Low Troponin Concentrations Research Articles

Impacts of high sensitivity troponin T reporting on care and outcomes in clinical practice: Interactions between low troponin concentrations and participant sex within two randomized clinical trials

BackgroundThe impacts of high sensitivity cardiac troponin (hs-cTn) reporting on downstream interventions amongst suspected acute coronary syndrome (ACS) in the emergency department (ED), especially amongst those with newly identified hs-cTn elevations and in consideration of well-established sex-related disparities, has not been critically evaluated to date. This investigation explores the impact of hs-cTnT reporting on care and outcomes, particularly by participant sex. MethodsTwo similarly ED-based randomized controlled trials conducted between July 2011 to March 2013 (n = 1988) and August 2015 to April 2019 (n = 3378) were comparatively evaluated. Clinical outcomes were adjudicated to the Fourth Universal Definition of MI. Changes in practice were assessed at 30 days, and death or MI were explored to 12 months. ResultsThe HS-Troponin study demonstrated no difference in death or MI with unmasking amongst those with hs-cTnT <30 ng/L, whereas the RAPID TnT study demonstrated a significantly higher rate. In RAPID TnT, there was significant increase in death or MI associated with unmasking for females with hs-cTnT <30 ng/L (masked: 11[1.5%], unmasked: 25[3.4%],HR: 2.27,95%C.I.:1.87–2.77,P < 0.001). Less cardiac stress testing with unmasking amongst those <30 ng/L was observed in males in both studies, which was significant in RAPID TnT (masked: 92[12.0%], unmasked: 55[7.0%], P = 0.008). In RAPID TnT, significantly higher rates of angiography in males were observed with unmasking, with no such changes amongst females <30 ng/L (masked: 28[3.7%], unmasked: 51[6.5%],P = 0.01). ConclusionCompared with males, there were no evident impacts on downstream practices for females with unmasking in RAPID TnT, likely representing missed opportunities to reduce late death or MI.

Exploring adherence to an early rule-out pathway for myocardial infarction in the emergency department using mixed-methods

Abstract Background Incorporating a high-sensitivity cardiac troponin assay into a care pathway for the assessment of suspected acute coronary syndrome has enabled myocardial infarction to be ruled out earlier. Purpose Using mixed methods, we explored adherence to an early rule-out pathway in the HiSTORIC (High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction) randomised controlled trial. Methods In 16,972 consecutive patients we evaluated clinician adherence to an early rule-out pathway for the assessment of suspected acute coronary syndrome. Adherence was defined in patients with presentation cardiac troponin I concentrations &amp;lt;5ng/L and symptom onset &amp;gt;2 hours from presentation without serial troponin testing (type 1 adherence); presentation troponin &amp;lt;5ng/L and symptom onset ≤2 hours from presentation with serial testing (type 2 adherence); or presentation troponin between 5ng/L and sex-specific 99th centile with serial testing (type 3 adherence). Semi-structured interviews were conducted with 23 clinicians to aid interpretation of the quantitative analysis. Qualitative data were coded and organized into themes. Results In patients with troponin &amp;lt;5ng/L presenting &amp;gt;2hr from symptom onset, adherence was achieved in 81% of patients. In patients presenting ≤2hr from symptom onset, 35% of patients had a second troponin test. In patients with an initial troponin concentration between 5ng/L and the 99th centile, 65% of patients had a second troponin test. Compared to patients managed by clinicians who were adherent to the pathway, patients with troponin over-testing (type 1 non-adherence) were more likely to be older (mean age 52±16 years versus 58±14, P&amp;lt;0.001) and have a history of coronary disease (11% versus 27%, P&amp;lt;0.001). In contrast, patients with under testing (type 2 non-adherence) tended to be younger (mean age 49±16 versus 63±15, P&amp;lt;0.001), female (50% versus 37%, P&amp;lt;0.001) and have lower presentation troponin levels (median concentration 1.0ng/L IQR 1.0 to 2.0, versus 5.0ng/L IQR 2.0–10.0) compared to those in whom testing was performed according to pathway recommendations. Semi-structured interview data revealed how pathway adherence was influenced by five main themes: guideline characteristics, patient characteristics, the healthcare practitioner, the healthcare system and scientific evidence. Clear visual pathway layout was fundamental in achieving optimal adherence. Strong clinical suspicion of acute coronary syndrome promoted repeat troponin testing and deviation from the pathway was felt to be justifiable by more senior clinicians. Conclusion This analysis revealed successful implementation of the early rule-out pathway with interview data aiding interpretation of trial data. Younger patients with lower troponin concentrations were less likely to receive pathway recommended serial troponin testing. Clinical judgement is one of the main reasons for discontinuation of pathway recommendations. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

