hsTnT Assay Research Articles

What Does Elevated High-Sensitive Troponin I in Stroke Patients Mean: Concomitant Acute Myocardial Infarction or a Marker for High-Risk Patients

Background: Acute ischemic stroke patients may occasionally suffer from concomitant acute coronary syndrome (ACS). Troponin I and T are established biomarkers to detect ACS. Recently introduced high-sensitive cardiac troponin (hs-TNI and hs-TNT) assays are increasingly used to identify ACS in stroke patients even without signs or symptoms of ACS. These new test systems very often detect elevated values of hs-troponin, although clinical relevance and consequences of elevated hs-TNI values in these patients are unclear so far. Patients and Methods: We examined hs-TNI values in 834 consecutive ischemic stroke patients admitted to our Comprehensive Stroke Center during a 1-year period. hs-TNI was measured immediately after admission and after 3 h if initial hs-TNI was elevated above the 99th percentile of normal values (>0.045 ng/ml). Patients with elevated values were divided into two groups: (1) constant and (2) dynamic hs-TNI values. The dynamic approach was defined as a 30% rise or fall of the hs-TNI value above the critical value within 3 h. All patients received stroke diagnostic and continuous monitoring according to international stroke unit standards, including a 12-lead ECG, blood pressure, body temperature and continuous ECG monitoring, as well as regular 6-hourly neurological and general physical examination (including NIHSS scores). The cardiologists - as members of the Stroke Unit team - evaluated clinical symptoms/examination, as well as laboratory, echocardiographic and ECG findings for the diagnosis of ACS. Results: 172/834 (20.6%) patients showed elevated hs-TNI levels on admission. Patients with elevated hs-TNI values exhibited a significantly (p < 0.001) increased rate of hypertension (89 vs. 77.2%), history of stroke (24.4 vs. 14.8%), history of coronary artery disease (65.7 vs. 34.1%), history of myocardial infarction (22.1 vs. 7.6%), heart failure (12.8 vs. 5.7%) and atrial fibrillation (44.2 vs. 23.6%). 82/136 patients showed constant and 54/136 patients dynamic hs-TNI values: among the latter, 5 patients were diagnosed with ST segment elevation myocardial infarction (STEMI) and 24 with non-STEMI (NSTEMI). Conclusion: Our data demonstrate that hs-TNI was elevated in about 20.6% of acute ischemic stroke patients but therapeutically relevant ACS was diagnosed only in the dynamic group. hs-TNI elevations without dynamic changes may occur in stroke patients without ACS due to different reasons that stress the heart. Therefore, we suppose that hs-TNI is a sensitive marker to detect high-risk patients but serial measurements are mandatory and expert cardiological workup is essential for best medical treatment and to accurately diagnose ACS in acute ischemic stroke patients.

The clinical introduction of high sensitivity cardiac troponin will redefine patient categories in acute coronary syndromes and increase prognostic information

Purpose: With the advent of high-sensitivity cardiac troponins (hscTn), detectable levels have become the norm and clinical challenge lies within distinction of normal and abnormal. We therefore sought to describe diagnostic and prognostic implications of the clinical introduction of hscTn. Methods: Myocardial infarction (MI) adjudication was based on hsTnT (Roche Diagnostics) and clinical setting. The 99% upper reference limit (URL) of 30 ng/L (10% CV) in the 4th generation TnT assay corresponds to 50 ng/L URL in the hsTnT assay. First, we used a 50 ng/L cut off (+dynamic changes) after the introduction of hsTnT in order to parallel MI diagnosis with the 4th generation assay. MI was then re-adjudicated by hsTnT levels >99% URL (>14 ng/L) with an absolute (abs.) change as rise/fall >50% of URL (>7 ng/L). We then compared hsTnT with a contemporary sensitivity TnI assay (sTnI) (Siemens Vista), with a 15 ng/L detection limit, a 45 ng/L 99% URL and significant abs. change of 20 ng/L. Results: In 335 chest pain patients with at least 2 values, 46 (13.7%) had MI by the 50 ng/l cut off. Re-adjudicating MI resulted in a 67% increase with 69 (20.6%) MI, 74% of the additional MI were type II. STnI only identified 51 of re-defined MI with modest 73.9% sensitivity (sens.) but high 95.9% specificity, yielding only 4.1% false positives, which was doubled (7.9%) with hsTnT. In 586 patients with at least 1 hsTnT value, 105 (17.9%) had undetectable levels (< 3 ng/L) at admission, ruling out all 1 year mortality [n = 81 (13.8%)] and all MI [n = 85 (14.5%)] with 100% sens. and NPV. 313 (53.4%) patients had hsTnT levels <14 ng/L, which predicted mortality with 96.3% sens. and 99% NPV, missing 3 events, and MI with 98.8% sens. and 99.7% NPV, missing 1 case. In 553 patients with at least 1 sTnI value, 376 (68%) had undetectable levels (< 15 ng/L) at admission, ruling out 1 year mortality [n = 73 (13.2%)] with 78.1% sens. and 95.7% NPV, missing 16 events. 430 (77.8%) had sTnI levels <45 ng/L, which predicted mortality with 58.9% sens. and 93% NPV, missing 30 events. MI at admission was ruled out with 86.7% sens. and 97.1% NPV by sTnI <15 ng/L, missing 11 cases, and with 75.9% sens. and 95.3% NPV by sTnI <45 ng/L, missing 20 cases. Conclusion: The advent of hscTn will substantially increase MI incidence, primarily type II. Fewer chest pain patients will have undetectable cTn but constitute a new very low risk population with absolute rule out of MI and 1 year all cause mortality. This implies higher rates of false positives with non-ischemic disease burden and diagnostic work up for MI is more important than ever.

