Sensitive Cardiac Troponin Assays Research Articles

Prevalence and outcome of clinical misdiagnosis of non-ST-elevation myocardial infarction

Abstract Background The prevalence of clinical misdiagnosis of non-ST-elevation myocardial infarction (NSTEMI) and its impact on patient outcomes is largely unknown. Methods We prospectively enrolled adult patients presenting with suspected acute coronary syndromes at 12 sites in five European countries. All patients provided written informed consent and were managed as per local clinical care using conventional, sensitive or high-sensitivity cardiac troponin (hs-cTn) assays. Study blood samples were taken at presentation and serially thereafter for measurements of hs-cTn concentrations. Final diagnoses were adjudicated by two independent cardiologists according to current guidelines and the 4th universal definition of myocardial infarction using all information including serial hs-cTnT measurements and imaging. The primary diagnostic endpoint was the prevalence of clinical NSTEMI misdiagnosis. Co-primary prognostic endpoints were 30 day and two year all-cause and cardiovascular (CV) death. Results In 7,678 patients (median age 61 [IQR 48-73], 34% women), the prevalence of adjudicated and clinical NSTEMI was 17.8% and 12.3%, respectively (P<0.001). Among 1,363 patients with an adjudicated NSTEMI (77% type 1 MI, 23% type 2 MI), 470/1,363 (34%) had a clinical NSTEMI misdiagnosis. These patients were older, more often female, had lower median cTn concentrations, and were more likely managed at centers using non-hs-cTn assays at time of enrolment. Compared to patients with an adjudicated and clinical NSTEMI diagnosis, missed patients were less likely to undergo coronary angiography or revascularization and less often discharged on evidence-based treatment (dual antiplatelet therapy 24% vs 79%, statin 64% vs 92%, betablocker 68% vs 81%, all P<0.001). Finally, patients with a clinical NSTEMI misdiagnosis were at much higher risk of premature all-cause (HR 1.51, 95% CI 1.18-1.94, P<0.001) and CV (HR 1.93, 95%CI 1.42-2.63, P<0.001) death. Conclusion One out of three adjudicated NSTEMI patients was misdiagnosed in routine clinical care. Clinical NSTEMI misdiagnosis was associated with lower use of guideline-recommended therapies and a substantial increase in premature death.Alluvial plotAll-cause death at 2-years

A Malaysian Expert Consensus on the Use of High-sensitivity Cardiac Troponin in the Emergency Department

Recent guidelines have recommended using high sensitivity cardiac troponin (hs-cTn) assays to triage patients with suspected acute coronary syndrome. Despite this, less sensitive point-of-care testing is often the preferred choice in majority of hospitals. The aim of this evidence-based, expert consensus is to provide guidance for healthcare professionals in understanding the role of hs-cTn, specifically its level of sensitivity and specificity as well as its practical application in the emergency department setting, particularly in resource-limited centres in Malaysia. An expert panel with clinical and research expertise in the diagnosis and treatment of acute coronary syndrome was convened. Recommendations were based on a comprehensive review of the existing literature using MEDLINE and Embase databases, alongside individual clinical experience within the regional and international context. This expert consensus provides a structured approach to using hs-cTn in the emergency department and remains the only one to date produced by a group of Malaysian experts to help guide Malaysian clinicians dealing with acute chest pain on a daily basis.

Determination of sex-specific 99th percentile upper reference limits for a point of care high sensitivity cardiac troponin I assay.

