Preface
The Agency for Healthcare Research and Quality (AHRQ), formerly the Agency for Health Care Policy and Research, through its Evidence-based Practice Centers (EPCs), sponsors the development of evidence reports and technology assessments to assist public and private-sector organizations in their efforts to improve the quality of health care in the United States. The reports and assessments provide organizations with comprehensive, science-based information on common, costly medical conditions and new health care technologies. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to developing their reports and assessments.
To bring the broadest range of experts into the development of evidence reports and health technology assessments, AHRQ encourages the EPCs to form partnerships and enter into collaborations with other medical and research organizations. The EPCs work with these partner organizations to ensure that the evidence reports and technology assessments they produce will become building blocks for health care quality improvement projects throughout the Nation. The reports undergo peer review prior to their release.
AHRQ expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality.
We welcome written comments on this evidence report. They may be sent to: Director, Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality, 6010 Executive Blvd., Suite 300, Rockville, MD 20852.
| John M. Eisenberg, M.D. | Douglas B. Kamerow, M.D. |
| Director
Agency for Healthcare Research and Quality | Director, Center for Practice and Technology Assessment
Agency for Healthcare Research and Quality |
| The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, test, treatment, or other clinical service. |
Structured Abstract
Objective. Unstable angina comprises a broad spectrum of ischemic heart disease and is associated with varying levels of risk for unfavorable outcomes including myocardial infarction and death. Despite development of various diagnostic approaches, the evaluation of patients with chest pain suggestive of unstable angina or myocardial infarction remains a common, costly problem, with approximately 5 million people undergoing evaluation in emergency departments annually at an estimated cost of over $6 billion. The American College of Cardiology and the American Heart Association established a committee to develop guidelines for the diagnosis and treatment of unstable angina. Under a contract with the Agency for Health Care Policy and Research to assist the committee to evaluate the current ability to predict risk for patients with unstable angina, we performed three systematic reviews. The first review concerned the value of the electrocardiogram, physical examination, and clinical history in predicting outcome for patients with unstable angina. The second review examined the ability of troponin to predict outcome in patients with proven or suspected unstable angina. The third review examined the efficacy of chest pain units and emergency department protocols in patients who have suspected unstable angina or myocardial infarction.
Search Strategy. We identified published studies (English language) through 1998 by searching the MEDLINE and EMBASE databases and by manually reviewing the bibliographies of identified articles.
Selection Criteria. For the review of clinical and electrocardiographic predictors of outcome, we restricted our review to only those studies that performed a multivariate analysis of the clinical and/or electrocardiographic predictors of adverse clinical events in patients with either chest pain suggestive of ischemia or diagnosed unstable angina in the emergency department or hospital. For the review of troponin efficacy, we included reports of patient cohorts with unstable angina or suspected unstable angina that noted subsequent myocardial infarction, death, or revascularization. For the review of chest pain units and emergency department protocols, we included trials that were randomized. We also included controlled clinical trials of chest pain protocols used in the emergency department.
Data Collection and Analysis. For the review of troponin studies, we pooled the data using odds ratios and relative risks for outcomes of death, subsequent myocardial infarction, and revascularization. Two independent reviewers abstracted each study.
Main Results. Characteristics of patients with suspected unstable angina that were associated with worse outcomes included advanced age, male sex, prior myocardial infarction, and diabetes. In addition, congestive heart failure, hypertension, and smoking may also be important prognostic factors from the clinical history, but specific descriptors of the chest pain did not provide prognostic information. The strongest electrocardiographic predictor of adverse outcomes was ST-segment depression greater than 0.1 millivolt, whereas a completely normal electrocardiogram was a strong predictor of reduced risk. A positive troponin finding increased the risk of subsequent death 5.3-fold at 4 weeks (95 percent confidence interval: 3.6-7.9). A positive troponin finding also increased the risk of subsequent death or myocardial infarction 12.3-fold at 4 weeks (95 percent confidence interval: 6.4-23.8) in patients with diagnosed unstable angina. The absolute increase in mortality was 3.9 percent (95 percent confidence interval: 3.0-4.4) for patients with a positive troponin level. The predictive value of troponin T and troponin I was not significantly different. Data are insufficient at present to determine if rapid bedside troponin tests and laboratory-based measurements provide similar or different prognostic information. Although randomized trials of chest pain units are few, they consistently have shown decreased hospital costs compared with usual care. All studies included in this report apply to adult men and women.
Conclusions. Several patient characteristics and electrocardiographic findings portend a worse prognosis in patients with suspected or diagnosed unstable angina including older age, male sex, past myocardial infarction, diabetes mellitus, and ST depression greater than 0.1 millivolt. Measurement of troponin T or troponin I provides additional independent prognostic information. Additional randomized trials of chest pain units are needed to determine more fully their health and economic benefits.
This document is in the public domain and may be used and reprinted without permission except those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders.
Suggested Citation:
Heidenreich PA, Go A, Melsop KA, et al. Prediction of risk for patients with unstable angina. Evidence Report/Technology Assessment No. 31 (prepared by the UCSF-Stanford Evidence-based Practice Center under Contract No. 290-97-0013). AHRQ Publication No. 01-E001. Rockville, MD: Agency for Healthcare Research and Quality. December 2000.
Summary
Overview
Coronary heart disease is the leading cause of death for both men and women in the United States. One of the most characteristic and troubling features of coronary disease is the sudden and unexpected onset of symptoms in clinically stable patients and sometimes in even previously healthy individuals.
The development of symptoms is associated with an increased risk of sudden death, acute myocardial infarction, and other life-threatening complications. The development of symptoms suggestive of coronary disease, therefore, mandates prompt and accurate diagnosis and treatment.
The cardinal symptom of coronary artery disease (CAD) is angina, which classically presents as a squeezing or strangulating deep chest discomfort that may radiate to the arm or jaw. Angina that is brought on by exercise stress and is relieved promptly after cessation of exertion is termed "typical angina." Stable angina is a pattern of symptoms that has been unchanged for 6 or more weeks. Unstable angina is a pattern of symptoms that is new in onset, changing in severity or frequency, occurring at rest, or lasting longer than 20 minutes.
The evaluation of suspected coronary disease is complicated by the fact that chest discomfort has many causes, and bona fide coronary disease may present in an atypical fashion. Thus, a population of patients with symptoms suggestive of coronary disease includes some patients with acute, life-threatening medical problems, some patients with other medical problems mimicking CAD, and even some "worried well" in need only of reassurance. The evaluation and treatment of this highly heterogeneous population is the difficult task for clinicians in emergency departments (EDs) and in office practice. The key goal of these clinicians must be to identify the patient's short-term risk. The high-risk patient may develop life-threatening complications and require hospitalization and immediate therapy. The low-risk patient may need further evaluation, but in a less urgent and less costly setting. Because identification of patient risk is central to all further patient management in unstable angina, this evidence report focuses on clinical and laboratory markers of patient risk, such as results of diagnostic tests (troponin values, stress testing, echocardiography, and nuclear scintigraphy). Because chest pain units attempt to "risk stratify" (group patients according to their degree of risk) based on readily available data, an assessment of the efficacy of the chest pain units is significant to this report. Our in-depth review focused on information that would be readily available to all providers caring for patients with suspected unstable angina. Information in this evidence report applies to adult men and women.
Reporting the Evidence
Key Questions
- 1
What are the immediate clinical and electrocardiographic characteristics that are independently associated with an increased risk of adverse outcomes in patients with either chest pain that raises suspicion of cardiac ischemia or diagnosed unstable angina?
- 2
What is the prognostic value of a positive or negative troponin test in patients with proven or suspected unstable angina?
- 3
Are chest pain units and ED protocols effective, cost-saving, and safe for triaging patients with suspected unstable angina or myocardial infarction (MI)?
Methodology
Prognostic Value of the History, Physical Examination, and Electrocardiogram
We conducted a systematic literature search of MEDLINE for relevant articles published between 1966 through 1998, and we manually searched references of retrieved articles to identify additional applicable published studies. Our search criteria included MEDLINE exact subject and keyword searches for:
-
Chest pain, angina pectoris, unstable angina, variant angina, vasospastic angina, or acute coronary syndrome
combined with the terms
risk, stratification, prognosis, outcome, and multivariate analysis.
We restricted our review only to those studies that performed a multivariate analysis of the clinical and/or electrocardiographic predictors of adverse clinical events in patients with either chest pain suspected to be ischemia or diagnosed unstable angina in the ED or hospital. We sought to determine those variables that provided independent risk prediction. Therefore, studies were excluded if they performed a multivariate analysis but did not provide the quantitative results with measures of significance (e.g., p value, standard error) in the form of regression estimates, relative risks, odds ratios, or rate ratios. A p value of <0.05 was considered statistically significant. We also excluded non-English language studies.
Predictor variables of interest included:
-
Demographic characteristics (age, sex, race/ethnicity).
-
Medical history (prior MI, unstable or stable angina, revascularization, congestive heart failure, cerebrovascular disease, hypertension, diabetes, and smoking history).
-
Symptom characteristics (frequency, duration, and pattern of chest pain).
-
Initial physical exam findings (blood pressure, heart rate, and pulmonary rales or Killip class I-IV for congestive heart failure).
-
Initial electrocardiographic features (ST-segment depression, transient ST elevation, isolated T-wave inversions, other findings, or a normal electrocardiogram).
We included studies that measured at least one of the following outcomes:
Candidate titles and abstracts were reviewed, and appropriate studies were selected for data extraction by an internist and a cardiologist with training in health services research.
Studies were stratified by type of patients evaluated (chest pain or diagnosed unstable angina), and multivariate results were grouped into:
-
Categories of demographic characteristics.
-
Medical history features.
-
Symptom characteristics.
-
Initial physical findings.
-
Electrocardiographic features.
Prognostic Value of Troponin
We searched MEDLINE (1966-98) and EMBASE (1974-98) and reviewed cited references of retrieved articles to identify relevant published studies. Our search criteria were: (1) the text word
troponin,
(2) the text words
angina
or unstable
or myocardial infarction
or ischemia,
and (3) language
English, excluding (4) the MeSH heading
animal.
Using this criteria set, we searched MEDLINE and then EMBASE. Finally, we reviewed the bibliographies of identified trials to locate other relevant studies.
We restricted our review to studies that evaluated patient cohorts with suspected ischemia. We excluded studies that only enrolled patients with myocardial infarction. We also excluded case-control studies and studies that did not report the outcomes of MI or death.
Study selection was performed initially by title review. Candidate abstracts were then reviewed and selected for data abstraction. Two independent reviewers abstracted data from each article on standardized electronic data forms. A third reviewer compared their results and settled any differences. In general, at least one reviewer of the pair had clinical cardiology expertise.
We used standard methods of meta-analysis to combine outcome data across trials and the Peto (fixed-effects) and DerSimonian-Laird (random-effects) methods to estimate summary odds ratios. We examined differences between study subgroups using analysis of variance. The previously specified subgroup comparisons of interest were studies for all patients with suspected ischemia versus patients in whom myocardial infarction had already been excluded. The former patients would be recruited from emergency departments, while the latter patients would all be hospitalized. Reported p values are two tailed with statistical significance at p<0.05.
Chest Pain Units and Emergency Department Protocols
We conducted a systematic literature search of MEDLINE for articles published between 1966 and 1998.
- 1
The first search strategy included the following terms: (random* [All Fields] AND (chest pain [MeSH Terms] OR
chest pain
[Text Word]) AND (emergencies
[MeSH Terms] OR
emergency [Text Word])).
- 2
The second search strategy included the following terms: (controlled clinical trial
[All Fields] AND (chest pain [MeSH Terms] OR
chest pain [Text Word]) AND (emergencies
[MeSH Terms] OR
emergency
[Text Word])).
Abstracts and titles from both searches were reviewed for appropriate studies. Randomized trials or controlled clinical trials were selected. Studies that assessed chest pain units, accelerated or rapid diagnostic protocols, or emergency department triage protocols were reviewed. Noncontrolled studies were selected if they reported outcomes for at least 1,000 patients with suspected acute coronary syndromes. We recorded the outcomes of hospital admission rate, cost of care, myocardial infarction, and death when available. Other outcomes reported by the trial were recorded if comparisons were made between control and intervention groups.
Findings
Prognostic Value of the History, Physical Examination, and Electrocardiogram
-
Demographic characteristics associated with worse outcomes included increasing age and male sex.
-
Prior medical conditions that consistently predicted poor outcomes included previous myocardial infarction and diabetes. In addition, prior congestive heart failure, hypertension, and smoking also may be important prognostic factors.
-
Congestive heart failure on presentation increased the risk of cardiac events.
-
Among patients with suspected or confirmed unstable angina, specific characteristics of the chest pain did not uniformly add any independent information useful in predicting adverse outcomes among the studies reviewed.
-
ST depression >0.1 mV was the strongest electrocardiographic predictor of adverse outcomes, while a completely normal electrocardiogram was a strong predictor of reduced risk.
Prognostic Value of Troponin
-
A positive troponin value increased the risk of death 5.3-fold over the 4 weeks subsequent to testing (95 percent confidence interval [CI]: 3.6-7.9).
-
The absolute increase in mortality was 3.9 percent (95 percent CI: 3.0-4.4) for patients with a positive troponin level.
-
A positive troponin value increased the risk of subsequent death or MI 12.3-fold at 4 weeks (95 percent CI: 6.4-23.8).
-
The absolute increase in the rate of death or subsequent MI was 14 percent (95 percent CI: 10-18) for patients with a positive troponin level.
-
The increased absolute risk associated with a positive troponin value was proportional to the overall risk of death.
-
The increased risk of death associated with a positive troponin value decreased over time.
-
The increased risk of death at 4 weeks was similar for elevated troponin T and troponin I values.
-
An increased troponin value was associated with a similar risk of death for both patients with unstable angina (MI excluded) and patients with suspected acute ischemia (chest pain with or without MI).
Evaluation of Chest Pain Units and Emergency Department Protocols
-
The few randomized trials of chest pain units have consistently shown decreased hospital days and hospital costs for patients as compared with usual emergency care for the duration of the initial encounter.
-
There is no evidence of increased harm from the more selective admissions that result from evaluation with chest pain units or protocols, but statistical power is limited in studies to date.
-
Patient satisfaction may be improved by chest pain units.
Future Research
More studies are needed that combine data from history, physical examination, and biochemical markers to determine the independent prognostic ability of each variable. Our qualitative review of clinical and electrocardiographic predictors of prognosis suggests that future studies should include the following variables in a multivariate prediction model:
-
Age.
-
ST depression.
-
ST elevation.
-
Troponin levels.
More randomized trials of chest pain units or chest pain protocols are needed to more fully determine their health and economic benefits.
Chapter 1. Introduction
Unstable angina comprises a broad spectrum of patients with varying levels of risk for suffering unfavorable outcomes such as death, myocardial infarction (MI), or other major cardiac complications. Despite development of various diagnostic approaches, the evaluation of patients with chest pain suggestive of acute ischemia or infarction remains a common, costly problem, with approximately 5 million people undergoing evaluation in emergency departments (EDs) annually at an estimated cost of over $6 billion (Barish, Doherty, and Browne, 1997). Patients with chest pain and ST-segment elevation on a standard electrocardiogram (ECG) are at substantially increased risk for myocardial infarction and cardiac complications, and current guidelines strongly recommend immediate reperfusion therapy (Ryan, Anderson, Antman, et al., 1996). The difficulty lies in predicting who will suffer an adverse event in those patients without ECG evidence of ST elevation or new, pathologic Q waves. This situation leads to many unnecessary hospital admissions (often for intensive monitoring) and to sending home a small proportion of patients who may incur infarction or death outside the hospital. Furthermore, of patients diagnosed with unstable angina, only 6 to 15 percent meet existing criteria for short-term risk of cardiac events low enough to be discharged home safely, based on guidelines from the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality [AHRQ]) (Braunwald, Jones, Mark, et al., 1994; Calvin, Klein, VandenBerg, et al., 1995)
Previous studies have concentrated on finding predictors of significant anatomic coronary artery disease (CAD) (Diamond and Forrester, 1979; Pryor, Harrell, Lee, et al., 1983), but estimating the probability of coronary artery disease in patients with chest pain does not necessarily address the short-term risk of an adverse event.
Although emerging diagnostic tests may assist the clinician in improving identification of higher or lower risk patients, their cost-effectiveness is measured by comparison with the basic evaluation using clinical history, vital signs, physical examination, and initial 12-lead electrocardiogram. Furthermore, many of these newer tests may not be widely available, may not yield timely diagnostic results for efficient triage and management, or may require specialized skills, technological capability, or facilities. Prior studies have tried to assess the utility of presenting clinical and electrocardiographic information in the initial diagnostic evaluation of unstable angina, but often did not determine whether these patient features were
independent
prognostic factors for clinical outcomes.
The American College of Cardiology and the American Heart Association established a committee to update guidelines on the initial evaluation and risk assessment of patients with unstable angina. At the request of the AHRQ and the Unstable Angina Committee, which had as its overall goal the accurate risk assessment of patients with unstable angina, we performed a literature review. Following preliminary review of the literature, the committee identified two related and relevant patient populations to study: patients with chest pain suspicious for cardiac ischemia in the emergency department setting and those with diagnosed unstable angina. To maximize generalizability, we concentrated on tools readily available to all clinicians at the time of initial evaluation: clinical history, comorbid conditions, vital signs, physical examination, and a standard 12-lead electrocardiogram. We prioritized our in-depth review to focus on information that would be readily available to all providers caring for patients with suspected unstable angina. Other risk factors that also may be important include stress testing, echocardiography, and nuclear scintigraphy. The first key question we sought to answer was the following:
1. What are the immediate clinical and electrocardiographic characteristics that are independently associated with an increased risk of adverse outcomes in patients with either chest pain that raises suspicion of cardiac ischemia or diagnosed unstable angina?
Serum markers of myocardial necrosis have been used in conjunction with the clinical and electrocardiographic characteristics to identify more accurately patients with acute myocardial infarction (AMI) and to predict risk for short- and long-term major adverse cardiac outcomes. The use of biochemical markers for cardiac ischemia has evolved over the last 35 years from aspartate aminotransferase (AST) in 1954 and lactate dehydrogenase (LDH) in 1955 to creatine phosphokinase (CK) in 1960 and the CK-myoglobin (MB) mass immunoassay developed in the 1980s (Gibler, Lewis, Erb, et al., 1990). Each new marker improved accuracy in the diagnosis of cardiac ischemia, and a protocol measuring CK-MB every 8 hours for 24 hours has long been considered the reference standard for biochemical diagnosis of AMI. Nevertheless, serial measurements of CK-MB outside a window of from 4 hours to 3 days after the onset of chest pain have a limited ability to detect myocardial ischemia or to risk stratify patients, and those drawn within the diagnostic window may be elevated because of noncardiac causes such as skeletal muscle injury. Immunoassay for myoglobin, a small molecular mass protein in both cardiac and skeletal tissue, has moderate sensitivity for diagnosis of AMI within the first 4 hours of myocyte injury, but its poor specificity and relatively rapid washout limit its usefulness in the majority of patients with acute coronary syndromes (Bakker, Koelemay, Gorgels, et al., 1994).
