hs-cTnT Concentrations Research Articles

Machine learning compared with rule-in/rule-out algorithms and logistic regression to predict acute myocardial infarction based on troponin T concentrations.

ObjectiveComputerized decision‐support tools may improve diagnosis of acute myocardial infarction (AMI) among patients presenting with chest pain at the emergency department (ED). The primary aim was to assess the predictive accuracy of machine learning algorithms based on paired high‐sensitivity cardiac troponin T (hs‐cTnT) concentrations with varying sampling times, age, and sex in order to rule in or out AMI.MethodsIn this register‐based, cross‐sectional diagnostic study conducted retrospectively based on 5695 chest pain patients at 2 hospitals in Sweden 2013–2014 we used 5‐fold cross‐validation 200 times in order to compare the performance of an artificial neural network (ANN) with European guideline‐recommended 0/1‐ and 0/3‐hour algorithms for hs‐cTnT and with logistic regression without interaction terms. Primary outcome was the size of the intermediate risk group where AMI could not be ruled in or out, while holding the sensitivity (rule‐out) and specificity (rule‐in) constant across models.ResultsANN and logistic regression had similar (95%) areas under the receiver operating characteristics curve. In patients (n = 4171) where the timing requirements (0/1 or 0/3 hour) for the sampling were met, using ANN led to a relative decrease of 9.2% (95% confidence interval 4.4% to 13.8%; from 24.5% to 22.2% of all tested patients) in the size of the intermediate group compared to the recommended algorithms. By contrast, using logistic regression did not substantially decrease the size of the intermediate group.ConclusionMachine learning algorithms allow for flexibility in sampling and have the potential to improve risk assessment among chest pain patients at the ED.

The effect of remote ischaemic preconditioning on postoperative cardiac and inflammatory biomarkers in pancreatic surgery: a randomized controlled trial.

BackgroundCardiac and inflammatory biomarkers have been associated with adverse outcome after major abdominal surgery. This study investigated the effect of remote ischaemic preconditioning (RIPC) on perioperative concentrations of high-sensitive cardiac troponin (hs-cTn) T and interleukin (IL) 6.MethodsAdult patients scheduled for elective pancreatic surgery between March 2017 and February 2019 were randomized to either three cycles of upper-limb ischaemia and reperfusion (each 5 min) or a sham procedure before surgery. The primary endpoint was the maximum postoperative hs-cTnT concentration within 48 h after surgery. Secondary endpoints were postoperative myocardial injury (PMI), defined as an absolute increase of hs-cTnT of at least 14 ng/l above baseline concentration, maximum concentration of IL-6 within 48 h after surgery and postoperative complications within 30 days of surgery.ResultsOf 99 eligible patients, 46 underwent RIPC and 46 a sham procedure. RIPC did not reduce the maximum hs-cTnT concentration after surgery (12.6 ng/l RIPC, 16.6 ng/l controls, P = 0.225), nor did it lessen the incidence of PMI (15/45 RIPC, 18/45 controls, P = 0.375). The maximum postoperative IL-6 concentration was 265 pg/ml after RIPC versus 385 pg/ml in controls (P = 0.108). Postoperative complications occurred in 23 RIPC and 24 control patients respectively.ConclusionsRemote ischaemic preconditioning did not reduce the maximum postoperative hs-cTnT concentration. Postoperative myocardial injury, IL-6 concentrations and postoperative complications were similar between RIPC patients and controls.Trial registrationClinicaltrials.gov identifier NCT03460938.

Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications.

Cardiac troponin T determination plays a dominant role in diagnosis of myocardial pathologies. Despite generally accepted use of high-sensitive cardiac troponin T assays (hscTnT) and clearly defined cut-off limit in adults, the uncertainty persists in infants. The aim of this study was to assess plasmatic concentrations of hscTnT and describe sequential age-related dynamic changes of hscTnT in healthy infants and toddlers. Seventy-eight children (52 males/26 females) from Czech Republic aged 44 to 872 days (median, interquartile range 271; 126 to 486 days) were consecutively enrolled in the single-center, prospective observational study. Plasma concentrations of hscTnT were analyzed by the electrochemiluminescent method, age-related reference intervals were calculated using the polynominal regression model. Amongst the study population (n=78), the upper limit of hscTnT concentration defined as the 99th percentile was calculated. The 99th percentile with 95 % confidence interval at the end of 2nd, 3rd, 4th, 5th, 6th and 7th month of postnatal life were: 81 (40.6 to 63.6), 61 (36.0 to 55.3), 47 (31.9 to 48.3), 37 (28.1 to 42.3), 30 (24.7 to 37.2) and 25 (21.5 to 32.7) ng/l, respectively. Concentration of adults 99th percentile (14 ng/l) was achieved approximately at 1 year of postnatal life. Statistically significant negative correlation of hscTnT concentration with age (r=-0.81, p<0.001) was found. Significant gender differences were not found (p>0.07). The study revealed substantially increased reference intervals of hscTnT levels in infants when compared with adult population. Based on our preliminary results, the age-related interpretation of hscTnT plasmatic concentration is recommended.

