Validation of a 0/1 h Algorithm for Rapid Diagnosis of Myocardial Infarction Using a High-Sensitivity Troponin I Assay.

BACKGROUND: Current guidelines recommend 0/1 h algorithms using high-sensitivity cardiac troponin (hs-cTn) for fast diagnosis of myocardial infarction (MI). Yet, for some assays, existing data is limited. We aimed to evaluate the diagnostic performance and the prognostic value of a rapid 0/1 h algorithm for the Access hs-cTnI assay. METHODS: In consecutive patients presenting with suspected MI, we measured concentrations of Access hs-cTnI at presentation and after 1 hour. Final diagnosis was adjudicated independently by 2 cardiologists. Parameters for diagnostic performance were calculated, applying the recently derived European Society of Cardiology (ESC) 0/1 h algorithm for Access hs-cTnI. Additionally, we assessed the prognostic utility of Access hs-cTnI for the composite end point of all-cause mortality and incident MI at 3 years. RESULTS: In 1879 patients, 257 non-ST-elevation MIs occurred. Application of the 0/1 h algorithm classified 44.5% as rule-out, 20.3% as rule-in, and triaged 35.1% to the observe group. High rule-out safety was confirmed with a sensitivity of 97.7% (95% CI, 95.0%-99.1%) and a negative predictive value of 99.3% (95% CI, 98.4%-99.7%). Rule-in capacity was moderate with a specificity of 88.0% (95% CI, 86.3%-89.6%) and a positive predictive value of 50.8% (95% CI, 45.7%-55.9%). After exclusion of patients with ST-elevation MI the results showed strong prognostic value, even after adjustment for cardiovascular risk factors and comorbidities, with adjusted hazard ratios of 2.51 (95% CI, 1.56-4.04) in the observe and 3.55 (95% CI, 2.18-5.79) in the rule-in group for the composite end point of all-cause mortality and incident MI at 3 years, compared to ruled-out patients. CONCLUSION: The ESC 0/1 h algorithm for Access hs-cTnI allows safe and efficient triage of patients with suspected MI and has strong prognostic utility up to 3 years after the initial evaluation.

Diagnostic Validation of a High-Sensitivity Cardiac Troponin I Assay.

BACKGROUND: Emergency departments worldwide are increasingly adopting rapid diagnosis of patients with suspected myocardial infarction (MI) based on high-sensitivity troponin. We set out to assess the diagnostic accuracy of a high-sensitivity cardiac troponin I (hs-cTnI) assay in a prospective study. METHODS: In a cohort study including 1800 patients presenting with suspected acute MI, we developed and temporally validated a 0/1 h diagnostic algorithm using the Siemens Atellica IM hs-cTnI assay. The algorithm was established in the first 928 patients and validated in the following 872 patients. RESULTS: The derived algorithm consisted of a baseline rule-out of non-ST-segment elevation MI using a cutoff <3 ng/L in patients with symptom onset ≥3 h or an admission troponin I level <6 ng/L with a Δ change of <3 ng/L from 0 h to 1 h. For rule-in, an admission troponin I level ≥120 ng/L or an increase within the first hour ≥12 ng/L was required. Application of the algorithm to the validation cohort showed a negative predictive value of 99.8% (95% CI, 98.7%-100.0%), sensitivity of 99.1% (95% CI, 95.1%-100.0%), and 48.3% of patients ruled out, whereas 15.1% were ruled in with a positive predictive value of 68.0% (95% CI, 59.1%-75.9%) and specificity of 94.4% (95% CI, 92.5%-96.0%). The diagnostic performance was comparable to guideline-recommended application of an established hs-cTnI assay in a rapid 0/1 h strategy. CONCLUSIONS: The Siemens hs-cTnI assay is well suited for application in rapid diagnostic stratification of patients with suspected MI. STUDY REGISTRATION: www.clinicaltrials.gov (NCT02355457).

Clinical application of the 4th Universal Definition of Myocardial Infarction.