Immunoassays for cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were approved by the Food and Drug Administration in 1994 and offer another biochemical marker for diagnosis of AMI and for risk stratification. The myofibrillar troponin complex, comprising three proteins (I, T, and C), regulates contraction of striated muscle. Troponin I inhibits actomyosin adenosine triphosphatase (ATPase), troponin T binds the troponin complex to the tropomyosin strand, and troponin C binds to calcium and regulates contraction. Troponin I and T have different amino acid sequences in adult skeletal and cardiac muscle; antibodies developed to recognize cardiac-specific sequences form the basis of cTnT and cTnI immunoassays. Troponin C has identical amino acid sequence in skeletal and cardiac muscle, so it has no role as a cardiac-specific marker of cell injury (Alonsozana and Christenson, 1996). Because of the small molecular mass of troponins I and T (24kDa and 36kDa, respectively), these markers are released rapidly from injured myocardium. The initial time course of troponin release parallels that of CK-MB, with initial detection at 4 to 6 hours postinjury and peak levels obtained at 12 to 18 hours. Unlike CK-MB, the levels of cTnI and cTnT remain elevated for up to 8 to 14 days, respectively, after cell injury (Ravkilde, 1998; Tanasijevic, Cannon, and Antman, 1999).
Prospective studies of troponin assays in acute coronary syndromes have demonstrated that cTnT and cTnI have diagnostic accuracy comparable to, if not better than CK-MB (Gerhardt, Katus, Ravkilde, et al., 1991; Johnson, Goldman, Sacks, et al., 1999; Polanczyk, Lee, Cook, et al., 1998) and can better predict long-term risk for adverse cardiac events (Antman, Tanasijevic, Thompson, et al., 1996; Hamm, Goldmann, Heeschen, et al., 1997; Ohman, Armstrong, Christenson, et al., 1996; Ravkilde, Horder, Gerhardt, et al., 1993; Ravkilde, Nissen, Horder, et al., 1995). However, interpretation of the aggregate data to date is hampered by differences in cutoff values used to define positive tests, lack of assay standardization (troponin I), heterogeneity in patient populations to which the tests have been applied, and variations in statistical analysis and presentation of results. The appropriate criterion for diagnosis of acute MI based on CK-MB and troponin findings is still unsettled. Indeed, the definition of acute MI in the face of this information is not yet clear. In this regard, the prognostic value of troponin measurement is of particular importance. To provide a better overall assessment of the prognostic value of cTnT and cTnI, we conducted a systematic review of published studies. Thus, the second key question we addressed was the following:
2. What is the prognostic value of a positive or negative troponin test in patients with proven or suspected unstable angina?
The initial risk stratification of patients with suspected acute ischemic syndromes is usually performed in the emergency department or other urgent care setting. In an attempt to improve diagnostic accuracy and reduce costs, many medical centers have developed standardized protocols for evaluating patients with chest pain. Frequently these protocols are carried out in chest pain centers within or adjacent to the emergency department. Because chest pain units attempt to risk stratify patients based on readily available data, an assessment of their efficacy is significant to this report. To evaluate the costs and effectiveness of these standardized risk stratification methods, we also performed a systematic literature review of chest pain units or chest pain-specific protocols. Therefore, the third key question we addressed was the following:
3. Are chest pain units and ED protocols effective, cost-saving, and safe for triaging patients with suspected unstable angina or myocardial infarction?
Chapter 2. Methodology
Prognostic Value of the History, Physical Examination, and Electrocardiogram
Data Sources
We conducted a systematic literature search of MEDLINE from 1966 to 1998 and hand searched references of retrieved articles to identify additional relevant published studies. Our search criteria included MEDLINE exact subject and keyword searches for (1)
chest pain,
angina pectoris,
unstable angina,
variant angina,
vasospastic angina, or
acute coronary syndrome
combined with (2) the terms
risk,
stratification,
prognosis,
outcome, and
multivariate analysis.
Study Selection
Our goal was to identify the factors in the clinical evaluation that identified higher risk patients. This evaluation is a continuing process in the care of the patient and is initiated in the emergency department (i.e., at the point of initial contact) for all patients with chest pain, and it continues after the initial triage and identification of patients with unstable angina. The literature contains studies conducted at both points in this process. We reviewed each separately, since risk factors may differ at various stages of evaluation. We also compared the high-risk features in each setting, as consistency across studies and through the evaluation process might reveal particularly valuable risk markers. We restricted our review to only those studies that performed a multivariate analysis of the clinical and/or electrocardiographic predictors of adverse clinical events in patients with either chest pain suggestive of ischemia or diagnosed unstable angina in the emergency department or hospital. We wished to determine those variables that provided independent risk prediction. Therefore, studies were excluded if they performed a multivariate analysis but did not provide the quantitative results with measures of significance (e.g., p value, standard error) in the form of regression estimates, relative risks, odds ratios, or rate ratios. A p value of <0.05 was considered statistically significant. Studies were also excluded if they did not evaluate clinical and electrocardiographic variables assessed on initial presentation in the emergency department or within the first 24 hours of admission to the hospital. Finally, studies only determining the importance of ST elevation on outcomes or characteristics about only patients with ST elevation were excluded, since this is a subgroup that should be considered for immediate reperfusion therapy (Ryan, Anderson, Antman, et al., 1996) and is not the population of interest for this report. We also excluded non-English language studies.
Predictor Variables
Predictor variables of interest included clinical and electrocardiographic information readily available at the time of initial presentation and diagnostic evaluation. These included demographic characteristics (age, sex, race/ethnicity), medical history (prior myocardial infarction, unstable or stable angina, revascularization, congestive heart failure, cerebrovascular disease, hypertension, diabetes, and smoking history), symptom characteristics (frequency, duration, and pattern of chest pain), initial physical examination findings (blood pressure, heart rate, and pulmonary rales or other evidence of congestive heart failure), and initial electrocardiographic features (ST-segment depression, transient ST-segment elevation, isolated T-wave inversions, other findings, or a normal electrocardiogram).
Outcome Measures
We included studies that measured at least one of the following outcomes: cardiac death (death due to cardiac causes), myocardial infarction, urgent revascularization, other major cardiac complication (congestive heart failure, nonfatal ventricular arrhythmia, high-degree heart block, atrioventricular dissociation, cardiogenic shock, cardiac arrest, emergent intubation, or insertion of an intra-aortic balloon pump). For the topic of
chest pain, we also included a confirmed diagnosis of unstable angina as an additional outcome. For the topic of
diagnosed unstable angina, we also included readmission for unstable angina as an additional outcome.
Data Extraction
Drs. Go and Heidenreich reviewed titles of identified articles. Candidate abstracts were then reviewed, and appropriate studies were selected for data extraction. Drs. Go and Heidenreich extracted relevant data from each article. One reviewer (Dr. Heidenreich) was a cardiologist; both reviewers had training in epidemiology and health services research.
Statistical Analysis and Reporting
Substantial differences existed across the included studies in the populations evaluated, predictor variables and outcomes assessed, and analysis techniques employed. This marked heterogeneity in the reviewed studies precluded use of quantitative pooled analysis or meta-analytic techniques to determine summary estimates for significant risk factors (Mulrow, Langhorne, and Grimshaw, 1997). Therefore, studies were stratified by type of patients evaluated (chest pain or diagnosed unstable angina), and multivariate results were grouped into categories of demographic characteristics, medical history features, symptom characteristics, initial physical findings, and electrocardiographic features. Several reports from the Multicenter Chest Pain Study provided overlapping data. To avoid duplicate information, we used data from the study by Lee (Lee, Ting, Shammash, et al., 1992). Risk factors were classified as possible independent risk factors or not significantly associated risk factors. Risk factors were included as possible independent risk factors if they were found to be statistically significant in a multivariate analysis in at least one study.
Table 1. Semiquantitative grading of the relative risk, odds ratio, or rate ratio
1
| <0.50 | -- |
| 0.50-0.99 | - |
| 1.0 or not statistically significant | NS |
| 1.1-2.0 | + |
| 2.1-3.0 | ++ |
| >3.0 | +++ |
To provide consistency of interpretation across studies that used different analytic techniques, we reported the estimates for statistically significant variables using a semiquantitative scale, as shown in
Table 1.
Prognostic Value of Troponin
Data Sources
We searched MEDLINE (1966-98) and EMBASE (1974-98) and reviewed cited references of retrieved articles to identify published studies. Our search criteria were (1) the text word
troponin,
and (2) the text words
angina
or unstable
or myocardial infarction
or ischemia,
and (3) language
English, excluding (4) the MeSH heading
animal.
Using this criteria set, we searched MEDLINE, using PubMed from the National Library of Medicine. A similar search strategy was performed using EMBASE, except that step 3 (language limitation) was not performed. Finally, we reviewed the bibliographies of identified trials to locate other relevant studies. We attempted to identify large unpublished cohort studies by contacting experts in the field of cardiac markers. No additional studies were identified for the time period of the study.
Study Selection
We restricted our review to cohort studies that evaluated patient cohorts with suspected ischemia. We excluded studies that only included patients with myocardial infarction. We also excluded case-control studies and studies that did not report the outcome of myocardial infarction or death. We excluded studies that included patients with ST-elevation MI unless they gave separate data on the non-ST-elevation MI patients.
Data Extraction
Study selection was performed initially by title review (Dr. Heidenreich). Candidate abstracts were then reviewed and selected for data retrieval. Two independent reviewers abstracted data for each article on standardized electronic data forms. A third reviewer compared their results and settled any differences. In general, at least one reviewer of the pair had clinical cardiology expertise.
Outcome Measures
We recorded the outcomes of myocardial infarction, death, or revascularization. A secondary analysis was performed for myocardial infarctions occurring at least 48 hours after presentation. If outcomes at more than one time period were reported, we used the value closest to 30 days following presentation.
Subgroup Comparisons
The prespecified subgroup comparisons of interest were studies of all patients with suspected ischemia versus patients in whom myocardial infarction had already been excluded. The former patients were those recruited from emergency departments, whereas the latter patients were those recruited from inpatient services. Reported p values are two-tailed with statistical significance at p<0.05.
Statistical Analysis
We used standard methods of meta-analysis to combine outcomes data across trials. We used the Peto (fixed-effects) and DerSimonian-Laird (random-effects) methods to estimate summary odds ratios for the outcomes of death and myocardial infarction (DerSimonian and Laird, 1986; Petitti, 1994). Fixed-effects results are presented unless otherwise stated. For studies that reported no events, we substituted 0.1 in place of 0 for the random-effects calculation. (Because events were rare, we chose a value below the more commonly used 0.5.) We tested homogeneity of study effect size using the Q statistic (Petitti, 1994). A summary rate difference was calculated for trials with one or more adverse events (Petitti, 1994). This measure complements the odds ratio by providing an absolute difference in the adverse event rate. We examined differences between study subgroups of trials using analysis of variance (Hedges, 1994). Data are presented as summary odds ratio with 95 percent confidence interval. Reported p values are two-tailed with statistical significance at p<0.05.
Evaluation of Chest Pain Units and Emergency Department Protocols
Data Sources
We conducted a systematic literature search of MEDLINE between 1966 and 1998. The first search strategy included the following search terms: (random* [All Fields] AND (chest pain
[MeSH Terms] OR
chest pain [Text Word]) AND (emergencies
[MeSH Terms] OR
emergency [Text Word]).
The second search strategy included the following terms: ( controlled clinical trial
[All Fields] AND (chest pain [MeSH Terms] OR
chest pain [Text Word]) AND (emergencies
[MeSH Terms] OR
emergency [Text Word]).
Abstracts and titles from both searches were reviewed for appropriate studies. References of selected articles were reviewed by hand to identify additional relevant published studies.
Study Selection
Randomized trials or controlled clinical trials were identified. Studies that assessed chest pain units, accelerated or rapid diagnostic protocols, or emergency department triage protocols were reviewed. Noncontrolled studies were also reviewed if they reported outcomes for at least 1,000 patients with suspected acute coronary syndromes.
Outcome Measures
We recorded the outcomes of hospital admission rate, cost of care, and myocardial infarction and death when available. Other outcomes reported by the trial were recorded if comparisons were made between control and intervention groups.
Key Questions
- 1
What are the immediate clinical and electrocardiographic characteristics that are independently associated with an increased risk of adverse outcomes in patients with either chest pain that raises suspicion of cardiac ischemia or diagnosed unstable angina?
- 2
What is the prognostic value of a positive or negative troponin test in patients with proven or suspected unstable angina?
- 3
Are chest pain units and ED protocols effective, cost-saving, and safe for triaging patients with suspected unstable angina or myocardial infarction?
Quality Control
In addition to performing the double abstraction method described above, we examined a random sample of 10 studies to determine errors in abstraction or database entry. Few errors were found in abstraction of primary outcomes.
Peer Review
Selected independent experts in fields of systematic review, emergency medicine, internal medicine, family practice, cardiology, epidemiology, pathology, and laboratory medicine reviewed the draft manuscript of the evidence report. In addition, the following organizations were invited to nominate individuals to review the manuscript: American College of Cardiology, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Hospital Association, National Association of State Emergency Medical Services Directors, National Association of EMS Educators, Society for Academic Emergency Medicine, Emergency Nurses Association, Society of Emergency Medicine Physician Assistants, American College of Clinical Pharmacology, American Society of Health-System Pharmacists, American Association of Pharmaceutical Scientists, and Roche Diagnostics.
The peer reviewers followed a format developed by Dr. Lisa Bero and Dr. Drummond Rennie from the San Francisco Cochrane Center. The reviews were sent to a criticism editor for synthesis and commentary. The authors responded to the editor's commentary and revised the document accordingly (Appendixes C and D).
Chapter 3. Results
Prognostic Value of the History, Physical Examination, and Electrocardiogram
Identified Articles
A total of 18 studies were identified from MEDLINE searches and citation review that met all of the criteria and underwent complete data extraction. Eight studies examined patients with chest pain suggestive of ischemia, and 10 studies examined patients with a diagnosis of unstable angina.
Chest Pain Suggestive of Acute Ischemia
Eight studies met criteria and had adequate data on multivariate predictors of clinical outcomes in patients with chest pain that could indicate acute ischemia (
Evidence Table 1). All studies enrolled patients seen in the emergency department, and one study enrolled only patients requiring admission to the cardiac care unit (
Rude, Poole, Muller, et al., 1983) (
Evidence Table 1). Consistent with the substantial heterogeneity observed across studies in the study design, type of enrolled patients, and chosen outcomes, there was a relatively wide range of observed cardiac event rates across studies (6 percent to 22 percent).
Despite these differences, certain clinical and electrocardiographic information fairly consistently predicted an increased risk of adverse outcomes. Demographic characteristics associated with worse outcomes included increasing age and male sex (
Evidence Table 2). Prior medical conditions that consistently predicted poor outcomes included prior myocardial infarction (MI) and diabetes (
Evidence Table 3). Prior congestive heart failure, hypertension, and smoking were less consistently significant predictors of outcome but were positive in some studies (
Evidence Table 3). Symptom characteristics were surprisingly unhelpful once the pain was judged an indication of cardiac ischemia (
Evidence Table 4). Regarding the initial vital signs and physical examination, only low blood pressure, congestive heart failure, or cardiogenic shock on admission portended a poor prognosis (
Evidence Table 5). ST-segment depression >0.1 millivolt (mV) was the strongest electrocardiographic predictor of adverse outcomes, whereas a completely normal electrocardiogram (ECG) was a strong negative predictor of outcomes (Evidence Tables 6 and 7).
Diagnosed Unstable Angina
Ten studies met criteria and had adequate data on multivariate predictors of clinical outcomes in patients with diagnosed unstable angina (
Evidence Table 8). All studies involved patients who had suspected or confirmed unstable angina; all but one (
Coronado, Griffith, Beshansky, et al., 1997) also required admission to the hospital, typically the cardiac care unit or stepdown unit. A variety of criteria were used for defining unstable angina; two studies also specifically excluded patients with non-Q-wave myocardial infarction (
Calvin, Klein, VandenBerg, et al., 1995;
van Miltenburg-van Zijl, Simoons, Veerhoek, et al., 1995). As with studies of patients with chest pain described above, there was substantial heterogeneity across studies in study design, predictors evaluated, and types and timing of outcomes assessed (
Evidence Table 8). The observed cardiac event rate ranged from 4 percent to 35 percent across studies, depending on the outcome chosen and duration of followup.
As in patients with troubling chest pain, certain clinical and electrocardiographic variables were consistently associated with an increased risk for poor outcomes in patients with diagnosed unstable angina. Important demographic characteristics included increasing age and probably male sex (
Evidence Table 9). Previous medical conditions associated with adverse outcomes included prior myocardial infarction, diabetes, and possibly hypertension (
Evidence Table 10). Regarding symptom characteristics, the presence of pain at rest or postinfarction angina was an indicator of poor prognosis (
Evidence Table 11), and low blood pressure and moderate to severe congestive heart failure on presentation also were markers of increased risk of cardiac events (
Evidence Table 12). The only consistent electrocardiographic predictor of adverse outcomes was ST-segment depression of >0.05-0.1 mV (
Evidence Table 13). Finally, evidence of recurrent chest pain or ischemia, the need for maximal antianginal therapy, and recent thrombolysis also seemed to be indicators of poor prognosis (
Evidence Table 14).
