Rule-out Of Myocardial Infarction Research Articles

Diagnostic performance of bedside transthoracic echocardiography in the management of patients with suspected myocardial infarction

Abstract Introduction The diagnostic management of patients with symptoms indicative of acute myocardial infarction (MI) is largely based on the clinical assessment of symptoms, ECG and diagnostic algorithms based on high-sensitivity cardiac troponin (hs-cTn). Additionally, guidelines recommend transthoracic echocardiography (TTE) for patients neither eligible for rule-out nor rule-in. Purpose To assess the diagnostic performance of TTE in the diagnostic management of patients with suspected MI. Methods We conducted a prospective, observational cohort study enrolling consecutive patients presenting with symptoms suggestive of MI to the emergency department of a tertiary care hospital. Management was at the discretion of the treating physician. The final diagnosis was adjudicated by two independent cardiologists according to the 4th Universal Definition of MI. Evaluation in the emergency department included TTE with an assessment of left-ventricular (LV) function and regional wall motion abnormalities (WMA). We calculated diagnostic performance parameters (sensitivity, specificity, and negative and positive predictive value [NPV, PPV] with 95% confidence intervals) to rule-out or rule-in MI, respectively, for the presence of WMA. Performance was calculated for patients stratified to the observe and rule-in groups after application the ESC 0/1-hour algorithm using hs-cTnI. Patients without available TTE and those with STEMI were excluded. WMA were only reported if the acoustic window allowed a reasonable evaluation. Variables associated with the conduction of coronary angiography were studied using logistic regression. Results Overall, 2,163 patients with available TTE were included, of those 1,707 (78.9%) patients had data on WMA available, with 360 (21.1%) having any WMA (hypokinesia or akinesia) detected. Median age was 64 (51, 75) years, 1,383 (63.9%) were males and 383 (17.7%) were diagnosed with MI. Application of the ESC 0/1-hour algorithm resulted in assignment of 729 (42.9%) and 308 (18.6%) patients to the rule-out and -in groups, respectively, with 599 (38.5%) patients remaining in the observe group. Of these, 45 (7.5%) had MI. Performance of the ESC 0/1-hour algorithm was good and is shown in Figure 1. In the observe group, detection of WMA poorly identified patients with MI (PPV 12.7%, Figure 1). Absence of WMA resulted in moderate performance to rule-out MI (NPV 94.0%, Figure 1). Adjusted for age, sex, symptoms, baseline hs-cTnI, presence of ischemic signs on ECG and cardiovascular risk factors, the presence of WMA was significantly associated with the conduction of coronary angiography at index presentation (OR 2.7 [1.8, 4.0], p < 0.001). Conclusion The diagnostic value of bedside TTE is limited for the rule-out or -in of MI. Still, patients with prevalent WMA were significantly more likely to undergo coronary angiography.Performance of TTE in ESC 0/1-hour alg.

Prognostic impact of stepwise 0/1/3h rule-out of myocardial infarction using high-sensitivity troponin T

Abstract Background The European Society of Cardiology (ESC) recommends the application of 0/1h-algorithms for rapid triage of patients with suspected myocardial infarction (MI). These algorithms enable rule-out or rule-in of MI at presentation and after 1 hour (h), depending on absolute high-sensitivity cardiac troponin (hs-cTn) concentrations and changes. Recently, specific cut-offs to allow for additional 3h triage have been derived for hs-cTnT, to reduce the relevant proportion of patients remaining in the observe zone after 1h. However, the prognostic implications of this 3h rule-out option is unclear. Objective We aimed to evaluate and directly compare the prognostic impact of three rule-out options at 0, 1 and 3h for the composite endpoint of major adverse cardiac events (MACE) and all-cause mortality at 90 days and 3 years. Methods We prospectively enrolled patients presenting with suspected MI to the emergency department of a tertiary hospital in Germany. Concentrations of hs-cTnT were measured at presentation (0h), after 1h and 3h. Final diagnoses were centrally adjudicated by two physicians independently according to the 4th Universal Definition of MI. Patients were followed-up for 5 years to assess all-cause mortality and major adverse cardiac events (MACE), composited of cardiac rehospitalization, revascularization, MI excluding index events, and death. We triaged patients into three rule-out categories applying the 0/1/3h-algorithm. Kaplan-Meier survival curves were created for the three rule-out groups and compared using the log-rank test. Further, Cox regression analyses comparing the risk of death and MACE at 90 days and 3 years were performed in patients ruled-out after 1h and 3h compared to patients ruled-out at 0h (reference). Results In 2514 patients, median age was 64 years and 63.6% were men. Application of the 0/1/3h algorithm ruled-out 371 (14.8%) patients at 0h, 961 (38.2%) after 1h, and 179 (7.1%) after 3h. Median follow-up time was 4.59 [4.51, 4.75] years with a total of 732 patients experiencing MACE and 256 patients dying within 3 years. Incidence of MACE increased with later time of rule-out at 90 days (5.0% vs. 7.0% vs. 9.1%, p=0,19) and 3 years (16.2% vs. 20.8% vs. 32.3%, p<0.001; Figure 1A). The same trend was observed for all-cause mortality, reaching statistical significance at 3 years (2.3% vs. 4.0% vs. 9.5%, p<0.001; Figure 1B). In the Cox regression analyses at 3 years, patients ruled-out after 3h showed a doubled risk for MACE (hazard ratio 2.11 (95%CI; 1.44, 3.08), p<0.001) and quadrupled risk for death (hazard ratio 4.33 (95%CI; 1.85, 10.12), p<0.001) compared to patients ruled-out directly at 0h (Table 1). Conclusion Application of the 0/1/3h algorithm for triage of patients with suspected MI has predictive value regarding short- and long-term prognosis, with patients ruled-out after 3h showing significantly higher risk of MACE and death over three years as compared to rule-out after 0h and 1h.Figure 1Kaplan-Meier sural curvesTable 1Cox-regression