High-sensitivity cardiac troponins: circadian rhythms

High-sensitivity cardiac troponins (hs-cTnI and hs-cTnT) contribute to a progression in the diagnosis and treatment of cardiovascular diseases: acceleration of diagnosis of acute myocardial infarction (early diagnostic algorithms: 0-1 h, 0-3 h), and earlier initiation of optimal treatment, expansion of diagnostic and prognostic potential (earlier detection of myocardial damage during chemotherapy, endocarditis, myocarditis and other diseases). However, increased sensitivity slightly reduced the specificity and created the need for a more thorough interpretation of elevated levels of hs-cTnI and hs-cTnT in a number of pathologies that damage cardiomyocytes. In addition, there was a need to introduce reference levels of hs-cTnI and hs-cTnT (99 percentile), taking into account sex. Recently, there has also been information about circadian (diurnal) variations in hs-cTnT and hs-cTnI levels. We analyze in detail the results of clinical studies that found circadian changes in hs-cTnI and hs-cTnT. Possible mechanisms underlying these changes in hs-cTnT and hs-cTnI concentrations are discussed.

High-Sensitivity Cardiac Troponin, Natriuretic Peptide, and Long-Term Risk of Acute Kidney Injury: The Atherosclerosis Risk in Communities (ARIC) Study.

Cardiac markers such as high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B natriuretic peptide (NTproBNP) are predictors of developing acute kidney injury (AKI) during hospitalization for surgery or revascularization. However, their associations with the long-term risk of AKI in the general population are uncharacterized. We conducted a prospective cohort study in 10669 participants of the Atherosclerosis Risk in Communities Study (visit 4, 1996-1998, mean age, 63 years, 56% female, 22% black race) to examine the association of plasma concentrations of hs-cTnT and NTproBNP with the incident hospitalization with AKI. We used multivariable Cox regression analysis to estimate hazard ratios (HRs). During follow-up, 1907 participants had an incident hospitalization with AKI. Participants with higher concentrations of hs-cTnT had a higher risk of hospitalization with AKI in a graded fashion (adjusted HR, 1.88 [95%CI , 1.59-2.21] for ≥14 ng/L, 1.36 [1.18-1.57] for 9-13 ng/L, and 1.16 [1.03-1.30] for 5-8 ng/L compared to <5 ng/L). The graded association was also observed for NTproBNP (HR, 2.27 [1.93-2.68] for ≥272.7 pg/mL, 1.67 [1.45-1.93] for 142.4-272.6 pg/mL, and 1.31 [1.17-1.47] for 64.0-142.3 pg/mL compared to <64.0 pg/mL). The addition of hs-cTnT and NTproBNP to a model with established predictors significantly improved 10-year risk prediction for hospitalization with AKI (Δc-statistic, 0.015 [95%CI, 0.006-0.024]). In middle-aged to older black and white adults in the community, higher concentrations of hs-cTnT and NTproBNP were robustly associated with an increased risk of hospitalization with AKI. These results suggest the usefulness of hs-cTnT and NT-proBNP to identify people at risk of AKI in the general population.

Reference limits of high-sensitive cardiac troponin T indirectly estimated by a new approach applying data mining. A special example for measurands with a relatively high percentage of values at or below the detection limit

Abstract A new model for the indirect estimation of reference limits (RLs) has been proposed recently and was coined TMC approach (truncated minimum chi-square estimation) which can be performed with R statistic. A spline function is applied to the RLs to get a continuous function if age is graphically presented vs. the RLs avoiding artificial “jumps” between different age groups. Most indirect models assume a power normal distribution and fail if this assumption is not fulfilled as e.g. if a relatively high percentage of measured values is below the detection limit and the data are distributed extremely skewed. This problem is handled by the TMC model. High-sensitive cardiac troponin T (hs cTnT) was chosen as an example. The hs cTnT concentration in serum or plasma is well accepted as a valuable marker in the diagnosis of acute myocardial infarction. Currently, the 99th percentile derived from a “healthy” subpopulation is the decision limit recommended by consensus groups. However, this decision limit is questioned by several authors for many reasons. In the present report, the 97.5th and the 99th percentile limits were reinvestigated by the TMC model with different subpopulations stratified according to age and sex and were finally compared to presently recommended decision limits. In summary, the generally recommended 99th percentile as a fixed decision limit should be reconsidered. It is suggested to apply more specific reference limits stratified for age and sex instead of a fixed decision limit.

High-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide in acute heart failure: Data from the ACE 2 study

BackgroundTo assess if cardiac troponins can improve diagnostics of acute heart failure (AHF) and provide prognostic information in patients with acute dyspnea. MethodsWe measured cardiac troponin T with a high-sensitivity assay (hs-cTnT) in 314 patients hospitalized with acute dyspnea. The index diagnosis was adjudicated and AHF patients were stratified into AHF with reduced or preserved ejection fraction (HFrEF/HFpEF). The prognostic and diagnostic merit of hs-cTnT was compared to the merit of N-terminal pro-B-type natriuretic peptide (NT-proBNP). ResultsIn the total population, median age was 73 (quartile [Q] 1–3 63–81) years and 48% were women. One-hundred-forty-three patients were categorized as AHF (46%) and these patients had higher hs-cTnT concentrations than patients with non-AHF-related dyspnea: median 38 (Q1-3 22–75) vs. 13 (4–25) ng/L; p < 0.001. hs-cTnT concentrations were similar between patients with HFrEF and HFpEF (p = 0.80), in contrast to NT-proBNP, which was higher in HFrEF (p < 0.001). C-statistics for discriminating HFpEF from non-AHF-related dyspnea was 0.80 (95% CI 0.73–0.86) for hs-cTnT, 0.79 (0.73–0.86) for NT–proBNP, and 0.83 (0.76–0.89) for hs-cTnT and NT-proBNP in combination. Elevated hs-cTnT remained associated with HFpEF in logistic regression analysis after adjusting for demographics, comorbidities and renal function. During median 27 months of follow-up, 114 (36%) patients died in the total population. Higher hs-cTnT concentrations were associated with increased risk of all-cause mortality after adjustment for clinical variables and NT-proBNP: hazard ratio 1.30 (95% CI 1.07–1.58), p = 0.009. Conclusionhs-cTnT measurements improve diagnostic accuracy for HFpEF and provide independent prognostic information in unselected patients with acute dyspnea.