High sensitivity (hs) cardiac troponin (cTn) assays are defined per the IFCC Committee on Clinical Application of Cardiac Biomarker (C-CB) by the ability to measure≥50% of concentrations greater than the limit of detection (LoD) with an impression of≤10% at sex-specific 99th percentiles. Our study determined the sex-specific 99th percentile upper reference limits for males and females utilizing heparinized plasma from AACC universal sample bank for the Siemens point of care (POC) Atellica® VTLi hs-cTnI immunoassay. Apparently healthy subjects, included overall 693, males 363, and females 330, following exclusionary surrogate biomarker use of hemoglobin A1c, NT-proBNP, and eGFR, along with statin medication. hs-cTnI was measured in a central laboratory, on multiple POC Atellica® VTLi immunoassay analyzers. The LoD was 1.24ng/L and the 10%CV concentration was 6.7 ng/L. 99th percentile URLs were determined by the nonparametric (NP) method. Histograms of the hs-cTnI concentrations (ng/L) for males and females were used to visualize the distributions and concentrations in men and women and differed significantly (pre- and post-exclusion, both p <0.001). 99th percentile URLs were: overall 23ng/L (90% CI 20-32ng/L); male 27ng/L (CI 21-37ng/L); female 18ng/L (CI 9-78ng/L). The percentages of subjects having a measurable concentration≥the LoD were: overall 83.7%, male 87.3%, female 79.7%. Our findings show the novel POC Atellica® VTLi hs-cTnI assay meets the designation of a 'high-sensitivity' assay using heparinized plasma.

Do age-adjusted sex-specific cut-off values improve the agreement between high sensitivity cardiac troponins I and T? A retrospective study

BackgroundMany reports noted a disagreement between High sensitivity cardiac Troponin (hs-cTn) assays on the diagnosis of Acute Coronary Syndrome (ACS). MethodsWe conducted a retrospective study aiming to assess the agreement between hs-cTn T (Roche) and hs-cTn I (Abbott) in patients presenting with a suspected ACS to the emergency department at Hotel-Dieu hospital between September 2017 and October 2019 using overall, sex-specific, and age-adjusted sex-specific cut-off values. This was measured using Cohen’s Kappa. We explored whether renal function, circadian rhythm, age and sex influenced the discordance. And we analyzed the trend of agreement between baseline and repeated measurements. Results4856 patients who had simultaneous hs-cTn I and T values were retained for the analysis. 53.5% had a hs-cTn T above the overall 99th percentile, compared to 19.9% for hs-cTn I. The numbers were significantly reduced when applying age-adjusted sex-specific 99th percentile.A disagreement was seen in 34% of cases using overall 99th percentile. Using sex-specific cut off values did not impact this discordance; however, age-adjusted sex-specific cut-off values reduced the percentage of discrepancies to 15.8%. The decreased renal function had a negative effect on the agreement while the circadian rhythm had minimal effect. This initial discordance was carried forward into repeated measurements. ConclusionThe disagreement between hs-cTn T and I assays could be imputed to the choice of cut-off values. The use of age-adjusted sex specific 99th percentile reduced majorly these discordances. Further studies are needed in order to evaluate their clinical utility in patients presenting with ACS.

Comparing conventional and high sensitivity troponin T measurements in identifying adverse cardiac events in patients admitted to an Asian emergency department chest pain observation unit.

BackgroundHigh sensitive cardiac troponin assays can be used for prediction of major adverse cardiac events (MACE) in patients with chest pain.MethodsWe included patients with symptoms suggestive of acute coronary syndrome in the emergency department observation unit. We compared the accuracy of conventional troponin T (cTnT) with high sensitive troponin T (hsTnT) at various ranges, as well as the utility of hsTnT and cTnT in prediction of 30-day and 1-year MACE.Results1023 patients were included (68.1% male, median age 56 years). There were 2712 hsTnT and cTnT values compared. hsTnT had a higher AUC than cTnT for 30-day and 1-year MACE. The optimal cut-off of 0-hour hsTnT for 30-day (PPV 34%, NPV 96.6%) and 1-year MACE (PPV 40.2%, NPV 94.2%) was 16 ng/L.For 844 patients who had values for both 0 and 2 h hsTnT, we proposed a rule-out cut-off of 0 and 2 h hsTnT < 16 ng/L (NPV 97.0%, 95%CI 95.5–98.1%) and a rule-in cut-off of 0 and 2 h hsTnT ≥ 26 ng/L (PPV 58.8%, 95%CI 40.7%-75.4%) for 30-day MACE. Negative 0–2 h delta-hsTnT had poor predictive discriminant capabilities on 30-day (PPV 8.2%) and 1-year MACE (PPV 12.3%).ConclusionThe cut off values of hsTnT used in the 0 and 2-hour algorithm to rule-out (16 ng/L) and rule-in MACE (26 ng/L) are in the range that previous cTnT assays are unable to measure accurately. Risk scores can be used to further improve NPV of the rule-out group. A fall in hsTnT level acutely is not predictive of MACE.

