Diercks, Deborah B.

Background Cardiac troponin (cTn) can be elevated in many patients presenting to the emergency department (ED) with chest pain but without a diagnosis of acute coronary syndrome (ACS). We compared the prognostic significance of cTn in these different populations. Methods We retrospectively analyzed the CHOPIN study, which enrolled patients who presented to the ED with chest pain. Patients were grouped as ACS, non-ACS cardiovascular disease, noncardiac chest pain and chest pain not otherwise specified (NOS). We examined the prognostic ability of cTnI for the clinical endpoints of mortality and major adverse cardiovascular event (MACE; a composite of acute myocardial infarction, unstable angina, revascularization, reinfarction, and congestive heart failure and stroke) at 180-day follow-up. Results Among 1982 patients analyzed, 14% had ACS, 21% had non-ACS cardiovascular disease, 31% had a noncardiac diagnosis and 34% had chest pain NOS. cTnI elevation above the 99th percentile was observed in 52, 18, 6 and 7% in these groups, respectively. cTnI elevation was associated with mortality and MACE, and their relationships were more prominent in noncardiac diagnosis and chest pain NOS than in ACS and non-ACS cardiovascular diagnoses for mortality, and in non-ACS patients than in ACS patients for MACE (hazard ratio for doubling of cTnI 1.85, 2.05, 8.26 and 4.14, respectively; P for interaction 0.011 for mortality; 1.04, 1.23, 1.54 and 1.42, respectively; P for interaction <0.001 for MACE). Conclusion In patients presenting to the ED with chest pain, cTnI elevation was associated with a worse prognosis in non-ACS patients than in ACS patients.

AbstractThis first Guideline for Reasonable and Appropriate Care in the Emergency Department (GRACE‐1) from the Society for Academic Emergency Medicine is on the topic: Recurrent, Low‐risk Chest Pain in the Emergency Department. The multidisciplinary guideline panel used The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding eight priority questions for adult patients with recurrent, low‐risk chest pain and have derived the following evidence based recommendations: (1) for those >3 h chest pain duration we suggest a single, high‐sensitivity troponin below a validated threshold to reasonably exclude acute coronary syndrome (ACS) within 30 days; (2) for those with a normal stress test within the previous 12 months, we do not recommend repeat routine stress testing as a means to decrease rates of major adverse cardiac events at 30 days; (3) insufficient evidence to recommend hospitalization (either standard inpatient admission or observation stay) versus discharge as a strategy to mitigate major adverse cardiac events within 30 days; (4) for those with non‐obstructive (<50% stenosis) coronary artery disease (CAD) on prior angiography within 5 years, we suggest referral for expedited outpatient testing as warranted rather than admission for inpatient evaluation; (5) for those with no occlusive CAD (0% stenosis) on prior angiography within 5 years, we recommend referral for expedited outpatient testing as warranted rather than admission for inpatient evaluation; (6) for those with a prior coronary computed tomographic angiography within the past 2 years with no coronary stenosis, we suggest no further diagnostic testing other than a single, normal high‐sensitivity troponin below a validated threshold to exclude ACS within that 2 year time frame; (7) we suggest the use of depression and anxiety screening tools as these might have an effect on healthcare use and return emergency department (ED) visits; and (8) we suggest referral for anxiety or depression management, as this might have an impact on healthcare use and return ED visits.

