Sensitivity For Acute Myocardial Infarction Research Articles

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.

Diagnostic accuracy of a high-sensitivity troponin I assay and external validation of 0/3 h rule out strategies.

The timely diagnosis and exclusion of acute coronary syndromes in the Emergency Department (ED) remains a challenge. This study aims to evaluate the diagnostic accuracy of a high-sensitivity cardiac troponin I assay (Siemens TNIH) on serial sampling for ED patients as standalone test and in rule-out algorithms as recommendations remain assay specific. This secondary analysis from a prospective diagnostic accuracy study at 14 centres included ED patients presenting with chest pain of suspected cardiac nature. Serum drawn on arrival and 3 h later was batchtested for TNIH. The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI). We evaluated the diagnostic accuracy of absolute and relative delta criteria and four rule-out strategies. Of 802 included patients, 13.8% had AMI. Absolute delta criteria had superior accuracy to relative criteria (C-statistic 0.94 vs. 0.76, P < 0.001). However, no delta criteria achieved >95.5% sensitivity for AMI when used alone. Ruling out AMI with TNIH below the 99th percentile at 0 and 3 h had 88.3% (95% confidence interval 80.8-93.6%) sensitivity. The adapted European Society of Cardiology (ESC) 0/2 h algorithm had higher sensitivity (98.2%) than both High-STEACS (93.7%, P = 0.03) and the ESC 0/3 h algorithm (79.3%, P < 0.001). These pathways ruled out 63%, 74%, and 88% patients, respectively. With serial sampling over 3 h, the Siemens TNIH assay should be used with a validated algorithm incorporating bespoke cut-offs and absolute delta criteria. In our analysis, the adapted ESC 0/2 h algorithm had greatest sensitivity. 'Ruling out' AMI using the 99th percentile of the assay cannot be recommended.

3298Prehospital assessment of the one-hour rule-in/rule-out algorithm using a high-sensitivity cardiac troponin t assay in a low-prevalence population for acute coronary syndrome (OUT-ACS)

Abstract Background The majority of patients with chest pain in Norway initially present to the primary health care system, which serves to triage them to the specialist health care services including hospitals. In some emergency primary care institutions, patients who are not hospitalised directly undergo further diagnostic testing to rule out acute myocardial infarction (AMI). Purpose Several studies have shown the advantage of using high-sensitivity assays for fast interpretation of cardiac troponins. The majority of these studies included patient populations from hospital emergency departments. In contrast, we aimed to investigate whether the 1-hour algorithm for high-sensitivity cardiac troponin T (hs-cTnT) is safe and useful for implementation in a primary care emergency setting where the patients have a much lower pre-test probability for an acute coronary syndrome. Methods In this prospective cohort study, we included 1672 patients with acute non-specific chest pain from November 2016 to October 2018 at a primary care emergency outpatient clinic in Norway. Serial hs-cTnT samples were analysed after 0, 1 and 4 hours on the Cobas 8000 e602 analyzer. We divided the results into one of three groups (rule-out, rule-in, or further observation), according to the 0/1-hour algorithm for hs-cTn from the current ESC guidelines on non-ST-elevation myocardial infarction. In the rule-out group, the 0/1-hour results were compared to the standard 4-hour hs-cTnT. Final hospital diagnoses were collected as a gold standard for the patients in the rule-in group. Results A total of 44 (2.6%) of 1672 patients were diagnosed with AMI. By applying the algorithm, 1274 (76.2%) patients were assigned to the rule-out group. One of the rule-out patients had a significant increase in hs-cTnT in the 4-hour sample. This results in a sensitivity for AMI of 97.7% (95% confidence interval [CI] 88.0–99.9) and negative predictive value of 99.9% (95% CI 99.6–100.0). There were 50 (3.0%) patients in the rule-in group, amongst whom 35 had a verified AMI. This gives a specificity for AMI of 99.1% (95% CI 98.5–99.5) and a positive predictive value at 70.0% (95% CI 55.4–82.1). Among the 348 (20.8%) patients assigned to further observation, eight patients had an AMI. The 15 rule-in patients who did not have an AMI, had other acute illnesses that required further diagnostic work-up at the hospital. Conclusions With a negative predictive value at 99.9%, the 1-hour algorithm for hs-cTnT seems safe and applicable for a faster assessment of patients with non-specific chest pain in a primary care emergency setting. Prehospital implementation of this algorithm may reduce the need for hospitalisation of these patients and hence may probably lower the costs. ClinicalTrial.gov identifier: NCT02983123 Acknowledgement/Funding Norwegian Research Fund for General Practice, The Norwegian Physicians' Association Fund for Quality Improvement and Patient Safety

