The role of cardiac testing with the 0/1-hour high-sensitivity cardiac troponin algorithm evaluating for acute myocardial infarction.

BACKGROUND: The role of cardiac testing in the 3 zones (rule-out, observation, and rule-in) of the 0/1-hour algorithm to evaluate for acute myocardial infarction (AMI) has not been well studied. This study evaluated the 0/1-hour algorithm with a high-sensitivity cardiac troponin (hs-cTnI) assay and investigated cardiac testing in the 3 zones. METHODS: Patients (n = 552) at a single urban center were enrolled if they were evaluated for AMI. Blood samples were obtained at presentation, 1 hour, and 3 hours for hs-cTnI. Follow-up at 30 to 45 days for death/AMI was done. The results of echocardiograms, stress testing, and coronary angiography were recorded. RESULTS: In total, 45 (8.2%) had AMI (27 Type 1 and 18 Type 2) during the index hospitalization while at follow-up death/AMI occurred in 11 (2.0%) of patients. The rule-out algorithm had a negative predictive value for AMI of 99.6% while the rule-in zone had a positive predictive value of 56.6%. The MACE rate at follow-up was 0.4% for those in the rule-out group. There were 6/95 (6.3%) abnormal stress tests in the rule-out zone and 4 of these were false positives. CONCLUSIONS: The 0/1-hour algorithm had high diagnostic sensitivity and negative predictive value for AMI, and adverse events were very low in patients in the rule-out zone. Noninvasive testing in rule-out zone patients had low diagnostic yield.

Ultrarapid Rule-out for Acute Myocardial Infarction Using the Generation 5 Cardiac Troponin T Assay: Results From the REACTION-US Study.

STUDY OBJECTIVE: We determine how well a new Food and Drug Administration-approved single cardiac troponin T (cTnT) Generation 5 baseline measurement below the level of quantification (6 ng/L) and a novel study-derived baseline and 30-minute cTnT Generation 5 algorithm might adequately exclude acute myocardial infarction in patients with suspected acute coronary syndrome in a US emergency department (ED). METHODS: Patients presenting with any symptoms suspicious for acute coronary syndrome were enrolled at a single US ED. Baseline and 30-minute blood samples were obtained and cTnT Generation 5 levels were later batch analyzed in an independent core laboratory. Acute myocardial infarction diagnosis was adjudicated by a cardiologist and an emergency physician. RESULTS: Of the 569 study patients, 44 (7.7%) had an acute myocardial infarction diagnosis. One hundred sixty-four patients (28.8%) had a presentation cTnT Generation 5 level less than 6 ng/L, and none of these individuals had an acute myocardial infarction (negative predictive value of 100% [95% confidence interval 97.8% to 100.0%] and sensitivity of 100% [95% confidence interval 92.0% to 100.0%]). A baseline cTnT Generation 5 value of less than 8 ng/L and a 30-minute Δ of less than 3 ng/L were present in 221 patients (41.0%), and none had acute myocardial infarction (negative predictive value of 100% [95% confidence interval 98.3% to 100.0%] and sensitivity of 100% [95% confidence interval 92.0% to 100.0%]). CONCLUSION: In a single US ED, a single baseline cTnT Generation 5 measurement less than 6 mg/L and values at baseline less than 8 ng/L and a 30-minute Δ of less than 3 ng/L ruled out acute myocardial infarction in 28.8% and 41.0% of patients, respectively. Additional multicenter US studies evaluating these ultrarapid acute myocardial infarction rule-out guidelines are needed, especially to narrow the confidence intervals.

Differentiating type 1 and 2 acute myocardial infarctions using the N-terminal pro B-type natriuretic peptide/cardiac troponin T ratio.

PURPOSE: Differentiation of type 1 (T1MI) from type 2 myocardial infarction (T2MI) is important as recommended treatments for each differ. Patients with T2MI may have more/earlier cardiac wall stress resulting in an increased N-terminal pro B-type natriuretic peptide (NT-proBNP)/cTnT generation 5 ratio (cTnT Gen 5). METHODS: Emergency Department (ED) patients presenting with symptoms suspicious for acute coronary syndrome (ACS) were enrolled from 2013 to 2015. Baseline blood samples were collected within 60 min of a triage ECG, with additional draws at 30, 60 and 180 min. NT-proBNP and cTnT Gen 5 levels were measured later in an independent laboratory. Acute myocardial infarction (AMI) was adjudicated using the Third Universal Definition of Myocardial Infarction. RESULTS: 575 patients were enrolled with 44 (7.7%) having AMI [25 T1MI (59.1%) and 18 T2MI (40.9%)]. Patient characteristics showed very few AMI type differences so accurate clinical differentiation was difficult. The median NT-proBNP/cTnT Gen 5 ratios were significantly higher in T2MI when compared to T2MI at baseline and 30, 60 and 180 min later [7.3 v 53.0 (p = 0.003), 5.8 v 49.5 (p = 0.002), 6.3 v 47.5 (p = 0.003) and 4.3 v 33.7 (p = 0.016) respectively]. CONCLUSIONS: The clinical determination of whether an AMI is type 1 or 2 is difficult as the ED patient characteristics of each are similar. The NT-proBNP/cTnT Gen 5 ratio can aid in making this differentiation. Additional multicenter trials are needed to validate our results.