Introduction: Copeptin has demonstrated a role in early rule out for acute myocardial infarction in combination with a negative troponin. However, the value of copeptin in patients with a positive troponin is not established. Hypothesis: The addition of a baseline copeptin at chest pain presentation will improve risk stratification in patients with mild troponin elevation. Methods: The multi-center CHOPIN trial enrolled 2071 acute chest pain patients. All subjects with ST segment elevations were excluded from this analysis. Of the remaining patients, 124 had a mildly elevated troponin (defined by < 2x URL) and were included in the study cohort. Baseline cTnI and copeptin levels were drawn on presentation, and another cTnI at 2 hours. Copeptin ≤14 pmol/l and troponin deltas ≤10% from baseline were considered positive. Two independent blinded cardiologists adjudicated AMI diagnosis. The value of a baseline copeptin in this cohort was assessed using AMI incidence, odds ratio, sensitivity, and negative predictive value (NPV). Results: Of the 124 patients in the study cohort, 73 (59%) had an elevated copeptin and an associated AMI incidence of 25% (18 AMIs). The remaining 51 patients (41%) were copeptin negative and diagnosed with 3 AMIs, an incidence of 5.9% (p = 0.006, figure 1). A positive copeptin increased the likelihood of AMI diagnosis with an odds ratio of 5.3 (95% CI: 1.5-19.2). The sensitivity and NPV for AMI were 86% and 94%, both of which were higher than the delta troponin (table 1). When an initial copeptin was combined with the delta troponin the sensitivity and NPV for AMI improved to 100%. Conclusion: Use of copeptin in chest pain patients with mild troponin elevation provides further risk stratification. The combination of copeptin with a delta troponin may aid in earlier AMI rule out in this subset of patients. This approach could be especially relevant as the increasing use of high sensitivity troponin assays leads to greater rates of mild troponin elevations.

Background: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. Methods: Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. Results: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P =0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI. Conclusions: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.

Background: Copeptin in combination with troponin has been shown to have incremental value for the early rule-out of myocardial infarction, but its performance in Black patients specifically has never been examined. In light of a potential for wider use, data on copeptin in different relevant cohorts are needed. This is the first study to determine whether copeptin is equally effective at ruling out myocardial infarction in Black and Caucasian races. Methods: This analysis of the CHOPIN trial included 792 Black and 1075 Caucasian patients who presented to the emergency department with chest pain and had troponin-I and copeptin levels drawn. Results: One hundred and forty-nine patients were diagnosed with myocardial infarction (54 Black and 95 Caucasian). The negative predictive value of copeptin at a cut-off of 14 pmol/l (as in the CHOPIN study) for myocardial infarction was higher in Blacks (98.0%, 95% confidence interval (CI) 96.2–99.1%) than Caucasians (94.1%, 95% CI 92.1–95.7%). The sensitivity at 14 pmol/l was higher in Blacks (83.3%, 95% CI 70.7–92.1%) than Caucasians (53.7%, 95% CI 43.2–64.0%). After controlling for age, hypertension, heart failure, chronic kidney disease and body mass index in a logistic regression model, the interaction term had a P value of 0.03. A cut-off of 6 pmol/l showed similar sensitivity in Caucasians as 14 pmol/l in Blacks. Conclusions: This is the first study to identify a difference in the performance of copeptin to rule out myocardial infarction between Blacks and Caucasians, with increased negative predictive value and sensitivity in the Black population at a cut-off of 14 pmol/l. This also holds true for non-ST-segment elevation myocardial infarction and, although numbers were small, similar trends exist in the normal troponin population. This may have significant implications for early rule-out strategies using copeptin.

AbstractBackgroundPatients at low risk for acute coronary syndrome are frequently admitted for observation and cardiac testing, resulting in substantial burden and cost to the patient and the health care system.ObjectivesThe purpose of this investigation was to measure the effect of the Chest Pain Choice (CPC) decision aid on overall health care utilization as well as utilization of specific services both during the index emergency department (ED) visit and in the subsequent 45 days.MethodsThis was a planned secondary analysis of data from a pragmatic multicenter randomized trial of shared decision making in adults presenting to the ED with chest pain who were being considered for observation unit admission for cardiac stress testing or coronary computed tomography angiography. The trial compared an intervention group engaged in shared decision making facilitated by the CPC decision aid to a control group receiving usual care. Hospital‐level billing data were used to measure utilization for the index ED visit and during the following 45 days. Patients in both groups also were asked to keep a diary recording health care utilization over the same 45‐day period. Outcomes assessed included length of time in the ED and observation, ED visits, office visits, hospitalizations, testing, imaging, and procedures.ResultsOf the 898 patients included in the original trial, we were able to contact 834 (92.9%) patients for 45‐day health care diary review. There was no difference in patient‐reported health care utilization between the study arms. Hospital‐level billing data were obtained for all 898 (100%) patients. During the initial ED visit the length of stay (LOS) was similar, and there was no difference in the frequency of observation unit admission between study arms. However, the mean observation unit LOS was 95 minutes (95% confidence interval [CI] = 40.8–149.8) shorter in the CPC arm and the mean number of tests was lower in the CPC arm (decrease in 19.4 imaging studies per 100 patients, 95% CI = 15.5–23.3). When evaluating the entire encounter and follow‐up period, the intervention arm underwent fewer tests (decrease in 125.6 tests per 100 patients, 95% CI = 29.3–221.6). More specifically, there were fewer advanced cardiac imaging tests completed (25.8 fewer per 100 patients, 95% CI = 3.74–47.9) in the intervention arm.ConclusionsShared decision making in low‐risk chest pain can lead to decreased diagnostic testing without worsening outcomes measured over 45 days.

