Sensitive cTn Assays Research Articles

Temporal trends in acute coronary syndrome hospitalisation rates: a comparison of administrative diagnosis coding and cardiac biomarker testing

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Victor Chang Cardiac Research Institute. Background/aims Accurate monitoring of trends in acute coronary syndromes (ACS) provides important information on the impacts of primary and secondary prevention. Use of cardiac troponin (cTn) assays with increasing sensitivity and specificity during the past 20 years have likely increased the rates of diagnosis of myocardial infarction (MI), particularly NSTEMI. We aimed to determine the correlation of ICD-coded ACS hospitalisation rates with biomarker-classified ACS rates to inform population-level monitoring of ACS trends in Australia. Methods We used linked hospitalisation, emergency department, mortality, and pathology data from all tertiary hospitals in Western Australia (WA). We identified all patients aged >20years with a principal diagnosis of STEMI or NSTEMI (ICD-10-AM I21.0-I21.4) or unstable angina (UA) (ICD-10-AM I20.0) from 2001-2017. Creatine kinase (CK) and cTn test results including high-sensitivity (hs-Tn) assays were classified as elevated based on the ESC/AHA Universal Definition using the upper reference limit value for each assay. We calculated age-standardised rates (ASRs) for ICD-10 coded STEMI, NSTEMI and UA hospitalisations, and those which were cTn positive (cTn+), or any biomarker positive including CK (Bm+). We assessed annual ASR ratios over time (reference: ICD-coded rates) and estimated annual % changes in admissions using Poisson regression models adjusting for 5-year age-group and sex. Results The cohort comprised 143,231 ICD-coded ACS hospitalisations for 91,701 patients. 60.5% of the patients were male and 95.2% of the ACS hospitalisations had linked cardiac biomarker records. Despite slightly lower ASRs, Bm+ based rates were consistent with patterns in ICD-coded admissions in both MI sub-types (Figure) with no significant differences stratified by sex. Average annual decline in STEMI admissions was -3.7% (95% CI -4.1%,-3.4%) and -3.2% (95% CI -3.6%, -2.9%) in ICD-coded and Bm+ hospitalisations respectively. The annual rise in ICD-coded NSTEMI ASRs was 4.1% (95% CI 3.9%, 4.4%) which correlated with the 4.4% (95% CI 4.1%, 4.7%) annual rise in Bm+ ACS hospitalisations. The age-standardised rate ratios of ICD-coded to Bm+ were 1.27 and 1.28 for STEMI and NSTEMI respectively in 2001 and remained consistent at 1.29 and 1.30 for STEMI and NSTEMI respectively in 2017, although this was not the case for cTn+:ICD-coded rate ratios. There was an inverse trend between ASRs of ICD-coded NSTEMI and UA over the study period which correlated with use of increasingly sensitive cTn assays. The proportion of UA admissions with Bm+ was consistently low (21%) over the study period. Conclusions Despite shifts from CK to cTn and hs-Tn assays during our study period, the present study highlights the validity of using linked hospitalisation data to monitor long term trends in ACS based on cardiac biomarker positivity. Figure legend. Age-standardised hospitalisation rates by classification status in ACS subtypes.

Troponin -T as a prognostic and diagnostic marker for myocardial infarction

Over the past decade, there has been a progressive evolution of cardiac marker testing in patients with acute coronary syndromes. Myocardial infarction (MI) is the leading cause of death in the developed world. Biomarkers have an vital role in analysis, risk stratification, administrative running and medical assessment making in the setting of patients presenting with signs and symptoms of MI. Cardiac troponin (cTn) rose to prominence during the 1990s and has evolved to be the cornerstone for diagnosis of MI. Cardiac troponins are released from myocytes following myocardial damage and loss of membrane integrity. Troponin T are member of a group of cardiac regulatory proteins which function to regulate the calcium mediated interaction of muscle filaments actin and myosin resulting in contraction and relaxation of striated muscle. New algorithms integrating Brain natriuretic peptide (BNP), NT-proBNP, and more sensitive cTn assays footing potential for more rapid diagnosis of MI, allowing for appropriate management steps to be initiated and more efficient and effective utilization of healthcare resources.

