Measurement Of High-sensitivity Cardiac Troponin Research Articles

Prognostic Value of Cardiovascular Biomarkers in the Population

Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Investigation into the effect of hyperbaric hyperoxia on serum cardiac Troponin T levels as a biomarker of cardiac injury.

There is clinical equipoise as to whether hyperoxia is injurious to the myocardium, both in the setting of acute ischaemic insults and on the stable myocardium. This study examined the effect of extreme hyperoxia - in the form of hyperbaric oxygen treatment - on the myocardium through measurement of high-sensitivity cardiac troponin. Forty-eight individuals were enrolled to undergo a series of 30 exposures to hyperbaric oxygen for treatment of non-cardiac pathologies. High-sensitivity troponin T was measured before and after each session. There was no clinically significant difference in troponin measurements following acute or recurrent sequential exposures to extreme hyperoxia, despite the studied patient population having a high rate of previous ischaemic heart disease or cardiovascular risk factors. This study demonstrates that profound hyperoxaemia does not induce any measurable cardiac injury at a biochemical level. Neither is there a reduction in cardiac troponin to suggest a cardioprotective effect of hyperbaric hyperoxia. This provides some reassurance as to the cardiac safety of the routine use of hyperbaric oxygen treatment in management of non-cardiac pathology.

Troponin in early presenters to rule out myocardial infarction.

Whether a single cardiac troponin measurement can safely rule out myocardial infarction in patients presenting within a few hours of symptom onset is uncertain. The study aim was to assess the performance of troponin in early presenters. In patients with possible myocardial infarction, the diagnostic performance of a single measurement of high-sensitivity cardiac troponin I at presentation was evaluated and externally validated in those tested ≤3, 4-12, and >12 h from symptom onset. The limit-of-detection (2 ng/L), rule-out (5 ng/L), and sex-specific 99th centile (16 ng/L in women; 34 ng/L in men) thresholds were compared. In 41 103 consecutive patients [60 (17) years, 46% women], 12 595 (31%) presented within 3 h, and 3728 (9%) had myocardial infarction. In those presenting ≤3 h, a threshold of 2 ng/L had greater sensitivity and negative predictive value [99.4% (95% confidence interval 99.2%-99.5%) and 99.7% (99.6%-99.8%)] compared with 5 ng/L [96.5% (96.2%-96.8%) and 99.3% (99.1%-99.4%)]. In those presenting ≥3 h, the sensitivity and negative predictive value were similar for both thresholds. The sensitivity of the 99th centile was low in early and late presenters at 71.4% (70.6%-72.2%) and 92.5% (92.0%-93.0%), respectively. Findings were consistent in an external validation cohort of 7088 patients. In early presenters, a single measurement of high-sensitivity cardiac troponin I below the limit of detection may facilitate the safe rule out of myocardial infarction. The 99th centile should not be used to rule out myocardial infarction at presentation even in those presenting later following symptom onset.

Diagnostic performance of a device for acoustic heart sound analysis in patients with suspected myocardial infarction

BackgroundAs only a small proportion of patients with chest pain suffers from myocardial infarction (MI), safe rule-out of MI is of immense importance. Recently an ultrasensitive microphone performing diastolic heart...

Serial high-sensitivity cardiac troponin testing for the diagnosis of myocardial infarction: a scoping review

ObjectivesWe aimed to assess the diversity and practices of existing studies on several assays and algorithms for serial measurements of high-sensitivity cardiac troponin (hs-cTn) for risk stratification and the diagnosis...

Diagnostic discrimination of a novel high-sensitivity cardiac troponin I assay and derivation/validation of an assay-specific 0/1h-algorithm

