Addition of High-Sensitivity Troponin to Perioperative Risk Assessment Improves the Predictive Ability of Death in Non-Cardiac Surgery Patients. / Adição da Troponina Ultrassensível à Avaliação de Risco Perioperatório Melhora a Capacidade Preditiva de Morte em Pacientes Submetidos à Cirurgia Não Cardíaca.

BACKGROUND: Risk stratification is an important step in perioperative evaluation. However, the main risk scores do not incorporate biomarkers in their set of variables. OBJECTIVE: Evaluate the incremental power of troponin to the usual risk stratification. METHODS: A total of 2,230 patients admitted to the intensive care unit after non-cardiac surgery were classified according to three types of risk: cardiovascular risk (CVR), Revised Cardiac Risk Index (RCRI); and inherent risk of surgery (IRS). The main outcome was all-cause mortality. Cox regression was used as well as c-statistics before and after addition of high-sensitivity troponin (at least one measurement up to three days after surgery). Finally, net reclassification index and integrated discrimination improvement were used to assess the incremental power of troponin for risk stratification. Significance level was set at 0.05. RESULTS: Mean age of patients was 63.8 years and 55.6% were women. The prevalence of myocardial injury after non-cardiac surgery (MINS) was 9.4%. High CVR-patients had a higher occurrence of MINS (40.1 x 24.8%, p<0.001), as well as high IRS-patients (21.3 x 13.9%, p=0.004) and those with a RCRI≥3 (3.0 x 0.7%, p=0.009). Patients without MINS, regardless of the assessed risk, had similar mortality rate. The addition of troponin to the risk assessment improved the predictive ability of death at 30 days and at 1 year in all risk assessments. CONCLUSION: The prevalence of MINS is higher in the high-risk population. However, its prevalence in lower-risk population is not negligible and causes a higher risk of death. The addition of high-sensitivity troponin increased the predictive ability of risk assessment in all groups.

FUNDAMENTO: A estratificação ode risco é uma importante etapa na avaliação perioperatória. No entanto, os principais escores de risco não incorporam biomarcadores em seus conjuntos de variáveis. OBJETIVO: Avaliar o poder incremental da troponina à estratificação de risco tradicional. MÉTODOS: Um total de 2230 pacientes admitidos na unidade de terapia intensiva após cirurgia não cardíaca foram classificados de acordo com três tipos de risco: Risco Cardiovascular (RCV), Índice de Risco Cardíaco Revisado (IRCR), e Risco Inerente da Cirurgia (RIC). O principal desfecho foi mortalidade por todas as causas. A regressão de Cox foi usada, assim como a estatística C antes e após a adição de troponina ultrassensível (pelo menos uma medida até três dias após a cirurgia). Finalmente, o índice de reclassificação líquida e a melhoria de discriminação integrada foram usadas para avaliar o poder incremental da troponina para a estratificação de risco. O nível de significância usado foi de 0,05. RESULTADOS: A idade média dos pacientes foi 63,8 anos e 55,6% eram do sexo feminino. A prevalência de lesão miocárdica após cirurgia não cardíaca (MINS) foi 9,4%. Pacientes com um RCV elevado apresentaram uma maior ocorrência de MINS (40,1% x 24,8%, p<0,001), bem como pacientes com alto RIC (21,3 x 13,9%, p=0,004) e aqueles com IRCR≥3 (3,0 x 0,7%, p=0,009). Pacientes sem MINS, independentemente do risco avaliado, apresentaram taxa de mortalidade similar. A adição de troponina à avaliação de risco melhorou a capacidade preditiva de mortalidade em 30 dias e de mortalidade em um ano em todas as avaliações de risco. CONCLUSÃO: A prevalência de MINS é mais alta na população de alto risco. No entanto, sua prevalência na população de risco mais baixo não é desprezível e causa um maior risco de morte. A adição da troponina ultrassensível melhorou a capacidade preditiva da avaliação de risco em todos os grupos.

High-Sensitivity Troponin: A Review on Characteristics, Assessment, and Clinical Implications.