Differential associations of cardiac troponin T and cardiac troponin I with coronary artery pathology and dynamics in response to short-duration exercise

BackgroundWe aimed to assess the associations between cardiac troponin (cTn) T and I concentrations, physical exercise and the presence and severity of angiographic coronary artery disease (CAD) in patients evaluated for suspected chronic coronary syndrome (CCS). Methods and resultsAll patients performed an exercise stress test on a bicycle ergometer and underwent invasive coronary angiography with weighted anatomical evaluation using the Gensini score. Blood samples were collected before and after exercise and analysed with high-sensitivity (hs) cTnT and cTnI assays.Of 297 patients (median age 62 (Quartile [Q]1–3 56–69) years, 35% female), 46% were categorized as “severe CAD” (Gensini score ≥ 20).Resting hs-cTnT and hs-cTnI concentrations were detectable in 88% and 100% of patients, with medians of 6 (Q1-3 4–9) ng/L and 1.5 (0.9–2.4) ng/L, respectively.In adjusted normalized linear regression analyses, higher resting concentrations were associated with increasing Gensini score (hs-cTnT: B 0.19, 95% Confidence Interval [CI] [0.09–0.41], p < 0.001; hs-cTnI: B 0.18, [0.06–0.30], p = 0.002).The area under the receiver operating characteristics curve for predicting severe CAD was 0.72 (95% CI [0.66–0.78]) and 0.68 (0.62–0.74) for resting hs-cTnT and hs-cTnI, p = 0.11 for difference.The median (Q1-3) relative increase in hs-cTnT and hs-cTnI concentrations were 5 (0–12) % and 13 (3–27) %, respectively, with no significant associations with CAD severity. ConclusionsIn patients with suspected CCS, higher hs-cTn concentrations at rest were associated with increasing angiographic severity of CAD, without any significant differences between the troponin isotypes. Post-exercise hs-cTn concentrations did not have discriminatory power for CAD.

Abstract 17152: Artificial Intelligence ECG for the Detection of Cardiac Injury as Confirmed by High Sensitivity Cardiac Troponin T-Concentrations

Background: High-sensitivity cardiac troponin (hs-cTn) assays quantify cTn in patients at very low concentrations. Myocyte injury due to ischemia or other pathologies cause blood levels to increase, which is prognostic. A noninvasive, rapid, broadly available, home-based test to detect hs-cTn increases would facilitate risk-stratification. Since myocyte injury is associated with ECG changes, we hypothesized an artificial intelligence ECG (AI-ECG) could non-invasively predict current or impending hs-cTnT elevations. Objective: To develop an AI-ECG convolutional neural network (CNN) to detect an abnormal hs-cTnT (5 th Gen cTnT, Roche Diagnostics) concentration using a 12-lead ECG, and a single lead ECG (lead I), which would enable smartphone, home-based detection. Methods: We developed single lead and 12-lead ECG CNNs to detect a) hs-cTnT concentrations that were at or above the 6ng/L limit that can be reported b) above the 99 th percentile upper limits of &gt;15ng/L for men and &gt;10ng/L for women. All ECGs were recorded within one hour of the hs-cTnT measurements. We used 73,012 ECG and hs-cTnT pairs from 47,542 unique patients to train the network, 9031 ECGs from 5,811 patients for internal validation to optimize hyperparameters, and 18,276 ECG and hs-cTnT pairs from 11,904 different patients as a holdout test set to determine the area under the receiver-operator curve (AUC). Results: The mean age was 63.9±17.5 years, and 30,348 of the 59,446 patients (51%) were male. Of the 91,288 hs-cTnT pairs 73,271 (80.2%) were above 6ng/L and 50,799 (55.6%) are above the 99 th percentile. In the test set, the AUC for the detection of a hs-cTnT level higher than 6ng/L was 0.88 using the 12 lead ECG and 0.834 with the single lead. For the detection of hs-cTnT level above of 99 th percentile, the 12 lead ECG AUC was 0.853 and the single lead was 0.806. Conclusion: The AI-ECG permits detection of levels of hs-cTnT consistent with myocardial injury. This may allow a home-based, non-invasive test that would be massively scalable and could further enhance rapid-risk stratification and patient triage with potentially significant cost reductions and enable novel triage strategies at sites without hs-cTn assays.