We aimed to assess the diagnostic utility of the Dimension EXL LOCI High-Sensitivity Troponin I (hs-cTnI-EXL) assay. This multicenter study included patients with chest discomfort presenting to the emergency department. Diagnoses were centrally and independently adjudicated by two cardiologists using all available clinical information. Adjudication was performed twice including serial measurements of high-sensitivity cardiac troponin (hs-cTn) I-Architect (primary analysis) and serial measurements of hs-cTnT-Elecsys (secondary analysis) in addition to the clinically used (hs)-cTn. The primary objective was to assess and compare the discriminatory performance of hs-cTnI-EXL, hs-cTnI-Architect and hs-cTnT-Elecsys for acute myocardial infarction (MI). Furthermore, we derived and validated a hs-cTnI-EXL-specific 0/1h-algorithm. Adjudicated MI was the diagnosis in 204/1454 (14%) patients. The area under the receiver operating characteristics curve for hs-cTnI-EXL was 0.94 (95%CI, 0.93-0.96), and comparable to hs-cTnI-Architect (0.95; 95%CI, 0.93-0.96) and hs-cTnT-Elecsys (0.93; 95%CI, 0.91-0.95). In the derivation cohort (n=813), optimal criteria for rule-out of MI were <9ng/L at presentation (if chest pain onset >3h) or <9ng/L and 0h-1h-change <5ng/L, and for rule-in ≥160ng/L at presentation or 0h-1h-change ≥100ng/L. In the validation cohort (n=345), these cut-offs ruled-out 56% of patients (negative predictive value 99.5% (95%CI, 97.1-99.9), sensitivity 97.8% (95%CI, 88.7-99.6)), and ruled-in 9% (positive predictive value 83.3% (95%CI, 66.4-92.7), specificity 98.3% (95%CI, 96.1-99.3)). Secondary analyses using adjudication based on hs-cTnT measurements confirmed the findings. The overall performance of the hs-cTnI-EXL was comparable to best-validated hs-cTnT/I assays and an assay-specific 0/1h-algorithm safely rules out and accurately rules in acute MI. ClinicalTrials.gov number, NCT00470587.

Extending the no objective testing rules to patients triaged by the ESC 0/1-hour algorithms

Abstract Background It is unclear which patients, after rule-out of non-ST elevation myocardial infarction (NSTEMI) with the European Society of Cardiology (ESC) 0/1h-algorithms, require further objective anatomical or functional cardiac testing and which do not. Purpose To test the safety and efficacy of the no-objective-testing (NOT)-rules after NSTEMI rule-out by the well-validated ESC 0/1h-algorithms. Methods We prospectively enrolled adult patients presenting with acute chest pain to 12 emergency departments (ED) in five European countries in an international, prospective, diagnostic multicenter study. The final diagnosis of major adverse cardiovascular events (MACE), defined as nonfatal acute coronary syndromes (NSTEMI or unstable angina) or cardiovascular death was centrally adjudicated by two independent cardiologists applying the 4th Universal Definition of myocardial infarction using all information including cardiac imaging and serial measurements of high-sensitivity cardiac troponin (hs-cTn) T/I. The primary endpoints were the safety and efficacy of the NOT-rules for the rule-out of MACE within 30-days follow-up including index events. Secondary endpoints included MACE within 365 and 730 days. Results Among 4804 and 4569 eligible patients with available 0h and 1h hs-cTnT-Elecsys or hs-cTnI-Architect concentrations, 2783 (58%) and 2252 (49%) patients were eligible for application of the NOT-rules after rule-out of NSTEMI by the respective ESC hs-cTnT/I-0/1h-algorithm. The first rule (weighted score including age, sex, cardiovascular risk factors, previous MI or known coronary artery disease (CAD), nitrate use) identified 26% of patients, had a sensitivity of 100% (95% CI 98.3–100%), a negative predictive value (NPV) of 100% (95% CI, n.c.) for hs-cTnT-Elecsys and 99.4% (95% CI 96.7–99.9%) and 99.8% (95% CI 98.8–99.9%) for hs-cTnI-Architect, respectively. The dichotomized second (age &amp;lt;50y, no previous MI or known CAD, &amp;lt;3 risk factors, no nitrate use) and even simpler third rule (nitrate use omitted) both identified 31% of patients with 99.5% (95% CI 97.4–99.9%) sensitivity and a NPV of 99.9% (95% CI 99.2–99.9%) for hs-cTnT-Elecsys. Sensitivities were 98.8% (95% CI 95.7–99.9%) and NPV 99.7% (95% CI 98.9–99.9%) for hs-cTnI-Architect. High safety was confirmed with consistently very high sensitivities and NPV for 365-day and 2-year MACE. Conclusion All three NOT-rules performed very well for rule-out of MACE. The third NOT-rule best balanced feasibility, safety and efficacy by identifying nearly one out of three patients as low-risk, who may not require further cardiac testing. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Swiss Heart Foundation, University of Basel.

Using historical cardiac troponins to identify patients at a high risk of myocardial infarction

ObjectiveMany patients who present with chest pain have previous measurements of high-sensitivity cardiac troponin T (hs-cTnT). The clinical usefulness of incorporating these measurements in identifying patients who are at a...