Change in troponin concentrations in patients with macrotroponin: An in vitro mixing study

IntroductionMacrotroponin is a complex formed between endogenous cardiac troponin autoantibodies (cTnAABs) and circulating cardiac troponin (cTn). The potential effect of macrotroponin on current high sensitivity cTn assays has not been fully explored but has recently been identified as a major cause of discrepancy in cTn results between assays. In this study we investigated the effects of mixing troponin (cTn) standards to specimens with and without macrotroponin. MethodMacrotroponin was identified in specimens by a recovery of cTnI < 40% following protein A immunoglobulin depletion. Troponin standards containing cTn-IC and cTn-TIC complexes were mixed with serum samples, with (n = 20) and without (n = 10) the presence of macrotroponin. Specimens were tested for cTn before and after mixing by three commercially available high sensitivity cTn assays. Gel filtration chromatography was carried out on five specimens with macrotroponin and each fraction was analzyed by multiple cTn assays. FindingsFollowing mixing with cTn-TIC standard, all specimens with macrotroponin had a markedly reduced absolute increase in cTnI, indicating negative analytical interference due to macrotroponin. Following mixing with the cTn-IC standard, specimens with macrotroponin demonstrated highly variable changes in cTnI, suggesting significant heterogeneity in macrotroponin complex reactivity between individuals. When the ratio of change, calculated by dividing the absolute change between two cTn assays, was compared between specimens with and without macrotroponin, significant differences were observed (p < 0.001). These findings were supported by variable migration of peak cTn activity on gel filtration chromatography. ConclusionMacrotroponin leads to assay dependent analytical interference affecting current high sensitivity troponin I assays. Furthermore, endogenously occurring cTnAABs are conformationally specific and the analytical effects vary between assays and individuals.

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI. Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.

Laboratory-related issues in the measurement of cardiac troponins with highly sensitive assays.

A number of assay-related issues can affect the performance of cardiac troponin (cTn) measurement in everyday practice. In this respect, it is vital that all information on cTn assays is known and that the performance characteristics of assays are objectively assessed and adequately described. The advent of the latest generation of more sensitive cTn assays has heralded a new wave of information about low concentrations of cTn in blood. These recent generation assays have improved analytical sensitivity and corresponding performance at low cTn concentrations when compared to their predecessors, providing a convincing goal for laboratory medicine in helping clinicians in the diagnosis of acute myocardial infarction. Crucial to the clinical utility of highly sensitive cTn assays is the laboratorians' role in closely scrutinizing proposed assays and defining their value in relation to available evidence. Analytical, as well as pre-analytical and post-analytical, aspects must be documented. In this review, we describe what laboratory professionals should know about their cTn assay performance characteristics and the pre-analytical prerequisites for robustness to ensure optimal post-analytical reporting.

P3599Minicare high sensitivity troponin: a novel point-of-care tool to improve ACS workflows

Abstract Background Cardiac troponin (cTn) has been broadly accepted as the biomarker of choice in the diagnosis of patients presenting with Acute Coronary Syndrome (ACS). Point-of-care (POC) cTn testing, defined as testing near the patient with rapid availability of results, has attracted a strong interest in the emergency department (ED) setting. It offers the potential to improve workflows, expedite clinical decisions and to reduce the length of stay. Workflows could be further optimized when a first measurement can already be performed by the emergency medical services prior to admission to the hospital. Advances in assay technology have led to high sensitive (HS) cTn assays that have a profound impact on clinical practice, providing early results at presentation and 1 hour after admission which speed up clinical decision-making. Here we evaluate the Minicare HS cTnI POC test under development, which has the potential to combine the benefits of HS-cTnI protocols with a POC workflow. Objective Evaluate the analytical and clinical capability of the Minicare HS-cTnI test under development to meet the criteria‡ for HS cTn of having a 10% CV &lt;99th percentile and a percentage measurable (&gt;LoD) of &gt;50%. Methods The evaluation is based on the Clinical Laboratory Standards Institute (CLSI) guidelines. Li-heparin whole blood and Li-heparin plasma samples were used to establish LoB, LoD, and LoQ, sample matrix comparison and linearity in the low range. The clinical performance for Minicare HS-cTnI was assessed and compared to Abbott Architect high-sensitivity troponin using banked samples from patients with ACS and collected at t=2–4h after admission. The percentage measurable was assessed and compared to Abbott Architect high-sensitivity troponin in a healthy population of 165 individuals. Results With a time to result within 10 minutes, the LoB is determined at 1.0 ng/L and the LoD at 2.1 ng/L. Plasma and whole blood results correlated well and showed comparable results. The 10% and 20% CV LoQ are established at 7.9 ng/L and 3.1 ng/L, well below the anticipated 99th percentile of 26 ng/L. With a percentage measurable of 77%, the criteria for a HS-cTnI assay are met in a POC device. A sensitivity of 93% and an NPV of 99% are found for Minicare HS-cTnI for a t=2–4h protocol vs 90% and 98% for Abbott Architect high-sensitivity troponin. In this study the area under the curve is 0.98 for Minicare HS-cTnI and 0.97 for Architect HS-cTnI. ROC curve t=2-4 h Conclusions With HS-cTnI capability on the Minicare platform, we show the potential to support a 0/1 h sampling protocol, combined with the speed of a POC workflow. This may enable even more rapid and safe rule-out of patients with ACS.