Performance of the High-STEACS Early Rule-Out Pathway for High Sensitivity Cardiac Troponin T at 30-days in a US population

Abstract Background The High-STEACS Early Rule-Out Pathway for High Sensitivity Cardiac Troponin T (hs-cTnT) is an algorithm designed to rule-out myocardial infarction (MI) in ED patients with symptoms concerning for acute coronary syndrome (ACS). High-STEACS was validated in the United Kingdom but has yet to be evaluated in the US. Purpose The objective of this secondary analysis of the STOP-CP (High Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification) United States (US) multicenter study is to determine the performance of the High-STEACS hs-cTnT Pathway in a multisite US cohort. Methods Patients (≥ 21 years old) presenting to the (ED) with symptoms suggestive of ACS were enrolled (1/25/2017-9/6/2018) at 8 US medical centers. Participants with 0- and 1-hour hs-cTnT measures were stratified into outpatient and admission dispositions using the established High-STEACS hs-cTnT cut-points. Cardiac death or MI and major adverse cardiovascular events (MACE; a composite of cardiac death, MI, and coronary revascularization) at 30-days were adjudicated. Negative and positive predictive values (NPV and PPV) and negative and positive likelihood ratios (-LR and +LR) for the High-STEACS pathway were calculated for each outcome with 95% confidence intervals. Results Overall, 1430 patients were studied. 54.2% (775/1430) were male with a mean age of 57.6 ± 12.8 years. At 30-days, 12.8% (183/1430) of patients experienced cardiac death or MI and 14.2% (203/1430) had MACE. High-STEACS classified 59.9% (857/1430) to the outpatient disposition and 40.1% (573/1430) to admission. Among patients stratified to the outpatient group, 1.9% (16/857) experienced cardiac death or MI and 3.4% (29/857) had MACE at 30-days. The NPV and -LR for High-STEACS were 98.1% (95%CI 97.0-98.9) and 0.13 (95%CI 0.08-0.21) for 30-day cardiac death or MI and 96.6% (95%CI 95.2-97.7) and 0.21 (95%CI 0.15-0.30) for 30-day MACE. For patients stratified to admission, 29.1% (167/573) had 30-day cardiac death or MI and 30.4% (174/573) had MACE. This yielded a PPV and +LR for 30-day cardiac death or MI of 29.1% (95%CI 25.5-33.1) and 2.8 (95%CI 2.6-3.1) and 30.4% (95%CI 26.6-34.3) and 2.6 (95%CI 2.4-2.9) for 30-day MACE. Conclusions The High-STEACS hs-cTnT Pathway stratified nearly 60% of patients to an outpatient disposition, but these patients had high rates of 30-day cardiac events. These findings suggest that providers should be cautious before using this pathway among US patients with possible ACS.

Sex Differences in the Diagnosis, Management, and Outcomes of Suspected Non-ST-Elevation Acute Coronary Syndromes Meeting Rapid Rule-Out Criteria.

(1) Background: patients who meet current rapid rule-out criteria for myocardial infarction (MI) are considered low risk, yet their management remains nebulous, especially among women. We aimed to examine sex differences in the diagnosis, management, and outcomes of patients meeting the rapid rule-out criteria. (2) Methods: by simulating application of the rapid rule-out MI criteria, we analyzed consecutively triaged men and women with suspected NSTE-ACS who had high-sensitivity cardiac troponin T (hs-cTnT) values that met criteria (n = 11,477), in particular, those who were admitted (n = 3775). (3) Results: men constituted ~55% of triaged patients who met the rule-out criteria, whether admitted or discharged. Men were more likely to be admitted (33.7% vs. 31.9%, p = 0.04), more commonly with hs-cTnT values between level of detection (LOD, 5 ng/ml) and the 99th percentile (59.4% of all admissions vs. 40.5% for women), whereas women were more likely to be admitted with values < level of blank (LOB, 3 ng/mL; 22.9% vs. 9.2% for men). Thirty-day mortality (1 man and 1 woman) and in-hospital MI (9 men vs. 1 woman) were uncommon among admitted patients, yet resource utilization during 3-4 hospitalization days was substantial for both sexes, with men undergoing coronary angiography (6.8% vs. 2.9%) and revascularization (3.4% vs. 1.1%) more commonly. Long-term survival for both men and women, whether admitted or discharged, was significantly worse for hs-cTnT values between LOD and the 99th percentile, even after adjusting for age and cardiovascular comorbidities. (4) Conclusions: reporting actual hs-cTnT values < 99th percentile allows for better risk stratification, especially for women, possibly closing the sex gap.