Summary Table 1. Summary findings for independent clinical and ECG predictors of adverse outcomes (death, MI, major complications): Chest pain suspicious for cardiac ischemia
| Demographic features | Increasing age (5/7)
Male gender (3/7) | Race (2/2) |
| Medical history | Prior MI (2/6)
Diabetes (2/4)
CHF (1/3)
HTN (1/4)
Smoking (1/4) | Prior stable angina (3/3)
Prior CABG (1/1) |
| Symptom characteristics | Typical angina (1/2)
Duration (1/3) | Pressing or crushing (2/2)
Radiation pattern (1/1)
Comparison with prior angina (1/1)
Constant or dull (1/1)
Episodic (1/1)
Sharp or pleuritic (1/1)
Nausea (1/1)
Pleuritic (1/1)
Diaphoresis (1/1)
Dyspnea (1/1)
|
| Initial physical exam | CHF on admission (1/3)
Blood pressure (1/3) | Heart rate (2/2) |
| Electrocardiogram
3 | ST depression (1/4)
ST-T changes (1/2)
Any evidence of ischemia (1/1) | T-wave inversions (2/2) |
| Miscellaneous | Shock after admission (1/1)
S3 (1/2) | Atypical chest pain (1/1)
Cyanosis (1/1)
S4 (1/1)
Chest wall tenderness (1/1)
Marital status (1/1)
Family history of coronary artery disease (1/1)
Peripheral edema (1/1)
Hypercholesterolemia (1/1) |
Summary Table 2. Summary findings for independent clinical and ECG predictors of adverse outcomes (death, MI, major complications): Diagnosed unstable angina
| Demographic features | Increasing age (7/8)
Gender (2/9)
3 | Race/ethnicity (4/4) |
| Medical history | Prior MI (4/9)
Diabetes (5/7)
Hypertension (2/7)
Absence of prior revascularization (1/1)
Prior CABG (1/2)
Prior CHF (1/4)
Prior angina (1/5) | Smoking (5/5)
Prior PTCA (1/1)
Prior stroke (1/1) |
| Symptom characteristics | Postinfarction angina (1/2)
Rest pain after admission (1/2)
Rest angina within 48 h before admission (1/1)
| Frequency (1/1)
Rest pain < or >48 h (1/1) |
| Initial physical exam | CHF on presentation (2/4)
Heart rate (1/1)
Blood pressure (1/2) | |
| Electrocardiogram | ST depression >0.1 mV (2/3)
ST deviation > 0.5 mV (1/1)
Evolutionary T-wave changes (1/1)
Left bundle branch block (1/2) | T-wave inversion (3/3)
Transient ST-T changes (1/1)
Abnormal ECG (1/1)
Right bundle branch block (1/1)
Old Q wave (1/1) |
| Miscellaneous | No prior beta-blocker therapy (2/4)
Requiring IV NTG (2/2)
Recurrent severe chest pain (2/2)
Maximal antianginal therapy (1/1)
Thrombolysis in prior week (1/1)
Other major illness (1/1)
Nitrate use in week before admission (1/1) | Calcium blocker therapy (2/2)
Positive family hx (1/1)
Exacerbating condition (1/1)
Charlson comorbidity score (1/1)
Cardiogenic shock (1/1)
NQWMI at entry (1/1)
Unstable angina class (1/1) |
A summary of the independent clinical and ECG predictors of adverse outcomes is listed for patients with chest pain suggestive of cardiac ischemia (
Summary Table 1) and for patients with unstable angina (
Summary Table 2). Several factors were consistent markers of increased risk in both populations: increased age, prior MI, diabetes, and ST changes on the ECG.
Prognostic Value of Troponin
Identified Articles
A total of 501 articles were identified with the MEDLINE and EMBASE searches and citation review.
Excluded Studies
Figure 1. Reasons for study exclusion
We excluded articles using a hierarchical method beginning with 171 studies that were not articles about troponin in suspected unstable angina based on their title (). Of the remaining 330 articles, 185 were excluded based on the abstract because they were not studies of troponin in patients with suspected or proven unstable angina. The remaining 145 articles were reviewed, and 93 were excluded for the following reasons: 33 studies were review articles and did not provide new data, 5 studies did not evaluate troponin, 17 studies were not cohort evaluations of patients with suspected ischemia, 6 studies only included patients with myocardial infarction, 1 study included only postoperative patients, 24 studies were excluded because they did not report the outcomes of interest (death or myocardial infarction), and 7 studies were excluded because they provided duplicate information included in other studies. The remaining 52 articles (from 51 studies: one study reported troponin T and I in separate manuscripts) were abstracted (Evidence Tables 15 to 35). The MEDLINE search identified 47 (90 percent) articles; EMBASE but not MEDLINE identified 5; and the citation search identified no additional articles beyond those found in our MEDLINE or EMBASE searches.
Patient Characteristics
The mean age of enrolled patients was 61 years; 64 percent were male, 37 percent had a history of myocardial infarction, and 52 percent had a history of coronary artery disease (CAD). A history of hypertension was noted in 44 percent of the patients, diabetes in 19 percent, and smoking in 40 percent (Evidence Tables 15 to 25). The included studies had a median followup of 4 weeks (mean 12 weeks, maximum 147 weeks).
Quality of Study Reports
Of the 51 included studies (52 reports), 17 (33 percent) did not report patient exclusion criteria (
Evidence Table 19). In 15 (29 percent) studies, there was no statement noting whether health care providers were blinded to the troponin results (
Evidence Table 21). Three (6 percent) studies did not report whether study deaths referred to total or cardiac deaths. Three (6 percent) studies did not indicate how myocardial infarction was defined. Overall, 26 (51 percent) studies did not report one of these measures of report quality. Troponin methodology studies varied in the precise assay used for both troponin T and troponin I. Also, the definition of "elevated level" varied among studies. Studies did not generally report results using different definitions of a positive test, so this report is limited to assessing the prognostic value of the test based only on authors' definition. There is evidence that, using a single assay system, higher values of troponin are associated with higher event rates (
Ohman, Armstrong, Christenson, et al., 1996)
Myocardial Infarction During Admission
There were 3,2 myocardial infarctions in 11,477 patients in 38 trials reporting data (
Evidence Table 26). There were 1,995 infarctions in studies of troponin T and 1,658 in studies of troponin I (several studies reported both troponin T and I data). For patients with a diagnosis of myocardial infarction, the troponin T was positive in 1,498 (sensitivity 75 percent, 1,498/1,995). Troponin I was positive in 1,098 patients with a myocardial infarction (sensitivity 66 percent, 1,098/1,658). For troponin T, the specificity was 94 percent, the negative predictive value was 91 percent, and the positive predictive value was 83 percent. For troponin I, the specificity was 92 percent, the negative predictive value was 88 percent, and the positive predictive value was 75 percent.
Death During Admission
There were 38 in-hospital deaths in 1,918 patients in 7 trials with at least 1 in-hospital death reported (
Evidence Table 27). Death was reported as all-cause mortality in five of seven studies (71 percent) and as cardiac death in two studies (29 percent). There were 35 deaths in studies of troponin T and 14 in studies of troponin I with some studies examining both markers. The troponin T was positive in 24 of 35 inpatient deaths (sensitivity 69 percent). Troponin I was positive in 14 of 14 patients who died during hospitalization (sensitivity 1 percent). For troponin T, the specificity was 85 percent, the negative predictive value was 99 percent, and the positive predictive value was 8 percent. For troponin I, the specificity was 87 percent, the negative predictive value was 1 percent, and the positive predictive value was 6 percent.
Composite Endpoints During Admission
There were 344 composite endpoints reached during admission in 2,979 patients in 10 trials reporting data (
Evidence Table 28). One-half of the trials (6/12) reported the combination of death and myocardial infarction. Another six included additional cardiac events or procedures as endpoints. A composite endpoint was reported in 227 patients in studies of troponin T compared with 137 in studies of troponin I (data on both were reported for 20 patients). The troponin T was positive in 107 patients with a composite endpoint (sensitivity 47 percent). Troponin I was positive in 78 patients with a composite endpoint (sensitivity 57 percent). For troponin T, the specificity was 89 percent, the negative predictive value was 95 percent, and the positive predictive value was 26 percent. For troponin I, the specificity was 86 percent, the negative predictive value was 98 percent, and the positive predictive value was 17 percent.
Angioplasty During Admission
There were 133 percutaneous transluminal coronary angioplasties (PTCAs) with or without stenting during admission in 366 patients in 5 trials reporting data (
Evidence Table 29). There were 65 PTCAs in studies of troponin T and 68 in studies of troponin I. For patients undergoing PTCA during admission, the troponin T was positive in 32 (49 percent, 32/65). Troponin I was positive in 25 patients undergoing PTCA during admission (37 percent, 25/68). For a positive troponin T result, the specificity was 83 percent, the negative predictive value was 88 percent, and the positive predictive value was 39 percent. For troponin I, the specificity was 88 percent, the negative predictive value was 86 percent, and the positive predictive value was 42 percent. Physicians may have been more likely to refer to revascularization if they believed that troponin-positive patients would benefit. However, there were no obvious differences in PTCA use during admission between studies that did and did not state that providers were blinded to troponin results.
Bypass Surgery During Admission
There were 56 coronary artery bypass grafting (CABG) operations performed during the initial hospitalization in 366 patients in 5 trials reporting data (
Evidence Table 30). There were 45 bypass operations during admission in studies of troponin T and 11 in studies of troponin I. In patients undergoing bypass grafting, troponin T was positive in 14 (31 percent, 14/45). Troponin I was positive in 6 patients undergoing bypass grafting (55 percent, 6/11). For troponin T, the specificity was 79 percent, the negative predictive value was 89 percent, and the positive predictive value was 17 percent. For troponin I, the specificity was 85 percent, the negative predictive value was 98 percent, and the positive predictive value was 10 percent. There were no obvious differences in CABG use during admission between studies that did and did not state that providers were blinded to troponin results.
Myocardial Infarction During Followup
There were 147 myocardial infarctions following discharge in 3,338 patients in 15 trials reporting data over a mean followup of 15±15 weeks (
Evidence Table 31). There were 138 infarctions in studies of troponin T and 56 in studies of troponin I. In patients with a myocardial infarction following discharge, troponin T was positive in 80 (sensitivity 58 percent). Troponin I was positive in 32 patients with a subsequent infarction (sensitivity 57 percent). For troponin T, the specificity was 79 percent, the negative predictive value was 98 percent, and the positive predictive value was 11 percent. For troponin I, the specificity was 88 percent, the negative predictive value was 99 percent, and the positive predictive value was 7 percent.
Death During Followup
There were 167 deaths during 15±15 weeks of followup in 5,667 patients in 18 trials reporting data (
Evidence Table 32). There were 131 deaths in studies of troponin T and 65 in studies of troponin I. The troponin T was positive in 89 of the patients that died (68 percent), and troponin I was positive in 52 patients that died (80 percent). For troponin T, the specificity was 78 percent, the negative predictive value was 99 percent, and the positive predictive value was 7 percent. For troponin I, the specificity was 82 percent, the negative predictive value was 99 percent, and the positive predictive value was 5 percent. The relative risk of death for patients with a positive troponin test decreased with increasing followup, suggesting that early adverse outcomes are most strongly associated with the troponin level.
Composite Endpoints During Followup
There were 1,465 composite endpoints reached during a mean 18±35 weeks of followup in 7,189 patients in 26 trials reporting data (
Evidence Table 33). Approximately one-half of the trials (14/26) reported the combination of death and myocardial infarction. The remainder (12/26) included additional cardiac events or procedures as endpoints. A composite endpoint was reached in 1,292 patients in studies of troponin T, compared with 882 in studies of troponin I. The troponin T was positive in 568 patients with a composite endpoint (sensitivity 44 percent). Troponin I was positive in 325 patients with a composite endpoint (sensitivity 37 percent). For troponin T, the specificity was 90 percent, the negative predictive value was 85 percent, and the positive predictive value was 57 percent. For troponin I, the specificity was 97 percent, the negative predictive value was 83 percent, and the positive predictive value was 82 percent.
Angioplasty During Followup
There were 182 PTCAs with or without stenting during a mean followup of 41±60 weeks of followup in 1,316 patients in 5 trials reporting data (
Evidence Table 34). There were 182 PTCAs in studies of troponin T and 51 in studies of troponin I. For patients undergoing PTCA during followup, the troponin T was initially positive in 79 (43 percent). The troponin I was positive in 22 undergoing PTCA during followup (43 percent). For troponin T, the specificity was 62 percent, the negative predictive value was 87 percent, and the positive predictive value was 15 percent. For troponin I, the specificity was 85 percent, the negative predictive value was 97 percent, and the positive predictive value was 10 percent.
Bypass Grafting During Followup
There were 233 bypass graft surgeries performed during a mean followup of 38±54 weeks of followup in 1,445 patients in 6 trials reporting data (
Evidence Table 35). Bypass surgeries were performed in 169 patients in studies of troponin T compared with 51 patients in studies of troponin I. For patients undergoing bypass grafting during followup, the troponin T was initially positive in 78 (46 percent). The troponin I was positive in 22 undergoing bypass grafting during followup (43 percent). For troponin T, the specificity was 63 percent, the negative predictive value was 90 percent, and the positive predictive value was 14 percent.
For troponin I, the specificity was 86 percent, the negative predictive value was 98 percent, and the positive predictive value was 10 percent.
Subgroup Comparisons: Risk of Death
Figure 2. Risk of death: Troponin T
Figure 3. Risk of death: Troponin I
Figure 4. Risk of total death
Figure 5. Risk of cardiac death
Figure 6. Risk of death: Unstable angina patients
Figure 7. Risk of death: Chest pain patients
Figure 8. Risk of death: Rapid bedside testing
Figure 9. Risk of death: Non-bedside testing
The relative risk of death and the combination of death or myocardial infarction for a patient with a positive troponin T or I test for each trial is displayed in Figures and and Summary Tables 3 to 6. An elevated troponin value was associated with an increased risk of death regardless of whether total death or only cardiac death was reported (Figures and ). Similarly, an elevated troponin level indicated a poor prognosis in unstable angina patients and in chest pain patients for whom myocardial infarction had been excluded (Figures and ). There were few studies of rapid bedside tests, but these showed a similar likelihood of a positive study when compared with studies of nonbedside methods of testing (Figures and ).
The absolute increased risk of death with a positive troponin test varied with time of followup. When followup was limited to fewer than 2 weeks, the mean increase in risk of death was 9 percent. For studies with longer followup, the absolute increased risk of death was 5 percent. This finding is consistent with the hypothesis that an elevated troponin level indicates risk of ischemic death that decreases over time following the initial event and the risk of other causes of death remains constant.
Figure 10. Correlation between mortality and troponin positive risk
The absolute risk of death was also associated with the baseline risk of death (relative risk [RR]=0.36, p=0.01, ). An increase in the overall mortality rate of 1 percent was associated with a 0.6 percent additional increase in the risk of death in troponin-positive patients.
Meta-Analysis of the Relative Risk of Death
When studies of troponin T were pooled, the relative risk for an increased risk of death was 3.1 (95 percent CI: 2.0-4.9) for total death, and 3.8 (95 percent CI: 2.4-6.0) for cardiac death (Summary Tables 3 and 7). Similar risks were observed when trials of unstable angina or chest pain patients (unstable angina and MI) were examined separately.
For studies of troponin I, the pooled relative risk for an increased risk of death was 3.9 (95 percent CI: 2.9-5.3) for total death, and 25 (95 percent CI: 11-56) for cardiac death (Summary Tables 4 and 7). As with troponin T, similar risks were observed when trials of unstable angina or chest pain patients (unstable angina and MI) were examined separately.
When all troponin studies were combined, the pooled relative risk for increased risk of death was 3.9 (95 percent CI: 3.0-5.3). The absolute increase in mortality was 3.9 percent (95 percent CI: 3.0-4.4) for patients with a positive troponin level.
The majority of studies used a threshold for a positive troponin between 0.1 and 0.2 ng/ml. The relative risk for increased risk of death was 4.0 (95 percent CI: 2.9-5.5) for the 10 trials of troponin T that used a cutoff of between 0.1 and 0.2 ng/ml. This result was not obviously different from those in the two trials that used a higher cutoff (relative risk 3.7, 95 percent CI: 1.9-7.5).
We evaluated the effect of followup time on the relative risk for increased risk of death by grouping trials into those with short-term followup (1-4 weeks, N=7), and long-term followup (greater than 4 weeks, N=7). There was a clear trend toward decreasing relative risk with increasing followup time. At 1-4 weeks, the relative risk was 5.3 (95 percent CI: 3.6-7.9). For longer term studies, the relative risk was 2.7 (95 percent CI: 1.8-4.2).
Meta-Analysis of the Relative Risk of Death or Myocardial Infarction
We examined the risk of death or subsequent myocardial infarction in the six trials of unstable angina that reported this data (Summary Tables 5 and 8). When all troponin studies were combined, the pooled odds ratio for increased risk of death or myocardial infarction was 3.8 (95 percent CI: 2.6-5.5). The weighted average for risk of death or subsequent MI in patients with a negative troponin was 6.4 percent (median followup: 4 weeks). For patients with a positive troponin test result, 20.8 percent had died or had a nonfatal myocardial infarction during the same period. The absolute increase in the rate of death or MI was 14 percent (95 percent CI: 10-18).
For studies of troponin T, the pooled relative risk for an increased risk of death or myocardial infarction was 3.8 (95 percent CI: 2.6-5.5) for patients with unstable angina (Summary Tables 5 and 8).
For studies of troponin I, the pooled relative risk for an increased risk of death or myocardial infarction was 5.7 (95 percent CI: 1.8--19) for patients with unstable angina (Summary Tables 6 and 8).
We evaluated the effect of followup time on the relative risk for increased risk of death by grouping trials into those with short-term followup (1--4 weeks, N=4), and long-term followup (greater than 4 weeks, N=2). The relative risk decreased with increasing followup time. At 1 to 4 weeks, the relative risk was 12.3 (95 percent CI: 6.4-23.8). For longer term studies, the relative risk was 2.0 (95 percent CI: 1.3-3.2).
Evaluation of Chest Pain Units and Emergency Department Protocols
Randomized Trials of Chest Pain Units
Three randomized trials assessing chest pain units or accelerated diagnostic protocols in the ED were published (
Evidence Table 36). Patients presenting to the ED who were determined to be at low risk for infarction or intermediate risk for unstable angina were randomized to a specified ED-based or chest pain unit protocol (intervention) or to routine hospital or telemetry unit care (control) (
Evidence Table 36). Patient baseline characteristics were not significantly different between intervention and control groups for all three studies (
Evidence Table 37). Patients randomized to the intervention group in all three studies were administered aspirin, monitored for ECG changes during varying observation periods, and assessed for CK-MB enzyme levels at varying time points (
Evidence Table 38). Patients with positive enzyme tests, recurrent chest pain, or ECG changes indicative of ischemia during observation were admitted (Evidence Tables 39 and 40). Patients with negative enzyme and ECG results underwent cardiac stress testing (
Evidence Table 41). In two studies, patients who were unable to perform treadmill exercise stress tests were administered pharmacologic stress tests (
Evidence Table 41). Nuclear imaging or echocardiography was also conducted in two of the studies. Positive or indeterminate stress test or imaging results also led to admission of intervention patients (Evidence Tables 39 and 40).
Deaths or myocardial infarctions that occurred during the hospital stay or within 30-day followup were considered "early events" (
Evidence Table 42). There were no statistically significant differences in the number of early events between intervention and control groups in all studies (
Evidence Table 42). Similarly, there were no statistically significant differences for subsequent events between intervention and control groups in all studies (
Evidence Table 43). Each study assessed the number of patients returning to the ED or hospital after initial hospital stay (
Evidence Table 44). There were no significant differences between intervention or control groups for ED or hospital returns in all studies. Survival analysis performed in one study (data not shown) (
Farkouh, Smars, Reeder, et al., 1998) determined that there were no significant differences between the intervention and control groups for survival free of a primary event (nonfatal myocardial infarction, death, acute congestive heart failure, stroke, or out-of-hospital cardiac arrest) during 6 months of followup. All events that occurred in the intervention group were in patients who met criteria for hospital admission, and most events occurred within the first month after randomization (
Farkouh, Smars, Reeder, et al., 1998).