The utility of the triage electrocardiogram for the detection of ST-segment elevation myocardial infarction.

INTRODUCTION: Current AHA/ACC guidelines on the management of ST-elevation myocardial infarction (STEMI) suggest that an ECG is indicated within 10minutes of arrival for patients arriving to the Emergency Department (ED) with symptoms concerning for STEMI. In response, there has been a creep towards performing ECGs more frequently in triage. The objectives of this study were to quantify the number of triage ECGs performed at our institution, assess the proportion of ECGs performed within current hospital guidelines, and evaluate the rate of STEMI detection in triage ECGs. METHODS: A retrospective chart review of all emergency department patients presenting over a period of 8days who had a triage ECG performed. Cases of bradycardia or tachycardia were excluded. Data collection included patient demographics, presenting complaint, cardiac risk factors, troponin values, and final diagnosis. Summary statistics are reported in a descriptive manner. RESULTS: During the study period, 538 patients had a triage ECG for possible STEMI with no STEMI identified and 16 NSTEMI diagnoses (confirmed as positive troponins following ED assessment). Sixty-three (11.7%) patients did not meet internal criteria for a triage ECG. A NSTEMI ED diagnosis was identified in 3% of patients who met internal triage ECG criteria and 1.6% who did not meet criteria (p=0.29). A cost analysis was performed using an average of 50 STEMI cases diagnosed in our ED per given year. Current institutional ECG billing rates for ECGs performed and interpreted is $125 per ECG, providing an estimated triage ECG charge to detect one STEMI at $54,295. DISCUSSION: This retrospective study of 538 triage ECG's performed over an 8day period identified no STEMIs and 16 NSTEMIs. A very large number of ECGs were done at triage overall and included patients who do not meet our own hospital criteria. Given the extremely low yield and high associated charges, current guidelines for triage ECG for identifying a possible STEMI should be reviewed.

Presenting phenotypes of acute heart failure patients in the ED: Identification and implications.

BACKGROUND: There is little known about the baseline hemodynamic (HD) profiles (beyond pulse/blood pressure) of patients presenting to the Emergency department (ED) with acute heart failure (AHF). Assessing these baseline parameters could help differentiate underlying HD phenotypes which could be used to develop specific phenotypic specific approaches to patient care. METHODS: Patients with suspected AHF were enrolled in the PREMIUM (Prognostic Hemodynamic Profiling in the Acutely Ill Emergency Department Patient) multinational registry and continuous HD monitoring was initiated on ED presentation using noninvasive finger cuff technology (Nexfin, BMEYE, Edwards Lifesciences, Irvine, California). Individuals with clinically suspected and later confirmed AHF were included in this analysis and initial 15minute averages for available HD parameters were calculated. K-means clustering was performed to identify out of 23 HD variables a set that provided the greatest level of inter-cluster discrimination and intra-cluster cohesions. RESULTS: A total of 127 patients had confirmed AHF. The final model, using mean normalized patient baseline HD values was able to differentiate these individuals into 3 distinct phenotypes. Cluster 1: normal cardiac index (CCI) and systemic vascular resistance index (SVRI); cluster 2: very low CI and markedly increased SVRI: and cluster 3: low CI and an elevated SVRI. These clusters were not differentiated using clinically available ED information. CONCLUSIONS: Three distinct clusters were defined using novel noninvasive presenting HD monitoring technology in this cohort of ED AHF patients. Further studies are needed to determine whether phenotypic specific therapies based on these clusters can improve outcomes.

Hemodynamic characteristics of suspected stroke in the emergency department.