Analytical Considerations in Deriving 99th Percentile Upper Reference Limits for High-Sensitivity Cardiac Troponin Assays: Educational Recommendations from the IFCC Committee on Clinical Application of Cardiac Bio-Markers.

The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation and utilization of cardiac biomarkers in clinical laboratories and practice. The committee's goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed.

Perioperative myocardial injury and mortality after revision surgery for orthopaedic device-related infection.

Periprosthetic joint infections (PJIs) and fracture-related infections (FRIs) are associated with a significant risk of adverse events. However, there is a paucity of data on cardiac complications following revision surgery for PJI and FRI and how they impact overall mortality. Therefore, this study aimed to investigate the risk of perioperative myocardial injury (PMI) and mortality in this patient cohort. We prospectively included consecutive patients at high cardiovascular risk (defined as age ≥ 45 years with pre-existing coronary, peripheral, or cerebrovascular artery disease, or any patient aged ≥ 65 years, plus a postoperative hospital stay of > 24 hours) undergoing septic or aseptic major orthopaedic surgery between July 2014 and October 2016. All patients received a systematic screening to reliably detect PMI, using serial measurements of high-sensitivity cardiac troponin T. All-cause mortality was assessed at one year. Multivariable logistic regression models were applied to compare incidence of PMI and mortality between patients undergoing septic revision surgery for PJI or FRI, and patients receiving aseptic major bone and joint surgery. In total, 911 consecutive patients were included. The overall perioperative myocardial injury (PMI) rate was 15.4% (n = 140). Septic revision surgery for PJI was associated with a significantly higher PMI rate (43.8% (14/32) vs 14.5% (57/393); p = 0.001) and one-year mortality rate (18.6% (6/32) vs 7.4% (29/393); p = 0.038) compared to aseptic revision or primary arthroplasty. The association with PMI persisted in multivariable analysis with an adjusted odds ratio (aOR) of 4.7 (95% confidence interval (CI) 2.1 to 10.7; p < 0.001), but was not statistically significant for one-year mortality (aOR 1.9 (95% CI 0.7 to 5.4; p = 0.240). PMI rate (15.2% (5/33) vs 14.1% (64/453)) and one-year mortality (15.2% (5/33) vs 9.1% (41/453)) after FRI revision surgery were comparable to aseptic long-bone fracture surgery. Patients undergoing revision surgery for PJI were at a risk of PMI and death compared to those undergoing aseptic arthroplasty surgery. Screening for PMI and treatment in specialized multidisciplinary units should be considered in major bone and joint infections. Cite this article: Bone Joint J2022;104-B(6):696-702.

Can the Addition of NT-proBNP and Glucose Measurements Improve the Prognostication of High-Sensitivity Cardiac Troponin Measurements for Patients with Suspected Acute Coronary Syndrome?

Guidelines published in 2021 have supported natriuretic peptide (NP) testing for the prognostication in patients with acute coronary syndrome (ACS) and for the diagnosis of chronic and acute heart failure (HF). Our objective was to determine if the addition of N-terminal pro B-type NP (NT-proBNP) and glucose to high-sensitivity cardiac troponin (hs-cTn) could better identify emergency department (ED) patients with potential ACS at low- and high-risk for a serious cardiovascular outcome over the next 72 h. The presentation sample in two different ED cohorts which enrolled patients with symptoms suggestive of ACS within six hours of pain onset (Cohort-1, n = 126 and Cohort-2, n = 143) that had Abbott hs-cTnI, Roche hs-cTnT, NT-proBNP and glucose were evaluated for NT-proBNP alone and combined with hs-cTn and glucose for the primary outcome (composite which included death, myocardial infarction, HF, serious arrhythmia and refractory angina) via receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC) and diagnostic estimates derived. The AUC for NT-proBNP for the primary outcome was 0.68 (95% confidence interval (CI): 0.59–0.76) and 0.75 (95%CI: 0.67–0.82) in Cohort-1 and 2, respectively, with the 125 ng/L cutoff yielding a higher sensitivity (≥75%) as compared to the 300 ng/L cutoff (≥58%). Using the 125 ng/L cutoff for NT-proBNP with the published glucose and hs-cTn cutoffs for risk-stratification produced a new score (GuIDER score for Glucose, Injury and Dysfunction in the Emergency-setting for cardiovascular-Risk) and yielded higher AUCs as compared to NT-proBNP (p < 0.05). GuIDER scores of 0 and 5 using either hs-cTnI/T yielded sensitivity estimates of 100% and specificity estimates > 92% for the primary outcome. A secondary analysis assessing MI alone in the overall population (combined Cohorts 1 and 2) also achieved 100% sensitivity for MI with a GuIDER cutoff ≥ 2, ruling-out 48% (Roche) and 38% (Abbott) of the population at presentation for MI. Additional studies are needed for the GuIDER score in both the acute and ambulatory setting to further refine the utility, however, the preliminary findings reported here may present a pathway forward for inclusion of NP testing for ruling-out serious cardiac events and MI in the emergency setting.