AIMS: The recently released 4th version of the Universal Definition of Myocardial Infarction (UDMI) introduces an increased emphasis on the entities of acute and chronic myocardial injury. We applied the 4th UDMI retrospectively in patients presenting to the emergency department with symptoms potentially indicating myocardial infarction (MI) to investigate its effect on diagnosis and prognosis. METHODS AND RESULTS: We included 2302 patients presenting to the emergency department with symptoms suggestive of MI. The final diagnosis was adjudicated sequentially according to the 3rd and 4th UDMI. Reclassification after readjudication was assessed. Established diagnostic algorithms for patients with suspected MI were applied to compare diagnostic accuracy. All patients were followed to assess mortality, recurrent MI, revascularization, and rehospitalization to investigate the effect of the 4th UDMI on prognosis. After readjudication, 697 patients were reclassified. Most of these patients were reclassified as having acute (n = 78) and chronic myocardial injury (n = 585). Four hundred and thirty-four (18.9%) patients were diagnosed with MI, compared with 501 (21.8%) MIs when adjudication was based on the 3rd UDMI. In the non-MI population, patients with myocardial injury (n = 663) were older, more often female and had worse renal function compared with patients without myocardial injury (n = 1205). Application of diagnostic algorithms for patients with suspected MI revealed a high accuracy after readjudication. Reclassified patients had a substantially higher rate of cardiovascular events compared with not-reclassified patients, particularly patients reclassified to the category of myocardial injury. CONCLUSION: By accentuating the categories of acute and chronic myocardial injury the 4th UDMI succeeds to identify patients with higher risk for cardiovascular events and poorer outcome and thus seems to improve risk assessment in patients with suspected MI. Application of established diagnostic algorithms remains safe when using the 4th UDMI.

Immediate Rule-Out of Acute Myocardial Infarction Using Electrocardiogram and Baseline High-Sensitivity Troponin I.

AIMS: Serial measurements of high-sensitivity troponin are used to rule out acute myocardial infarction (AMI) with an assay specific cutoff at the 99th percentile. Here, we evaluated the performance of a single admission troponin with a lower cutoff combined with a low risk electrocardiogram (ECG) to rule out AMI. METHODS: Troponin I measured with a high-sensitivity assay (hs-TnI) was determined at admission in 1040 patients presenting with suspected AMI (BACC study). To rule out AMI we calculated the negative predictive value (NPV) utilizing the optimal hs-TnI cutoff combined with a low risk ECG. The results were validated in 3566 patients with suspected AMI [2-h Accelerated Diagnostic Protocol to Assess Patients With Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker (ADAPT) studies]. Patients were followed for 6 or 12 months. RESULTS: 184 of all patients were diagnosed with AMI. An hs-TnI cutoff of 3 ng/L resulted in a NPV of 99.3% (CI 97.3-100.0), ruling out 35% of all non-AMI patients. Adding the information of a low risk ECG resulted in a 100% (CI 97.5-100.0) NPV (28% ruled out). The 2 validation cohorts replicated the high NPV of this approach. The follow-up mortality in the ruled out population was low (0 deaths in BACC and Stenocardia, 1 death in ADAPT). CONCLUSIONS: A single hs-TnI measurement on admission combined with a low risk ECG appears to rule out AMI safely without need for serial troponin testing. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02355457).

Diagnostic and prognostic value of the sex-specific 99th percentile of four high-sensitivity cardiac troponin assays in patients with suspected myocardial infarction.

