- Email: [email protected]
Long-Term Prognosis of Low-Risk Women Presenting to the Emergency Department with Chest Pain
Accepted Manuscript Longterm Prognosis of Low Risk Women Presenting to the Emergency Department with Chest Pain Moneer Eddin, MD, Sandhya Venugopal, MD MHPE, Brittany Chatterton, MD, Angela Thinda, MD, Ezra A. Amsterdam, MD PII:
S0002-9343(17)30400-X
DOI:
10.1016/j.amjmed.2017.03.056
Reference:
AJM 14050
To appear in:
The American Journal of Medicine
Received Date: 15 March 2017 Revised Date:
26 March 2017
Accepted Date: 27 March 2017
Please cite this article as: Eddin M, Venugopal S, Chatterton B, Thinda A, Amsterdam EA, Longterm Prognosis of Low Risk Women Presenting to the Emergency Department with Chest Pain, The American Journal of Medicine (2017), doi: 10.1016/j.amjmed.2017.03.056. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Longterm Prognosis of Low Risk Women Presenting to the
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Emergency Department with Chest Pain
Moneer Eddin MD, Sandhya Venugopal MD MHPE, Brittany Chatterton MD, Angela
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Thinda MD, Ezra A Amsterdam MD
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Division of Cardiovascular Medicine, Department of Internal Medicine, University of California (Davis) Medical Center, Sacramento CA
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Funding: None Conflict of Interest: All authors declare that we have no conflicts of interest. Authorship: All authors had access to the data and participated in writing the manuscript. Article Type: Clinical Research Study
Word count: 2543 (including abstract, text, and acknowledgements, but not including tables, references, or the title page) KEY WORDS
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Chest pain, Low risk women, Chest pain unit, Prognosis, Predischarge testing
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Correspondence:
EA Amsterdam MD Division of Cardiovascular Medicine Department of Internal Medicine University of California (Davis) Medical Center 4860 Y St., Suite 0200 Sacramento, CA 95817 Phone: (916) 734-3764 Fax: (916) 734-8394 E-mail: [email protected]
ACCEPTED MANUSCRIPT CHEST PAIN PROGNOSIS IN LOW RISK WOMEN
2
ABSTRACT BACKGROUND: Prognosis of low risk women presenting to the emergency department with chest pain has not been clarified. We assessed early and longterm outcomes of such
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patients and determined the need for predischarge testing METHODS: Retrospective assessment of consecutive low risk women presenting to the ED with chest pain evaluated in a chest pain unit (CPU). Criteria of low risk: age ≤51 yr, no history of cardiovascular disease, diabetes or smoking, negative initial
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electrocardiogram (ECG), and cardiac troponin. Predischarge testing (treadmill or stress imaging) was performed at discretion of the CPU attending physician.
RESULTS: The study group comprised of 214 consecutive women. Predischarge testing
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was performed in 142 patients (66%, age 43.9 yr.) and 72 patients (34%, age 43.1 yr.) had no predischarge testing. Predischarge testing comprised exercise treadmill (n=102, 72%) or stress imaging (n=40, 28%). Length of stay with no predischarge testing was 4.1 hr compared to 8.6 hr with predischarge testing (p = .04). There were no cardiovascular events in the index presentation; during a 5 year interval (100% follow-up), there were 2
0.93%]).
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cardiovascular events (fatal heart failure, 1 patient; fatal stroke, 1 patient [total, 2/214,
CONCLUSIONS: Low risk women presenting to the emergency department with chest pain have an excellent short and longterm prognosis. A majority of patients did not
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receive predischarge testing and their length of stay was reduced by >50% compared to those with predischarge testing. These findings suggest that such patients may not
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require predischarge testing for disposition from a CPU, which can reduce length of stay, decrease cost and improve resource utilization.
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Optimal management of patients presenting to the emergency department with chest pain is a continuing challenge.1 These patients number over 8 million annually in this country, of which a large majority is at low risk for acute coronary syndrome based on negative
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examination, normal electrocardiogram (ECG) and negative cardiac injury markers.2 Half of these patients are women, most of whom do not have an acute coronary syndrome or other life-threatening condition and are therefore considered low risk.1,2 However,
women often present a diagnostic challenge because atypical symptoms of myocardial
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ischemia are frequent in this group,2, 3-5 inadvertent discharge of women with acute
coronary syndrome is not rare, 6 and a high complication rate has been reported in young
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women with acute coronary syndrome.7 Because of concern for patient safety and medico-legal liability, it is imperative to detect acute coronary syndrome in this important minority within this population.8 To enhance evaluation of low risk patients presenting with chest pain, accelerated diagnostic protocols, chest pain units (CPU), and cardiac imaging methods have been developed to provide safe, rapid, and cost-effective management of patients who do not require admission and identification of those for
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whom admission is indicated 2, 9-13.
Accelerated diagnostic protocols comprise serial ECGs and cardiac injury markers, which if negative, are usually followed by a predischarge functional test.. The latter is typically
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an exercise treadmill test, stress imaging study or computed tomography coronary angiography (CTA) to exclude inducible myocardial ischemia or anatomic coronary
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artery disease and thereby endorse the safety of direct discharge from the CPU. However, it has recently been reported that with high sensitivity cardiac troponin (hscTn) testing, low risk patients can be safely discharged from the CPU without predischarge testing after exclusion of acute coronary syndrome using serial ECGs and cardiac markers.14-15 These results suggest that all low risk patients, including women, may not require predischarge testing. Using standard cardiac injury markers as part of our CPU evaluation, we have compared short- and longterm outcomes in a group of low risk women presenting to the emergency department with chest pain, some of whom received predischarge testing while others did not.