LO61: Test characteristics of high sensitivity troponin T performed at emergency department arrival for acute myocardial infarction in patients with reduced kidney function

Introduction: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular events, and have worse outcomes following acute myocardial infarction (AMI). Cardiac troponin is often elevated in CKD, making the diagnosis of AMI challenging in this population. We sought to quantify test characteristics for AMI of a high-sensitivity troponin T (hsTnT) assay performed at emergency department (ED) arrival in CKD patients with chest pain, and to derive rule-out cutoffs specific to patient subgroups stratified by estimated glomerular filtration rate (eGFR). We also quantified the sensitivity and classification performance of the assays limit of detection (5 ng/L) and the FDA-approved limit of quantitation (6 ng/L) for ruling out AMI at ED arrival. Methods: Consecutive patients in four urban EDs from the 2013 calendar year with suspected cardiac chest pain who had a Roche Elecsys hsTnT assay performed on arrival were included f. This analysis was restricted to patients with an eGFR&lt; 60 ml/min/1.73m2. The primary outcome was 7-day AMI. Secondary outcomes included major adverse cardiac events (death, AMI and revascularization). Test characteristics were calculated and ROC curves were generated for eGFR subgroups. Results: 1416 patients were included. 7-day AMI incidence was 10.1%. 73% of patients had an initial hsTnT concentration greater than the assays 99th percentile (14 ng/L). TCurrently accepted cutoffs to rule out MI at ED arrival ( 5 ng/L and 6 ng/L) had 100% sensitivity for AMI, but no patients with an eGFR less than 30 ml/min/1.73M had hsTnT concentrations below these thresholds. We derived eGFR-adjusted cutoffs to rule out MI with sensitivity &gt;98% at ED arrival, which were able to rule out 6-42% of patients, depending on eGFR category. The proportion of patients able to be accurately ruled-in with a single hsTnT assay was substantially lower among patients with an eGFR &lt;30 ml/min/1.73m2 (6-20% vs 25-43%). We also derived eGFR-adjusted cutoffs to rule-in AMI with specificity &gt;90%, which accurately ruled-in up to 18% of patients. Conclusion: Cutoffs achieving acceptable diagnostic performance for AMI using single hsTnT sampling on ED arrival may have limited clinical utility, particularly among patients with very low eGFR. The ideal diagnostic strategy for AMI in patients with CKD likely involves serial high-sensitivity troponin testing with diagnostic thresholds customized to different eGFR categories.

Diagnostic Accuracy of a New High-Sensitivity Troponin I Assay and Five Accelerated Diagnostic Pathways for Ruling Out Acute Myocardial Infarction and Acute Coronary Syndrome

This diagnostic accuracy study describes the performance of 5 accelerated chest pain pathways, calculated with the new Beckman's Access high-sensitivity troponin I assay. High-sensitivity troponin I was measured with presentation and 2-hour blood samples in 1,811 patients who presented to an emergency department (ED) in Australia. Patients were classified as being at low risk according to 5 rules: modified accelerated diagnostic protocol to assess patients with chest pain symptoms using troponin as the only biomarker (m-ADAPT), the Emergency Department Assessment of Chest Pain Score (EDACS) pathway, the History, ECG, Age, Risk Factors, and Troponin (HEART) pathway, the No Objective Testing Rule, and the new Vancouver Chest Pain Rule. Endpoints were 30-day acute myocardial infarction and acute coronary syndrome. Measures of diagnostic accuracy for each rule were calculated. Data included 96 patients (5.3%) with acute myocardial infarction and 139 (7.7%) with acute coronary syndrome. The new Vancouver Chest Pain Rule and No Objective Testing Rule had high sensitivity for acute myocardial infarction (100%; 95% confidence interval [CI] 96.2% to 100% for both) and acute coronary syndrome (98.6% [95% CI 94.9% to 99.8%] and 99.3% [95% CI 96.1% to 100%]). The m-ADAPT, EDACS, and HEART pathways also yielded high sensitivity for acute myocardial infarction (96.9% [95% CI 91.1% to 99.4%] for m-ADAPT and 97.9% [95% CI 92.7% to 99.7%] for EDACS and HEART), but lower sensitivity for acute coronary syndrome (≤95.0% for all). The m-ADAPT, EDACS, and HEART rules classified more patients as being at low risk (64.3%, 62.5%, and 49.8%, respectively) than the new Vancouver Chest Pain Rule and No Objective Testing Rule (28.2% and 34.5%, respectively). In this cohort with a low prevalence of acute myocardial infarction and acute coronary syndrome, using the Beckman's Access high-sensitivity troponin I assay with the new Vancouver Chest Pain Rule or No Objective Testing Rule enabled approximately one third of patients to be safely discharged after 2-hour risk stratification with no further testing. The EDACS, m-ADAPT, or HEART pathway enabled half of ED patients to be rapidly referred for objective testing.

