stress tests, PCI, cardiology evaluations, and hospital admissions in patients with chest pain relative to patients with other symptoms.

Use of historical high-sensitivity cardiac troponin T levels to rule out myocardial infarction.

OBJECTIVE: Several high-sensitivity cardiac troponin (hs-cTn)-based strategies exist for rule-out of myocardial infarction (MI). It is unknown whether historical hs-cTnT concentrations can be used. This study aim to evaluate the performance of a rule-out strategy based on the European Society of Cardiology (ESC) 0/1-hour algorithm, using historical hs-cTnT concentrations. METHODS: All visits among patients with chest pain in the emergency department at nine different hospitals in Sweden from 2012 to 2016 were eligible (221 490 visits). We enrolled patients with a 0-hour hs-cTnT of <12 ng/L, a second hs-cTnT measured within 3.5 hours, and ≥1 historical hs-cTnT available. We calculated the risks of MI and all-cause mortality using two rule-out strategies: (1) a delta hs-cTnT of <3 ng/L between the 0-hour hs-cTnT and the second hs-cTnT (modified ESC algorithm) and (2) a historical hs-cTnT <12 ng/L and a delta hs-cTnT of <3 ng/L in relation to the 0-hour hs-cTnT (historical-hs-cTnT algorithm). RESULTS: A total of 8432 patients were included, of whom 84 (1.0%) had an MI. The modified ESC algorithm triaged 8100 (96%) patients toward ruled-out, for whom 30-day MI risk and negative predictive value (NPV) for MI (95% CI) were 0.4% (0.3% to 0.6%) and 99.6% (99.4% to 99.7%), respectively. The historical-hs-cTnT algorithm ruled out 6700 (80%) patients, with a 30-day MI risk of 0.5% (0.4% to 0.8%) and NPV of 99.5% (99.2% to 99.6%). CONCLUSIONS: The application of algorithm resulted in similar MI risk and NPV to an established algorithm. The usefulness of historical hs-cTnT concentrations should merit further attention.

EMS blood collection from patients with acute chest pain reduces emergency department length of stay.

BACKGROUND: Expediting the measurement of serum troponin by leveraging EMS blood collection could reduce the diagnostic time for patients with acute chest pain and help address Emergency Department (ED) overcrowding. However, this practice has not been examined among an ED chest pain patient population in the United States. METHODS: A prospective observational cohort study of adults with non-traumatic chest pain without ST-segment elevation myocardial infarction was conducted in three EMS agencies between 12/2016-4/2018. During transport, paramedics obtained a patient blood sample that was sent directly to the hospital core lab for troponin measurement. On ED arrival HEART Pathway assessments were completed by ED providers as part of standard care. ED providers were blinded to troponin results from EMS blood samples. To evaluate the potential impact on length of stay (LOS), the time difference between EMS blood draw and first clinical ED draw was calculated. To determine the safety of using troponin measures from EMS blood samples, the diagnostic performance of the HEART Pathway for 30-day major adverse cardiac events (MACE: composite of cardiac death, myocardial infarction (MI), coronary revascularization) was determined using EMS troponin plus arrival ED troponin and EMS troponin plus a serial 3-h ED troponin. RESULTS: The use of EMS blood samples for troponin measures among 401 patients presenting with acute chest pain resulted in a mean potential reduction in LOS of 72.5 ± SD 35.7 min. MACE at 30 days occurred in 21.0% (84/401), with 1 cardiac death, 78 MIs, and 5 revascularizations without MI. Use of the HEART Pathway with EMS and ED arrival troponin measures yielded a NPV of 98.0% (95% CI: 89.6-100). NPV improved to 100% (95% CI: 92.9-100) when using the EMS and 3-h ED troponin measures. CONCLUSIONS: EMS blood collection used for core lab ED troponin measures could significantly reduce ED LOS and appears safe when integrated into the HEART Pathway.

Impact of coronary risk scores on disposition decision in emergency patients with chest pain.