Continuation of Over-the-Counter Biotin Supplements in the Inpatient Setting: An Unexpected Source of Laboratory Error.

Over the past decade, use of high-dose biotin has increased significantly and can lead to erroneous results on some clinical immunoassays. In collaboration with pharmacists at our institution, we discovered that high biotin doses were being administered to inpatients as a continuation of patient-reported home biotin use. This retrospective study evaluated high-dose biotin administration in 226 inpatient encounters from 2009 to 2019 and its potential impact on concurrent immunoassay testing. In 96% of cases, biotin was administered in the inpatient setting as a continuation of patient-reported home use. In total, 322 immunoassays capable of biotin interference were performed across 100 inpatient encounters with high-dose biotin administration. Troponin T and TSH were the most commonly performed immunoassays in this cohort. Even though less than 5% of all high-dose biotin orders at our institution are placed for inpatients, hospitalized patients are still at risk for mismanagement due to erroneous immunoassay results. Immunoassay testing susceptible to biotin interference was performed in approximately 45% of inpatient encounters with biotin administration. Laboratories utilizing biotin-susceptible, sensitive cardiac troponin assays should be particularly cautious. Pharmacokinetic data for biotin clearance is especially lacking for certain populations likely to be hospitalized, such as those with renal failure. Given that medical conditions requiring high-dose biotin therapy are extremely rare, we recommend restricting biotin dosing during inpatient encounters for all other patients.

Highly Sensitive Cardiac Troponins: The Evidence Behind Sex-Specific Cutoffs.

Emergence of various highly sensitive cardiac troponin assays into clinical practice provides a new tool for clinicians diagnosing acute coronary syndrome. These assays also create a challenge for laboratories and clinicians who have yet to familiarize themselves with sex‐specific cutoffs. Healthy men and women, studied across various age groups and geographic locations, have notable differences in baseline values of highly sensitive cardiac troponin I and T, leading to establishment of sex‐specific upper reference limits and cutoffs. Several differences in cardiac physiology, size, and structure may account for baseline differences in highly sensitive cardiac troponins and outcomes between the sexes. The clinical utility of implementing sex‐specific cutoffs for diagnosis and management of acute coronary syndrome remains unclear. Presently, the only prospective study failed to show improved outcomes for men or women with use of sex‐specific cutoffs; however, a major limitation is the frequent lack of diagnostic, therapeutic, and preventive interventions prescribed to women with low‐level troponin elevations. Based on the current literature, we posit that there may nonetheless be clinical value in the use of sex‐specific cutoffs for evaluating suspected acute coronary syndrome, especially in select patient populations such as younger women who tend to have lower baseline values of highly sensitive cardiac troponins. Future studies should prospectively evaluate differences in diagnostic, pharmacologic, and interventional management in men and women using myocardial infarctions classified with sex‐specific cutoffs of the highly sensitive cardiac troponin assays.

Analytical validation of a highly sensitive point-of-care system for cardiac troponin I determination.