Cardiac troponins and beyond in acute coronary syndrome

Cardiac biomarkers are an integral component of the diagnostic work-up of patients with suspected acute coronary syndrome (ACS). Cardiac troponin (cTn) is the most sensitive diagnostic biomarker for patients with ACS and enables the differentiation of acute non-ST-elevation myocardial infarction (NSTEMI) from unstable angina. All cardiac and non-cardiac differential diagnoses must be taken into consideration. The use of cTn has a prognostic value in amultitude of acute and chronic diseases apart from ACS. Highly sensitive cTn (hsTn) assays should be preferentially used. Point-of-care (POC) troponin assays can be used for rule-in of acute MI but are generally not useful for rule-out of MI due to their lack of sensitivity compared to hsTn assays. This, however, may change with recent developments of newer and improved POC troponin assays. For exclusion of MI using hsTn assays, there are various protocols available, such as the instant rule-out with undetectable hsTn levels at admission or normal hsTn/cTn levels combined with normal copeptin levels or rule-out with serial controls of hsTn after 1, 2 or 3 h. This article provides an overview of guideline-recommended rule-out protocols for patients with suspected ACS and discusses recent advances in POC troponin assays.

Predicting Acute Myocardial Infarction with a Single Blood Draw.

We desired to determine cardiac troponin (cTn) concentrations necessary to achieve a positive predictive value (PPV) of ≥75% for acute myocardial infarction (AMI) to justify immediate admission of patients to a monitored unit and, in general, early coronary angiography. In a prospective multicenter diagnostic study enrolling patients presenting to the emergency department with symptoms suggestive of AMI, final diagnoses were adjudicated by 2 independent cardiologists based on clinical information including cardiac imaging. cTn concentrations were measured using 5 different sensitive and high-sensitivity cTn (hs-cTn) assays in a blinded fashion at presentation and serially thereafter. The diagnostic end point was PPV for rule-in of AMI of initial cTn concentrations alone and in combination with early changes. Among 3828 patients, 616 (16%) had an AMI. At presentation, 7% to 14% of patients had cTnT/I concentrations associated with a PPV of ≥75%. Adding absolute or relative changes did not significantly further increase the PPV. PPVs increased from 46.5% (95% CI, 43.6-49.4) for hs-cTnT at presentation >14 ng/L to 78.9% (95% CI, 74.7-82.5) for >52 ng/L (P < 0.001), whereas PPVs in higher hs-cTnT strata remained largely unchanged [e.g., 82.4% (95% CI, 77.5-86.7) for >80 ng/L vs 83.9% (95% CI, 76.0-90.1) for >200 ng/L (P = 0.72)]. The addition of early changes in hs-cTnT further increased the PPV up to 60 ng/L, but not for higher concentrations. Serial sampling does not seem necessary for predicting AMI and concurrent decision-making in about 10% of patients, as it only marginally increases the PPV for AMI and not in a statistically or clinically significant way. NCT00470587.