Personalized diagnosis in suspected myocardial infarction

BackgroundIn suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hs-cTn)-based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays.MethodsIn 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability (ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients.ResultsEleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline-recommended strategy.ConclusionWe developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care.Trial Registration numbersData of following cohorts were used for this project: BACC (www.clinicaltrials.gov; NCT02355457), stenoCardia (www.clinicaltrials.gov; NCT03227159), ADAPT-BSN (www.australianclinicaltrials.gov.au; ACTRN12611001069943), IMPACT (www.australianclinicaltrials.gov.au, ACTRN12611000206921), ADAPT-RCT (www.anzctr.org.au; ANZCTR12610000766011), EDACS-RCT (www.anzctr.org.au; ANZCTR12613000745741); DROP-ACS (https://www.umin.ac.jp, UMIN000030668); High-STEACS (www.clinicaltrials.gov; NCT01852123), LUND (www.clinicaltrials.gov; NCT05484544), RAPID-CPU (www.clinicaltrials.gov; NCT03111862), ROMI (www.clinicaltrials.gov; NCT01994577), SAMIE (https://anzctr.org.au; ACTRN12621000053820), SEIGE and SAFETY (www.clinicaltrials.gov; NCT04772157), STOP-CP (www.clinicaltrials.gov; NCT02984436),UTROPIA (www.clinicaltrials.gov; NCT02060760).Graphical

Diagnostic performance of a device for acoustic heart sound analysis in patients with suspected myocardial infarction

BackgroundAs only a small proportion of patients with chest pain suffers from myocardial infarction (MI), safe rule-out of MI is of immense importance. Recently an ultrasensitive microphone performing diastolic heart...

Suspected Non-ST-elevation acute coronary syndrome meeting rapid rule-out criteria: resource utilization, diagnostic yield, and clinical outcomes of hospital admission.

Many patients with suspected non-ST-elevation (NSTE) acute coronary syndromes (ACS) are admitted, even those with initial high-sensitivity cardiac troponins (hs-cTn) values who meet rapid rule-out criteria for myocardial infarction (MI). We examined the clinical outcomes, resource utilization, and diagnostic yield of suspected NSTE-ACS patients, who presented with hs-cTnT values meeting these criteria but were nevertheless hospitalized. Applying the 2020 European Society of Cardiology (ESC) rapid rule-out MI criteria, we identified consecutive patients with an initial value of hs-cTnT <5ng/L or an initial value of ≥5ng/L but <14ng/L (99th percentile) and a small increment in a subsequent test, who were nevertheless admitted. The majority (85.4%) of patients presented to the emergency department (ED) with suspected NSTE-ACS had an initial hs-cTnT <99th percentile. We examined 3775 admitted patients out of 11 477 patients who were triaged and met MI rule-out criteria. Only 0.32% (12 patients) of admitted patients experienced index MI or overall death within 30 days. Resource utilization in terms of ED stay, hospital stay, noninvasive and invasive tests was substantial, yet revascularization was uncommon (2.5%). Multivariate adjustment for age, gender, and baseline cardiovascular risk factors demonstrates similar survival of admitted vs. discharged patients (P=0.88). Initial hs-cTnT even below the 99th percentile provided a prognostic stratification for long term mortality. Our findings support a policy of ED discharge of suspected NSTE-ACS patients meeting rapid MI rule-out criteria and subsequent ambulatory evaluation, sparing resource-consuming admissions. In-hospital and ensuing prognosis were better with lower initial hs-cTnT values.

Diagnostic discrimination of a novel high-sensitivity cardiac troponin I assay and derivation/validation of an assay-specific 0/1h-algorithm

We aimed to assess the diagnostic utility of the Dimension EXL LOCI High-Sensitivity Troponin I (hs-cTnI-EXL) assay. This multicenter study included patients with chest discomfort presenting to the emergency department. Diagnoses were centrally and independently adjudicated by two cardiologists using all available clinical information. Adjudication was performed twice including serial measurements of high-sensitivity cardiac troponin (hs-cTn) I-Architect (primary analysis) and serial measurements of hs-cTnT-Elecsys (secondary analysis) in addition to the clinically used (hs)-cTn. The primary objective was to assess and compare the discriminatory performance of hs-cTnI-EXL, hs-cTnI-Architect and hs-cTnT-Elecsys for acute myocardial infarction (MI). Furthermore, we derived and validated a hs-cTnI-EXL-specific 0/1h-algorithm. Adjudicated MI was the diagnosis in 204/1454 (14%) patients. The area under the receiver operating characteristics curve for hs-cTnI-EXL was 0.94 (95%CI, 0.93-0.96), and comparable to hs-cTnI-Architect (0.95; 95%CI, 0.93-0.96) and hs-cTnT-Elecsys (0.93; 95%CI, 0.91-0.95). In the derivation cohort (n=813), optimal criteria for rule-out of MI were <9ng/L at presentation (if chest pain onset >3h) or <9ng/L and 0h-1h-change <5ng/L, and for rule-in ≥160ng/L at presentation or 0h-1h-change ≥100ng/L. In the validation cohort (n=345), these cut-offs ruled-out 56% of patients (negative predictive value 99.5% (95%CI, 97.1-99.9), sensitivity 97.8% (95%CI, 88.7-99.6)), and ruled-in 9% (positive predictive value 83.3% (95%CI, 66.4-92.7), specificity 98.3% (95%CI, 96.1-99.3)). Secondary analyses using adjudication based on hs-cTnT measurements confirmed the findings. The overall performance of the hs-cTnI-EXL was comparable to best-validated hs-cTnT/I assays and an assay-specific 0/1h-algorithm safely rules out and accurately rules in acute MI. ClinicalTrials.gov number, NCT00470587.

