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.

GRACE scores or high-sensitivity troponin for timing of coronary angiography in non-ST-elevation acute coronary syndromes.

BACKGROUND: The GRACE risk score is generically recommended by guidelines for timing of invasive coronary angiography without stating which score should be used. The aim was to determine the diagnostic performance of different GRACE risk scores in comparison to the ESC 0/1 h-algorithm using high-sensitivity cardiac troponin (hs-cTn). METHODS: Prospectively enrolled patients presenting with symptoms suggestive of myocardial infarction (MI) in two large studies testing biomarker diagnostic strategies were included. Five GRACE risk scores were calculated. The amount of risk reclassification and the theoretical impact on guideline-recommended timing of invasive coronary angiography was studied. RESULTS: Overall, 8,618 patients were eligible for analyses. Comparing different GRACE risk scores, up to 63.8% of participants were reclassified into a different risk category. The proportion of MIs identified (i.e., sensitivity) dramatically differed between GRACE risk scores (range 23.8-66.5%) and was lower for any score than for the ESC 0/1 h-algorithm (78.1%). Supplementing the ESC 0/1 h-algorithm with a GRACE risk score slightly increased sensitivity (P < 0.001 for all scores). However, this increased the number of false positive results. CONCLUSION: The substantial amount of risk reclassification causes clinically meaningful differences in the proportion of patients meeting the recommended threshold for pursuing early invasive strategy according to the different GRACE scores. The single best test to detect MIs is the ESC 0/1 h-algorithm. Combining GRACE risk scoring with hs-cTn testing slightly increases the detection of MIs but also increases the number of patients with false positive results who would undergo potential unnecessarily early invasive coronary angiography.

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.

Role of Copeptin and hs-cTnT to Discriminate AHF from Uncomplicated NSTE-ACS with Baseline Elevated hs-cTnT-A Derivation and External Validation Study.

BACKGROUND: In light of overlapping symptoms, discrimination between non-ST-elevation (NSTE) acute coronary syndrome (ACS) and acute heart failure (HF) is challenging, particularly in patients with equivocal clinical presentation for suspected ACS. We sought to evaluate the diagnostic and prognostic properties of copeptin in this scenario. METHODS: Data from 1088 patients from a single-center observational registry were used to test the ability of serial high sensitivity cardiac troponin T (hs-cTnT)-compared to copeptin, or a combination of copeptin with hs-cTnT-to discriminate acute HF from uncomplicated non-ST-elevation myocardial infarction (NSTEMI) and to evaluate all-cause mortality after 365 days. Patients with STEMI, those with unstable angina and either normal or undetectable hs-cTnT concentrations were excluded. The findings were validated in an independent external NSTE-ACS cohort. RESULTS: A total of 219 patients were included in the analysis. The final diagnosis was acute HF in 56 and NSTE-ACS in 163, with NSTEMI in 78 and unstable angina having stable elevation of hs-cTnT >ULN in 85. The rate of all-cause death at 1 year was 9.6% and occurred significantly more often in acute HF than in NSTE-ACS (15 vs. 6%, p < 0.001). In the test cohort, the area under the receiver operator curve (AUC) for the discrimination of acute HF vs. NSTE-ACS without HF was 0.725 (95% confidence interval [CI] 0.625-0.798) for copeptin and significantly higher than for hs-cTnT at 0 h (AUC = 0.460, 0.370-0.550) or at 3 h (AUC = 0.441, 0.343-0.538). Copeptin and hs-cTnT used either as continuous values or at cutoffs optimized to yield 90% specificity for acute HF were associated with significantly higher age- and sex-adjusted risk for all-cause mortality at 365 days. The findings from the test cohort were consistently replicated in the independent external NSTE-ACS validation cohort. CONCLUSIONS: High concentrations of copeptin in patients with suspected NSTE-ACS and equivocal clinical presentation suggest the presence of acute HF compared to uncomplicated NSTE-ACS and are associated with higher rates of all-cause death at 365 days.

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.

High-sensitivity troponin I with or without ultra-sensitive copeptin for the instant rule-out of acute myocardial infarction.

Background: The instant, single-sampling rule-out of acute myocardial infarction (AMI) is still an unmet clinical need. We aimed at testing and comparing diagnostic performance and prognostic value of two different single-sampling biomarker strategies for the instant rule-out of AMI. Methods: From the Biomarkers in Acute Cardiac Care (BACC) cohort, we recruited consecutive patients with acute chest pain and suspected AMI presenting to the Emergency Department of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany. We compared safety, effectiveness and 12-month incidence of the composite endpoint of all-cause death and myocardial infarction between (i) a single-sampling, dual-marker pathway combining high-sensitivity cardiac troponin I (hs-cTnI) and ultra-sensitive copeptin (us-Cop) at presentation (hs-cTnI ≤ 27 ng/L, us-Cop < 10 pmol/L and low-risk ECG) and (ii) a single-sampling pathway based on one-off hs-cTnI determination at presentation (hs-cTnI < 5 ng/L and low-risk ECG). As a comparator, we used the European Society of Cardiology (ESC) 0/1-h dual-sampling algorithm. Results: We enrolled 1,136 patients (male gender 65%) with median age of 64 years (interquartile range, 51-75). Overall, 228 (20%) patients received a final diagnosis of AMI. The two single-sampling instant rule-out pathways yielded similar negative predictive value (NPV): 97.4% (95%CI: 95.4-98.7) and 98.7% (95%CI: 96.9-99.6) for dual-marker and single hs-cTnI algorithms, respectively (P = 0.11). Both strategies were comparably safe as the ESC 0/1-h dual-sampling algorithm and this was consistent across subgroups of early-comers, low-intermediate risk (GRACE-score < 140) and renal dysfunction. Despite a numerically higher rate of false-negative results, the dual-marker strategy ruled-out a slightly but significantly higher percentage of patients compared with single hs-cTnI determination (37.4% versus 32.9%; P < 0.001). There were no significant between-group differences in 12-month composite outcome. Conclusions: Instant rule-out pathways based on one-off determination of hs-cTnI alone or in combination with us-Cop are comparably safe as the ESC 0/1 h algorithm for the instant rule-out of AMI, yielding similar prognostic information. Instant rule-out strategies are safe alternatives to the ESC 0/1 h algorithm and allow the rapid and effective triage of suspected AMI in patients with low-risk ECG. However, adding copeptin to hs-cTn does not improve the safety of instant rule-out compared with the single rule-out hs-cTn at very low cut-off concentrations.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.

