Few studies have comprehensively examined high-sensitivity cardiac troponin I (hs-cTnI) based diagnostic pathways for myocardial infarction (MI) in early presenters using a Siemens ADVIA Centaur hs-cTnI assay.

We conducted a prospective multicenter cohort study in Emergency Departments involving 414 patients suspected of MI within 6 h of symptom onset. We evaluated three hs-cTnI-based pathways (High-STEACS, ESC 0/1-h, 0/2-h); and four pathways incorporating medical history and physical findings (ADAPT, EDACS, HEART, GRACE). We evaluated negative predictive value (NPV) and sensitivity as safety measures, and percentage ruled out as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days.

Median age was 72 years (interquartile range 58-82), and 30.4 % (126/414) of patients were over 80. Females comprised 44.2 % (183/414) of patients, 87.7 % (363/414) had chest pain, and the primary outcome occurred in 9.2 % (38/414). The High-STEACS pathway ruled out 62.0 % of patients without missing a case of an MI. The ESC 0/1-h and 0/2-h pathways showed high NPV and sensitivities; however, they ruled out fewer patients (35.9 % and 45.2 %, respectively). The ADAPT, EDACS, and HEART pathways demonstrated high NPV and sensitivities but ruled out fewer patients (15-27 %). The GRACE pathway missed 2 cases with primary clinical outcomes. Among patients over 80 without MI, initial hs-cTnI concentration was ≥ 3 ng/L in 99.1 % and ≥ 5 ng/L in 84.1 %.

The High-STEACS pathway was the most efficient among the hs-cTnI-based pathways while maintaining excellent safety performance in early presenters.

The 99th percentile of cardiac troponin assays for determining the presence of acute myocardial infarction (AMI) was set when assay analytical performance was much less precise than currently and was chosen, in part, to reduce the frequency of 'false-positive' results. A result greater than 99th percentile criterion has been a requirement of each version of the universal definition of MI. It also became used as a dichotomous decision-making threshold in diagnostic strategies for investigating AMI in acute care settings. There are numerous difficulties in deriving the 99th percentile which undermine its reliability as a standalone test threshold. It is important for patient safety that all users are aware of the challenges and pitfalls of using the 99th percentile for decision-making. We present a focused review of the 99th percentile, highlighting some difficulties with its use as a decision threshold as well as possible adjunctive strategies and alternative approaches.

The Fourth Universal Definition of Myocardial Infarction recommends a classification based on aetiology, in recognition that the underlying pathophysiology of myocardial infarction influences the approach to investigation and treatment. Type 1 myocardial infarction occurs due to atherosclerotic plaque rupture with thrombosis, whereas type 2 myocardial infarction occurs due to an imbalance in myocardial oxygen supply or unmet need in myocardial oxygen demand, without atherothrombosis, usually in the context of another acute illness. In this state-of-the-art review, the diagnosis, investigation, and treatment of patients with type 2 myocardial infarction are considered, with general advice for clinical practice and a consideration of future research directions.

A blood-based biomarker that accurately reflects neuronal injury in acute ischemic stroke could be an easily accessible and cost-effective complement to clinical and radiological evaluation. Here, we investigate whether plasma levels of the novel biomarker brain-derived tau (BD-tau) reflect cerebral infarct volumes and whether BD-tau can improve clinical outcome prediction.

The present study included 713 consecutive cases from two different hospital-based cohorts, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) and SAHLSIS phase 2 (SAHLSIS2). Acute stroke severity was determined by the Scandinavian Stroke Scale converted to the National Institutes of Health stroke scale (NIHSS) in SAHLSIS and by the NIHSS in SAHLSIS2. All participants were assessed for functional outcome 3 months after stroke by the modified Rankin Scale, and 254 participants in SAHLSIS had quantitative neuroimaging available.

Plasma BD-tau concentrations and cerebral infarct volumes were highly correlated (ρ 0.72, p < 0.001). BD-tau improved the prognostic accuracy of suffering an unfavorable outcome over age and stroke severity in the whole cohort. However, the gain in predictive power was dependent on stroke severity and infarct location. The largest improvement was observed for mild ischemic strokes (NIHSS <5; area under the curve [AUC] = 0.73 for age + NIHSS versus AUC = 0.84 with addition of BD-tau; DeLong p 0.02), posterior circulation stroke (AUC = 0.75 vs. AUC = 0.84; DeLong p 0.06) and more specifically for infarcts in the brainstem/cerebellum (AUC = 0.74 vs. 0.87; DeLong p 0.009).

Plasma BD-tau can provide information on the extent of acute neuronal damage in ischemic stroke and adds prognostic value for outcome, especially for mild and posterior circulation strokes.

In Acute Coronary Syndrome without ST-segment elevation, the use of high-sensitivity troponins in rapid protocols is considered the gold standard for diagnostic exclusion/confirmation, in conjunction with clinical stratification. The biggest concern regarding the techniques for troponin evaluation is the time required between collection and delivery of the result.

The objective of the present study is the clinical/laboratory validation of a POCT device for TnI.