BACKGROUND: Coronary risk scores (CRS) including History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) score and Emergency Department Assessment of Chest pain Score (EDACS) can help identify patients at low risk of major adverse cardiac events. In the emergency department (ED), there are wide variations in hospital admission rates among patients with chest pain. OBJECTIVE: This study aimed to evaluate the impact of CRS on the disposition of patients with symptoms suggestive of acute coronary syndrome in the ED. METHODS: This retrospective cohort study included 3660 adult patients who presented to the ED with chest pain between January and July in 2019. Study inclusion criteria were age > 18 years and a primary position International Statistical Classification of Diseases and Related Health Problems-10th revision coded diagnosis of angina pectoris (I20.0-I20.9) or chronic ischemic heart disease (I25.0-I25.9) by the treating ED physician. If the treating ED physician completed the electronic structured variables for CRS calculation to assist disposition planning, then the patient would be classified as the CRS group; otherwise, the patient was included in the control group. RESULTS: Among the 2676 patients, 746 were classified into the CRS group, whereas the other 1930 were classified into the control group. There was no significant difference in sex, age, initial vital signs, and ED length of stay between the two groups. The coronary risk factors were similar between the two groups, except for a higher incidence of smokers in the CRS group (19.6% vs. 16.1%, p = 0.031). Compared with the control group, significantly more patients were discharged (70.1% vs. 64.6%) directly from the ED, while fewer patients who were hospitalized (25.9% vs. 29.7%) or against-advise discharge (AAD) (2.6% vs. 4.0%) in the CRS group. Major adverse cardiac events and mortality at 60 days between the two groups were not significantly different. CONCLUSIONS: A higher ED discharge rate of the group using CRS may indicate that ED physicians have more confidence in discharging low-risk patients based on CRS.

Prospective Validation and Comparative Analysis of Coronary Risk Stratification Strategies Among Emergency Department Patients With Chest Pain.

Background Coronary risk stratification is recommended for emergency department patients with chest pain. Many protocols are designed as "rule-out" binary classification strategies, while others use graded-risk stratification. The comparative performance of competing approaches at varying levels of risk tolerance has not been widely reported. Methods and Results This is a prospective cohort study of adult patients with chest pain presenting between January 2018 and December 2019 to 13 medical center emergency departments within an integrated healthcare delivery system. Using an electronic clinical decision support interface, we externally validated and assessed the net benefit (at varying risk thresholds) of several coronary risk scores (History, ECG, Age, Risk Factors, and Troponin [HEART] score, HEART pathway, Emergency Department Assessment of Chest Pain Score Accelerated Diagnostic Protocol), troponin-only strategies (fourth-generation assay), unstructured physician gestalt, and a novel risk algorithm (RISTRA-ACS). The primary outcome was 60-day major adverse cardiac event defined as myocardial infarction, cardiac arrest, cardiogenic shock, coronary revascularization, or all-cause mortality. There were 13 192 patient encounters included with a 60-day major adverse cardiac event incidence of 3.7%. RISTRA-ACS and HEART pathway had the lowest negative likelihood ratios (0.06, 95% CI, 0.03-0.10 and 0.07, 95% CI, 0.04-0.11, respectively) and the greatest net benefit across a range of low-risk thresholds. RISTRA-ACS demonstrated the highest discrimination for 60-day major adverse cardiac event (area under the receiver operating characteristic curve 0.92, 95% CI, 0.91-0.94, P<0.0001). Conclusions RISTRA-ACS and HEART pathway were the optimal rule-out approaches, while RISTRA-ACS was the best-performing graded-risk approach. RISTRA-ACS offers promise as a versatile single approach to emergency department coronary risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03286179.

Single high-sensitivity troponin levels to assess patients with potential acute coronary syndromes.

