Article, Cardiology

Young patients with chest pain: 1-year outcomes

Original Contribution

Young patients with chest pain: 1-year outcomes

Mark J. Collin BA, Benjamin Weisenthal, Kristy M. Walsh BS,

Christine M. McCusker RN, BSN, Frances S. Shofer PhD, Judd E. Hollander MD?

Department of Emergency Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104-4283, USA

Received 31 August 2009; revised 23 September 2009; accepted 24 September 2009

Abstract

Objective: Prior studies found that young adult chest pain patients without known cardiac disease with either no cardiac risk factors or a normal electrocardiogram (ECG) are at low risk (b1%) for acute coronary syndromes and 30-day cardiovascular events. Longer-term event rates in this subset of patients are unknown. We hypothesized that patients younger than 40 years without past cardiac history and a normal ECG are at less than 1% risk for 1-year adverse cardiovascular events.

Methods: We conducted a prospective cohort study in an urban university emergency department evaluating patients younger than 40 years who received an ECG for evaluation of potential ACS. cocaine users, cancer patients, and patients with a history of myocardial infarction or revascularization were excluded. Structured data collection at presentation included demographics, chest pain description, history, laboratory results, and ECG data. Hospital course was followed. Follow-up was obtained by telephone, record review, and social security death index search. Our main outcome was 1-year adverse cardiovascular events (death; acute myocardial infarction [AMI]; or revascularization–percutaneous coronary intervention [PCI] or coronary artery bypass graft). Descriptive statistics and 95% confidence intervals were used.

Results: Of 3846 chest pain patients, 609 met criteria. Of those, 35.5% were admitted. Patients had a mean age of 34.8 years (SD, 3.8 years). They were most often female (57.6%) and black (69.5%). There were 7 patients (1.1%; 95% CI, 0.5%-2.4%) with adverse cardiovascular events over the year. Of the subset of 560 patients with a normal/nonspecific ECG, there were 2 deaths (0.4%), 3 AMI (0.5%), and 2 PCIs (0.4%) by 1 year for a composite adverse cardiovascular event rate of 6 (1.1%; 95% CI, 0.4%-2.3%). Of the subset of 269 patients with no cardiac risk factors and a normal/nonspecific ECG, there were no deaths, 1 AMI, and 1 PCI for a composite adverse cardiovascular event rate at 1 year of 0.3% (0.01%-2.1%). The addition of an initial cardiac marker to this group resulted in a cohort that was event-free at 1 year (95% CI, 0%-1.4%).

Conclusions: Patients younger than 40 years without a cardiac history who present to the ED with symptoms consistent with ACS but have either no risk factors or a normal or nonspecific ECG have a very low rate of adverse events during the subsequent year.

(C) 2011

Introduction

* Corresponding author. Department of Emergency Medicine, Univer- sity of Pennsylvania, Philadelphia, PA 19104-4283, USA. Tel.: +1 215 662 2767; fax: +1 215 662 3953.

E-mail address: [email protected] (J.E. Hollander).

Chest pain is the second most common presenting complaint to the emergency department (ED) [1]. It accounts for approximately 8 million ED visits, but only 500 000 to 1 200 000 of these patients are ultimately diagnosed with acute myocardial infarction (AMI) [2,3]. Of all ED patients with

0735-6757/$ – see front matter (C) 2011 doi:10.1016/j.ajem.2009.09.031

chest pain, 14% are patients younger than 40 years [4,5], yet patients younger than 40 years account for only 4% to 8% of the AMIs each year [4-6]. Young patients with AMI have different demographic characteristics and risk factors, more equivocal results on provocative testing, less severe coronary artery disease, and better cardiovascular outcomes relative to older patients with AMI [2,3,7-16]. The distinctive char- acteristics of AMI in patients younger than 40 years suggest the approach to these patients should differ than the approach to old patients with similar symptoms.