The use of high-sensitivity cardiac troponin (hs-cTn) assays has become part of the daily practice in most of the laboratories worldwide in the initial evaluation of the typical chest pain. Due to their early surge, the use of hs-cTn may reduce the time needed to recognise myocardial infarctions (MI), which is vital for the patients presenting in the emergency departments for chest pain. The latest European Society of Cardiology Guidelines did not only recognise their central role in the diagnosis algorithm but also recommended their use for rapid rule-in/rule-out of MI. High-sensitivity cardiac troponins are also powerful prognostic markers for long-term events and mortality, not only in a wide spectrum of other cardiovascular diseases (CVD) but also in several non-CVD pathologies. Moreover, these biomarkers became a powerful tool in special populations, such as paediatric patients and, most recently, COVID-19 patients. Although highly investigated, the assessment and interpretation of the hs-cTn changes are still challenging in the patients with basal elevation such as CKD or critically ill patients. Moreover, there are still various analytical characteristics not completely understood, such as circadian or sex variability, with major clinical implications. In this context, the present review focuses on summarizing the most recent research in the current use of hs-cTn, with a main consideration for its role in the diagnosis of MI but also its prognostic value. We have also carefully selected the most important studies regarding the challenges faced by clinicians from different specialties in the correct interpretation of this biomarker. Moreover, future perspectives have been proposed and analysed, as more research and cross-disciplinary collaboration are necessary to improve their performance.

Coronavirus disease 2019 in patients with cardiovascular disease: clinical features and implications on cardiac biomarkers assessment.

INTRODUCTION: Previous cardiovascular disease (CVD) and myocardial involvement are common in coronavirus disease-19 (COVID-19). We investigated relationships between CVD, cardiac biomarkers and outcome in COVID-19. METHODS: We analyzed n = 252 patients from a multicenter study and provided comparison according to the presence or absence of underlying CVD. Cardiac biomarkers high-sensitivity Troponin [upper reference of normality (URN) 35 pg/ml for Troponin I and 14 pg/ml for Troponin T] and natriuretic peptides (Nt-pro-B-type natriuretic peptide, URN 300 pg/ml and B-type natriuretic peptide, URN 100 pg/ml) were both available in n = 136. RESULTS: Mean age was 69 ±â€Š16 years (56% men, 31% with previous CVD). Raised hs-Troponin and natriuretic peptides were detected in 36 and 50% of the cases respectively. Age, chronic obstructive pulmonary disease, hemoglobin, hs-Troponin and natriuretic peptides were independently associated with underlying CVD (P < 0.05 for all). Compared with the normal biomarkers subgroups, patients with isolated hs-Troponin elevation had higher in-hospital mortality (31 vs. 4%, P < 0.05), similar CVD prevalence (15 vs. 11%) and trend towards higher D-dimer (930 vs. 397 ng/ml, P = 0.140). Patients with both biomarkers elevated had higher age, D-dimer, CVD and in-hospital mortality prevalence compared with other subgroups (all P < 0.05 for trend). Outcome analysis revealed previous CVD [model 1: OR 2.72 (95% CI 1.14-6.49), P = 0.024. model 2: OR 2.65 (95% CI 1.05-6.71), P = 0.039], hs-Troponin (log10) [OR 2.61 (95% CI 1.21-5.66), P = 0.015] and natriuretic peptides (log10) [OR 5.84 (95%CI 2.43-14), P < 0.001] to be independently associated with in-hospital mortality. CONCLUSION: In our population, previous CVD was part of a vulnerable phenotype including older age, comorbidities, increased cardiac biomarkers and worse prognosis. Patients with isolated increase in hs-Troponin suffered higher mortality rates despite low prevalence of CVD, possibly explained by higher COVID-19-related systemic involvement.

Comparison of Patients With Nonobstructive Coronary Artery Disease With Versus Without Myocardial Infarction (from the VA Clinical Assessment Reporting and Tracking [CART] Program).

Comparisons of the outcomes of patients with myocardial infarction with nonobstructive coronary artery disease (MINOCA) and patients with nonobstructive coronary artery disease (CAD) without myocardial infarction (MI) are limited. Here we compare the outcomes of patients with MINOCA and patients with nonobstructive CAD without MI and assess the influence of medical therapy on outcomes in these patients. Veterans who underwent coronary angiography between 2008 to 2017 with nonobstructive CAD were divided into those with or without pre-procedural troponin elevation. Patients with prior revascularization, heart failure, or who presented with cardiogenic shock, STEMI, or unstable angina were excluded. After propensity matching, outcomes were compared between groups. The primary outcome was major adverse cardiovascular events (MACE: mortality, myocardial infarction, and revascularization) within one year: 3,924 patients with nonobstructive CAD and a troponin obtained prior to angiography were identified (n=1,986 with elevated troponin) and restricted to 1,904 patients after propensity-matching. There was a significantly higher risk of MACE among troponin-positive patients compared with those with a negative troponin (HR 2.37; 95% CI, 1.67 to 3.34). Statin (HR 0.32; 95% CI, 0.22 to 0.49) and ACE inhibitor (HR 0.49; 95% CI, 0.32 to 0.75) therapy after angiography was associated with decreased MACE, while P2Y12 inhibitor, calcium-channel and beta-blocker therapy were not associated with outcomes. In conclusion, Veterans with MINOCA are at increased risk for MACE compared with those with nonobstructive CAD and negative troponin at the time of angiography. Specific medications were associated with a reduction in MACE, suggesting an opportunity to explore novel approaches for secondary prevention in this population.