Troponin Limit of Detection Plus Cardiac Risk Stratification Scores to Rule Out Acute Myocardial Infarction and 30-Day Major Adverse Cardiac Events in ED Patients.

When screening for acute myocardial infarction (AMI), troponin levels below the 99th percentile, including those below the limit of detection (LOD), are considered normal. We hypothesized that a low-risk HEART score (0-3) or ACS Pretest Probability Assessment <2% plus a single troponin below the LOD would rule out both AMI and 30-day major adverse cardiac events (MACE). We studied all patients who presented to a single academic emergency department and received a troponin I (Siemens Ultra Troponin I) from September 1, 2013, to November 13, 2013 (n=888). Demographic and clinical data were abstracted from the electronic medical record. Primary outcome was a final encounter diagnosis of myocardial infarction. Secondary outcome was 30-day MACE, defined as composite of myocardial infarction, revascularization, or death from a cardiac or uncertain etiology. Sensitivities of low-risk HEART score and ACS Pretest Probability <2% alone were 98% (95% confidence interval [CI], 89%-100%) and 96% (95% CI, 86%-100%) for AMI and 94% (95% CI, 86%-98%) and 95% (95% CI, 88%-99%), respectively, for 30-day MACE. When combined with troponin below the LOD, sensitivity for AMI was 100% (95% CI, 93%-100%; difference 2%; 95% CI, -2% to 6%) for low-risk HEART Score and 100% (95% CI, 93%-100%; difference 4%; 95% CI, -1.5% to 10%) for ACS Pretest Probability <2%. When combined with troponin below the LOD, sensitivity for 30-day MACE was 100% (95% CI, 95%-100%; difference 6%; 95% CI, 1%-12%) for low-risk HEART Score and 100% (95% CI, 95%-100%; difference 5%; 95% CI, 0.2%-10%) for ACS Pretest Probability <2%. Addition of a single troponin below the LOD to these scores improves sensitivity for 30-day MACE.

Differentiation between acute and chronic myocardial infarction by means of texture analysis of late gadolinium enhancement and cine cardiac magnetic resonance imaging

The purpose of this study was to differentiate acute from chronic myocardial infarction using machine learning techniques and texture features extracted from cardiac magnetic resonance imaging (MRI). The study group comprised 22 cases with acute myocardial infarction (AMI) and 22 cases with chronic myocardial infarction (CMI). Cine and late gadolinium enhancement (LGE) MRI were analyzed independently to differentiate AMI from CMI. A total of 279 texture features were extracted from predefined regions of interest (ROIs): the infarcted area on LGE MRI, and the entire myocardium on cine MRI. Classification performance was evaluated by a nested cross-validation approach combining a feature selection technique with three predictive models: random forest, support vector machine (SVM) with Gaussian Kernel, and SVM with polynomial kernel. The polynomial SVM yielded the best classification performance. Receiver operating characteristic curves provided area-under-the-curve (AUC) (mean±standard deviation) of 0.86±0.06 on LGE MRI using 72 features; AMI sensitivity=0.81±0.08 and specificity=0.84±0.09. On cine MRI, AUC=0.82±0.06 using 75 features; AMI sensitivity=0.79±0.10 and specificity=0.80±0.10. We concluded that texture analysis can be used for differentiation of AMI from CMI on cardiac LGE MRI, and also on standard cine sequences in which the infarction is visually imperceptible in most cases.