Walker et al [17] described the characteristics and outcomes of young adult patients with chest pain and defined 2 low-risk groups. Patients without a cardiac history who had a normal electrocardiogram (ECG) and patients without a cardiac history who had no cardiac risk factors were both at less than 1% risk of 30-day adverse events [17]. Marsan et al [18] found that the addition of an initial set of normal cardiac markers to the rule described by Walker reduced the risk of ACS or adverse cardiovascular events at 30 days to less than 0.2%. Christenson et al [19] developed the “Vancouver Rule” for rapid discharge of ED patients with chest pain. According to this rule, patients younger than 40 years with a normal ECG and no history of myocardial infarction, angina, or Nitrate use can be discharged for outpatient follow-up with their primary care provider without additional cardiac testing. However, there are no data on the long-term cardiovascular outcomes of these young patients. The purpose of this study was to evaluate the 1-year adverse cardiovascular outcomes of young adult patients with chest pain.

Methods

Study design

We conducted a prospective, observational study evalu- ating 1-year adverse cardiovascular events (death, AMI, percutaneous intervention [including angioplasty, stents, and coronary artery bypass graft]) of ED patients younger than 40 years who received an ECG for evaluation of potential ACS. The study was approved by the local institutional review board.

Study setting

The study was performed in the ED of the Hospital of the University of Pennsylvania in Philadelphia between 2003 and 2007. The ED has approximately 57 000 adult patient visits per year.

Participants

All ED patients with chest pain were screened for study eligibility. Patients were included if their age was less than

40 years and they had an ECG performed for evaluation of potential ACS. Patients were excluded if they self-reported or tested positive for cocaine use because these patients are managed differently than other young patients with chest pain [20]. Patients were also excluded if they had a history of coronary artery disease, congestive heart failure, myocardial infarction, or revascularization or they had cancer that would limit Life expectancy to less than 1 year.

Study protocol

Patients were identified by trained research assistants and a standardized data collection form was completed by the treating physician at the time of the ED evaluation. Data collected included demographics, cardiac risk factors (hypertension, elevated cholesterol level, Tobacco use, diabetes mellitus, and family history of premature coronary artery disease), cocaine use, and cardiac history. The duration, location, quality, and radiation of the pain and the presence or absence of associated symptoms were recorded. The recorded physical examination included the initial vital signs and the presence or absence of jugular venous distention, rales, or S4 heart sound. The decision to discharge from the ED or to admit the patient was based on the treating physician’s standard clinical evaluation. At the time of the initial ED evaluation, the treating physician categorized the ECG into 1 of 7 categories: (1) normal–no evidence for ischemia; (2) nonspecific–abnormal T-wave axis in lead III, atrial fibrillation/flutter, nonspecific ST/T- wave changes; (3) early repolarization–early repolariza- tion changes without any other abnormalities; (4) abnormal but not diagnostic of ischemia–prolonged PR, QRS, QTc intervals, bundle-branch blocks, left ventricular hypertro- phy with strain, nonspecific intraventricular conduction delays, or nonspecific ST/T-wave changes not meeting the definition of ischemia; (5) ischemia (old, unchanged ECG)–ST depression more than 0.1 mV measured 80 milliseconds from the J point, inverted T waves more than

0.3 mV, or Q waves at least 30 milliseconds but without any change from the prior ECG; (6) ischemia (not known to be old)–ST depression more than 0.1 mV measured 80 milliseconds from the J point, inverted T waves more than

0.3 mV, or Q waves at least 30 milliseconds but no prior ECG available or different from old ECG; and (7) suggestive of myocardial infarction–ST elevation more than 0.1 mV measured 80 milliseconds from the J point in 2 or more contiguous leads, with or without reciprocal ST depressions. The need for cardiac markers was left to the judgment of the physician caring for the patient. During the study period, the department used both creatine kinase-MB and second-generation cardiac troponin I. The hospital course was reviewed by trained chart abstractors at the end of the ED or hospital stay. Results of tests assessing adverse cardiovascular events defined as AMI, percutaneous intervention, and death were recorded as well as final diagnosis.