Abstract 16416: Associations of NT-proBNP and High Sensitivity Cardiac Troponin T Concentrations With 6-year Changes in Left Ventricular Structure and Function in Older Adults: The Atherosclerosis Risk in Community (ARIC) Study

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT) improve prediction of incident heart failure (HF) and are cross-sectionally associated with left ventricular (LV) remodeling, but their associations with changes in cardiac structure and function are unclear. Hypothesis: Concentrations of NT-proBNP and hs-cTnT associate with 6-year change in cardiac structure in older adults. Methods: We studied 1,916 participants aged 67-88 in the ARIC Study free of overt cardiovascular disease at baseline (study Visit 5; 2011-13). We quantified the associations of baseline NT-proBNP and hs-cTnT with subsequent changes in LV structure and systolic and diastolic function assessed by echocardiography over a median of 6.6 (IQR 6.1-7.0) years using multivariable linear regression and restricted cubic spline models. Models adjusted for demographics, systolic blood pressure, heart rate, body mass index, diabetes, hypertension, kidney function, and the baseline echocardiographic value of interest at Visit 5. Results: Mean age was 75±4 years, 60% were female, 23% were black, median hs-cTnT was 9 (IQR 6-13) ng/L and NT-proBNP was 88 (50-157) ng/L at Visit 5. In adjusted models, higher hs-cTnT was modestly associated with 6-year increase in LV wall thickness (p=0.02) but not with changes in LV function. In contrast, higher NT-proBNP at Visit 5 was associated with 6-year increase in LV mass, decline in LV systolic function (ejection fraction, longitudinal and circumferential strain), and worsening of diastolic function (left atrium volume, E/e’, tricuspid regurgitation peak velocity) (all p&lt;0.01, Figure ). These associations were non-linear. Conclusions: Higher NT-proBNP, but not hs-cTnT, concentrations are associated with greater declines in LV systolic and diastolic function over ~6 years in late life.

Direct comparison of the accuracy of preoperative high-sensitivity cardiac troponin T to predict mortality, acute heart failure and perioperative myocardial infarction/injury after non-cardiac surgery

Abstract Background Death, acute heart failure (AHF) and perioperative myocardial infarction/injury (PMI) are the most relevant cardiovascular complications following non-cardiac surgery. Unfortunately, the incidence of these complications are higher than expected. Currently available tools to predict these complications have only modest accuracy. Purpose To determine the accuracy of preoperative high-sensitivity cardiac troponin T (hs-cTnT) concentrations for prediction of mortality, AHF and PMI after non-cardiac surgery. Methods We prospectively included 4,709 patients at high cardiovascular risk undergoing non-cardiac surgery. Hs-cTnT concentrations were measured before surgery and, daily after surgery, for two days. PMI was defined as an absolute increase of 14ng/L (the 99th percentile of the assay used) from hs-cTnT baseline values. The primary endpoint was the diagnostic accuracy of preoperative hs-cTnT concentration to predict death, AHF and PMI within 30 days, as quantified by the area under the receiving-operating curve (AUC). Multivariate logistic regression analysis was performed to test the association between preoperative hs-cTnT and each endpoint. Results All-cause mortality occurred in 133 (3%), AHF in 84 (2%) and PMI in 742 (16%) patients. Preoperative hs-cTnT concentrations had good accuracy for prediction of death, AHF and PMI (AUC = 0.75 [95% CI, 0.71–0.79], 0.72 [95% CI, 0.67–0.77] and 0.73 [95% CI, 0.71–0.75], respectively). After adjusting for confounders, hs-cTnT remained an independent predictor for death with an adjusted odds ratio (aOR) of 2.1 (95% CI, 1.7–2.7, P&amp;lt;0.001) and for PMI (aOR 2.2, 95% CI, 1.9–2.4, P&amp;lt;0.001), but not for AHF (aOR 1.0, 95% CI, 0.7–1.4, P=0.99). An hs-cTnT concentration below 5ng/L was found in 526 (11%) patients, and this cut-off yielded a negative predictive value of 99.6% for the occurrence of death, 99.2% for AHF and 95.6% for PMI. Conclusion The preoperative hs-cTnT concentration has a good accuracy to predict mortality, AHF and PMI after non-cardiac surgery, but is an independent predictor only for mortality and PMI. A cut-off value of 5ng/L identifies a subgroup of patients at low risk for these complications. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Foundation, Swiss Herat Foundation

Rise and fall of high-sensitivity cardiac troponin T after coronary artery bypass grafting surgery in relation to current definitions of myocardial infarction: a systematic review and meta-analysis