AIMS: High-sensitivity cardiac troponin (hs-cTn) assays are used for detection of myocardial infarction (MI). Ninety-ninth percentiles show wide inter-assay variation. The use of sex-specific cut-offs is recommended as definitory cut-off for MI. We compared diagnostic performance and prognostic value of sex-specific 99th percentiles of four hs-cTn assays in patients with suspected MI. METHODS AND RESULTS: Concentrations of four hs-cTn assays were measured at presentation and after 3 h in patients with suspected MI. Final diagnoses were adjudicated according to the 4th Universal Definition of MI. Unisex and sex-specific 99th percentiles were evaluated as diagnostic cut-offs following the ESC 0/3 h algorithm. These cut-offs were used in Cox-regression analyses to investigate the association with a composite endpoint of MI, revascularization, cardiac rehospitalization, and death. Non-ST-elevation MI was diagnosed in 368 of 2718 patients. Applying the unisex 99th percentile, Elecsys hs-cTnT provided highest negative predictive value (NPV) of 99.7 and a positive predictive value (PPV) of 75.9. The analysed hs-cTnI assays showed slightly lower NPVs and comparable PPVs [Architect (NPV 98.0, PPV of 71.4); Atellica (NPV 97.7, PPV of 76.1); Pathfast (NPV 97.7, PPV of 66.6)]. Application of sex-specific 99th percentiles did not significantly affect diagnostic performance. Concentrations above 99th percentile were independent predictors for impaired long-term outcome (hazard ratios 1.2-1.5, P < 0.001). CONCLUSION: We describe a good diagnostic accuracy of four hs-cTn assays using the assay-specific 99th percentile for detection of MI. Application of sex-specific 99th percentiles did neither affect diagnostic performance nor prognostic value significantly. Finally, values above the 99th percentile were associated with poor long-term outcome.

Impact of Quantitative ST-T Analysis in Patients With Suspected Myocardial Infarction Presenting With Right Bundle Branch Block.

BACKGROUND: While left bundle branch block (LBBB) is a well-known risk feature in patients with acute myocardial infarction, and a rapid invasive management is recommended, data supporting this strategy for patients with right bundle branch block (RBBB) is less robust. METHODS: In total, 2139 patients with suspected ST-elevation myocardial infarction (STEMI) were triaged to acute coronary angiography based on a prehospital 12-lead electrocardiogram (ECG). Sensitivity and specificity for STEMI-ECG criteria were compared in RBBB and non-BBB patients. Adjusted hazard ratios for 1-year overall mortality were computed. RESULTS: STEMI was adjudicated in 1832/2139 (85.6%) of all patients and in 102/117 (87.2%) of RBBB patients. ST-segment deviation followed typical ST-T patterns in most RBBB patients. Of 17 RBBB patients without significant ST changes, STEMI was adjudicated in 14 (82%). Diagnostic accuracy of STEMI criteria was comparable in RBBB and non-RBBB patients for inferior (sensitivity: 51.1% vs 59.1%, P = .14; specificity: 66.7% vs 52.1%, P = .33) and anterior STEMI (sensitivity: 35.2% vs 36.6%, P = .80; specificity: 58.3% vs 49.5%, P = .55). Diagnostic performance was lower for lateral STEMI in RBBB patients (sensitivity: 14.8% vs 4.4%, P = .001; specificity: 75.0% vs 98.4%, P < .001). Patients with RBBB had higher 1-year mortality compared with non-BBB patients (hazard ratio 2.3%; 95% confidence interval, 1.25-4.21. CONCLUSION: ECG criteria used for detection of STEMI showed comparable diagnostic accuracy in RBBB and non-BBB patients. However, STEMI was frequently present in RBBB patients not fulfilling diagnostic ECG criteria. RBBB patients showed poorer outcome after 1 year. Consequently, the presence of RBBB in suspected STEMI cases signifies a high-risk feature, aligning with established guidelines.

Pre-hospital admission of heparin in patients with suspected non-ST segment elevation acute coronary syndrome.