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METHODS
Data Source
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We conducted a retrospective study of low risk women presenting to the emergency department with chest pain between 1/1/97 and 12/31/06. We queried the electronic
medical record (EMR) of the University of California, Davis (UCD), Health System
Chest Pain Unit database to identify consecutive women presenting to the UCD Medical Center emergency department with a principle diagnosis of non-traumatic chest pain
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interval was approximately 42,000 patient visits.
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(ICD-9-CM 786.50). The total annual emergency department volume during the study
Study Cohort
All patients in this study were subscribers to the UCD Health System Health Maintenance Organization. The study population comprised consecutive women who were considered low risk for acute coronary syndrome and its complications. Low risk was defined by 1) age 35-51 years and no history of cardiovascular disease, diabetes, or
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smoking; 2) normal physical examination; 3) normal ECG, which allowed interpretation of exercise-induced ischemic ST segment alterations and 4) normal cardiac injury markers (contemporary troponin I and/or MB fraction of creatinine kinase [CKMB]). Patients were excluded if they were not subscribers to the UCD Health System, if they
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Evaluation
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had known cardiovascular disease, or if they did not meet the inclusion criteria.
After documentation of low risk on presentation to the emergency department, patients were transferred to the CPU where they underwent evaluation by serial ECGs and 1-2 sets of additional cardiac injury markers at the discretion of the CPU attending physician. Traditional cardiac risk factors (hypertension, hyperlipidemia, smoking, diabetes, family history) were assessed directly from the patients and their EMR records.
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If the CPU evaluation was negative, it was followed by one of the following approaches: 1) direct discharge home from the CPU without further testing, 2) a predischarge exercise treadmill test (symptom limited, Bruce protocol), or 3) a predischarge exercise or pharmacologic stress imaging test (myocardial perfusion
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scintigraphy [MPS]) or dobutamine stress echocardiography [DSE]). Selection of stress imaging tests was based on preference of the CPU attending physician and/or patients’ limited exercise capacity. Patients with a positive exercise treadmill test received further
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evaluation by a stress imaging test (MPS or DSE) or invasive coronary angiography.
The criteria for positive (ischemic) functional tests were: 1) Exercise treadmill test -
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≥1.0 mm exercise-induced ST segment depression 60-80 mm after the J point; 2) MPS a new stress-induced left ventricular perfusion defect; 3) DSE - a new stress-induced left ventricular wall motion abnormality. Exercise treadmill tests associated with ≤1.0 mm ST segment depression in which patients did not reach ≥85% of age-predicted maximal heart rate were considered non-diagnostic and additional testing was considered in this group on an individual basis. Coronary angiography was considered
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positive if a stenosis in a major coronary artery or principal branch was ≥70% of the vessel’s lumen diameter; a stenosis of 50% in the left main coronary artery was considered positive.
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Follow-up: Follow-up was obtained by review of patients’ records in the EMR. The
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Social Security Death Index was queried for mortality data.
Statistical Analysis: Continuous data are presented as mean ± SD. The significance of differences between continuous mean data was analyzed by Student’s t-test and chisquare test was applied to assess the differences in categorical variables. Differences were considered significant if p<0.05.
The institutional review board of the University of California, Davis, approved this study.
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RESULTS
Between January 1, 1997 and December 31, 2006, 215 women fulfilling the inclusion criteria were admitted to the CPU. During the accelerated diagnostic protocol in the
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CPU, none of the patients had ECG or cardiac injury marker evidence of acute coronary syndrome and none had a cardiovascular complication. Clinical characteristics of the
patients who did and did not undergo predischarge testing are summarized in Table 1. Two-thirds of the patients received predischarge testing and the remainder were
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discharged directly from the CPU after a negative accelerated diagnostic protocol without a functional test. There were no significant differences in age or number of cardiac risk
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factors in the predischarge testing and no predischarge testing groups.
Functional Tests
Of the 142 predischarge testing patients, almost three-fourths received exercise treadmill test and approximately one fourth were evaluated by stress imaging studies (Table 2). In 102 of these patients, the initial test was exercise treadmill test, in 22 it was DSE, and 18
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patients received MPS. Exercise treadmill test was negative in 84% of patients, positive in 12% and non-diagnostic in 4%. Of the 12 patients with a positive exercise treadmill test, 9 received further evaluation by DSE and one by MPS, all of which were negative. Two of the 12 positive exercise treadmill test were considered to be false positives and
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the patients were discharged without further testing. The basis for the interpretation of false positive results of the exercise treadmill tests in these two patients included absence
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of symptoms, functional capacity of 8 and 14 METs, 101% and 89% of age-predicted maximum heart rates and rapid resolution of 1.0 mm ST-segment depression (<30 sec). Four patients had non-diagnostic exercise treadmill tests, of whom 3 were considered to have very low clinical risk based on their cardiac risk factor profiles, good-excellent functional capacity on exercise treadmill test and absence of exercise-induced symptoms. These patients were discharged to home from the CPU and the fourth patient with a nondiagnostic exercise treadmill test was transferred to an outside hospital. In the 40 patients in whom stress imaging was the initial functional test (DSE 22, MPS 18), all but two results (DSEs) were negative. These two patients with positive DSEs underwent
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invasive coronary angiography prior to discharge, which demonstrated angiographically normal coronary arteries.
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Follow-up
Follow-up was 100% during an average interval of 5.0 ± 2.8 years. All except one patient was followed for ≥1.5 years with the longest interval >10 years. There were 3 clinical events during follow-up. One patient was hospitalized with heart failure related to a
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peripartum cardiomyopathy 5 years after CPU evaluation; one had a stroke 2 years after CPU evaluation and a normal coronary angiogram 3 years following CPU admission; and
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the third patient died of necrotizing pancreatitis 3 years after discharge from the CPU. There was no other mortality and none of the remaining 211 patients developed a
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diagnosis of cardiovascular disease or other morbidity during follow-up.