Single High-Sensitivity Cardiac Troponin I to Rule Out Acute Myocardial Infarction

BackgroundThis study examined the performance of single high-sensitivity cardiac troponin I (hs-cTnI) measurement strategies to rule out acute myocardial infarction. MethodsThis was a prospective, observational study of consecutive patients presenting to the emergency department (n = 1631) in whom cTnI measurements were obtained using an investigational hs-cTnI assay. The goals of the study were to determine 1) negative predictive value (NPV) and sensitivity for the diagnosis of acute myocardial infarction, type 1 myocardial infarction, and type 2 myocardial infarction; and 2) safety outcome of acute myocardial infarction or cardiac death at 30 days using hs-cTnI less than the limit of detection (LoD) (<1.9 ng/L) or the High-STEACS threshold (<5 ng/L) alone and in combination with normal electrocardiogram (ECG). ResultsAcute myocardial infarction occurred in 170 patients (10.4%), including 68 (4.2%) type 1 myocardial infarction and 102 (6.3%) type 2 myocardial infarction. For hs-cTnI<LoD (27%), the NPV and sensitivity for acute myocardial infarction were 99.6% (95% confidence interval 98.9%-100%) and 98.8 (97.2%-100%). For hs-cTnI<5 ng/L (50%), the NPV and sensitivity for acute myocardial infarction were 98.9% (98.2%-99.6%) and 94.7% (91.3%-98.1%). In combination with a normal ECG, 1) hs-cTnI<LoD had an NPV of 99.6% (98.9%-100%) and sensitivity of 99.4% (98.3%-100%); and 2) hs-cTnI<5 ng/L had an NPV of 99.5% (98.8%-100%) and sensitivity of 98.8% (97.2%-100%). The NPV and sensitivity for the safety outcome were excellent for hs-cTnI<LoD alone or in combination with a normal ECG, and for hs-cTnI<5 ng/L in combination with a normal ECG. ConclusionStrategies using a single hs-cTnI alone or in combination with a normal ECG allow the immediate identification of patients unlikely to have acute myocardial infarction and who are at very low risk for adverse events at 30 days.

Evaluation of High-Sensitivity Cardiac Troponin I Levels in Patients With Suspected Acute Coronary Syndrome.

Low concentrations of high-sensitivity cardiac troponin I determined on presentation to the emergency department (ED) have been shown to have an excellent negative predictive value (NPV) for the identification of acute myocardial infarction. The sensitivity, and therefore clinical applicability, of such testing strategies is unknown. To determine the diagnostic performance of low concentrations of high-sensitivity cardiac troponin I in patients with suspected cardiac chest pain and an electrocardiogram showing no ischemia as an indicator of acute myocardial infarction. A pooled analysis of 5 international (Australia, New Zealand, and England) prospective, observational cohort studies with blinded outcome assessment and 30-day follow-up was conducted. A total of 3155 patients presenting with symptoms suggestive of cardiac ischemia were included in the analysis. Eligible patients had a nonischemic electrocardiogram determined and high-sensitivity troponin I measured at presentation. The lower limit of detection (1.2 ng/L) as well as cutoff concentrations rounded to the nearest integer for a high-sensitivity troponin I assay were used in the analysis. Recruitment was undertaken from November 1, 2007, to August 10, 2013. The primary outcome was fatal or nonfatal acute myocardial infarction occurring within 30 days of ED presentation, adjudicated with serial troponin testing. The secondary outcome was the proportion of patients potentially suitable for early discharge at each cutoff concentration. Of the 3155 eligible patients, 1771 were male (56.1%), and mean (SD) age was 57.4 (13.3) years. Acute myocardial infarction developed in 291 individuals (9.2%). The 1.2-ng/L limit of detection gave a sensitivity of 99.0% (95% CI, 96.8%-99.7%) and an NPV of 99.5% (95% CI, 98.4%-99.9%). This cutoff level would allow for early discharge of 594 patients (18.8%). All higher rounded cutoff values had sensitivities less than 98.0%. Diagnostic performance of the limit of detection was maintained when patients were stratified by age, sex, risk factors, presence of coronary artery disease, and early presentation. High-sensitivity troponin I concentrations determined at presentation to the ED that were below the limit of detection identified 18.8% of patients potentially suitable for discharge, with a high sensitivity for acute myocardial infarction. Rounded cutoff values above the limit of detection may not have the required sensitivity for clinical implementation.

Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T

We aim to prospectively validate the diagnostic accuracy of the recently developed 0-h/1-h algorithm, using high-sensitivity cardiac troponin T (hs-cTnT) for the early rule-out and rule-in of acute myocardial infarction. We enrolled patients presenting with suspected acute myocardial infarction and recent (<6 hours) onset of symptoms to the emergency department in a global multicenter diagnostic study. Hs-cTnT (Roche Diagnostics) and sensitive cardiac troponin I (Siemens Healthcare) were measured at presentation and after 1 hour, 2 hours, and 4 to 14 hours in a central laboratory. Patient triage according to the predefined hs-cTnT 0-hour/1-hour algorithm (hs-cTnT below 12 ng/L and Δ1 hour below 3 ng/L to rule out; hs-cTnT at least 52 ng/L or Δ1 hour at least 5 ng/L to rule in; remaining patients to the "observational zone") was compared against a centrally adjudicated final diagnosis by 2 independent cardiologists (reference standard). The final diagnosis was based on all available information, including coronary angiography and echocardiography results, follow-up data, and serial measurements of sensitive cardiac troponin I, whereas adjudicators remained blinded to hs-cTnT. Among 1,282 patients enrolled, acute myocardial infarction was the final diagnosis for 213 (16.6%) patients. Applying the hs-cTnT 0-hour/1-hour algorithm, 813 (63.4%) patients were classified as rule out, 184 (14.4%) were classified as rule in, and 285 (22.2%) were triaged to the observational zone. This resulted in a negative predictive value and sensitivity for acute myocardial infarction of 99.1% (95% confidence interval [CI] 98.2% to 99.7%) and 96.7% (95% CI 93.4% to 98.7%) in the rule-out zone (7 patients with false-negative results), a positive predictive value and specificity for acute myocardial infarction of 77.2% (95% CI 70.4% to 83.0%) and 96.1% (95% CI 94.7% to 97.2%) in the rule-in zone, and a prevalence of acute myocardial infarction of 22.5% in the observational zone. The hs-cTnT 0-hour/1-hour algorithm performs well for early rule-out and rule-in of acute myocardial infarction.

Abnormal repolarization in the acute myocardial infarction patients: a frequency-based characterization.

Despite ST elevation having poor sensitivity for acute myocardial infarction (AMI), it remains the main electrocardiographic (ECG) repolarization index for AMI diagnosis. Aim of the present study was to propose a new f99 index, defined as the frequency at which the repolarization normalized cumulative energy reaches 99%, for ECG AMI discrimination from health with good sensitivity and good specificity. Evaluation of such f99 index was performed on 12-standard-lead (I, II, III, aV1, aVr, aVf, V1 to V6) ECG recordings of 47 healthy controls and 108 acute myocardial infarction (AMI) patients. Repolarization dispersion caused f99 distributions to be significantly lead dependent. In most leads (leads I, II, aVl, aVr, V2-V6), f99 median value was lower in the healthy controls (10-17 Hz) than in the AMI patients (12-38 Hz) indicating higher frequency components (i.e. a more fragmented repolarization) in the latter population. AMI patients from healthy controls discrimination by f99, evaluated in terms of sensitivity (Se) and specificity (Sp), was also lead dependent. Single-lead analysis indicated leads I (Se=80%, Sp=77%) and aVl (Se=84%, Sp=74%) as optimal. Instead, lead-system analysis, performed to overcome dispersion issues, provided the best results when averaging over the 6 precordial leads (Se= 81% and Sp=74%). In conclusion, our new f99 index appears as a promising tool for non-invasively and reliably discriminate AMI patients from healthy subjects.

High-sensitivity troponin T as a diagnostic tool for acute coronary syndrome in the real world