OBJECTIVE: We tested the hypothesis that patients with a potential acute coronary syndrome (ACS) and very low levels of high-sensitivity cardiac troponin I can be efficiently and safely discharged from the emergency department after a single troponin measurement. METHODS: This prospective cohort study recruited 2255 consecutive patients aged ≥18 years presenting to the Emergency Department, Royal Perth Hospital, Western Australia, with chest pain without high-risk features but requiring the exclusion of ACS. Patients were managed using a guideline-recommended pathway or our novel Single Troponin Accelerated Triage (STAT) pathway. The primary outcome was the percentage of patients discharged in <3 hours. Secondary outcomes included the duration of observation and death or acute myocardial infarction in the next 30 days. RESULTS: The study enrolled 1131 patients to the standard cohort and 1124 to the STAT cohort. Thirty-eight per cent of the standard cohort were discharged directly from emergency department compared with 63% of the STAT cohort (p<0.001). The median duration of observation was 4.3 (IQR 3.3-7.1) hours in the standard cohort and 3.6 (2.6-5.4) hours in the STAT cohort (p<0.001), with 21% and 38% discharged in <3 hours, respectively (p<0.001). No patients discharged directly from the emergency department died or suffered an acute myocardial infarction within 30 days in either cohort. CONCLUSIONS: Among low-risk patients with a potential ACS, a pathway which incorporates early discharge based on a single very low level of high-sensitivity cardiac troponin increases the proportion of patients discharged directly from the emergency department, reduces length of stay and is safe. TRIAL REGISTRATION NUMBER: ACTRN12618000797279.

COVID-19 associated pulmonary embolism with D-dimer values within the referent range: a case report and review of the literature.

OBJECTIVE: COVID-19 is associated with an increased incidence of pulmonary embolism (PE). Elevated D-dimer levels are linked to an increased risk of PE and poor clinical outcome. We reported a case of PE in a COVID-19 patient with normal D-dimer levels and conducted a review of the literature on the subject. CASE REPORT: A 38-year-old man with no prior comorbidities returned to the COVID-19 outpatient clinic 36 hours after being discharged from the hospital, where he had been treated for COVID-19 pneumonia. He reported a sudden feeling of dyspnea and chest pain. The physical examination was unremarkable. No new changes were detected on the chest X-ray. D-dimer and cardiac-specific markers values were within the referent range. The patient underwent an urgent computerized tomography pulmonary angiography which revealed signs of bilateral arterial thrombosis. He was treated with a therapeutic dose of low molecular weight heparin and discharged after 15 days, with a recommendation to use a direct oral anticoagulant. CONCLUSIONS: Healthcare professionals should be aware that PE can occur as a late complication of COVID-19. Clinical suspicion of PE should lead physicians to use additional diagnostic methods to confirm or rule out PE, even if D-dimer levels are within the referent range.

A Practical Approach for the Use of High-Sensitivity Cardiac Troponin Assays in the Evaluation of Patients With Chest Pain.

Chest pain is a common clinical presentation, especially in the emergency department. Both rapid identification of patients with myocardial infarction as well as those with noncardiac chest pain is important in order to start therapy in the former and avoid unnecessary investigations and delay in discharge in the latter. Beside electrocardiogram, cardiac biomarkers are a key element in decision making. Conventional creatinine kinase and troponin assays are not sensitive enough and have to be repeated at least 6 to 12 hours after initial evaluation. New high-sensitivity cardiac troponin (hs-cTn) tests are currently available and if used appropriately can substantially improve management. Because of their high sensitivity and accuracy, these tests allow measurement of very low serum troponin levels, such as those present in healthy individuals and can detect small changes in troponin concentration within a short time frame. These tests are thus, very useful for the early diagnosis of myocardial infarction but can also be elevated in several other conditions that result in myocardial injury. A good understanding of the analytical characteristics of these assays is of uppermost importance for their appropriate use in clinical practice.

A nomogram to predict major adverse cardiovascular events of patients with acute chest pain, Non-ST-segment deviation, and normal troponin concentrations.