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Discussion It has been established that low clinical risk in patients presenting to the emergency department with chest pain can be identified on presentation.2, 14-16 However, because a
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small proportion of these patients may have acute coronary syndrome or other serious
etiology of their symptoms, it has become current practice to evaluate these patients with an accelerated protocol to determine those who can be directly discharged and those who require admission.17 This evaluation is commonly performed in a CPU and typically
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includes cardiac functional testing. However, our study suggests that not all low risk
patients require predischarge functional testing. This concept is supported by both the early and longterm minimal rate of clinical events in our patients. Further, to our
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knowledge, there is only one other study of low risk chest pain patients discharged from a short stay unit with a follow-up duration comparable to ours.18 However, in that study, all patients received predischarge cardiac functional testing whereas a large minority of our patients did not receive predischarge testing. These findings have potentially important
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implications for patient management and resource utilization.
Studies of patients discharged from a CPU without undergoing predischarge testing are limited, particularly in women. The rationale for functional testing in the CPU is its capacity to refine the evaluation of low risk patients by identifying those with and
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without inducible myocardial ischemia or anatomic coronary artery disease, which is pivotal to the decision of whether to discharge or admit these patients. This group accounts for a significant proportion of women presenting to the emergency department
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with chest pain.2,19 Furthermore, young women with acute coronary syndrome have a high morbidity and mortality and are a group in which acute coronary syndrome diagnosis is most frequently missed in the emergency department.6,7 This approach helps avoid inadvertent discharge of patients with acute coronary syndrome, a crucial concern that was raised by a report early in this century.6 Additionally, recent studies have questioned the need for, and cost-effectiveness of, predischarge testing in low risk chest pain patients.14-15,20
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Our results extend these findings by demonstrating excellent prognosis, which was predicted without predischarge testing, in a large minority (34%) of low risk women. In addition, evaluation in the CPU was not only safe but also more efficient and shorter than in other reports in the literature, including those comparing usual care versus CTA.21 In
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this regard, one study reported that CTA significantly reduced length of stay compared to usual care (31 to 23 hrs) in low risk chest pain patients.21 However, exclusion of
predischarge testing in our patients was associated with an length of stay of 4.1 hrs.
Indeed, our time to discharge was decreased by >50% in the no predischarge testing
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group compared to our predischarge testing patients (no predischarge testing 4.1 hrs vs.
predischarge testing 8.6 hrs, p<0.05). To our knowledge, 4.1 hrs is the shortest length of
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stay in studies of low risk patients presenting with chest pain. No predischarge testing is also particularly advantageous in women in that no radiation exposure, such as that with MPS and CTA, is associated with this strategy.
Our follow-up of over 5 years is similar to that of the CHEER trial11 which is considerably longer than that of other reports on low risk patients presenting to the
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emergency department with chest pain. In CHEER, direct patient discharge from the CPU after a negative cardiac stress test was not associated with increased adverse outcomes during longterm follow-up. Our findings extend the results of CHEER by demonstrating that evaluation in a CPU can also identify low risk patients in whom
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predischarge testing is not mandatory to reveal those at very low risk for adverse outcome
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on longterm follow-up.
An important development in the evaluation of low risk chest pain patients is the application of high-sensitivity cardiac troponin (hs-cTn) in this setting. Use of this injury marker has allowed safe discharge of low risk chest pain patients with hs-cTn <5 ng/l, negative ECG and no functional testing.14 These findings were extended by report of a validated 2-hour diagnostic protocol utilizing hs-cTn, negative ECG, and zero Thrombolysis in Myocardial Infarction score in low risk patients, which excluded myocardial infarction without functional testing.15 We recently reported excellent shortterm follow-up in low risk chest pain patients utilizing conventional cTn, some of whom
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did not undergo predischarge testing.13 The latter study assessed follow-up at 30 days whereas the average follow-up in our current study was over 5 years. Furthermore, the benign clinical course of all but a very small number of our patients suggests that the
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initial presentation was not related to cardiovascular disease.
Shorter length of stay improves resource utilization and enhances patient management in the emergency department. The excellent early and longterm course of our patients who did not undergo predischarge testing supports the concept that this group, which can be
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readily identified shortly after presentation, may not require predischarge testing for disposition from a CPU. Our study group of young non-diabetic women without a
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history of smoking proved to be very low risk and it is possible that our approach might also apply to men with a similar clinical profile presenting to the emergency department with chest pain.
LIMITATIONS
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This is a retrospective study with the limitations inherent in this method. It is also based on a single center experience and therefore may not be generalizable to other institutions. A further limitation is that patient selection for predischarge testing or no predischarge testing was by the CPU physicians based on their individual judgment, which also may
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not be generalizable. Finally, the excellent longterm prognosis of our patients may have
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been in part related to subsequent management by their primary care physicians.
CONCLUSION
Low risk women presenting to the emergency department with chest pain can be identified by clinical assessment. As a group, these women have a favorable early and longterm course. Our results support the concept that these patients may not all require predischarge testing, which can thereby reduce length of stay, enhance resource utilization, and maintain safe evaluation.
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REFERENCES 1.
Lee TH and Goldman L. Evaluation of the patient with acute chest pain. N Engl J
2.
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Med. 2000. 342(16): 1187-95.
Amsterdam EA, Kirk JD, Bluemke DA, et al. Testing of low risk patients
presenting to the emergency department with chest pain: a scientific statement
3.