In the first phase of the study, samples from 108 patients with known troponin values High Sensitivity Automated Troponin T (TnT) assay from Roche Diagnostics were analyzed for analytical comparability between hs-cTnI of the Analyzer Atellica® vTLi and hs-cTnT Cobas®. The second phase of the study was performed with samples from 51 patients who reported to the emergency department with chest pain for a clinical prospective evaluation and correlation between the hs-cTnI assays of the Analyzer Atellica® vTLi, hs-cTnT Cobas® and Atellica IM 1300.

There was a correlation between the POCT Atellica® vTLi and hs-cTnT Cobas® in the serum samples of the control group (r = 0.660, p < 0.0001). Besides, there was a correlation between the Atellica® vTLi, serum hs-cTnT Cobas®, plasma hs-cTnT Cobas®, serum Atellica IM and plasma Atellica IM 1300 platforms in the second phase (p < 0.0001 in all cases).

In the present study, the Siemens POCT Atellica® vTLi device showed excellent performance in laboratory validation and correlation with the high-sensitivity TnT assay in different troponin concentration ranges. Given these results, the device can be used in institutions that intend to use a POCT device for 0- and 1-hour chest pain protocols.

Individuals with a restrictive spirometric pattern have a high burden of cardiovascular and metabolic morbidity.

To assess prevalence of elevated cardiac biomarkers among individuals with a restrictive spirometric pattern compared to those with a normal lung function and to evaluate the association between cardiac biomarkers and mortality.

In 2002-04, individuals with airway obstruction were identified from population-based cohorts, together with age- and sex-matched non-obstructive referents. The analysis population consisted of the non-obstructive referents stratified according to whether they had a restrictive spirometric pattern or normal lung function in whom cardiac biomarkers were measured. Deaths were recorded until 31 December 2010.

Participants with a restrictive spirometric pattern were older and more likely to be obese with a higher burden of cardiovascular risk factors than those with normal function. Elevated cardiac troponin but not natriuretic peptide levels were more common in those with a restrictive spirometric pattern independent of age, sex, BMI, or risk factors (adjusted OR 1.8, 95% CI 1.29-2.74). At 5 years, death occurred more frequently in participants with restrictive spirometric pattern compared to those with normal function (15.7% [31/197] versus 7.6% [57/751]), with highest mortality rate in those with restriction and elevated cardiac troponin (28.7% [27/94]). Cardiac troponin was independently associated with death among those with a restrictive spirometric pattern (HR 4.91, 95% CI 1.58-15.26) but not in those with normal lung function.

Cardiac troponin was elevated more often in people with a restrictive spirometric pattern in whom it was a strong independent predictor of death.

The aim of this study was determine the incidence of major adverse cardiac events within 30 and 365-days among patients discharged from emergency departments (EDs), following a single high-sensitivity cardiac troponin I test result below or close to the limits of detection (LoD).

Patients ≥20 years old who presented to four EDs from mid-2014 to end-2015, underwent a single high-sensitivity troponin test and were discharged were included. Data from ED presentations, hospital admissions, mortality records, and pathology laboratories were linked and harmonized. High-sensitivity troponin levels were categorized as below (<2 ng/L) or close to (<5 ng/L) the LoD. The primary outcome was cardiovascular death and myocardial infarction (MI), identified using ICD-10-AM codes. In a cohort of 6633 patients, 49% had high-sensitivity troponin levels below the LoD (<2 ng/L), and 79% had levels <5 ng/L. There were no primary outcome events at 30-day follow-up among patients with high-sensitivity troponin results below 2 or 5 ng/L. At 365-days, there were 5 (0.15%) and 11 (0.21%) primary outcome events for patients with high-sensitivity troponin results below 2 and 5 ng/L, indicating negative predictive values of 99.85% and 99.79%.

These findings confirm that patients with a single very low level of high-sensitivity troponin on presentation to EDs are at low risk of MI and cardiovascular death at 30 and 365 days, supporting the safety of a triage strategy incorporating a single high-sensitivity troponin result below the LoD to identify patients at low-risk, who may be suitable for expedited discharge.

The purpose of this study was to assess the impact of adoption of a new cardiac chest pain pathway that included hs-cTnI in the emergency department (ED) when evaluating chest pain patients.

A new pathway incorporating both hs-cTnI testing (Seimens Healthineers Atellica) and risk stratification tools was developed. The impact of the new algorithm was assessed through a retrospective observational review of patients admitted to the ED with chest pain before implementation and after implementation. Before implementation, the conventional Seimens troponin Vista assay was utilized without a defined algorithmic approach. Bivariate analyses were performed comparing the time periods to determine differences in patient discharge dispositions, length of stay, outcomes, and rate of diagnostic cardiac catheterization.

The proportion of patients discharged from the ED increased while the proportion of patients placed in observation or admitted as in-patient decreased. Variation amongst providers regarding patient disposition decreased. The stress testing rate of patients placed in observation decreased over baseline. There was no change in 30-day MACE rate, but there was a decrease in 30-day MI rate.

The new standardized hs-cTnI algorithm approach is safe as demonstrated by no change in 30-day MACE and is also more appropriate and efficient for patients presenting to the ED with chest pain compared to the non-standardized approach with cTnI used previously.