The 2011 European Society of Cardiology guidelines state that acute coronary syndrome (ACS) may be excluded with a rapid 3 h high-sensitivity troponin T (HsTnT) sampling protocol. We aimed to evaluate the diagnostic and prognostic performance of HsTnT in patients with chest pain admitted with possible ACS in routine care. A total of 773 consecutive patients admitted for in-hospital care for chest pain suspicious of ACS were included retrospectively. HsTnT values at admission and at 3-4 and 6-7 h were analysed for diagnostic performance. In addition, prognostic performance towards a combined 60-day endpoint of ACS, nonelective revascularization or death of all causes was studied. Twenty-three per cent of the patients had ACS during the hospital stay and 1.6% had an endpoint after discharge but within 60 days. The sensitivity of HsTnT for ACS at admission, 3-4 and 6-7 h was only 68, 79 and 81%, respectively. Sensitivity and negative predictive value for acute myocardial infarction alone were 80 and 93% on admission and 97 and 99% at 3-4 h. Among patients aged 75 years and older, 63% had a positive HsTnT on admission, but only 39% of these had an ACS during hospital stay. Our data confirm that prolonged testing with HsTnT after 3-4 h does not improve diagnostic performance for ACS. However, although sensitivity for acute myocardial infarction was very good, sensitivity for ACS was insufficient to rule out ACS even at 6-7 h. Less than half of all recorded positive HsTnT were true positives. On the basis of these results, we find it unlikely that HsTnT has improved the diagnosis of ACS in the emergency care setting.

Circulating Cardiac Troponin T Exhibits a Diurnal Rhythm

The goal of this study was to test the unverified assumption that chronically elevated cardiac troponin T (cTnT) levels fluctuate randomly around a homeostatic set point. The introduction of high-sensitivity cardiac troponin (cTn) assays has improved sensitivity for acute myocardial infarction (AMI). However, many patients with a single positive cTn test result do not have AMI. Therefore, the diagnosis of AMI relies strongly on serial testing and interpretation of cTn kinetics. Essential in this regard is a profound understanding of the biological variation of cTn. Two studies were conducted to assess biological cTnT variation and to investigate the presence of a diurnal rhythm of cTnT. Study 1 comprised 23 male subjects with type 2 diabetes, with no acute cardiovascular disease. Serial venous blood samples were drawn over an 11-h period (8:30 am to 7:30 pm). In study 2, the presence of a diurnal cTnT rhythm was investigated by hourly sampling of 7 subjects from study 1 over 25 h. In study 1, we observed a gradual decrease in cTnT concentrations during the day (24 ± 2%). This decrease was present in all participants and was most prominent in subjects with the highest baseline cTnT values (Pearson's R 0.93). Diurnal variation of cTnT, as assessed in study 2, was characterized by peak concentrations during morning hours (8:30 am, 17.1 ± 2.9 ng/l), gradually decreasing values during daytime (8:30 pm, 11.9 ± 1.6 ng/l), and rising concentrations during nighttime (8:30 am the next day, 16.9 ± 2.8 ng/l). A diurnal cTnT rhythm substantiates the recommendation that all dynamic changes in cTnT should be interpreted in relation to the clinical presentation. Epidemiological studies and risk-stratification protocols with the use of cTnT may benefit from standardized sampling times. (Exercise and Glycemic Control in Type 2 Diabetes; NCT00945165).

Diagnostic Performance of High-Sensitivity Troponin T, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A Assays for Triage of Patients with Acute Myocardial Infarction

BackgroundEarly diagnosis is the cornerstone of management of acute myocardial infarction (AMI). We aimed to compare the diagnostic accuracy of high-sensitivity troponin T (hs-cTnT) with myeloperoxidase (MPO) and pregnancy-associated plasma protein A (PAPP-A) for early diagnosis of AMI in patients at the time of presentation to the emergency department (ED).MethodsWe enrolled 289 patients who presented at the ED of the National Institute of Heart Disease (NIHD) Rawalpindi, Pakistan, within 4 hr of onset of chest pain. Clinical assessment, electrocardiography (ECG), and angiography were carried out. Blood samples were collected at 0, 3, 6, and 12 hr. Analyses of plasma hs-cTnT, MPO, and PAPP-A were carried out using commercial kits.ResultsOut of 289 subjects who presented to the ED, we diagnosed 180 patients with coronary heart disease as having AMI (N= 61) and 119 as without AMI (stable coronary artery disease, N=61; unstable angina, N=58). Compared to non-AMI patients, the patients with AMI had significantly higher levels (represented here as median [inter quartile range]) of plasma hs-cTnT (136 [39-370] vs. 12 [7-21] ng/L), MPO (906 [564-1,631] vs. 786 [351-1,299] pmol/L) and PAPP-A (5.78 [2.67-13.4] vs. 2.8 [1.8-4.9] mIU/L). Receiver operator characteristic curves (95% CI) for hs-cTnT (0.952 [0.909-0.978]) were significantly higher (P<0.001) than those for MPO (0.886 [0.830-0.929]) and PAPP-A (0.797 [0.730-0.854]), with AMI sensitivity and specificity percentages of 87% and 98% (hs-cTnT), 82% and 84% (MPO), and 65% and 87% (PAPP-A), respectively.ConclusionsThe diagnostic performance of hs-cTnT was superior to that of MPO and PAPP-A for early triage and diagnosis of AMI among patients of coronary heart disease presenting with chest pain to the ED.