Challenges of serial troponin testing: A symphony in need for harmony

In an earlier issue of this journal [1], we reported on early rule-out and rule-in of non-STEMI using 3 h and 6 h protocols of high sensitivity cardiac troponin T in an emergency department population. With interest, we now read a letter to the editor from Dr. Lippi [2] referring to a recent studybyCardinaels et al. [3]who found several cTnT degradation products in sera of patients admitted for STEMI and underwent primary PCI. Lippi now raised the possibility that cTnT degradation products might confound serial troponin testing that is endorsed by current ESC Guidelines on patients with non-ST segment elevationacute coronary syndromes [4]. The observationof Cardinaels et al. [3] is interesting but requires further validation of Western blot findings, as well as clinical evaluation of its clinical relevance. Lippi and Cervellin [2] suspect that antibodies of the current hsTnT assaymay fail to detect variousmolecular isoformsdue toheterogeneous immunoreactivity. For support, they refer to Cardinaels et al. [3] who demonstrated a consistentdegradationpatternusingantibodies directed against the C-terminal end of cTnTas compared to the pattern seenwith standard cTnT antibodies, but no fragments when the antibody was directed against the N-terminal end. Notably, the epitope of the cTnT assay is located centrally and thereby protected against epitope loss by protease cleavage [5,6]. In fact, this issue might be more relevant for some cTnI assays due to a higher susceptibility to posttranslational modifications, and heterogeneous epitope locations [5]. In addition to the central location of the epitope, cTnT is not prone to oxidation– reduction, phosphorylation or major modifications [5]. Nevertheless, it would be scientifically interesting to investigate the effect of degradation on measurable cTnT and cTnI concentrations over time. In clinical practice, the strength of hsTnT is earlier andmore accurate detection of NSTEMI. For STEMI, monitoring of reperfusion success is nowadays less important than in the era of fibrinolytic therapy, and estimation of infarct size using values beyond the first 24 h is not within the label. Therefore, the hsTnT assay was optimized at the low concentration range and truncated at the upper range as compared to the 4th generation cTnT assay [7]. Due to the excellent negative predictive value of hsTn assays in large clinical trials [8,9], current ESC guidelines on NSTE-ACS [4] endorse an early rule-out protocol with cTnTmeasurements on admission and after 3 h (optionally after 6 h). The finding that intact cTnT disappears 4 h after admission to the ED, and cTnT fragments start to become themajor fraction of cTnT does however not support the notion that cTnT fragments might disturb the diagnostic performance of hsTnT for early rule-out of NSTEMI. In addition, the mechanisms behind the formation of cTn degradation products remain unclear. Further work is needed to investigate the occurrenceof degradationproducts after small myocyte necrosis as compared to large STEMI with the subsequent release of large quantities of proteases, or the role of ischemia/ reperfusion injury after primary PCI. Although, the concerns of Dr. Lippi cannot be ruled out fully, his hypothesis is not supported by clinical experience where clinicians are rather confronted with issues of overdiagnosis of NSTEMI due to reduced clinical specificity rather than underdiagnosis. At least, at the moment, no data support an underestimation of MI due to epitope loss or modification, and the study by Cardinaels et al. [3] studied cTnT degradation products in a patient population that is not in the scope of troponin testing. In addition, as this is thefirst report,findings require confirmationusingmass spectroscopy followed by peptide sequencing to validate the identity of peptides. Furthermore, testing for fragments should be executed in heparin plasma, as well. Another issue raised by Dr. Lippi [2] is the analytical imprecision of hsTnT values below the LoQ which depends on the analytical platform used. Accordingly, Lippi [2] questioned the interpretation of small absolute concentration values for the diagnosis of NSTEMI. In our study [1], a diagnosis of NSTEMI was not only based on the presence of respective hsTnTchanges but required that the first or second hsTnT value exceeded the 99th percentile value of 14 ng/L. So far, the symphony is ready to be played but musicians still need to practice for harmony.