BACKGROUND: Evidence supporting pre-hospital heparin administration in patients with suspected non-ST segment elevation acute coronary syndrome (NSTE-ACS) is lacking. We aim to evaluate if pre-hospital heparin administration by emergency medical service improves clinical outcome in patients with suspected NSTE-ACS. METHODS: Patients with suspected myocardial infarction (MI) presenting to the emergency department were prospectively enrolled from 2013 to 2021, excluding those with ST segment elevation MI. Patients with and without prehospital heparin administration were compared using propensity score matching. To assess the association between pre-hospital heparin loading, 30-day and 1-year mortality, Kaplan-Meier estimations and Cox regression models were used. RESULTS: Among 1,234 patients, median age was 69 years, 755 (61.2%) were male, 867 (70.5%) with known hypertension, 177 (14.4%) had diabetes, 280 (23.1%) were current smokers, and 444 (36.0%) had a history of CAD. Compared to patients without pre-hospital heparin administration, heparin pre-treated patients were more often active smokers (26.5% vs. 20.8%). After propensity matching, 475 patients with vs. without pre-hospital heparin administration were compared, with no significant difference in 30-day mortality (no-heparin 1.3% vs. heparin 0.4%) and 1-year mortality (no-heparin 7.2% vs. heparin 5.5%, adjusted HR 0.98, CI 0.95-1.01, p = 0.22). Bleeding events occurred at a low frequency (< 2%) and did not differ between groups. CONCLUSIONS: In this study, pre-hospital heparin administration was not associated with improved clinical outcome in patients with suspected NSTE-ACS. These findings question pre-hospital heparin therapy in this patient population and might potentially warrant a more restricted utilization pending in-hospital risk assessment.

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

BACKGROUND: As 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 sound analysis (CADScorSystem) for rule-out of coronary artery disease (CAD) has emerged. In this explorational study, we aimed to evaluate the feasibility of the CADScorSystem for diagnosis of MI in the setting of a large emergency department. METHODS: Patients presenting to the emergency department with suspected MI were included. Acoustic heart sound analysis was performed in all patients and automated CAD-score values were calculated via a device-embedded algorithm, which also requires inclusion of three clinical variables: age, sex and presence of hypertension. Patients additionally received serial high-sensitive troponin T measurement measurements to assess the final diagnosis according to third Universal Definition of Myocardial Infarction applying the European Society of Cardiology 0 hour/3 hours algorithm. Diagnostic parameters for MI, considering different CAD-score cut-offs, were computed. RESULTS: Of 167 patients, CAD-scores were available in 61.1%. A total of eight patients were diagnosed with MI. At a cut-off value of <20, CAD-score had a negative predictive value (NPV) of 90.7 (78.4-96.3). The corresponding positive predictive value (PPV) was 6.8 (2.7-16.2). For the adjusted CAD-score (age, sex, hypertension), at a cut-off value of <20, NPV was 90.0 (59.6-99.5) with a PPV of 10.8 (5.3-20.6). CONCLUSION: In this explorative analysis, a transcutaneous ultrasensitive microphone for heart sound analysis resulted in a high NPV analogous to the findings in rule-out of stable CAD in elective patients yet inferior to serial high-sensitivity cardiac troponin measurements and does not seem feasible for application in an emergency setting for rule-out of MI. TRIAL REGISTRATION NUMBER: NCT02355457.

Prognostic utility of a multi-biomarker panel in patients with suspected myocardial infarction.

BACKGROUND: The accurate identification of patients with high cardiovascular risk in suspected myocardial infarction (MI) is an unmet clinical need. Therefore, we sought to investigate the prognostic utility of a multi-biomarker panel with 29 different biomarkers in in 748 consecutive patients with symptoms indicative of MI using a machine learning-based approach. METHODS: Incident major cardiovascular events (MACE) were documented within 1 year after the index admission. The selection of the best multi-biomarker model was performed using the least absolute shrinkage and selection operator (LASSO). The independent and additive utility of selected biomarkers was compared to a clinical reference model and the Global Registry of Acute Coronary Events (GRACE) Score, respectively. Findings were validated using internal cross-validation. RESULTS: Median age of the study population was 64 years. At 1 year of follow-up, 160 cases of incident MACE were documented. 16 of the investigated 29 biomarkers were significantly associated with 1-year MACE. Three biomarkers including NT-proBNP (HR per SD 1.24), Apolipoprotein A-I (Apo A-I; HR per SD 0.98) and kidney injury molecule-1 (KIM-1; HR per SD 1.06) were identified as independent predictors of 1-year MACE. Although the discriminative ability of the selected multi-biomarker model was rather moderate, the addition of these biomarkers to the clinical reference model and the GRACE score improved model performances markedly (∆C-index 0.047 and 0.04, respectively). CONCLUSION: NT-proBNP, Apo A-I and KIM-1 emerged as strongest independent predictors of 1-year MACE in patients with suspected MI. Their integration into clinical risk prediction models may improve personalized risk stratification. Prognostic utility of a multi-biomarker approach in suspected myocardial infarction. In a cohort of 748 patients with symptoms indicative of myocardial infarction (MI) to the emergency department, we measured a 29-biomarker panel and performed regressions, machine learning (ML)-based variable selection and discriminative/reclassification analyses. We identified three biomarkers as top predictors for 1-year major adverse cardiovascular events (MACE). Their integration into a clinical risk prediction model and the Global Registry of Acute Coronary Events (GRACE) Score allowed for marked improvement in discrimination and reclassification for 1-year MACE. Apo apolipoprotein; CRP C-reactive protein; CRS clinical risk score; ECG electrocardiogram; EN-RAGE extracellular newly identified receptor for advanced glycation end-products binding protein; FABP fatty acid-binding protein; GS Grace Score; hs-cTnI high-sensitivity cardiac troponin I; KIM-1 kidney injury molecule-1; LASSO least absolute shrinkage and selection operator; MACE major adverse cardiovascular events; MI myocardial infarction; NRI net reclassification improvement; NT-proBNP N-terminal prohormone of brain natriuretic peptide.