Definitions

An AMI was considered to occur if the patient had prolonged chest pain and either elevation of cardiac markers or Standard ECG evolution of AMI. A normal cardiac biomarker was defined as a cardiac troponin I level of less than 0.4 ng/mL [17,18]. Normal ECG was defined as normal, nonspecific, or early repolarization only. One-year adverse cardiovascular events were defined as all-cause mortality, AMI, or revascularization.

Follow-up

At the time of index visit, we recorded patient home, work, cell and family member phone numbers. At the time follow-up contact commenced, we used the following sequence of procedures: calling the patient at all patient contact numbers during the day, evening, and weekend; calling the proxy or family member at the contact number provided; reviewing the medical records for our institution and the closest hospital; searching the social security death index. The death index search was done at least 2 years after index visit to allow more than recommended time for the event to be recorded.

Data Analysis

For patients who presented more than once during the study period, only the initial ED visit was used for analysis.

Table 1 Demographics and risk factors of study population

n %

Sex

Male 258 42

Female 351 58

Age (y)

Younger than 25 14 2

25-29 35 6

30-34 237 39

35-39 323 53

Race

Asian 11 2

Black 423 69

Hispanic 14 2

White 156 26

Other 5 1

Cardiac risk factors

Tobacco use 157 26

Hypertension 157 26

Family history of early CAD 62 10

Hypercholesterolemia 51 8

Diabetes mellitus 48 8

No. of cardiac risk factors

None 288 47

1 211 35

2 75 12

N2 35 6

CAD indicates coronary artery disease.

n %

Location of chest pain

Mid chest 275 45

Left arm/left chest 220 36

Right chest 45 7

Epigastrium 13 2

Other/unknown 56 9

Quality

Pressure/tightness/crushing 234 38

Stabbing 184 30

Aching 74 12

Burning 37 6

Tearing 5 1

Other/unknown 75 12

radiation of pain

Left arm 105 17

Neck 34 6

Back 61 10

Right arm 37 6

Other 19 3

Associated symptoms

Shortness of breath 275 45

Diaphoresis 87 14

Nausea 110 18

Vomiting 48 8

Lightheadedness 97 16

Syncope 16 3

Palpitations 81 13

Data are summarized and presented as frequency and percentage of occurrence. Main outcomes are reported with 95% confidence intervals (CIs).

Table 2 Chest pain characteristics

Results

Of 3846 total chest pain visits with ECG performed, there were 722 First visits by young patients. After excluding the 59 patients who used cocaine, 3 patients with cancer, and 51 patients with cardiac medical history, 609 patients met the criteria. These patients comprised the study group. Direct follow-up to confirm presence or absence of events was accomplished in 77%. For the other 23%, no events were documented in the medical records nor were the patients deceased per the social security death index. Most patients were female and black (Table 1). Approximately one third of the patient visits (217; 35.6%) resulted in hospital admission. Approximate- ly one third of the patients presented with features of typical ischemic chest pain (Table 2). Shortness of breath was the most common associated symptom (45%) followed by nausea (18%), lightheadedness (16%), and diaphoresis (14%). For 89% of patients, the ECG was normal or nonspecific (Table 3).

n % (95% CI)

No cardiac history with a normal ECG (n = 560)

All-cause mortality 2 0.4 (0.04-1.3)

AMI 3 0.5 (0.1-1.6)

Percutaneous intervention 2 0.4 (0.04-1.3)

Composite cardiovascular events 6 1.1 (0.4-2.3) No cardiac history or cardiac risk factors (n = 288)

All-cause mortality 0 0 (0-1.3)

AMI 1 0.3 (0.01-1.9)

Percutaneous intervention 1 0.3 (0.01-1.9)

Composite cardiovascular events 1 0.3 (0.01-1.9)

No cardiac history or cardiac risk factors, and a normal ECG (n = 269)

All-cause mortality 0 0 (0-1.4)

AMI 1 0.4 (0.01-2.1)

Percutaneous intervention 1 0.4 (0.01-2.1)