All studies assessed length of stay and cost for intervention and control groups (Evidence Tables 45 and 46). In two studies, the length of stay for controls was significantly longer than for intervention patients (
Evidence Table 45). Cost analysis showed that, in general, patients initially admitted to the hospital incur significantly higher costs for cardiac care (
Evidence Table 46). One study used resource-based relative-value unit analysis and determined that costs were approximately 61 percent higher for in-hospital care compared with chest pain unit care costs (
Evidence Table 46). In addition, this study indicated that use of cardiac tests and procedures during 6 months of followup was significantly greater in the hospital care group (
Farkouh, Smars, Reeder, et al., 1998). One study, using charge data as a proxy for cost, showed that initial stay and 30-day followup costs were significantly higher in the routine care group (
Evidence Table 46). Routine care protocols were typically less consistent and often involved more expensive testing such as thallium scans and coronary arteriography compared with graded exercise or dobutamine stress testing that was used routinely in chest pain unit protocols. The impact of these cardiac tests and interventional therapies on length of stay and cost outcomes is significant.
Emergency Department Protocols
Two controlled clinical trials evaluating an acute cardiac ischemia predictability triage protocol were published. The acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) was used in multicenter and single-center settings (
Evidence Table 47) and provides ED physicians with a 0 to 1 percent probability of ACI to incorporate into triage decisionmaking. The variables used to calculate the probability by logistic regression modeling include the following: (1) age, (2) gender, (3) presence or absence of chest pain or pressure or left arm pain, (4) whether chest pain or pressure was the patient's most important presenting symptom, (5) the presence or absence of ECG Q waves, (6) the presence and degree of ECG ST-segment elevation or depression, and (7) the presence and degree of ECG T-wave elevation or inversion. Using an alternating 7-month study design, two investigative groups assessed triage accuracy, time to triage, 30-day mortality, and rehospitalization rates during months when ACI-TIPI results were printed on initial ECG readings (intervention), and during months when ACI-TIPI results were not printed on initial ECG readings (control). Baseline patient characteristics were not significantly different between intervention and control groups in both studies (
Evidence Table 48). Patient diagnostic characteristics were similar between intervention and control groups in both studies (
Evidence Table 49).
The use of ACI-TIPI at hospitals with high-capacity cardiac care units (CCUs) reduced admissions to the CCU for patients without cardiac ischemia and increased discharges to home (
Evidence Table 50). These results were considered of borderline significance (p=0.09). Patients who were identified as having a lower predictive probability of acute cardiac ischemia (<10 percent) experienced greater reductions in admission rates (odds ratio, 0.51 [95 percent CI: 0.28-0.91]) than patients in higher risk groups (odds ratio, 0.74 [95 percent CI: 0.52-1.05], data not shown) (
Selker, Beshansky, Griffith, et al., 1998). There were no significant differences in admissions to the CCU or non-CCU wards or discharges home between intervention and control groups of patients without cardiac ischemia at hospitals with low-capacity CCUs (
Evidence Table 51).
There were significant reductions in CCU admissions in high-capacity CCU hospitals for patients diagnosed with stable angina pectoris when ACI-TIPI was used (
Evidence Table 52). Admissions to non-CCU wards and discharges home increased with ACI-TIPI (overall p=0.02) (
Evidence Table 52). In low-capacity CCU hospitals, use of ACI-TIPI improved triage by decreasing non-CCU admissions and increasing discharges home (overall p=0.02) (
Evidence Table 53). Patients identified as having a low or low-mid predictive probability of acute cardiac ischemia (< 25 percent) experienced greater reductions in admission rates (odds ratio, 0.36 [95 percent CI: 0.13-0.999]) than patients in high-mid or high probability groups (>25 percent) (odds ratio, 0.73 [95 percent CI: 0.34-1.58], data not shown) (
Selker, Beshansky, Griffith, et al., 1998). For patients diagnosed with acute myocardial infarction or unstable angina, the use of ACI-TIPI had no effect on triage in all hospitals (Evidence Tables 54 and 55).
There were no significant differences in 30-day mortality or 30-day rehospitalization for patients during ACI-TIPI intervention or ACI-TIPI control months in either study (Evidence Tables 56 and 57). No significant reductions in time to triage were seen when ACI-TIPI was used (
Evidence Table 58). However, when novice clinicians (physicians in their first emergency department rotation) used ACI-TIPI and patients were diagnosed with acute cardiac ischemia, the time of triage from ED presentation to ED release decreased by 0.7 hours (p=0.7) (data not shown) (
Sarasin, Reymond, Griffith, et al., 1994).
Chest Pain Unit Safety
To address chest pain unit safety, two nonrandomized, noncontrolled studies with large population numbers are discussed. First, the Heart Emergency Room (ER) program enrolled 1,010 patients with possible acute ischemic coronary syndrome to assess a comprehensive diagnostic 9-hour evaluation (Gibler, Runyon, Levy, et al., 1995). This study has the highest cohort number of any studies evaluating chest pain unit protocol efficacy for low- to moderate-risk patients to date (data not shown). After the standard 9-hour observation period, 829 (82.1 percent) patients were released home. Positive serial CK-MB assay results, ECG results, or echocardiography results consistent with MI or evolving MI led to 153 patient admissions (15.1 percent). Fifty-two patients (34 percent) were diagnosed with cardiac disease; of those, 12 (23 percent) had a diagnosis of MI and 31 (59.6 percent) were diagnosed with angina or unstable angina. During 1 month of followup, one patient (0.12 percent) was rehospitalized for AMI 3 days after discharge home with negative heart ED evaluation. Another patient with negative heart ED evaluation died 3 weeks later of unknown cause. The mean age of the study population was 45.0 years. The incidence of MI in the heart ER population was 1.2 percent, a low-risk population.
Second, a multiple-site registry study of eight established chest pain units evaluated a total of 23,407 patients presenting to study hospitals' emergency departments with chest pain (Graff, Dallara, Ross, et al., 1997). A comparison population was used from five previous studies involving a total of 12,405 patients. The study measured the proportion of ED patients who underwent "rule-out MI" evaluation and the rate of "missed MIs" who returned to the ED. A higher proportion of the chest pain unit population, relative to the comparison population, underwent a rule-out MI evaluation (67 percent versus 57 percent, p<0.1). Consequently, fewer MIs were missed during the initial ED visit (0.4 percent versus 4.5 percent, p<0.1). A lower proportion of chest pain unit patients were admitted after the initial ED evaluation (41 percent versus 57 percent, p<0.1). Costs were lower for patients evaluated in chest pain units than for patients evaluated by routine hospital care. Followup mortality data were not reported by these authors.
Chest Pain Units and Patient Satisfaction
One randomized trial retrieved from our search criteria assessed patient satisfaction with care in an emergency chest pain observation unit (CPOU) (data not shown) (Rydman, Zalenski, Roberts, et al., 1997). Evaluation of 104 patients randomized to the CPOU or to inpatient care found that scores on global satisfaction indicators-quality of service, receipt of desired service, fulfillment of hospital needs, recommendation of service, satisfaction with service, effective handling of problem, overall satisfaction-were consistently higher for the CPOU. Higher scores for quality of service, recommendation of service, effective treatment of health problem, and overall satisfaction were statistically significant. Patients reported fewer total problems related to CPOU service than inpatient service (p=0.02), including areas of patient communication, fulfillment of special needs or preferences, and physical comfort. Patients' perceived length of stay did not differ significantly between CPOU or inpatient service (data not shown).
Investigators in this study compared their findings with national reference data and found that overall satisfaction with care was most strongly correlated with fewer problems in the areas of communication, total number of problems, special needs or preferences, emotional support, physical comfort, patient education, and discharge preparation (data not shown). The authors do not mention the impact of the "Hawthorne effect" (greater effort and enthusiasm put forth by staff in a newer unit and their effect on patients relative to staff in an established CCU or telemetry unit) on their data. However, the authors also do not indicate the "age" of the CPOU evaluated.
Chapter 4. Conclusions
In patients with chest pain raising suspicion of acute ischemia or diagnosed unstable angina, we found both common positive predictors of outcomes, as well as several variables that were consistently not associated with adverse
events (Evidence Tables 15 and 16). Common positive independent predictors included increasing age, male sex (more consistently in the undiagnosed unstable angina cohorts), prior myocardial infarction, diabetes mellitus, hypertension, congestive heart failure or cardiogenic shock on admission, and ST-segment depression. Interestingly, several variables that were consistently found not to be significantly associated with outcomes included race/ethnicity, prior stable angina, and isolated T-wave inversions. However, given the methodologic limitations and relatively small number of studies evaluating these characteristics, the latter results should be interpreted cautiously. Furthermore, several of the potentially important clinical and electrocardiographic variables were not specifically evaluated as independent predictors in any of the reviewed studies (e.g., prior stroke or transient ST elevation).
Tests of troponin T or I were predictive of cardiac events including death and myocardial infarction. Patients with elevated troponin levels were also more likely to undergo coronary revascularization. The increased risk appears to be independent of history and electrocardiographic findings and is proportional to the overall risk of cardiac death or myocardial infarction.
Chest pain units or protocols that use history, physical electrocardiographic, cardiac marker, and selective stress-testing data to determine the degree and location of care demonstrated reduced costs with no obvious increase in risk to the patient, but sample sizes were small and statistical power to detect increased risk was limited in studies to date. Although the ED protocol studies described did not evaluate costs, it is assumed that an increase in the number of patients discharged home and a decrease in CCU admissions would lower cost.
All information presented in this evidence report applies to adult men and women.
Limitations
One focus of this report was to identify independent predictors of cardiac outcomes in suspected or confirmed unstable angina based on results from multivariate analyses that attempted to control for potential confounding in these observational studies. Therefore, we did not include studies that involved decision support tools previously shown to be helpful in clinical decisionmaking for patients with chest pain or other symptoms suggestive of acute ischemia or infarction. Examples include decision trees based on recursive partitioning (Goldman, Cook, Brand, et al., 1988; Goldman, Weinberg, Weisberg, et al., 1982). These models are recognized as valuable and clinically useful decision support tools for patients presenting with chest pain or suspected cardiac ischemia but did not meet the necessary inclusion criteria for our analysis. Other caveats of our review are that many studies did not specifically address all of the available clinical and electrocardiographic predictor variables and there was substantial heterogeneity in all other aspects of the reviewed prognostic studies including study design, enrollment criteria, predictor variables, outcomes of interest, duration of followup, and methods of analysis. Finally, we were only able to provide semiquantitative estimates for individual predictors based on limitations in the available data across studies. In multivariate prognostic studies, the method of totaling the number of times variables were found to be significant needs to be interpreted cautiously because many studies were small and lacked power to find clinically important differences.
Studies of troponin T and I rarely reported long-term followup (longer than 6 months); thus, the implications for long-term survival with an abnormal troponin result are unclear. There is no standard troponin I assay; thus, we could not compare threshold values across studies. In addition, we cannot determine which assay is most predictive of outcome. The limitations may make it difficult to observe the true magnitude of risk associated with a symptom or marker. In contrast, if studies included ST-elevation patients, the prognostic value of troponin will likely be greater than that of non-ST-elevation patients and mixing the two will lead to an intermediate risk value. The definition of unstable angina varied across studies, which limits the ability to compare results. Underreporting of negative studies may have increased the strength of the relationship between elevated troponin levels and outcome.
Chapter 5. Future Research
Although numerous studies have examined the impact of patient characteristics, electrocardiographic findings, and serum marker levels on prognosis, more data are needed to allow the clinician to combine all of this information into an overall prognosis score. Our qualitative review of clinical and electrocardiographic predictors of prognosis suggests that future studies should include the following variables in a multivariate prediction model: age, male sex, prior MI, diabetes, heart failure on presentation, ST depression, and ST elevation. Future prognostic studies in these patient groups should at least account for the identified risk factors and should strive towards standardized data collection of initially available clinical and electrocardiographic information. Furthermore, uniform collection of race or ethnic and gender data, particularly as it relates to presenting symptoms, will provide the basis for determining if predictors of risk differ between ethnic groups or genders. Future studies should also include either troponin T or I as a variable in any multivariate analysis.
To directly address the actual impact of these variables, future efforts are needed to develop standard variable definitions and data collection across studies to allow for combination of study results for pooled analysis or meta-analytic techniques similar to that used by the American College of Cardiology National Cardiovascular Data Registry for cardiac catheterization procedures. If accomplished, this might provide clinicians a more refined ability to immediately and accurately risk stratify patients with suspected or confirmed unstable angina. It would also provide a precise baseline for which the incremental cost-effectiveness of new diagnostic tests in this patient population could be evaluated.
Further comparative studies are needed between different cardiac markers to determine the optimal combination for prognosis. Additional studies are needed to determine if a positive troponin T or I should be used to guide early therapy, such as early revascularization. The marginal cost-effectiveness of testing with troponin compared with relying on older estimates of risk should be examined. If troponin testing is found to be cost-effective, then additional studies can examine the marginal cost-effectiveness of also performing stress testing or coronary angiography. Standardization of troponin I assays is needed in order to investigate the effect of the threshold level on prognosis.
More information is needed regarding certain subgroups of patients with unstable angina. In particular, the prognostic value of troponin testing in patients with renal dysfunction and in the elderly needs clarification.
More randomized trials of chest pain units or chest pain protocols are needed to determine their health and economic benefits. Whether chest pain units are a safe alternative to routine evaluation of patients presenting with chest pain will be better determined when larger study populations including older, low- and intermediate-risk patients are evaluated. Similarly, longer term patient outcome measures (2 or 3 years of followup) are required to better determine effectiveness, safety, and long-term cost-effectiveness of chest pain units relative to routine care.
Summary Tables
Summary Table 1. Summary findings for independent clinical and ECG predictors of adverse outcomes (death, MI, major complications): Chest pain suspicious for cardiac ischemia
Summary Table 2. Summary findings for independent clinical and ECG predictors of adverse outcomes (death, MI, major complications): Diagnosed unstable angina
Summary Table 3. Risk of death with positive troponin T
| Antman | 1998 | 2 | 1.5% | 0.3% | 1.18 | 0.25 | 5.63 |
| Gokhan Cin | 1996 | 1 | 11.1% | 20.8% | 6.00 | 1.31 | 27.53 |
| Hamm | 1992 | 1 | 7.1% | 13.2% | 7.73 | 0.94 | 63.23 |
| Hamm | 1997 | 4 | 2.6% | 12.4% | 21.14 | 7.19 | 62.16 |
| Luscher | 1997 | 4 | 1.7% | 2.8% | 8.58 | 1.08 | 68.10 |
| Mockel | 1998 | 12 | 2.8% | 7.0% | 4.32 | 0.43 | 43.85 |
| Ohman | 1996 | 4 | 5.3% | 7.8% | 4.69 | 1.56 | 14.06 |
| Pettijohn | 1997 | 24 | 3.9% | 2.5% | 1.79 | 0.31 | 10.27 |
| Ravkilde | 1993 | 24 | 3.1% | 5.6% | 5.66 | 0.61 | 52.81 |
| Ravkilde | 1995 | 112 | 4.8% | 9.0% | 3.96 | 0.85 | 18.45 |
| Stubbs | 1996 | 147 | 14.2% | 7.8% | 1.67 | 0.82 | 3.39 |
Summary Table 3. Risk of death with positive troponin T
Summary Table 4. Risk of death with positive troponin I
| Antman | 1996 | 6 | 1.5% | 2.7% | 3.81 | 1.70 | 8.53 |
| Brscic | 19981 | 4 | 2.2% | 6.2% | 3.18 | 0.48 | 21.29 |
| Christenson | 1998 | 4 | 3.4% | 7.5% | 2.71 | 1.59 | 4.61 |
| Hamm | 1997 | 4 | 2.5% | 10.9% | 66.89 | 9.02 | 496.09 |
| Luscher | 1997 | 4 | 1.4% | 2.6% | 4.98 | 1.04 | 23.73 |
Summary Table 4. Risk of death with positive troponin I
Summary Table 5. Risk of death or MI with positive troponin T
| Antman | 1995 | 1 | 7.0% | 15.8% | 6.76 | 1.39 | 32.79 |
| DeFilippi | 1998 | 52 | 5.3% | 13.1% | 6.77 | 1.77 | 25.83 |
| Hamm | 1992 | 1 | 13.1% | 28.3% | 15.45 | 2.07 | 115.17 |
| Hamm | 1997 | 4 | 2.6% | 7.6% | 6.46 | 2.73 | 15.26 |
| Lindahl | 1996 | 20 | 10.2% | 8.4% | 2.91 | 1.41 | 6.00 |
| Luscher | 1997 | 4 | 7.6% | 6.3% | 2.41 | 1.25 | 4.66 |
| Luscher | 1998 | 12 | 9.8% | 16.5% | 5.70 | 1.25 | 25.91 |
| Olatidoye | 1998 | 4 | 7.5% | 32.5% | 11.07 | 2.97 | 41.30 |
| Ravkilde | 1995 | 112 | 8.9% | 18.9% | 4.75 | 1.58 | 14.32 |
| Rebuzzi | 1998 | 12 | 14.7% | 40.9% | 5.50 | 2.37 | 12.78 |
| Stubbs | 1996 | 147 | 21.3% | 11.7% | 1.67 | 0.97 | 2.90 |
| Yang | 1995 | 1 | 12.8% | 30.7% | 19.41 | 2.62 | 143.93 |
Summary Table 5. Risk of death or MI with positive troponin T
Summary Table 6. Risk of death or MI with positive troponin I
| Galvani | 1997 | 4 | 9.9% | 16.9% | 3.92 | 1.15 | 13.33 |
| Hamm | 1997 | 4 | 2.6% | 5.7% | 5.28 | 2.19 | 12.71 |
| Luscher | 1997 | 4 | 7.6% | 5.5% | 2.04 | 1.11 | 3.78 |
| Olatidoye | 1998 | 4 | 7.5% | 35.3% | 12.05 | 3.26 | 44.60 |
Summary Table 6. Risk of death or MI with positive troponin I
Summary Table 7. Subgroup analysis of the risk of death associated with a positive troponin test
| Troponin T | | | | | |
| Total death | 32/1,187 | 46/473 | 3.1 | 2.0-4.9 | 5 |
| Cardiac death | 31/1,689 | 52/744 | 3.8 | 2.4-6.0 | 7 |
| Unstable angina patients
1 | 21/397 | 26/198 | 2.5 | 1.4-4.5 | 5 |
| Chest pain patients
1 | 42/2,479 | 72/1,019 | 4.0 | 2.7-5.9 | 7 |
| Troponin I | | | | | |
| Total death | 34/1,451 | 49/815 | 3.1 | 2.0-4.9 | 3 |
| Cardiac death | 3/905 | 26/384 | 25 | 11-55 | 2 |
| Unstable angina patients
1 | 2/70 | 2/22 | 3.2 | 0.3-40 | 1 |
| Chest pain patients
1 | 35/2,286 | 73/1,177 | 5.1 | 3.4-7.6 | 4 |
| Troponin T and I Combined2 | | | | | | |
| Total death | 42/2,088 | 69/1,068 | 3.3 | 2.2-4.8 | 7 |
| Cardiac death | 28/1,641 | 55/792 | 5.0 | 3.2-7.9 | 7 |
Summary Table 7. Subgroup analysis of the risk of death associated with a positive troponin test
Summary Table 8. Subgroup analysis of the risk of death or myocardial infarction associated with a positive troponin test in patients with unstable angina
| Troponin T | 43/667 | 62/301 | 3.7 | 2.5-5.6 | 5 |
| Troponin I | 7/163 | 10/35 | 5.7 | 1.8-19 | 2 |
| Troponin T and I Combined
1 | 47/737 | 67/322 | 3.8 | 2.6-5.5 | 6 |
Summary Table 8. Subgroup analysis of the risk of death or myocardial infarction associated with a positive troponin test in patients with unstable angina
Appendices
Appendix A. Acknowledgments
Peer Reviewers
At-large Reviewers
Ezra A. Amsterdam, MD
Division of Cardiovascular Medicine
4150 "V" Street, Suite 3500
Sacramento, CA 95817
Dr. N. Curzen, Ph.D., MRCP
Consultant Cardiologist
Manchester Heart Centre
Manchester Royal Infirmary
Oxford Road
Manchester M13 9WL
Andrew M. Hauser, MD
Director, Cardiac Ultrasound Laboratory
William Beaumont Hospital
Royal Oak, MI
David Holmes, Jr., MD
Cardiovascular Diseases & Internal Medicine
Mayo Clinic
200 First Street SW
Rochester, Minnesota 55905
Spencer B. King III, M.D.
