Negative Troponin Levels Research Articles

The role of myeloperoxidase as a biomarker in atherosclerotic cardiovascular disease

Myeloperoxidase (MPO), a heme-containing protein integral to the innate immune system, plays a pivotal role in both bactericidal activity and inflammation regulation. In this comprehensive review, we aim to delve into the extensive literature on MPO’s involvement in cardiovascular disease. Through exhaustive searches of reputable databases such as PubMed, Scopus, and Web of Science, we conducted a thorough analysis to elucidate MPO’s potential as a predictor for cardiovascular disease risk. Evidence suggests that MPO serves as a valuable biomarker, particularly in identifying vulnerable lesions predisposed to rupture,leading to myocardial infarction, especially in the context of acute coronary syndrome. Its early release in response to symptom onset positions MPO as a promising tool for triaging chest pain patients in emergency departments, offering advantages over conventional markers like cardiac troponins. Moreover, studies have demonstrated a correlation between elevated MPO levels and higher mortality rates in patients with acute coronary syndrome, both in short- and long-term follow-up. However, the widespread adoption of MPO as a routine clinical biomarker faces significant challenges. Standardizing measurement techniques and determining the optimal timing of assessments are crucial for ensuring reliability and comparability across studies. Furthermore, while MPO shows promise as a complement to existing risk stratification protocols, questions remain regarding its superiority over troponins and its utility in stable coronary artery disease. Addressing these issues necessitates large-scale prospective cohort studies to clarify MPO’s comparative effectiveness alongside conventional biomarkers. Despite these challenges, MPO emerges as a potentially valuable addition to risk assessment strategies, particularly for patients with persistently negative troponin levels, helping guide therapeutic interventions and enhancing clinical decision-making in cardiovascular medicine.

Association Between All-Cause Mortality and High-Sensitivity Cardiac Troponin Concentrations in Patients With Chest Pain.

We assessed the association between troponin levels and all-cause mortality in individuals with chest pain who presented to the Charleston Area Medical Center Emergency Department (CAMC). We identified adult patients with chest pain as defined in the International Classification of Diseases 10 (R07) family group from the CAMC data warehouse between June 6, 2020, and June 6, 2021. These cases required a visit to the emergency room. We created 3 different cohorts to assess the endpoints of all-cause mortality at 30days and 6months. Patients were divided into the following 3 categories: negative troponin level, defined as high sensitivity troponin I (HSTNI) assay ≤15pg/mL for women and ≤20pg/mL for men; weakly positive, 21-88pg/mL for men and 16-88pg/mL for women; and strongly positive, >88pg/mL for men and women. A propensity score matching analysis was also conducted using the negative group as a control; the weakly and strongly positive groups were compared to the control across differing cardiology covariates. This study introduces novel cutoffs for high-sensitivity troponin I (Beckman Coulter assay, Beckman Coulter, Inc., Chaska Campus, 1000 Lake Hazeltine Drive, Chaska, Minnesota 55318).

