Yonathan Freund

Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis

Background High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose To estimate the ability of a single hs-cTnT concentration below the limit of detection (<0.005 µg/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain. Data Sources EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016). Study Selection Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization. Data Extraction Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements <0.005 µg/L) and the number who had AMI during hospitalization (primary outcome) or a major adverse cardiac event (MACE) or death within 30 days (secondary outcomes), by risk classification (low or not low risk). Two independent epidemiologists rated risk of bias of studies. Data Synthesis Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died. Limitation Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies. Conclusion A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome. Primary Funding Source Emergency Care Foundation.

High-sensitivity versus conventional troponin in the emergency department for the diagnosis of acute myocardial infarction

IntroductionRecently, newer assays for cardiac troponin (cTn) have been developed which are able to detect changes in concentration of the biomarker at or below the 99th percentile for a normal population. The objective of this study was to compare the diagnostic performance of a new high-sensitivity troponin T (HsTnT) assay to that of conventional cTnI for the diagnosis of acute myocardial infarction (AMI) according to pretest probability (PTP).MethodsIn consecutive patients who presented to our emergency departments with chest pain suggestive of AMI, levels of HsTnT were measured at presentation, blinded to the emergency physicians, who were asked to estimate the empirical PTP of AMI. The discharge diagnosis was adjudicated by two independent experts on the basis of all available data.ResultsA total of 317 patients were included, comprising 149 (47%) who were considered to have low PTP, 109 (34%) who were considered to have moderate PTP and 59 (19%) who were considered to have high PTP. AMI was confirmed in 45 patients (14%), 22 (9%) of whom were considered to have low to moderate PTP and 23 (39%) of whom were considered to have high PTP (P < 0.001). In the low to moderate PTP group, HsTnT levels ≥ 0.014 μg/L identified AMI with a higher sensitivity than cTnI (91%, 95% confidence interval (95% CI) 79 to 100, vs. 77% (95% CI 60 to 95); P = 0.001), but the negative predictive value was not different (99% (95% CI 98 to 100) vs. 98% (95% CI 96 to 100)). There was no difference in area under the receiver operating characteristic (ROC) curve between HsTnT and cTnI (0.93 (95% CI 0.90 to 0.98) vs. 0.94 (95% CI 0.88 to 0.97), respectively).ConclusionsIn patients with low to moderate PTP of AMI, HsTnT is slightly more useful than cTnI. Our results confirm that the use of HsTnT has a higher sensitivity than conventional cTnI.

Influence of Age and Renal Function on High-Sensitivity Cardiac Troponin T Diagnostic Accuracy for the Diagnosis of Acute Myocardial Infarction

Concerns have been raised about the performance of highly sensitive cardiac troponin assays to accurately detect acute myocardial infarction (AMI), particularly in non-ST segment elevation (NSTEMI), in elderly patients, and in patients with renal failure. We evaluated whether increased age and low estimated glomerular filtration rate (eGFR) alter diagnostic performance of high-sensitivity cardiac troponin T (HScTnT). In a prospective multicentric study, HScTnT levels were measured blindly at presentation in patients with acute chest pain. Three hundred and sixty-seven patients were enrolled, including 84 patients ≥70 years. Final diagnosis was AMI for 57 patients (16%) and NSTEMI for 43 patients (12%). NSTEMI was more frequent in elderly patients (p = 0.008). Sensitivity and specificity of HScTnT >14 ng/L at admission for AMI were 96% and 51% in patients ≥70 years versus 91% (NS) and 88% (p <0.0001) in younger patients; the same observations were done for the diagnosis of NSTEMI. Given an HScTnT >53.5 ng/L for the diagnosis of AMI and NSTEMI, respective sensitivities were 87% and 84% and respective specificities were 87% and 87% in elderly patients. Using a cutoff at 35.8 ng/L (for AMI) or 43.2 ng/L (for NSTEMI), sensitivities were 94% and 92%, and specificities were 86% and 88% in patients with low eGFR. Older age, but not low eGFR, was an independent predictive factor of an elevated HScTnT at admission (odds ratio 2.2 [1.2-3.9], p = 0.007). In conclusion, adapted thresholds of HScTnT are required for an accurate diagnosis of AMI/NSTEMI in patients aged ≥70 and in those with low eGFR.

Comparison of conventional and high-sensitivity troponin in patients with chest pain: A collaborative meta-analysis

BACKGROUND Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain. METHODS MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data. RESULTS From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up (P < .001) compared with both negative. CONCLUSION High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up.

