Identification of patients at higher risk for myocardial injury following elective coronary artery intervention.

OBJECTIVES: To evaluate myocardial injury and infarction (MI) following elective percutaneous coronary intervention (PCI). BACKGROUND: The substantially higher analytical power of high-sensitivity troponin (hsTn) assays allows detection of minor cardiac troponin (cTn) levels, which may be useful in monitoring myocardial injury and guiding therapies. METHODS: Serial hsTnT measurements were conducted in patients undergoing elective PCI and were related to the extent of coronary artery disease (CAD) as reflected by the SYNTAX score risk categories and American College of Cardiology/American Heart Association classification of coronary lesions. Myocardial injury and MI were diagnosed according to the second and third versions of universal MI definition. RESULTS: The study population consisted of 530 patients, who were grouped into low (41.3%), intermediate (35.4%), and high (23.3%) SYNTAX risk categories. The treated coronary lesions were classified into A 7.8%, B1 24.1%, B2 21.1%, C1 24.6%, and C2 22.4%. Postprocedural hsTnT increases correlated significantly with the complexity of treated coronary lesions (p < .05) and CAD magnitude (p < .05). Rates of MI type 4a according to the second and third MI definition criteria were 98 (27.5%) and 15 (4.2%) cases in patients with normal baseline hsTnT values (N = 357, 67.4%), as well as 137 (79.2%) and 27 (15.6%) cases in those with elevated baseline hsTnT values (N = 173, 32.6%), respectively. CONCLUSIONS: After elective PCI, cTn releases correlate significantly with lesion complexity and CAD extent. Use of hsTnT assay enables precise monitoring of PCI-related myocardial injury and may identify patients at higher risk for ischemic events, who may benefit from potent platelet inhibition, which needs to be investigated in randomized trials.

Amyloid-ß (1-40) and Mortality in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: A Cohort Study.

Background: Amyloid-ß (1-40) (Aß40) is implicated in mechanisms related to plaque destabilization and correlates with adverse outcomes in stable coronary artery disease. Objective: To determine the prognostic and reclassification value of baseline circulating levels of Aß40 after adjustment for the Global Registry of Acute Coronary Events (GRACE) score, which is widely recommended for risk stratification in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Design: Retrospective cohort study using data from 2 independent prospective cohorts, the Heidelberg study (n = 1145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study (n = 734). Setting: Academic hospitals in 7 European countries. Participants: Patients with adjudicated NSTE-ACS followed for a median of 21.9 and 24.9 months in the Heidelberg and APACE studies, respectively. Measurements: All-cause mortality was the primary end point. Results: Amyloid-ß (1-40) was associated with mortality after multivariate adjustment for age, sex, diabetes mellitus, high-sensitivity cardiac troponin T and C-reactive protein, revascularization, and ACS type (Heidelberg cohort hazard ratio [HR] for 80th vs. 20th percentiles, 1.66 [95% CI, 1.06 to 2.61; P = 0.026]; APACE cohort HR, 1.50 [CI, 1.15 to 1.96; P = 0.003]). It was also associated with mortality after adjustment for the GRACE score (Heidelberg cohort HR for 80th vs. 20th percentiles, 1.11 [CI, 1.04 to 1.18; P = 0.001]; APACE cohort HR, 1.39 [CI, 1.02 to 1.88; P = 0.036]). Amyloid-ß (1-40) correctly reclassified risk for death over the GRACE score (net reclassification index, 33.4% and 47.1% for the Heidelberg and APACE cohorts, respectively) (P < 0.05). Limitation: At low concentrations of Aß40, dose-response associations with mortality differed between cohorts, possibly because of varying blood preparations used to measure Aß40. Conclusion: Circulating Aß40 is a predictor of mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score recommended by clinical guidelines. The clinical application of Aß40 as a novel biomarker in NSTE-ACS should be further explored and validated. Primary Funding Source: German Cardiac Society.

Prognostic value of elevated high-sensitivity cardiac troponin T in patients admitted to an emergency department with atrial fibrillation.