Background Highly sensitive cardiac troponin assays (hs-cTn) are not available as point-of-care (POC) measurements. As rapid testing cannot be achieved at the expense of clinical performance, there is an urgent need to develop and rigorously validate POC hs-cTn. Konica Minolta (KM) has recently developed a surface plasmon-field enhanced fluorescence spectroscopy-based POC hs-cTn I system. Methods We validated the analytical characteristics of the KM POC system according to the international guidelines. Results Limit of blank (LoB) and limit of detection (LoD) were 0.35 and 0.62 ng/L, respectively, hs-cTn I concentrations corresponding to a total CV of 20%, 10% and 5% were 1.5, 3.9 and 11.0 ng/L, respectively. Method comparison studies showed that KM calibration was successfully traced to higher-order references. Limit of quantitation (LoQ), i.e. the hs-cTn I concentration having a total error of measurement of ≤34%, was 10.0 ng/L. The upper reference limit (URL) for 600 healthy blood donors was calculated at 12.2 ng/L (90% confidence interval [CI]: 9.2-39.2), while sex-partitioned URLs were 20.6 (males) and 10.7 ng/L (females), respectively (p < 0.0001). KM assay measured hs-cTn I concentrations >LoD in 65.7% of all reference individuals, in 76.7% of males and in 54.7% of females, respectively. Conclusions The KM system joins the characteristics of POC systems to the analytical performance of hs-cTn.

High-Sensitivity Cardiac Troponin and the Universal Definition of Myocardial Infarction.

The introduction of more sensitive cardiac troponin assays has led to increased recognition of myocardial injury in acute illnesses other than acute coronary syndrome. The Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin testing and classification of patients with myocardial injury based on pathogenesis, but the clinical implications of implementing this guideline are not well understood. In a stepped-wedge cluster randomized, controlled trial, we implemented a high-sensitivity cardiac troponin assay and the recommendations of the Universal Definition in 48 282 consecutive patients with suspected acute coronary syndrome. In a prespecified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death and secondary outcome of noncardiovascular death at 1 year across diagnostic categories. Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4471), type 2 myocardial infarction by 22% (205/916), and acute and chronic myocardial injury by 36% (443/1233) and 43% (389/898), respectively. Compared with those without myocardial injury, the rate of the primary outcome was highest in those with type 1 myocardial infarction (cause-specific hazard ratio [HR] 5.64 [95% CI, 5.12-6.22]), but was similar across diagnostic categories, whereas noncardiovascular deaths were highest in those with acute myocardial injury (cause specific HR 2.65 [95% CI, 2.33-3.01]). Despite modest increases in antiplatelet therapy and coronary revascularization after implementation in patients with type 1 myocardial infarction, the primary outcome was unchanged (cause specific HR 1.00 [95% CI, 0.82-1.21]). Increased recognition of type 2 myocardial infarction and myocardial injury did not lead to changes in investigation, treatment or outcomes. Implementation of high-sensitivity cardiac troponin assays and the recommendations of the Universal Definition of Myocardial Infarction identified patients at high-risk of cardiovascular and noncardiovascular events but was not associated with consistent increases in treatment or improved outcomes. Trials of secondary prevention are urgently required to determine whether this risk is modifiable in patients without type 1 myocardial infarction. https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Abstract 16746: Single High-Sensitivity Cardiac Troponin I Measurement Using the Siemens Atellica IM Assay to Rule-Out Acute Myocardial Infarction at Presentation in Low Risk in Patients Evaluated in the Emergency Department