Impacts of High Sensitivity Troponin T Reporting on Care and Outcomes in Clinical Practice: Interactions between Low Troponin Concentrations and Participant Sex within Two Randomized Clinical Trials

Impacts of High Sensitivity Troponin T Reporting on Care and Outcomes in Clinical Practice: Interactions between Low Troponin Concentrations and Participant Sex within Two Randomized Clinical Trials

Troponin to risk stratify patients with suspected acute coronary syndrome for computed tomography coronary angiography

Abstract Background Patients with suspected acute coronary syndrome in whom myocardial infarction has been ruled-out are at risk of future adverse cardiac events. However, the optimal approach to risk stratify and investigate these patients is uncertain. Methods We performed a prospective cohort study of 250 patients presenting to the Emergency Department with suspected acute coronary syndrome and troponin concentrations below the sex-specific 99th centile (16 ng/L for women and 34 ng/L for men). Patients were recruited in a 2:1 fashion stratified by peak high-sensitivity cardiac troponin I concentration above and below the early rule-out threshold of 5 ng/L (167 patients with intermediate troponin concentrations between 5 ng/L and the sex-specific 99th centile threshold and 83 patients with troponin concentrations &amp;lt;5 ng/L). All patients underwent computed tomography coronary angiography after they were discharged from hospital. Results Overall, 37.6% (94/250) of patients had normal coronary arteries whilst 36.0% (90/250) and 26.4% (66/250) had non-obstructive and obstructive coronary artery disease, respectively. Patients with intermediate troponin concentrations were more likely to have coronary artery disease than those with troponin concentrations &amp;lt;5 ng/L (71.9% [120/167] versus 43.4% [36/83]; odds ratio 3.33 [95% confidence interval 1.92–5.78]). This association persisted irrespective of whether patients had anginal symptoms. Conversely, there was no difference in the prevalence of coronary artery disease between those with and without anginal symptoms (63.2% [67/106] and versus 61.8% [89/144]; odds ratio 0.92 [0.48–1.76]). The majority of patients found to have coronary artery disease did not have a prior diagnosis and were not on optimal preventative medical therapy prior to undergoing computed tomography coronary angiography (50.8% [61/120] and 61.0% [22/36], versus 61.7% [74/120] and 69.4% [25/36] in patients with intermediate versus low troponin concentrations, respectively). Conclusions In patients with suspected acute coronary syndrome who have myocardial infarction ruled out, those with intermediate cardiac troponin concentrations are three-times more likely to have coronary artery disease than those with low troponin concentrations. Conversely anginal symptoms did not discriminate between those with and without coronary artery disease. Further studies are required to determine if targeting computed tomography coronary angiography to those with intermediate cardiac troponin concentrations can improve the use of preventative medical therapies and clinical outcomes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The British Heart Foundation Odds ratio of coronary artery diseaseCumulative proportion with CAD

Effect of Particle Size and Surface Chemistry of Photon-Upconversion Nanoparticles on Analog and Digital Immunoassays for Cardiac Troponin.

Sensitive immunoassays are required for troponin, a low-abundance cardiac biomarker in blood. In contrast to conventional (analog) assays that measure the integrated signal of thousands of molecules, digital assays are based on counting individual biomarker molecules. Photon-upconversion nanoparticles (UCNP) are an excellent nanomaterial for labeling and detecting single biomarker molecules because their unique anti-Stokes emission avoids optical interference, and single nanoparticles can be reliably distinguished from the background signal. Here, the effect of the surface architecture and size of UCNP labels on the performance of upconversion-linked immunosorbent assays (ULISA) is critically assessed. The size, brightness, and surface architecture of UCNP labels are more important for measuring low troponin concentrations in human plasma than changing from an analog to a digital detection mode. Both detection modes result approximately in the same assay sensitivity, reaching a limit of detection (LOD) of 10 pg mL-1 in plasma, which is in the range of troponin concentrations found in the blood of healthy individuals.