Aims: Elevated levels of high-sensitivity cardiac troponin T (hsTnT) indicate underlying heart disease and are known to predict adverse outcomes in various patient populations. Their role in atrial fibrillation (AF) is still under debate. Methods and results: This retrospective study included 2898 consecutive patients presenting with AF to the emergency department of the Department of Cardiology, Heidelberg University Hospital. Multivariable Cox regression was used to assess associations between hsTnT and mortality. Elevated hsTnT levels were associated with increased risk of all-cause mortality in all patients with AF, as well as in each subtype of AF. After adjustment for multiple risk factors, both detectable hsTnT below the 99th percentile (5-14 ng/L, adjusted hazard ratio (HR): 4.86 [95% CI: 1.77-13.34], P = 0.002) and elevated hsTnT (>14 ng/L, adjusted HR: 13.42 [95% CI: 4.95-36.40], P < 0.001) were associated with a higher risk of mortality in patients with AF, compared to undetectable hsTnT (<5 ng/L). Elevated hsTnT was also associated with higher mortality after exclusion of patients with myocardial infarction, as well as in the subgroup of patients with AF as main admission diagnosis. The inclusion of hsTnT significantly improved the performance of the multivariable model for mortality prediction. Conclusion: Elevated hsTnT levels are associated with higher mortality in patients with AF, and provide added prognostic information independent of major cardiovascular risk factors and clinical characteristics. Measurement of hsTnT should be considered for risk assessment in patients presenting to an emergency department with AF. Clinical trial registration: http://www.clinicaltrials.gov; Unique identifier: NCT02542189.

Serial Sampling of High-Sensitivity Cardiac Troponin T May Not Be Required for Prediction of Acute Myocardial Infarction Diagnosis in Chest Pain Patients with Highly Abnormal Concentrations at Presentation.

BACKGROUND: Guidelines for diagnosing acute myocardial infarction (AMI) recommend adding kinetic changes to the initial cardiac troponin (cTn) blood concentration to improve AMI diagnosis. We hypothesized that kinetic changes may not be required in patients presenting with highly abnormal cTn. METHODS: Patients presenting with suspected AMI to the emergency department were enrolled in a prospective diagnostic study. We assessed the positive predictive value (PPV) of initial high-sensitivity cardiac troponin T (hs-cTnT) blood concentrations alone and in combination with kinetic changes for AMI. Predefined relative changes (δ change of ≥20%) and absolute changes (Δ change ≥9.2 ng/L) within different time intervals (1 h, 2 h, and 4-14 h after presentation) were assessed. The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS: Among 1282 patients, 213 (16.6%) patients had a final diagnosis of AMI. For AMI prediction, PPVs increased from 48.8% for an initial hs-cTnT >14 ng/L to 87.2% for >60 ng/L, whereas PPVs remained unchanged for higher hs-cTnT concentrations at baseline (87.1% for both >80 ng/L and >100 ng/L). With addition of 20% relative Δ change, PPVs were not further improved in patients with baseline hs-cTnT >80 ng/L using the 1-h (84.0%) and 2-h (88.9%) intervals, and only minimally when extending the interval to 4-14 h (91.2% for >80 ng/L and 90.4% for >100 ng/L, respectively). Similar findings were observed when applying absolute changes. CONCLUSIONS: In chest pain patients with highly abnormal hs-cTnT concentrations at presentation, subsequent blood draws may not be required, as they do not provide incremental diagnostic value for prediction of AMI diagnosis.

Impact of leading presenting symptoms on the diagnostic performance of high-sensitivity cardiac troponin T and on outcomes in patients with suspected acute coronary syndrome.

BACKGROUND: Diagnostic performance of high-sensitivity cardiac troponin T (hs-cTnT) varies depending on presenting symptoms in patients with suspected acute coronary syndrome (ACS). METHODS: We compared performance measures of hs-cTnT among patients admitted to the emergency department with typical chest pain (angina), dyspnea, and atypical symptoms and assessed outcomes by leading presenting symptoms. RESULTS: A total of 658 patients suspected of ACS and presenting with typical chest pain (n = 241, 36.6%), dyspnea (n = 142, 21.6%), or atypical symptoms (n = 275, 41.8%) were included. Diagnostic accuracy of hs-cTnT on admission was higher among patients with typical chest pain compared to those with atypical symptoms [area under the curve (AUC) 0.823 vs AUC 0.776 vs AUC 0.705, P > 0.05 and P = 0.04]. Absolute concentration changes within 6 h improved accuracy among all subgroups, with the smallest added benefit in typical chest pain and dyspnea (ΔAUC, 0.078; P = 0.02 and 0.05, P > 0.05). During 1-year follow-up, dyspnea was associated with a higher risk of death (hazard ratio, 2.36; 95% CI, 1.26-4.43, P = 0.008) and death/AMI (hazard ratio, 2.23; 95% CI, 1.21-4.11, P = 0.01) compared to typical chest pain. Optimal discriminating values for hs-cTnT were higher among patients presenting with dyspnea compared to those with typical chest pain (91.2 vs 14.1 ng/L, P < 0.001). CONCLUSION: The diagnostic performance of hs-cTnT in patients with suspected ACS depends on the leading presenting symptom. Patients admitted with dyspnea represent a high-risk cohort in which the diagnosis of ACS is less frequent and with inferior performance of serial hs-cTnT measurements. Higher hs-cTnT cutoffs at baseline and absolute changes after 6 h help to identify non-STEMI (ST segment elevation myocardial infarction) in this population.