Assessment and Management of Cardiotoxicity in Hematologic Malignancies.

With the increasing overall survival of cancer patients due to recent discoveries in oncology, the incidence of side effects is also rising, and along with secondary malignancies, cardiotoxicity is one of the most concerning side effects, affecting the quality of life of cancer survivors. There are two types of cardiotoxicity associated with chemotherapy; the first one is acute, life-threatening but, fortunately, in most of the cases, reversible; and the second one is with late onset and mostly irreversible. The most studied drugs associated with cardiotoxicity are anthracyclines, but many new agents have demonstrated unexpected cardiotoxic effect, including those currently used in multiple myeloma treatment (proteasome inhibitors and immunomodulatory agents), tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia and some forms of acute leukemia, and immune checkpoint inhibitors recently introduced in treatment of refractory lymphoma patients. To prevent irreversible myocardial damage, early recognition of cardiac toxicity is mandatory. Traditional methods like echocardiography and magnetic resonance imaging are capable of detecting structural and functional changings, but unable to detect early myocardial damage; therefore, more sensible biomarkers like troponins and natriuretic peptides have to be introduced into the current practice. Baseline assessment of patients allows the identification of those with high risk for cardiotoxicity, while monitoring during and after treatment is important for early detection of cardiotoxicity and prompt intervention.

Facility Variation in Troponin Ordering Within the Veterans Health Administration.

BACKGROUND: Current United States guidelines recommend troponin as the preferred biomarker in assessing for acute coronary syndrome, but recommendations are limited about which patients to test. Variations in troponin ordering may influence downstream health care utilization. METHODS: We performed a cross-sectional analysis of 3,308,131 emergency department (ED) visits in all 121 acute care facilities within the Veterans Health Administration from 2015 to 2017. We quantified the degree to which case mix and facility characteristics accounted for variations in facility rates in troponin ordering. We then assessed the association between facility quartiles of risk-adjusted troponin ordering and downstream resource utilization [inpatient admissions, noninvasive testing (stress tests, echocardiograms), and invasive procedures (coronary angiograms, percutaneous coronary interventions, and coronary artery bypass grafting surgeries)]. RESULTS: The proportion of ED visits with troponin orders ranged from 2.2% to 64.5%, with a median of 37.1%. Case mix accounted for 9.5% of the variation in troponin orders; case mix and differences in facility characteristics accounted for 34.6%. Facilities in the highest quartile of troponin ordering, as compared with those in the lowest quartile, had significantly higher rates of inpatient admissions, stress tests, echocardiograms, coronary angiograms, and percutaneous coronary intervention. CONCLUSIONS: Significant variation in troponin utilization exists across Veterans Health Administration facilities and that variation is not well explained by case mix alone. Facilities with higher rates of troponin ordering were associated with more downstream resource utilization.

Decreasing the Overuse of Troponin Testing- An Interventional Study in a Regional Hospital.

INTRODUCTION: The purpose of this study was to determine the effect of recommendations to limit troponin testing to patients with either chest pain or ischemic electrocardiographic changes. METHODS: We included all adult patients hospitalized in a regional hospital in internal medicine, cardiology, and intensive care departments in 2014-2016 and in 2019 after recommending limiting troponin testing to patients with either chest pain or ischemic electrocardiographic changes. RESULTS: After the intervention, testing decreased from 51.5% (11,634/22,581) to 34.6% (3417/9882). However, if only those with ischemia or chest pain were tested, the frequency would be 9.4% (924/9882) with a 95% confidence interval of 8.8%-9.9%. Variables increasing the odds of ordering a troponin test were older age, male sex, a discharge diagnosis of tachyarrhythmia, congestive heart failure, and dizziness or syncope as well as lower albumin and higher glucose, uric acid, and blood urea nitrogen test results. There were lower odds in those with nonspecific symptoms and infections of the skin, soft tissues, and the urinary tract. Auditing increased the effectiveness of the intervention in 1 internal medicine department (odds ratio 0.70, 95% confidence limit 0.60-0.82) after adjustment for other significant independent variables. The area under the curve was 0.713. CONCLUSION: We found that an educational program with clear recommendations decreased the proportion of patients with troponin testing in hospitalized internal medicine departments, but the intervention was only partially effective and did not include patients with congestive heart failure and other conditions in which expert recommendations for testing are discordant.