BACKGROUND: Systemic hemodynamic characteristics of patients with suspected acute ischemic stroke are poorly described. The objective of this study was to identify baseline hemodynamic characteristics of emergency department (ED) patients with suspected acute stroke. METHODS: This was a planned analysis of the stroke cohort from a multicenter registry of hemodynamic profiling of ED patients. The registry prospectively collected non-invasive hemodynamic measurements of patients with suspicion for acute stroke within 12h of symptom onset. K-means cluster analysis identified hemodynamic phenotypes of all suspected stroke patients, and we performed univariate hemodynamic comparisons based on final diagnoses. RESULTS: There were 72 patients with suspected acute stroke, of whom 38 (53%) had a final diagnosis of ischemic stroke, 10 (14%) had hemorrhagic stroke, and 24 (33%) had transient ischemic attack (TIA). Analysis defined three phenotypic clusters based on low or normal cardiac index (CI) and normal or high systemic vascular resistance index (SVRI). Patients with TIA had lower mean CI (2.3L/min/m2) compared to hemorrhagic or ischemic stroke patients (p<0.01). CONCLUSIONS: The study demonstrates the feasibility of defining hemodynamic phenotypes of ED patients with suspected stroke.

Presenting hemodynamic phenotypes in ED patients with confirmed sepsis.

OBJECTIVES: To derive distinct clusters of septic emergency department (ED) patients based on their presenting noninvasive hemodynamic (HD) measurements and to determine if any clinical parameters could identify these groups. METHODS: Prospective, observational, convenience study of individuals with confirmed systemic infection. Presenting, pretreatment noninvasive HD parameters were compiled using Nexfin (Bmeye/Edwards LifeSciences) from 127 cases. Based on normalized parameters, k-means clustering was performed to identify a set of variables providing the greatest level of intercluster discrimination and intracluster cohesion. RESULTS: Our best HD clustering model used 2 parameters: the cardiac index (CI [L/min per square meter]) and systemic vascular resistance index (SVRI [dynes·s/cm5 per square meter]). Using this model, 3 different patient clusters were identified. Cluster 1 had high CI with normal SVRI (CI, 4.03 ± 0.61; SVRI, 1655.20 ± 348.08); cluster 2 low CI with increased vascular tone (CI, 2.50 ± 0.50; SVRI, 2600.83 ± 576.81); and cluster 3 very low CI with markedly elevated SVRI (CI, 1.37 ± 0.81; SVRI, 5951.49 ± 1480.16). Cluster 1 patients had the lowest 30-day overall mortality. Among clinically relevant variables available during the initial patient evaluation in the ED age, heart rate and temperature were significantly different across the 3 clusters. CONCLUSIONS: Emergency department patients with confirmed sepsis had 3 distinct cluster groupings based on their presenting noninvasively derived CI and SVRI. Further clinical studies evaluating the effect of early cluster-specific therapeutic interventions are needed to determine if there are outcome benefits of ED HD phenotyping in these patients.

The inability of emergency physicians to adequately clinically estimate the underlying hemodynamic profiles of acutely ill patients.

OBJECTIVE: Emergency physicians (EPs) estimate the underlying hemodynamics of acutely ill patients and use them to help both diagnose and formulate a treatment plan. This trial compared the EP clinically derived estimates of cardiac output (CO) and systemic vascular resistance (SVR) to those measured noninvasively. METHODS: Forty acutely ill emergency department patients with a broad range of diagnosis and blood pressure (BP) and pulse were monitored for 2 hours using novel noninvasive finger cuff technology (Nexfin; BMEYE, Amsterdam, The Netherlands). The Nexfin device provides continuous BP monitoring and, from the resulting pulse pressure waveform, calculates beat-to-beat CO and SVR. At baseline assessment and after 2 hours of testing and therapy, treating EPs were asked to estimate the CO and SVR (low, normal, or high), and these were compared with Nexfin measurements. RESULTS: Twenty-five men and 15 women were enrolled with a mean age of 62.2 years (SD, 12.6 years). Eighteen had acute shortness of breath; 11, with probable stroke syndrome; 3, with suspected sepsis; and 8, with a systolic BP greater than 180 or less than 100 mm Hg. Concordance tables showed that there was very little agreement (κ values) between either the compared initial CO (-0.0873) and SVR (-0.0645) or the 2-hour values (-0.0645 and -0.1949, respectively). CONCLUSIONS: Emergency physicians cannot accurately estimate the underlying hemodynamic profiles of acutely ill patients when compared with more objective measurements. This inaccuracy may have important clinical ramifications. Further study is needed to determine how to use these measured continuous CO and SVR monitoring values.

Machine Learning to Assess for Acute Myocardial Infarction Within 30 Minutes.