Cytokine Profiles in Sepsis Have Limited Relevance for Stratifying Patients in the Emergency Department: A Prospective Observational Study

Introduction Morbidity, mortality and social cost of sepsis are high. Previous studies have suggested that individual cytokines levels could be used as sepsis markers. Therefore, we assessed whether the multiplex technology could identify useful cytokine profiles in Emergency Department (ED) patients. Methods ED patients were included in a single tertiary-care center prospective study. Eligible patients were >18 years and met at least one of the following criteria: fever, suspected systemic infection, ≥2 systemic inflammatory response syndrome (SIRS) criteria, hypotension or shock. Multiplex cytokine measurements were performed on serum samples collected at inclusion. Associations between cytokine levels and sepsis were assessed using univariate and multivariate logistic regressions, principal component analysis (PCA) and agglomerative hierarchical clustering (AHC). Results Among the 126 patients (71 men, 55 women; median age: 54 years [19–96 years]) included, 102 had SIRS (81%), 55 (44%) had severe sepsis and 10 (8%) had septic shock. Univariate analysis revealed weak associations between cytokine levels and sepsis. Multivariate analysis revealed independent association between sIL-2R (p = 0.01) and severe sepsis, as well as between sIL-2R (p = 0.04), IL-1β (p = 0.046), IL-8 (p = 0.02) and septic shock. However, neither PCA nor AHC distinguished profiles characteristic of sepsis. Conclusions Previous non-multiparametric studies might have reached inappropriate conclusions. Indeed, well-defined clinical conditions do not translate into particular cytokine profiles. Additional and larger trials are now required to validate the limited interest of expensive multiplex cytokine profiling for staging septic patients.

Copeptin for rapid rule out of acute myocardial infarction in emergency department

BACKGROUND Copeptin, in combination with conventional troponin (cTn), has been suggested as a means of rapid rule out of the diagnosis of acute myocardial infarction (AMI). This study aims to assess the value of copeptin for rule out of AMI, according to the pre-test probability (PTP). METHODS In a prospective multicentric study, we enrolled patients presenting into emergency departments with chest pain <6h, copeptin was measured, and PTP was quoted. The discharge diagnosis was adjudicated by 2 independent experts using all available data, including cTnI. RESULTS 317 patients were included: 148 (46%) had low, 110 (35%) moderate and 59 (19%) high PTP. Final diagnosis was AMI in 45 patients (14%). Median copeptin level was higher in AMI patients compared with that in patients having other diagnoses (23.2 vs. 9.9 pmol/L, p=0.01). A copeptin level ≥10.7 pmol/L in combination with cTnI detected AMI with higher sensitivity than for cTnI alone (98 [87-100] vs. 71 [55-83] %, p=0.001), whatever the PTP. The negative predictive value of the combination copeptin+cTnI was increased, compared to that of cTnI alone (99 [97-100] vs. 95 [92-97] %, p<0.05). CONCLUSIONS In triage of chest pain patients, the additional use of copeptin with conventional cTnI might allow a rapid and reliable rule out of the diagnosis of AMI regardless of the PTP.

Unscheduled Return Visits to the Emergency Department: Consequences for Triage

OBJECTIVES The objective was to conduct a survey of unscheduled revisits (URs) to the emergency department (ED) within 8 days of a prior visit, to test the hypothesis that patients making these URs are disproportionately likely to suffer short-term mortality or manifest a need for any admission to the hospital (adverse events [AEs]) at the time of the UR, compared to patients triaged at the same level who did not have an unscheduled ED revisit within 8 days. METHODS This was a 1-year retrospective study of patients with an UR to the ED of an urban, 1,600-bed tertiary care center and teaching hospital. The criteria for inclusion as an UR were: 1) making an emergency visit to our adult ED during 2008, without being admitted to our hospital nor being transferred to another hospital; and 2) subsequently making an UR to the same ED within 8 days following the first one. Patients who were contacted by members of our staff and specifically asked to make return visits to our ED (such as those who returned for wound care follow-up visits), and those who made more than five visits to our ED during 2008, were excluded. AEs were defined as death or hospitalization within 8 days of the second visit. RESULTS During 2008, there were 946 patients with URs (2% of patients treated and released after the first ED visit), and 931 were analyzed (n = 15 missing values). Associated with the second visit, an AE was noted for 276 (30%) patients. Eight variables were significantly associated with AE: age ≥ 65 years, previously diagnosed cancer, previously diagnosed cardiac disease, previously diagnosed psychiatric disease, presence of a relative at the time of the UR, arrival with a letter from a general practitioner at the time of the UR, a higher level of severity assigned at triage for the UR than for the first ED visit, and having had blood sample analysis performed during the first visit. The median triage score for the UR was not significantly different from that groups median triage score for the first ED visit, whereas the proportion of admissions to the hospital (29%) or to the intensive care unit (ICU; 2%) was greater overall in the UR group than in the patients making their first ED visit. CONCLUSIONS The authors observed that 2% of patients had an UR. This UR population was at greater risk of AE at the time of their URs compared to their initial visits, but the median triage nurse score was not significantly different between the first visit and the UR. This suggests that the triage score should be systematically upgraded for UR patients.

Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection

Objective: To study the contribution of lactate and procalcitonin (PCT) serum measurements for the diagnosis and the risk-stratification of patients with suspected infection presenting to the ED. Methods: Single-center one year observational study on 462 consecutive patients. Multivariate analysis to assess variables associated with sepsis, severe sepsis, septic shock and severe outcome. Results: Multivariate analysis (Odds ratio [95% CI]), showed that PCT was the best independent variable to identify sepsis (3.98 [2.60–6.10]), while lactate was the best to diagnose severe sepsis (10.88 [6.51–18.19]). Patients with both lactate above 2 mmol·L−1 and PCT above 0.8 ng·mL−1 had an enhanced risk of severe outcome. Conclusions: the dosages of lactate and PCT are complementary for the diagnosis and risk-stratification of patients evaluated in the ED for suspected infection.

Concordance between capnography and capnia in adults admitted for acute dyspnea in an ED

BACKGROUND End-tidal carbon dioxide pressure (etCO(2)) is widely used in anaesthesia and critical care in intubated patients. The aim of our preliminary study was to evaluate the feasibility of a simple device to predict capnia in spontaneously breathing patients in an emergency department (ED). PATIENTS AND METHODS This study was a prospective, nonblind study performed in our teaching hospital ED. We included nonintubated patients with dyspnea (> or =18 years) requiring measurement of arterial blood gases, as ordered by the emergency physician in charge. There were no exclusion criteria. End-tidal CO(2) was measured by an easy-to-use device connected to a microstream capnometer, which gave a continuous measurement and graphical display of the etCO(2) level of a patients exhaled breath. RESULTS A total of 43 patients (48 measurements) were included, and the majority had pneumonia (n = 12), acute cardiac failure (n = 8), asthma (n = 7), or chronic obstructive pulmonary disease exacerbation (n = 6). Using simple linear regression, the correlation between etCO(2) and Paco(2) was good (R = 0.82). However, 18 measurements (38%) had a difference between etCO(2) and Paco(2) of 10 mm Hg or more. The mean difference between the Paco(2) and etCO(2) levels was 8 mm Hg. Using the Bland and Altman matrix, the limits of agreement were -10 to +26 mm Hg. CONCLUSION In our preliminary study, etCO(2) using a microstream method does not seem to accurately predict Paco(2) in patients presenting to an ED for acute dyspnea.

Relation between pulse oximetry plethysmographic waveform amplitude induced by passive leg raising and cardiac index in spontaneously breathing subjects.

INTRODUCTION Previous studies suggested that variation of pulse oximetric plethysmographic (POP) waveform amplitude (Delta POP) could predict fluid responsiveness in mechanically ventilated patients. Our objective was to correlate the variations of Delta POP and the variations of cardiac index (CI) induced by passive leg raising (PLR) in spontaneously breathing volunteers. METHODS We studied 26 spontaneously breathing volunteers using a pulse oximeter attached to the middle finger. We assessed hemodynamic variables, including Delta POP (%) (POP(max) - POP(min))/[(POP(max) + POP(min))/2] and CI determined by transthoracic echocardiography at baseline (eg, semirecumbent position), during PLR at 60 degrees, and back to baseline. RESULTS Cardiac index significantly increased from 2.2 to 2.5 L/min x m(2) (P < .01) at 60 degrees PLR. Conversely, Delta POP significantly decreased from 22% to 15% (P < .01) at 60 degrees PLR. There was a weak correlation between CI and Delta POP variations at 60 degrees PLR (r = 0.40; P < .01). The area under curve of the receiver operating characteristic curve for Delta POP as a predictor of an increase of CI of 15% was not significant (0.67 +/- 0.10; P = .16). CONCLUSION The variation of Delta POP induced by PLR is not an accurate predictor of increase in CI.