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.

Recent Advances in T1 and T2 Mapping in the Assessment of Fulminant Myocarditis by Cardiac Magnetic Resonance.

PURPOSE OF REVIEW: This review was undertaken to summarise recent data relating to T1 and T2 relaxation times in the assessment of myocarditis using cardiac MRI, and the effect new studies have had on the established diagnostic criteria, leading to recently proposed revised criteria for the cardiac MRI assessment of myocarditis. RECENT FINDINGS: In 2018, updates to the 2009 Lake Louise Criteria (LLC) were proposed, based on studies showing improved accuracy of T1 mapping techniques over T1 signal intensity ratio-based imaging, although for the detection of myocardial oedema either T2-weighted images or increased T2 relaxation times can be used. Non-ischaemic distribution of scar on late gadolinium-enhanced (LGE) T1-weighted imaging remains in the newly revised criteria, which, although can have low sensitivity due to fibrosis presenting diffusely or due to CMR being performed early in the disease process before scar formation, remains in the LLC due to its high specificity. Early gadolinium enhancement has been removed from the LLC, as T1 quantification has higher diagnostic accuracy for the detection of myocardial injury. In the CMR assessment of myocarditis, T1 and T2 quantifications are now recommended over T1- and T2-weighted imaging. Late gadolinium enhancement in a non-ischaemic pattern remains in the updated criteria, whereas early gadolinium enhancement has been superseded by T1 quantification.

Undetectable high-sensitivity troponin in combination with clinical assessment for risk stratification of patients with chest pain and normal troponin at hospital arrival.

BACKGROUND: Undetectable high-sensitivity cardiac troponin (hs-cTn) in a single determination upon admission may rule out acute coronary syndrome. We investigated undetectable hs-cTnT (

A Multicenter Assessment of the Sensitivity and Specificity for a Single High-Sensitivity Cardiac Troponin Test at Emergency Department Presentation for Hospital Admission.

BACKGROUND: Studies have illustrated how a low or undetectable high-sensitivity cardiac troponin (hs-cTn) concentration at emergency department (ED) presentation can rule out myocardial infarction (MI). A problem with using an undetectable hs-cTn cutoff is that this value may be defined differently among hospitals and is also difficult to monitor. In the present study, we assess the diagnostic performance of a clinical chemistry score (CCS) vs hs-cTn alone in the presentation blood sample in the ED for patient hospital admission in a multicenter setting. METHODS: From January 1 to June 30, 2018, consecutive patients with random glucose, creatinine (for an estimated glomerular filtration rate calculation), and hs-cTnI (Abbott, 2 hospitals, Hamilton, Ontario, n = 10496) or hs-cTnT (Roche, 4 hospitals, Calgary, Alberta, n = 25177) were assessed for hospital admission with the CCS (range of scores, 0-5) or hs-cTn alone. Sensitivity, specificity, predicative values, and likelihood ratios were calculated for a CCS of 0 and 5 and for hs-cTn alone (hs-cTnI cutoffs, 5 and 26 ng/L; hs-cTnT cutoffs, 6 and 14 ng/L). RESULTS: The CCS of 0 (CCS <1) identified approximately 10% of all patients as low risk and had a sensitivity for hospital admission of nearly 98% as compared to <93% when hs-cTnT (<6 ng/L) or hs-cTnI (<5 ng/L) cutoffs alone were used. A CCS ≥5 had a specificity for hospital admission >95%, with approximately 14% of patients at high risk. CONCLUSIONS: An ED disposition (admit or send home) using the presentation blood sample could occur in nearly 25% of all patients by use of the CCS.