OBJECTIVE: To explore the potential indicators including patients' characteristics, electrocardiogram (ECG), echocardiography, and serological assay in predicting the major adverse cardiovascular events (MACE) within 1 year for patients with low-risk chest pain with a nomogram. PATIENTS AND METHODS: The detected indicators of patients with low-risk chest pain were obtained as the alternative predictors for MACE. After the 1-year follow-up, patients with MACE were enrolled in the MACE group while the remained patients were in the non-MACE group. A nomogram was constructed based on the multivariable Cox regression to link the independent predictors and the MACE within 1 year for patients with low-risk chest pain. RESULTS: The incidence of MACE within 1 year was 6.94% according to the follow-up result. Multivariate analysis revealed that risk factors of CAD, P-terminal force in lead V1 (PTFV1), C-reactive protein (CRP), and transmitral inflow early diastolic peak velocity (E wave) /peak early diastolic velocity (Em) (E/Em) were the independent predictors for the MACE. A nomogram incorporating these independent predictors with a good discrimination (0.79 in C-index) and calibration was constructed to predict the incidence of MACE within 1 year. It could be used to help select the patients with a high risk of MACE and develop preventive treatment strategies. CONCLUSIONS: Risk factors of CAD, PTFV1, CRP, and E/Em were the independent predictors for the MACE within 1 year in patients with low-risk chest pain. The present nomogram provides a user friendly tool in the prediction of MACE for these patients.

NMR plasma metabolomics study of patients overcoming acute myocardial infarction: in the first 12 h after onset of chest pain with statistical discrimination towards metabolomic biomarkers.

Acute myocardial infarction (AMI) is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia is essential for the ischemic patient's prevention and treatment. Despite the great prevalence and incidence only a small number of studies utilize a metabolomic approach to describe AMI condition. Recent studies have shown the impact of metabolites on epigenetic changes, in these studies plasma metabolites were related to neurological outcome of the patients making metabolomic studies increasingly interesting. The aim of this study was to describe metabolomic response of an organism to ischemic stress through the changes in energetic metabolites and aminoacids in blood plasma in patients overcoming acute myocardial infarction. Blood plasma from patients in the first 12 h after onset of chest pain was collected and compared with volunteers without any history of ischemic diseases via NMR spectroscopy. Lowered plasma levels of pyruvate, alanine, glutamine and neurotransmitter precursors tyrosine and tryptophan were found. Further, we observed increased plasma levels of 3-hydroxybutyrate and acetoacetate in balance with decreased level of lipoproteins fraction, suggesting the ongoing ketonic state of an organism. Discriminatory analysis showed very promising performance where compounds: lipoproteins, alanine, pyruvate, glutamine, tryptophan and 3-hydroxybutyrate were of the highest discriminatory power with feasibility of successful statistical discrimination.

A comparative 30-day outcome analysis of inpatient evaluation vs outpatient testing in patients presenting with chest pain in the high-sensitivity troponin era. A propensity score matched case-control retrospective study.

BACKGROUND: The best disposition of chest pain patients who rule out for myocardial infarction (MI) but have non-low clinical risk scores in the high-sensitivity troponin era is not well studied. HYPOTHESIS: In carefully selected patients who rule out for MI, and have a high-sensitivity troponin T ≤ 50 ng/L with an absolute increase less than 5 ng/L on repeat measurements, early emergency room (ER) discharge might be equivalent to inpatient evaluation in regards to 30-day incidence of adverse cardiac events (ACEs) regardless of the clinical risk score. METHODS: A total of 12 847 chest pain patients presenting to our health system ERs from January 2017 to September 2019 were retrospectively investigated. A propensity score matching algorithm was used to account for baseline differences between admitted and discharged cohorts. We then estimated and compared the incidence of 30-day and 1-year composite ACEs (MI, urgent revascularization, or cardiovascular death) between both groups. A multivariate Cox regression model was used to evaluate the effect of admission on outcomes. RESULTS: A total of 2060 patients were matched in 1:1 fashion. The primary endpoint of 30-day composite ACEs occurred in 0.6% and 0.4% of the admission and the discharged cohorts, respectively (P = .76). One-year composite ACEs was also similar between both groups (4% vs 3.7%, P = .75). In a multivariate Cox regression model, the effect of inpatient evaluation was neutral (hazard ratio 1.1, confidence interval 0.62-1.9, P = .75). CONCLUSIONS: Inpatient evaluation was not associated with better outcomes in our selected group of patients. Larger-scale randomized trials are needed to confirm our findings.