Shedding light on the grey zone: characterisation and predictors of poor outcome in patients with suspected myocardial infarction triaged to the observe zone

Abstract Background To facilitate a rapid triage of patients with suspected myocardial infarction (MI), the European Society of Cardiology (ESC) recommends the application of a 0/1h-algorithm based on cardiac troponin. Patients, in whom neither rule-in nor rule-out of MI is possible, are assigned to the observe zone. Management of these patients can be challenging due to their heterogeneous nature. We aimed to characterize patients in the observe zone and identify predictors of incident cardiovascular events in these patients. Methods Patients with suspected MI presenting to the emergency department of a German tertiary center were prospectively enrolled. High-sensitivity cardiac troponin I (hs-cTnI) was measured at baseline and after 1 hour. Based on the ESC 0/1h algorithm, patients were stratified into rule-in, rule-out and observe zones. The final diagnosis was adjudicated according to the 4th Universal Definition of MI. We performed uni- and multivariable Cox regression analyses to identify predictors of major cardiovascular events (MACE), defined as the composite of all-cause mortality, recurrent MI and cardiac hospitalisation at 1 year in the observe zone. Results We included 2491 patients, of which 1046 (42.0%) were triaged to the rule-out zone, 512 (20.6%) to the rule-in zone and 933 (37.4%) to the observe zone. Observe patients were significantly older (median age 71 years vs. 56 years for rule-out vs. 69 years for rule-in) and more often male than patients in the rule-in and rule-out zone, respectively (67.1% vs. 58.8% vs. 66.6%). Cardiovascular risk factors were comparably frequent in observe and rule-in patients, but significantly more common than in rule-out patients. Angiography and consecutive percutaneous interventions during the index presentation were performed less frequently in observe patients (22.6% and 9.2%) than in rule-in patients (62.5% and 36.5%) but more often than in rule-out patients (9.9% and 3.8%). Among observe patients, 50 (5.4%) were diagnosed with MI and 452 (48.4%) with acute or chronic myocardial injury. At 1 year, the rate of MACE in the observe zone was significantly higher (25.0%) than in rule-out patients (12.2%) but only slightly lower than in rule-in patients (29.7%). Univariable and consecutive multivariable analyses with a backward selection process identified atrial fibrillation, hs-cTnI at 1h, hypertension, diabetes and a higher NYHA class as independent predictors of MACE (Table 1). Conclusion About one third of patients with suspected MI are categorized into the observe zone. These patients had almost comparably poor outcome as rule-in patients. Atrial fibrillation, hs-cTnI at 1h, hypertension, diabetes and a higher NYHA class were identified as predictors of an impaired outcome. These predictors could contribute to improving the identification of subjects at high risk in the observe zone and thereby facilitate management of these patients. Funding Acknowledgement Type of funding sources: None.

Serial high-sensitivity troponin T concentrations and long-term outcomes in patients with suspected acute coronary syndrome

Abstract Background High-sensitivity troponin assays allow for accurate and rapid rule-in or rule-out of myocardial infarction (MI) among patients with acute-onset chest pain. However, prognostic implications of serial high-sensitivity troponin concentrations are unknown. Purpose To determine short- and long-term prognostic implications of high-sensitivity troponin T (hsTnT) concentrations and their changes from baseline, in patients with suspected acute coronary syndrome. Methods Retrospective cohort study based on Danish national registries. We identified all patients discharged from the hospital with either MI, unstable angina, suspected MI, or chest pain from January 2012 through December 2019 and merged these individuals with all records of two serial hsTnT measurements obtained ≤7 hours apart during the same hospitalization. The primary outcome was death at days 0–30 and 31–365. Prognostic implications of serial hsTnT were examined in accordance with the 2012 ESC algorithm stratifying patients for normal baseline concentrations and relative changes of 20% and 50% from baseline. In case of a normal baseline concentration, 20% and 50% of the upper reference level (14 ng/l) were used as thresholds instead, i.e., 3 ng/l and 7 ng/l, respectively. Absolute risks were calculated through multivariable logistic regression with average treatment effect modeling (G-formula). Results Complete data were available in 28,902 individuals (median age [25th-75th percentile] 65.2 [53.4–75.4] years, 11,632 [40.2%] women). Of these, 11,116 (38.5%) had a final diagnosis of MI, 1518 (5.3%) of unstable angina, and 16,268 (56.3%) of either suspected MI or chest pain. Median baseline hsTnT was 18 ng/l (25th-75th percentile, 10–69), second hsTnT 21 ng/l (25th-75th percentile, 10–248), relative hsTnT change 3.6% (25th-75th percentile, 0–66.7), and time between samples 4.0 hours (25th-75th percentile, 3.2–5.4). Most patients had either two normal hsTnT concentrations (9483, 32.8%) or two elevated hsTnT concentrations (18,235, 63.1%). At 30 days, 796 (2.8%) individuals had died, while an additional 1287 (4.6% of 30-day survivors) died between days 31–365. Baseline hsTnT and the relative hsTnT change both displayed a significant, non-linear association with death and interacted with each other (P&amp;lt;0.001). Tables 1 and 2 show the standardized, absolute risks of death (with 95% confidence intervals) from days 0–30 and from days 31–365, respectively. Patients with two normal hsTnT concentrations had very low mortality rates, irrespective of the magnitude of relative change. Conversely, patients with two elevated hsTnT concentrations consistently had high mortality rates. Conclusions This is the first study to assess both short- and long-term outcomes as a function of both baseline hsTnT and its change from first to second measurement. In general, patients with two normal hsTnT concentrations have an excellent prognosis while those with two elevated concentrations require scrutiny. Funding Acknowledgement Type of funding sources: None.