Variations in high-sensitivity cardiac troponin I by age and sex along with various sampling times can make the evaluation for acute myocardial infarction (AMI) challenging. Machine learning integrates these variables to allow a more accurate evaluation for possible AMI. The goal was to test the diagnostic and prognostic utility of a machine learning algorithm in the evaluation of possible AMI. We applied a machine learning algorithm (myocardial-ischemic-injury-index [MI3]) that incorporates age, sex, and high-sensitivity cardiac troponin I levels at time 0 and 30 minutes in 529 patients evaluated for possible AMI in a single urban emergency department. MI3 generates an index value from 0 to 100 reflecting the likelihood of AMI. Patients were followed at 30-45 days for major adverse cardiac events (MACEs). There were 42 (7.9%) patients that had an AMI. Patients were divided into 3 groups by the MI3 score: low-risk (≤ 3.13), intermediate-risk (> 3.13-51.0), and high-risk (> 51.0). The sensitivity for AMI was 100% with a MI3 value ≤ 3.13 and 353 (67%) ruled-out for AMI at 30 minutes. At 30-45 days, there were 2 (0.6%) MACEs (2 noncardiac deaths) in the low-risk group, in the intermediate-risk group 4 (3.0%) MACEs (3 AMIs, 1 cardiac death), and in the high-risk group 4 (9.1%) MACEs (4 AMIs, 2 cardiac deaths). The MI3 algorithm had 100% sensitivity for AMI at 30 minutes and identified a low-risk cohort who may be considered for early discharge.

Noninvasive continuous or intermittent blood pressure and heart rate patient monitoring in the ED.

OBJECTIVE: Continuous invasive blood pressure (BP) and heart rate (HR) monitoring in the emergency department (ED) is valuable in managing critically ill patients. Novel noninvasive finger cuff technology allows this same uninterrupted monitoring for almost any individual. This exploratory study compares ED noninvasive continuous to intermittent measurements of these variables. METHODS: A variety of acutely ill ED patients (n = 40) with broad ranges of BP and HR underwent simultaneous monitoring using interval standard automated ED devices and continuous finger cuff technology (Nexfin; Bmeye, Amsterdam, The Netherlands) over a period of 2 hours. At baseline and at 15-minute intervals, simultaneous measurements for BP and HR were recorded and compared. RESULTS: There were 25 men and 15 women enrolled with a mean age of 62.2 years (SD, 12.6). Eighteen had acute dyspnea, 11 with probable stroke syndrome, 3 with suspected sepsis, and 8 with a systolic BP greater than 180 or less than 100 mm Hg. Blood pressure and HR values (n = 344) simultaneously measured by automated ED equipment and the Nexfin finger cuff device were compared. The Pearson correlation coefficients were high, and the Bland-Altman plots showed good agreement between the 2 determinations. CONCLUSION: Continuous BP and HR monitoring measured by the Nexfin finger cuff device in this trial showed reasonable agreement when compared with the intermittent values obtained by automated ED equipment. However, theoretically, noninvasive and continuous monitoring of the BP and HR might better reflect underlying hemodynamics than these same measurements obtained intermittently and, thus, could be important in patient management. More study is needed to determine the optimal method of monitoring these parameters.

Is Duration of Symptoms Predictive of Acute Myocardial Infarction?

Patient interviews regarding the duration of symptoms are commonly conducted when evaluating a patient with possible acute myocardial infarction (AMI) and are believed to distinguish between AMI and non-AMI symptoms. In a single center, 569 patients evaluated in the emergency department (ED) for possible AMI from May 2013 to April 2015 were prospectively studied. Patients in the ED were asked by trained research personnel about the duration of their predominant symptom. The final diagnosis of AMI was determined by an independent cardiologist and emergency medicine physician in accordance with the third universal definition of AMI. Disagreements were settled by a third physician (cardiologist) who reviewed the case. There were 44 (8%) AMIs and 484 (85%) patients had chest pain as their predominant symptom. In the 26 type 1 AMIs, the median symptom duration was 3.3 hours, while in the 18 type 2 AMIs it was 1.3 hours. AMI was not present if symptom duration was under 20 minutes and was more likely during the 20-59 minute period. In conclusion, clinical symptoms still play a prominent role in the evaluation of a patient with possible AMI in the ED. Duration of symptoms was not very helpful in distinguishing between patients with AMI and those with non-AMI, except in the time interval of 20-59 minutes.

Baseline High Sensitivity Cardiac Troponin I Level Below Limit of Quantitation Rules Out Acute Myocardial Infarction in the Emergency Department.