High sensitivity troponin and COVID-19 outcomes

Background Recent reports have demonstrated high troponin levels in patients affected with COVID-19. In the present study, we aimed to determine the association between admission and peak troponin levels and COVID-19 outcomes. Methods This was an observational multi-ethnic multi-centre study in a UK cohort of 434 patients admitted and diagnosed COVID-19 positive, across six hospitals in London, UK during the second half of March 2020. Results Myocardial injury, defined as positive troponin during admission was observed in 288 (66.4%) patients. Age (OR: 1.68 [1.49–1.88], p < .001), hypertension (OR: 1.81 [1.10–2.99], p = .020) and moderate chronic kidney disease (OR: 9.12 [95% CI: 4.24–19.64], p < .001) independently predicted myocardial injury. After adjustment, patients with positive peak troponin were more likely to need non-invasive and mechanical ventilation (OR: 2.40 [95% CI: 1.27–4.56], p = .007, and OR: 6.81 [95% CI: 3.40–13.62], p < .001, respectively) and urgent renal replacement therapy (OR: 4.14 [95% CI: 1.34–12.78], p = .013). With regards to events, and after adjustment, positive peak troponin levels were independently associated with acute kidney injury (OR: 6.76 [95% CI: 3.40–13.47], p < .001), venous thromboembolism (OR: 11.99 [95% CI: 3.20–44.88], p < .001), development of atrial fibrillation (OR: 10.66 [95% CI: 1.33–85.32], p = .026) and death during admission (OR: 2.40 [95% CI: 1.34–4.29], p = .003). Similar associations were observed for admission troponin. In addition, median length of stay in days was shorter for patients with negative troponin levels: 8 (5–13) negative, 14 (7–23) low-positive levels and 16 (10–23) high-positive (p < .001). Conclusions Admission and peak troponin appear to be predictors for cardiovascular and non-cardiovascular events and outcomes in COVID-19 patients, and their utilisation may have an impact on patient management.

A cardiac computed tomography first strategy to evaluate chest pain in a rural setting: outcomes and cost implications.

Chest pain continues to be a major burden on the healthcare system with more than eight million patients being evaluated in the emergency department (ED) setting annually at a cost of greater than 10 billion dollars. Missed chest pain diagnoses for ischemia are the leading cause of malpractice lawsuits for ED physicians. The use of cardiac computed tomography angiography (CCTA) to assess acute chest pain was adopted at the Chickasaw Nation Medical Center to attempt to accurately diagnose low to intermediate risk chest pain and potentially reduce the cost of chest pain evaluation to the system while still transferring appropriate high-risk patients. Patients presenting to the ED with low to moderate risk chest pain were evaluated with at least two negative troponin levels, an ECG, and in most instances overnight observation followed by CCTA in the morning if eligible. High-risk patients were transported to a tertiary care facility with cardiac catheterization capabilities. Medical records were checked to determine if any adverse events had occurred during follow-up. Adverse events were defined as myocardial infarction, death, and/or revascularization. Mean follow-up was 28 months. Of the 368 patients studied, 29 patients were transferred due to findings of at least moderate obstructive disease. Of those 29 patients transferred, 11 patients underwent revascularization (10 underwent percutaneous coronary intervention and one underwent coronary artery bypass grafting). The average coronary artery calcium score for patients transferred was 96.1. The average coronary artery calcium score for patients undergoing revascularization was 174.6. Six patients had normal coronary arteries on catheterization. The remaining 12 patients had the moderate obstructive disease by catheterization that was not physiologically significant by either invasive fractional flow reserve or in two instances, negative stress perfusion testing. At 24 months, two patients had undergone revascularization and one patient had died suddenly. The cost savings associated with a CCTA first strategy to evaluate chest pain were ~$1 200 244.10. For a self-insured health system such as the Chickasaw Nation, these are very important cost savings.

Value of the coronary artery disease consortium rule in patients with acute chest pain and negative troponins referred for exercise stress testing.

To assess the value of the pretest probability (PTP) of coronary artery disease (CAD) for predicting stress testing results and coronary events in patients with acute chest pain and negative troponins. A total of 3527 patients without a history of CAD referred to our chest pain unit with suspected acute coronary syndromes, nondiagnostic ECGs, and negative troponin levels underwent exercise stress testing. PTP was estimated with the CAD consortium prediction rule, and was categorized as low (<15%), low-intermediate (15-65%), intermediate-high (66-85%), and high (>85%). The endpoints were the presence of signs of inducible myocardial ischemia on stress testing and the occurrence of coronary events within 6 months. The probability of exercise-induced myocardial ischemia was 2.6, 12.6, 42.9, and 82.1% in patients with low, low-intermediate, intermediate-high, and high PTP, respectively (Ptrend<0.001). The cumulative rate of coronary events within 6 months was also significantly lower in patients with low PTP of CAD (0.8%) than in those with low-intermediate (6.9%), intermediate-high (32.5%), or high PTP (66.7%) (Ptrend<0.001). Per 10% increment in PTP of CAD, the adjusted odds ratios for inducible myocardial ischemia and coronary events within 6 months were, respectively, 1.71 (95% confidence interval: 1.61-1.85) and 1.87 (95% confidence interval: 1.74-2.01). PTP was associated strongly with the likelihood of exercise-induced myocardial ischemia and coronary events in patients with suspected acute coronary syndromes and negative troponins. The yield of stress testing in the subset of patients with low PTP was very low.