The combination of high sensitivity troponin T and copeptin facilitates early rule-out of ACS: a prospective observational study.

BackgroundThe combination of the new high sensitivity troponin T (hsTnT) assays and copeptin, a biomarker of endogenous stress, has been suggested to have the potential of early rule-out of acute coronary syndrome (ACS). The aim of this study was to examine the ability of this combination to rule out ACS in patients presenting with chest pain and to compare the diagnostic performance to hsTnT alone.MethodIn this prospective observational study, patients with chest pain admitted for observation were consecutively included. Patients presenting with ST elevation were excluded. Copeptin and hsTnT were analyzed at admission and hsTnT was thereafter determined approximately every 3rd hour as long as clinically indicated. The follow-up period was 60 days. A combined primary endpoint of ACS, non-elective percutanous coronary intervention, non-elective coronary artery bypass surgery and death of all causes was used.Results478 patients were included. 107 (22%) patients were diagnosed with ACS during hospital stay. 70 (14%) had non-ST-segment elevation myocardial infarction (NSTEMI) and 37 (8%) had unstable angina pectoris (UAP).The combination of hsTnT >14 ng/L or copeptin ≥14 pmol/L at admission identified ACS with a higher sensitivity than hsTnT alone: 0.83 (95% confidence interval (CI): 0.74-0.89) versus 0.69 (95% CI: 0.59-0.77), p <0.001. Negative predictive values (NPV) 91% (95% CI: 86-94) versus 89% (95% CI: 84-92). A repeated hsTnT analyzed 3-4 hours after admission resulted in a sensitivity of: 0.77 (95% CI: 0.65-0.86), p =0.031 for comparison with the combination analyzed at admission.ConclusionsIn patients presenting with chest pain admitted for observation, the combination of hsTnT and copeptin analyzed at admission had a significantly higher sensitivity to diagnose ACS than hsTnT alone. We report a sensitivity of 83% and a NPV of 91% for the combination of hsTnT and copeptin and we conclude that biomarkers alone are not sufficient to rule out ACS. However, the combination of hsTnT and copeptin seems to have a significantly higher sensitivity to identify ACS than a repeated hsTnT test, and thus enables an earlier risk stratification of chest pain patients. This can be time-saving and beneficial for the individual patient by contributing to early decisions on treatment, need of further assessment and level of care.

Predictive value of troponins and simplified pulmonary embolism severity index in patients with normotensive pulmonary embolism

BackgroundTo investigate whether 2 cardiac troponins [conventional troponin-T(cTnT) and high sensitive troponin-T(hsTnT)] combined with simplified pulmonary embolism severity index (sPESI), or either test alone are useful for predicting 30-day mortality and 6 months adverse outcomes in patients with normotensive pulmonary embolism(PE).MethodsThe prospective study included 121 consecutive patients with normotensive PE confirmed by computerized tomographic(CT) pulmonary angiography. The primary end point of the study was the 30-day all-cause mortality. The secondary end point included the 180-day all-cause mortality, the nonfatal symptomatic recurrent PE, or the nonfatal major bleeding.ResultsOverall, 16 (13.2%) out of 121 patients died during the first month of follow up. The predefined hsTnT cutoff value of 0.014 ng/mL combined with a sPESI ≥1 'point(s) were the most significant predictor for 30-day mortality [OR: 27.6 (95% CI: 3.5–217) in the univariate analysis. Alone, sPESI ≥1 point(s) had the highest negative predictive value for both 30-day all-cause mortality and 6-months adverse outcomes,100% and 91% respectively.ConclusionsThe hsTnT assay combined with the sPESI may provide better predictive information than the cTnT assay for early death of PE patients. Low sPESI (0 points) may be used for identifying the outpatient treatment for PE patients and biomarker levels seem to be unnecessary for risk stratification in these patients.

Predictive value of troponins and simplified pulmonary embolism severity index in patients with normotensive pulmonary embolism