Myocardial injury in transient global amnesia: a case-control study.

Elevation of cardiac troponin (cTn), a sensitive biomarker of myocardial injury, is frequently observed in severe acute neurological disorders. Case reports suggest that cardiac dysfunction may also occur in patients with transient global amnesia (TGA). Until now, no study has systematically assessed this phenomenon. We performed a case-control study using data of consecutive patients presenting with TGA from 2010 to 2015. Multiple logistic regression analysis accounting for age, sex and cardiovascular risk factors was performed to compare the likelihood of myocardial injury [defined as elevation of cTn>99th percentile (≥14ng/L); highly sensitive cardiac troponin T assay] in TGA with three reference groups: migraine with aura, vestibular neuritis and transient ischaemic attack (TIA). Cardiac troponin elevation occurred in 28 (25%) of 113 patients with TGA. Patients with TGA with cTn elevation were significantly older, more likely to be female and had higher blood pressure on admission compared with those without. The likelihood of myocardial injury following TGA was at least more than twofold higher compared with all three reference groups [adjusted odds ratio, 5.5; 95% confidence interval (CI), 1.2-26.4, compared with migraine with aura; adjusted odds ratio, 2.2; 95% CI, 1.2-4.4, compared with vestibular neuritis; adjusted odds ratio, 2.3; 95% CI, 1.3-4.2, compared with TIA]. One out of four patients with TGA had evidence of myocardial injury as assessed by highly sensitive cTn assays. The likelihood of myocardial injury associated with TGA was even higher than in TIA patients with a more pronounced cardiovascular risk profile. Our findings suggest the presence of a TGA-related disturbance of brain-heart interaction that deserves further investigation.

Unstable Angina in the Era of Cardiac Troponin Assays with Improved Sensitivity—A Clinical Dilemma

BackgroundThere is an expectation that with the adoption of more sensitive cardiac troponin (cTn) assays, unstable angina would become a rarity. However, recent data from the SWEDEHEART registry demonstrated that 15% of patients admitted with non-ST-elevation acute coronary syndrome still were regarded as having unstable angina. We aimed to further investigate the clinical characteristics and outcome of these patients. MethodsThis was a retrospective, registry-based analysis (SWEDEHEART) including 3204 unstable patients, 18,194 non-ST-elevation myocardial infarction (NSTEMI) patients, and 977 controls without acute cardiovascular disease. All patients had available data on peak cTnT levels (more sensitive assay) and 1-year outcome. ResultsThe annual proportions of patients with unstable angina (2009-2013) among those with non-ST-elevation acute coronary syndrome ranged from 9.4% to 15.3%. Only 1239 unstable angina patients (39.7%) had a peak cTnT level ≤14 ng/L. Patients with unstable angina tended to be younger than those with NSTEMI but had higher prevalence of most cardiovascular risk factors and more advanced coronary artery disease. Compared with controls, the adjusted hazard ratios (95% confidence interval) regarding major cardiovascular events were 2.97 (1.30-6.78) and 5.44 (2.54-11.65) in unstable angina patients with peak cTnT ≤14 ng/L and >14 ng/L, respectively. ConclusionThe diagnosis of unstable angina is still commonly used, even in the era of more sensitive cTn assays. Minor cTnT elevation is common, which makes unstable angina difficult to distinguish from NSTEMI. Patients with unstable angina have a nonneglectable cardiovascular risk. We suggest that the clinical management of patients presenting with unstable symptoms should depend on their estimated cardiovascular risk rather than on strictly applied diagnostic criteria.