Abstract Background Cardiac troponins are the preferred biomarkers for the diagnosis of myocardial infarction (MI) and play an important role in coronary artery bypass grafting (CABG) related MI (type 5 MI). Different cut-off values, as defined by multiples of the 99th percentile upper reference limit (URL) for isolated and non-isolated troponin elevations have been proposed. Also, these definitions are based on arbitrarily chosen and varying values (3rd and 4th Universal definition: 10xURL, Society for Cardiovascular Angiography and Interventions (SCAI): 35 and 70xURL) and electrocardiographical or imaging findings. In addition to the controversy in MI definitions, the introduction of high-sensitivity cardiac troponin (hs-cTn) assays and their subsequent lower thresholds warrant a thorough re-assessment of hs-cTn dynamics after CABG. Purpose To evaluate the rise and fall of hs-cTn after CABG in relation to the definitions of myocardial infarction. Methods Studies published between 2008 and 2020 reporting hs-cTn concentrations in relation to CABG were searched through Pubmed and reviewed by 2 independent screeners. The search terms were “coronary artery bypass” AND “high-sensitivity cardiac troponin”, including alternative names and abbreviations. Inclusion criteria were the use of a hs-cTn assay in the postoperative phase, either for cardiac troponin T or I. This study was performed in agreement with the PRISMA guidelines. Results Out of 37 screened studies, 15 studies were included (2860 patients). The overall preoperative hs-cTnT concentration (median, 25th-75th percentile) was 43.5 (16.3–57.9) ng/L. Subsequently, in &amp;gt;80% of CABG patients, preoperative hs-cTnT was elevated &amp;gt;14 ng/L. Hs-cTnT was highly variable over time, with a peak of 408.7 (14.9–717.2) ng/L 6–8 h after CABG. Postoperative peak hs-cTnT concentrations rose &amp;gt;10xURL (Universal definition) in 100% of CABG patients. Peak hs-cTnT &amp;gt;35xURL and ±20% &amp;gt;70xURL (SCAI definition) during the first 48 h was 30% and ∼20%, respectively (estimated from data depicted in Figure 1). Electrocardiographic and imaging findings were available for only 1 study (554 patients). Overall 30-day mortality was 1.7 (0.8–4.0)%, reported by 7 studies (2291 patients). Data regarding the association of hs-cTnT and clinical outcome was reported by 1 study. As only 4 studies (217 patients) reported on the results of hs-cTnI, using assays from different vendors, a meta-analysis for hs-cTnI could not be performed. Conclusion The different definitions of type 5 MI propose arbitrarily chosen cTn cut-off values, varying enormously between the definitions. The current thresholds may not apply to the majority of CABG patients, since &amp;gt;80% had elevated preoperative hs-cTnT. Furthermore, hs-cTnT obtained within 48 h after CABG is highly variable over time. Therefore, further research is needed to establish clinically relevant hs-cTn thresholds and timing of sampling for a more accurate diagnosis of CABG procedure related MI. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): ZonMw Veni grant

Early diagnosis of acute myocardial infarction in patients with a history of percutaneous coronary intervention

Abstract Background Recurrence of acute chest pain after percutaneous coronary intervention (PCI) is common. The early detection of acute myocardial infarction (AMI) as a possible cause of acute chest pain can be challenging in patients with a history of PCI due to e.g. pre-existing electrocardiographic abnormalities. It is unknown, whether high-sensitivity cardiac troponin T (hs-cTnT) concentrations and hs-cTnT-based rapid algorithms perform equally well in patients with a history of PCI. Purpose To investigate the impact of prior PCI on the diagnostic performance of hs-cTnT concentrations for early rule-out and rule-in of AMI. Methods In an ongoing multicentre international study, we prospectively enrolled unselected patients presenting to the emergency department (ED) with symptoms suggestive of AMI. Final diagnoses were centrally adjudicated by two independent cardiologists using all available medical records obtained during clinical care including 90 day follow-up information and cardiac imaging. High-sensitivity cTnT concentrations at presentation and after 1h were compared against the adjudicated final diagnosis. Patients were stratified according to the presence or absence of previous PCI. Results Among 5536 patients (1313 with and 4223 without previous PCI), incidence of AMI was significantly higher in patients with previous PCI (26.3% versus 21.4%; p&amp;lt;0.001). Patients with prior PCI and a final diagnoses other than AMI had significantly higher concentrations of hs-cTnT at presentation to the ED (median 9ng/l [IQR 6 to 15.8] vs 5.5ng/l [IQR 3 to 10]; p&amp;lt;0.001). However, in patients with final adjudicated diagnosis of AMI, hs-TnT concentrations at presentation were lower in patients with previous PCI (median 46ng/l [IQR 23 to 94] vs 55ng/l [IQR 25 to 175]; p=0.003). The diagnostic accuracy of hs-cTnT was high in patients with history of PCI, but significantly lower compared to patients without PCI (AUC 0.91 [95% CI 0.89–0.92] versus AUC 0.94 [95% CI 0.94–0.95]; p&amp;lt;0.001, respectively). When applying the ESC 0/1-algorithm among patients with previous history of PCI, the rule out pathway showed also very high safety in patients with a history of PCI (sensitivity 99.2 [95% CI 97.2–99.8] and negative predictive value 99.6 [95% CI 98.5–99.9]). However, the efficacy of the ESC 0/1h-algorithm for early rule out of NSTEMI was lower in the PCI group compared to no PCI (45.2% vs 65.1%; P&amp;lt;0.001, respectively), triaging more patients to the observe zone (36.8% versus 18.8%; p&amp;lt;0.001). Time to discharge from the ED was significantly longer in patients with prior PCI (334 min vs 290 min; p&amp;lt;0.001). When stratified for index AMI, patients with history of PCI waited longer for a final diagnoses of AMI (285 vs 217 min; p&amp;lt;0.001). Conclusions History of PCI impacts on the diagnostic performance of hs-cTnT. Although the ESC 0/1h-algorithm still performs very safe when applied to patients with a history of PCI, its efficacy is significantly reduced. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the Stiftung für kardiovaskuläre Forschung Basel the University of Basel and the University Hospital Basel

Blood-based biomarkers for the long-term prognosis after acute ischemic stroke – results of the Linz Stroke Unit (LISU) study