The problem(s) with troponin

Cardiac troponin has long been the preferred biomarker for the evaluation of acute coronary syndrome. Successive improvements in analytical performance have significantly enhanced the clinical utility of troponin assays, and the high sensitivity versions now in use are capable of measuring extremely low concentrations of troponin with high precision. Such assays have allowed contraction of the time frame required to confidently rule in and rule out acute myocardial infarction, permitting earlier intervention and earlier discharge, respectively. Robust analytical performance is essential to support clinical decision making, yet high sensitivity troponin assays are afflicted by a range of analytical issues that can undermine their value. These include a high rate of non-reproducible errors, or ‘fliers’, affecting certain assays; a high prevalence of macro-troponin interference affecting multiple assays; and possible loss of cardiac specificity of the troponin T assay in the setting of skeletal muscle disease. This talk will characterise the pitfalls and problems affecting troponin assays, and the risks they confer to patients, laboratories and health care services. Tension between the clinical importance of high sensitivity troponin assays and their analytical shortcomings highlights the need for continued innovation and solutions from our manufacturers.

The value of ultra-sensitive troponin I in determining the prognosis of patients with the suspected acute coronary syndrome in the emergency department

Aim: Acute coronary syndromes (ACS) have significant mortality and morbidity in our country and the world. With the development of technology, early diagnosis and treatment may be possible. Ultra-sensitive troponin I (us-TnI) test developed a few years ago has provided accurate detection of even lower troponin concentrations using a microparticle immunoassay. There are very few studies in the literature about us-TnI showing prognosis. In this study, we aimed to find the value of the newly introduced us-TnI in determining mortality in one-month and three-month follow-ups. Materials and Methods: The study included all patients who were admitted to our tertiary emergency department (ED) between November 2015 and June 2016 and whose us-TnI levels was studied considering ACS. Whether the follow-up of the patients included in the study resulted in death was determined. The patients were classified according to the date of death based on their mortality status at the end of the first month and third month. Results: It was found that of the patients, 4.0% (n=264) died within 1 month after the first troponin measurement, while 6.8% (n=444) died within 3 months after the first troponin measurement. The AUC of the baseline us-TnI value in determining cardiac death at the end of the first month was 0.803 (95% Cl: 0.793-0.813) and the AUC of the baseline us-TnI value in determining cardiac death at the end of the third month was 0.763 (95% Cl: 0.752-0.773). Conclusion: Us-TnI studied at the time of admission to ED is an early indicator of mortality in patients with the diagnosis of ACS.

High-sensitivity troponin and the risk of atrial fibrillation in chronic kidney disease: Results from the Chronic Renal Insufficiency Cohort Study

Patients with chronic kidney disease (CKD) are at an increased risk of atrial fibrillation (AF). There is a need for novel biomarkers to reliably and accurately predict AF in this population. High-sensitivity troponin (HsTP) allows the detection of low troponin concentrations. The utility of HsTP for evaluating the risk of AF in CKD has not been established. We sought to explore the association between HsTP and the risk of incident AF in CKD. The Chronic Renal Insufficiency Cohort is a prospective cohort of 3939 individuals with mild to moderate CKD. HsTP was measured at study enrollment. Patients with a history of AF were excluded. Patients were followed for new-onset AF, and the association between HsTP and incident AF was examined using the Cox regression model. A total of 3217 participants were included. Over a median follow-up period of 7.1 years (interquartile range 5.0-8.4 years), 252 patients developed new-onset AF (12 events per 1000 person-years of follow-up). The incidence of new-onset AF was 2.46%, 7.06%, and 11.5% at 3, 6, and 9 years, respectively. Compared with the lowest quartile of HsTP, patients in the third quartile of HsTP (hazard ratio 2.40; 95% confidence interval 1.58-3.65; P < .001) and the fourth quartile of HsTP (hazard ratio 4.43; 95% confidence interval 2.98-6.59; P < .001) had a higher incidence of AF. HsTP levels are associated with an increased risk of AF in patients with mild to moderate CKD. This association remains significant despite adjustment for traditional AF risk factors and chronic renal disease.