Diagnostic Performance of Serial High-Sensitivity Cardiac Troponin Measurements in the Emergency Setting.

Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using serial measurements while incorporating absolute concentration changes for MI or death following ED presentation. We sought to determine the diagnostic estimates of these three algorithms and if one was superior in two different Canadian ED patient cohorts with serial hsTnI measurements. An undifferentiated ED population (Cohort-1) and an ED population with symptoms suggestive of acute coronary syndrome (ACS; Cohort-2) were clinically managed with non-hsTn testing with the hsTnI testing performed in real-time with physicians blinded to these results (i.e., hsTnI not reported). The three algorithms evaluated were the European Society of Cardiology (ESC), the High-STEACS pathway, and the COMPASS-MI algorithm. The diagnostic estimates were derived for each algorithm for the 30-day MI/death outcome for the rule-out and rule-in arm in each cohort and compared to proposed diagnostic benchmarks (i.e., sensitivity ≥ 99.0% and specificity ≥ 90.0%) with 95% confidence intervals (CI). In Cohort-1 (n = 2966 patients, 15.3% had outcome) and Cohort-2 (n = 935 patients, 15.6% had outcome), the algorithm that obtained the highest sensitivity (97.8%; 95% CI: 96.0–98.9 and 98.6%; 95% CI: 95.1–99.8, respectively) in both cohorts was COMPASS-MI. Only Cohort-2 with both the ESC and COMPASS-MI algorithms exceeded the specificity benchmark (97.0%; 95% CI: 95.5–98.0 and 96.7%; 95% CI: 95.2–97.8, respectively). Patient selection for serial hsTnI testing will affect specificity estimates, with no algorithm achieving a sensitivity ≥ 99% for 30-day MI or death.

High-Sensitivity Cardiac Troponin I vs a Clinical Chemistry Score for Predicting All-Cause Mortality in an Emergency Department Population

BackgroundFor patients investigated for suspected acute coronary syndrome, there is uncertainty if a single measurement of high-sensitivity cardiac troponin I (hs-cTnI) at emergency department (ED) presentation can identify patients at both low and high risk for mortality. MethodsWe included consecutive adult patients in the ED who had a Clinical Chemistry Score (CCS) taken at presentation (ie, combination of glucose, creatinine for estimated glomerular filtration rate determination, and hs-cTnI assay) in a Canadian city between 2012 and 2013. Outcomes were 3-month, 1-year, and 5-year all-cause mortality using the provincial death registry. Mortality rates and test performance (eg, sensitivity and specificity) with 95% confidence intervals (CIs) were obtained for the CCS or hs-cTnI assay alone using established cutoffs for these tests. ResultsOur cohort included 5974 patients with a 1-year mortality rate of 17.2% (95% CI, 16.2-18.3). A CCS ≥ 1 yielded a sensitivity of 99.2% (95% CI, 98.4-99.6) compared with the hs-cTnI ≥ 5 ng/L cutoff sensitivity of 88.4% (95% CI, 86.3-90.3), with the mortality rate being significantly lower for patients with CCS < 1 (2.0%; 95% CI, 0.9-4.0) vs patients with hs-cTnI < 5 ng/L (5.0%; 95% CI, 4.2-6.0) at 1 year (P = 0.01). A CCS of 5 also yielded a higher specificity (88.5%; 95% CI, 87.5-89.3) compared with hs-cTnI > 26 ng/L (83.9%; 95% CI, 82.9-84.9), with no difference in mortality rates (37.4% vs 36.3%; P = 0.66). This trend was consistent at 3-month and 5-year mortality. ConclusionFor patients in the ED with a potential cardiac issue, using the CCS cutoffs can better identify patients at low and high risk for mortality than using published cutoffs for hs-cTnI alone.