Abstract Background The aim of our study was to evaluate the long-term prognostic value of blood-based biomarkers in comparison to the established National Institute of Health stroke scale (NIHSS) score in patients with acute ischemic stroke. Methods We measured plasma concentrations of IL-6, NT-proBNP, D-dimer, hs-cTnT, sST2, MR-proADM, MR-proANP, CT-proET-1, Copeptin, and Procalcitonin in 721 consecutive acute ischemic stroke patients within 24 h after admission to our stroke unit. Endpoint was all-cause mortality at 3 years. Results During follow-up, 199 patients died (28%). In univariate Cox proportional hazards regression analyses using a dichotomized approach according to median values, all blood-based biomarkers were associated with prognosis. However, in the multivariate analysis after adjustment for several clinical variables, only IL-6 &amp;gt;7 pg/mL (risk ratio, 3.00; 95% CI, 2.03–4.44; P&amp;lt;0.001), NT-proBNP &amp;gt;447 ng/L (risk ratio, 2.67; 95% CI, 1.81–3.92; P&amp;lt;0.001), NIHSS score &amp;gt;3 (risk ratio, 2.24; 95% CI, 1.63–3.07; P&amp;lt;0.001), Copeptin &amp;gt;13 pmol/L (risk ratio, 1.87; 95% CI, 1.34–2.61; P&amp;lt;0.001), and hs-cTnT &amp;gt;14 ng/L (risk ratio, 1.74; 95% CI, 1.21–2.49; P=0.001) remained independent predictors. ROC curve analysis for mortality prediction demonstrated a higher area under the curve (AUC) for IL-6 and NT-proBNP, respectively, when compared to the NIHSS score (IL-6 AUC 0.81 vs. NIHSS AUC 0.75; P=0.016 and NT-proBNP AUC 0.80 vs. NIHSS AUC 0.75; P=0.039) and similar AUCs when comparing the NIHSS with hs-TnT (hs-TnT AUC 0.77) and Copeptin (Copeptin AUC 0.72). Conclusions In this large cohort of patients with acute ischemic stroke the blood-based biomarkers IL-6, NT-proBNP, hs-cTnT, and Copeptin were strong and independent prognostic markers for 3-year all-cause mortality. IL-6 and NT-proBNP even outperformed the NIHSS score for long-term mortality prediction. ROC plots for 3-year all-cause mortality Funding Acknowledgement Type of funding source: None

Impact of the period of the day on mortality and major cardiovascular complications after vascular surgeries

Abstract Introduction Patients submitted to arterial vascular surgeries are at a high risk of postoperative cardiac and non-cardiac complications, therefore developing strategies to lower perioperative complications is essential to optimize outcomes for this subgroup. Recent studies have suggested that the period of the day in which surgeries are performed may influence postoperative major cardiovascular complications but there is still no evidence of this association in vascular surgeries. Purpose Our goal is to evaluate whether the period of the day in which surgeries are performed may influence mortality and cardiovascular outcomes in patients undergoing non-cardiac vascular procedures. Methods Patients who underwent non-cardiac vascular surgeries between 2012 and 2018 were prospectively included at our cohort. For this analysis, subjects were categorized into two groups: those who underwent surgery in the morning (7am - 12am) and those who underwent surgery in the afternoon/night (12:01pm - 6:59am). The primary endpoints were to compare the incidence of major adverse cardiac events (MACE - acute myocardial infarction, acute heart failure, arrhythmias, and cardiovascular death) and total mortality between morning and afternoon/night surgeries within 30 days and one year. The secondary endpoint was the incidence of perioperative myocardial injury (PMI) in both groups. PMI was defined as an absolute elevation of high-sensitivity cardiac troponin T (hs-cTnT) concentrations ≥14ng/L. Multivariable analysis using Cox proportional regression (with Hazard Ratio – HR and Confidence Interval – 95% CI) was performed to adjust for confounding variables, including emergency and urgent surgeries. Results Of 1267 patients included, 1002 (79.1%) underwent vascular surgery in the morning and 265 (20.9%) in the afternoon/night. After adjusting for confounding variables, the incidence of MACE at 30 days was higher among those who underwent surgery in the afternoon/night period (37.4% vs 20.4% – HR 1.43, 95% CI: 1.10–1.85; p=0.008). Mortality rates were also elevated in the afternoon/night group (21.5% vs 9.9%, HR 1.59, 95% CI: 1.10–2.29; p=0.013). After one-year of follow-up the worst outcomes persisted in patients operated in the afternoon/night: higher incidence of MACE (37.7% vs 21.2%, HR 1.37, 95% CI: 1.06–1.78; p=0.017) and mortality (35.8% vs 17.6%, HR 1.72, 95% CI 1.31–2.27; p&amp;lt;0.001). There was no significant difference in the incidence of PMI between groups (p=0.8). Conclusions In this group of patients, being operated in the afternoon/night period was independently associated with increased mortality rates and incidence of MACE. Mortality and MACE at one year Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): FAPESP - Fundação de Amparo a Pesquisa do Estado de São Paulo

Evaluation of European Society of Cardiology (ESC) 0/1-hour algorithm in the diagnosis of 90-day major adverse cardiovascular events: a multicenter United States cohort study