Safety and efficacy of the 0 h/3 h protocol for rapid rule out of myocardial infarction

The early and accurate diagnosis of acute myocardial infarction (AMI) is an important medical and economic challenge. We aimed to prospectively evaluate the performance of the new European Society of Cardiology rapid 0-hour/3-hour (0 h/3 h) rule out protocol for AMI. We enrolled 2,727 consecutive patients presenting with suspected AMI without persistent ST-segment elevation to the emergency department in a prospective international multicenter study. The final diagnosis was adjudicated by 2 independent cardiologists. The performance of the 0 h/3 h rule out protocol was evaluated using 4 high-sensitivity (primary analysis) and 3 sensitive cardiac troponin (cTn) assays. Acute myocardial infarction was the final diagnosis in 473 patients (17.3%). Using the 4 high-sensitivity cTn assays, the 0-hour rule out protocol correctly ruled out 99.8% (95% [confidence interval] CI, 98.7%-100%), 99.6% (95% CI, 98.5%-99.9%), 100% (95% CI, 97.9%-100%), and 100% (95% CI, 98.0%-100%) of late presenters (>6 h from chest pain onset). The 3-hour rule out protocol correctly ruled out 99.9% (95% CI, 99.1%-100%), 99.5% (95% CI, 98.3%-99.9%), 100% (95% CI, 98.1%-100%), and 100% (95% CI, 98.2%-100%) of early presenters (<6 h from chest pain onset). Using the 3 sensitive cTn assays, the 0-hour rule out protocol correctly ruled out 99.6% (95% CI, 98.6%-99.9%), 99.0% (95% CI, 96.9%-99.7%), and 99.1% (95% CI, 97.2%-99.8%) of late presenters; and the 3-hour rule out protocol correctly ruled out 99.4% (95% CI, 98.3%-99.8%), 99.2% (95% CI, 97.3%-99.8%), and 99.0% (95% CI, 97.2%-99.7%) of early presenters. Overall, the 0 h/3 h rule out protocol assigned 40% to 60% of patients to rule out. None of the patients assigned rule out died during 3-months follow-up. The 0 h/3 h rule out protocol seems to allow the accurate rule out of AMI using both high-sensitivity and sensitive cTn measurements in conjunction with clinical assessment. Additional studies are warranted for external validation.

Transitioning high sensitivity cardiac troponin I (hs-cTnI) into routine diagnostic use: More than just a sensitivity issue

ObjectivesHigh sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI) assays show analytical, diagnostic and prognostic improvement over contemporary sensitive cTn assays. However, given the importance of troponin in the diagnosis of myocardial infarction, implementing this test requires rigorous analytical and clinical verification across the total testing pathway. This was the aim of this study. Design and methodsAnalytical verification included assessment of critical outlier frequency, for hs-cTnI and cTnI assays. Concordance for paired cTnI and hs-cTnI measurements (n=1096) was verified using 99th percentiles for both genders (cTnI: 30ng/L, hs-cTnI: 25ng/L) and for men and women separately (hs-cTnI: M: 34;F: 16ng/L). Discordant data was correlated with clinical and laboratory information. Diagnosis of Acute Coronary Syndrome (ACS) or Non-ACS was adjudicated by two cardiologists independently. ResultsThe hs-cTnI assay showed a lower (10-fold) critical outlier rate (0.091%) and more detectable results above the limit of detection (LOD) (23.4%) and 99th percentile (2.4%), compared to cTnI. Analytical concordance between the two assays was high (94.5%) but decreased (91.7%) when gender-specific hs-cTnI cut-offs were used. The hs-cTnI assay gave fewer false negatives (up to 1.0%) but disproportionately more false positives (up to 6.7%) overall, which improved (3.9%) for serial measurements. ConclusionsLaboratories should analytically and clinically verify hs-cTn assays before use, with attention to performance and the clinical and diagnostic algorithms that support appropriate testing and result interpretation. Work in the pre- and post-analytical phases is necessary to augment the analytical improvement in the new era of troponin testing.

Highly sensitive cardiac troponin assays: a comprehensive review of their clinical utility.