Cardiac Troponin T.

Cardiac troponins (cTns) T and I are exclusively expressed at high concentrations in cardiac muscle and have emerged as the preferred biomarker in the universal definition of myocardial infarction (MI). With the recent introduction of high-sensitivity (hs) assays, diagnostic sensitivity for earlier detection of MI has substantially improved. However, lowering the diagnostic cut-off has increased the detection of myocardial injuries in various non-acute coronary syndrome (ACS) conditions, which are not related to myocardial ischemia, leading to rising difficulties in diagnosing MI in clinical situations. Several approaches, such as serial sampling and incorporation of relative or absolute δ-changes, have been proposed to overcome the limitation of decreased sensitivity for MI diagnosis with hs-cTn assays. Current consensus for rapid rule-in proposes a 20% increase within 3 or 6h when baseline cTn levels are elevated. In the case of negative baseline values, relative increases ≥50% above the 99th percentile were found to be adequate to improve accuracy of MI diagnosis. Besides improved diagnostic accuracy for myocardial injury, even minor cTn elevations provide important prognostic information, and increased levels of cTn are associated with adverse outcomes in both the ACS and non-ACS condition, irrespective of whether the underlying cause is an acute or chronic illness. Thus, it is highly likely that lowering the diagnostic cut-off with even more sensitive assays might improve risk stratification in both conditions.

Cardiac troponin T: from diagnosis of myocardial infarction to cardiovascular risk prediction.

Cardiac troponins (cTns) T and I are exclusively expressed at high concentrations in cardiac muscle and have emerged as the preferred biomarker in the universal definition of myocardial infarction (MI). With the recent introduction of high-sensitivity (hs) assays, diagnostic sensitivity for earlier detection of MI has substantially improved. However, lowering the diagnostic cut-off has increased the detection of myocardial injuries in various non-acute coronary syndrome (ACS) conditions, which are not related to myocardial ischemia, leading to rising difficulties in diagnosing MI in clinical situations. Several approaches, such as serial sampling and incorporation of relative or absolute δ-changes, have been proposed to overcome the limitation of decreased sensitivity for MI diagnosis with hs-cTn assays. Current consensus for rapid rule-in proposes a 20% increase within 3 or 6h when baseline cTn levels are elevated. In the case of negative baseline values, relative increases ≥50% above the 99(th) percentile were found to be adequate to improve accuracy of MI diagnosis. Besides improved diagnostic accuracy for myocardial injury, even minor cTn elevations provide important prognostic information, and increased levels of cTn are associated with adverse outcomes in both the ACS and non-ACS condition, irrespective of whether the underlying cause is an acute or chronic illness. Thus, it is highly likely that lowering the diagnostic cut-off with even more sensitive assays might improve risk stratification in both conditions.

Effect of older age on diagnostic and prognostic performance of high-sensitivity troponin T in patients presenting to an emergency department.