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from the American Heart Association. Circulation. 2010;122(17): 1756-1776. Milner KA, Funk M, Richards S, Wilmes RM, Vaccarino V, Krumholz HM.
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Gender differences in symptome presentation associated with coronary heart disease. Am J Cardiol 1999;84:396-399 4.
Patel H, Rosengren A, Ekman I. Symptoms in acute coronary syndromes: does sex make a difference? Am Heart J 2004;148:27-33.
Bairey Merz CN, Shaw LJ, Reis SE, et al. Insights from the NHLBI-Sponsored
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5.
Women's Ischemia Syndrome Evaulation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based
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pathophysiology of atherosclerosis and macrovascular coronary disease. J Am Coll Cardiol 2006;47(Suppl 3):S21-S29. Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac
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6.
ischemia in the emergency department. N Engl J Med, 2000. 342(16):1163-1170.
7.
Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. Sex-based differences in early mortality after myocardial infarction. New Engl J Med 1999;341:217-225
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12
Stein RA, Chaitman BR, Balady GJ, et al. Safety and utility of exercise testing in emergency room chest pain centers: An advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology,
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American Heart Association. Circulation, 2000. 102(12):1463-1467. 9.
Hutter AM Jr, Amsterdam EA, and Jaffe AS. 31st Bethesda Conference.
Emergency Cardiac Care. Task force 2: Acute coronary syndromes: Section 2B--
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Chest discomfort evaluation in the hospital. J Am Coll Cardiol, 2000. 35(4): 853862.
Lewis WR and Amsterdam EA. Defining the role of chest pain units. J Am Coll
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10.
Cardiol, 2001. 37(8):2050-2052. 11.
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
1888. 12.
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Emergency Room (CHEER) Investigators. N Engl J Med, 1998. 339(26):1882-
Lewis WR and Amsterdam EA. Chest pain emergency units. Curr Opin Cardiol,
13.
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1999. 14(4):321-328.
Stauber SM, Teleten A, Li Z, Venugopal S, Amsterdam EA. Prognosis of Low
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risk Young Women Presenting to the Emergency Department With Chest Pain. Am J Cardiol. 2016 Jan 1;117(1):36-9.
14.
Bandstein N, Ljung R, Eggers K, Holzmann M. Risk of revisits to the emergency
department in admitted versus discharged patients with chest pain and undetectable high-sensitivity cardiac troponin T levels. J Am Coll Cardiol.
2015;1097(15); 129-132
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Than M, Aldous S, Lord SJ, et al. A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. JAMA Intern Med 2014;174:51e58. Lee TH, Cook EF, Weisberg M, Sargent RK, Wilson C, Goldman L. Acute chest
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16.
pain in the emergency room. Identification and examination of low risk patients. Arch Intern Med, 1985. 145(1): p. 65-9.
Amsterdam EA, Lewis WR, and Yadlapalli S. Evaluation of low risk patients
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17.
with chest pain in the emergency department: value and limitations of recent
18.
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methods. Cardiol Rev, 1999. 7(1):17-26.
Cullen MW, Reeder GS, Farkouh ME, et. al. Outcomes in patients with chest pain evaluated in a chest pain unit: The Chest Pain Evaluation in the Emergency Room
19.
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study cohort .American Heart Journal 2011;161:871-7
Amsterdam EA, Kirk JD, Diercks DB, Lewis WR, Turnipseed SD. Immediate exercise testing to evaluate low-risk patients presenting to the emergency
20.
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department with chest pain. J Am Coll Cardiol 2002;40:251-256 Winchester DE, Brandt J, Schmidt C, Allen B, Payton T, Amsterdam EA.
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Diagnostic yield of routine noninvasive cardiovascular testing in low risk acute chest pain patients. Am J Cardiol 2015;116:204-207.
21.
Hoffman U, Truong QA, Schoenfeld DA, et al. ROMICAT-II Investigators. Coronary CT Angiography versus standard evaluation in the acute chest pain. N Engl J Med. 2012;367(4):299-308.
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Table 1. Patient Demographics
Total Cohort n=214 Age (yr)
NPDT
n=142 (66%) 43.9
0 0 42 (30%) 33 (23%) 52 (37%) 15 (10%)
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Smoking Diabetes mellitus Hypertension Dyslipidemia Family history CAD No risk factors
p value ns ns
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Cardiac risk factors
n=72 (34%) 43.1
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PDT
0 0 20 (28%) 7 (10%) 14 (19%) 31 (43%)
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PDT - predischarge testing, NPDT - no predischarge testing, CAD - coronary artery disease
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Table 2. Exercise treadmill test or stress imaging test Total PDT (n=142) 102 (72%)
Positive PDT (n=14) 12 (12%)
Dobutamine stress echo
22 (15%)
2(9%)
Myocardial perfusion scintigraphy
18 (13%)
0 (0%)
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Initial Test Exercise treadmill
PDT - predischarge test
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Table 1. Patient Demographics PDT n=142 (66%) 43.9
Cardiac risk factors
p value ns ns
0 0 20 (28%) 7 (10%) 14 (19%) 31 (43%)
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0 0 42 (30%) 33 (23%) 52 (37%) 15 (10%)
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Smoking Diabetes mellitus Hypertension Dyslipidemia Family history CAD No risk factors
n=72 (34%) 43.1
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Total Cohort n=214 Age (yr)
NPDT
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PDT - predischarge testing, NPDT - no predischarge testing, CAD - coronary artery disease
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Table 2. Exercise treadmill test or stress imaging test Total PDT (n=142) 102 (72%)
Positive PDT (n=14) 12 (12%)
Dobutamine stress echo
22 (15%)
2(9%)
Myocardial perfusion scintigraphy
18 (13%)
0 (0%)
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Initial Test Exercise treadmill
PDT - predischarge test
ACCEPTED MANUSCRIPT UNIVERSITY OF CALIFORNIA, DAVIS BERKELEY ● DAVIS ● IRVINE ● LOS ANGELES ● MERCED ● RIVERSIDE ● SAN DIEGO ● SAN FRANCISCO
UC DAVIS MEDICAL CENTER DIVISION OF CARDIOVASCULAR MEDICINE 4860 Y STREET, SUITE 2820 SACRAMENTO, CA 95817 Phone (916) 734-3764 Fax (916) 734-8394
● SANTA BARBARA ● SANTA CRUZ
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SCHOOL OF MEDICINE
Longterm Prognosis of Low Risk Women Presenting to the Emergency
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Department with Chest Pain
MD, Ezra A Amsterdam MD
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Moneer Eddin MD, Sandhya Venugopal MD MHPE, Brittany Chatterton MD, Angela Thinda
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Clinical significance of your manuscript: “Take Home” Points
1) The risk of missing acute coronary syndrome is increased in women presenting to the ED with chest pain.