High-sensitivity troponin I for cardiovascular risk stratification in the general asymptomatic population: Perspectives from Asia-Pacific

Cardiac troponin is a sensitive and specific biomarker for acute myocardial injury and has been used in the diagnosis of acute coronary syndromes, and has emerged as a tool for identifying high risk individuals for primary preventive therapy. Recent evidence has emerged indicating that high-sensitivity cardiac troponin assays, which allow robust detection of very low troponin concentrations, could detect subclinical injury in asymptomatic patients. On 24 March 2018, a group of cardiologists from the Asia Pacific region convened to review the data and discuss the potential utility of high-sensitivity troponin I (hsTnI) in the risk assessment of cardiovascular disease in the general population. The group recognized the immense burden of cardiovascular disease in the Asia-Pacific region, and the limitations of current risk stratification strategies. Data demonstrates that cardiac biomarkers like hsTnI could improve risk stratification, and thresholds for hsTnI in cardiovascular disease risk classification have been developed in Caucasian populations but not validated in Asian populations. There is an urgent need to improve cardiovascular risk assessment in the Asia Pacific general population, validate the Asian threshold of high risk and prove the utility of targeting these high-risk individuals for primary preventive strategies.

Diagnosing myocardial infarction: a highly sensitive issue

Diagnosing myocardial infarction: a highly sensitive issue

The importance of low level QC for high sensitivity troponin assays

BackgroundWith the advent of the new high-sensitivity troponin assays, it is becoming critical to measure troponin accurately to low concentrations. To ensure assay performance is acceptable, appropriate QC must be run. MethodsIn addition to the routine use of commercial QC material, we prepared pools of human QC material with low troponin concentrations close to the limit of quantitation, and ran these regularly on our laboratory analysers. ResultsOver 3 years we found no drift or shift in our hs-cTnI assay. We found that only the very low concentration human QC material gave warning of precision problems with the hs-cTnI assay. At the time of the documented poor assay precision, the higher concentration QC material indicated satisfactory performance. ConclusionsChoice of QC material with an appropriate concentration is important for any assay. For hs-cTn assays, it is of particular importance to use control material with a concentration near to the limit of quantitation.

Unstable angina in the era of high-sensitivity troponin testing: a genuine entity and a cautionary tale

High-sensitivity cardiac troponin assays have emerged as a powerful tool in the management of patients presenting acutely to hospital with suspected cardiac chest pain. Recent guidelines emphasize the reassurance offered by low troponin concentrations early after admission. We describe a patient with known coronary artery disease, who presented with a classical history of recurrent myocardial ischaemia. High-sensitivity cardiac Troponin-I concentrations remained in the low-normal sex-specific reference range, despite serial testing on the day of admission, and despite recurrent pain with dynamic ECG changes. Urgent coronary angiography confirmed severe multi-vessel disease. He required an intra-aortic balloon pump within 24 h due to clinical instability, and had urgent coronary artery bypass surgery a few days later. This case confirms that "unstable angina" remains a genuine entity. It highlights the hazards of over-reliance on any single test and serves as a reminder of the importance of integrating tests with clinical assessment.

DYNAMIC CHANGES IN HIGH SENSITIVITY CARDIAC TROPONIN I IN RESPONSE TO ANTHRACYCLINE-BASED CHEMOTHERAPY: A PILOT STUDY FOR THE CARDIAC CARE TRIAL

Treatment advances have improved cancer outcomes and shifted interest towards minimising iatrogenic complications. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of troponin and may allow early detection of anthracycline-related myocyte injury.