BACKGROUND: The effect of age on diagnostic and prognostic performance of high-sensitivity cardiac troponin T (hs-cTnT) has not been addressed adequately, so far. METHODS: High-sensitivity cardiac troponin T was measured serially in patients with acute symptoms presenting to our emergency department. We tested the diagnostic and prognostic performance of baseline and serial hs-cTnT concentrations related to age in all consecutive patients with acute coronary syndrome (ACS) (n = 342) or hs-cTnT increases not due to ACS (n = 442). RESULTS: Prevalence of elevated hs-cTnT in the study population was higher among patients ≥75 years compared with younger patients (89.1 % vs 73.3 %, hazard ratio [HR] 1.2, P < .0001). Elevated hs-cTnT was more likely due to ACS in the younger patients (HR 1.4, P = .001) and conversely more frequently due to non-ACS conditions in the elderly patients (HR 1.3, P = .0001). Diagnostic performance of hs-cTnT using the 99th percentile was significantly superior in younger than in elderly patients (P < .0001). For receiver operating characteristic-optimized cutoffs, a trend to significance was found between younger and older patients (area under the curve 0.87 vs 0.79, P = .074), with higher sensitivities (98.2 % vs 72.6%) and negative predictive values (97.3% vs. 78.5%) for patients <75 years. Moreover, receiver operating characteristic-optimized cutoff values for diagnosis of non-ST-segment elevation myocardial infarction were significantly higher in elderly patients (32.9 ng/L) compared with younger patients (12.9 ng/L). The prognostic information of single and serial hs-cTnT measurements was comparably poor in both age groups, showing no better prognostic information to hs-cTnT measurement on presentation. CONCLUSIONS: Elevated hs-cTnT is more common in the elderly due to higher prevalence of non-ACS conditions and significantly impairs diagnostic performance in discriminating non-ST-segment elevation myocardial infarction.

Absolute and relative kinetic changes of high-sensitivity cardiac troponin T in acute coronary syndrome and in patients with increased troponin in the absence of acute coronary syndrome.

BACKGROUND: We evaluated kinetic changes of high-sensitivity cardiac troponin T (hs-cTnT) in patients with acute coronary syndrome (ACS) and patients with hs-cTnT increases not due to ACS to rule in or rule out non-ST-segment elevation myocardial infarction (STEMI). METHODS: hs-cTnT was measured serially in consecutive patients presenting to the emergency department. Patients with ACS who had at least 2 hs-cTnT measurements within 6 h and non-ACS patients with hs-cTnT concentrations above the 99th percentile value (14 ng/L) were enrolled to compare absolute and relative kinetic changes of hs-cTnT. RESULTS: For discrimination of non-STEMI (n=165) in the entire study population (n=784), the absolute δ change with the ROC-optimized value of 9.2 ng/L yielded an area under the curve of 0.898 and was superior to all relative δ changes (P<0.0001). The positive predictive value for the absolute δ change was 48.7%, whereas the negative predictive value was 96.5%. In a specific ACS population with exclusion of STEMI (n=342), the absolute δ change with the ROC-optimized value of 6.9 ng/L yielded a positive predictive value of 82.8% and a negative predictive value of 93.0%. In comparison to the ≥20% relative δ change, the ROC-optimized absolute δ change demonstrated a significantly added value for the entire study population and for the ACS cohort (net reclassification index 0.331 and 0.499, P<0.0001). CONCLUSIONS: Absolute δ changes appear superior to relative δ changes in discriminating non-STEMI. A rise or fall of at least 9.2 ng/L in the entire study population and 6.9 ng/L in selected ACS patients seems adequate to rule-out non-STEMI. However, δ-values are useful to rule-in non-STEMI only in a specific ACS population.

Cathepsin S Levels and Survival Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are at high residual risk for long-term cardiovascular (CV) mortality. Cathepsin S (CTSS) is a lysosomal cysteine protease with elastolytic and collagenolytic activity that has been involved in atherosclerotic plaque rupture. OBJECTIVES: The purpose of this study was to determine the following: 1) the prognostic value of circulating CTSS measured at patient admission for long-term mortality in NSTE-ACS; and 2) its additive value over the GRACE (Global Registry of Acute Coronary Events) risk score. METHODS: This was a single-center cohort study, consecutively recruiting patients with adjudicated NSTE-ACS (n = 1,112) from the emergency department of an academic hospital. CTSS was measured in serum using enzyme-linked immunosorbent assay. All-cause mortality at 8 years was the primary endpoint. CV death was the secondary endpoint. RESULTS: In total, 367 (33.0%) deaths were recorded. CTSS was associated with increased risk of all-cause mortality (HR for highest vs lowest quarter of CTSS: 1.89; 95% CI: 1.34-2.66; P < 0.001) and CV death (HR: 2.58; 95% CI: 1.15-5.77; P = 0.021) after adjusting for traditional CV risk factors, high-sensitivity C-reactive protein, left ventricular ejection fraction, high-sensitivity troponin-T, revascularization and index diagnosis (unstable angina/ non-ST-segment elevation myocardial infarction). When CTSS was added to the GRACE score, it conferred significant discrimination and reclassification value for all-cause mortality (Delta Harrell's C: 0.03; 95% CI: 0.012-0.047; P = 0.001; and net reclassification improvement = 0.202; P = 0.003) and CV death (AUC: 0.056; 95% CI: 0.017-0.095; P = 0.005; and net reclassification improvement = 0.390; P = 0.001) even after additionally considering high-sensitivity troponin-T and left ventricular ejection fraction. CONCLUSIONS: Circulating CTSS is a predictor of long-term mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score.