Background: To investigate whether 2 cardiac troponins [conventional troponin-T(cTnT) and high sensitive troponin-T(hsTnT)] combined with simplified pulmonary embolism severity index (sPESI), or either test alone are useful for predicting 30-day mortality and 6 months adverse outcomes in patients with normotensive pulmonary embolism(PE). Methods: The prospective study included 121 consecutive patients with normotensive PE confirmed by computerized tomographic(CT) pulmonary angiography. The primary end point of the study was the 30-day all-cause mortality. The secondary end point included the 180-day all-cause mortality, the nonfatal symptomatic recurrent PE, or the nonfatal major bleeding. Results: Overall, 16 (13.2%) out of 121 patients died during the first month of follow up. The predefined hsTnT cutoff value of 0.014 ng/mL combined with a sPESI ≥1 'point(s) were the most significant predictor for 30-day mortality [OR: 27.6 (95% CI: 3.5–217) in the univariate analysis. Alone, sPESI ≥1 point(s) had the highest negative predictive value for both 30-day all-cause mortality and 6-months adverse outcomes,100% and 91% respectively. Conclusions: The hsTnT assay combined with the sPESI may provide better predictive information than the cTnT assay for early death of PE patients. Low sPESI (0 points) may be used for identifying the outpatient treatment for PE patients and biomarker levels seem to be unnecessary for risk stratification in these patients.

High-sensitive Troponin T increase after exercise in patients with pulmonary arterial hypertension

BackgroundThe current study aimed to investigate the release of myocardial high-sensitive Troponin T (hsTnT) in patients with pulmonary arterial hypertension (PAH) in response to maximal physical exercise.MethodsIn 24 patients with PAH, symptom-limited cardiopulmonary exercise testing was performed. hsTnT was measured by the novel hsTnT assay with a lower limit of detection of 2 ng/L and a total imprecision of less than 10% at the 99th percentile value. hsTnT was related to NT-proBNP, WHO functional class and right ventricular (RV) function. Serial measurement was performed before and 30 min, 180 min, and 300 min after exercise. Healthy volunteers served as a control group.ResultsIn 21 PAH patients, hsTnT levels were detectable before exercise with a close correlation between hsTnT and NT-proBNP. hsTnT was detectable in all PAH patients after exercise and significantly increased from 7.5 ng/L at baseline to 14.62 ng/L after 300 min, whereas levels of NT-proBNP remained constant with time.ConclusionsUsing the novel hsTnT assay, the current study provides first evidence that hsTnT levels increase in PAH patients after maximal physical exercise, while levels of other biomarkers remain constant after exercise testing. This might provide new insights into pathophysiology and individual risk assessment in patients with PAH.

Identification of high-risk plaques associated with peri-procedural myocardial injury following elective percutaneous coronary intervention: Assessment by high-sensitivity troponin-T measurements and optical coherence tomography

A worse prognosis of peri-procedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) has been reported in patients displaying an isolated elevation of cardiac troponin-T (TnT) or troponin-I [1,2]. Highly sensitive assay for TnT (hs-TnT) is newly developed, permitting measurement of TnT than those measurable limit with conventional assays [3,4]. Thus, procedural changes in TnT values following PCI using the hs-TnT assay may identify more minute myocardial injury. Optical coherence tomography (OCT) with high-resolution images (≈15 μm) allows detailed information such as fibrous cap thickness, and lipid distribution of the atherosclerotic plaque in vivo [5]. Therefore, this study has focused on precise assessments for PMI and lesion characteristics using both the hs-TnT measurements and OCT imaging. We enrolled 79 patients (59 males, age range: 42 to 86 years) who underwent elective coronary stent implantationwith OCTguidance for de novo atherosclerotic lesions. All patients were diagnosed as having stable angina pectoris (SAP) defined as a positive stress test for myocardial ischemia and no change in clinical symptoms within 4 weeks. The quantitative coronary angiography (QCA) findings were analyzed with a computer-assisted, automated edge detection algorithm(CMS,MEDIS, Nuenen, TheNetherlands). TheOCTprocedure has been previously reported [5]. Characterizations of the plaque components, such as lipid, fibrous, or calcified tissue and thrombus were validated based on the established criteria [6]. For all images with an OCT-determined lipid plaque, the angle of lipid tissue (AL), thinnest fibrous cap thickness (TFCT) and length of lipid tissue (LL) were measured as previously reported [5]. Blood samples were obtained before PCI and from 18 to 24 h following PCI. Serum hs-TnT was measured using an electrochemiluminescence pre-commercial immunoassay (Roche Diagnostics Ltd, Rotkreuz, Switzerland) [3]. According to the recent universal definition, the current study defined PMI as hsTnT values increased more than three times the 99th percentile upper reference limit (0.014 ng/ml) during PCI [7]. The patientswere divided into two groups, PMI and non-PMI groups. Thereafter, we analyzed which factors correspond to PMI by considering the patients' demographics, angiographic findings or lesion characteristics, and procedures. All statistical analyses were performed using the SPSS software program (version 11.0.1, SPSS Inc., Chicago, IL) and the MedCalc software package (version 10.1.4, MedCalc Software, Mariakerke, Belgium). A univariate logistic regression analysis was performed to obtain the odds ratio for PMI. Thereafter, a multivariate logistic regression analysis was performed using the variables with P values b 0.10 in the univariate analysis for examining their independent association with PMI. The receiver operating characteristic (ROC) curve analyseswereperformed to examine the ability of the OCTfindings to identify subjects at high-risk for PMI. All statistical tests were 2-sided, and a P value b 0.05 was considered to be significant. The mean patient age was higher than that of non-PMI group (71.0 ± 10.9 vs. 65.2 ± 9.7, P = 0.016), while the other baseline characteristics including coronary risk factors, prescription of pharmacological agents, lipid profile, estimated glomerular filtration rate or ejection fraction did not differ significantly between the groups. There were significant differences in the American Heart Association/American College of Cardiology's (AHA/ACC) classification (P = 0.023) and bifurcation lesions between the groups (20% vs. 5%, P = 0.013). Other angiographic parameters such as reference vessel diameter, minimum lumen diameter, or diameter stenosis were not different between the 2 groups. In a univariate logistic regression analysis (Table 1), age, AHA/ACC classification, thrombus, plaque rupture/fissure and each quartile increment in the AL, TFCT, and LL had a significantly increased odds ratio for PMI, and a International Journal of Cardiology 168 (2013) 2860–3148