High-sensitivity cardiac troponin (hs-cTn) assays have significantly refined the resolution of biomarker-level detection and have emerged as the gold standard cardiac biomarker in evaluating myocardial injury. Since its introduction, hs-cTn has been integrated into the Fourth Universal Definition of Myocardial Infarction and various European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the evaluation and diagnosis of chest pain syndromes. However, despite its integral role in caring for patients with chest pain, there are still substantive gaps in our knowledge of the clinical interpretation of dynamic changes in hs-cTn values. Whether a relative or absolute hs-cTn delta should be used to detect acute myocardial injury remains debatable. There are also emerging considerations of possible sex and racial/ethnic differences in clinically significant troponin deltas. In the emergency department, there is debate about the optimal time frame to recheck hs-cTn after symptom onset for myocardial infarction rule-out and whether hs-cTn deltas should be integrated into clinical risk scores. In this review, we will provide an overview of the history of clinical utilization of cardiac biomarkers, the development of hs-cTn assays, and the ongoing search for a meaningful delta that can be clinically applicable.

Guidelines recommend the use of risk scores to select patients for further investigation after myocardial infarction has been ruled out but their utility to identify those with coronary artery disease is uncertain.

In a prospective cohort study, patients with intermediate high-sensitivity cardiac troponin I concentrations (5 ng/L to sex-specific 99th percentile) in whom myocardial infarction was ruled out were enrolled and underwent coronary CT angiography (CCTA) after hospital discharge. History, ECG, Age, Risk factors, Troponin (HEART), Emergency Department Assessment of Chest Pain Score (EDACS), Global Registry of Acute Coronary Event (GRACE), Thrombolysis In Myocardial Infarction (TIMI), Systematic COronary Risk Evaluation 2 and Pooled Cohort Equation risk scores were calculated and the odds ratio (OR) and diagnostic performance for obstructive coronary artery disease were determined using established thresholds.

Of 167 patients enrolled (64±12 years, 28% female), 29.9% (50/167) had obstructive coronary artery disease. The odds of having obstructive disease were increased for all scores with the lowest and highest increase observed for an EDACS score ≥16 (OR 2.2 (1.1-4.6)) and a TIMI risk score ≥1 (OR 12.9 (3.0-56.0)), respectively. The positive predictive value (PPV) was low for all scores but was highest for a GRACE score >88 identifying 39% as high risk with a PPV of 41.9% (30.4-54.2%). The negative predictive value (NPV) varied from 77.3% to 95.2% but was highest for a TIMI score of 0 identifying 26% as low risk with an NPV of 95.2% (87.2-100%).

In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been excluded, clinical risk scores can help identify patients with and without coronary artery disease, although the performance of established risk thresholds is suboptimal for utilisation in clinical practice.

NCT04549805.

Guidelines recommend high-sensitivity cardiac troponin to risk stratify patients with possible myocardial infarction and identify those eligible for discharge. Our aim was to evaluate adoption of this approach in practice and to determine whether effectiveness and safety varies by age, sex, ethnicity, or socioeconomic deprivation status.

A multi-centre cohort study was conducted in 13 hospitals across the United Kingdom from November 1st, 2021, to October 31st, 2022. Routinely collected data including high-sensitivity cardiac troponin I or T measurements were linked to outcomes. The primary effectiveness and safety outcomes were the proportion discharged from the Emergency Department, and the proportion dead or with a subsequent myocardial infarction at 30 days, respectively. Patients were stratified using peak troponin concentration as low (<5 ng/L), intermediate (5 ng/L to sex-specific 99th percentile), or high-risk (>sex-specific 99th percentile).

In total 137,881 patients (49% [67,709/137,881] female) were included of whom 60,707 (44%), 42,727 (31%), and 34,447 (25%) were stratified as low-, intermediate- and high-risk, respectively. Overall, 65.8% (39,918/60,707) of low-risk patients were discharged from the Emergency Department, but this varied from 26.8% [2200/8216] to 93.5% [918/982] by site. The safety outcome occurred in 0.5% (277/60,707) and 11.4% (3917/34,447) of patients classified as low- or high-risk, of whom 0.03% (18/60,707) and 1% (304/34,447) had a subsequent myocardial infarction at 30 days, respectively. A similar proportion of male and female patients were discharged (52% [36,838/70,759] versus 54% [36,113/67,109]), but discharge was more likely if patients were <70 years old (61% [58,533/95,227] versus 34% [14,428/42,654]), from areas of low socioeconomic deprivation (48% [6697/14,087] versus 43% [12,090/28,116]) or were black or asian compared to caucasian (62% [5458/8877] and 55% [10,026/18,231] versus 46% [35,138/75,820]).

Despite high-sensitivity cardiac troponin correctly identifying half of all patients with possible myocardial infarction as being at low risk, only two-thirds of these patients were discharged. Substantial variation in the discharge of patients by age, ethnicity, socioeconomic deprivation, and site was observed identifying important opportunities to improve care.

UK Research and Innovation.

Clinical decision-making for risk stratification for possible myocardial infarction (MI) uses high-sensitivity cardiac troponin (hs-cTn) thresholds that range from the limit of detection to several-fold higher than the upper reference limit (URL). To establish a minimum analytical variation standard, we can quantify the effect of variation on the population clinical measures of safety (sensitivity) and effectiveness [proportion below threshold, or positive predictive value (PPV)].