Composite cardiovascular events 1 0.4 (0.01-2.1)

No cardiac history, cardiac risk factors, a normal ECG, and initially normal cardiac markers (n = 268)

All-cause mortality 0 0 (0-1.4)

AMI 0 0 (0-1.4)

Percutaneous intervention 0 0 (0-1.4)

Composite cardiovascular events 0 0 (0-1.4)

During the index visit, 7 patients (1.1%; 95% CI, 0.5%- 2.4%) had adverse cardiovascular events. There were 4 AMI (0.7%), 2 percutaneous interventions (0.3%), and 2

Table 3 Electrocardiogram interpretation for whole study population

Table 4 One-year adverse cardiovascular event rates for the prespecified subgroups

n %

Interpretation for ischemia a

Normal 427 70

Nonspecific 117 19

Early repolarization only 15 2

Abnormal but not diagnostic 28 5

Ischemia (known to be old) 3 b1

Ischemia (not known to be old) 14 2

Suggestive of AMI 4 b1 ST elevation

None 580 95

1-2 mm 26 4

N2 mm 2 b1

ST depression

None 592 97

0.5-1 mm 12 2

1-2 mm 4 b1

T-wave inversion

None 521 86

Flattening 41 7

1-5 mm 45 7

N5 mm 1 b1

Hyperacute T waves N5 mm 6 1

Pathologic Q-waves 11 2

right bundle-branch block 9 1

Left bundle-branch block 3 b1

a One was unavailable for review.

deaths (0.3%).

Of the 609 enrolled patients, 560 patients had a normal or nonspecific ECG. In this subgroup, there were 3 AMI (0.5%) and 1 percutaneous intervention (0.2%) during the index visit (Table 4). There were 2 deaths (0.4%), no AMI, and 1 (0.2%) percutaneous intervention during 1-year follow-up period. The composite risk of 1-year adverse cardiovascular events was 1.1% (95% CI, 0.4%-2.3%). One of the 49 patients included in the study but not meeting criteria for this subgroup sustained an AMI and received a PCI.

In the subgroup of 288 patients with a normal or nonspecific ECG who had no cardiac risk factors, there was 1 AMI patient who also received PCI (0.3%) during the index visit. No additional events were reported by 1 year. The composite risk of 1-year adverse cardiovascular events was therefore 0.3% (95% CI, 0.01%-1.9%).

There were 269 patients with no cardiac risk factors and a normal or nonspecific ECG. The patient noted above still remained within the subset. Thus, this subset of patients had

1 AMI (0.4%) and 1 percutaneous intervention (0.4%) during the index visit. No cases of AMI, percutaneous intervention, or death were reported at 1-year follow-up, for an overall 1-year adverse cardiovascular event rate of 0.4%

(95% CI, 0.01%-2.1%). The addition of initially normal cardiac markers, as suggested by Marsan et al [18], to this last subgroup would have identified all patients with adverse cardiovascular events. The group of patients without a cardiac history or cardiac risk factors who had a normal or nonspecific ECG and had an initially normal cardiac marker had no adverse cardiovascular events within 1 year (95% CI, 0%-1.4%).

Discussion

Most research on risk stratification of patients with chest pain has centered on patients older than 40 years as they are the age group predominantly affected by coronary artery disease [6,21,22]. Well-accepted chest pain risk stratification schemes such as the Thrombolysis In Myocardial Infarction score found that patients older than 65 years are at increased risk but did not address patients younger than 40 years.

Two previous studies focused on the clinical character- istics and 30-day outcomes of patients younger than 40 years and defined a subset of patients at less than 1% risk for adverse cardiovascular events [17,18]. The “Vancouver Rule” also found that patients younger than 40 years, with a normal ECG and no history of myocardial infarction, angina, or nitrate use, reduced the need for additional cardiac testing [20]. Our study extends all these results to 1 year, suggesting that patients younger than 40 years are at extremely low risk of adverse cardiovascular events, and

therefore, those patients who meet the specified criteria may be a candidate for discharge from the ED. The extension of the 30-day results to 1 year is particularly important in this era of Uninsured patients where follow-up and outpatient testing for possible coronary disease are not guaranteed.