Single Resting hsTnT Level Predicts Abnormal Myocardial Stress Test in Acute Chest Pain Patients With Normal Initial Standard Troponin

The goal of this study was to determine the ability of a single, resting high-sensitivity troponin T (hsTnT) measurement to predict abnormal myocardial perfusion imaging (MPI) in patients presenting with acute chest pain to the emergency department (ED). HsTnT assays precisely detect very low levels of troponin T, which may be a surrogate for the presence and extent of myocardial ischemia. We included all patients from the ROMICAT I (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial, an observational cohort study, who underwent both single-photon emission computed tomography (SPECT)-MPI stress testing and 64-slice computed tomography angiography (CTA) and in whom hsTnT measurements were available. We assessed the discriminatory value of hsTnT for abnormal SPECT-MPI and the association of reversible myocardial ischemia by SPECT-MPI and the extent of coronary atherosclerosis by CTA to hsTnT levels. Of the 138 patients (mean age 54 ± 11 years, 46% male), 19 (13.7%) had abnormal SPECT-MPI. Median hsTnT levels were significantly different between patients with normal and abnormal SPECT-MPI (9.41 pg/ml [interquartile range (IQR): 5.73 to 19.20 pg/ml] vs. 4.89 pg/ml [IQR: 2.34 to 7.68 pg/ml], p = 0.001). Sensitivity of 80% and 90% to detect abnormal SPECT-MPI was reached at hsTnT levels as low as 5.73 and 4.26 pg/ml, respectively. Corresponding specificity was 62% and 46%, and negative predictive value was 96% and 96%, respectively. HsTnT levels had good discriminatory ability for prediction of abnormal SPECT-MPI (area under the curve: 0.739, 95% confidence interval: 0.609 to 0.868). Both reversible myocardial ischemia and the extent of coronary atherosclerosis (combined model r(2) = 0.19 with partial of r(2) = 0.12 and r(2) = 0.05, respectively) independently and incrementally predicted the measured hsTnT levels. In patients with acute chest pain, myocardial perfusion abnormalities and coronary artery disease are predicted by resting hsTnT levels. Prospective evaluations are warranted to confirm whether resting hsTnT could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and improve the effectiveness of patient management.

High-sensitive Troponin T measurements early after heart transplantation predict short- and long-term survival

Following heart transplantation, cardiac biomarkers remain elevated for several weeks eventually as a result of membrane leakage of the donor organ. We now test the predictive power of blood levels of troponin T (TNT) measured by the new hsTNT assay (Roche Diagnostics, Roche Diagnostics, Mannheim, Germany) early after heart transplantation. TNT was determined in 141 cardiac allograft recipients and 40 controls. Our findings demonstrate that patients who died within the first year after transplantation had significantly higher median hsTNT serum levels 6weeks after transplantation (156ng/l±203 vs. 29ng/l±21, P=0.0002). Using ROC analysis, a serum hsTNT concentration of 33.55ng/l 6weeks after transplantation was found to be the best cutoff to predict death at 1 year (HR 0.16, 95%CI:0.05-0.46, P=0.001) with a sensitivity of 90.91% and a specificity of 70.97%. In addition, survival at 5years (HR 0.15, 95% CI 0.06-0.35, P<0.0001) was significantly better among patients below that cutoff value. In multivariate analysis, hsTNT serum level 6weeks after transplantation emerged as an independent predictor for first-year mortality (hsTNT-HR 0.90, 95% CI: 0.81-1.00, P=0.03). Cardiac troponin T concentrations early after transplantation as measured with a highly sensitive assay represent a strong and independent risk predictor of death after heart transplantation.