From large datasets of patients investigated for possible MI with the Abbott hs-cTnI and Roche hs-cTnT assays, we synthesized datasets of 1 000 000 simulated patients. Troponin concentrations were randomly varied several times based on absolute deviations of 0.5 to 3 ng/L and relative changes of 2% to 20% around the low-risk threshold (5 ng/L) and URLs, respectively.

For both assays at the low-risk thresholds, there were negligible differences in sensitivity (<0.3%) with increasing analytical variation. The proportion of patients characterized as low risk reduced by 30% to 29% (Roche) and 53% to 44% (Abbott). At the URL, increasing analytical variation also did not change sensitivity; the PPV fell by less than 3%. For risk stratification, increased delta thresholds (change between serial troponin concentrations) increased sensitivity at the cost of a decreased percentage of patients below the delta threshold, with the largest changes at the greatest analytical variation.

At the low-risk threshold, analytical variation up to 3 ng/L minimally impacted the safety metric (sensitivity) but marginally reduced effectiveness. Similarly, at the URL even relative variation up to 25% minimally impacted safety metrics and effectiveness. Analytical variation for delta thresholds did not negatively impact sensitivity but decreased effectiveness.

Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The turn-around time from blood draw to posting results in the clinical portal for central laboratory analysers is ~1-2 hours. New generation, high-sensitivity, point-of-care cardiac troponin I (POC-cTnI) assays use whole blood on a bedside (or near bedside) analyser that provides a rapid (8 min) result. This may expedite clinical decision-making and reduce length of stay. Our purpose is to determine if utilisation of a POC-cTnI testing reduces ED length of stay. We also aim to establish an optimised implementation process for the amended clinical pathway.

This quality improvement initiative has a pragmatic multihospital stepped-wedge cross-sectional cluster randomised design. Consecutive patients presenting to the ED with symptoms suggestive of possible AMI and having a cTn test will be included. Clusters (comprising one or two hospitals each) will change from their usual-care pathway to an amended pathway using POC-cTnI-the 'intervention'. The dates of change will be randomised. Changes occur at 1 month intervals, with a minimum 2 month 'run-in' period. The intervention pathway will use a POC-cTnI measurement as an alternate to the laboratory-based cTn measurement. Clinical decision-making steps and logic will otherwise remain unchanged. The POC-cTnI is the Siemens (Erlangen Germany) Atellica VTLi high-sensitivity cTnI assay. The primary outcome is ED length of stay. The safety outcome is cardiac death or AMI within 30 days for patients discharged directly from the ED.

Ethics approval has been granted by the New Zealand Southern Health and Disability Ethics Committee, reference 21/STH/9. Results will be published in a peer-reviewed journal. Lay and academic presentations will be made. Māori-specific results will be disseminated to Māori stakeholders.

ACTRN12619001189112.

Periprocedural myocardial infarction (PMI) and injury, pertinent to both cardiac and non-cardiac procedures, have gained increasing recognition in clinical practice. Over time, diverse definitions for diagnosing PMI have been developed and validated among patient populations undergoing coronary revascularization. However, this variety in definitions presents considerable challenges in clinical settings and complicates both the design and interpretation of clinical trials. The necessity to accurately diagnose PMI has spurred significant interest in establishing universally accepted and prognostically meaningful thresholds for cardiac biomarkers elevation and supportive ancillary criteria. In fact, elevations in cardiac biomarkers in line with the 4th Universal Definition of Myocardial Infarction, have been extensively confirmed to be associated with increased mortality and cardiovascular events. In the context of non-coronary cardiac procedures, such as Transcatheter Aortic Valve Implantation, there is a growing acknowledgment of both the high incidence rates and the adverse impact of PMI on patient outcomes. Similarly, emerging research underscores the significance of PMI and injury in non-cardiac surgery, highlighting the urgent need for effective prevention and risk management strategies in this domain.

To accurately evaluate non-ST-elevated acute cardiac syndrome (NSTE-ACS), the quality of high-sensitive cardiac troponin (hs-cTn) assays is of vital importance. The 2020 revision of the NSTE-ACS guideline includes clinical decision-limits (CDL's) to both rule-in and rule-out NSTE-ACS for most commercially available platforms, providing both 0/1 h and 0/2 h delta limits. Our study evaluated whether laboratories are able to meet the analytical performance specifications for imprecision (APS) for hs-cTnT.

Results from external quality assurance (EQA) in commutable samples were used to evaluate the current and historic performance of analyzers. The performance of analyzers that either passed or failed to comply with 0/1 h-APS were used on a real-world dataset of first hs-cTnT-values to simulate 10.000 samples of t=0, t=1 and t=2 h values with multiple delta's for all relevant CDL's. We compared the simulated values to the input values to obtain the percentage of aberrant results simulated.

The majority of analyzers complies with APS for rule-in in 2022 (0/1 h: 90.4 % and 0/2 h: 100 %), compliance for the 0/1 h rule-out is still far from optimal (0/1 h: 30.7 %, 0/2 h: 75.4 %), with improving compliance over the past years (rule-in p=<0.0001, rule-out p=0.011, χ2). Whilst 0/1 h-APS-passing analyzers have a minute risk to falsely rule-out patients whom should be ruled-in (0.0001 %), failing performance increases this risk to 2.1 % upon using 0/1 h CDL's. Here, adopting 0/2 h CDL's is favorable (0.01 %).