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2) Longterm (5 year) prognosis of low risk women presenting to the ED with chest pain is excellent.
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3) Omission of predischarge cardiac testing in low risk women presenting with chest pain is safe, accurate and decreases length of stay.
S0002-9343(17)30400-X
DOI:
10.1016/j.amjmed.2017.03.056
Reference:
AJM 14050
To appear in:
The American Journal of Medicine
Received Date: 15 March 2017 Revised Date:
26 March 2017
Accepted Date: 27 March 2017
Please cite this article as: Eddin M, Venugopal S, Chatterton B, Thinda A, Amsterdam EA, Longterm Prognosis of Low Risk Women Presenting to the Emergency Department with Chest Pain, The American Journal of Medicine (2017), doi: 10.1016/j.amjmed.2017.03.056. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Longterm Prognosis of Low Risk Women Presenting to the
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Emergency Department with Chest Pain
Moneer Eddin MD, Sandhya Venugopal MD MHPE, Brittany Chatterton MD, Angela
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Thinda MD, Ezra A Amsterdam MD
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Division of Cardiovascular Medicine, Department of Internal Medicine, University of California (Davis) Medical Center, Sacramento CA
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Funding: None Conflict of Interest: All authors declare that we have no conflicts of interest. Authorship: All authors had access to the data and participated in writing the manuscript. Article Type: Clinical Research Study
Word count: 2543 (including abstract, text, and acknowledgements, but not including tables, references, or the title page) KEY WORDS
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Chest pain, Low risk women, Chest pain unit, Prognosis, Predischarge testing
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Correspondence:
EA Amsterdam MD Division of Cardiovascular Medicine Department of Internal Medicine University of California (Davis) Medical Center 4860 Y St., Suite 0200 Sacramento, CA 95817 Phone: (916) 734-3764 Fax: (916) 734-8394 E-mail: [email protected]
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2
ABSTRACT BACKGROUND: Prognosis of low risk women presenting to the emergency department with chest pain has not been clarified. We assessed early and longterm outcomes of such
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patients and determined the need for predischarge testing METHODS: Retrospective assessment of consecutive low risk women presenting to the ED with chest pain evaluated in a chest pain unit (CPU). Criteria of low risk: age ≤51 yr, no history of cardiovascular disease, diabetes or smoking, negative initial
SC
electrocardiogram (ECG), and cardiac troponin. Predischarge testing (treadmill or stress imaging) was performed at discretion of the CPU attending physician.
RESULTS: The study group comprised of 214 consecutive women. Predischarge testing
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was performed in 142 patients (66%, age 43.9 yr.) and 72 patients (34%, age 43.1 yr.) had no predischarge testing. Predischarge testing comprised exercise treadmill (n=102, 72%) or stress imaging (n=40, 28%). Length of stay with no predischarge testing was 4.1 hr compared to 8.6 hr with predischarge testing (p = .04). There were no cardiovascular events in the index presentation; during a 5 year interval (100% follow-up), there were 2
0.93%]).
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cardiovascular events (fatal heart failure, 1 patient; fatal stroke, 1 patient [total, 2/214,
CONCLUSIONS: Low risk women presenting to the emergency department with chest pain have an excellent short and longterm prognosis. A majority of patients did not
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receive predischarge testing and their length of stay was reduced by >50% compared to those with predischarge testing. These findings suggest that such patients may not
AC C
require predischarge testing for disposition from a CPU, which can reduce length of stay, decrease cost and improve resource utilization.
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3
Optimal management of patients presenting to the emergency department with chest pain is a continuing challenge.1 These patients number over 8 million annually in this country, of which a large majority is at low risk for acute coronary syndrome based on negative
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examination, normal electrocardiogram (ECG) and negative cardiac injury markers.2 Half of these patients are women, most of whom do not have an acute coronary syndrome or other life-threatening condition and are therefore considered low risk.1,2 However,
women often present a diagnostic challenge because atypical symptoms of myocardial
SC
ischemia are frequent in this group,2, 3-5 inadvertent discharge of women with acute
coronary syndrome is not rare, 6 and a high complication rate has been reported in young
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women with acute coronary syndrome.7 Because of concern for patient safety and medico-legal liability, it is imperative to detect acute coronary syndrome in this important minority within this population.8 To enhance evaluation of low risk patients presenting with chest pain, accelerated diagnostic protocols, chest pain units (CPU), and cardiac imaging methods have been developed to provide safe, rapid, and cost-effective management of patients who do not require admission and identification of those for
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whom admission is indicated 2, 9-13.