Journal-related Activities and Other Special Activities at the 2012 American Society of Anesthesiologists Annual Meeting

Journal-related Activities and Other Special Activities at the 2012 American Society of Anesthesiologists Annual Meeting

122 The Effect of Implementing High-Sensitivity Troponin Testing on Operational Efficiency in Three Large Urban Emergency Departments

New highly sensitive cardiac Troponin T (hsTnT) assays are becoming widely adopted in Canadian hospitals, raising the possibility of improved throughput times for emergency department (ED) assessment. Few studies have addressed the effects of introducing the hsTnT assay on ED and hospital resource consumption. In this study, we evaluate the impact of hsTnT implementation on ED length of stay (LOS), consultation and admission rates for patients with suspected AMI. This time-series analysis involved a cohort of all patients presenting to three Calgary adult EDs evaluated using hsTnT or its predecessor, conventional TnT (cTnT). The hsTnT assay was implemented on January 31, 2012. An educational intervention for ordering physicians and nurses preceded the implementation of hsTnT testing. The cutoff value used for diagnosis of AMI was 50 ng/ml. Data was collected for February 12, 2011-April 22, 2011: control period one year prior to hsTnT implementation (Ctrl1yrPre); November 20, 2011-January 28, 2012: immediately pre-hsTnT implementation (Immed-pre); February 12, 2012- April 21, 2012: immediately post-hsTnT implementation (Post). Subjects included all ED patients, excluding physician-confirmed STEMIs, who had at least one cTnT or hsTnT drawn as a marker for symptoms suspicious of AMI. The ED information system database was used to collect outcome data. Categorical variables were analyzed using Pearson's Chi-squared test. The Mann-Whitney U test was used to compare median values between the three study periods. We analyzed data from 6742 patients Ctrl1yrPre, 6952 Immed-pre and 5822 Post; demographic characteristics between the groups were similar. A smaller proportion of patients had troponin assays performed in the Post period, compared to the Ctrl1yrPre and Immed-pre periods (12.5% Post vs. 15.8% Ctrl1yrPre and 15.4% Immed-pre). A significant reduction in median ED LOS was observed following hsTnT implementation: 6.53 hours (h) in Ctrl1yrPre, 6.52 h in Immed-pre, and 6.04 h in Post (p<0.001). The proportion of patients with third troponins ordered decreased from 7.9% in Ctrl1yrpre and 7.2% in Immed-pre to 5.9% in Post (p<0.001). There was no statistically significant change in the number of Cardiology consultations or admissions following hsTnT implementation. Implementing hsTnT testing at three centers with an equivalent cutoff value and a change in nurse-initiated TnT ordering resulted in a decreased ED LOS for patients with suspected AMI and no increase in cardiology resource utilization. This finding may be attributable to a carefully considered hsTnT assay implementation strategy that reduced the number of unnecessary TnT assays performed.

Highly sensitive troponin T for risk stratification of acutely destabilized heart failure

A highly sensitive assay for troponin T (hsTnT) has been recently developed, which allows for the detection of even minor myocardial necrosis with high precision. It remains unexplored whether hsTnT provides incremental prognostic accuracy beyond conventional (c)TnT in patients with acutely decompensated heart failure (ADHF). A total of 202 consecutive patients admitted with ADHF and without criteria for acute myocardial infarction were studied. Troponin T was measured using the highly sensitive assay and compared with the conventional method. Patients were clinically followed up at a median of 406 days, with a primary outcome measure of all-cause mortality. The high-sensitive assay detected measurable TnT in 98% of patients vs 56% for cTnT; 81% had an hsTnT above the 99th percentile for a healthy reference population, and it reclassified 60% of those with undetectable cTnT. Both TnT methods predicted the risk of death in adjusted multivariable Cox regression analyses, without a superiority of hsTnT over cTnT in the entire population (area under the curve 0.67 vs 0.71, P = .2). Among patients with a cTnT below 0.03 ng/mL (the lowest cut-point with <10% imprecision; n = 134), solely hsTnT improved the prediction of death over clinical risk factors (relative integrated discrimination improvement +36%, P = .01) and hsTnT above 20 pg/mL identified a significant higher risk of death (hazard ratio 4.7, 95% CI 1.6-13.8, P = .005). Among patients with ADHF, myocardial necrosis (as detected with the hsTnT assay) was nearly ubiquitous. The highly sensitive assay for TnT provides comparable prognostic information to cTnT overall, but among those in whom the cTnT method was less precise or frankly negative, the hsTnT assay provided prognostic information.