Predictive risk stratification using HEART (history, electrocardiogram, age, risk factors, and initial troponin) and TIMI (thrombolysis in myocardial infarction) scores in non-high risk chest pain patients: An African American urban community based hospital study.

Validated risk scoring systems in African American (AA) population are under studied. We utilized history, electrocardiogram, age, risk factors, and initial troponin (HEART) and thrombolysis in myocardial infarction (TIMI) scores to predict major adverse cardiovascular events (MACE) in non-high cardiovascular (CV) risk predominantly AA patient population.A retrospective emergency department (ED) charts review of 1266 chest pain patients where HEART and TIMI scores were calculated for each patient. Logistic regression model was computed to predict 6-week and 1-year MACE and 90-day cardiac readmission. Decision curve analysis (DCA) was constructed to differentiate between clinical strategies in non-high CV risk patients.Of the 817 patients included, 500 patients had low HEART score vs. 317 patients who had moderate HEART score. Six hundred sixty-three patients had low TIMI score vs. 154 patients had high TIMI score. The univariate logistic regression model shows odds ratio of predicting 6-week MACE using HEART score was 3.11 (95% confidence interval [CI] 1.43-6.76, P = .004) with increase in risk category from low to moderate vs. 2.07 (95% CI 1.18-3.63, P = .011) using TIMI score with increase in risk category from low to high and c-statistic of 0.86 vs. 0.79, respectively. DCA showed net benefit of using HEART score is equally predictive of 6-week MACE when compared to TIMI.In non-high CV risk AA patients, HEART score is better predictive tool for 6-week MACE when compared to TIMI score. Furthermore, patients presenting to ED with chest pain, the optimal strategy for a 2% to 4% miss rate threshold probability should be to discharge these patients from the ED.

Biomarkers of neonatal stress assessment: A prospective study.

INTRODUCTION: Early diagnosis of perinatal asphyxia, the major cause of neonatal mortality and morbidity, might be improved by the detection of neonatal stress biomarkers such as cardiac troponin (CTn)T, CTnI, NT-Terminal-pro-Brain Natriuretic Peptide (NT-pro-BNP), copeptin, and high sensitivity C-reactive protein (hs-CRP). However, reference values in neonates are lacking. The objective of our study was therefore to establish a reference range of these biomarkers in healthy full term newborns and to analyze the influence of delivery mode on their cord blood concentrations. PATIENTS AND METHODS: CTnT, CTnI, NT-pro-BNP, Copeptin and hs-CRP levels were determined in 201 neonates enrolled in this prospective study and correlated to the delivery mode and post-natal outcome. RESULTS: Using the 99th percentile, the upper reference limit in healthy newborns was established for all biomarkers. Neonates born after complicated delivery had significantly higher values of CTnT, CTnI and Copeptin than those born after uncomplicated delivery. In the multiple regression models with CTnT as dependent variable, the delivery mode was the statistically significant independent variable. CONCLUSION: In this study, we established reference values of cord blood concentrations of cardiac stress biomarkers in healthy newborns. We showed that cardiac-related birth stress is dependent on delivery mode.

Routine cardiac troponin assessment after percutaneous coronary intervention: useful or hype?

: Although the angiographic and procedural success of percutaneous coronary intervention (PCI) is now very high, some severe complications may still develop, including periprocedural myocardial infarction (MI). An accurate diagnosis of this condition is essential for guiding the clinical management, as these patients may need a tailored management. The current recommendations for diagnosing periprocedural myocardial infarction based on the fourth universal definition appear at first sight straightforward, but the clinical and prognostic significance of routine periprocedural cardiac troponin (cTn) assessment remains uncertain. The current scientific evidence suggests that the likelihood of observing increased periprocedural values of cTn is high, comprising between 30 and 90%. Moreover, cTn values after PCI do not straightforwardly predict major adverse cardiovascular events or all-cause mortality. Although it seems still premature to classify many cases as 'false positive' periprocedural MIs, it is now clear that an isolate 'biochemical diagnosis' of myocardial injury during or immediately after PCI does not translate into early unfavourable clinical consequences. At this point in time, it seems reasonable to suggest that serial cTn assessment should not be routinely performed, but should be reserved for a high-risk subset of PCI patients who have also developed new ECG changes or symptoms suggestive of myocardial ischemia.

[Assessment of the extent of myocardial necrosis following radiofrequency catheter ablation of different supraventricular arrhythmias]. / A myocardialis necrosis mértékének vizsgálata eltéro supraventricularis szívritmuszavarok rádiófrekvenciás katéterablatiós kezelését követoen.