Long-term outcome of patients presenting with myocardial injury or myocardial infarction.

AIMS: Patients with acute or chronic myocardial injury are frequently identified in the context of suspected myocardial infarction (MI). We aimed to investigate their long-term follow-up. METHODS AND RESULTS: We prospectively enrolled 2714 patients with suspected MI and followed them for all-cause mortality and a composite cardiovascular endpoint (CVE; cardiovascular death, MI, unplanned revascularization) for a median of 5.1 years. Final diagnoses were adjudicated by two cardiologists according to the Fourth Universal Definition of MI, including 143 (5.3%) ST-elevation MI, 236 (8.7%) non-ST-elevation MI (NSTEMI) Type 1 (T1), 128 (4.7%) NSTEMI T2, 86 (3.2%) acute and 677 (24.9%) with chronic myocardial injury, and 1444 (53.2%) with other reasons for chest pain (reference). Crude event rates per 1000 patient-years for all-cause mortality were highest in patients with myocardial injury (81.6 [71.7, 92.3]), and any type of MI (55.9 [46.3, 66.7]), compared to reference (12.2 [9.8, 15.1]). Upon adjustment, all diagnoses were significantly associated with all-cause mortality. Moreover, patients with acute (adj-HR 1.92 [1.08, 3.43]) or chronic (adj-HR 1.59 [1.16, 2.18]) myocardial injury, and patients with NSTEMI T1 (adj-HR 2.62 [1.85, 3.69]) and ST-elevation MI (adj-HR 3.66 [2.41, 5.57]) were at increased risk for cardiovascular events. CONCLUSION: Patients with myocardial injury are at a similar increased risk for death and cardiovascular events compared to patients with acute MI. Further studies need to determine appropriate management strategies for patients with myocardial injury. REGISTRATION: Clinicaltrials.gov (NCT02355457).

Rising and Falling High-Sensitivity Cardiac Troponin in Diagnostic Algorithms for Patients With Suspected Myocardial Infarction.

Background High-sensitivity cardiac troponin (hs-cTn)-based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs-cTnI and hs-cTnT and applied the European Society of Cardiology 0/1- and 0/3-hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs-cTnI study population. The positive predictive value for patients with an FP was significantly reduced compared with patients with an RP (0/1-hour: FP, 53.3% [95% CI, 45.0-61.4] versus RP, 76.9 [95% CI, 71.6-81.7]; 0/3-hour: FP, 56.9% [95% CI, 42.2-70.7] versus RP, 78.1% [95% CI, 74.0-81.8]). The proportion of patients in the observe zone was larger in the FP using 0/1-hour (31.3% versus 55.8%) and 0/3-hour (14.6% versus 38.6%) algorithms. Alternative cutoffs did not improve algorithm performances. Compared with stable hs-cTn, the risk for death or MI was highest in those with an FP (adjusted hazard ratio [HR], hs-cTnI 2.3 [95% CI, 1.7-3.2]; RP adjusted HR, hs-cTnI 1.8 [95% CI, 1.4-2.4]). Findings were similar for hs-cTnT tested in 3647 patients overall. Conclusions The positive predictive value to rule in MI by the European Society of Cardiology 0/1- and 0/3-hour algorithms is significantly lower in patients with FP than RP. These are at highest risk for incident death or MI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02355457, NCT03227159.

Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes.

Background: While cardiac-specific troponin (cTn) allows for rapid diagnosis of acute type 1 myocardial infarction (T1MI), its performance to differentiate acute myocardial injury (AI) or type 2 myocardial infarction (T2MI) is limited. The objective was to combine biomarkers to improve discrimination of different myocardial infarction (MI) aetiologies. Methods: We determined levels of cardiac troponin T and I (cTnT, cTnI), cardiac myosin-binding protein C (cMyBP-C), NT-proBNP and ten miRNAs, known to be associated with cardiac pathology in a total of n = 495 serial plasma samples at three time points (on admission, after 1 h and 3 h) from 57 NSTEMI (non-ST-elevation myocardial infarction), 18 AI, and 31 STEMI patients, as defined by fourth universal definition of MI (UDMI4) and 59 control individuals. We then applied linear mixed effects model to compare the kinetics of all molecules in these MI sub-types. Results: Established (cTnT, cTnI) and novel (cMyBP-C) cardiac necrosis markers failed in differentiating T1MI vs T2MI at early time points. All cardiac necrosis markers were higher in T1MI than in T2MI at 3 h after admission. Muscle-enriched miRNAs (miR-1 and miR-133a) were correlated with cardiac necrosis protein markers and did not offer better discrimination. Established cardiac strain marker NT-proBNP differentiated AI and T1MI at all time points but failed to discriminate T2MI from T1MI. However, the combination of NT-proBNP and cTnT along with age returned an overall AUC of 0.76 [95 % CI 0.67-0.84] for differentiating T1MI, T2MI and AI. Conclusions: Rather than using single biomarkers of myocardial necrosis, a combination of clinical biomarkers for cardiac necrosis (troponin) and cardiac strain (NT-proBNP) might aid in differentiating T1MI, T2MI and AI.

Prognostic Implications of a Second Peak of High-Sensitivity Troponin T After Myocardial Infarction.

BACKGROUND: After an acute myocardial infarction (MI), repeated measurement of cardiac biomarkers is commonly performed, although not recommended in current guidelines. There is only limited data on the kinetics of troponin in this phase. For high-sensitivity cardiac troponin T (hs-cTnT), but not high-sensitivity cardiac troponin I (hs-cTnI), late increases in terms of a second peak have been described. Their impact on the prognosis of patients with MI remains unclear. METHODS: We included 2,305 patients presenting to the emergency department with symptoms suggestive of MI. Five hundred and seven were diagnosed with MI. Hs-cTnT, creatine kinase (CK) and the MB fraction of CK (CK-MB) were measured at admission, after 1 and 3 h and thereafter as indicated by the treating physician. A mixed-model approach was applied for modeling the biomarker kinetics. All patients were followed up to assess a composite endpoint of mortality, recurrent MI, revascularization and rehospitalization and to investigate the effect of a second hs-cTnT peak on prognosis. RESULTS: Out of 507 patients with MI, 192 had a sufficient amount of hs-cTnT measurements after the index MI. In 111 (57.8%) patients a second hs-cTnT peak was found after 4.48 days. For CK and CK-MB a second peak could not be identified. Regarding the composite endpoint there was no significant difference between patients with and without a second hs-cTnT peak. CONCLUSION: In our analyses, a second peak of hs-cTnT after an acute MI was common, but not associated with poorer outcome. Thus, the clinical value of hs-cTnT for monitoring myocardial ischemia might be limited in this phase and other biomarkers might be more suitable.Trial Registration: www.ClinicalTrials.gov, identifier: NCT02355457, Date of registration: February 4, 2015.