P1695Incidence and outcomes of unstable angina compared to non-ST elevation myocardial infarction

Abstract Objective Assess the incidence and compare characteristics and outcome of unstable angina (UA) and Non-ST-Elevation myocardial infarction (NSTEMI) Design Two independent prospective multicenter diagnostic studies (Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) and High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome (High-STEACS)) enrolling patients with acute chest discomfort presenting to the emergency department. Central adjudication of the final diagnosis was done by two independent cardiologists using all clinical information including serial measurements of high-sensitivity cardiac troponin (hs-cTn). All-cause death and future non-fatal MI were assessed at 30-days and 1-year. Results 8992 patients were enrolled at 11 centres. UA was adjudicated in 366/4122 (8.9%) and 137/4870 (2.8%) patients in APACE and High-STEACS, respectively, and NSTEMI in 622 (15.1%) and 651 (13.4%). Coronary artery disease was pre-existing in 73% and 76% of patients with unstable angina. At 30-days, all-cause mortality in UA was substantially lower as compared to NSTEMI (0.5% versus 3.7%, p=0.002 in APACE, 0.7% versus 7.4%, p=0.004 in High-STEACS). Similarly, at 1-year in UA all-cause mortality was 3.3% [95% CI 1.2–5.3] vs 10.4% [7.9–12.9] in APACE, and 5.1% [0.7–9.5] vs 22.9% [19.3–26.4] in High-STEACS, and similar to non-cardiac chest pain (NCCP). In contrast, future non-fatal MI in APACE was comparable in UA and NSTEMI (11.2%, [7.8–14.6] and 7.9%, [5.7–10.2]), and higher than in NCCP (0.6%, [0.2–1.0]). 1-year survival free from future AMI Conclusions The incidence and the mortality of UA is substantially lower than that of NSTEMI, while the rate of future non-fatal MI is similar. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, British Heart Foundation Project Grants, Butler S

1269Dual antiplatelet therapy to inhibit myocardial injury in patients with high-risk coronary artery plaque: a randomized controlled trial

Abstract Background High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy. Purpose To determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque with 18F-fluoride uptake. Methods In a randomized double-blind placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary 18F-fluoride positron emission tomography-computed tomography and measurement of high-sensitivity cardiac troponin I and were randomized (1:1) to ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary 18F-fluoride uptake. Results In total, 202 patients were randomized and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary 18F-fluoride uptake (n=120/191) there was no evidence that ticagrelor had an effect on plasma troponin concentrationsat 30 days (ratio of geometric means for ticagrelor versusplacebo, 1.11, [95% confidence interval 0.90 to 1.36], p=0.32) (Table 1). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary 18F-fluoride uptake (ratio of geometric means, 0.86, 95% confidence interval 0.63 to 1.17, p=0.33). Table 1 Adjusted Geometric Mean (GSE) Ratio of Geometric Means p-value Ticagrelor Placebo (95% CI) Cardiac troponin I, ng/L (18F-fluoride activity) 3.8 (1.1) 3.4 (1.1) 1.11 (0.90 to 1.36) 0.32 Cardiac Troponin I, ng/L (No 18F-fluoride activity) 2.4 (1.1) 2.3 (1.1) 1.02 (0.80 to 1.31) 0.87 Plasma high-sensitivity cardiac troponin I concentration (ng/L) at 30 days for the per-protocol population.Estimates are back transformed estimates from analysis of log transformed values at 30 days adjusting for age, sex and log transformed baseline troponin. Ratio of geometric means is Ticagrelor divided by Placebo. GSE, geometric standard error. Conclusions Dual antiplatelet therapy with ticagrelor does not reduce plasma troponin concentrations in patients with coronary 18F-fluoride uptake. This suggests that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. Clinical Trials Study ID: NCT02110303Study ID: NCT02110303 Acknowledgement/Funding Wellcome Trust Senior Investigator Award WT103782AIA

Ticagrelor to Reduce Myocardial Injury in Patients With High-Risk Coronary Artery Plaque

ObjectivesThe goal of this study was to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque. BackgroundHigh-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy. MethodsIn a randomized, double-blind, placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary 18F-fluoride positron emission tomography/coronary computed tomography scanning and measurement of high-sensitivity cardiac troponin I. Patients were randomized (1:1) to receive ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary 18F-fluoride uptake. ResultsIn total, 202 patients were randomized to treatment, and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary 18F-fluoride uptake (120 of 191), there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor vs. placebo: 1.11; 95% confidence interval: 0.90 to 1.36; p = 0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary 18F-fluoride uptake (ratio of geometric means: 0.86; 95% confidence interval: 0.63 to 1.17; p = 0.33). ConclusionsDual antiplatelet therapy with ticagrelor did not reduce plasma troponin concentrations in patients with high-risk coronary plaque, suggesting that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. (Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND]; NCT02110303)

Increased Ratio of Circulating T-Helper 1 to T-Helper 2 Cells and Severity of Coronary Artery Disease in Patients with Acute Myocardial Infarction: A Prospective Observational Study.