Abstract Background The ESC 0/1-hour algorithm using high sensitivity troponin (ESC 0/1-h) is a rapid triage protocol for diagnosing acute coronary syndrome, however the classification performance of the algorithm in the US population is uncertain. Further, evidence for the use of ESC 0/1-h in the long-term diagnosis of major adverse cardiovascular events (MACE) remains limited. Purpose To evaluate the performance of the ESC 0/1-h algorithm in diagnosing 90-day MACE in a diverse US cohort. Methods In this prospective, multicenter, observational cohort study, adult emergency department patients who were evaluated for suspected ACS were enrolled at eight sites in the US. Serial 1-hour blood samples were collected and high sensitivity troponin T (hs-cTnT) concentrations were measured in a central laboratory using the hs-cTnT assay. Primary outcome included major adverse cardiovascular events (MACE) within 90 (+30) days of enrollment. MACE defined as myocardial infarction (MI), cardiovascular or uncertain death, and coronary revascularization. Presence of MI and cardiovascular death were adjudicated by independent reviewers blinded to hs-cTnT results. Each participant was stratified to one of three risk groups as determined by ESC 0/1-h algorithm. Diagnostic classification performance metrics with exact confidence intervals (i.e. negative predictive value [NPV], positive predicted value [PPV], sensitivity, and specificity) were evaluated for each risk group where appropriate. Results Among 1430 eligible participants, 45.8% (655/1430) were women and 36.6% (524/1430) were African American with a mean age of 57.6±12.8 years. MACE at 90-days occurred in 15.5% (221/1430). ESC 0/1-h stratified 59.5% (851/1430) subjects in Rule-Out range and 13.0% (186/1430) subjects in Rule-In range. The Rule-Out criteria had an NPV and sensitivity for 90-day MACE of 96.8% (95% CI: 95.4–97.9%) and 87.8% (95% CI: 82.7–91.8%), respectively. For 90-day cardiovascular death or MI, Rule-Out criteria had an NPV of 98.2% (95% CI: 97.1–99.0%) and sensitivity was 92.4% (95% CI: 87.8–95.7%). The Rule-In criteria had a PPV of 60.8% (95% CI: 53.3–67.8%) for both outcomes. Rule-In criteria had a specificity for 90-day MACE and 90-day cardiovascular death or MI of 94.0% (95% CI: 92.5–95.2%) and 94.1% (95% CI: 92.6–95.3%), respectively. Among the 27.5% (393/1430) participants classified in neither risk groups, the prevalence of 90-day MACE was 20.6% (81/393) and the prevalence of 90-day cardiovascular death or MI was 17.8% (70/393) Conclusion In a prospective, multicenter, US cohort, the ESC 0/1-h algorithm was unable to achieve a sufficiently high NPV to safely exclude the diagnosis of MACE within 90 days after emergency department presentation. New hs-cTn algorithms specific to the US population may be warranted. ESC 0/1-h 90 Day Outcomes Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics

External validation of a suggested extension of the ESC 0/1h-algorithm for early rule out of myocardial infarction

Abstract Background The European Society of Cardiology (ESC) high sensitivity cardiac troponin T 0/1h-algorithm has substantially improved the management of patients with suspected acute myocardial infarction (AMI) by triaging about 75% of patients to rapid rule-out and/or rapid rule-in. However, about 25% of patients remain in the “observe-zone”, and the optimal management of these patients is unknown. Recently, a pilot single center study with a low prevalence of AMI suggested that an absolute change of less than 7ng/L between the 0h and 3h hs-cTnT concentration would allow to help in the evaluation of patients in the observe-zone and allow triage towards rule-out with very high negative predictive value [NPV]. Purpose To externally validate this suggested modification of the ESC 0/1h-algorithm for early rule out of AMI. Methods In an ongoing multicentre international study, we prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of MI. Final diagnoses were centrally adjudicated by two independent cardiologists using all available medical records obtained during clinical care including 90 day follow-up information and cardiac imaging. High sensitivity-cTnT (Elecsys) concentrations were measured at presentation and after 1 and 3 hours. The primary outcome was safety, quantified by the sensitivity and NPV for early rule out of NSTEMI. Results Among 1633 enrolled patients with available 0, 1 and 3h hs-cTnT concentrations, NSTEMI was the adjudicated final diagnosis in 337 (20.6%) patients. The ESC 0/1h-algorithm ruled out 918 (56.2%) patients, with a sensitivity of 98.8% (95% confidence interval [CI], 97.0–99.5) and a NPV of 99.6% (95% CI, 98.9–99.8). A total of 428 patients (26.2%) remained in the observe zone. After applying the suggested 0–3 hour absolute change cut-off criteria of 7ng/L, 393 (92.0%) additional patients from the observe zone were triaged towards ruled out. However, the safety of this triage step was poor with 62 patients with NSTEMI missed, resulting in a sensitivity of 33.3% and a NPV of 84.2% for rule-out. Conclusions The suggested 0/3h absolute change cut-off of 7ng/L for patients remaining in the observe zone of the ESC 0/1h-algorithm does NOT allow safe rule-out of AMI and should therefore NOT be implemented into routine clinical care. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, the Swiss Heart Foundation, the Stiftung für kardiovaskuläre Forschung Basel, the University of Basel and the University Hospital Basel

High-Sensitive Cardiac Troponin T as a Reliable Biochemical Signature for Improvements of Mortality Prediction in Patients with Intracerebral Haemorrhage