Combined testing of high-sensitivity troponin T and copeptin on presentation at prespecified cutoffs improves rapid rule-out of non-ST-segment elevation myocardial infarction.

BACKGROUND: Two recent clinical trials showed that adding copeptin to a conventional cardiac troponin assay improved diagnostic performance for patients with chest pain early after symptom onset. We prospectively tested whether copeptin adds information to that provided by a high-sensitivity cardiac troponin T (hscTnT) assay in the early evaluation of patients with suspected acute myocardial infarction, particularly non-ST-segment elevation myocardial infarction (non-STEMI). METHODS: We enrolled 503 patients with suspected acute coronary syndrome and onset of chest pain occurring within the previous 12 h. Copeptin was measured on presentation, and hscTnT was measured serially at baseline and after 3 and 6 h. We used ROC curve analysis and likelihood ratio χ² statistics for nested models. Diagnostic sensitivities, specificities, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated for admission values of copeptin alone, hscTnT alone, and the combination of both markers. RESULTS: For ruling out non-STEMI (after excluding STEMI), an hscTnT concentration <14 ng/L (99th percentile) plus a copeptin concentration <14 pmol/L yielded a diagnostic sensitivity of 97.7% (95% CI, 91.9%-99.7%), an NPV of 99.03% (95% CI, 96.6%-99.9%), a diagnostic specificity of 55.9% (95% CI, 50.6%-61.0%), and a PPV of 34.4% (95% CI, 28.5%-40.7%). ROC curve analysis of the continuous biomarker values on admission demonstrated no added value of using this marker combination for ruling out non-STEMI when hscTnT was used as the standard for diagnosing non-STEMI. CONCLUSIONS: A strategy using copeptin with hscTnT at prespecified cutoffs improves the ruling out of non-STEMI, compared with using hscTnT alone; thus, this strategy could help to obviate a prolonged stay in the emergency department.

Validation of two severity scores as predictors for outcome in Coronavirus Disease 2019 (COVID-19).

BACKGROUND: An established objective and standardized reporting of clinical severity and disease progression in COVID-19 is still not established. We validated and compared the usefulness of two classification systems reported earlier-a severity grading proposed by Siddiqi and a system from the National Australian COVID-19 guideline. Both had not been validated externally and were now tested for their ability to predict complications. METHODS: In this retrospective, single-centre observational study, patients hospitalized with confirmed COVID-19 across all severity stages were enrolled. The clinical severity was graded at admission and during hospitalization. Multivariate Cox regression was used to identify independent risk factors for mortality, a composite primary (mortality, incident acute respiratory distress syndrome, incident mechanical ventilation), a secondary endpoint (mortality, incident acute myocardial injury, incident venous thrombosis, pulmonary embolism or stroke) and progression of severity grades. RESULTS: Of 109 patients 17 died, 31 and 48 developed the primary and secondary endpoint, respectively. Worsening of the severity grade by at least one stage occurred in 27 and 28 patients, respectively. Siddiqi and Australian classification were identified as independent predictors for the primary endpoint (adjusted hazard ratio (aHR) 2.30, p<0.001 and aHR 2.08, p<0.001), for the secondary endpoint (aHR 2.12, p<0.001 and aHR 1.79, p<0.001) and mortality (aHR 2.30, p = 0.071 and aHR 1.98, p = 0.017). Both classification systems showed very good agreement regarding initial grading and good agreement regarding progression of severity stages. CONCLUSIONS: Standardized and objective severity grading is useful to unequivocally stratify patients presenting with COVID-19 for their individual risk of complications.

Diagnostic value of circulating microRNAs compared to high-sensitivity troponin T for the detection of non-ST-segment elevation myocardial infarction.