Cardiovascular disease is a major source of morbidity and remains the leading cause of death in the United States. To evaluate patients with suspected cardiovascular disease, several laboratory markers of cardiac injury are available including creatinine kinase, creatinine kinase isoenzyme MB, myoglobin, and cardiac troponins (cTn) I and T. cTns have become the preferred marker of cardiac damage because they are highly sensitive and are almost completely cardiac specific. Recently, highly sensitive cTn (hs-cTn) assays were developed and have been used across the world to more quickly and accurately diagnose myocardial infarction. In the United States, these assays have not been U.S. Food and Drug Association approved for clinical practice and therefore are only being used for research purposes. Advancements have taken place over the years in diagnosing and treating cardiovascular disease, but predicting who will suffer future cardiovascular events still remains elusive. A comprehensive review of the literature was conducted to discover how new hs-cTn are being utilized throughout other parts of the world and what potential future use they may serve here in the United States. Major subject points discussed in this article include the prevalence of detectable troponins in the general population, the use of hs-cTn assays in diagnosing a myocardial infarction, determining prognosis in patients who have experienced an acute coronary syndrome and in patients with congestive heart failure, predicting future risk of cardiovascular events in patients with coronary heart disease, and its potential role as a screening tool in primary prevention. The implementation of hs-cTn testing in the United States may be very beneficial to patients; however, more research will need to be done to fully elucidate the potential use of hs-cTn in clinical practice.

Elevation of cardiac troponins measured after recreational resistance training

BackgroundWhereas elevated cardiac troponin (cTn) concentrations i.e. above the 99th percentile of healthy reference population (recommended cutoff for the diagnosis of myocardial infarction) are well-documented in healthy individuals after prolonged and/or intensive exercises such as marathons, data on less-strenuous sports are scarce. Therefore, our aim was to investigate cTnI and cTnT release in response to recreational resistance training, here a single-bout of 1-h kettlebell workout. MethodsSerum samples were collected from 11 apparently healthy volunteers the previous day (pre-exercise), three hours after the kettlebell class (post-exercise), the next day and three days later. The aliquoted samples were analyzed with Abbott Laboratories' Architect high-sensitivity (hs)-cTnI assay (limit of detection, LoD=2ng/L), our 3+1-type cTnI assay free from cTn-specific autoantibody interference (LoD=3ng/L) and Roche Diagnostics' hs-cTnT assay (LoD=5ng/L). ResultsThe post-exercise cTn concentrations were significantly higher than the pre-exercise values (median 5.5–9.6ng/L vs. <LoD, P<0.05 for all) and they correlated strongly between the three assays (Spearman r=0.881–0.960, P<0.001 for all). Furthermore, a few post-exercise concentrations even exceeded the 99th percentile of Architect hs-cTnI (>26ng/L, n=2) and/or hs-cTnT (>14ng/L, n=4). The cTn concentrations returned to baseline during the three days of follow-up. ConclusionsOur study demonstrates abnormally elevated cTns with well-validated sensitive cTn assays after resistance training. This confirms that different kinds of recreational physical activity are yet another confounder that may affect the determination and use of 99th percentile reference values. Therefore, exercise-associated changes should be carefully addressed as part of the evaluation what is “normal cTn”.

Sex differences of troponin test performance in chest pain patients

BackgroundCurrent guidelines recommend troponin as the preferred biomarker to diagnose acute myocardial infarction (AMI) irrespective of the patient's sex. Recent reports have shown that sex-specific cut-offs should be considered but studies investigating sex-differences in the diagnostic accuracy of cardiac troponins are sparse. ObjectiveTo evaluate whether the diagnostic performance of cardiac troponin at admission (cTn) under routine conditions is influenced by patient's sex. MethodsBetween 15th of February 2009 and 15th of February 2010, women (n=1648) and men (n=2305) who presented to the emergency department with chest pain (n=3954) were enrolled.The diagnostic performance of the routine, contemporary sensitive cTn assays (TnI; Stratus® CS, Siemens and TnT; Roche Diagnostics) at baseline for the diagnosis of non-ST-elevation myocardial infarction (NSTEMI) was analyzed. ResultsNSTEMI was diagnosed in 7.3% (n=287) of all patients. Men were more likely to be diagnosed with NSTEMI (8.8%; n=202) as compared to women (5.2%; n=85; p<0.001). Sensitivity was 56.1% (95% CI: 44.7–67.0%) in women and 70.1% (95% CI: 63.1–76.4%) in men. Specificity was 96.8% (95% CI: 95.6–97.7%) in women and 94.5% (95% CI: 93.3–95.6%) in men. This resulted in a lower positive predictive value (PPV) for women (53.5%; 95% CI: 42.4–64.3) as compared to men (60.8%; 95% CI: 54.1–67.2) and a slightly higher negative predictive value (NPV) for women: 97.1% (95% CI: 96.0–97.9) vs. 96.3% (95% CI: 95.2–97.2) in men. ConclusionsThe findings of this study underline that the performance of cTn for the diagnosis of NSTEMI depends on a patient's sex, with a lower sensitivity and NPV in women. The definition and implementation of sex-specific cut-off values for cTn into clinical routine seems to be highly recommendable.