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

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: clinicaltrials.gov (NCT02355457 and NCT03227159).

A Biomarker Model to Distinguish Types of Myocardial Infarction and Injury.

BACKGROUND: Discrimination among patients with type 1 myocardial infarction (T1MI), type 2 myocardial infarction (T2MI), and myocardial injury is difficult. OBJECTIVES: The aim of this study was to investigate the discriminative value of a 29-biomarker panel in an emergency department setting. METHODS: Patients presenting with suspected myocardial infarction (MI) were recruited. The final diagnosis in all patients was adjudicated on the basis of the fourth universal definition of MI. A panel of 29 biomarkers was measured, and multivariable logistic regression analysis was used to evaluate the associations of these biomarkers with the diagnosis of MI or myocardial injury. Biomarkers were chosen using backward selection. The model was internally validated using bootstrapping. RESULTS: Overall, 748 patients were recruited (median age 64 years), of whom 138 had MI (107 T1MI and 31 T2MI) and 221 had myocardial injury. In the multivariable model, 4 biomarkers (apolipoprotein A-II, N-terminal prohormone of brain natriuretic peptide, copeptin, and high-sensitivity cardiac troponin I) remained significant discriminators between T1MI and T2MI. Internal validation of the model showed an area under the curve of 0.82. For discrimination between MI and myocardial injury, 6 biomarkers (adiponectin, N-terminal prohormone of brain natriuretic peptide, pulmonary and activation-regulated chemokine, transthyretin, copeptin, and high-sensitivity troponin I) were selected. Internal validation showed an area under the curve of 0.84. CONCLUSIONS: Among 29 biomarkers, 7 were identified to be the most relevant discriminators between subtypes of MI or myocardial injury. Regression models based on these biomarkers allowed good discrimination. (Biomarkers in Acute Cardiac Care [BACC]; NCT02355457).

Performance of the ESC 0/1-h and 0/3-h Algorithm for the Rapid Identification of Myocardial Infarction Without ST-Elevation in Patients With Diabetes.

OBJECTIVE: Patients with diabetes mellitus (DM) have elevated levels of high-sensitivity cardiac troponin (hs-cTn). We investigated the diagnostic performance of the European Society of Cardiology (ESC) algorithms to rule out or rule in acute myocardial infarction (AMI) without ST-elevation in patients with DM. RESEARCH DESIGN AND METHODS: We prospectively enrolled 3,681 patients with suspected AMI and stratified those by the presence of DM. The ESC 0/1-h and 0/3-h algorithms were used to calculate negative and positive predictive values (NPV, PPV). In addition, alternative cutoffs were calculated and externally validated in 2,895 patients. RESULTS: In total, 563 patients (15.3%) had DM, and 137 (24.3%) of these had AMI. When the ESC 0/1-h algorithm was used, the NPV was comparable in patients with and without DM (absolute difference [AD] -1.50 [95% CI -5.95, 2.96]). In contrast, the ESC 0/3-h algorithm resulted in a significantly lower NPV in patients with DM (AD -2.27 [95% CI -4.47, -0.07]). The diagnostic performance for rule-in of AMI (PPV) was comparable in both groups: 0/1-h (AD 6.59 [95% CI -19.53, 6.35]) and 0/3-h (AD 1.03 [95% CI -7.63, 9.7]). Alternative cutoffs increased the PPV in both algorithms significantly, while improvements in NPV were only subtle. CONCLUSIONS: Application of the ESC 0/1-h algorithm revealed comparable safety to rule out AMI comparing patients with and without DM, while this was not observed with the ESC 0/3-h algorithm. Although alternative cutoffs might be helpful, patients with DM remain a high-risk population in whom identification of AMI is challenging and who require careful clinical evaluation.

Predictive Value of Serial ECGs in Patients with Suspected Myocardial Infarction.