Introduction: High sensitivity cardiac troponin (hs-cTn) assays are able to quantitate low concentrations of cTn and provide an opportunity to rule out acute myocardial infarction (MI) at an early stage following a patient’s presentation to an emergency department. Hypothesis: The objectives of the current study were to examine the performance of single hs-cTnI measurement strategy to rule out acute MI and predict 30-day safety outcomes at presentation in these patients. Methods: This was a prospective, observational study of patients (n = 2342) presenting to US emergency departments with suspected acute coronary syndrome in whom cTnI measurements were obtained using the Siemens Atellica IM High Sensitivity Troponin I Assay (Siemens Healthcare Diagnostics). Clinical data and hs-cTnI results were analyzed to determine: 1) clinical sensitivity and negative predictive value (NPV) for ruling out acute MI and 2) safety outcomes of acute MI and death at 30 days, using the hs-cTnI limit of detection (LoD) 1.6 ng/L concentration. Results: Acute MI occurred in 306 patients (13.1%). In patients with a hs-cTnI &lt;LoD (n=421, 18.0%), the clinical sensitivity and negative predictive value (NPV) for acute MI were 100% (95% CI 99.0,100) and 100% (CI 99.3,100), respectively. Further, the sensitivity and NPV for the safety outcome of acute MI or death within 30 days for hs-cTnI &lt;LoD were 99.4% (CI 98.5, 99.9) and 99.5% (CI 98.9, 99.9), respectively. Only 2 patients (0.85%) had an event. Conclusion: A strategy of using a single hs-cTnI &lt;LoD at presentation allowed the immediate identification of 18.0% of patients highly unlikely to have acute MI and who were at very low risk for events at 30 days. Additional studies to understand the clinical utility and cost-savings of this strategy are needed.

Role for Cystatin C–Based Risk Stratification for Patients After Acute Coronary Syndrome in the Era of High Sensitivity Cardiac Troponin Assays

Role for Cystatin C–Based Risk Stratification for Patients After Acute Coronary Syndrome in the Era of High Sensitivity Cardiac Troponin Assays

Risk stratification and role for additional diagnostic testing in patients with acute chest pain and normal high-sensitivity cardiac troponin levels.

BackgroundNormal high sensitivity cardiac troponin (hs-cTn) assays rule out acute myocardial infarction (AMI) with great accuracy, but additional non-invasive testing is frequently ordered. This observational study evaluates whether clinical characteristics can contribute to risk stratification and could guide referral for additional testing.Methods918 serial patients with acute chest pain and normal hs-cTnT levels were prospectively included. Major adverse cardiac events (MACE) and non-invasive test results were assessed during one-year follow-up. Patients were classified as low and high risk based on clinical characteristics.ResultsMACE occurred in 6.1% of patients and mainly comprised revascularizations (86%). A recent abnormal stress test, suspicious history, a positive family history and higher baseline hs-cTnT levels were independent predictors of MACE with odds ratios of 16.00 (95%CI:6.25–40.96), 16.43 (6.36–42.45), 2.33 (1.22–4.42) and 1.10 (1.01–1.21), respectively. Absence of both recent abnormal stress test and suspicious history identified 86% of patients. These patients were at very low risk for MACE (0.4% in 30-days and 2.3% in one-year). Despite this, the majority (287/345 = 83%) of additional tests were performed in low risk patients, with <10% abnormal test findings. The diagnostic yield was significantly higher in the remaining higher risk patients, 40% abnormal test findings and a positive predictive value of 70% for MACE. Similar results were observed in patients without known coronary artery disease.ConclusionsClinical characteristics can be used to identify low risk patients with acute chest pain and normal hs-cTnT levels. Current strategies in the emergency department result in numerous additional tests, which are mostly ordered in patients at very low risk and have a low diagnostic yield.