Application and interpretation of high-sensitivity cardiac troponin assays in patients with acute ischemic stroke.

Cerebrovascular and cardiovascular diseases are major causes of death and disability worldwide. Ischemic stroke is a frequent complication in cardiac disease and, vice versa, cardiac complications commonly cause early clinical worsening and death after stroke.1 Adverse cardiac events account for the second largest group of deaths during the acute phase after stroke and are important determinants of long-term survival.2 Because of the close association between stroke and cardiac disease, current AHA/ASA guidelines for the early management of patients with acute ischemic stroke recommend assessment of cardiac biomarkers (preferably cardiac troponin [cTn]) in all patients presenting with acute ischemic stroke.3 Although the guidelines point out the potential prognostic significance of cTn, there are currently no recommendations on how to interpret cTn levels in the setting of ischemic stroke. Practice guidelines for interpretation of cTn generally include patients with stroke; specific recommendations, however, are scarce.4 Interpretation of cTn elevation in patients primarily presenting with ischemic stroke is complex because other conditions apart from acute thrombotic coronary artery disease (CAD) may also lead to the finding of an elevated cTn.4–6 What is more, clinical complaints associated with acute coronary syndromes may be atypical or masked by neurological deficits. Although early invasive coronary revascularization and potent antithrombotic therapy are lifesaving in patients with myocardial infarction (MI), caution is warranted in the context of an acute ischemic cerebral lesion. Recently, high-sensitivity cTn assays were developed, which enable detection of small amounts of circulating cTn.7,8 However, the marked increase in sensitivity for myocardial injury is accompanied by a reduced specificity for diagnosis of acute CAD. Consequently, the above-mentioned practice guidelines for applying highly sensitive cTn assays refer to stroke as one of the multiple clinical conditions, in which cTn testing has created clinical uncertainty.4 In …

The diagnostic utility of High-Sensitivity Cardiac Troponin T in acute coronary syndrome

Abstract Background Coronary artery disease (CAD), its acute form, and acute coronary syndrome (ACS) are the leading cause of death all over the world. For initial assessment of a patient with ACS, ECG, imaging techniques and serum biomarkers all contribute in confirming the diagnosis. Cardiac Troponin (cTn) I and T are the current gold standard for the detection of myocardial necrosis. However, there is also emerging evidence suggesting that with the use of sensitive or high-sensitive cTn assays, a blood sample collected 2 or 3 h after presentation might be appropriate for an earlier rule in and rule out diagnosis of AMI compared with the recommended second blood draw 6–9 h after admission using conventional Troponin assay. Aim The aim of this study was to examine the ability of High-Sensitivity Cardiac Troponin T for early detection of AMI in comparison with conventional Troponin assay. In addition, to study the clinical utility of kinetic changes of High-Sensitivity Cardiac Troponin T for diagnosis of ACS. Methods This study was conducted on sixty subjects. Fifty patients who presented to emergency department in Ain-Shams University Hospital complaining of chest pain were highly suspicious to have acute cardiac ischemia, having no or non-specific ECG changes and their Cardiac Troponin I level on admission was below the test threshold value (100 ng/L). In addition, ten subjects serving as a healthy control group were also recruited. The fifty patients were subdivided into subgroup A which included 16 patients, with hs-TnT n = 17) and group D, representing cases of NSTEMI ( n = 33). Results Results of the current study revealed that median serum levels of hs-TnT showed highly significant difference between patients with ACS and healthy subjects, and also between patients with NSTEMI and those with UA. Receiver operating characteristic (ROC) curve analysis was applied to assess the diagnostic performance of hs-TnT in discriminating patients from control group. The best cutoff was 4.8 ng/L. This cutoff had a diagnostic sensitivity, specificity, PPV, NPV and efficiency of 96%, 100%, 100%, 83.3% and 96.7% respectively. Another receiver operating characteristic (ROC) curve analysis was applied to assess the diagnostic performance of hs-TnT for discriminating NSTEMI patients from UA patients. The best diagnostic cutoff for hs-TnT was 13.7 ng/L. This had a diagnostic sensitivity, specificity, NPV, PPV and efficiency of 97%, 88.2%, 93.8%, 94.1% and 94% respectively. Conclusion Our study demonstrated highly significant absolute and relative kinetic changes in hs-TnT levels in patients with AMI. The hs-TnT can be used for early rule in patients with MI as it could detect 97% of cases with MI whose Troponin I was negative and could detect 100% of cases of MI after 6–8 h compared to Troponin I which could detect only 21.2% of cases. This can be of great importance in the future introduction and use of the new high sensitive assay as a non-invasive reliable diagnostic tool to replace the currently used invasive diagnostic techniques for patients with ACS.