Accelerated diagnostic protocols comprise serial ECGs and cardiac injury markers, which if negative, are usually followed by a predischarge functional test.. The latter is typically
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an exercise treadmill test, stress imaging study or computed tomography coronary angiography (CTA) to exclude inducible myocardial ischemia or anatomic coronary
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artery disease and thereby endorse the safety of direct discharge from the CPU. However, it has recently been reported that with high sensitivity cardiac troponin (hscTn) testing, low risk patients can be safely discharged from the CPU without predischarge testing after exclusion of acute coronary syndrome using serial ECGs and cardiac markers.14-15 These results suggest that all low risk patients, including women, may not require predischarge testing. Using standard cardiac injury markers as part of our CPU evaluation, we have compared short- and longterm outcomes in a group of low risk women presenting to the emergency department with chest pain, some of whom received predischarge testing while others did not.
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METHODS
Data Source
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We conducted a retrospective study of low risk women presenting to the emergency department with chest pain between 1/1/97 and 12/31/06. We queried the electronic
medical record (EMR) of the University of California, Davis (UCD), Health System
Chest Pain Unit database to identify consecutive women presenting to the UCD Medical Center emergency department with a principle diagnosis of non-traumatic chest pain
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interval was approximately 42,000 patient visits.
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(ICD-9-CM 786.50). The total annual emergency department volume during the study
Study Cohort
All patients in this study were subscribers to the UCD Health System Health Maintenance Organization. The study population comprised consecutive women who were considered low risk for acute coronary syndrome and its complications. Low risk was defined by 1) age 35-51 years and no history of cardiovascular disease, diabetes, or
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smoking; 2) normal physical examination; 3) normal ECG, which allowed interpretation of exercise-induced ischemic ST segment alterations and 4) normal cardiac injury markers (contemporary troponin I and/or MB fraction of creatinine kinase [CKMB]). Patients were excluded if they were not subscribers to the UCD Health System, if they
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Evaluation
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had known cardiovascular disease, or if they did not meet the inclusion criteria.
After documentation of low risk on presentation to the emergency department, patients were transferred to the CPU where they underwent evaluation by serial ECGs and 1-2 sets of additional cardiac injury markers at the discretion of the CPU attending physician. Traditional cardiac risk factors (hypertension, hyperlipidemia, smoking, diabetes, family history) were assessed directly from the patients and their EMR records.
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If the CPU evaluation was negative, it was followed by one of the following approaches: 1) direct discharge home from the CPU without further testing, 2) a predischarge exercise treadmill test (symptom limited, Bruce protocol), or 3) a predischarge exercise or pharmacologic stress imaging test (myocardial perfusion
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scintigraphy [MPS]) or dobutamine stress echocardiography [DSE]). Selection of stress imaging tests was based on preference of the CPU attending physician and/or patients’ limited exercise capacity. Patients with a positive exercise treadmill test received further
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evaluation by a stress imaging test (MPS or DSE) or invasive coronary angiography.
The criteria for positive (ischemic) functional tests were: 1) Exercise treadmill test -
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≥1.0 mm exercise-induced ST segment depression 60-80 mm after the J point; 2) MPS a new stress-induced left ventricular perfusion defect; 3) DSE - a new stress-induced left ventricular wall motion abnormality. Exercise treadmill tests associated with ≤1.0 mm ST segment depression in which patients did not reach ≥85% of age-predicted maximal heart rate were considered non-diagnostic and additional testing was considered in this group on an individual basis. Coronary angiography was considered
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positive if a stenosis in a major coronary artery or principal branch was ≥70% of the vessel’s lumen diameter; a stenosis of 50% in the left main coronary artery was considered positive.
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Follow-up: Follow-up was obtained by review of patients’ records in the EMR. The
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Social Security Death Index was queried for mortality data.
Statistical Analysis: Continuous data are presented as mean ± SD. The significance of differences between continuous mean data was analyzed by Student’s t-test and chisquare test was applied to assess the differences in categorical variables. Differences were considered significant if p<0.05.
The institutional review board of the University of California, Davis, approved this study.
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RESULTS
Between January 1, 1997 and December 31, 2006, 215 women fulfilling the inclusion criteria were admitted to the CPU. During the accelerated diagnostic protocol in the
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CPU, none of the patients had ECG or cardiac injury marker evidence of acute coronary syndrome and none had a cardiovascular complication. Clinical characteristics of the
patients who did and did not undergo predischarge testing are summarized in Table 1. Two-thirds of the patients received predischarge testing and the remainder were
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discharged directly from the CPU after a negative accelerated diagnostic protocol without a functional test. There were no significant differences in age or number of cardiac risk
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factors in the predischarge testing and no predischarge testing groups.
Functional Tests
Of the 142 predischarge testing patients, almost three-fourths received exercise treadmill test and approximately one fourth were evaluated by stress imaging studies (Table 2). In 102 of these patients, the initial test was exercise treadmill test, in 22 it was DSE, and 18
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patients received MPS. Exercise treadmill test was negative in 84% of patients, positive in 12% and non-diagnostic in 4%. Of the 12 patients with a positive exercise treadmill test, 9 received further evaluation by DSE and one by MPS, all of which were negative. Two of the 12 positive exercise treadmill test were considered to be false positives and
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the patients were discharged without further testing. The basis for the interpretation of false positive results of the exercise treadmill tests in these two patients included absence
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of symptoms, functional capacity of 8 and 14 METs, 101% and 89% of age-predicted maximum heart rates and rapid resolution of 1.0 mm ST-segment depression (<30 sec). Four patients had non-diagnostic exercise treadmill tests, of whom 3 were considered to have very low clinical risk based on their cardiac risk factor profiles, good-excellent functional capacity on exercise treadmill test and absence of exercise-induced symptoms. These patients were discharged to home from the CPU and the fourth patient with a nondiagnostic exercise treadmill test was transferred to an outside hospital. In the 40 patients in whom stress imaging was the initial functional test (DSE 22, MPS 18), all but two results (DSEs) were negative. These two patients with positive DSEs underwent
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invasive coronary angiography prior to discharge, which demonstrated angiographically normal coronary arteries.