Laboratories that fail to meet hs-cTnT 0/1 h-APS should improve their performance to the required and achievable level. Until performance is reached clinics should adopt the 0/2 h CDL's.

Myocardial infarction can be ruled out in patients with a single cardiac troponin measurement. Whether use of a uniform rule-out threshold has resulted in sex differences in care remains unclear.

The purpose of this study was to evaluate implementation of a uniform rule-out threshold in females and males with possible myocardial infarction, and to derive and validate sex-specific thresholds.

The implementation of a uniform rule-out threshold (<5 ng/L) with a high-sensitivity cardiac troponin I assay was evaluated in consecutive patients presenting with possible myocardial infarction. The proportion of low-risk patients discharged from the emergency department and incidence of myocardial infarction or cardiac death at 30 days were determined. Sex-specific thresholds were derived and validated, and proportion of female and male patients were stratified as low-risk compared with uniform threshold.

In 16,792 patients (age 58 ± 17 years; 46% female) care was guided using a uniform threshold. This identified more female than male patients as low risk (73% vs 62%), but a similar proportion of low-risk patients were discharged from the emergency department (81% for both) with fewer than 5 (<0.1%) patients having a subsequent myocardial infarction or cardiac death at 30 days. Compared with a uniform threshold of <5 ng/L, use of sex-specific thresholds would increase the proportion of female (61.8% vs 65.9%) and reduce the proportion of male (54.8% vs 47.8%) patients identified as low risk.

Implementation of a uniform rule-out threshold for myocardial infarction was safe and effective in both sexes. Sex-specific rule-out thresholds should be considered, but their impact on effectiveness and safety may be limited.

Single-sample (screening) rule-out of acute myocardial infarction (AMI) with troponin requires derivation of a single-test screening threshold. In data sets with small event numbers, the lowest one or two concentrations of myocardial infarction (MI) patients dictate the threshold. This is not optimal. We aimed to demonstrate a process incorporating both real and synthetic data for deriving such thresholds using a novel pre-production high-precision point-of-care assay.

cTnI concentrations were measured from thawed plasma using the Troponin I Next (TnI-Nx) assay (i-STAT; Abbott) in adults on arrival to the emergency department with symptoms suggestive of AMI. The primary outcome was an AMI or cardiac death within 30 days. We used internal-external validation with synthetic data production based on clinical and demographic data, plus the measured TnI-Nx concentration, to derive and validate decision thresholds for TnI-Nx. The target low-risk threshold was a sensitivity of 99% and a high-risk threshold specificity of >95%.

In total, 1356 patients were included, of whom 191 (14.1%) had the primary outcome. A total of 500 synthetic data sets were constructed. The mean low-risk threshold was determined to be 5 ng/L. This categorized 38% (95% CI, 6%-68%) to low-risk with a sensitivity of 99.0% (95% CI, 98.6%-99.5%) and a negative predictive value of 99.4% (95% CI, 97.6%-99.8%). A similarly derived high-risk threshold of 25 ng/L had a specificity of 95.0% (95% CI, 94.8%-95.1%) and a positive predictive value of 74.8% (95% CI, 71.5%-78.0%).

With the TnI-Nx assay, we successfully demonstrated an approach using synthetic data generation to derive low-risk thresholds for safe and effective screening.

We sought to validate the clinical performance of a rapid assessment pathway incorporating the Siemens Atellica IM high sensitivity cardiac troponin I (hs-cTnI) assay in patients presenting to the emergency department (ED) with suspected acute myocardial infarction (AMI).

This was a multicentre prospective observational study of adult ED patients presenting to five Australian hospitals between November 2020 and September 2021. Participants included those with symptoms of suspected AMI (without ST-segment elevation MI on presentation ECG). The Siemen's Atellica IM hs-cTnI laboratory-based assay was used to measure troponin concentrations at admission and after 2-3 hours and cardiologists adjudicated final diagnoses. The HighSTEACS diagnostic algorithm was evaluated, incorporating hs-cTnI concentrations at presentation and absolute changes within the first 2 to 3 hours. The primary outcome was index AMI, including type 1 or 2 non-ST segment elevation MI (NSTEMI) or ST-elevation MI (STEMI) following presentation. 30-day major adverse cardiac outcomes (including AMI, urgent revascularisation or cardiac death) were also reported. The trial was registered with the Australian and New Zealand Clinical Trials Registry.

1994 patients were included. The average age was 56.2 years (SD=15.6), and 44.9% were women. 118 (5.9%) patients had confirmed index AMI. The 2-hour algorithm defined 61.3% of patients as low risk. Sensitivity was 99.1% (94.0%-99.9%) and negative predictive value was 99.9% (99.3%-100%). 24.4% of patients were deemed intermediate risk. When applying the parameters for high risk, 252 (14.3%) were identified, with a specificity of 91.5% (88.7%-93.6%) and a PPV of 42.0% (35.6-48.7%).