Impact of time from symptom onset on the diagnostic performance of high-sensitivity cardiac troponin for type 1 myocardial infarction

Abstract Background High-sensitivity cardiac troponin has enabled the rapid rule-out and rule-in of myocardial infarction at presentation. However, increases in cardiac troponin may not be detectable early after symptom onset, and uncertainty remains as to how time of symptom onset influences diagnostic performance. Purpose To evaluate the impact of time from symptom onset on the diagnostic performance of high-sensitivity cardiac troponin for type 1 myocardial infarction. Methods In a secondary analysis of a prospective multicentre randomised controlled trial of consecutive patients with suspected acute coronary syndrome, we evaluated the diagnostic performance of high-sensitivity cardiac troponin I measurements at presentation stratified by time of symptom onset to blood sampling. Diagnostic performance was evaluated in four groups (≤3 hours, 4–6 hours, 7–12 hours and &amp;gt;12 hours from symptom onset) for recommended thresholds to rule-out (sex-specific 99th centile and optimised threshold [64 ng/L]) type 1 myocardial infarction. Results This analysis included 41,104 patients (median 60 [interquartile range 49–74] years, 46% female) of which 12,595 (31%), 10,298 (25%), 7,171 (17%) and 11,040 (27%) presented ≤3 hours, 4–6 hours, 7–12 hours and &amp;gt;12 hours, respectively. Type 1 myocardial infarction was the adjudicated diagnosis in 3,692 (9%) patients. For the rule-out of type 1 myocardial infarction, sensitivity was highest in those tested 7–12 hours from symptom onset and lowest in those tested ≤3 hours. In early presenters, a threshold of &amp;lt;2 ng/L had greater sensitivity and negative predictive value (99.4% [95% CI 98.9 to 99.7%] and 99.7% [95% CI 99.5 to 99.9%]) compared to &amp;lt;5 ng/L (96.7% [95% CI 95.7 to 97.6%] and 99.3% [95% CI 99.1 to 99.5%], respectively). In those tested &amp;gt;3 hrs from symptom onset, the sensitivity and negative predictive value for both thresholds were similar, but a threshold of &amp;lt;5 ng/L correctly ruled out more patients (60% [17,056/28,506] versus 29% [8,316/28,506]). For the rule-in of myocardial infarction, the sensitivity of the 99th centile and 64 ng/L was lowest in patients tested within 3 hours (71.7% [95% CI 69.3 to 74.1%] and 46.5% [95% CI 44.1 to 49.2%], respectively), and increased in those tested later from symptom onset. The specificity and positive predictive value were highest when testing was performed 7–12 hours from symptom onset for the sex-specific 99th centile (92.4% [95% CI 91.8 to 93.0%] and 51.3% [95% CI 48.2–54.5%]) and 64 ng/L (96.2% [95% CI 95.7 to 96.7%] and 61.2% [95% CI 57.3 to 65.2%]). Conclusions The diagnostic performance of cardiac troponin for myocardial infarction is strongly influenced by the time from symptom onset to testing. In early presenters the limit of detection may facilitate immediate rule-out of myocardial infarction, but otherwise testing at least 3 hours from symptom onset is needed with the optimal time to rule-in myocardial infarction being 7–12 hours from the onset of symptoms. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation (BHF)Medical Research council UK (MRC)

Machine learning to optimise use of cardiac troponin in the diagnosis of acute myocardial infarction

Abstract Background Guidelines recommend fixed cardiac troponin thresholds for the assessment of patients with suspected acute coronary syndrome, however, performance varies in important patient groups as concentrations are influenced by age, sex and comorbidities. This limitation can be addressed using machine learning algorithms. Methods Machine learning algorithms were developed that integrate cardiac troponin concentrations at presentation or on serial testing with age, sex and clinical features in 10,038 consecutive emergency patients with suspected acute coronary syndrome. The primary outcome was an adjudicated diagnosis of type 1, type 4b or type 4c myocardial infarction. The best performing algorithm was selected for the CoDE-ACS (Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome) decision-support tool, and performance was externally validated in 3,035 patients pooled from three prospective studies. Findings CoDE-ACS had excellent discrimination and calibration using cardiac troponin at presentation (area under curve [AUC] 0.959, 95% confidence interval 0.948–0.971, Brier score 0.040), in the pooled external validation cohort. At presentation, the rule-out score identified 62.1% (1,885/3,035) of all patients as low-probability of myocardial infarction with a 99.5% (99.1–99.7%) negative predictive value and 97.0% (96.3–97.6%) sensitivity. The rule-in score identified 8.3% (252/3,035) of patients as high-probability with an 83.7% (82.4–85.0%) positive predictive value and 98.5% (98.0–98.9%) specificity. Performance of the rule-out and rule-in scores was consistent across patient subgroups (Figure 1 and Figure 2). CoDE-ACS incorporating a second cardiac troponin measurement also had excellent discrimination and calibration (AUC 0.971 [0.962–0.980], Brier score 0.039) and refined the individualised probabilities in the 29.5% (898/3,035) of patients neither ruled-out or ruled-in at presentation to guide further investigation. Conclusions We developed and externally validated the CoDE-ACS decision-support tool using machine learning to aid in the diagnosis of myocardial infarction. CoDE-ACS had excellent diagnostic performance to rule-out and rule-in myocardial infarction at presentation, performed consistently across patient subgroups, and provided individualised probabilities to guide further care in those who require serial troponin measurements. Conclusions We developed and externally validated the CoDE-ACS decision-support tool using machine learning to aid in the diagnosis of myocardial infarction. CoDE-ACS had excellent diagnostic performance to rule-out and rule-in myocardial infarction at presentation, performed consistently across patient subgroups, and provided individualised probabilities to guide further care in those who require serial troponin measurements. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health ResearchBritish Heart Foundation

Cost-minimisation analysis of acute myocardial infarction rule-out in low-risk patients: primary care emergency setting versus hospital setting