BackgroundThis study aimed to determine the association between CD4-positive T-helper (Th) cell subsets, T-helper 1 (Th1) and T-helper 2 (Th2) in patients with acute myocardial infarction (AMI) and the severity of coronary artery disease (CAD) determined by coronary artery angiography.Material/MethodsThree groups of patients with AMI who underwent coronary angiography and percutaneous coronary intervention (PCI) included patients with stable CAD (n=35), ST-segment elevation myocardial infarction (STEMI) (n=30), and non-STEMI (NSTEMI) (n=35), and controls (n=33). Measurement of high-sensitivity cardiac troponin T (hs-cTnT) was performed. The numbers of circulating CD4-positive Th1 and Th2 cells were measured using flow cytometry. Plasma levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were measured using enzyme-linked immunosorbent assay (ELISA).ResultsAn increase in the Th1 lymphocyte population was associated with more CAD, and an increased Th1/Th2 ratio was found in patients with NSTEMI and STEMI (controls 7.27±2.98; stable CAD 7.58±2.52; NSTEMI 16.62±2.74; and STEMI 22.32±7.35) (P<0.001). The proportion of Th1 cells and the Th1/Th2 ratio increased as the number of affected arteries, the degree of stenosis, and the lesion length increased. At a median follow-up of 18.2 months, patients with CAD and an increased Th1/Th2 ratio had a significant increase in adverse cardiac events compared with patients with a reduced Th1/Th2 ratio (log-rank, P=0.042).ConclusionsAn increased ratio of circulating Th1 to Th2 cells in patients with AMI was associated with the severity of CAD determined by angiography.

High-sensitivity cardiac troponin assays and acute coronary syndrome: a matter of sex?

: Advances in technology have led to an improvement in the ability to detect and quantify acute cardiomyocyte injury with the measurement of high-sensitivity cardiac troponin as compared with conventional assays. The upper reference limit for the high-sensitivity cardiac troponin assays is defined as the 99th percentile cutoff value in a healthy reference population. Since sex-related threshold levels of high-sensitivity cardiac troponin assays have been proposed, this review will focus on the diagnostic and prognostic implications of adopting sex-specific threshold troponin values in patients with a suspected acute coronary syndrome.

Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain-the WESTCOR study: study design

Objectives. The main aim of the Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain (WESTCOR-study) (Clinical Trials number NCT02620202) is to improve diagnostic pathways for patients presenting to the Emergency department (ED) with acute chest pain. Design. The WESTCOR-study is a two center, cross-sectional and prospective observational study recruiting unselected patients presenting to the ED with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). Patient inclusion started September 2015 and we plan to include 2250 patients, finishing in 2019. The final diagnosis will be adjudicated by two independent cardiologists based on all available information including serial high sensitivity cardiac troponin measurements, coronary angiography, coronary CT angiography and echocardiography. The study includes one derivation cohort (N = 985) that will be used to develop rule out/rule in algorithms for NSTEMI and NSTE-ACS (if possible) using novel troponin assays, and to validate established NSTEMI algorithms, with and without clinical scoring systems. The study further includes one subcohort (n = 500) where all patients are examined with coronary CT angiography independent of biomarker status, aiming to assess the associations between biomarkers and the extent and severity of coronary atherosclerosis. Finally, an external validation cohort (N = 750) will be included at Stavanger University Hospital. Prospective studies will be based on the merged cohorts. Conclusion. The WESTCOR study will provide new diagnostic algorithms for early inclusion and exclusion of NSTE-ACS and insights in the associations between cardiovascular biomarkers, CT-angiographic findings and short and long-term clinical outcomes.

Is high-sensitivity troponin, alone or in combination with copeptin, sensitive enough for ruling out NSTEMI in very early presenters at admission? A post hoc analysis performed in emergency departments

ObjectivesCopeptin and high-sensitivity cardiac troponin (HS-cTn) assays improve the early detection of non-ST-segment elevation myocardial infarction (NSTEMI). Their sensitivities may, however, be reduced in very early presenters.SettingWe performed a post...