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Follow-up
Follow-up was 100% during an average interval of 5.0 ± 2.8 years. All except one patient was followed for ≥1.5 years with the longest interval >10 years. There were 3 clinical events during follow-up. One patient was hospitalized with heart failure related to a
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peripartum cardiomyopathy 5 years after CPU evaluation; one had a stroke 2 years after CPU evaluation and a normal coronary angiogram 3 years following CPU admission; and
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the third patient died of necrotizing pancreatitis 3 years after discharge from the CPU. There was no other mortality and none of the remaining 211 patients developed a
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diagnosis of cardiovascular disease or other morbidity during follow-up.
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Discussion It has been established that low clinical risk in patients presenting to the emergency department with chest pain can be identified on presentation.2, 14-16 However, because a
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small proportion of these patients may have acute coronary syndrome or other serious
etiology of their symptoms, it has become current practice to evaluate these patients with an accelerated protocol to determine those who can be directly discharged and those who require admission.17 This evaluation is commonly performed in a CPU and typically
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includes cardiac functional testing. However, our study suggests that not all low risk
patients require predischarge functional testing. This concept is supported by both the early and longterm minimal rate of clinical events in our patients. Further, to our
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knowledge, there is only one other study of low risk chest pain patients discharged from a short stay unit with a follow-up duration comparable to ours.18 However, in that study, all patients received predischarge cardiac functional testing whereas a large minority of our patients did not receive predischarge testing. These findings have potentially important
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implications for patient management and resource utilization.
Studies of patients discharged from a CPU without undergoing predischarge testing are limited, particularly in women. The rationale for functional testing in the CPU is its capacity to refine the evaluation of low risk patients by identifying those with and
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without inducible myocardial ischemia or anatomic coronary artery disease, which is pivotal to the decision of whether to discharge or admit these patients. This group accounts for a significant proportion of women presenting to the emergency department
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with chest pain.2,19 Furthermore, young women with acute coronary syndrome have a high morbidity and mortality and are a group in which acute coronary syndrome diagnosis is most frequently missed in the emergency department.6,7 This approach helps avoid inadvertent discharge of patients with acute coronary syndrome, a crucial concern that was raised by a report early in this century.6 Additionally, recent studies have questioned the need for, and cost-effectiveness of, predischarge testing in low risk chest pain patients.14-15,20
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Our results extend these findings by demonstrating excellent prognosis, which was predicted without predischarge testing, in a large minority (34%) of low risk women. In addition, evaluation in the CPU was not only safe but also more efficient and shorter than in other reports in the literature, including those comparing usual care versus CTA.21 In
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this regard, one study reported that CTA significantly reduced length of stay compared to usual care (31 to 23 hrs) in low risk chest pain patients.21 However, exclusion of
predischarge testing in our patients was associated with an length of stay of 4.1 hrs.
Indeed, our time to discharge was decreased by >50% in the no predischarge testing
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group compared to our predischarge testing patients (no predischarge testing 4.1 hrs vs.
predischarge testing 8.6 hrs, p<0.05). To our knowledge, 4.1 hrs is the shortest length of
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stay in studies of low risk patients presenting with chest pain. No predischarge testing is also particularly advantageous in women in that no radiation exposure, such as that with MPS and CTA, is associated with this strategy.
Our follow-up of over 5 years is similar to that of the CHEER trial11 which is considerably longer than that of other reports on low risk patients presenting to the
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emergency department with chest pain. In CHEER, direct patient discharge from the CPU after a negative cardiac stress test was not associated with increased adverse outcomes during longterm follow-up. Our findings extend the results of CHEER by demonstrating that evaluation in a CPU can also identify low risk patients in whom
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predischarge testing is not mandatory to reveal those at very low risk for adverse outcome
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on longterm follow-up.
An important development in the evaluation of low risk chest pain patients is the application of high-sensitivity cardiac troponin (hs-cTn) in this setting. Use of this injury marker has allowed safe discharge of low risk chest pain patients with hs-cTn <5 ng/l, negative ECG and no functional testing.14 These findings were extended by report of a validated 2-hour diagnostic protocol utilizing hs-cTn, negative ECG, and zero Thrombolysis in Myocardial Infarction score in low risk patients, which excluded myocardial infarction without functional testing.15 We recently reported excellent shortterm follow-up in low risk chest pain patients utilizing conventional cTn, some of whom
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did not undergo predischarge testing.13 The latter study assessed follow-up at 30 days whereas the average follow-up in our current study was over 5 years. Furthermore, the benign clinical course of all but a very small number of our patients suggests that the
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initial presentation was not related to cardiovascular disease.
Shorter length of stay improves resource utilization and enhances patient management in the emergency department. The excellent early and longterm course of our patients who did not undergo predischarge testing supports the concept that this group, which can be
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readily identified shortly after presentation, may not require predischarge testing for disposition from a CPU. Our study group of young non-diabetic women without a
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history of smoking proved to be very low risk and it is possible that our approach might also apply to men with a similar clinical profile presenting to the emergency department with chest pain.