Summary: BackgroundHigh-sensitive cardiac troponin T (hs-cTnT), as a preferred biomarker, has been used for auxiliary diagnosis and risk stratification of acute myocardial infarction. The prognostic value of hs-cTnT in intracerebral haemorrhage (ICH) remains unclear. Methods: To gauge if the hs-cTnT, either alone or combined with other risk factors, has the potential to predict in-hospital mortality among the ICH population in a diverse clinical scenario setting. We performed a multi-center, population-based, retrospective cohort study between November 2016 and December 2018. Admission hs-cTnT in serum was accessed, and additional information, including the demographics, baseline laboratory parameters. Clinical and imaging characteristic was collected as well. The primary outcome was in-hospital all-cause mortality. The associations between hs-cTnT and in-hospital death were assessed by multinomial logistic regression. We also use the Net Reclassification Index analysis strategy to address the incremental prognostic impact of hs-cTnT. Findings: Elevated high-sensitivity cardiac troponin (hs-cTnT) was observed in the entire population of 485 non-survival ICH patients, but show diversity by age, gender, and disease severity. After adjusting for confounding factors, a normalization of hs-cTnT concentrations was significantly associated with higher in-hospital death (odd's ratio 1.84, 95% CI: 1.31, 2.59, P=0.0005). Notably, patients with the highest quartile of hs-cTnT levels face a 6.98-fold higher risk of in-hospital death compared with those in the lowest quartile (OR 6.98, 95%CI 2.11-23.10; P=0.0015). More importantly, incorporating hs-cTnT into the conventional risk factor model significantly increased the C statistic in predicting in-hospital mortality (0.859 vs. 0.874; P= 0.0188). Further subgroup analyses suggested the additional prediction value of hs-cTnT was more sensitive to younger adults (P=0.0208), males (P=0.0189), and tend to those with severity ICH stage (P=0.0975). Interpretation: Elevated hs-cTnT is independently associated with an increased risk of in-hospital death. A combination of hs-cTnT and conventional risk factors promoted the prognostic value of ICH, in particular, sensitive to young adults, males, and severity stage of ICH, highlighting the value of heterogeneity and personalized care in the management of ICH. Funding Statement: This paper presents independent research funded by the significant application demonstration project of the Chengdu Science and Technology Bureau (2019-YF09-00211-SN). CY is supported by 1.3.5 project for disciplines of excellence, West China Hospital,Sichuan University (18HXFH010). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The Biomedical Research Ethics Committee of West China Hospital approved this study. The requirement for informed consent was waived for this retrospective analysis of anonymous data.

Gradient-Based Rapid Digital Immunoassay for High-Sensitivity Cardiac Troponin T (hs-cTnT) Detection in 1 μL Plasma.

Rapid and sensitive detection of biomarkers is the key to the diagnosis of acute diseases. One example is the detection of troponin in myocardial infarction. Here, we report a gradient-based digital immunoassay method, which can achieve high-sensitivity cardiac troponin T (hs-cTnT) detection with only 1 μL of plasma sample. We designed a multizone microfluidic channel functionalized with capture antibody specific to troponin. Taking advantage of limited sample volume, a troponin concentration gradient is created along the channel because of binding induced depletion. We quantified the concentration gradient by counting the detection antibody conjugated gold nanoparticles bound to different test zones with optical imaging. Differential counting between the zones removes most common noises and nonspecific bindings. The total analytical time is about 30 min, and the limit of quantification is 6.2 ng/L. We examined 41 clinical plasma samples from 15 patients and the change in hs-cTnT concentration in serial samples showed good linear correlation with clinical results (R2 = 0.98). Therefore, this simple and sensitive gradient-based digital immunoassay method is a promising technology for clinical hs-cTnT detection and could be adapted for detection of other biomarkers.

Potential role of high sensitivity cardiac troponin T in subclinical coronary atherosclerosis in systemic lupus erythematosus patients

Aim of the workTo determine the role of high sensitivity cardiac troponin T (HS cTnT) in subclinical coronary atherosclerosis in SLE patients at an apparent low risk for CVD according to traditional risk factors. Patients and methodsThe presence of subclinical coronary atherosclerosis was assessed by non-contract coronary computerized tomography and calcium score was measured using Agatston score in 30 SLE patients asymptomatic for CVD and 30 age and sex matched apparently healthy controls. SLE disease activity index (SLEDAI) was assessed. Serum HScTnT concentration was measured using enzyme-linked immunosorbent assay (ELISA). ResultsThe mean age of the patients was 33 ± 5.7 years, disease duration of 33.7 ± 22 months and mean SLEDAI 8.1 ± 5.02. The mean HS cTnT level was 12.8 ± 11.3 ng/L (1–36 ng/L). Their Framingham score was 4.8 ± 3.1 (1–12). Framingham score was low in both SLE patients (range 1–12%) and controls (1–9%) (p = 0.12). 11 (36.7%) patients, but none of the controls, had coronary artery calcification (CAC). Serum HScTnT concentration was detectable (>3 ng/L) in 16 (53.3%) patients and 2 (6.7%) control (p < 0.001). Interestingly, it was detectable in all patients with CAC, but in only 26.3% of patients without (p < 0.001). HScTnT significantly correlated with Agatston (r = 0.63, p = 0.04), with erythrocyte sedimentation rate (r = −0.65, p = 0.03), and with C-reactive protein (r = 0.76, p = 0.03) in SLE patients with CAC. ConclusionSerum HScTnT level is high and associated with CAC in SLE patients who are at an apparently low risk for CVD according to the Framingham risk score. HS cTnT may be a useful biomarker for SLE-associated subclinical atherosclerosis.