Serum Cardiac Troponin T Levels in Asymptomatic Elderly Nursing Home Residents

BackgroundThe definition of myocardial infarction relies on elevated troponin levels. However, elevated levels of high sensitive cardiac troponin (hs-cTnT) assays have been reported in elderly patients without acute myocardial infarction. We sought to determine whether elevated hs-cTnT levels have a prognostic value in stable elderly subjects without any acute illness. MethodsThe study cohort included residents of a nursing home who were asymptomatic without any acute medical problem. Serum hs-cTnT levels were measured, and participants were divided into high and low hs-cTnT groups. We measured hs-cTnT levels of young healthy volunteers as well and compared them with hs-cTnT levels of those nursing home residents. ResultsFifty-seven nursing home residents and 14 young volunteers were included in the study. The average age of nursing home residents was 83 ± 14 years, compared with 37 ± 3 years of the volunteers. Levels of hs-cTnT were significantly higher in the elderly compared with the volunteers (0.02 ± 0.016 ng/mL vs 0.005 ± 0.0003 ng/mL; P < .001); accordingly, we chose a cutoff of 0.02 ng/mL hs-cTnT and divided the 57 patients into 2 subgroups for further evaluation. After adjustment for age, gender, and glomerular filtration rate, the hs-cTnT was still an independent predictor of 1-year mortality (relative risk 2.04 [95% conficence interval, 2.009-29.45], P = .003). ConclusionsMild elevations of hs-cTnT levels are common in elderly patients, and hs-cTnT level is an independent marker of mortality risk in this population. For patients older than 70 years, a different hs-cTnT cutoff is required (eg, higher than 0.014 ng/mL).

The prognostic value of highly sensitive cardiac troponin assays for adverse events in men and women with stable heart failure and a preserved vs. reduced ejection fraction.

Circulating biomarkers are important in the diagnosis, risk stratification and management of patients with heart failure (HF). Given the current lack of biomarkers in HF with preserved ejection fraction (HFpEF), we aimed to investigate the prognostic performance of the newly developed high-sensitivity (hs) assays for cardiac troponin I (hsTnI) compared with troponin T (hsTnT) for adverse events in HFpEF vs. HF with reduced ejection fraction (HFrEF). Findings in these two HF subgroups were also compared with those in the recently defined HF with mid-range ejection fraction (HFmrEF) subgroup. Both hsTnI and hsTnT were measured in 1096 patients with HFrEF [left ventricular ejection fraction (LVEF) <50%; n = 853] or HFpEF (LVEF ≥50%; n = 243) enrolled in the Singapore Heart Failure Outcomes and Phenotypes (SHOP) study. Both troponin assays were more strongly associated with the composite endpoint (all-cause mortality or first rehospitalization for HF) in HFpEF than in HFrEF. The hsTnT assay provided the greatest additional prognostic value in HFpEF in comparison with hsTnI and NT-proBNP. TnI was more strongly associated with composite events in men with HFpEF [hazard ratio (HR) 3.33, 95% confidence interval (CI) 1.82-6.09; P < 0.001 per standard deviation (SD) increase in log-transformed hsTnI] than in women with HFpEF (HR 1.35, 95% CI 0.94-1.93; P = 0.10 per SD increase in log-transformed hsTnI). There is a potential role for the prognostic use of high-sensitivity troponin assays, particularly hsTnT, in men and women with HFpEF. The predictive association of hsTnI with outcome appears strongest in men with HFpEF.

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.

Use of copeptin for rapid rule-out of acute myocardial infarction.

Copeptin is currently understood as a quantitative marker of endogenous stress. It rises rapidly in multiple acute disorders including acute myocardial infarction. As a single variable, it has only modest diagnostic accuracy for acute myocardial infarction. However, the use of copeptin within a dual-marker strategy together with conventional cardiac troponin increases the diagnostic accuracy and particularly the negative predictive value of cardiac troponin alone for acute myocardial infarction. The rapid rule-out of acute myocardial infarction is the only application in acute cardiac care mature enough to merit consideration for routine clinical care. However, the dual-marker approach seems to provide only very small incremental value when used in combination with sensitive or high-sensitivity cardiac troponin assays. This review aims to update and educate regarding the potential and the procedural details, as well as the caveats and challenges of using copeptin in clinical practice.

HIGH-SENSITIVITY CARDIAC TROPONIN AND THE CLASSIFICATION OF MYOCARDIAL INFARCTION

Background: Guidelines recommend classification of myocardial infarction due to plaque rupture (type 1) or myocardial oxygen supply-demand mismatch (type 2). Whether more sensitive cardiac troponin assays can help to differentiate between subtypes is uncertain. Methods: Consecutive patients (n=4,

A Rational Adoption of the High Sensitive Assay for Cardiac Troponin I in Diagnostic Routine.