Professor of Medicine (Cardiology)
Emory U. School of Medicine
Director, Interventional Cardiology
Emory U. Hospital
1364 Clifton Rd. NE, Suite F606
Atlanta, GA 30322
Michael C. Kontos, MD
Associate Director, Acute Cardiac Care
Assistant Professor, Cardiology and Emergency Medicine
1200 E Marshall St
PO Box 980051
Richmond, VA 23298-0051
Thomas H. Lee, MD
Associate Professor of Medicine
Harvard Medical School
Medical Director
Partners Community HealthCare, Inc.
Prudential Tower, 11th floor
800 Boylston Street
Boston, MA 02199
Wiliam C. Little, MD
Professor of Medicine
Chief, Cardiology Section
Department of Internal Medicine
Wake Forest School of Medicine
The Bowman Gray Campus
Medical Center Boulevard
Winston-Salem, North Carolina 27157
David Malenka, MD
Associate Professor of Medicine
Section of Cardiology
Darthmouth-Hitchcock Medical Center
Lebanon, NH 03756
Emile R. Mohler III, MD
Presbyterian Medical Center
Philadelphia Heart Institute Building, Room 432-B
39th and Market Streets
Philadelphia, PA 19104
John Sarko, MD
Department of Emergency Medicine
Maricopa Medical Center
2601 E. Roosevelt
Phoeniz, AZ 85008
Alan H.B. Wu, MD
Department of Pathology and Laboratory Medicine
Hartford Hospital
80 Seymore Street
Hartford, Connecticut 06102-5037
and
Professor, Department of Laboratory Medicine
University of Connecticut Health Center
Farmington, CT 06030
Robert J. Zalenski, MD, MA
Department of Emergency Medicine
Wayne State University School of Medicine
4201 St Antoine
Detroit, Michigan 48201
Technical Reviewer
Magnus Ohman, MD, FACC
Associate Professor of Medicine
Division of Cardiology
Co-Director, Clinical Trials
Duke Clinical Research
2400 Pratt Street, Room 0311
Terrace Level
Durham, NC 27705
Nominated Reviewers
American College of Physicians
Gottlieb C. Friesinger II, MD, MACP
Professor of Medicine and the
Betty and Jack Bailey
Professor of Cardiology in the
Department of Medicine
Vanderbilt University
Division of Cardiology
2220 Pierce Avenue
Nashville, TN 37232
American Society of Health-System Pharmacists
G. Dennis Clifton, PharmD
College of Pharmacy
Washington State University
The Heart Institute of Spokane
122 W. 7th Avenue, Suite 230
Spokane, WA 99204
Sarah A. Spinler, PharmD, FCCP
Associate Professor of Clinical Pharmacy
Philadelphia College of Pharmacy
University of the Sciences in Philadelphia
600 South 43rd Street
Philadelphia, PA 19104-9938
American College of Emergency Physicians
Earl E. Smith III, MD, FACEP
1503 Blackbird Lane
San Antonio, TX 78248
Francis M. Fesmire, MD, FACEP
Director, Heart-Stroke Center
Erlanger Medical Center
Assistant Professor of Medicine
University of Tennessee College of Medicine
PO Box 4045
Chattanooga, TN 37405
American Hospital Association
Donald M. Nielsen, MD
Senior Vice President for Quality Leadership
American Hospital Association
325 Seventh Street, NW
Washington, DC 20004
Society of Emergency Medicine Physician Assistants
Terry Mize, PA-C
Past President, SEMPA
Society of Emergency Medicine PAs
1564 S. Josephine Street
Denver, CO 80210
Emergency Nurses Association
Cindy Abel, RN, MSN, CEN
President, Emergency Nurses Association
Clinical Nurse Specialist
Emergency Department
Rush-Copley Medical Center
Aurora, IL 60505
S. Kay Sedlak, RN, MS, CEN
Saint Mary's Health Network
235 West 6th Street
Reno, Nevada 89520
Suzanne M. Wall, RN, MS CEN
54 Lackine Drive
Rochester, NY 14618
Roche Diagnostics
Christopher De Filippi, MD
Assistant Professor of Medicine
Department of Cardiology
University of Texas
Medical Branch at Galveston
Director, Chest Pain Unit
5.106 John Sealy Annex
301 University Blvd.
Galvaston, TX 77555-0553
Kristin Newby, MD, FACC
Assistant Professor of Medicine
Division of Cardiology
Duke University Medical Center and
Duke Clinical Research Institute
PO Box 17969
Durham, NC 27715
Criticism Editor
Patricia Huston, MD, MPH
Scientific Communications International, Inc.
585 Island Park Crescent
Ottawa, ON K1Y 3P3
Data Abstractors
Dena Bravata, M.D.
Bill Fearon, M.D.
Byron K. Lee, M.D.
Tina Lee, M.D., M.S.
Lynnette Lissin, M.D.
Eric Putz, M.D.
Mark Schleinitz, M.D.
Lane Medical Library, Stanford University
Christopher Stave, M.L.S.
Staff, Document Delivery Services
Appendix B. Research Team
The team was led by cardiologists Mark Hlatky and Paul Heidenreich. Further information about the UCSF-Stanford Evidence-based Practice Center can be found at:
http://www.stanford.edu/group/epc/
(alphabetical listing)
Thomas Alloggiamento, M.D. (Research Associate)
Alan Go, M.D., M.P.H. (Research Associate)
Vivian Hagan (Research Assistant)
Trevor Hastie, Ph.D. (Biostatistician)
Mark A. Hlatky, M.D. (Project Director)
Paul A. Heidenreich, M.D., M.S. (Assistant Director)
Kathryn M. McDonald, M.M. (Center Coordinator)
Kathryn A. Melsop, M.S. (Research Assistant)
Elaine Steel (Project Assistant)
Appendix C. Acronyms
ACE: angiotensin-converting enzyme
ACI: acute cardiac ischemia
ACI-TIPI: acute cardiac ischemia time-insensitive predictive instrument
Adm: admission
ADP: accelerated diagnostic protocol
AHCPR: Agency for Health Care Policy and Research
AHRQ: Agency for Healthcare Research and Quality
AMI: acute myocardial infarction
ASA: aspirin
AST: aspartate aminotransferase
ATPase: adenosine triphosphatase
AV: atrioventricular
BP: blood pressure
bpm: beats per minute
CABG: coronary artery bypass graft
CAD: coronary artery disease
CCB: calcium channel blocker
CCSC: Canadian Cardiovascular Society Class
CCU: cardiac care unit
CE: composite endpoint
CHD: coronary heart disease
CHF: congestive heart failure
CI: confidence interval
CK :creatinine phosphokinase
CK-MB: creatinine phosphokinase, MB fraction
CPOU: chest pain observation unit
cTnI: cardiac troponin I
cTnT: cardiac troponin T
CV: cardiovascular
CVA: cerebrovascular accident
DBP: diastolic blood pressure
Def'n: definition
Dept: department
DM: diabetes mellitus
dx: diagnosis
ECG: electrocardiogram
ED: emergency department
EPC: evidence-based practice center
F: female
GUSTO: Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries
HD: heart disease
HR: heart rate
HTN: hypertension
hx: history
IABP:intra-aortic balloon pump
IV:intravenous
LBBB: left bundle branch block
LDH:lactate dehydrogenase
LOS:length of stay
LVEF: left ventricular ejection fraction
LVH: left ventricular hypertrophy
M: male
MB: myoglobin
MGH: Massachusetts General Hospital
MI: myocardial infarction
MILIS: Multicenter Investigation of the Limitation of Infarct Size
mmHg:millimeters of mercury
mV: millivolt
n/a: not available
NA: not available
NQWMI: non-Q-wave myocardial infarction
NS: nonsignificant
NTG: nitroglycerine
Pos: positive
Post-OP: postoperative
PTCA: percutaneous transluminal coronary angioplasty
PVC: premature ventricular contraction
RBBB: right bundle branch block
revasc: revascularization
RR: relative risk
S3: third heart sound
S4: fourth heart sound
SBP: systolic blood pressure
SD: standard deviation
STT: ST-segment or T-wave
TIA: transient ischemic attack
TIMI: Thromobolysis in Myocardial Infarction
TWI: T-wave inversion
VF: ventricular fibrillation
VT: ventricular tachycardia
W: white
References
Alonsozana GL, Christenson RH.
The case for cardiac troponin T: Marker for effective risk stratification of patients with acute cardiac ischemia.
Clin Chem.
1996; 42(5): 803–8. [PubMed]
Adams JE 3rd, Schechtman KB, Landt Y, et al.
Comparable detection of acute myocardial infarction by creatine kinase MB isoenzyme and cardiac troponin I.
Clin Chem.
1994; 40(7 Pt 1): 1291–5. [PubMed]
Antman EM, Grudzien C, Sacks DB.
Evaluation of a rapid bedside assay for detection of serum cardiac troponin T.
JAMA.
1995; 273(16): 1279–82. [PubMed]
Antman EM, Sacks DB, Rifai N, et al.
Time to positivity of a rapid bedside assay for cardiac-specific troponin T predicts prognosis in acute coronary syndromes: A Thrombolysis in Myocardial Infarction (TIMI) 11A substudy.
J Am Coll Cardiol.
1998; 31(2): 326–30. [PubMed]
Antman EM, Tanasijevic MJ, Thompson B, et al.
Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes.
N Engl J Med.
1996; 335(18): 1342–9. [PubMed]
Apple FS, Voss E, Lund L, et al.
Cardiac troponin, CK-MB and myoglobin for the early detection of acute myocardial infarction and monitoring of reperfusion following thrombolytic therapy.
Clin Chim Acta.
1995; 237(1-2): 59–66. [PubMed]
Armstrong PW, Fu Y, Chang WC, et al. Acute coronary syndromes in the GUSTO-IIb trial: Prognostic insights and impact of recurrent ischemia.
The GUSTO-IIb Investigators. Circulation.
1998; 98(18): 1860–8.
Bakker AJ, Gorgels JP, van Vlies B, et al. The mass concentrations of serum troponin T and creatine kinase-MB are elevated before creatine kinase and creatine kinase-MB activities in acute myocardial infarction.
Eur J Clin Chem Clin Biochem.
1993a; 31(11): 715–24.
Bakker AJ, Koelemay MJ, Gorgels JP, et al. Failure of new biochemical markers to exclude acute myocardial infarction at admission.
Lancet.
1993b; 342(8881): 1220–2.
Bakker AJ, Koelemay MJ, Gorgels JP, et al. Troponin T and myoglobin at admission: Value of early diagnosis of acute myocardial infarction.
Eur Heart J.
1994; 15(1): 45–53.
Barish RA, Doherty RJ, Browne BJ. Reengineering the emergency evaluation of chest pain.
J Healthc Qual.
1997; 19(5): 6–12; quiz 60.
Benamer H, Steg PG, Benessiano J, et al.
Comparison of the prognostic value of C-reactive protein and troponin I in patients with unstable angina pectoris.
Am J Cardiol.
1998; 82(7): 845–50. [PubMed]
Braunwald E, Jones RH, Mark DB, et al.
Diagnosing and managing unstable angina. Agency for Health Care Policy and Research.
Circulation.
1994; 90(1): 613–22. [PubMed]
Brscic E, Chiappino I, Bergerone S, et al.
Prognostic implications of detection of troponin I in patients with unstable angina pectoris.
Am J Cardiol.
1998; 82(8): 971–3. [PubMed]
Calvin JE, Klein LW, VandenBerg BJ, et al.
Risk stratification in unstable angina. Prospective validation of the Braunwald classification.
JAMA.
1995; 273(2): 136–41. [PubMed]
Cannon CP, McCabe CH, Stone PH, et al. The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: Results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia
J Am Coll Cardiol 1997. 30(1):133–40.View this and related citations using
.
Castaner A, Roig E, Serra A, et al.
Risk stratification and prognosis of patients with recent onset angina.
Eur Heart J.
1990; 11(10): 868–75. [PubMed]
Chang CC, Ip MP, Hsu RM, et al.
Evaluation of a proposed panel of cardiac markers for the diagnosis of acute myocardial infarction in patients with atraumatic chest pain.
Arch Pathol Lab Med.
1998; 122(4): 320–4. [PubMed]
Chin MH, Cook EF, Lee TH, et al.
Correlates of major complications and mortality in patients presenting to the emergency department with chest pain and more than bibasilar rales.
J Gen Intern Med.
1994; 9(12): 659–65. [PubMed]
Christenson RH, Duh SH, Newby LK, et al.
Cardiac troponin T and cardiac troponin I: Relative values in short-term risk stratification of patients with acute coronary syndromes. GUSTO-IIa Investigators.
Clin Chem.
1998; 44(3): 494–501. [PubMed]
Coronado BE, Griffith JL, Beshansky JR, et al.
Hospital mortality in women and men with acute cardiac ischemia: A prospective multicenter study.
J Am Coll Cardiol.
1997; 29(7): 1490–6. [PubMed]
Cunningham MA, Lee TH, Cook EF, et al.
The effect of gender on the probability of myocardial infarction among emergency department patients with acute chest pain: A report from the Multicenter Chest Pain Study Group.
J Gen Intern Med.
1989; 4(5): 392–8. [PubMed]
D'Costa M, Fleming E, Patterson MC.
Cardiac troponin I for the diagnosis of acute myocardial infarction in the emergency department.
Am J Clin Pathol.
1997; 108(5): 550–5. [PubMed]
deFilippi CR, Parmar RJ, Potter MA, et al.
Diagnostic accuracy, angiographic correlates and long-term risk stratification with the troponin T ultra sensitive Rapid Assay in chest pain patients at low risk for acute myocardial infarction.
Eur Heart J.
1998; 19(Suppl N): N42–N47. [PubMed]
DerSimonian R, Laird N.
Meta-analysis in clinical trials.
Control Clin Trials.
1986; 7(3): 177–88. [PubMed]
de Winter RJ, Koster RW, Schotveld JH, et al.
Prognostic value of troponin T, myoglobin, and CK-MB mass in patients presenting with chest pain without acute myocardial infarction.
Heart.
1996; 75(3): 235–9. [PubMed]
Diamond GA, Forrester JS.
Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease.
N Engl J Med.
1979; 300(24): 1350–8. [PubMed]
Farkouh ME, Smars PA, Reeder GS, et al.
A clinical trial of a chest-pain observation unit for patients with unstable angina. Chest Pain Evaluation in the Emergency Room (CHEER) Investigators.
N Engl J Med.
1998; 339(26): 1882–8. [PubMed]
Galvani M, Ottani F, Ferrini D, et al.
Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina.
Circulation.
1997; 95(8): 2053–9. [PubMed]
Gerhardt W, Katus H, Ravkilde J, et al.
S-troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentrations of S-creatine kinase isoenzyme MB.
Clin Chem.
1991; 37(8): 1405–11. [PubMed]
Gerhardt W, Ljungdahl L.
Detection of myocardial damage by serial measurements of cardiac troponin T, CK MBmass, and TROPT rapid test.
Cardiovasc Drugs Ther.
1997; 11(Suppl 1): 227–40. [PubMed]
Gerhardt W, Ljungdahl L, Collinson PO, et al.
An improved rapid troponin T test with a decreased detection limit: A multicentre study of the analytical and clinical performance in suspected myocardial damage.
Scand J Clin Lab Invest.
1997; 57(6): 549–57. [PubMed]
Gerhardt W, Ljungdahl L, Herbert AK.
Troponin-T and CK MB (mass) in early diagnosis of ischemic myocardial injury. The Helsingborg Study, 1992.
Clin Biochem.
1993; 26(4): 231–40. [PubMed]
Gibler WB, Lewis LM, Erb RE, et al.
Early detection of acute myocardial infarction in patients presenting with chest pain and nondiagnostic ECGs: Serial CK-MB sampling in the emergency department [published erratum appears in Ann Emerg Med 1991 Apr;20(4):420].
Ann Emerg Med.
1990; 19(12): 1359–66. [PubMed]
Gibler WB, Runyon JP, Levy RC, et al.
A rapid diagnostic and treatment center for patients with chest pain in the emergency department.
Ann Emerg Med.
1995; 25(1): 1–8. [PubMed]
Gokhan Cin V, Gok H, Kaptanoglu B.
The prognostic value of serum troponin T in unstable angina.
Int J Cardiol.
1996; 53(3): 237–44. [PubMed]
Goldman L, Cook EF, Brand DA, et al.
A computer protocol to predict myocardial infarction in emergency department patients with chest pain.
N Engl J Med.
1988; 318(13): 797–803. [PubMed]
Goldman L, Weinberg M, Weisberg M, et al.
A computer-derived protocol to aid in the diagnosis of emergency room patients with acute chest pain.
N Engl J Med.