AbstractBackgroundGuidelines suggest that “upstream” P2Y12 receptor antagonists should be considered in patients with non–ST‐segment elevation acute coronary syndromes (NSTE‐ACS).HypothesisEarly use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency.MethodsIn the PLATO trial, 6792 NSTE‐ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of “early” (<3h) vs “late” (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes.ResultsOverall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85‐1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year.ConclusionsThe benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor.

Background. We test the hypotheses that use of the Chest Pain Choice (CPC) decision aid (DA) would be similarly effective in potentially vulnerable subgroups but increase knowledge more in patients with higher education and trust in physicians more in patients from racial minority groups. Methods. This was a secondary analysis of a multicenter randomized trial in adults with chest pain potentially due to acute coronary syndrome. The trial compared an intervention group engaged in shared decision making (SDM) using CPC to a control group receiving usual care (UC). We assessed for subgroup effects based on age, sex, race, income, insurance, education, literacy, and numeracy. We dichotomized each characteristic and tested for interactions using regression models with indicators for arm assignment and study site. Results. Of 898 patients (451 DA, 447 UC), over 50% were female, over one-third were black, nearly one-third had a high school education or less, and over 60% had “low” health literacy. The DA did not increase knowledge more in patients with higher education ( P for interaction = 0.06) but did increase knowledge more in the “typical” than in the “low” numeracy subgroup (10.6% v. 4.7%, absolute difference [AD] = 5.9%, P for interaction = 0.025). The DA did not significantly increase patient trust in physicians in racial minorities ( P for interaction = 0.06) but did increase trust more in patients with “low” literacy compared with those with “typical” literacy (3.7% v. –1.4%, AD = 5.1, P for interaction = 0.011). Conclusions. CPC benefited all sociodemographic groups to a similar extent, with greater knowledge transfer in patients with higher numeracy and greater physician trust in patients with “low” health literacy. Tailoring SDM interventions to patient characteristics may be necessary for optimal effectiveness.

AbstractObjectivesChest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR‐proADM) in prediction of mortality and major adverse cardiac events (MACE).MethodsThis was a subanalysis of the CHOPIN study, a 16‐center prospective trial that enrolled 2,071 patients presenting with chest pain within 6 hours of onset. The primary endpoint was 6‐month all‐cause mortality and the secondary endpoint was 30‐day and 6‐month MACE: ED visits or hospitalization for acute myocardial infarction, unstable angina, reinfarction, revascularization, and heart failure.ResultsMR‐proADM performed similarly to troponin (cTnI; c‐statistic = 0.845 and 0.794, respectively) for mortality prediction in all subjects and had similar results in those with noncardiac diagnoses. MR‐proADM concentrations were stratified by decile, and the cohort in the top decile had a 9.8% 6‐month mortality risk versus 0.9% risk for those in the bottom nine deciles (p < 0.0001). MR‐proADM, history of coronary artery disease (CAD), and hypertension were predictors of short‐term MACE, while history of CAD, hypertension, cTnI, and MR‐proADM were predictors of long‐term MACE.ConclusionsIn patients with chest pain, MR‐proADM predicts mortality and MACE in all‐comers with chest pain and has similar prediction in those with a noncardiac diagnosis. This exploratory analysis is primarily hypotheses‐generating and future prospective studies to identify its utility in risk stratification should be considered.