Periprocedural myocardial infarction and injury in elective coronary stenting.

To assess the incidence, risk factors and prognosis of periprocedural myocardial infarction (MI) and myocardial injury in patients undergoing elective percutaneous coronary intervention (PCI). We included all consecutive patients who underwent elective PCI with a negative troponin level at admission from 1 January 2014 to 31 December 2015. The primary endpoint was defined as the composite of periprocedural MI (Type 4a MI), stent thrombosis (Type 4b MI), and myocardial injury according to the Third universal definition of MI. Multivariable analysis was performed to identify independent predictors of periprocedural MI and myocardial injury and its relation to 30-day and 1-year clinical outcome. Of the 1390 elective PCI patients, the primary endpoint occurred in 28.7% of patients, including 7.0% of Type 4a MI, 0.14% of Type 4b MI, and 21.6% of myocardial injury. Independent risk factors for the occurrence of the primary endpoint were left main PCI, total stent length >30 mm, multiple stenting, chronic kidney disease (estimated glomerular filtration rate <60 mL/min) and age >75 years. At 30 days, patients with periprocedural MI and myocardial injury had a higher rate of cardiovascular events [5.5% vs. 1.2%, adjusted hazard ratio (adjHR) = 3.8, 95% confidence interval (CI) 1.9-6.9; P < 0.001] mainly driven by ischaemic events (3.2% vs. 0.6%, HR 5.9, 95% CI 2.9-20; P < 0.0001). At 1-year, the risk of ischemic events remained higher in the periprocedural MI and myocardial injury group (adjHR = 1.7, 95% CI 1.1-2.6; P = 0.004). Periprocedural MI and injury are frequent complications of elective PCI associated with an increased rate of cardiovascular events at 30 days and 1 year.

Incremental value of exercise echocardiography over exercise electrocardiography in a chest pain unit

BackgroundLimited data are available on the added value of exercise echocardiography (ExEcho) over exercise electrocardiography (ExECG) in patients with suspected acute coronary syndromes (ACS) referred to a chest pain unit. We aimed to assess the incremental value of ExEcho over ExECG in this setting. MethodsExECG and ExEcho were performed in parallel in 1052 patients with suspected ACS, nondiagnostic but interpretable electrocardiograms, and negative serial troponin results. The primary outcome was a composite of coronary death, nonfatal myocardial infarction or unstable angina with angiographic documentation of significant coronary artery disease within 6months. ResultsThe primary outcome occurred in 2/614 patients (0.3%) with both negative ExECG and ExEcho, 3/60 (5%) with positive ExECG and negative ExEcho, 73/135 (54.1%) with negative ExECG and positive ExEcho, 106/136 (77.9%) with both positive ExECG and ExEcho, and 8/107 (7.5%) with inconclusive results. The addition of ExEcho data to a model based on clinical and ExECG data significantly increased the c statistic from 0.898 to 0.968 (change +0.070, 95% confidence interval 0.052–0.092), with a continuous net reclassification improvement of 1.56 and an integrated discrimination improvement of 22% (p<0.001). Decision curve analysis showed that a strategy of referral to coronary angiography based on ExEcho was associated with the highest net benefit and with the largest reduction in unnecessary coronary angiographies. ConclusionExEcho provides significant incremental prognostic information and higher net clinical benefit than a strategy based on ExECG in patients referred to a chest pain unit for suspected ACS and negative troponin levels.