Abstract Background Hospital management of low-risk chest pain contributes to extensive use of healthcare resources and emergency department crowding. High efficacy rule-out, with subsequent reduction in costs and length of stay, has been demonstrated for the ESC 0/1-hour algorithm using high-sensitivity cardiac troponins (hs-cTn) in hospital cohorts. Purpose To estimate potential differences in healthcare costs by assessing patients with low risk for acute coronary syndromes (ACS) in a primary care emergency setting using the ESC 0/1-hour algorithm compared to routine management in a hospital setting. Methods This cost-minimisation analysis compared direct costs of applying the 0/1-hour algorithm in a low-risk primary care cohort to a low-risk chest pain cohort at a large general hospital in Norway. Data from the prospective OUT-ACS study (One-hoUr Troponin in a low-prevalence population of Acute Coronary Syndrome,[1] inclusion period 2016–2018) were used to calculate costs per patient at a primary care emergency clinic. For the hospital setting estimates, anonymous data were extracted for all low-risk chest pain patients treated at a large general hospital in 2018. Cost items include complete hospital costs per different diagnosis-related groups as defined in national assessments, as well as resource items required to use the algorithm in primary care, including personnel time and test- and treatment costs. Primary outcome was the difference in healthcare costs when assessing the low-risk cohort in a primary care setting compared to a hospital setting. The secondary outcome was the difference in length of stay. Results The costs of assessing the low-risk cohort at the primary care emergency clinic and the general hospital were estimated at €178 and €1480, respectively (Table 1). Thus, the estimated reduction in health care costs among patients assessable by the 0/1-hour algorithm outside of hospital was €1302 per patient, with a mean decrease in length of stay of 18.9 hours. Additional diagnostic procedures (e.g. stress ECG and echocardiogram) were performed in 31.9% (n=181/567) of the low-risk hospital cohort, which was part of the cost-driving estimate. Conclusion Assessment of patients considered as low-risk for ACS with the ESC 0/1-hour algorithm in a primary care emergency setting seems to decrease healthcare costs significantly, in addition to a reduction in both length of stay and potentially unnecessary hospitalisations. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Norwegian Research Fund for General PracticeThe Norwegian Committee on Research in General Practice

External validation of a high-sensitive troponin I algorithm for rapid evaluation of acute myocardial infarction in a Danish cohort.

An accelerated diagnostic algorithm for ruling-in or ruling-out myocardial infarction (MI) after 1 hour (1 h) has recently been derived and internally validated for the Siemens ADVIA Centaur TNIH assay. We aimed to validate the diagnostic performance of the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in a Danish cohort. Patients with chest pain suggestive of MI were prospectively enrolled. High-sensitive troponin I (TNIH) was measured at admission (0 h) and after 30 minutes (30 m), 1 h, and 3 hours (3 h). We externally validated the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in Danish patients. Moreover, we applied the algorithm using the second TNIH measurement at 30 m instead of 1 h. We enrolled 1003 patients: median (Q1-Q3) age 64 (52-74) years, 42% female, and 23% with previous MI. Myocardial infarction was the final diagnosis in 9% of patients. Median (Q1-Q3) times from admission to 30 m and 1 h blood draw were 35 min (30-37 min) and 67 min (62-75 min), respectively. Using the 0 h and 1 h results, 468 (47%) patients were assigned to rule-out, 104 (10%) to rule-in, and 431 (43%) to the observational zone. This resulted in a negative predictive value of 100% (95% confidence interval: 99.2-100%), sensitivity of 100% (95.9-100%), positive predictive value of 79.8 (70.8-87.0%), and specificity of 97.7% (96.5-98.6%). The diagnostic performance after 30 m was similar. The TNIH 0 h/1 h algorithm ad modum Boeddinghaus performed excellently for rule-out of MI in a Danish cohort. The Boeddinghaus algorithm also performed excellently after only 30 m. NCT03634384. Rapid Use of High-Sensitive Cardiac Troponin I for Ruling-in and Ruling-out Acute Myocardial Infarction (RACING-MI), https://clinicaltrials.gov/ct2/show/NCT03634384.

Single troponin measurement to rule-out acute myocardial infarction in early presenters

BackgroundA single high-sensitive cardiac troponin (hs-cTn) can be used to rule-out acute myocardial infarction (MI) in patients presenting >3 hours (3 h) after chest pain onset to the emergency department. This study aimed to investigate the safety of ruling-out MI in early presenters with chest pain ≤3 h using a single hs-cTnI at admission. MethodsWe prospectively enrolled patients presenting with chest pain suggestive of MI. Hs-cTnI (Siemens ADVIA Centaur TNIH, Limit of detection: 2.2 ng/L) was measured at admission. Two physicians adjudicated final diagnosis. A diagnostic cut-off value <3 ng/L was used to rule-out MI. Patients were classified as early (chest pain ≤3 h) or late presenters (>3 h). ResultsWe included 1370 patients with available admission hs-cTnI results: median (Q1–Q3) age 65 (52–74), female sex: 43%, previous MI: 22%. We confirmed MI in 118 (8.6%) patients. Overall, 470 (34%) patients were classified as early, 770 (56%) as late presenters, and 130 (9%) patients had unknown onset. When applying the diagnostic cut-off value, MI was correctly ruled-out at admission in 370 (27%) patients: 134 (29%) early presenters, 206 (27%) late presenters and 30 (23%) patients with unknown onset. This resulted in an overall negative predictive value of 100% (95% CI: 99.0–100%), with both 100% (97.3–100%) for early and 100% (98.2–100%) for late presenters, respectively. Sensitivity was similarly high in the two groups. ConclusionMI could be safely ruled-out in all patients presenting with chest pain ≤3 h when using a single hs-cTnI value <3 ng/L as diagnostic cut-off. Trial registration numberNCT03634384.