1982; 307(10): 588–96. [PubMed]
Gomez MA, Anderson JL, Karagounis LA, et al. An emergency department-based protocol for rapidly ruling out myocardial ischemia reduces hospital time and expense: Results of a randomized study (ROMIO)
J Am Coll Cardiol 1996. 28(1):25–33.View this and related citations using
.
Graff LG, Dallara J, Ross MA, et al.
Impact on the care of the emergency department chest pain patient from the chest pain evaluation registry (CHEPER) study.
Am J Cardiol.
1997; 80(5): 563–8. [PubMed]
Green GB, Beaudreau RW, Chan DW, et al.
Use of troponin T and creatine kinase-MB subunit levels for risk stratification of emergency department patients with possible myocardial ischemia.
Ann Emerg Med.
1998; 31(1): 19–29. [PubMed]
Gust R, Gust A, Bottiger BW, et al.
Bedside troponin T testing is not useful for early out-of-hospital diagnosis of myocardial infarction.
Acta Anaesthesiol Scand.
1998; 42(4): 414–7. [PubMed]
Hamm CW, Goldmann BU, Heeschen C, et al.
Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I.
N Engl J Med.
1997; 337(23): 1648–53. [PubMed]
Hamm CW, Ravkilde J, Gerhardt W, et al.
The prognostic value of serum troponin T in unstable angina.
N Engl J Med.
1992; 327(3): 146–50. [PubMed]
Hedges L. Fixed effects models. In: Cooper H, Hedges L, editors. The handbook of research synthesis. New York: Russel Sage Foundation; 1994. p. 307-35.
Heeschen C, Goldmann BU, Moeller RH, et al.
Analytical performance and clinical application of a new rapid bedside assay for the detection of serum cardiac troponin I.
Clin Chem.
1998; 44(9): 1925–30. [PubMed]
Herlitz J, Karlson BW, Sjolin M, et al.
Predictors of death and mode of death among patients with acute chest pain in various age groups.
Coron Artery Dis.
1997; 8(11-12): 719–26. [PubMed]
Hetland O, Dickstein K.
Cardiac markers in the early hours of acute myocardial infarction: Clinical performance of creatine kinase, creatine kinase MB isoenzyme (activity and mass concentration), creatine kinase MM and MB subform ratios, myoglobin and cardiac troponin T.
Scand J Clin Lab Invest.
1996; 56(8): 701–13. [PubMed]
Hetland O, Dickstein K.
Cardiac troponins I and T in patients with suspected acute coronary syndrome: A comparative study in a routine setting.
Clin Chem.
1998; 44(7): 1430–6. [PubMed]
Johnson PA, Goldman L, Sacks DB, et al.
Cardiac troponin T as a marker for myocardial ischemia in patients seen at the emergency department for acute chest pain.
Am Heart J.
1999; 137(6): 1137–44. [PubMed]
Katus HA, Remppis A, Neumann FJ, et al.
Diagnostic efficiency of troponin T measurements in acute myocardial infarction.
Circulation.
1991; 83(3): 902–12. [PubMed]
Kontos MC, Jesse RL, Schmidt KL, et al.
Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain.
J Am Coll Cardiol.
1997; 30(4): 976–82. [PubMed]
Kost GJ, Kirk JD, Omand K.
A strategy for the use of cardiac injury markers (troponin I and T, creatine kinase-MB mass and isoforms, and myoglobin) in the diagnosis of acute myocardial infarction.
Arch Pathol Lab Med.
1998; 122(3): 245–51. [PubMed]
Koukkunen H, Penttila K, Kemppainen A, et al.
Troponin T and creatinine kinase isoenzyme MB mass in the diagnosis of myocardial infarction.
Ann Med.
1998; 30(5): 488–96. [PubMed]
Laurino JP, Pelletier TE, Eadry R, et al.
Thrombus precursor protein and the measurement of thrombosis in patients with acute chest pain syndrome.
Ann Clin Lab Sci.
1997; 27(5): 338–45. [PubMed]
Lee TH, Ting HH, Shammash JB, et al.
Long-term survival of emergency department patients with acute chest pain.
Am J Cardiol.
1992; 69(3): 145–51. [PubMed]
Lindahl B, Venge P, Wallentin L.
Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. The FRISC study group.
Circulation.
1996; 93(9): 1651–7. [PubMed]
Lloyd-Jones DM, Camargo CA Jr, Lapuerta P, et al.
Electrocardiographic and clinical predictors of acute myocardial infarction in patients with unstable angina pectoris.
Am J Cardiol.
1998; 81(10): 1182–6. [PubMed]
Lundin P, Eriksson SV, Fredrikson M, et al.
Prognostic information from on-line vectorcardiography in unstable angina pectoris.
Cardiology.
1995; 86(1): 60–6. [PubMed]
Luscher MS, Ravkilde J, Thygesen K.
Clinical application of two novel rapid bedside tests for the detection of cardiac troponin T and creatine kinase-MB mass/myoglobin in whole blood in acute myocardial infarction.
Cardiology.
1998; 89(3): 222–8. [PubMed]
Luscher MS, Thygesen K, Ravkilde J, et al.
Applicability of cardiac troponin T and I for early risk stratification in unstable coronary artery disease. TRIM Study Group. Thrombin Inhibition in Myocardial Ischemia.
Circulation.
1997; 96(8): 2578–85. [PubMed]
Mockel M, Stork T, Heller G Jr, et al.
Troponin T in patients with low grade or atypical angina. Identification of a high risk group for short- and long-term cardiovascular events.
Eur Heart J.
1998; 19(12): 1802–7. [PubMed]
Mohler ER 3rd, Ryan T, Segar DS, et al.
Clinical utility of troponin T levels and echocardiography in the emergency department.
Am Heart J.
1998; 135(2 Pt 1): 253–60. [PubMed]
Mulrow C, Langhorne P, Grimshaw J.
Integrating heterogeneous pieces of evidence in systematic reviews.
Ann Intern Med.
1997; 127(11): 989–95. [PubMed]
Ohman EM, Armstrong PW, Christenson RH, et al.
Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators.
N Engl J Med.
1996; 335(18): 1333–41. [PubMed]
Olatidoye AG, Wu AH, Feng YJ, et al.
Prognostic role of troponin T versus troponin I in unstable angina pectoris for cardiac events with meta-analysis comparing published studies.
Am J Cardiol.
1998; 81(12): 1405–10. [PubMed]
Patel DJ, Knight CJ, Holdright DR, et al.
Long-term prognosis in unstable angina. The importance of early risk stratification using continuous ST segment monitoring.
Eur Heart J.
1998; 19(2): 240–9. [PubMed]
Petitti D. Statistical methods in meta-analysis.In: Meta-analysis, decision analysis and cost-effectiveness analysis. New York: Oxford University Press; 1994. p. 90-114.
Pettijohn TL, Doyle T, Spiekerman AM, et al.
Usefulness of positive troponin-T and negative creatine kinase levels in identifying high-risk patients with unstable angina pectoris.
Am J Cardiol.
1997; 80(4): 510–1. [PubMed]
Polanczyk CA, Lee TH, Cook EF, et al. Cardiac troponin I as a predictor of major cardiac events in emergency department patients with acute chest pain
J Am Coll Cardiol 1998. 32(1):8–14.View this and related citations using
.
Pryor DB, Harrell FE Jr, Lee KL, et al.
Estimating the likelihood of significant coronary artery disease.
Am J Med.
1983; 75(5): 771–80. [PubMed]
Ravkilde J.
Creatine kinase isoenzyme MB mass, cardiac troponin T, and myosin light chain isotype 1 as serological markers of myocardial injury and their prognostic importance in acute coronary syndrome.
Dan Med Bull.
1998; 45(1): 34–50. [PubMed]
Ravkilde J, Horder M, Gerhardt W, et al.
Diagnostic performance and prognostic value of serum troponin T in suspected acute myocardial infarction.
Scand J Clin Lab Invest.
1993; 53(7): 677–85. [PubMed]
Ravkilde J, Nissen H, Horder M, et al. Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction. Analysis of 28 months of follow-up in 196 patients
J Am Coll Cardiol 1995. 25(3):574–81.View this and related citations using
.
REACTT Study.
Heart and Stroke Facts: 1996 Statistical Supplement. American Heart Association, 1996. Evaluation of a bedside whole-blood rapid troponin T assay in the emergency department. Rapid Evaluation by Assay of Cardiac Troponin T (REACTT) Investigators Study Group.
Acad Emerg Med.
1997; 4(11): 1018–24. [PubMed]
Rebuzzi AG, Quaranta G, Liuzzo G, et al.
Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris.
Am J Cardiol.
1998; 82(6): 715–9. [PubMed]
Roberts RR, Zalenski RJ, Mensah EK, et al.
Costs of an emergency department-based accelerated diagnostic protocol vs. hospitalization in patients with chest pain: A randomized controlled trial.
JAMA.
1997; 278(20): 1670–6. [PubMed]
Rude RE, Poole WK, Muller JE, et al.
Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients.
Am J Cardiol.
1983; 52(8): 936–42. [PubMed]
Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction)
J Am Coll Cardiol 1996. 28(5):1328–428.View this and related citations using
.
Rydman RJ, Zalenski RJ, Roberts RR, et al.
Patient satisfaction with an emergency department chest pain observation unit.
Ann Emerg Med.
1997; 29(1): 109–15. [PubMed]
Sarasin FP, Reymond JM, Griffith JL, et al.
Impact of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) on the speed of triage decision making for emergency department patients presenting with chest pain: A controlled clinical trial.
J Gen Intern Med.
1994; 9(4): 187–94. [PubMed]
Sayre MR, Kaufmann KH, Chen IW, et al.
Measurement of cardiac troponin T is an effective method for predicting complications among emergency department patients with chest pain.
Ann Emerg Med.
1998; 31(5): 539–49. [PubMed]
Seino Y, Tomita Y, Hoshino K, et al.
Pathophysiological analysis of serum troponin T release kinetics in evolving ischemic myocardial injury.
Jpn Circ J.
1996; 60(5): 265–76. [PubMed]
Seino Y, Tomita Y, Takano T, et al. Early identification of cardiac events with serum troponin T in patients with unstable angina.
Lancet.
1993; 342(8881): 1236–7.
Selker HP, Beshansky JR, Griffith JL, et al.
Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial.
Ann Intern Med.
1998; 129(11): 845–55. [PubMed]
Stokke M, Gronvold T, Siebke AM, et al.
Serial measurements of cardiac markers to rule in or out acute myocardial damage less than 3 h after admission in acute chest pain patients without ECG-signs of acute myocardial infarction.
Scand J Clin Lab Invest.
1998; 58(4): 331–8. [PubMed]
Stork T, Mockel M, Gareis R, et al. Laboratory-based diagnosis of acute coronary syndromes: Results of the NOWIS pilot study.
Clin Lab.
1997; 43(12): 1091–102.
Stubbs P, Collinson P, Moseley D, et al.
Prospective study of the role of cardiac troponin T in patients admitted with unstable angina.
Br Med J.
1996; 313(7052): 262–4. [PubMed]
Tanasijevic MJ, Cannon CP, Antman EM.
The role of cardiac troponin-I (cTnI) in risk stratification of patients with unstable coronary artery disease.
Clin Cardiol.
1999; 22(1): 13–6. [PubMed]
Tierney WM, Roth BJ, Psaty B, et al.
Predictors of myocardial infarction in emergency room patients.
Crit Care Med.
1985; 13(7): 526–31. [PubMed]
Tucker JF, Collins RA, Anderson AJ, et al.
Early diagnostic efficiency of cardiac troponin I and Troponin T for acute myocardial infarction.
Acad Emerg Med.
1997; 4(1): 13–21. [PubMed]
van Miltenburg-van Zijl AJ, Simoons ML, Veerhoek RJ, et al. Incidence and follow-up of Braunwald subgroups in unstable angina pectoris
J Am Coll Cardiol 1995. 25(6):1286–92.View this and related citations using
.
Villanueva FS, Sabia PJ, Afrookteh A, et al.
Value and limitations of current methods of evaluating patients presenting to the emergency room with cardiac-related symptoms for determining long-term prognosis.
Am J Cardiol.
1992; 69(8): 746–50. [PubMed]
Wilcox I, Freedman SB, Allman KC, et al. Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris
J Am Coll Cardiol 1991. 18(3):677–83.View this and related citations using
.
Wu AH, Abbas SA, Green S, et al.
Prognostic value of cardiac troponin T in unstable angina pectoris.
Am J Cardiol.
1995; 76(12): 970–2. [PubMed]
Yang Z, Zhang W, Liu Y. Prognostic efficacy of troponin T measurement in angina pectoris.
Chin Med J (Eng).
1995; 108(8): 626–30.
Bibliography
Adams JE 3rd, Schechtman KB, Landt Y, et al.
Comparable detection of acute myocardial infarction by creatine kinase MB isoenzyme and cardiac troponin I.
Clin Chem.
1994; 40(7 Pt 1): 1291–5. [PubMed]
Alonsozana GL, Christenson RH.
The case for cardiac troponin T: Marker for effective risk stratification of patients with acute cardiac ischemia.
Clin Chem.
1996; 42(5): 803–8. [PubMed]
Amsterdam EA, Lewis WR.
Identification of low risk patients with chest pain in the emergency department: Another look at cardiac troponins.
J Am Coll Cardiol.
1998; 32(1): 15–6. [PubMed]
Antman EM, Grudzien C, Sacks DB.
Evaluation of a rapid bedside assay for detection of serum cardiac troponin T.
JAMA.
1995; 273(16): 1279–82. [PubMed]
Antman EM, Sacks DB, Rifai N, et al.
Time to positivity of a rapid bedside assay for cardiac-specific troponin T predicts prognosis in acute coronary syndromes: A thrombolysis in myocardial infarction (TIMI) 11A substudy.
J Am Coll Cardiol.
1998; 31(2): 326–30. [PubMed]
Antman EM, Tanasijevic MJ, Thompson B, et al.
Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes.
N Engl J Med.
1996; 335(18): 1342–9. [PubMed]
Apple FS, Voss E, Lund L, et al.
Cardiac troponin, CK-MB and myoglobin for the early detection of acute myocardial infarction and monitoring of reperfusion following thrombolytic therapy.
Clin Chim Acta.
1995; 237(1-2): 59–66. [PubMed]
Armstrong PW, Fu Y, Chang WC, et al.
Acute coronary syndromes in the GUSTO-IIb trial: Prognostic insights and impact of recurrent ischemia. The GUSTO-IIb Investigators.
Circulation.
1998; 98(18): 1860–8. [PubMed]
Aufderheide TP, Hendley GE, Thakur RK, et al.
The diagnostic impact of prehospital 12-lead electrocardiography.
Ann Emerg Med.
1990; 19(11): 1280–7. [PubMed]
Aufderheide TP, Kereiakes DJ, Weaver WD, et al.
Planning, implementation, and process monitoring for prehospital 12-lead ECG diagnostic programs.
Prehospital Disaster Med.
1996; 11(3): 162–71. [PubMed]
Ayres SM. The electrocardiogram in the acute coronary syndromes
J Am Coll Cardiol 1990. 16(4):1026–8.View this and related citations using
.
Bakker AJ, Gorgels JP, van Vlies B, et al. The mass concentrations of serum troponin T and creatine kinase-MB are elevated before creatine kinase and creatine kinase-MB activities in acute myocardial infarction.
Eur J Clin Chem Clin Biochem.
1993a; 31(11): 715–24.
Bakker AJ, Koelemay MJ, Gorgels JP, et al. Failure of new biochemical markers to exclude acute myocardial infarction at admission.
Lancet.
1993b; 342(8881): 1220–2.
Bakker AJ, Koelemay MJ, Gorgels JP, et al. Troponin T and myoglobin at admission: Value of early diagnosis of acute myocardial infarction.
Eur Heart J.
1994; 15(1): 45–53.
Barish RA, Doherty RJ, Browne BJ. Reengineering the emergency evaluation of chest pain.
J Healthc Qual.
1997; 19(5): 6–12; quiz 60.
Bell MR, Montarello JK, Steele PM.
Does the emergency room electrocardiogram identify patients with suspected myocardial infarction who are at low risk of acute complications?
Aust N Z J Med.
1990; 20(4): 564–9. [PubMed]
Benamer H, Steg PG, Benessiano J, et al.
Comparison of the prognostic value of C-reactive protein and troponin I in patients with unstable angina pectoris.
Am J Cardiol.
1998; 82(7): 845–50. [PubMed]
Bertolet BD, Dinerman J, Hartke R Jr, et al.
Unstable angina: Relationship of clinical presentation, coronary artery pathology, and clinical outcome.
Clin Cardiol.
1993; 16(2): 116–22. [PubMed]
Betriu A, Heras M, Cohen M, et al. Unstable angina: Outcome according to clinical presentation
J Am Coll Cardiol 1992. 19(7):1659–63.View this and related citations using
.
Braunwald E, Jones RH, Mark DB, et al.
Diagnosing and managing unstable angina. Agency for Health Care Policy and Research.
Circulation.
1994; 90(1): 613–22. [PubMed]
Braunwald E, Maseri A, Armstrong PW, et al.
Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute coronary syndromes.
Eur Heart J.
1998; 19 Suppl D: D22–D30. [PubMed]
Bresler MJ, Gibler WB.
Acute myocardial infarction: Subtleties of diagnosis in the emergency department.
Ann Emerg Med.
1990; Suppl: 1–15. [PubMed]
Brscic E, Chiappino I, Bergerone S, et al.
Prognostic implications of detection of troponin I in patients with unstable angina pectoris.
Am J Cardiol.
1998; 82(8): 971–3. [PubMed]
Bugiardini R, Borghi A, Sassone B, et al.
Prognostic significance of silent myocardial ischemia in variant angina pectoris.
Am J Cardiol.
1991; 68(17): 1581–6. [PubMed]
Cairns JA, Singer J, Gent M, et al.
One year mortality outcomes of all coronary and intensive care unit patients with acute myocardial infarction, unstable angina or other chest pain in Hamilton, Ontario, a city of 375,000 people.
Can J Cardiol.
1989; 5(5): 239–46. [PubMed]
Califf RM, Mark DB, Harrell FE Jr, et al. Importance of clinical measures of ischemia in the prognosis of patients with documented coronary artery disease
J Am Coll Cardiol 1988. 11(1):20–6.View this and related citations using
.
Calvin JE, Klein LW, VandenBerg BJ, et al.
Risk stratification in unstable angina. Prospective validation of the Braunwald classification.
JAMA.
1995; 273(2): 136–41. [PubMed]
Cannon CP, McCabe CH, Stone PH, et al. The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: Results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia
J Am Coll Cardiol 1997. 30(1):133–40.View this and related citations using
.
Castaner A, Roig E, Serra A, et al.
Risk stratification and prognosis of patients with recent onset angina.
Eur Heart J.
1990; 11(10): 868–75. [PubMed]
Chang CC, Ip MP, Hsu RM, et al.