AIMS: To assess the diagnostic value of microRNAs (miRNAs) for the detection of non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: A total of 1042 patients presenting between August 2014 and April 2017 to the emergency department with the suspected acute coronary syndrome were included. Non-ST-segment elevation myocardial infarction was diagnosed per criteria of the fourth Universal definition of myocardial infarction (UDMI) using high-sensitivity troponin T (hs-cTnT). Expression levels of eleven microRNAs (miR-21, miR-22, miR-29a, miR-92a, miR-122, miR-126, miR-132, miR-133, miR-134, miR-191, and miR-423) were determined using RT-qPCR. Discrimination of NSTEMI was assessed for individual and a panel of miRNAs compared to the hs-cTnT reference using C-statistics and reclassification analysis. NSTEMI was diagnosed in 137 (13.1%) patients. The area under the curve (AUC) of the hs-cTnT based reference was 0.937. In a multivariate model, three miRNAs (miR-122, miR-133, and miR-134) were found to be associated with NSTEMI with AUCs between 0.506 and 0.656. A panel consisting of these miRNAs revealed an AUC of 0.662 for the diagnosis of NSTEMI. The AUC of the combination of the miRNA panel and troponin reference was significantly lower than the reference standard (AUC: 0.897 vs. 0.937, P = 0.006). Despite a significant improvement of NSTEMI reclassification measured by IDI and NRI, miRNAs did not improve the specificity of hs-cTnT kinetic changes for the diagnosis of NSTEMI (ΔAUC: 0.04). CONCLUSION: Although single miRNAs are significantly associated with the diagnosis of NSTEMI a miRNA panel does not add diagnostic accuracy to the hs-cTnT reference considering baseline values and kinetic changes as recommended by the fourth version of UDMI. CLINICAL TRIALS IDENTIFIER: NCT02116153.

Effects of crowding in the emergency department on the diagnosis and management of suspected acute coronary syndrome using rapid algorithms: an observational study.

OBJECTIVES: Fast diagnostic algorithms using high-sensitivity troponin (hsTn) in suspected acute coronary syndrome (ACS) are regarded as beneficial to expedite diagnosis and safe discharge of patients in crowded emergency departments (ED). This study investigates the effects of crowding on process times related to the diagnostic protocol itself or other time delays, and outcomes. DESIGN: Prospective single-centre observational study. SETTING: ED (Germany). PARTICIPANTS: Final study population of 2525 consecutive patients with suspected ACS within 12 months, after exclusion of patients with ST-elevation myocardial infarction, missing blood samples, referral from other hospitals or repeated visits. INTERVENTIONS: Use of fast algorithms as per 2015 European Society of Cardiology guidelines. MAIN OUTCOME MEASURES: Crowding was defined as mismatch between patient numbers and monitoring capacities, or mean physician time per case, categorised as normal, high and very high crowding. Outcome measures were length of ED stay, direct discharge from ED, laboratory turn around times (TAT), utilisation of fast algorithms, absolute and relative non-laboratory time, as well as mortality. RESULTS: Crowding was associated with increased length of ED stay (3.75-4.89 hours, p<0.001). While median TAT of the first hsTnT increased (53-57 min, p<0.001), total TAT of serial hsTnT did not increase significantly with higher crowding (p=0.170). Lower utilisation of fast algorithms (p=0.009) and increase of additional hsTnT measurements after diagnosis (p=0.001) were observed in higher crowding. Most importantly, crowding was significantly associated with prolonged absolute (p<0.001), and particularly relative non-laboratory time (63.3%-71.3%, p<0.001). However, there was no significant effect of crowding on mortality, even after adjustment for relevant clinical variables. CONCLUSIONS: Process times, and particularly non-laboratory times, are prolonged in a crowded ED diminishing some positive effects of fast diagnostic algorithms in suspected ACS. Higher crowding levels were not significantly associated with higher all-cause mortality rates. TRIAL REGISTRATION NUMBER: NCT03111862.

Prognostic Value of Elevated Copeptin and High-Sensitivity Cardiac Troponin T in Patients with and without Acute Coronary Syndrome: The ConTrACS Study.