INTRODUCTION: Levels of cardiac necroenzymes, high-sensitive troponin (hsTnT) and creatine kinase muscle-brain (CKMB) increase as a result of a myocardial damage following catheter ablation. AIM: To analyze the mid-term alteration of hsTnT and CKMB levels following radiofrequency ablation (RFCA) for atrial fibrillation (AF), atrial flutter (AFlu), AV-nodal reentry tachycardia (AVNRT) and electrophysiological studies (EPS) without ablation. METHOD: Patients undergoing RFCA for various indications and EPS were consecutively enrolled in our prospective study. Concentrations of hsTnT and CKMB were measured from serial blood samples directly before and after the procedure, 4 and 20 hours later and at 3 months follow-up. RESULTS: Forty-seven patients (10 EPS, 12 AVNRT, 13 AFlu, 12 AF) with mean age of 55 ± 13 were included. hsTnT levels increased significantly in all groups after the procedures, while CKMB changed only in the AF group. hsTnT exceeded the reference value in all patients with ablation and in 80% of patients with EPS 4 hours post-ablation. Peak average hsTnT levels for EPS, AVNRT, AFlu were 24 ± 11, 260 ± 218 and 541 ± 233 ng/L, respectively. The highest hsTnT level was measured in the AF group (799 ± 433 ng/L). We found a positive correlation between hsTnT levels and ablation time after RFCA. CONCLUSIONS: The hsTnT levels significantly change after EPS and RFCA, in all patients who underwent ablation, and in 80% of those with EPS had hsTnT positivity in the early post-procedural phase. hsTnT levels depended significantly on the type of the subgroups and correlated with the ablation time. Awareness of those observations is essential to correctly interpret elevated hsTnT levels following RFCA. Orv Hetil. 2019; 160(14): 540-548.

The appropriateness of coronary investigation in myocardial injury and type 2 myocardial infarction (ACT-2): A randomized trial design.

BACKGROUND: Elevated troponin level findings among patients presenting with suspected acute coronary syndrome (ACS) or another intercurrent illness undeniably identifies patients at increased risk of mortality. Whilst enhancing our capacity to discriminate risk, the use of high-sensitivity troponin assays frequently identifies patients with myocardial injury (i.e. troponin rise without acute signs of myocardial ischemia) or type 2 myocardial infarction (T2MI; oxygen supply-demand imbalance). This leads to the clinically challenging task of distinguishing type 1 myocardial infarction (T1MI; coronary plaque rupture) from myocardial injury and T2MI in the context of concurrent acute illness. Diagnostic discernment in this context is crucial because MI classification has implications for further investigation and care. Early invasive management is of well-established benefit among patients with T1MI. However, the appropriateness of this investigation in the heterogeneous context of T2MI, where there is high competing mortality risk, remains unknown. Although coronary angiography in T2MI is advocated by some, there is insufficient evidence in existing literature to support this opinion as highlighted by current national guidelines. OBJECTIVE: The objective is to evaluate the clinical and economic impact of early invasive management with coronary angiography in T2MI in terms of all-cause mortality and cost effectiveness. DESIGN: This prospective, pragmatic, multicenter, randomized trial among patients with suspected supply demand ischemia leading to troponin elevation (n=1,800; T2MI [1,500], chronic myocardial injury [300]) compares the impact of invasive angiography (or computed tomography angiography as per local preference) within 5 days of randomization versus conservative management (with or without functional testing at clinician discretion) on all-cause mortality by 2 years. Randomized treatment allocation will be stratified by baseline estimated risk of mortality using the Acute Physiology, Age, and Chronic Health Evaluation (APACHE) III risk score. Cost-effectiveness will be evaluated by follow-up on clinical events, quality of life, and resource utilization over 24 months. SUMMARY: Ascertaining the most appropriate first-line investigative strategy for these commonly encountered high-risk T2MI patients in a randomized comparative study will be pivotal in informing evidence-based guidelines that lead to better patient and health care outcomes.

Randomised controlled trial of the Limit of Detection of Troponin and ECG Discharge (LoDED) strategy versus usual care in adult patients with chest pain attending the emergency department: study protocol.