A 2-hour algorithm based on the HighSTEACS strategy using the Siemens Atellica IM hs-cTnI laboratory-based assay enables safe and efficient risk assessment of emergency patients with suspected AMI.

ACTRN12621000053820.

The cardiac stress for veteran football players during match is considerable. In this specific elderly population, the kinetics of exercise-induced cardiac troponin I (cTnI) and B-Type natriuretic peptide (BNP) could potentially be related to cardiovascular risk factors (CVRF) and cardiovascular disease and are therefore be investigated for their usefulness as an complement to established screening measures.

cTnI and BNP was measured in 112 veteran football players (age: 51 ± 10 years) within 30 minutes pre- and post-match. Players with elevated cTnI (cTnI-positive) and a control group (out of the 112 veteran players) with normal cTnI (cTnI-negative) underwent cardiac follow-up 4.2 ± 3.5 months post-match, comprising history, resting and stress ECG (including 30 minutes pre- and post cTnI and BNP), and echocardiography.

In 33 players (29%) cTnI and in 6 players BNP (5%) exceeded the upper range limit for increased risk of myocardial damage (cTnI ≥ 5 ng/l) and myocardial wall stress (BNP ≥ 100 pg/ml) post-match, respectively. No correlation was observed between Δ cTnI (pre- vs. post-match) and the number of CVRF (r = -0.06, p = 0.50). Follow-up was conducted in 62 players (31 cTnI-positive and 31 cTnI-negative players) of which 6 (10%, 3 cTnI positive and 3 cTnI negative players) had cardiac abnormalities (hypertrophic cardiomyopathy n = 2, coronary artery disease n = 2, coronary artery anomaly n = 1, hypertensive heart disease n = 1).

Veterans' football matches elicit increases in BNP and particularly cTnI in a considerable number of players. However, these biochemical alterations do not indicate acute cardiac damage as evidenced by follow-up. Routine determination of cardiac biomarkers is unlikely to improve cardiovascular screening in veteran football players.

It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS).

Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%).

Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements.

The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) 0/2-h algorithm is unclear among U.S. emergency department (ED) patients with acute chest pain.

A preplanned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 2-h hs-cTnT measures prospectively enrolled at eight U.S. EDs from January 2017 to September 2018 were stratified into rule-out, observation, and rule-in zones using the hs-cTnT 0/2-h algorithm alone and combined with the history, electrocardiogram, age, and risk factor (HEAR) score. The primary outcome was adjudicated 30-day cardiac death or myocardial infarction (CDMI). The sensitivity and negative predictive value (NPV) of the 0/2-h rule-out zone and specificity and positive predictive value (PPV) of the rule-in zone for 30-day CDMI were calculated.

Of the 1307 patients accrued, 53.6% (700/1307) were male and 58.6% (762/1307) were White, with a mean ± SD age of 57.5 ± 12.7 years. At 30 days, CDMI occurred in 12.9% (168/1307) of participants. The 0/2-h algorithm ruled out 61.4% (802/1307) of patients. Among rule-out patients, 1.9% (15/802) experienced 30-day CDMI, resulting in a sensitivity of 91.1% (95% confidence interval [CI] 85.7%-94.9%) and NPV of 98.1% (95% CI 96.9%-98.9%). The 0/2-h algorithm ruled in 12.4% (162/1307) patients of whom 61.7% (100/162) experienced 30-day CDMI. The rule-in zone specificity was 94.6% (95% CI 93.1%-95.8%) and PPV was 61.7% (95% CI 53.8%-69.2%) for 30-day CDMI. The 0/2-h algorithm combined with HEAR score ruled out 30.7% (401/1307) of patients with a sensitivity and NPV for 30-day CDMI of 98.2% (95% CI 94.9%-99.6%) and 99.3% (95% CI 97.8%-99.8%), respectively.

The hs-cTnT 0/2-h algorithm ruled out most patients. With NPV of <99% for 30-day CDMI, the hs-cTnT 0/2-h algorithm, many emergency physicians may not consider it safe to use for U.S. ED patients. When combined with a low-risk HEAR score, NPV was >99% for 30-day CDMI at the cost of reduced efficacy.

Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment.

The purpose of this study was to investigate cardiovascular mortality and medication use after takotsubo syndrome.

In a case-control study, all patients with takotsubo syndrome in Scotland between 2010 and 2017 (n = 620) were age, sex, and geographically matched to individuals in the general population (1:4, n = 2,480) and contemporaneous patients with acute myocardial infarction (1:1, n = 620). Electronic health record data linkage of mortality outcomes and drug prescribing were analyzed using Cox proportional hazard regression models.

Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow-up. This exceeded mortality rates in the general population (N = 374 [15%]; HR: 1.78 [95% CI: 1.48-2.15], P < 0.0001), especially for cardiovascular (HR: 2.47 [95% CI: 1.81-3.39], P < 0.001) but also noncardiovascular (HR: 1.48 [95% CI: 1.16-1.87], P = 0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR: 0.76 [95% CI: 0.62-0.94], P = 0.012), which was attributable to lower rates of cardiovascular (HR: 0.61 [95% CI: 0.44-0.84], P = 0.002) but not non-cardiovascular (HR: 0.92 [95% CI: 0.69-1.23], P = 0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P = 0.01), anti-inflammatory (P = 0.002), and psychotropic (P < 0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome.