Myocardial wall motion and thickening assessment in early gated SPECT images of acute coronary syndrome patients likely to have inferolateral perfusion defects

The purpose of this study was to compare semi-quantitative visual scores of perfusion, motion and thickening with an automated hypoperfusion index (HI) in patients with suspected acute inferolateral perfusion defects. In the absence of perfusion defects motion and thickening abnormalities were assessed. Sixty-eight patients with chest pain at rest and either ST depression ≥0.1 mV in ≥1 of leads I, aVL, V1-V6 on 12-lead ECG or ST elevation ≥0.05 mV in ≥1 posterior lead on the body surface map comprised the study population. A rest gated perfusion scan was performed within 24 h of symptoms. Scans were scored for perfusion, motion and thickening semi-quantitatively. The scores were compared to the automated HI. A 12 h Troponin T >0.09 ng/ml indicated myocardial infarction (MI). Sixty-five patients (96%, 65/68) had MI. The summed perfusion score correlated well with the HI (ρ = 0.90, P < 0.01) and agreement between scorers was good (κ = 0.77, 95% CI = 0.57-0.94). The summed motion score correlated with the HI (ρ = -0.61, P < 0.01) and agreement between scorers was moderate (κ = 0.65, 95% CI = 0.52-0.79). Summed thickening score correlated with HI (ρ = -0.67, P < 0.01) and agreement between scorers was good (κ = 0.74, 95% CI = 0.64-0.88). Of the 1156 segments assessed (68 × 17), 542 had normal perfusion. Of these normally perfused segments, 113 (21%, 113/542) had a motion abnormality and 102 (19%, 102/542) had a thickening abnormality. Three patients with proven myocardial infarction had normal myocardial perfusion (HI ≤ 5) but exhibited wall motion and thickening abnormalities. In conclusion, assessment of wall motion and thickening in addition to perfusion in acute myocardial perfusion imaging may improve the diagnostic sensitivity for acute MI. Of the scores addressing motion and thickening, interobserver agreement was better for the summed thickening score.

Investigation of a multimarker approach to the initial assessment of patients with acute chest pain

Early identification of acute coronary syndrome (ACS) is important to guide therapy at a time when it is most likely to be of value. In addition, predicting future risk helps identify those most likely to benefit from ongoing therapy. Cardiac troponin T (cTnT) is useful for both purposes although cannot reliably rule out ACS until 12 hours after pain onset and does not fully define future risk. In this review article we summarize our previously published research, which assessed the value of myocyte injury, vascular inflammation, hemostatic, and neurohormonal markers in the early diagnosis of ACS and risk stratification of patients with ACS. In addition to cTnT, we measured heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, high-sensitivity C-reactive protein, myeloperoxidase, matrix metalloproteinase 9, pregnancy-associated plasma protein-A, D-dimer, soluble CD40 ligand, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Of the 664 patients enrolled, 415 met inclusion criteria for the early diagnosis of acute myocardial infarction (MI) analysis; 555 were included in the risk stratification analysis and were followed for 1 year from admission. In patients presenting <4 hours from pain onset, initial H-FABP had higher sensitivity for acute MI than cTnT (73% vs. 55%; P=0.043) but was of no benefit beyond 4 hours when compared to cTnT. On multivariate analysis, H-FABP, NT-proBNP, and peak cTnT were independent predictors of 1-year death/MI. Our research demonstrated that, in patients presenting within 4 hours from pain onset, H-FABP may improve detection of ACS. Measuring H-FABP and proBNP may help improve long-term risk stratification.