AIMS: We aimed to assess the prognostic role of copeptin in patients presenting to the emergency department with acute symptoms and increased high-sensitivity cardiac troponin T. METHODS: A total of 3890 patients presenting with acute symptoms to the emergency department of Heidelberg University Hospital were assessed for increased hs-cTnT (>14 ng/L) from three cohorts: the Heidelberg Acute Coronary Syndrome (ACS) Registry (n = 2477), the BIOPS Registry (n = 320), and the ACS OMICS Registry (n = 1093). In a pooled analysis, 1956 patients remained, comprising of 1600 patients with ACS and 356 patients with non-ACS. RESULTS: Median follow-up was 1468 days in the ACS cohort and 709 days in the non-ACS cohort. Elevated copeptin levels (>10 pmol/L) were found in 1174 patients (60.0%) in the entire cohort (58.1% in ACS and 68.5% in non-ACS, respectively) and mortality rates were significantly higher than in patients with normal copeptin levels (29.0% vs. 10.7%, p < 0.001). In a multivariate Cox regression, elevated copeptin was independently associated with all-cause death in the ACS (HR = 1.7, 1.3-2.3, p = 0.002) and non-ACS cohort (HR = 2.7, 1.4-5.0, p = 0.0018). CONCLUSION: Copeptin may aid in identifying patients at risk for adverse outcomes in patients with increased levels of hs-cTnT in ACS patients and in non-ACS conditions.

RAPID-CPU: a prospective study on implementation of the ESC 0/1-hour algorithm and safety of discharge after rule-out of myocardial infarction.

BACKGROUND: Although the value of fast diagnostic protocols in suspected acute coronary syndrome has been validated, there is insufficient real world evidence including patients with lower pre-test probability, atypical symptoms and confounding comorbidities. The feasibility, efficacy and safety of European Society of Cardiology (ESC) 0/1 and 0/3-hour algorithms using high-sensitivity troponin T were evaluated in a consecutive cohort with suspected acute coronary syndrome. METHODS: During 12 months, 2525 eligible patients were enrolled. In a pre-implementation period of 6 months, the prevalence of protocols, disposition, lengths of emergency department stay and treatments were registered. Implementation of the 0/1-hour protocol was monitored for another 6 months. Primary endpoints comprised the change of diagnostic protocols and 30-day mortality after direct discharge from the emergency department. RESULTS: Use of the ESC 0/1-hour algorithm increased by 270% at the cost of the standard 0/3-hour protocol. After rule-out (1588 patients), 1309 patients (76.1%) were discharged directly from the emergency department, with an all-cause mortality of 0.08% at 30 days (one death due to lung cancer). Median lengths of stay were 2.9 (1.9-3.8) and 3.2 (2.7-4.4) hours using a single high-sensitivity troponin T below the limit of detection (5 ng/L) at presentation and the ESC 0/1-hour algorithm, respectively, as compared to 5.3 (4.7-6.5) hours using the ESC 0/3-hour rule-out protocol (P<0.001). Discharge rates increased from 53.9% to 62.8% (P<0.001), without excessive use of diagnostic resources within 30 days. CONCLUSION: Implementation of the ESC 0/1-hour algorithm is feasible and safe, is associated with shorter emergency department stay than the ESC 0/3-hour protocol, and an increase in discharge rates. TRIAL REGISTRATION: ClinicalTrials.gov , Unique identifier: NCT03111862.

Management and outcomes of patients with unstable angina with undetectable, normal, or intermediate hsTnT levels.

BACKGROUND: Patients with unstable angina (UA) are regarded to be at low risk for future coronary events. Guidelines discourage routine coronary angiography and recommend early discharge after individualized risk stratification. The relative value of clinical risk indicators as compared to cardiac troponin (cTn) alone is unsettled in the era of high-sensitivity cardiac troponin (hsTn) assays. We aimed to investigate the clinical characteristics, therapies, and outcomes of UA patients with different hsTnT concentrations. METHODS: During 12 months, 2525 patients were enrolled. UA was defined as unstable symptoms and either undetectable (< 5 ng/L), normal (5-14 ng/L) or stable elevated hsTnT (15-51 ng/L). Follow-up for 1-year mortality was available in 98.7%. RESULTS: A total of 280 patients (11.1%) received a diagnosis of UA. Mortality rates at 12 months were 0%, 1.9% and 6.9% in presence of undetectable, normal and stable elevated hsTnT. Elevated hsTnT > 99th percentile but not unstable symptoms carried an independent 3.25-fold (1.78-5.93) higher risk for all-cause death after adjustment for other clinical risk indicators or the GRACE score. Utilization of guideline-recommended therapies was high albeit lower than for non-ST-elevation myocardial infarction (NSTEMI). Significantly fewer patients with UA received dual antiplatelet therapy (DAPT, odds ratio (OR) 0.51 [95% CI 0.44-0.59], P < 0.0001), coronary angiography (CA, OR 0.79, [95% CI 0.74-0.87], P < 0.0001), and percutaneous coronary intervention (PCI, OR 0.50, [95% CI 0.40-0.61], P < 0.0001), compared to NSTEMI. However, prevalence of significant obstructive coronary artery disease requiring PCI was 31.8%, even in patients with undetectable hsTnT, indicating the need for stress testing. CONCLUSIONS: The current dichotomization of patients into UA and NSTEMI is no longer appropriate. Additional risk stratification seems warranted including the presence and magnitude of hsTn concentration and additional risk indicators. Clinical Trials Identifier: NCT03111862.