In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use.

High-sensitivity cardiac troponin (hs-cTn) assays are used for detection of myocardial infarction (MI). Ninety-ninth percentiles show wide inter-assay variation. The use of sex-specific cut-offs is recommended as definitory cut-off for MI. We compared diagnostic performance and prognostic value of sex-specific 99th percentiles of four hs-cTn assays in patients with suspected MI.

Concentrations of four hs-cTn assays were measured at presentation and after 3 h in patients with suspected MI. Final diagnoses were adjudicated according to the 4th Universal Definition of MI. Unisex and sex-specific 99th percentiles were evaluated as diagnostic cut-offs following the ESC 0/3 h algorithm. These cut-offs were used in Cox-regression analyses to investigate the association with a composite endpoint of MI, revascularization, cardiac rehospitalization, and death. Non-ST-elevation MI was diagnosed in 368 of 2718 patients. Applying the unisex 99th percentile, Elecsys hs-cTnT provided highest negative predictive value (NPV) of 99.7 and a positive predictive value (PPV) of 75.9. The analysed hs-cTnI assays showed slightly lower NPVs and comparable PPVs [Architect (NPV 98.0, PPV of 71.4); Atellica (NPV 97.7, PPV of 76.1); Pathfast (NPV 97.7, PPV of 66.6)]. Application of sex-specific 99th percentiles did not significantly affect diagnostic performance. Concentrations above 99th percentile were independent predictors for impaired long-term outcome (hazard ratios 1.2-1.5, P < 0.001).

We describe a good diagnostic accuracy of four hs-cTn assays using the assay-specific 99th percentile for detection of MI. Application of sex-specific 99th percentiles did neither affect diagnostic performance nor prognostic value significantly. Finally, values above the 99th percentile were associated with poor long-term outcome.

An early diagnosis of atherosclerosis, particularly in subclinical status, can play a remarkable role in reducing mortality and morbidity. Because of coronary artery calcification (CAC) nature in radiation exposure, finding biomarkers associated with CAC could be useful in identifying individuals at high risk of CAC score. In this review, we focused on the association of cardiac troponins (hs-cTns) and CAC to achieve insight into the pathophysiology of CAC. In October 2022, we systematically searched Web of Science, Scopus, PubMed, and Embase databases to find human observational studies which have investigated the association of CAC with cardiac troponins. To appraise the included articles, we used the Newcastle Ottawa scale (NOS). Out of 520 records, 10 eligible studies were included. Based on findings from longitudinal studies and cross-sectional analyses, troponin T and I were correlated with occurrence of CAC and its severity. Two of the most important risk factors that affect the correlation between hs-cTns serum levels and CAC were age and gender. The elevation of cardiac troponins may affect the progression of CAC and future cardiovascular diseases. Verifying the association between cardiac troponins and CAC may lead to identify individuals exposed to enhanced risk of cardiovascular disease (CVD) complications and could establish innovative targets for pharmacological therapy.

Chest pain is the second leading cause of all emergency department (ED) visits in adults in the United States, with nearly 11 million encounters yearly. While identifying low-risk patients is crucial for early discharge, identifying high-risk patients in ED is vital in timely and appropriate acute coronary syndrome (ACS) management. Traditional methods such as physical examination, cardiac markers, or imaging tests cannot reliably confirm or rule out ACS; they cannot be singularly incorporated to risk stratify patients. Various clinical risk scores have been proposed to address this challenge for risk stratification in patients being evaluated for suspected ACS. The ideal risk score should demonstrate high sensitivity and specificity to accurately differentiate between patients with varying levels of risk, particularly in identifying those at high risk for major adverse cardiovascular events. Simultaneously, an ideal scoring system should also be able to compute information for other non-coronary etiologies of chest pain that require time-sensitive interventions and workups (eg, aortic dissection and pulmonary embolism). In this review, we have assembled major risk scores used for risk stratification in patients with acute chest pain in ED. We have abbreviated their salient features to assist readers in their clinical decision-making.

Rapid and accurate triage of patients presenting with chest pain to an emergency department (ED) is critical to prevent ED overcrowding and unnecessary resource use in individuals at low risk of acute myocardial infarction (AMI) and to efficiently and effectively guide patients at high risk to definite therapy. The use of biomarkers for rule-out or rule-in of suspected AMI has evolved substantially over the last several decades. Previously well-established biomarkers have been replaced by cardiac troponin (cTn). High-sensitivity cTn (hs-cTn) assays represent the newest generation of cTn assays and offer tremendous advantages, including improved sensitivity and precision. Still, implementation of these assays in the United States lags behind several other areas of the world. Within this educational review, we discuss the evolution of biomarker testing for detection of myocardial injury, address the specifics of hs-cTn assays and their recommended use within triage algorithms, and highlight potential challenges in their use. Ultimately, we focus on implementation strategies for hs-cTn assays, as they are now clearly ready for prime time.