Serial creatinine kinase (CK) MB testing during the emergency department evaluation of chest pain: Utility of a 2-hour ΔCK-MB of +1.6 ng/ml

Background Traditional methods of using creatinine kinase (CK)-MB to diagnose acute myocardial necrosis rely on the total CK-MB exceeding a threshold of normalcy before being considered diagnostic. Because the CK-MB rapid immunoassay is both sensitive and precise, a small difference between two serial samples over an appropriate time interval may result in an increased sensitivity for acute myocardial infarction (AMI) compared with traditional methods if an appropriate cutoff value is chosen.Methods and Results Baseline and 2-hour CK-MB immunoassay measurements were performed in 710 patients with chest pain whose baseline CK-MB was less than two times upper limits of normal (<12 ng/ml) to determine whether a rise in CK-MB ≥+1.6 ng/ml is more sensitive and specific than an abnormal 2-hour CK-MB in the detection of patients with AMI during the initial emergency department evaluation of chest pain. The baseline (MB0) or 2-hour (MB2) CK-MB was considered positive if the CK-MB level was ≥6 ng/ml. MBΔ was defined as the difference of MB2 and MB0 and was considered positive if the value was ≥+1.6 ng/ml. A positive MB2 was more sensitive for the detection of AMI (75.2% vs 17.7%; p < 0.0001) than a positive MB0. A positive MBΔ was more sensitive for the detection of AMI (93.8% vs 75.2%; p < 0.0001) than a positive MB2. There were no statistically significant differences in specificities for AMI for any test modality.Conclusions A rise in CK-MB of ≥+1.6 ng/ml in 2 hours is a useful marker of AMI during the initial emergency department evaluation of patients with chest pain. (Am Heart J 1998;136:237-44.)

Measurement of Cardiac Troponin T Is an Effective Method for Predicting Complications Among Emergency Department Patients With Chest Pain

Study Objectives: To determine the test performance characteristics of serum cardiac troponin T (cTnT) measurement for diagnosis of acute myocardial infarction (AMI), and to determine the ability of cTnT to stratify emergency department patients with chest pain into high- and low-risk groups for cardiac complications. Methods: We conducted a prospective observational cohort study with convenience sampling in a tertiary care, urban ED. The study sample comprised 667 patients presenting to the ED with a complaint of chest pain or other symptoms suggesting acute ischemic coronary syndrome (AICS). Patients were assigned to different blood sampling protocols for cTnT therapy on the basis of their ECG at presentation: nondiagnostic for AMI at 0, 3, 6, 9, 12, and 24 hours after ED presentation; or ECG diagnostic for AMI at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 18, and 24 hours after ED presentation. Results: Of 667 patients, 34 had AMI diagnosed within 24 hours of ED arrival. Using a .2 μg/L discrimination level for cTnT, sensitivity for AMI within 24 hours of ED arrival was 97% (95% confidence interval, 91.4% to 99.9%), and specificity was 92% (89.8%-94.1%). When the effects of age, race, sex, and creatine kinase–MB isoenzyme subunit test results were controlled, a patient with cTnT of .2 μg/L or greater was 3.5 (1.4 to 9.1) times more likely to have a cardiac complication within 60 days of ED arrival than a patient with a cTnT value below .2 μg/L. Conclusion: Measurement of cTnT will accurately identify myo cardial necrosis in patients presenting to the ED with possible AICS. Elevated cTnT values identify patients at increased risk of cardiac complications. [Sayre MR, Kaufmann KH, Chen I-W, Sperling M, Sidman RD, Diercks DB, Liu T, Gibler WB: Measurement of cardiac troponin T is an effective method for predicting complications among emergency department patients with chest pain. Ann Emerg Med May 1998;31:539-549.]

The diagnosis of acute myocardial infarction in the emergency department; Part 2

At present, routine use of cardiac enzymes in the emergency department (ED) cannot be justified, except possibly as a final screen prior to discharge. Computer-derived predictive instruments do not surpass the physician's diagnostic sensitivity for acute myocardial infarction (AMI), but do demonstrate significantly higher specificity. Limited data exist on the utility of echocardiography and thallium scanning in the ED. Methods of triaging patients on the basis of prognosis are well supported in the literature. The physician's high diagnostic sensitivity is maintained at the cost of significant numbers of admissions who subsequently rule out for AMI. No single clinical variable or combination of clinical variables can reliably confirm or exclude AMI in the ED. Ultimately, the physician's clinical assessment must remain the final determinant of the necessity for admission. However, judicious use of prediction rules and prognostic indicators should improve resource utilization.