The electrocardiogram (ECG) is an important diagnostic tool for patients with suspected acute myocardial infarction (AMI). Current guidelines recommend serial ECGs in case of persisting symptoms. We aimed to analyze the predictive value of ischemic ECG-signs in patients with suspected AMI. Patients presenting to the emergency department with suspected AMI were included. All patients with ST-elevation AMI were excluded from analyses. Patients received 12-lead-ECG and high-sensitive Troponin T (hs-TnT)-measurement at admission and after 3 h. Four groups were defined: no ischemic signs in either ECG; new ischemic signs in the second ECG; resolved ischemic signs in the second ECG; and persistent ischemic signs in both ECGs. Patients were followed for 2 years to assess the composite endpoint of all-cause-mortality, AMI, and coronary revascularization. Using a 30-day landmark analysis, a Cox regression with ischemic signs as the variable of interest, adjusted by cardiovascular risk factors, was calculated. Of 1675 patients, 1321 showed no ischemic signs, in 25 new-, in 92 resolved- and in 237 patients, persistent ischemic signs were documented. Patients with persistent ischemic signs had significantly worse outcomes, compared to those without. Compared to no ischemic signs, adjusted hazard ratios for the combined endpoint were 0.81 (95% CI 0.20, 3.31; p-value = 0.77) for new-, 0.59 (95% CI 0.26, 1.34; p-value = 0.21) for resolved-, and 1.47 (95% CI 1.102, 2.13; p-value = 0.041) for persistent ischemic signs. In patients with suspected AMI, persistent ischemic ECG-signs are predictive of a higher rate of all-cause-mortality, AMI, and revascularization.

Application of a machine learning-driven, multibiomarker panel for prediction of incident cardiovascular events in patients with suspected myocardial infarction.

Background: In patients with suspected myocardial infarction (MI), we sought to validate a machine learning-driven, multibiomarker panel for prediction of incident major adverse cardiovascular events (MACE). Methodology & results: A previously described prognostic panel for MACE consisting of four biomarkers was measured in 748 patients with suspected MI. The investigated end point was incident MACE within 1 year. The prognostic value of a continuous score and an optimal cut-off was investigated. The area under the curve was 0.86 for the overall model. Using the optimal cut-off resulted in a negative predictive value of 99.4% for incident MACE. Patients with an elevated prognostic score were at high risk for MACE. Conclusion: Among patients with suspected MI, we validated a multibiomarker panel for predicting 1-year MACE. Clinical Trial Registration: NCT02355457 (ClinicalTrials.gov).

Prognostic Value of a Novel and Established High-Sensitivity Troponin I Assay in Patients Presenting with Suspected Myocardial Infarction.

: High-sensitivity troponin has proven to be a promising biomarker for the prediction of future adverse cardiovascular events. We aimed to assess the prognostic value of high-sensitivity troponin I (hs-TnI) on admission in patients with suspected acute myocardial infarction (AMI) analyzed by a novel (Singulex Clarity cTnI) and established hs-TnI assay (ARCHITECT STAT hs-TnI, Abbott). Hs-TnI was measured in a total of 2332 patients from two prospective cohort studies presenting to the emergency department with suspected AMI. The prognostic impact for overall and cardiovascular mortality of both hs-TnI assays was assessed in the total patient cohort as well as in the subgroups of patients with AMI (n = 518) and without AMI (non-AMI) (n = 1814). Patients presenting with highest hs-TnI levels showed higher overall and cardiovascular mortality rates compared to those with lower troponin levels, irrespective of the assay used. Both hs-TnI assays indicated association with overall mortality according to adjusted hazard ratio (HR) among the entire study population (HR for Singulex assay: 1.16 (95% CI 1.08-1.24) and HR for Abbott assay: 1.17 (95% CI 1.09-1.25)). This finding was particularly pronounced in non-AMI patients, whereas no association between hs-TnI and overall mortality was found in AMI patients for either assay. In non-AMI patients, both assays equally improved risk prediction for cardiovascular mortality beyond conventional cardiovascular risk factors. Hs-TnI is independently predictive for adverse outcomes in patients with suspected AMI, especially in the subset of patients without confirmed AMI. There was no difference between the established and the novel assay in the prediction of mortality.