The objective of our study was to determine the utility of a baseline high sensitivity cardiac troponin (hs-cTnI) value below the limit of quantitation to rule-out acute myocardial infarction (AMI) in patients presenting to the emergency department (ED) with any suspicious symptoms of a cardiac etiology. We enrolled subjects presenting to the ED with symptoms suspicious for AMI. Blood specimens were collected within 1 hour after a triage electrocardiogram. Cardiac troponin I was measured using the Beckman Coulter Access hs-cTnI assay. The diagnosis of AMI was adjudicated by 2 cardiologists using the Third Universal Definition of AMI and Roche Diagnostics Troponin T Generation 5 assay with all available clinical data at 30 days after presentation. A total of 567 subjects had all data required for data analyses. AMI was diagnosed in 46 (8.1%) patients. Two hundred thirty-two (40.9%) individuals had presentation hs-cTnI results <4.0 ng/L. None of the patients with baseline hs-cTnI <4.0 ng/L had an AMI, yielding a negative predictive value of 100.0% and a sensitivity of 100%, and a good prognosis (no AMIs or cardiac-related deaths at 30 days). In this single-center ED study, a baseline presenting novel hs-cTnI value of <4.0 ng/L effectively ruled out AMI in 40.9% of all patients presenting to the ED and having any symptoms suspicious for AMI. Importantly all patients, not only those with chest pain, and those having symptoms for any duration or those with end-stage renal disease requiring dialysis were included.

Continuous hemodynamic monitoring in acute stroke: an exploratory analysis.

INTRODUCTION: Non-invasive, continuous hemodynamic monitoring is entering the clinical arena. The primary objective of this study was to test the feasibility of such monitoring in a pilot sample of Emergency Department (ED) stroke patients. Secondary objectives included analysis of hemodynamic variability and correlation of continuous blood pressure measurements with standard measurements. METHODS: This study was a secondary analysis of 7 stroke patients from a prospectively collected data set of patients that received 2 hours of hemodynamic monitoring in the ED. Stroke patients were included if hemorrhagic or ischemic stroke was confirmed by neuroimaging, and symptom onset was within 24 hours. They were excluded for the presence of a stroke mimic or transient ischemic attack. Monitoring was performed using the Nexfin device (Edwards Lifesciences, Irvine CA). RESULTS: The mean age of the cohort was 71 ± 17 years, 43% were male, and the mean National Institute of Health Stroke Scale (NIHSS) was 6.9 ± 5.5. Two patients had hemorrhagic stroke. We obtained 42,456 hemodynamic data points, including beat-to-beat blood pressure measurements with variability of 18 mmHg and cardiac indices ranging from 1.8 to 3.6 l/min/m2. The correlation coefficient between continuous blood pressure measurements with the Nexfin device and standard ED readings was 0.83. CONCLUSION: This exploratory investigation revealed that continuous, noninvasive monitoring in the ED is feasible in acute stroke. Further research is currently underway to determine how such monitoring may impact outcomes in stroke or replace the need for invasive monitoring.

Noninvasive hemodynamic monitoring in emergency patients with suspected heart failure, sepsis and stroke: the PREMIUM registry.

INTRODUCTION: Noninvasive hemodynamic (HD) assessments in the emergency department (ED) might assist in the diagnosis, therapeutic plan development and risk stratification of acutely ill patients. This multinational observational study was designed to initiate noninvasive HD measurements prior to any ED patient therapeutic interventions and broadly evaluate them for potential diagnostic, therapeutic and predictive value. METHODS: We enrolled patients with suspected acute heart failure (AHF), sepsis or stroke. Continuous noninvasive HD monitoring was begun using the Nexfin finger cuff device (Edwards LifeSciences, BMEYE, Amsterdam, Netherlands). Beat-to-beat HD measurements were averaged for the initial 15 minutes, prior to therapeutic intervention. We performed suspected disease group comparisons and evaluated HD predictors of 30-day mortality. RESULTS: Of 510 patients enrolled: 185 (36%) AHF, 194 (38%) sepsis and 131 (26%) stroke. HD variables were significantly different (p<0.05) amongst the groups. Cardiac output and index and stroke volume index (SVI) were highest in sepsis (6.5, 3.5, 36), followed by stroke (5.5, 2.7, 35.8), and lowest in AHF (5.4, 2.7, 33.6). The in-group HD standard deviations and ranges measurements were large, indicating heterogeneous underlying HD profiles. Presenting SVI predicted 30-day mortality for all groups. CONCLUSION: Presenting ED noninvasive HD data has not been previously reported in any large patient population. Our data suggest a potential role for early noninvasive HD assessments aiding in diagnosing of patients, individualizing therapy based on each person's unique HD values and predicting 30-day mortality. Further studies and analyses are needed to determine how HD assessments should be best used in the ED.