High-sensitivity cardiac troponin in acute conditions.

We aim to help clinicians to use and interpret high-sensitivity cardiac troponins (cTns) in different acute care settings. This guidance is timely and relevant as high-sensitivity cTns are currently replacing conventional cTn assays in most parts of the world. cTn I and T are structural proteins unique to the heart. Detection of cTn in peripheral blood indicates cardiomyocyte injury. Although acute myocardial infarction is a very common, dangerous, but treatable and therefore clinically important cause of cardiomyocyte injury, multiple other acute conditions are associated with substantial amounts of cardiomyocyte injury and corresponding elevations in cTn. These include acute heart failure, tachyarrhythmias, pulmonary embolism, sepsis, shock, and noncardiac surgery. Recent advances in assay technology have led to more sensitive and precise cTn assays that now allow the detection and exact quantification of cardiomyocyte injury also in many predominately noncardiac acute conditions. In all of these, elevated levels of high-sensitivity cTn are associated with increased mortality risk. In some of these, concepts are evolving as to how the pathophysiological signal of cardiomyocyte injury could be used to alter patient management and potentially improve outcomes.

Cardiac troponin T elevation associated with transient global amnesia: another differential diagnosis of ‘troponosis’

Elevated cardiac troponin (cTn) levels can be detected in a variety of diseases with or without signs of myocardial ischaemia. Acute neurological disorders such as subarachnoid haemorrhage, stroke, transient ischaemic attack, epileptic seizures, and traumatic head injury can cause cTn elevation with and without myocardial wall motion abnormalities. We report a case of transient global amnesia with elevation and dynamic rise of highly sensitive troponin T (hsTnT) without clinical symptoms or signs of ischaemia. Cardiac work up was otherwise normal, with no signs of atherosclerotic coronary artery disease on coronary angiogram. Myocardial systolic function was also normal. In the era of highly sensitive cTn assays, dynamic elevations of cTn are seen in a number of acute conditions unrelated to myocardial ischaemia. Transient global amnesia should be added to the list of acute neurological disorders where cTn release can be present, even in the absence of stress-induced cardiomyopathy.

Myokardinfarkt

The third version of the Universal Definition of Myocardial Infarction (MI) was published in 2012. The diagnosis of acute myocardial infarction (AMI) should only be made in a clinical setting consistent with acute myocardial ischaemia when evidence of myocardial necrosis is present. The diagnostic criteria for MI are fulfilled when a rise and/or fall of cardiac biomarkers (preferentially troponins) occurs with at least one value above the 99th percentile of the upper reference limit. In addition, there should be symptoms of ischaemia, new changes in electrocardiogram (ECG), imaging evidence of a new loss of viable myocardium or new regional wall motion abnormality, or the identification of an intracoronary thrombus by angiography or autopsy. This revised definition updates previous versions by including changes to diagnostic ECG criteria, placing a higher emphasis on cardiac imaging, modifying the criteria for subtypes of MI and implementing high sensitivity cardiac troponin (cTn) assays. A guideline-based algorithm for management of patients with suspected acute coronary syndrome allowing "early rule-in" and "rule-out" of non-STEMI with high sensitivity cTn assays is also presented.