LO04: Very low concentrations of high-sensitivity troponin T at presentation can rapidly exclude acute myocardial infarction in a significant proportion of ED chest pain patients

Introduction: Chest pain is one of the most common presenting complaints to emergency departments (EDs) across the world, and the exclusion of acute myocardial infarction (AMI) using troponin testing is central to the care of many of these patients. Testing strategies using conventional troponin assays require repeat testing over many hours to avoid missed diagnoses. This study aims to validate the ability of very low concentrations of troponin at presentation to exclude AMI in ED chest pain patients. Methods: This prospective cohort study was conducted at a single urban tertiary centre and regional percutaneous coronary intervention site in Calgary, Alberta. Patients were eligible for enrolment if they presented to the ED with chest pain, were 25-years or older and required biomarker testing to rule out AMI at the discretion of the attending emergency physician. Patients were excluded if they had clear acute ischemic ECG changes, new arrhythmia or renal failure requiring hemodialysis. High-sensitivity troponin-T (Roche Elecsys hs-cTnT) results were obtained in all patients at presentation. Relevant outcomes were obtained from administrative data. The primary outcome was AMI within 30-days of ED visit, the secondary outcome was 30-day major adverse cardiac events (MACE). The study was REB approved. Results: A total of 1,016 patients were enrolled from August 2014-September 2016, of which 174 (17.1%) patients had an initial troponin below the limit of blank (&amp;lt;3 ng/L) and 369 (36.3%) had a level below the limit of detection (&amp;lt;5 ng/L). The sensitivity and negative predictive value (NPV) of a troponin below limit of blank (&amp;lt;3 ng/L) for 30-day AMI were 100% (95% CI 89.3%-100%) and 100% (95% CI 97.8-100%), respectively. The sensitivity and NPV of a troponin below limit of detection (&amp;lt;5 ng/L) for 30-day AMI were 93.8% (95% CI 80.0-98.3%) and 99.5% (95% CI 98.1-99.9%) respectively. Sensitivity for 30-day MACE at both cutoffs was lower: 96.1% (95% CI 92.5-98.0%) for &amp;lt;3 ng/L, and 88.4% (95% CI 83.3-92.1%) for &amp;lt;5 ng/L, respectively. Conclusion: A high sensitivity troponin T result below the limit of blank is highly sensitive at excluding AMI and identifies patients at reasonably low risk of 30-day MACE. A result below the limit of detection will identify a larger population of patients as low risk but has a greater risk of missed AMI and MACE.

Appropriate use of serum troponin testing in general practice: a narrative review.

The troponin assay was designed to assist in diagnosis and improve risk stratification for people presenting to the emergency setting with symptoms suggestive of an acute coronary syndrome. Newly developed high sensitivity assays provide reliable detection of very low concentrations of troponin and offer earlier risk stratification of patients with possible acute coronary syndrome. Cardiac troponin testing in general practice should be limited to patients presenting with ischaemic symptoms that occurred more than 24 hours previously. If these patients have no high risk clinical features and a normal electrocardiogram (ECG), they may be assessed with a single troponin assay but should be referred urgently to hospital if the result is elevated. In patients presenting with symptoms of possible acute coronary syndrome within the preceding 24 hours, or if they otherwise have symptoms consistent with unstable angina, high risk clinical features or ECG abnormalities, a serum troponin test should not be ordered and patients should be referred immediately to an emergency department. When a single troponin assay is appropriate, the test should be labelled as urgent and systems must be in place to ensure the result is conveyed immediately to the medical practitioner, as it has prognostic implications and may require an urgent action plan.

Two-hour diagnostic algorithms for early assessment of patients with acute chest pain — Implications of lowering the cardiac troponin I cut-off to the 97.5th percentile

AimsAssessment of patients with suspected non-ST elevation myocardial infarction (NSTEMI) is based on cardiac troponin (cTn) levels with the 99th percentile as cut-off. However, cardiovascular risk starts already at lower troponin concentrations. We therefore, aimed to investigate the utility of 2-hour algorithms using the high-sensitivity cardiac troponin I (hs-cTnI) 97.5th percentile as cut-off which corresponds to the standard URL for most biomarkers. MethodsHs-cTnI was measured at presentation and 2h in 1624 chest pain patients. Diagnostic algorithms were developed applying hs-cTnI levels dichotomized at the 99th and 97.5th percentiles combined with hs-cTnI changes and/or ECG findings. ResultsThe prevalence of NSTEMI was 13.9%. The adjusted odds ratios for 1-year mortality were 2.7 (95% CI 1.4–5.1) for the 99th percentile and 3.1 (95% CI 1.6–5.9) for the 97.5th percentile. The best-performing 99th percentile-based algorithms provided a positive predictive value (PPV) of 86.3% and a negative predictive value (NPV) of 99.3%. Using 97.5th percentile-based algorithms to define NSTEMI resulted in few reclassifications and yielded similar diagnostic estimates (PPV 85.4%, NPV 99.4%). ConclusionThe hs-cTnI 97.5th percentile integrated into 2-hour algorithms provided high diagnostic estimates and could, due to better prognostic properties serve as an alternative to the 99th percentile.