Gender-specific reference values for high-sensitivity cardiac troponin T and I in well-phenotyped healthy individuals and validity of high-sensitivity assay designation.

OBJECTIVE: To determine gender-specific reference limits of high-sensitivity (hs) cardiac troponins (cTn) and validity of hs assay designation for both genders. METHODS: After screening with a questionnaire, 827 presumably healthy individuals were further selected based on clinical criteria (n = 740), clinical criteria plus cardiac imaging including stress magnetic resonance imaging or stress echocardiography (n = 726), and extended cardio-pulmonary parameters (n = 626). Blood samples were measured with hs-cTnT (Roche Diagnostics) on a cobas e602 analyzer as well as hs-cTnI (Abbott Diagnostics) on an ARCHITECTi2000SR. The impact of health definition, statistical methods, instrument selection and limit of detection (LoD) on overall and gender-specific 99th percentiles was assessed. RESULTS: Median age was 56 years (50.9% female) for the total study cohort. 99th percentiles for females and males ranged between 13.1 and 13.3 ng/L and 16.8-19.9 ng/L for hs-cTnT as well as 10.3-12.5 ng/L and 27.4-29.7 ng/L for hs-cTnI depending on health definition. Utilization of stricter health definition criteria reduced the difference of the gender-specific 99th percentiles between males and females for hs-cTnT to 3.7 ng/L (males 16.8 ng/L, females 13.1 ng/L), whereas the difference rather increased for hs-cTnI to 19.4 ng/L (males 29.7 ng/L, females 10.3 ng/L). Values > LoD could be measured in the majority of males and females using hs-TnT (81.4-83.3% and 96.5-96.9%, respectively). In contrast, values > LoD could not be observed in the majority of females using hs-cTnI (38.4-41.1%). CONCLUSIONS: In a well-phenotyped healthy cohort, reference values for hs-cTnT were slightly higher, whereas hs-cTnI cut-offs were considerably lower than previously observed. Gender differences were more pronounced in hs-cTnI than in hs-cTnT and were further reduced for hs-cTnT by application of stricter health definition criteria. Contrary to hs-cTnI, hs-cTnT fulfilled criteria for hs designation for both genders.

Guideline-adherence regarding critical time intervals in the German Chest Pain Unit registry.

BACKGROUND: Since 2008, the German Cardiac Society certified 256 Chest Pain Units (CPUs). Little is known about adherence to recommended performance measures in patients with suspected acute coronary syndrome (ACS) presenting to CPUs. We investigated guideline-adherence regarding critical time intervals and selected performance measures in German Chest Pain Units. METHODS: From 2008 to 2014, 23,804 consecutive patients with suspected ACS were prospectively enrolled in the Chest Pain Unit registry of the German Cardiac Society. RESULTS: Median time from symptom onset to first medical contact was 2 h in patients with ST-elevation myocardial infarction (STEMI) and 4 h in patients with unstable angina and non-STEMI (NSTEMI). In patients with STEMI, median time from hospital admission to percutaneous coronary intervention (PCI) was 40 min and median time from first medical contact to PCI was 1 h 35 min. Primary PCI was performed in 94.7% of patients with STEMI, 70.0% of patients with NSTEMI and 37.4% of patients with unstable angina. PCI was performed during the first 24 h in 79.5% of patients with NSTEMI and the first 72 h in 89.0% of patients with unstable angina. Electrocardiograms were performed in 99.5% after a median of 6 min after admission and obtained within 10 min in 71%. Interestingly, 56.1% of patients were found to have non-ACS diagnoses, underlining the importance of access to additional diagnostic modalities including echocardiography, stress testing or computed tomography. CONCLUSIONS: Guideline-adherence regarding critical time intervals and primary PCI rates is good in German Chest Pain Units. More than half of patients admitted with suspected ACS had non-ACS diagnoses. Improvements in pre-hospital time delays through public awareness programmes are warranted.