Acute myocardial infarction (AMI) is a leading cause of mortality globally, highlighting the need for timely and accurate diagnostic strategies. Cardiac troponin has been the biomarker of choice for detecting myocardial injury. A dynamic change in concentrations supports the diagnosis of AMI in the setting of evidence of acute myocardial ischemia. The new generation of high-sensitivity cardiac troponin (hs-cTn) assays has significantly improved analytical sensitivity but at the expense of decreased clinical specificity. As a result, sophisticated algorithms are required to differentiate AMI from non-AMI patients. Establishing optimal hs-cTn cutoffs for these algorithms to rule out and rule in AMI has been the subject of intensive investigations. These efforts have evolved from examining the utility of the hs-cTn 99th percentile upper reference limit, comparing the percentage versus absolute delta thresholds, and evaluating the performance of an early European Society of Cardiology-recommended 3 h algorithm, to the development of accelerated 1 h and 2 h algorithms that combine the admission hs-cTn concentrations and absolute delta cutoffs to rule out and rule in AMI. Specific cutoffs for individual confounding factors such as sex, age, and renal insufficiency have also been investigated. At the same time, concerns such as whether the small delta thresholds exceed the analytical and biological variations of hs-cTn assays and whether the algorithms developed in European study populations fit all other patient cohorts have been raised. In addition, the accelerated algorithms leave a substantial number of patients in a non-diagnostic observation zone. How to properly diagnose patients falling in this zone and those presenting with elevated baseline hs-cTn concentrations due to the presence of confounding factors or comorbidities remain open questions. Here we discuss the developments described above, focusing on criteria and underlying considerations for establishing optimal cutoffs. In-depth analyses are provided on the influence of biological variation, analytical imprecision, local AMI rate, and the timing of presentation on the performance metrics of the accelerated hs-cTn algorithms. Developing diagnostic strategies for patients who remain in the observation zone and those presenting with confounding factors are also reviewed.

To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay.

We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated a) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or b) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days.

We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%).

The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Objectives  Troponins are classically raised in acute coronary syndrome (ACS) although other cardiovascular and non-cardiovascular causes are recognized. We aimed to see the association of high sensitivity (Hs) Troponin I values exceeding the sex-specific 99th percentile upper reference limit (URL) with diagnoses, emergency department (ED) outcomes, 30-day outcomes of admitted patients and predictors of ACS in both genders. Materials and Methods  A retrospective study of all patients presenting to the emergency department from January 2019 to April 2021 with suspicion of ACS and Hs-Troponin I values greater than the sex-specific 99th percentile URL. Statistical Analysis  SPSS version 24 was used, Pearson's chi-square tests, Fisher's exact test, Kruskal-Wallis test, Mann-Whitney U test, and odds ratios, including the 95% confidence intervals, for each characteristic were used for analysis. A p -value of < 0.05 was considered significant. Results  There were a total of 5,982 patients (3,031 males, 2,951 females), out of which 878 patients were admitted under the cardiology specialty. In patients who were admitted to the ward, mortality was higher in females (8.2%) with less than a 10-fold rise in Hs-Troponin I while similar in both genders (7.6%) in patients with Hs-troponin I greater than 10-fold of sex-specific 99th percentile URL. Raised low-density lipoprotein-cholesterol was a significant factor associated with 2.4 times higher odds of ACS. Conclusion  Women with Hs-Troponin values up to 10 times the URL, i.e., 15.6-160 ng/L have higher mortality than their male counterparts. LDL-cholesterol is a significant risk factor for ACS which should be controlled for its prevention.

Cardiac troponin is used for risk stratification of patients with acute coronary syndromes; however, the role of testing in other settings remains unclear.

The aim of this study was to evaluate whether cardiac troponin testing could enhance risk stratification in patients with chronic coronary artery disease independent of disease severity and conventional risk measures.

In a prospective cohort of consecutive patients with symptoms suggestive of stable angina attending for outpatient coronary angiography, high-sensitivity cardiac troponin I was measured before angiography, and clinicians were blinded to the results. The primary outcome was myocardial infarction or cardiovascular death during follow-up.

In 4,240 patients (age 66 years [IQR: 59-73 years], 33% female), coronary artery disease was identified in 3,888 (92%) who had 255 (6%) primary outcome events during a median follow-up of 2.4 years (IQR: 1.3-3.6 years). In patients with coronary artery disease, troponin concentrations were 2-fold higher in those with an event compared with those without (6.7 ng/L [IQR: 3.2-14.2 ng/L] vs 3.3 ng/L [IQR: 1.7-6.6 ng/L]; P < 0.001). Troponin concentrations were associated with the primary outcome after adjusting for cardiovascular risk factors and coronary artery disease severity (adjusted HR: 2.3; 95% CI: 1.7-3.0, log10 troponin; P < 0.001). A troponin concentration >10 ng/L identified patients with a 50% increase in the risk of myocardial infarction or cardiovascular death.

In patients with chronic coronary artery disease, cardiac troponin predicts risk of myocardial infarction or cardiovascular death independent of cardiovascular risk factors and disease severity. Further studies are required to evaluate whether routine testing could inform the selection of high-risk patients for treatment intensification. (Myocardial Injury in Patients Referred for Coronary Angiography [MICA]; ISRCTN15620297).