The association of anaemia and high-sensitivity cardiac troponin and its effect on diagnosing myocardial infarction.

Anaemia is common in patients with acute myocardial infarction (MI). We investigated the association of high-sensitivity cardiac troponin (hs-cTn) and haemoglobin (Hb) and the influence of anaemia on the performance of diagnostic protocols for suspected MI. Patients with suspected MI were consecutively enrolled at a tertiary centre. Final diagnoses were independently adjudicated by two cardiologists. Performance measures of hs-cTn-based algorithms were compared for anaemic and non-anaemic patients (Hb <12 g/dL in women and <13 g/dL in men). The influence of anaemia on survival (median follow-up 1.7 years) was investigated using multivariable cox-regression analysis and the association of Hb and hs-cTn by multivariable linear regression analysis. Overall, 2223 patients were included, of whom 415 (18.7%) had anaemia. In anaemic patients, the incidence of MI was similar; however, chronic myocardial injury was significantly more prevalent (20.1% vs. 48.2%). The negative predictive value to rule-out MI was similar for both algorithms and all assays in patients with anaemia, although the positive predictive value to rule-in MI was partly reduced for the 0/3-h algorithm. Fewer anaemic patients were triaged after 1 h. Anaemia was an independent predictor of death. Adjusted for patient characteristics, Hb was significantly associated with hs-cTn. By providing a point-based tool, the Hb-associated hs-cTn concentration and thus chronic myocardial injury may be predicted. Anaemia partly affects the rule-in, but not the rule-out of MI in hs-cTn-based diagnostic protocols. Hs-cTn concentrations and thus chronic myocardial injury may be predicted by clinical variables and Hb. clinicaltrials.gov (NCT02355457 and NCT03227159).

High-sensitivity cardiac troponin concentrations at presentation in patients with ST-segment elevation myocardial infarction

Abstract Background The widespread adoption of high-sensitivity cardiac troponin testing has encouraged the use of pathways to accelerate the rule-out and rule-in myocardial infarction in the Emergency Department. These pathways are not recommended for patients with ST-segment elevation, but there is a risk they may be applied incorrectly given that interpretation of the electrocardiogram is subjective, dependent on experience, and signs may be masked in those with posterior myocardial infarction. Methods Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge cluster randomized controlled trial across ten hospitals in Scotland. The index diagnosis was adjudicated two clinicians independently in all patients with high-sensitivity cardiac troponin I concentrations above the sex-specific 99th centile on serial testing and abnormalities on the electrocardiogram recorded. The proportion of patients with ST-segment elevation myocardial infarction and concentrations below the rule-out threshold (&amp;lt;5 ng/L), 99th centile (&amp;lt;16 ng/L and &amp;lt;34 ng/L for women and men) and rule-in threshold (&amp;lt;52 ng/L) at presentation were determined. Results In total 48,282 patients were recruited between June 2013, and March 2016 of which 22% (10,360/48,282) had peak cardiac troponin concentrations above the 99th centile. The adjudicated diagnosis was type 1 myocardial infarction in 55% (4,981/9,115) of patients and 10% (925/9,115) had ST-segment elevation myocardial infarction (age 65 [14] years, 68% men). The majority presented within 6 hours of symptom onset (67%, 619/925), and 84% (772/925) had cardiac troponin concentrations above the 99th centile at presentation. However, troponin concentrations were below the rule-out threshold in 2% (20/925) and the rule-in threshold in 26% (240/925) of patients with ST-segment elevation myocardial infarction. Discussion In patients with suspected acute coronary syndrome who have a final diagnosis of ST-segment elevation myocardial infarction, high-sensitivity cardiac troponin concentrations are below the rule-out and rule-in threshold at presentation in 1 in 50 and 1 in 4 patients, respectively. Clinicians should not rely on cardiac troponin concentrations to guide initial treatment decisions in patients with possible ST-segment elevation myocardial infarction. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Early diagnosis of myocardial infarction in patients presenting late after chest pain onset

Abstract Background The European Society of Cardiology (ESC) recommends the clinical use of the 0/1h-algorithms in patients with suspected acute coronary syndrome (ACS) to rule-out or rule-in non-ST elevation myocardial infarction (NSTEMI). However, the diagnostic performance of the ESC 0/1h-algorithms was only validated in patients presenting within 12 hours after chest pain onset (=early presenters) to the emergency department (ED). To this date, evidence regarding their performance in patients with chest pain onset &amp;gt;12h (=late presenters) is lacking. Purpose To evaluate the diagnostic performance of the ESC 0/1h-algorithms in late presenters. Methods We prospectively enrolled patients presenting to the ED with symptoms suggestive of ACS such as acute chest discomfort. Two independent cardiologists adjudicated the final diagnoses based on all available clinical information including serial hs-cTn concentrations, follow-up information and cardiac imaging. Hs-cTnT/I concentrations at 0h and 1h were measured in a blinded fashion. The primary diagnostic endpoint was the diagnostic performance of the hs-cTnT/I ESC 0/1h-algorithms in patients presenting late after chest pain onset compared to those presenting early. Diagnostic performance was quantified by safety of rule-out (sensitivity and negative predictive value), accuracy of rule-in (specificity and positive predictive value), and efficacy (proportion of patients) classified as rule-out or rule-in within 1 hour after presentation to the ED. The primary prognostic endpoint was all-cause mortality after 30-days and two-years in patients in whom NSTEMI was ruled-out by the ESC 0/1h-algorithms. Results Among 4733 patients, 308/4733 (7%) presented late to the ED. The ESC hs-cTnT 0/1h-algorithm ruled-out 185/308 (60%) of late presenters with a sensitivity of 100% (95% CI, 93.7–100) and a negative predictive value (NPV) of 100% (95% CI, 98.0–100). Sixty-one of 308 (20%) were ruled-in with a specificity of 95.2 (95% CI, 91.8–97.2) and a positive predictive value (PPV) of 80.3% (95% CI, 68.7–88.4). The remaining 62/308 (20%) were classified as observe with a NSTEMI prevalence of 13%. In comparison, 59% of early presenters were ruled-out (sensitivity 99.3% [95% CI, 98.4–99.7]; NPV 99.8 [99.5–99.9]), 17% were ruled-in (specificity 96.2 [95% CI, 95.5–96.8]; PPV 81.4 [95% CI, 78.4–84.0]), and 45% were classified as observe. Late presenters in whom NSTEMI was ruled-out had 30-day and two-year survival rates of 100% and 98.2%, respectively. Similar findings were made for the ESC hs-cTnI 0/1h-algorithm. Conclusion The ESC hs-cTnT/I algorithms also provide excellent diagnostic performance for early triage and specifically safe rule-out of NSTEMI in patients presenting late after chest pain onset to the ED. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss Heart Foundation, Swiss National Science Foundation