Overall, the 1-year adverse cardiovascular event rate for the entire cohort was 1.1%. This is consistent with the rates of 2.1% and 2.2% found in the prior studies [17,18]. Our 1- year survival rate of 99.7% was consistent with the 98% 3- year survival rate found in the subset of patients 30 to 39 years old studied by Lee et al [23], the 99.2% 30-day survival found by Walker et al [17], and the 99.6% 30-day survival found by Marsan et al [18].

We found that in the subgroup of patients, defined by Walker et al [17], with a normal ECG who did not have a known cardiac history, the 1-year adverse cardiovascular event rate was 1.1%. The subgroup of young adults with no cardiac history and no risk factors for coronary artery disease had a 1-year adverse cardiovascular event rate of 0.3%. The addition of initial ECG findings did not identify the patient who had AMI. However, the addition of one set of negative cardiac markers correctly identified all patients with adverse cardiovascular events. Therefore, in patients with a normal or nonspecific ECG, no cardiac history, no cardiac risk factors, and initially normal cardiac markers (n = 268), the risk of adverse cardiovascular events was 0% (95% CI, 0%-1.4%). Analysis of the cohort suggested by Marsan et al [18], which is patients without a cardiac history, either no classic cardiac risk factors or a normal ECG, had a 1-year cardiovascular event rate of 1.0%. Adding a negative initial set of cardiac markers, there was 0.9% risk of adverse cardiovascular events at 1 year. Of the 7 patients with adverse cardiovascular events by 1 year, 6 had cardiac risk factors, 1 had an Abnormal ECG, and 2 had initially elevated cardiac Troponin I levels. The addition of normal initial cardiac biomarkers was helpful in these algorithms. Use of these rules could identify a cohort of patients who may be candidates for discharge with a risk of less than 1% for 1- year adverse cardiovascular events, limiting unnecessary

hospital admissions.

Limitations

There are some limitations to this study that need to be addressed. All patients with chest pain that prompted an ECG were included in analysis. Broad inclusion criteria were selected to make the study more generalizable. Cocaine users were excluded because this population has been addressed in other studies and the approach to cocaine chest pain may differ from the approach to other young patients with chest pain [20,24,25]. We relied on Self-reported use and optional urine screening at the physician’s discretion to exclude these patients. Some patients who did not self-report use and did not receive

urine screening may have been included in the study. This would bias the study toward having higher Adverse event rates. Cardiac risk factors were recorded based on self- reporting of the patient to the treating physician. As the patients are young, some cardiac risk factors such as diabetes mellitus or hypercholesterolemia may be present but have never been diagnosed and therefore are unknown to the patient. Again, this would likely bias our results toward a higher event rate. The use of all-cause mortality as an adverse cardiovascular outcome may have included patients who died of nonCardiovascular causes. This would have led to a higher rate of composite adverse cardiovas- cular events. This study was only conducted at a single urban institution, and our predominant patient population is female and black. Therefore, although this demographic is representative of our patient population, it is hard to be sure if this is generalizable to other settings and other groups of patients who may have different thresholds for presenting to the ED.

In conclusion, we found that adults younger than 40 years with chest pain with no known cardiac history, and either no classic cardiac risk factors or a normal ECG, had a less than 1% risk of 1-year adverse cardiovascular events. The addition of a negative set of cardiac markers at the time of ED arrival reduced the risk of 1-year cardiovascular outcomes even further. In young patients without a known cardiac history, either no classic cardiac risk factors or a normal ECG, and initially normal cardiac marker studies, the risk of adverse cardiovascular events was less than 1%, although it should be noted that the upper limit of the CI was greater than 1%. We believe that this decision rule, if validated, could be used to refer a cohort of young patients for outPatient evaluation of their chest pain, limiting unnecessary hospital admissions.

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