INTRODUCTION: Observational data suggest a single high-sensitivity troponin blood test taken at emergency department (ED) presentation could be used to rule out major adverse cardiac events (MACE) in 10%-60% of ED patients with chest pain. This is done using an 'undetectable' cut-off (the Limit of Detection: LoD). We combined the LoD cut-off with ECG findings to create the LoDED strategy. We aim to establish whether the LoDED strategy works under real-life conditions, when compared with existing strategies, in a way that is cost-effective and acceptable to patients. METHODS AND ANALYSIS: This is a parallel-group pragmatic randomised controlled trial across UK EDs. Adults presenting to ED with suspected cardiac chest pain will be randomised 1:1. Existing rule-out strategies in current use across study centres, using serial high-sensitivity troponin testing, will be compared with the LoDED strategy. The primary outcome is successful early discharge (discharge from hospital within 4 hours of arrival) without MACE occurring within 30 days. Secondary outcomes include initial length of hospital stay; comparative costs; patient satisfaction and acceptability to patients. To detect a 9% difference between the early discharge rates (assuming an 8% rate in the standard care group) with 90% power, 594 patients need to be recruited, assuming a 95% follow-up rate. ETHICS AND DISSEMINATION: The study has been approved by the Frenchay Research Ethics Committee (reference 18/SW/0038). Results will be published in an international peer-reviewed journal. Lay summaries will be made available to patients. TRIAL REGISTRATION NUMBER: ISRCTN86184521; Pre-results.

Value of Prehospital Troponin Assessment in Suspected Non-ST-Elevation Acute Coronary Syndrome.

There is an increasing awareness that prehospital risk stratification in patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) is important. The HEART score accurately identifies patients at low risk and is nowadays fully assessable outside the hospital after the development of point-of-care (POC) troponin tests. However, the added value of the troponin component to the prehospital HEART score has not yet been assessed. This is a prospective cohort study including 700 patients with suspected NSTE-ACS in which prehospital risk stratification using the HEART score was performed by paramedics. Low risk was defined as HEAR or HEART score ≦3. Troponin was measured by a POC troponin T Test device (Roche Cobas h232). Troponin <40 ng/l scored 0 point, troponin ≥40 ng/l scored 2 points. Primary end point was major adverse cardiac events (MACE) within 45 days after inclusion. Mean HEAR score was 4.5 ± 1.6, mean HEART score was 4.7 ± 1.7. Using the HEAR score, a total of 183 patients (26%) were stratified as low risk, whereas using the HEART score, 172 patients (25%) were stratified as low risk (p = 0.001). In both low-risk groups, there were no deaths within 45 days. Using HEAR, MACE occurred in 13 patients (7%) in the low-risk group, whereas using HEART, MACE occurred in 5 patients in the low-risk group (3%, p <0.001). The use of HEART (Area under the curve 0.74) obtained a higher predictive value compared to HEAR (Area under the curve 0.65, p <0.001) for MACE. In conclusion, in patients with suspected NSTE-ACS, the prehospital troponin component of the HEART score has important added predictive value.

Sex-Related Aspects of Biomarkers in Cardiac Disease.

Biomarkers play an important role in the clinical management of cardiac care. In particular, cardiac troponins (cTn) and natriuretic peptides are the cornerstones for the diagnosis of acute myocardial infarction (AMI) and for the diagnosis of heart failure (HF), respectively. Current guidelines do not make a distinction between women and men. However, the commonly used "one size fits all" algorithms are topic of debate to improve assessment of prognosis, particularly in women. Due to the high-sensitivity assays (hs-cTn), lower cTn levels (and 99th percentile upper reference limits) were observed in women as compared with men. Sex-specific diagnostic thresholds may improve the diagnosis of AMI in women, though clinical relevance remains controversial and more trials are needed. Also other diagnostic aspects are under investigation, like combined biomarkers approach and rapid measurement strategies. For the natriuretic peptides, previous studies observed higher concentrations in women than in men, especially in premenopausal women who might benefit from the cardioprotective actions. Contrary to hs-cTn, natriuretic peptides are particularly incorporated in the ruling-out algorithms for the diagnosis of HF and not ruling-in. Clinical relevance of sex differences here seems marginal, as clinical research has shown that negative predictive values for ruling-out HF were hardly effected when applying a universal diagnostic threshold that is independent from sex or other risk factors. Apart from the diagnostic issues of AMI in women, we believe that in the future most sex-specific benefits of cardiac biomarkers can be obtained in patient follow-up (guiding therapy) and prognostic applications, fitting modern ideas on preventive and personalized medicine.