We describe the adoption of high sensitive troponin I (hsTnI) in clinical practice in two hospital settings in Italy. Samples from 426 consecutive patients (mean age 68.8 ± 17.0) admitted to the Emergency Department with a suspected acute coronary syndrome (ACS) have been tested at admittance and after 3 and 6 hours by contemporary TnI and hsTnI. Results have been compared to the final clinical diagnosis. Troponin was detectable in 68.6% by TnI and 89.9% by hsTnI. Since hsTnI has a lower threshold for females, 38/41 patients with positive values only by hsTnI were women. The correlation between the assays was very high (r = 0.92). A diagnosis of acute myocardial infarction (AMI) was made in 45 cases (10.5%). The negative and positive predictive values for a 50% troponin variation at 3 hours were 95.8% and 66.7% for hsTnI and 95.0% and 52.6% for TnI and at 6 hours 90.3% and 100% for hsTnI and 88.9% and 78.9% for TnI, respectively. Receiver operating characteristic (ROC) curve analysis demonstrated a greater efficiency by hsTnI at 3 hours versus 6 hours (AUC = 0.91 versus 0.72). The main benefits of hsTnI are the adoption of gender-specific 99th percentile and the shortening of time to decision.

Myocardial Infarction Type 2 and Myocardial Injury.

The development and implementation of sensitive and high-sensitivity cardiac troponin assays has not only expedited the early ruling in and ruling out of acute myocardial infarction, but has also contributed to the identification of patients at risk for myocardial injury with necrosis, as confirmed by the presence of cardiac troponin concentrations above the 99th percentile. Myocardial injury with necrosis may occur either in the presence of overt ischemia from myocardial infarction, or in the absence of overt ischemia from myocardial injury accompanying other conditions. Myocardial infarction type 2 (T2MI) has been a focus of attention; conceptually T2MI occurs in a clinical setting with overt myocardial ischemia where a condition other than an acute atherothrombotic event is the major contributor to a significant imbalance between myocardial oxygen supply and/or demand. Much debate has surrounded T2MI and its interrelationship with myocardial injury. We provide a detailed overview of the current concepts and challenges regarding the definition, diagnosis, management, and outcomes of T2MI, as well as the interrelationship to myocardial injury, and emphasize several critical clinical concepts for both clinicians and researchers moving forward. T2MI and myocardial injury are frequently encountered in clinical practice and are associated with poor outcomes in both the short term and long term. Diagnostic strategies to facilitate the clinical distinction between ischemic myocardial injury with or without an acute atheroma-thrombotic event vs non-ischemic-mediated myocardial injury conditions are urgently needed, as well as evidence-based therapies tailored toward improving outcomes for patients with T2MI.

Strategies to overcome misdiagnosis of type 1 myocardial infarction using high sensitive cardiac troponin assays.

High sensitive cardiac troponin assays have become the gold standard in the diagnosis of an acute type 1 myocardial infarction (MI) in the absence of ST-segment elevation. Several acute or chronic conditions that impact cardiac troponin levels in the absence of a MI might lead to a misdiagnosis of MI. For example, patients with impaired renal function as well as elderly patients often present with chronically increased cardiac troponin levels. Therefore, the diagnosis of MI type 1 based on the 99th percentile upper limit of normal threshold is more difficult in these patients. Different diagnostic approaches might help to overcome this limitation of reduced MI specificity of sensitive troponin assays. First, serial troponin measurement helps to differentiate chronic from acute troponin elevations. Second, specific diagnostic cut-offs, optimized for a particular patient group, like elderly patients, are able to regain specificity. Such an individualized use and interpretation of sensitive cardiac troponin measurements improves diagnostic accuracy and reduces the amount of misdiagnosed MI type 1.