Evaluation of a proposed panel of cardiac markers for the diagnosis of acute myocardial infarction in patients with atraumatic chest pain.
Arch Pathol Lab Med.
1998; 122(4): 320–4. [PubMed]
Chin MH, Cook EF, Lee TH, et al.
Correlates of major complications and mortality in patients presenting to the emergency department with chest pain and more than bibasilar rales.
J Gen Intern Med.
1994; 9(12): 659–65. [PubMed]
Christenson RH, Duh SH, Newby LK, et al.
Cardiac troponin T and cardiac troponin I: Relative values in short- term risk stratification of patients with acute coronary syndromes. GUSTO-IIa Investigators.
Clin Chem.
1998; 44(3): 494–501. [PubMed]
Cohen M, Hawkins L, Greenberg S, et al.
Usefulness of ST-segment changes in greater than or equal to 2 leads on the emergency room electrocardiogram in either unstable angina pectoris or non-Q-wave myocardial infarction in predicting outcome.
Am J Cardiol.
1991; 67(16): 1368–73. [PubMed]
Collinson PO, Moseley D, Stubbs PJ, et al.
Troponin T for the differential diagnosis of ischaemic myocardial damage.
Ann Clin Biochem.
1993; 30(Pt 1): 11–6. [PubMed]
Coronado BE, Griffith JL, Beshansky JR, et al.
Hospital mortality in women and men with acute cardiac ischemia: A prospective multicenter study.
J Am Coll Cardiol.
1997; 29(7): 1490–6. [PubMed]
Cunningham MA, Lee TH, Cook EF, et al.
The effect of gender on the probability of myocardial infarction among emergency department patients with acute chest pain: A report from the Multicenter Chest Pain Study Group.
J Gen Intern Med.
1989; 4(5): 392–8. [PubMed]
Davis MA, Keerbs A, Hoffman JR, et al.
Admission decisions in emergency department chest pain patients at low risk for myocardial infarction: Patient versus physician preferences.
Ann Emerg Med.
1996; 28(6): 606–11. [PubMed]
D'Costa M, Fleming E, Patterson MC.
Cardiac troponin I for the diagnosis of acute myocardial infarction in the emergency department.
Am J Clin Pathol.
1997; 108(5): 550–5. [PubMed]
deFilippi CR, Parmar RJ, Potter MA, et al.
Diagnostic accuracy, angiographic correlates and long-term risk stratification with the troponin T ultra sensitive rapid assay in chest pain patients at low risk for acute myocardial infarction.
Eur Heart J.
1998; 19(Suppl N): N42–N47. [PubMed]
DerSimonian R, Laird N.
Meta-analysis in clinical trials.
Controlled Clin Trials.
1986; 7(3): 177–88. [PubMed]
de Winter RJ, Koster RW, Schotveld JH, et al.
Prognostic value of troponin T, myoglobin, and CK-MB mass in patients presenting with chest pain without acute myocardial infarction.
Heart.
1996; 75(3): 235–9. [PubMed]
Diamond GA, Forrester JS.
Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease.
N Engl J Med.
1979; 300(24): 1350–8. [PubMed]
Douglas PS, Ginsburg GS.
The evaluation of chest pain in women.
N Engl J Med.
1996; 334(20): 1311–5. [PubMed]
Dracup K, Alonzo AA, Atkins JM, et al.
The physician's role in minimizing prehospital delay in patients at high risk for acute myocardial infarction: Recommendations from the National Heart Attack Alert Program. Working Group on Educational Strategies to Prevent Prehospital Delay in Patients at High Risk for Acute Myocardial Infarction.
Ann Intern Med.
1997; 126(8): 645–51. [PubMed]
Duncan B, Fulton M, Morrison SL, et al.
Prognosis of new and worsening angina pectoris.
Br Med J.
1976; 1(6016): 981–5. [PubMed]
Farkouh ME, Smars PA, Reeder GS, et al.
A clinical trial of a chest-pain observation unit for patients with unstable angina. Chest Pain Evaluation in the Emergency Room (CHEER) Investigators.
N Engl J Med.
1998; 339(26): 1882–8. [PubMed]
Fesmire FM, Percy RF, Wears RL, et al.
Risk stratification according to the initial electrocardiogram in patients with suspected acute myocardial infarction.
Arch Intern Med.
1989; 149(6): 1294–7. [PubMed]
Fineberg HV, Scadden D, Goldman L.
Care of patients with a low probability of acute myocardial infarction. Cost effectiveness of alternatives to coronary-care-unit admission.
N Engl J Med.
1984; 310(20): 1301–7. [PubMed]
Fleischmann KE, Goldman L, Robiolio PA, et al.
Echocardiographic correlates of survival in patients with chest pain.
J Am Coll Cardiol.
1994; 23(6): 1390–6. [PubMed]
Galvani M, Ottani F, Ferrini D, et al.
Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina.
Circulation.
1997; 95(8): 2053–9. [PubMed]
Gazes PC, Mobley EM Jr, Faris HM Jr, et al.
Preinfarctional (unstable) angina-a prospective study-ten year follow-up. Prognostic significance of electrocardiographic changes.
Circulation.
1973; 48(2): 331–7. [PubMed]
Gerhardt W, Katus H, Ravkilde J, et al.
S-troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentrations of S-creatine kinase isoenzyme MB.
Clin Chem.
1991; 37(8): 1405–11. [PubMed]
Gerhardt W, Ljungdahl L.
Detection of myocardial damage by serial measurements of cardiac troponin T, CK MB mass, and TROPT rapid test.
Cardiovasc Drugs Ther.
1997; 11(Suppl 1): 227–40. [PubMed]
Gerhardt W, Ljungdahl L, Collinson PO, et al.
An improved rapid troponin T test with a decreased detection limit: A multicentre study of the analytical and clinical performance in suspected myocardial damage.
Scand J Clin Lab Invest.
1997; 57(6): 549–57. [PubMed]
Gerhardt W, Ljungdahl L, Herbert AK.
Troponin-T and CK MB (mass) in early diagnosis of ischemic myocardial injury. The Helsingborg Study, 1992.
Clin Biochem.
1993; 26(4): 231–40. [PubMed]
Gibler WB.
Chest pain evaluation in the ED: beyond triage.
Am J Emerg Med.
1994a; 12(1): 121–2. [PubMed]
Gibler WB.
Evaluating patients with chest pain in the ED: Improving speed, efficiency, and cost-effectiveness, or teaching an old dog new tricks.
Ann Emerg Med.
1994b; 23(2): 381–2. [PubMed]
Gibler WB. Evaluation of chest pain in the emergency department.
Ann Intern Med.
1995; 123(4): 317–8.
Gibler WB.
Chest pain units: do they make sense now?
Ann Emerg Med.
1997; 29(1): 168–71. [PubMed]
Gibler WB, Kereiakes DJ, Dean EN, et al.
Prehospital diagnosis and treatment of acute myocardial infarction: A north-south perspective. The Cincinnati Heart Project and the Nashville Prehospital TPA Trial.
Am Heart J.
1991; 121(1 Pt 1): 1–11. [PubMed]
Gibler WB, Lewis LM, Erb RE, et al.
Early detection of acute myocardial infarction in patients presenting with chest pain and nondiagnostic ECGs: Serial CK-MB sampling in the emergency department [published erratum appears in Ann Emerg Med 1991 Apr;20(4):420].
Ann Emerg Med.
1990; 19(12): 1359–66. [PubMed]
Gibler WB, Runyon JP, Levy RC, et al.
A rapid diagnostic and treatment center for patients with chest pain in the emergency department.
Ann Emerg Med.
1995; 25(1): 1–8. [PubMed]
Gibler WB, Sayre MR, Levy RC, et al.
Serial 12-lead electrocardiographic monitoring in patients presenting to the emergency department with chest pain.
J Electrocardiol.
1993; 26(Suppl): 238–43.
[PubMed]
Gibler WB, Young GP, Hedges JR, et al.
Acute myocardial infarction in chest pain patients with nondiagnostic ECGs: Serial CK-MB sampling in the emergency department. The Emergency Medicine Cardiac Research Group.
Ann Emerg Med.
1992; 21(5): 504–12. [PubMed]
Gokhan Cin V, Gok H, Kaptanoglu B.
The prognostic value of serum troponin T in unstable angina.
Int J Cardiol.
1996; 53(3): 237–44. [PubMed]
Goldman L.
Using prediction models and cost-effectiveness analysis to improve clinical decisions: Emergency department patients with acute chest pain.
Proc Assoc Am Physicians.
1995; 107(3): 329–33. [PubMed]
Goldman L, Cook EF, Brand DA, et al.
A computer protocol to predict myocardial infarction in emergency department patients with chest pain.
N Engl J Med.
1988; 318(13): 797–803. [PubMed]
Goldman L, Cook EF, Johnson PA, et al.
Prediction of the need for intensive care in patients who come to the emergency departments with acute chest pain.
N Engl J Med.
1996; 334(23): 1498–504. [PubMed]
Goldman L, Weinberg M, Weisberg M, et al.
A computer-derived protocol to aid in the diagnosis of emergency room patients with acute chest pain.
N Engl J Med.
1982; 307(10): 588–96. [PubMed]
Gomez MA, Anderson JL, Karagounis LA, et a. An emergency department-based protocol for rapidly ruling out myocardial ischemia reduces hospital time and expense: Results of a randomized study (ROMIO)
J Am Coll Cardiol 1996. 28(1):25–33.View this and related citations using
.
Graff L, Joseph T, Andelman R, et al.
American College of Emergency Physicians information paper: Chest pain units in emergency departments-a report from the Short-Term Observation Services Section.
Am J Cardiol.
1995; 76(14): 1036–9. [PubMed]
Graff L, Zun LS, Leikin J, et al.
Emergency department observation beds improve patient care: Society for Academic Emergency Medicine debate.
Ann Emerg Med.
1992; 21(8): 967–75. [PubMed]
Graff LG, Dallara J, Ross MA, et al.
Impact on the care of the emergency department chest pain patient from the chest pain evaluation registry (CHEPER) study.
Am J Cardiol.
1997; 80(5): 563–8. [PubMed]
Green GB, Beaudreau RW, Chan DW, et al.
Use of troponin T and creatine kinase-MB subunit levels for risk stratification of emergency department patients with possible myocardial ischemia.
Ann Emerg Med.
1998; 31(1): 19–29. [PubMed]
Gust R, Gust A, Bottiger BW, et al.
Bedside troponin T testing is not useful for early out-of-hospital diagnosis of myocardial infarction.
Acta Anaesthesiol Scand.
1998; 42(4): 414–7. [PubMed]
Haines DE, Raabe DS, Gundel WD, et al.
Anatomic and prognostic significance of new T-wave inversion in unstable angina.
Am J Cardiol.
1983; 52(1): 14–8. [PubMed]
Hamm CW, Goldmann BU, Heeschen C, et al.
Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I.
N Engl J Med.
1997; 337(23): 1648–53. [PubMed]
Hamm CW, Ravkilde J, Gerhardt W, et al.
The prognostic value of serum troponin T in unstable angina.
N Engl J Med.
1992; 327(3): 146–50. [PubMed]
Hargarten KM, Aprahamian C, Stueven H, et al.
Limitations of prehospital predictors of acute myocardial infarction and unstable angina.
Ann Emerg Med.
1987; 16(12): 1325–9. [PubMed]
Hedges JR, Gibler WB, Young GP, et al.
Multicenter study of creatine kinase-MB use: Effect on chest pain clinical decision making.
Acad Emerg Med.
1996; 3(1): 7–15. [PubMed]
Hedges JR, Young GP, Henkel GF, et al.
Serial ECGs are less accurate than serial CK-MB results for emergency department diagnosis of myocardial infarction.
Ann Emerg Med.
1992; 21(12): 1445–50. [PubMed]
Hedges JR, Young GP, Henkel GF, et al.
Early CK-MB elevations predict ischemic events in stable chest pain patients.
Acad Emerg Med.
1994; 1(1): 9–16. [PubMed]
Hedges L. Fixed effects models. In: Cooper H, Hedges L, editors. The handbook of research synthesis. New York: Russel Sage Foundation; 1994. p. 307-35.
Heeschen C, Goldmann BU, Moeller RH, et al.
Analytical performance and clinical application of a new rapid bedside assay for the detection of serum cardiac troponin I.
Clin Chem.
1998; 44(9): 1925–30. [PubMed]
Heng MK, Norris RM, Singh BM, et al.
Prognosis in unstable angina.
Br Heart J.
1976; 38(9): 921–5. [PubMed]
Herlitz J, Karlson BW, Sjolin M, et al.
Predictors of death and mode of death among patients with acute chest pain in various age groups.
Coron Artery Dis.
1997; 8(11-12): 719–26. [PubMed]
Hetland O, Dickstein K.
Cardiac markers in the early hours of acute myocardial infarction: Clinical performance of creatine kinase, creatine kinase MB isoenzyme (activity and mass concentration), creatine kinase MM and MB subform ratios, myoglobin and cardiac troponin T.
Scand J Clin Lab Invest.
1996; 56(8): 701–13. [PubMed]
Hetland O, Dickstein K.
Cardiac troponins I and T in patients with suspected acute coronary syndrome: A comparative study in a routine setting.
Clin Chem.
1998; 44(7): 1430–6. [PubMed]
Hlatky MA.
Evaluation of chest pain in the emergency department.
N Engl J Med.
1997; 337(23): 1687–9. [PubMed]
Hoekstra JW, Gibler WB.
Chest pain evaluation units: An idea whose time has come.
JAMA.
1997; 278(20): 1701–2. [PubMed]
Hoekstra JW, Gibler WB, Levy RC, et al.
Emergency-department diagnosis of acute myocardial infarction and ischemia: A cost analysis of two diagnostic protocols.
Acad Emerg Med.
1994; 1(2): 103–10. [PubMed]
Hoekstra JW, Hedges JR, Gibler WB, et al.
Emergency department CK-MB: A predictor of ischemic complications. National Cooperative CK-MB project group.
Acad Emerg Med.
1994; 1(1): 17–27. [PubMed]
Holmvang L, Luscher MS, Clemmensen P, et al.
Very early risk stratification using combined ECG and biochemical assessment in patients with unstable coronary artery disease (A thrombin inhibition in myocardial ischemia [TRIM] substudy).
Circulation.
1998; 98(19): 2004–9. [PubMed]
Johnson PA, Goldman L, Sacks DB, et al.
Cardiac troponin T as a marker for myocardial ischemia in patients seen at the emergency department for acute chest pain.
Am Heart J.
1999; 137(6): 1137–44. [PubMed]
Karlson BW, Herlitz J, Pettersson P, et al.
One-year prognosis in patients hospitalized with a history of unstable angina pectoris.
Clin Cardiol.
1993; 16(5): 397–402. [PubMed]
Katus HA, Remppis A, Neumann FJ, et al.
Diagnostic efficiency of troponin T measurements in acute myocardial infarction.
Circulation.
1991; 83(3): 902–12. [PubMed]
Kaul S, Abbott RD.
Evaluation of chest pain in the emergency department.
Ann Intern Med.
1994; 121(12): 976–8. [PubMed]
Kereiakes DJ, Weaver WD, Anderson JL, et al.
Time delays in the diagnosis and treatment of acute myocardial infarction: A tale of eight cities. Report from the Pre-hospital Study Group and the Cincinnati Heart Project.
Am Heart J.
1990; 120(4): 773–80. [PubMed]
Kirk JD, Turnipseed S, Lewis WR, et al.
Evaluation of chest pain in low-risk patients presenting to the emergency department: The role of immediate exercise testing.
Ann Emerg Med.
1998; 32(1): 1–7. [PubMed]
Klootwijk P, Hamm C.
Acute coronary syndromes: Diagnosis.
Lancet.
1999; 353(Suppl 2): SII10–SII15. [PubMed]
Kontos MC, Jesse RL, Schmidt KL, et al.
Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain.
J Am Coll Cardiol.
1997; 30(4): 976–82. [PubMed]
Kost GJ, Kirk JD, Omand K.
A strategy for the use of cardiac injury markers (troponin I and T, creatine kinase-MB mass and isoforms, and myoglobin) in the diagnosis of acute myocardial infarction.
Arch Pathol Lab Med.
1998; 122(3): 245–51. [PubMed]
Koukkunen H, Penttila K, Kemppainen A, et al.
Troponin T and creatinine kinase isoenzyme MB mass in the diagnosis of myocardial infarction.
Ann Med.
1998; 30(5): 488–96. [PubMed]
Kowalenko T, Kereiakes DJ, Gibler WB.
Prehospital diagnosis and treatment of acute myocardial infarction: A critical review.
Am Heart J.
1992; 123(1): 181–90. [PubMed]
Kudenchuk PJ, Maynard C, Cobb LA, et al. Utility of the prehospital electrocardiogram in diagnosing acute coronary syndromes: The Myocardial Infarction Triage and Intervention (MITI) Project
J Am Coll Cardiol 1998. 32(1):17–27.View this and related citations using
.
Langer A, Freeman MR, Armstrong PW. ST segment shift in unstable angina: Pathophysiology and association with coronary anatomy and hospital outcome
J Am Coll Cardiol 1989. 13(7):1495–502.View this and related citations using
.
Larsen GC, Griffith JL, Beshansky JR, et al.
Electrocardiographic left ventricular hypertrophy in patients with suspected acute cardiac ischemia-its influence on diagnosis, triage, and short-term prognosis: A multicenter study.
J Gen Intern Med.
1994; 9(12): 666–73. [PubMed]
Laurino JP, Pelletier TE, Eadry R, et al.
Thrombus precursor protein and the measurement of thrombosis in patients with acute chest pain syndrome.
Ann Clin Lab Sci.
1997; 27(5): 338–45. [PubMed]
Lee HS, Cross SJ, Rawles JM, et al.
Patients with suspected myocardial infarction who present with ST depression.
Lancet.
1993; 342(8881): 1204–7. [PubMed]
Lee TH, Cook EF, Weisberg M, et al.
Acute chest pain in the emergency room. Identification and examination of low-risk patients.
Arch Intern Med.
1985; 145(1): 65–9. [PubMed]
Lee TH, Cook EF, Weisberg MC, et al.
Impact of the availability of a prior electrocardiogram on the triage of the patient with acute chest pain.
J Gen Intern Med.
1990; 5(5): 381–8. [PubMed]
Lee TH, Juarez G, Cook EF, et al.
Ruling out acute myocardial infarction. A prospective multicenter validation of a 12-hour strategy for patients at low risk.
N Engl J Med.
1991; 324(18): 1239–46. [PubMed]
Lee TH, Rouan GW, Weisberg MC, et al.
Sensitivity of routine clinical criteria for diagnosing myocardial infarction within 24 hours of hospitalization.
Ann Intern Med.