Optical Coherence Tomography and Highly Sensitivity Troponin T for Evaluating Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy (CAV) is a major impediment to long-term graft survival after heart transplantation. Intravascular ultrasound (IVUS) is more sensitive than coronary angiography for diagnosis, but the identification of specific plaque components or plaque composition is limited. In addition, there is an evident need for other noninvasive tools for diagnosing CAV. The aim of this study was to assess the utility of 2 new techniques for evaluating CAV: optical coherence tomography (OCT), and new high-sensitivity troponin T (hsTnT) assays. In 21 heart transplantation patients, coronary arteriography with IVUS and OCT were performed. Maximal intimal thickness (MIT) and luminal area at the most severe site were measured using the 2 techniques. Immediately before cardiac catheterization, blood samples were obtained and hsTnT levels measured. The evaluation of CAV by OCT showed a good correlation with IVUS measurements, with a mean difference in MIT of 0.0033 (95% confidence interval -0.049 to 0.043), taking advantage of lower interobserver variability (r = 0.94 for OCT vs r = 0.78 for IVUS) and better plaque characterization. When independent predictors of MIT were assessed in a multiple linear regression model, time after transplantation (β = 0.488, p = 0.004) and hsTnT (β = 0.392, p = 0.011) were the only independent predictors of MIT (R(2) = 0.591). In conclusion, this study is the first to evaluate 2 new techniques, OCT and hsTnT, in the challenging setting of CAV. The findings suggest that OCT provides lower interobserver variability and better plaque characterization than IVUS. Also, hsTnT could become a useful tool for ruling out CAV.

Comparison of diagnostic accuracy between three different rules of interpreting high sensitivity troponin T results

With the introduction of high sensitivity troponin-T (hs-TnT) assay, clinicians face more patients with 'positive' results but without myocardial infarction. Repeated hs-TnT determinations are warranted to improve specificity. The aim of this study was to compare diagnostic accuracy of three different interpretation rules for two hs-TnT results taken 6 h apart. After adjusting for clinical differences, hs-TnT results were recoded according to the three rules. Rule1: hs-TnT >13 ng/L in at least one determination. Rule2: change of >20 % between the two measures. Rule3: change >50 % if baseline hs-TnT 14-53 ng/L and >20 % if baseline >54 ng/L. The sensitivity, specificity and ROC curves were compared. The sensitivity analysis was used to generate post-test probability for any test result. Primary outcome was the evidence of coronary critical stenosis (CCS) on coronary angiography in patients with high-risk chest pain. 183 patients were analyzed (38.3 %) among all patients presenting with chest pain during the study period. CCS was found in 80 (43.7 %) cases. The specificity was 0.62 (0.52-0.71), 0.76 (0.66-0.84) and 0.83 (0.74-0.89) for rules 1, 2 and 3, respectively (P < 0.01). Sensitivity decreased with increasing specificity (P < 0.01). Overall diagnostic accuracy did not differ among the three rules (AUC curves difference P = 0.12). Sensitivity analysis showed a 25 % relative gain in predicting CCS using rule 3 compared to rule 1. Changes between two determinations of hs-TnT 6 h apart effectively improved specificity for CCS presence in high-risk chest pain patients. There was a parallel loss in sensitivity that discouraged any use of such changes as a unique way to interpret the new hs-TnT results.

Perioperative myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery

ObjectiveCardiovascular complications are important causes of morbidity and mortality in elective non-cardiac surgery. Although difficult to diagnose, perioperative myocardial infarction (MI) remains prognostically important. High-sensitivity troponin T (hs-TnT) assays allow...

The performance of high sensitivity troponin for the diagnosis of acute myocardial infarction is underestimated

Many papers evaluating high sensitivity troponin assays make the diagnosis of myocardial infarction based on conventional troponin assays in clinical use at the time of recruitment. Such analyses often do not show superiority of high sensitivity assays compared with contemporary assays meeting precision guidelines. Three hundred and twenty-two patients presenting to the emergency department between November 2006 and April 2007 for evaluation for acute coronary syndrome had serial (0 h and >6 h) bloods taken to compare troponin assays (Roche hsTnT, Abbott TnI, Roche TnT and Vitros TnI). The diagnosis of myocardial infarction was made using each troponin assay separately with which that same assay was analysed for diagnostic performance. The rate of myocardial infarction would be 38.9% using serial hsTnT, 31.3% using serial Abbott TnI, 27.1% using serial TnT and 26.4% using serial Vitros TnI. The baseline sensitivities (0 h) are 89.9% (85.2-93.3) for hsTnT, 77.9% (71.0-87.5) for Abbott TnI, 73.0% (65.6-78.7) for TnT and 86.8% (74.6-94.4%) for Vitros TnI. The specificities (peak 0 h and >6 h samples) are 93.1% (91.2-93.1) for hsTnT, 88.3% (86.5-88.3) for Abbott TnI, 92.2% (90.5-92.2) for TnT and 90.6% (70.1-90.6) for Vitros TnI. hsTnT has superior sensitivity for myocardial infarction than even assays at or near guideline precision requirements (Abbott and Vitros TnI). The specificity of hsTnT assay is not as poor as previous analyses suggest.