LIMITATIONS
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This is a retrospective study with the limitations inherent in this method. It is also based on a single center experience and therefore may not be generalizable to other institutions. A further limitation is that patient selection for predischarge testing or no predischarge testing was by the CPU physicians based on their individual judgment, which also may
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not be generalizable. Finally, the excellent longterm prognosis of our patients may have
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been in part related to subsequent management by their primary care physicians.
CONCLUSION
Low risk women presenting to the emergency department with chest pain can be identified by clinical assessment. As a group, these women have a favorable early and longterm course. Our results support the concept that these patients may not all require predischarge testing, which can thereby reduce length of stay, enhance resource utilization, and maintain safe evaluation.
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Lee TH and Goldman L. Evaluation of the patient with acute chest pain. N Engl J
2.
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Med. 2000. 342(16): 1187-95.
Amsterdam EA, Kirk JD, Bluemke DA, et al. Testing of low risk patients
presenting to the emergency department with chest pain: a scientific statement
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from the American Heart Association. Circulation. 2010;122(17): 1756-1776. Milner KA, Funk M, Richards S, Wilmes RM, Vaccarino V, Krumholz HM.
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Gender differences in symptome presentation associated with coronary heart disease. Am J Cardiol 1999;84:396-399 4.
Patel H, Rosengren A, Ekman I. Symptoms in acute coronary syndromes: does sex make a difference? Am Heart J 2004;148:27-33.
Bairey Merz CN, Shaw LJ, Reis SE, et al. Insights from the NHLBI-Sponsored
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pathophysiology of atherosclerosis and macrovascular coronary disease. J Am Coll Cardiol 2006;47(Suppl 3):S21-S29. Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac
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Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. Sex-based differences in early mortality after myocardial infarction. New Engl J Med 1999;341:217-225
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Stein RA, Chaitman BR, Balady GJ, et al. Safety and utility of exercise testing in emergency room chest pain centers: An advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology,
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American Heart Association. Circulation, 2000. 102(12):1463-1467. 9.
Hutter AM Jr, Amsterdam EA, and Jaffe AS. 31st Bethesda Conference.
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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
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Emergency Room (CHEER) Investigators. N Engl J Med, 1998. 339(26):1882-
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department in admitted versus discharged patients with chest pain and undetectable high-sensitivity cardiac troponin T levels. J Am Coll Cardiol.
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Than M, Aldous S, Lord SJ, et al. A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. JAMA Intern Med 2014;174:51e58. Lee TH, Cook EF, Weisberg M, Sargent RK, Wilson C, Goldman L. Acute chest
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Table 1. Patient Demographics
Total Cohort n=214 Age (yr)
NPDT
n=142 (66%) 43.9
0 0 42 (30%) 33 (23%) 52 (37%) 15 (10%)
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Smoking Diabetes mellitus Hypertension Dyslipidemia Family history CAD No risk factors
p value ns ns
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Cardiac risk factors
n=72 (34%) 43.1
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PDT
0 0 20 (28%) 7 (10%) 14 (19%) 31 (43%)
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PDT - predischarge testing, NPDT - no predischarge testing, CAD - coronary artery disease
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Table 2. Exercise treadmill test or stress imaging test Total PDT (n=142) 102 (72%)
Positive PDT (n=14) 12 (12%)
Dobutamine stress echo
22 (15%)
2(9%)
Myocardial perfusion scintigraphy
18 (13%)
0 (0%)
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Initial Test Exercise treadmill
PDT - predischarge test
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Table 1. Patient Demographics PDT n=142 (66%) 43.9
Cardiac risk factors
p value ns ns
0 0 20 (28%) 7 (10%) 14 (19%) 31 (43%)
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0 0 42 (30%) 33 (23%) 52 (37%) 15 (10%)
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Smoking Diabetes mellitus Hypertension Dyslipidemia Family history CAD No risk factors
n=72 (34%) 43.1
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Total Cohort n=214 Age (yr)
NPDT
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PDT - predischarge testing, NPDT - no predischarge testing, CAD - coronary artery disease
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Table 2. Exercise treadmill test or stress imaging test Total PDT (n=142) 102 (72%)
Positive PDT (n=14) 12 (12%)
Dobutamine stress echo
22 (15%)
2(9%)
Myocardial perfusion scintigraphy
18 (13%)
0 (0%)
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Initial Test Exercise treadmill
PDT - predischarge test
ACCEPTED MANUSCRIPT UNIVERSITY OF CALIFORNIA, DAVIS BERKELEY ● DAVIS ● IRVINE ● LOS ANGELES ● MERCED ● RIVERSIDE ● SAN DIEGO ● SAN FRANCISCO
UC DAVIS MEDICAL CENTER DIVISION OF CARDIOVASCULAR MEDICINE 4860 Y STREET, SUITE 2820 SACRAMENTO, CA 95817 Phone (916) 734-3764 Fax (916) 734-8394
● SANTA BARBARA ● SANTA CRUZ
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SCHOOL OF MEDICINE
Longterm Prognosis of Low Risk Women Presenting to the Emergency
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Department with Chest Pain
MD, Ezra A Amsterdam MD
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Moneer Eddin MD, Sandhya Venugopal MD MHPE, Brittany Chatterton MD, Angela Thinda
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Clinical significance of your manuscript: “Take Home” Points
1) The risk of missing acute coronary syndrome is increased in women presenting to the ED with chest pain.
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2) Longterm (5 year) prognosis of low risk women presenting to the ED with chest pain is excellent.
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3) Omission of predischarge cardiac testing in low risk women presenting with chest pain is safe, accurate and decreases length of stay.