1987; 106(2): 181–6. [PubMed]
Lee TH, Ting HH, Shammash JB, et al.
Long-term survival of emergency department patients with acute chest pain.
Am J Cardiol.
1992; 69(3): 145–51. [PubMed]
Lewis WR, Amsterdam EA.
Evaluation of the patient with "rule out myocardial infarction.".
Arch Intern Med.
1996; 156(1): 41–5. [PubMed]
Lindahl B, Venge P, Wallentin L.
Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. The FRISC Study Group.
Circulation.
1996; 93(9): 1651–7. [PubMed]
Lloyd-Jones DM, Camargo CA Jr, Lapuerta P, et al.
Electrocardiographic and clinical predictors of acute myocardial infarction in patients with unstable angina pectoris.
Am J Cardiol.
1998; 81(10): 1182–6. [PubMed]
Lundin P, Eriksson SV, Fredrikson M, et al.
Prognostic information from on-line vectorcardiography in unstable angina pectoris.
Cardiology.
1995; 86(1): 60–6. [PubMed]
Luscher MS, Ravkilde J, Thygesen K.
Clinical application of two novel rapid bedside tests for the detection of cardiac troponin T and creatine kinase-MB mass/myoglobin in whole blood in acute myocardial infarction.
Cardiology.
1998; 89(3): 222–8. [PubMed]
Luscher MS, Thygesen K, Ravkilde J, et al.
Applicability of cardiac troponin T and I for early risk stratification in unstable coronary artery disease. TRIM Study Group. Thrombin Inhibition in Myocardial Ischemia.
Circulation.
1997; 96(8): 2578–85. [PubMed]
Mair J, Smidt J, Lechleitner P, et al.
A decision tree for the early diagnosis of acute myocardial infarction in nontraumatic chest pain patients at hospital admission.
Chest.
1995; 108(6): 1502–9. [PubMed]
Mark DB, Califf RM, Morris KG, et al.
Clinical characteristics and long-term survival of patients with variant angina.
Circulation.
1984; 69(5): 880–8. [PubMed]
Marmur JD, Freeman MR, Langer A, et al.
Prognosis in medically stabilized unstable angina: Early Holter ST-segment monitoring compared with predischarge exercise thallium tomography.
Ann Intern Med.
1990; 113(8): 575–9. [PubMed]
Maseri A, Crea F, Kaski JC, et al.
Mechanisms and significance of cardiac ischemic pain.
Prog Cardiovasc Dis.
1992; 35(1): 1–18. [PubMed]
McNutt RA, Selker HP.
How did the acute ischemic heart disease predictive instrument reduce unnecessary coronary care unit admissions?
Med Decis Making.
1988; 8(2): 90–4. [PubMed]
Miller DH, Kligfield P, Schreiber TL, et al.
Relationship of prior myocardial infarction to false-positive electrocardiographic diagnosis of acute injury in patients with chest pain.
Arch Intern Med.
1987; 147(2): 257–61. [PubMed]
Mockel M, Stork T, Heller G Jr, et al.
Troponin T in patients with low grade or atypical angina. Identification of a high risk group for short- and long-term cardiovascular events.
Eur Heart J.
1998; 19(12): 1802–7. [PubMed]
Mohler ER 3d, Ryan T, Segar DS, et al.
Clinical utility of troponin T levels and echocardiography in the emergency department.
Am Heart J.
1998; 135(2 Pt 1): 253–60. [PubMed]
Mulcahy R, Daly L, Graham I, et al.
Unstable angina: Natural history and determinants of prognosis.
Am J Cardiol.
1981; 48(3): 525–8. [PubMed]
Mulrow C, Langhorne P, Grimshaw J.
Integrating heterogeneous pieces of evidence in systematic reviews.
Ann Intern Med.
1997; 127(11): 989–95. [PubMed]
Murabito JM, Anderson KM, Kannel WB, et al.
Risk of coronary heart disease in subjects with chest discomfort: The Framingham Heart Study.
Am J Med.
1990; 89(3): 297–302. [PubMed]
Newby LK, Gibler WB, Ohman EM, et al.
Biochemical markers in suspected acute myocardial infarction: The need for early assessment.
Clin Chem.
1995; 41(9): 1263–5. [PubMed]
Nichol G, Walls R, Goldman L, et al.
A critical pathway for management of patients with acute chest pain who are at low risk for myocardial ischemia: Recommendations and potential impact.
Ann Intern Med.
1997; 127(11): 996–1005. [PubMed]
Nyman I, Areskog M, Areskog NH, et al.
Very early risk stratification by electrocardiogram at rest in men with suspected unstable coronary heart disease. The RISC Study Group.
J Intern Med.
1993; 234(3): 293–301. [PubMed]
Ohman EM, Armstrong PW, Christenson RH, et al.
Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators.
N Engl J Med.
1996; 335(18): 1333–41. [PubMed]
Olatidoye AG, Wu AH, Feng YJ, et al.
Prognostic role of troponin T versus troponin I in unstable angina pectoris for cardiac events with meta-analysis comparing published studies.
Am J Cardiol.
1998; 81(12): 1405–10. [PubMed]
Olson HG, Lyons KP, Aronow WS, et al.
The high-risk angina patient. Identification by clinical features, hospital course, electrocardiography and technetium-99m stannous pyrophosphate scintigraphy.
Circulation.
1981; 64(4): 674–84. [PubMed]
Ouyang P, Brinker JA, Mellits ED, et al.
Variables predictive of successful medical therapy in patients with unstable angina: Selection by multivariate analysis from clinical, electrocardiographic, and angiographic evaluations.
Circulation.
1984; 70(3): 367–76. [PubMed]
Patel DJ, Knight CJ, Holdright DR, et al.
Long-term prognosis in unstable angina. The importance of early risk stratification using continuous ST segment monitoring.
Eur Heart J.
1998; 19(2): 240–9. [PubMed]
Petitti D. Statistical methods in meta-analysis.In: Meta-analysis, decision analysis and cost-effectiveness analysis. New York: Oxford University Press; 1994. p. 90-114.
Pettijohn TL, Doyle T, Spiekerman AM, et al.
Usefulness of positive troponin-T and negative creatine kinase levels in identifying high-risk patients with unstable angina pectoris.
Am J Cardiol.
1997; 80(4): 510–1. [PubMed]
Polanczyk CA, Lee TH, Cook EF, et al. Cardiac troponin I as a predictor of major cardiac events in emergency department patients with acute chest pain
J Am Coll Cardiol 1998. 32(1):8–14.View this and related citations using
.
Pozen MW, D'Agostino RB, Mitchell JB, et al.
The usefulness of a predictive instrument to reduce inappropriate admissions to the coronary care unit.
Ann Intern Med.
1980; 92(2 Pt 1): 238–42. [PubMed]
Pozen MW, D'Agostino RB, Selker HP, et al.
A predictive instrument to improve coronary-care-unit admission practices in acute ischemic heart disease. A prospective multicenter clinical trial.
N Engl J Med.
1984; 310(20): 1273–8. [PubMed]
Pryor DB, Harrell FE Jr, Lee KL, et al.
Estimating the likelihood of significant coronary artery disease.
Am J Med.
1983; 75(5): 771–80. [PubMed]
Randolph AG, Guyatt GH, Calvin JE, et al.
Understanding articles describing clinical prediction tools. Evidence Based Medicine in Critical Care Group.
Crit Care Med.
1998; 26(9): 1603–12. [PubMed]
Ravkilde J.
Creatine kinase isoenzyme MB mass, cardiac troponin T, and myosin light chain isotype 1 as serological markers of myocardial injury and their prognostic importance in acute coronary syndrome.
Dan Med Bull.
1998; 45(1): 34–50. [PubMed]
Ravkilde J, Horder M, Gerhardt W, et al.
Diagnostic performance and prognostic value of serum troponin T in suspected acute myocardial infarction.
Scand J Clin Lab Invest.
1993; 53(7): 677–85. [PubMed]
Ravkilde J, Nissen H, Horder M, et al.
Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction. Analysis of 28 months of followup in 196 patients.
J Am Coll Cardiol.
1995; 25(3): 574–81. [PubMed]
REACTT Study.
Heart and Stroke Facts: 1996 Statistical Supplement. American Heart Association, 1996. Evaluation of a bedside whole-blood rapid troponin T assay in the emergency department. Rapid Evaluation by Assay of Cardiac Troponin T (REACTT) Investigators Study Group.
Acad Emerg Med.
1997; 4(11): 1018–24. [PubMed]
Rebuzzi AG, Quaranta G, Liuzzo G, et al.
Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris.
Am J Cardiol.
1998; 82(6): 715–9. [PubMed]
Roberts RR, Zalenski RJ, Mensah EK, et al.
Costs of an emergency department-based accelerated diagnostic protocol vs. hospitalization in patients with chest pain: A randomized controlled trial.
JAMA.
1997; 278(20): 1670–6. [PubMed]
Robinson K, Conroy RM, Mulcahy R, et al.
Risk factors and in-hospital course of first episode of myocardial infarction or acute coronary insufficiency in women.
J Am Coll Cardiol.
1988; 11(5): 932–6. [PubMed]
Rottbauer W, Greten T, Muller-Bardorff M, et al. Troponin T: A diagnostic marker for myocardial infarction and minor cardiac cell damage.
Eur Heart J.
1996; 17(Suppl F): 3–8.
Rude RE, Poole WK, Muller JE, et al.
Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients.
Am J Cardiol.
1983; 52(8): 936–42. [PubMed]
Ryan TJ.
Refining the classification of chest pain: A logical next step in the evaluation of patients for acute cardiac ischemia in the emergency department.
Ann Emerg Med.
1997; 29(1): 166–8. [PubMed]
Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction)
J Am Coll Cardiol 1996. 28(5):1328–428.View this and related citations using
.
Rydman RJ, Zalenski RJ, Roberts RR, et al.
Patient satisfaction with an emergency department chest pain observation unit.
Ann Emerg Med.
1997; 29(1): 109–15. [PubMed]
Sarasin FP, Reymond JM, Griffith JL, et al.
Impact of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) on the speed of triage decision making for emergency department patients presenting with chest pain: A controlled clinical trial.
J Gen Intern Med.
1994; 9(4): 187–94. [PubMed]
Savonitto S, Ardissino D, Granger CB, et al.
Prognostic value of the admission electrocardiogram in acute coronary syndromes.
JAMA.
1999; 281(8): 707–13. [PubMed]
Sayre MR, Gibler WB.
New approaches to ruling out acute ischemic coronary syndrome in the emergency department.
Ann Emerg Med.
1996; 27(1): 75–8. [PubMed]
Sayre MR, Kaufmann KH, Chen IW, et al.
Measurement of cardiac troponin T is an effective method for predicting complications among emergency department patients with chest pain.
Ann Emerg Med.
1998; 31(5): 539–49. [PubMed]
Schechtman KB, Capone RJ, Kleiger RE, et al.
Risk stratification of patients with non-Q wave myocardial infarction. The critical role of ST segment depression. The Diltiazem Reinfarction Study Research Group.
Circulation.
1989; 80(5): 1148–58. [PubMed]
Sclarovsky S, Rechavia E, Strasberg B, et al.
Unstable angina: ST segment depression with positive versus negative T wave deflections-clinical course, ECG evolution, and angiographic correlation.
Am Heart J.
1988; 116(4): 933–41. [PubMed]
Seino Y, Tomita Y, Hoshino K, et al.
Pathophysiological analysis of serum troponin T release kinetics in evolving ischemic myocardial injury.
Jpn Circ J.
1996; 60(5): 265–76. [PubMed]
Seino Y, Tomita Y, Takano T, et al. Early identification of cardiac events with serum troponin T in patients with unstable angina.
Lancet.
1993; 342(8881): 1236–7.
Selker HP, Beshansky JR, Griffith JL, et al.
Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial.
Ann Intern Med.
1998; 129(11): 845–55. [PubMed]
Selker HP, Griffith JL, Patil S, et al. A comparison of performance of mathematical predictive methods for medical diagnosis: Identifying acute cardiac ischemia among emergency department patients.
J Investig Med.
1995; 43(5): 468–76.
Selker HP, Zalenski RJ, Antman EM, et al.
An evaluation of technologies for identifying acute cardiac ischemia in the emergency department: Executive summary of a National Heart Attack Alert Program Working Group Report.
Ann Emerg Med.
1997; 29(1): 1–12. [PubMed]
Sharma GV, Deupree RH, Luchi RJ, et al.
Identification of unstable angina patients who have favorable outcome with medical or surgical therapy (eight-year follow-up of the Veterans Administration Cooperative Study).
Am J Cardiol.
1994; 74(5): 454–8. [PubMed]
Shesser R, Smith M.
The chest pain emergency department and the outpatient chest pain evaluation center: Revolution or evolution?
Ann Emerg Med.
1994; 23(2): 334–41. [PubMed]
Sox HC Jr, Hickam DH, Marton KI, et al.
Using the patient's history to estimate the probability of coronary artery disease: A comparison of primary care and referral practices [published erratum appears in Am J Med 1990 Oct;89(4):550].
Am J Med.
1990; 89(1): 7–14. [PubMed]
Stokke M, Gronvold T, Siebke AM, et al.
Serial measurements of cardiac markers to rule in or out acute myocardial damage less than 3 h after admission in acute chest pain patients without ECG-signs of acute myocardial infarction.
Scand J Clin Lab Invest.
1998; 58(4): 331–8. [PubMed]
Stork T, Mockel M, Gareis R, et al. Laboratory-based diagnosis of acute coronary syndromes: Results of the NOWIS pilot study.
Clin Lab.
1997; 43(12): 1091–102.
Stubbs P, Collinson P, Moseley D, et al.
Prospective study of the role of cardiac troponin T in patients admitted with unstable angina.
Br Med J.
1996; 313(7052): 262–4. [PubMed]
Stussman BJ.
National Hospital Ambulatory Medical Care Survey: 1995 emergency department summary.
Adv Data.
1997; 285: 1–19.
[PubMed]
Sullivan AK, Holdright DR, Wright CA, et al.
Chest pain in women: Clinical, investigative, and prognostic features.
Br Med J.
1994; 308(6933): 883–6. [PubMed]
Sweeney J, Goldschlager N.
Evaluating patients with chest pain.
West J Med.
1994; 161(5): 511–2. [PubMed]
Tanasijevic MJ, Cannon CP, Antman EM.
The role of cardiac troponin-I (cTnI) in risk stratification of patients with unstable coronary artery disease.
Clin Cardiol.
1999; 22(1): 13–6. [PubMed]
Tatum JL, Jesse RL, Kontos MC, et al.
Comprehensive strategy for the evaluation and triage of the chest pain patient.
Ann Emerg Med.
1997; 29(1): 116–25. [PubMed]
Tierney WM, Roth BJ, Psaty B, et al.
Predictors of myocardial infarction in emergency room patients.
Crit Care Med.
1985; 13(7): 526–31. [PubMed]
Tucker JF, Collins RA, Anderson AJ, et al.
Early diagnostic efficiency of cardiac troponin I and Troponin T for acute myocardial infarction.
Acad Emerg Med.
1997; 4(1): 13–21. [PubMed]
van Miltenburg-van Zijl AJ, Simoons ML, Veerhoek RJ, et al. Incidence and follow-up of Braunwald subgroups in unstable angina pectoris
J Am Coll Cardiol 1995. 25(6):1286–92.View this and related citations using
.
Victor MF, Likoff MJ, Mintz GS, et al.
Unstable angina pectoris of new onset: A prospective clinical and arteriographic study of 75 patients.
Am J Cardiol.
1981; 47(2): 228–32. [PubMed]
Villanueva FS, Sabia PJ, Afrookteh A, et al.
Value and limitations of current methods of evaluating patients presenting to the emergency room with cardiac-related symptoms for determining long-term prognosis.
Am J Cardiol.
1992; 69(8): 746–50. [PubMed]
Waters DD, Miller DD, Szlachcic J, et al.
Factors influencing the long-term prognosis of treated patients with variant angina.
Circulation.
1983; 68(2): 258–65. [PubMed]
Waters DD, Szlachcic J, Miller D, et al.
Clinical characteristics of patients with variant angina complicated by myocardial infarction or death within 1 month.
Am J Cardiol.
1982; 49(4): 658–64. [PubMed]
White LD, Lee TH, Cook EF, et al. Comparison of the natural history of new onset and exacerbated chronic ischemic heart disease. The Chest Pain Study Group
J Am Coll Cardiol 1990. 16(2):304–10.View this and related citations using
.
Wilcox I, Freedman SB, Allman KC, et al. Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris
J Am Coll Cardiol 1991. 18(3):677–83.View this and related citations using
.
Wilcox I, Freedman SB, McCredie RJ, et al.
Risk of adverse outcome in patients admitted to the coronary care unit with suspected unstable angina pectoris.
Am J Cardiol.
1989; 64(14): 845–8. [PubMed]
Wu AH, Abbas SA, Green S, et al.
Prognostic value of cardiac troponin T in unstable angina pectoris.
Am J Cardiol.
1995; 76(12): 970–2. [PubMed]
Wuerz RC, Meador SA.
Evaluation of a pre-hospital chest pain protocol.
Ann Emerg Med.
1995; 26(5): 595–7. [PubMed]
Yang Z, Zhang W, Liu Y. Prognostic efficacy of troponin T measurement in angina pectoris.
Chin Med J (Eng).
1995; 108(8): 626–30.
Young GP, Gibler WB, Hedges JR, et al.
Serial creatine kinase-MB results are a sensitive indicator of acute myocardial infarction in chest pain patients with nondiagnostic electrocardiograms: The second Emergency Medicine Cardiac Research Group Study.
Acad Emerg Med.
1997; 4(9): 869–77. [PubMed]
Young GP, Hedges JR, Gibler WB, et al.
Do CK-MB results affect chest pain decision making in the emergency department?
Ann Emerg Med.
1991; 20(11): 1220–8. [PubMed]
Yusuf S, Pearson M, Sterry H, et al.
The entry ECG in the early diagnosis and prognostic stratification of patients with suspected acute myocardial infarction.
Eur Heart J.
1984; 5(9): 690–6. [PubMed]
Zalenski RJ, Rydman RJ, Ting S, et al.
A national survey of emergency department chest pain centers in the United States.
Am J Cardiol.
1998; 81(11): 1305–9. [PubMed]
Zalenski RJ, Sloan EP, Chen EH, et al.
The emergency department ECG and immediately life-threatening complications in initially uncomplicated suspected myocardial ischemia.
Ann Emerg Med.
1988; 17(3): 221–6. [PubMed]
Zucker DR, Griffith JL, Beshansky JR, et al.
Presentations of acute myocardial infarction in men and women.
J Gen Intern Med.
1997; 12(2): 79–87. [PubMed]
ǀ
). An increase in the overall mortality rate of 1 percent was associated with a 0.6 percent additional increase in the risk of death in troponin-positive patients.