Predictive Value of the High-Sensitivity Troponin T Assay and the Simplified Pulmonary Embolism Severity Index in Hemodynamically Stable Patients With Acute Pulmonary Embolism

Background— The new, high-sensitivity troponin T (hsTnT) assay may improve risk stratification of normotensive patients with acute pulmonary embolism (PE). We externally validated the prognostic value of hsTnT, and of the simplified Pulmonary Embolism Severity Index (sPESI), in a large multicenter cohort. Methods and Results— We prospectively examined 526 normotensive patients with acute PE; of those, 31 (5.9%) had an adverse 30-day outcome. The predefined hsTnT cutoff value of 14 pg/mL was associated with a high prognostic sensitivity and negative predictive value, comparable to those of the sPESI. Both hsTnT ≥14 pg/mL (OR, 4.97 [95% CI, 1.71–14.43]; P =0.003) and sPESI ≥1 point(s) (OR, 9.51 [2.24–40.29]; P =0.002) emerged, besides renal insufficiency (OR, 2.97 [1.42–6.22]; P =0.004), as predictors of early death or complications; in a multivariable model, they remained independent predictors of outcome ( P =0.044 and 0.012, respectively). A total of 127 patients (24.1%) were identified as low risk by a sPESI of 0 and hsTnT &lt;14 pg/mL; none of them had an adverse 30-day outcome. During 6-month follow-up, 52 patients (9.9%) died. Kaplan-Meier analysis illustrated that patients with hsTnT ≥14 pg/mL ( P =0.001) and those with sPESI ≥1 ( P &lt;0.001) had a decreased probability of 6-month survival. Patients with sPESI of 0 and hsTnT &lt;14 pg/mL at baseline had a 42% reduction in the risk of dying (hazard ratio, 0.58 [0.01–0.42]; P =0.005). Conclusions— The hsTnT assay and the sPESI improve risk stratification of acute PE. Combination of both modalities may yield additive prognostic information and particularly identify possible candidates for out-of-hospital treatment.

Abstract 18097: Diagnostic and Prognostic Value of Serum Concentration of High-Sensitivity Cardiac Troponin T Relative to Heart-Type Fatty Acid-Binding Protein in the Early Hours of Suspected Acute Coronary Syndrome

Background: Heart-type fatty acid-binding protein (H-FABP), a low-molecular-mass cytoplasmic protein, has been proposed as an early biomarker for acute myocardial infarction (AMI). Thus, we prospectively investigated the diagnostic and prognostic value of serum level of high-sensitivity troponin T (hsTnT) relative to H-FABP in the early hours of acute coronary syndrome (ACS). Methods: Serum samples for measurements of hsTnT and H-FABP were drawn on admission in 460 consecutive patients (median age, 67.5 yrs) hospitalized to the cardiac emergency department for suspected ACS within 6 hrs (3.5 hrs) after the onset of chest symptom. Cardiac events, which were defined as cardiac death or rehospitalization for ACS or heart failure, were monitored for 12 months after admission. The final diagnosis was adjudicated by two independent cardiologists. Results: 224 (48.7%) patients were diagnosed as AMI [ST-segment elevation myocardial infarction in 154 (33.4%) patients; and emergent coronary angiography within 24 hrs after admission in 195 (42.4%) patients]. The area under the ROC curve was higher for hsTnT than for H-FABP (Table). The sensitivity and predictive accuracy of increased hsTnT (&gt; 0.014 ng/ml of 99th percentile) were higher than those of increased H-FABP (≥ 6.2 ng/ml of upper reference limit). Also, there was no significant difference in specificity between hsTnT and H-FABP. During 12-month follow-up period, there were 38 (8.3%) cardiac events including 11 cardiac deaths. In a stepwise Cox regression analysis, increased hsTnT (relative risk 14.5, P = 0.009), but not H-FABP, was independently associated with cardiac events. Patients with increased hsTnT had a higher risk of cardiac events within 12 months compared with those without (14.1% vs. 0.5%, P &lt; 0.0001). Conclusion: An hsTnT assay may provide diagnostic and prognostic information superior to H-FABP assay in the early hours of suspected ACS.

Arterial stiffness is associated with minimally elevated high-sensitivity cardiac troponin T levels in a community-dwelling population

ObjectivesArterial stiffness predicts an excess risk of future cardiovascular events, supposedly via myocardial damage. Minimally elevated levels of plasma cardiac troponin T (TnT), a marker of cardiomyocyte injury, can be...