TnI-Ultra assay measurements in cancer patients: Comparison with the conventional assay and clinical implication

The serial monitoring of cardiac troponin represents an effective approach for the early identification, assessment, and monitoring of chemotherapy-induced cardiac injury. Over the last few years new generations of troponin assays, referred to as sensitive and high sensitivity assays, able to detect very low concentrations of troponin, have been progressively released on different platforms. Some studies have assessed the comparability of the cTnI measurements with the new assays versus the conventional ones, but none of these in the oncological population. We compared the cTnI results determined on Stratus CS and ADVIA Centaur CP System in 70 breast cancer patients, for a total of 327 samples collected during different cycles of treatment. Correlation (Spearman = 0.732) and agreement (91.4%) between the assays were good (244 concordant negatives and 55 concordant positives), with a frequency of 8.6% discordant results among the cTnI measurements. Despite the well-known lack in the harmonization and standardization of the currently commercially available cTnI methods, we found a good clinical concordance of cTnI determination on both systems.

Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome

High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS) trials. The primary endpoint was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI. All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI ≥99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI <99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3-5.7; P < 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI (P-trend < 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (<10 ng/L) but hs-cTnI ≥26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI <26 ng/L (9.2% vs 2.9%, P = 0.002). Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.

The Effect of Hemolysis on Current Troponin Assays—A Confounding Preanalytical Variable?

The universal definition of myocardial infarction stipulates the detection of an increase and/or decrease in cardiac biomarkers [preferably troponin I (TnI)1 or T (TnT)], with at least 1 value >99th percentile of the upper reference limit, together with evidence of myocardial ischemia (1). With the emergence of more sensitive troponin assays, what constitutes a genuine increase and/or decrease becomes critically important(2). For analytical values to be considered different, it has been suggested that such values should vary by >3 SDs of the variance of the measurement method and that a 20% change for troponins is greater than what would be expected from analytical variation(1). At low troponin concentrations, either definition translates into small absolute changes. Good analytical precision is therefore critically important, as is careful consideration of preanalytical variables, such as sample type and particularly hemolysis. Hemolysis is known to be more prevalent in the emergency department environment, with rates of up to 20% of samples(3). Hemolysis …

Can Changes in Troponin Results Be Useful in Diagnosing Myocardial Infarction?

In 1979, the WHO defined 3 specific criteria for use in the diagnosis of myocardial infarction (MI)1 : (a) clinical symptoms typical for ischemic heart disease, (b) specific electrocardiogram changes, and (c) a typical change in serial measurements of cardiac enzymes (1). Later definitions have continued in the mold of listing specific criteria, and in the current definition of MI, a characteristic increase and/or decrease in a cardiac biomarker with at least 1 result >99 percentile of a healthy population and evidence of myocardial ischemia (either specific symptoms or electrocardiographic or ultrasound findings) are mandatory (2). During the last decade, troponin T or I molecules, which are found only in myocardial cells and released after cell necrosis, have been the preferred cardiac biomarkers because of their high sensitivity and specificity (3), although myocardial cell necrosis can be seen in conditions other than myocardial ischemia (renal failure, sepsis, treatment with cardiotoxic drugs, myocarditis, and so on). A common problem in clinical practice is how to diagnose an acute MI in a patient who already has increased troponin concentrations. The National Academy of Clinical Biochemistry has suggested that a 20% increase in troponin results can be used to diagnose an ischemic event. This recommendation is based on analytical variation for troponin analysis alone, without taking biological variation into account (4). Recently, troponin assays with better analytical sensitivity have become commercially available. These assays not only have opened up new diagnostic opportunities but also have challenged our understanding of ischemic heart disease, because the assays can detect low troponin concentrations, even in the healthy population (5)(6). The natural fluctuations of troponin concentrations around a homeostatic set point (i.e., within-person biological variation) as well as the between-person biological variation can be established, as is reported by Vasile et al. in …