Value of Cardiac Troponin and sPESI in Treatment of Pulmonary Thromboembolism at Outpatient Setting.

Currently, guidelines do not recommend any standard approach for treatment of pulmonary thromboembolism (PTE) at outpatient setting. We investigated the efficacy and safety of a 90-day anticoagulant treatment of outpatients diagnosed with PTE who had negative troponin levels and low-risk simplified pulmonary embolism severity index (sPESI) at presentation. This prospective cohort study included a total of 206 patients with objectively confirmed acute symptomatic PTE. Any troponin negative (cTn-) and low sPESI patients (as classified Group-1) were treated in outpatient setting. The primary endpoint was all-cause mortality during the first 90 days, and the secondary endpoint included non-fatal symptomatic recurrent PTE or non-fatal major bleeding. Presence of cancer was excluded from sPESI score. Fifty-two of 206 patients were eligible for had Group-1, and 31 were treated at outpatients settings. The 90-day all-cause mortality rate was 3.2 % among patients who received outpatient treatment. Otherwise cTn+ and high-risk sPESI 90-day mortality rate was 43.7 %. No difference was found in terms of secondary endpoints between the patients who received outpatient treatment and those who received inpatient treatment in Group-1 (p = NS). In our study, cancer was present in 16 (51.6 %) of the 31 outpatients. We observed that patients with acute PTE, low-risk sPESI, and negative troponin levels can be safely treated in the outpatient settings. Also the presence of cancer alone does not necessitate hospitalization.

Evaluation of serum thiol levels in patients with non ST elevation acute coronary syndrome

Imbalance between antioxidant and oxidant systems in the body play an important role in the pathogenesis of coronary atherosclerosis and its complications. The aim of this clinical study was to investigate total serum thiol (TS-H) levels in patients with non ST Elevation Acute Coronary Syndrome (NSTE-ACS) patients and relationships between these results and cardiac markers. This study included 55 patients and a control group consisted of 50 healthy people. Samples for serum total TS-H levels were obtained from the patients considered with NSTE-ACS at the time of admission to emergency department. The patient group was divided into two subgroups according to troponin levels; that is patients with positive troponin levels in the non-ST-elevation myocardial infarction (NSTEMI) group and, and patients with negative troponin levels in the unstable angina pectoris (USAP) group. SPSS for Windows Ver. 15.0 software packages were used for statistical analysis of data in patient and control groups. The patients group included a total of 55 patients with 40 men (72.7%) and 15 women (27.3%) and the control group included 50 healthy individuals people with 28 men (56%) and 22 women (44%). Total serum TS-H values were significantly lower in patients group when compared with the control group. Serum total TS-H values were significantly lower in USAP subgroup when compared with patients with NSTEMI. In addition, negative correlations between total serum TS-H values and troponin I and CK-MB were found. According to this study, total serum levels of thiol which is antioxidant marker TS-H may be useful as a confirming test in diagnosis of patients with NSTE-ACS and in differentiating patients with NSTEMI and USAP. J. Exp. Clin. Med., 2013; 30:295-299

Prognostic assessment in non-ST elevation acute coronary syndrome with negative troponin levels: a multimarker approach

Prognostic assessment in non-ST elevation acute coronary syndrome with negative troponin levels: a multimarker approach

Exercise echocardiography and risk of all-cause mortality in patients referred to a chest pain unit for acute chest pain, nondiagnostic electrocardiograms and negative troponin levels