Extracellular Vesicle cystatin c is associated with unstable angina in troponin negative patients with acute chest pain.

BACKGROUND: Despite the use of high-sensitive cardiac troponin there remains a group of high-sensitive cardiac troponin negative patients with unstable angina with a non-neglectable risk for future adverse cardiovascular events, emphasising the need for additional risk stratification. Plasma extracellular vesicles are small bilayer membrane vesicles known for their potential role as biomarker source. Their role in unstable angina remains unexplored. We investigate if extracellular vesicle proteins are associated with unstable angina in patients with chest pain and low high-sensitive cardiac troponin. METHODS: The MINERVA study included patients presenting with acute chest pain but no acute coronary syndrome. We performed an exploratory retrospective case-control analysis among 269 patients. Cases were defined as patients with low high-sensitive cardiac troponin and proven ischemia. Patients without ischemia were selected as controls. Blood samples were fractionated to analyse the EV proteins in three plasma-subfractions: TEX, HDL and LDL. Protein levels were quantified using electrochemiluminescence immunoassay. RESULTS: Lower levels of (adjusted) EV cystatin c in the TEX subfraction were associated with having unstable angina (OR 0.93 95% CI 0.88-0.99). CONCLUSION: In patients with acute chest pain but low high-sensitive cardiac troponin, lower levels of plasma extracellular vesicle cystatin c are associated with having unstable angina. This finding is hypothesis generating only considering the small sample size and needs to be confirmed in larger cohort studies, but still identifies extracellular vesicle proteins as source for additional risk stratification.

Thrombin generation's role in predicting coronary disease severity.

BACKGROUND: Thrombin, a key enzyme of the clotting system, is involved in thrombus formation, platelet activation, and atherosclerosis, thereby possessing a central role in the pathogenesis of ischemic heart disease. Studies have shown an association between thrombin generation (TG) and cardiovascular morbidity and mortality, but results have been equivocal. Our aim was to study the predictive ability of TG assay in evaluating coronary stenosis severity. METHODS: In this prospective study we recruited patients with acute coronary syndrome (ACS) or acute chest pain (without evidence of myocardial injury) planned for coronary angiography. Thrombin generation was evaluated by Calibrated Automated Thrombogram (CAT) prior to angiography. Primary end points were significant coronary stenosis and the Syntax I score evaluated by coronary angiography. RESULTS: From April 2018 through September 2019, we recruited 128 patients. In the primary analysis there was no significant association between TG and significant coronary stenosis nor between TG and syntax I score, however, there was a positive correlation between peak height and troponin peak (Spearman correlation coefficient 0.194, P-value = 0.035). In sub-group analysis, the chest pain group bare no association between TG and coronary stenosis. In unstable angina group there was an association between peak height and significant coronary stenosis (P-value = 0.029), and in non ST-elevation myocardial infarction group, TG values possessed a relatively good predictive ability of significant coronary stenosis (area under the receiver operating characteristic curve of ~65%) and a positive correlation between both lag time and ttpeak with the syntax I score was noticed (Spearman correlation coefficient 0.31, P-value = 0.099 and Spearman correlation coefficient 0.37, P-value = 0.045 respectively). CONCLUSION: In patients with acute chest pain, TG values, evaluated by CAT, do not predict severity of coronary stenosis, nor do they possess prognostic value. Yet, in ACS patients, TG may have the ability to predict coronary disease severity.