Short-term prognosis of unstable angina in the era of high-sensitivity cardiac troponin: insights for early rule-out strategies.

It is unclear if strategies to rule-out myocardial infarction (MI) based on a single high-sensitivity troponin T (hsTnT) measurement at the emergency department (ED) presentation may also exclude unstable angina. We measured hsTnT ex-post on the admission frozen blood sample of 644 subjects with Braunwald IIIB CK-MB-negative unstable angina. This analysis included the 240 patients with hsTnT value ≤99th percentile reference limit (UA). We evaluated the clinical outcome of UA patients and the applicability of two rule-out strategies based on the combination of a non-ischemic ECG with (1) a single hsTnT value below the Limit-of-Detection (LoD), (2) a TIMI risk score ≤1. UA patients with hsTnT ≤99th percentile reference limit had a favorable 30-day outcome [0.8% MI, 0% cardiovascular death (CVD)], but the rate of CVD/MI at 180-day was 4.7%. Sensitivities for UA were 94.6% according to the 'TIMI ≤1-strategy' and 75.4% according to 'hsTnT-below-LoD-strategy', accounting for 5.4 and 24.6% missed diagnoses, respectively. A prognostic risk stratification to guide appropriate outpatient assessment in potential discharged unrecognized UA patients was developed: a risk score based on the combination of age >60 years and C-reactive protein >4.5 mg/L effectively stratified the 180-day CVD/MI occurrence: 0, 2.5 and 12.7% for score 0, 1 and 2 (log-rank = 0.001, C-statistic = 0.776). Single measurement hsTnT strategies, successfully tested to rule-out MI, may allow safe ED discharge of patients with a suspected acute coronary syndrome: even if UA may not be excluded, its short-term prognosis is favorable. UA patients with a C-reactive protein >4.5 mg/L and older than 60 years have a substantial medium-term cardiovascular risk and may benefit from a timely outpatient diagnostic assessment.

LO17: Major adverse cardiac events in patients ruled-out by a validated high-sensitivity troponin algorithm for acute myocardial infarction

Introduction: Chest pain and symptoms of acute coronary syndrome are a leading cause of emergency department (ED) visits in Canada. Validated 2-hour high-sensitivity troponin algorithms can rapidly and accurately rule-in or rule-out myocardial infarction (MI) in most patients. The objective of this study was to quantify the incidence and timing of major adverse cardiac events (MACE: MI, death, or urgent revascularization) in the 30-days following the index ED encounter among patients who had MI ruled out using a 2-hour high-sensitivity troponin T (hs-cTnT) algorithm. We also sought to identify patient characteristics associated with very low risk of MACE. Methods: This was a secondary analysis of data prospectively collected from adult patients presenting with a primary complaint of chest pain or symptoms of ACS. This analysis focused on patients who had an MI ruled out using a validated 2-hour serial hs-cTnT diagnostic algorithm. Incidence of 30-day MACE was quantified. Sex-specific Kaplan-Meier curves were constructed to describe timing of MACE events after MI rule-out. Demographic and clinical variables of patients who did or did not have MACE were compared using simple bivariable analyses. Results: This analysis included 550 patients with serial 2h hs-cTnT testing. Of these, MI was ruled out in 344 (62.5% of patients), ruled in 67 (12.2%), and 139 (25.3%) had nondiagnostic hs-cTnT results. Among the 344 patients who had MI ruled out, 11 (3.2%) experienced a MACE in the 30 days following their index ED encounter. These included 10 (2.9%) unplanned revascularizations and 1 (0.3%) fatal MI. MACE occurred at a median of 5 days (range: 0-23 days) after the index ED encounter. Of the 11 patients experiencing MACE, 9 (81.8%) had a normal ECG at their index ED encounter. None of the 93 (27.0%) ruled-out patients under the age of 50 experienced a MACE in the follow-up period. Patients experiencing MACE were more likely to have a history of coronary disease and multiple vascular risk factors compared to those not experiencing MACE. Conclusion: The validated 2h hs-cTnT AMI algorithm ruled-out MI in a large proportion of patients. The 30-day MACE incidence after MI rule-out was 3%. Most MACE events were unplanned revascularizations. We determined that age &lt; 50 was associated with event-free survival and may be of value in identifying patients who do not need additional cardiac testing after MI has been ruled out using high-sensitivity troponin testing.