Purpose: To determine the predictors of all-cause mortality in patients with acute chest pain and negative troponin undergoing exercise echocardiography. Methods: A total of 1646 patients were referred to our chest pain unit for acute chest pain, nondiagnostic resting electrocardiograms and negative troponin I levels, and underwent exercise echocardiography within 24 hours of the chest pain episode. An abnormal exercise echocardiogram was defined as a peak wall motion score index (pWMSI) >1. The endpoint was all-cause mortality. Results: Mean age was 63.2±12.3 years, and 1068 patients were male. During an average follow-up of 2.35±1.50 years, 55 patients died. The 5-year mortality rate was 4.1% in patients with a normal exercise echocardiogram vs. 13.1% in those with abnormal results (p <0.001). In Cox regression analysis, male gender (HR 2.25, 95% CI 1.13-4.48), age (HR 1.06, 95% CI 1.03-1.09), exercise workload in METs (HR 0.85, 95% CI 0.76-0.95) and pWMSI (HR 2.67, 95% CI 1.38-5.14) remained predictors of all-cause mortality. ![Figure][1] Figure 1. Mortality curves according to pWMSI Conclusions: Exercise echocardiography provides significant prognostic information for the prediction of all-cause mortality in patients with acute chest pain, nondiagnostic resting electrocardiograms and negative troponin results. [1]: pending:yes

Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine

IntroductionCardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs.MethodsThis was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs.ResultsWe enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033).ConclusionsTroponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality.Trial registrationControlled-trials.com ISRCTN94845869

Isolated creatine kinase-MB rise with normal cardiac troponins

A 37-year-old man is admitted to the hospital for retrosternal chest pain lasting more than 30 min and nonspecific ECG findings. Serial assays of cardiac biomarkers reveal an isolated elevation of creatine kinase-MB and negative troponin levels. A coronary angiography shows normal vessels in the presence of a Thrombolysis in Myocardial Infarction (TIMI) 2 flow. How should this patient be managed and treated? Is it a myocardial infarction? We here provide a review of the relevant literature and suggest that such a strange condition, for which several explanations are possible, involves a worse prognosis than for normal creatine kinase-MB and troponins.

Influence of Timing of Troponin Elevation on Clinical Outcomes and Use of Evidence-Based Therapies for Patients With Non–ST-Segment Elevation Acute Coronary Syndromes

Previous studies in clinical trial populations have demonstrated that patients presenting with positive troponin levels have a higher risk of mortality than patients with later positive troponin levels, but the influence of the timing of troponin elevation has not been previously characterized. We evaluate the impact of the timing of troponin elevation on clinical outcomes and adherence to the American College of Cardiology/American Heart Association acute care guidelines for patients with non-ST-segment elevation acute coronary syndromes. We examined inhospital outcomes and use of acute (<24 hours) medications and invasive cardiac procedures in 23,184 high-risk patients with non-ST-segment elevation acute coronary syndromes (positive cardiac markers or ischemic ST-segment changes) during 2001 to 2002 from 396 US hospitals participating in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) Initiative. Baseline and peak troponin values were recorded and were designated as positive if above the cutoff value used at each institution to designate definite myocardial necrosis. In the study cohort, 53.2% of patients presented with baseline positive troponin levels, 30.6% had baseline negative/later positive troponin levels, and 16.2% had negative troponin levels during the entire hospitalization. Patients with baseline positive troponin levels had a higher risk of inhospital mortality than patients with baseline negative/later positive troponin levels (6.5% versus 4.1%) and were less likely to undergo early cardiac catheterization or percutaneous coronary intervention. The use of acute aspirin (in approximately 91% of patients), heparin (85%), and beta-blockers (78%) was similar in patients with baseline-positive versus later-positive troponin levels. These findings demonstrate that evidence-based therapies and interventions for non-ST-segment elevation acute coronary syndromes are underused in patients with elevated troponin levels, but baseline troponin elevations, which are associated with a higher risk of inhospital mortality, do not stimulate more aggressive care.

471 Six-months follow-up of patients coming to the emergency room with chest pain and negative troponin levels

471 Six-months follow-up of patients coming to the emergency room with chest pain and negative troponin levels