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).

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).

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).

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.

Derivation and External Validation of a High-Sensitivity Cardiac Troponin-Based Proteomic Model to Predict the Presence of Obstructive Coronary Artery Disease.

Background Current noninvasive modalities to diagnose coronary artery disease (CAD) have several limitations. We sought to derive and externally validate a hs-cTn (high-sensitivity cardiac troponin)-based proteomic model to diagnose obstructive coronary artery disease. Methods and Results In a derivation cohort of 636 patients referred for coronary angiography, predictors of ≥70% coronary stenosis were identified from 6 clinical variables and 109 biomarkers. The final model was first internally validated on a separate cohort (n=275) and then externally validated on a cohort of 241 patients presenting to the ED with suspected acute myocardial infarction where ≥50% coronary stenosis was considered significant. The resulting model consisted of 3 clinical variables (male sex, age, and previous percutaneous coronary intervention) and 3 biomarkers (hs-cTnI [high-sensitivity cardiac troponin I], adiponectin, and kidney injury molecule-1). In the internal validation cohort, the model yielded an area under the receiver operating characteristic curve of 0.85 for coronary stenosis ≥70% (P<0.001). At the optimal cutoff, we observed 80% sensitivity, 71% specificity, a positive predictive value of 83%, and negative predictive value of 66% for ≥70% stenosis. Partitioning the score result into 5 levels resulted in a positive predictive value of 97% and a negative predictive value of 89% at the highest and lowest levels, respectively. In the external validation cohort, the score performed similarly well. Notably, in patients who had myocardial infarction neither ruled in nor ruled out via hs-cTnI testing ("indeterminate zone," n=65), the score had an area under the receiver operating characteristic curve of 0.88 (P<0.001). Conclusions A model including hs-cTnI can predict the presence of obstructive coronary artery disease with high accuracy including in those with indeterminate hs-cTnI concentrations.

Sex-Specific Outcomes in Patients with Acute Coronary Syndrome.

Sex differences in patients with acute coronary syndrome (ACS) are a matter of debate. We investigated sex-specific differences in the incidence, outcomes, and related interventions in patients diagnosed with ACS in Germany over the past decade. All ACS cases from 2005 to 2015 were collected. Procedures and inhospital mortality were assessed by sex. Age-adjusted incidence rates were calculated. In total, 1,366,045 females and 2,431,501 males presenting with ACS were recorded. Females were older than males (73.1 vs. 66.4 years of age), had a longer mean hospital stay (7.7 vs. 6.9 days), and less frequently underwent coronary angiographies (55% vs. 66%) and coronary interventions (35% vs. 47%). The age-adjusted incidence rate of ACS was lower in females than in males, and decreased in both sexes from 2005 to 2015. The age-adjusted inhospital mortality rate was substantially higher in females than in males, but decreased in both sexes over time (in females, from 87 to 71 cases per 1000 person years; in males, from 57 to 51 cases per 1000 person years). In conclusion, we reported sex differences in the incidence, treatment, and outcomes of ACS patients in Germany within the past decade. Women had a substantially higher mortality rate and lower rate of coronary interventions.

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).

Temporal trends in incidence and outcome of acute coronary syndrome.

BACKGROUND: We aimed to investigate changes of incidence, outcome and related interventions of patients with acute coronary syndrome (ACS) over the past decade in Germany. METHODS: Data on the international statistical classification of diseases and procedural codes from the Federal Bureau of Statistics in Germany was used. This included all ACS cases in Germany in the years 2005-2015. Analyses were performed separately for the diagnoses of overall ACS, ST-elevation myocardial infarction (MI), non-ST-elevation MI and unstable angina pectoris. Procedures including coronary angiography and percutaneous coronary intervention and the endpoint in-hospital mortality were assessed. RESULTS: Between 2005 and 2015 a total of 3797,546 cases of ACS were recorded. The mean age was 69 years and 36% were females. In-hospital mortality was 6.3%, 62% underwent coronary angiography and 42% received percutaneous coronary intervention. In-hospital mortality was highest for patients with ST-elevation MI (12.0%) and lowest for patients with unstable angina pectoris (0.6%). From 2005 to 2015 the incidence rates of ACS, ST-elevation MI and unstable angina pectoris decreased, while the incidence rate of non-ST-elevation MI increased. The percentages of performed coronary angiographies and percutaneous coronary interventions increased from 52 to 70% and 34 to 50%, respectively. The adjusted incidence rate of in-hospital mortality decreased from 64.9 cases per 1000 person-years to 54.8 cases. CONCLUSION: In a large dataset including more than 3.7 million cases, we report an increase in coronary procedures and a reduction of ACS incidence and related mortality in the past decade in Germany.