Chest Pain in Repeated Emergency Department Visitors

Chest pain is the leading symptom in 5 to 8% of all emergency department (ED) visits [1-3] and is also one of the major reasons of repeated ED visits, causing around 6% of these cases [1]. Generally, in 15 to 25% of patients with chest pain, acute myocardial infarction (AMI) is the underlying cause [4-6]. International literature describes an all-population based, one-month mortality rate of AMI between 8 to 24% [7,8] and an all-population based, one-year mortality rate of 19% [9]. Therefore, AMI has to be diagnosed or ruled out quickly. For this purpose, a fast clinical assessment including cardiac biomarker testing and the rapid execution of an electrocardiogram (ECG) are necessary. Based on the leading symptoms and clinical presentation, ECG-findings and in combination Abstract

with elevated troponin levels, AMI can be defined as either a ST-segment elevation myocardial infarction (STEMI) or a non-ST-segment myocardial infarction (NSTEMI) [10]. In contrast, there are many other possible reasons for patients to present with chest pain, such as gastro-oesophageal, other cardiac or cardiovascular, neurological, psychological, or musculoskeletal causes [11].
There is no standardized definition of a "repeated ED visitor" in the literature. There is quite a wide range in the number of annual ED visits used for this definition [1,12,[20][21][22][23][24][25][26][27][28][29][30][31], of which the definition of ≥ 4 visits/year is the most common one [21,[31][32][33]. In our study, we defined a patient with four or more visits to the ED due to chest pain to be a "repeated" visitor. With regards to chest pain, studies have shown in general that chest pain patients tend to be in their mid-fifties [34,35], whereas patients with low risk for AMI are on average much younger [36] compared to high-risk patients [37]. In regard to the distribution of gender, study results vary [36][37][38]. Hospital admission rate for chest pain patients is between 19% and 27% [3,12]. Furthermore, anxiety has been shown to be associated with an increased risk of (repeated) ED visits in patients with low risk chest pain [39,40].
However, none of the reviewed literature investigated the rate of AMI in the subgroup of repeated ED visitors. Many studies have focused on the number of ED visits due to chest pain as an outcome [25,34,[41][42][43][44][45][46][47][48][49][50] in the general ED population and have not focused on the subgroup of repeated patients. Furthermore, almost all of the reviewed studies had important exclusion criteria, e.g. specific age limits [51], AMI on index ED visit [43], too many return ED visits [38], language barriers [50] or a known history of coronary artery disease (CAD) [52]. Even though many of these studies investigated the prevalence of AMI [53][54][55][56][57], only a few did so after a one-year follow-up [58,59].
To our knowledge, no data about chest pain in repeated ED visitors are available for Switzerland. Therefore, the aim of this current study was to determine the prevalence of AMI in patients who visited the ED due to chest pain more than once and to evaluate the aetiology of chest pain in those ED patients.

Materials and Methods
The University Hospital Zurich (UHZ)) is a tertiary referral hospital and is one of the biggest hospitals in Switzerland. The UHZ is affiliated to the University of Zurich. The ED of the UHZ offers the whole range of emergency medicine service and treated currently 45,000 adult patients in 2018.
We performed a retrospective study enrolling patients who presented with chest pain as a leading symptom and visited the ED of the UHZ at least twice between January 1st and December 31 st , 2015.
We excluded all patients who visited the ED only once due to chest pain in 2015. Additionally, all patients younger than 18 years old were excluded.
The study was approved by the ethic committee of canton Zurich, Switzerland (BASEC N° Req-2016-00195).

Definitions
We grouped the study population with recurrent chest pain into a group of patients who visited the ED two or three times (control group) and into one group of patients visiting the ED four times or more, which we defined as "repeated" ED visitors.

Endpoints
The first endpoint was to investigate the prevalence of AMI in ED patients who visited the ED due to the leading symptom "chest pain" at least four times during a one-year period (repeated visitors). Secondarily, we investigated whether an AMI had been correctly diagnosed in these repeated ED visits. Furthermore, we evaluated reasons of chest pain other than AMI.

Baseline parameters
In addition to the defined endpoints, we extracted the following parameters from the clinical information system: age, gender, medical history and cardiovascular risk-profile (e.g. smoking, diabetes, dyslipidaemia, obesity, history of cerebrovascular insult (CVI) or CAD, positive family history for CAD/AMI).
All patients presenting to the ED of the USZ are triaged with the Emergency Severity Index (ESI) [60][61][62][63] which is defining the urgency of symptoms, acuity and resource needs from a grade 1 (life-threatening) to 5 (least urgent, needing no resource). The ESI triage levels are described in the baseline parameters.
Baseline parameters also include rates of transport by paramedics, time presenting in the ED (day-, mid-, or nightshift), as well as all methods of diagnostics used in the ED (troponin levels, ECG, focused echocardiogram) and during hospital admission (tests for cardiac ischemia e.g. stress-testing, coronary-CT and cardiovascular interventions, e.g. stenting or bypass surgery). Furthermore, we investigated what kind of diagnostics such as stress testing or imaging and interventions they had received in previous visits. In addition, outcome parameters such as the need for a hospital admission or J Clin Cardiol. 2019 Volume 1, Issue 1 treatment in special care units, the need for intubation or cardiopulmonary resuscitation were recorded.

Statistics
First, a descriptive analysis of the entire patient population was performed. We expressed the distribution of variables using means and standard deviation (SD) for normally distributed data, and medians and interquartile ranges (IQR) for non-normally distributed data. We tested the data for normality with the Kolmogorov-Smirnov test and performed quantile-quantile plots.
The first endpoint (AMI) was reported as a frequency in percentage. Further secondary endpoints such as other reasons for chest pain were also reported as frequencies (%).
All statistical analyses were performed using STATA software (version 15, Stata Corp., College Station, Texas).

Results
At the ED of the UHZ, 27,998 patients accounted for 33,335 ED visits in 2015 due to a medical problem. Of these, 128 consecutive patients with at least two ED visits due to chest pain were included. These 128 patients (0.5% of the total ED patient population in 2015) accounted for 311 ED visits (0.9% of all ED visits).
Out of the 128 enrolled patients, 116 (90.6%) visited the ED two or three times due to chest pain (control group) and accounted for 252 (81%) of the total 311 ED visits. The remaining 12 patients (9.4%) had four or more ED visits due to chest pain (repeated group) and were responsible for 59 (19%) of the 311 ED visits. Table 1 shows the patients' characteristics of the entire chest pain patient population as well as grouped by the control and the repeated group. Compared to the control group, repeated chest pain ED visitors (≥ 4 annual ED visits) tended to be younger (50.3 vs. 59.4 years), of male gender (67.7% vs. 57.8%) and suffered less often from coronary heart diseases (16.7% vs. 44%) or diabetes (8.3% vs. 28.4%). A positive family history for heart disease was present in every fourth of the repeated chest pain group compared to 44.8% in the control group. The repeated chest pain ED visitors in turn had higher rates of arterial hypertensions (66.7% vs. 59.5%) and psychosomatic disorders (75% vs. 26.7%).

Causes and severity of chest pain
Out of all the 311 ED visits caused by these 128 patients, 111 visits (35.7%) were due to cardiac disorders, 104 visits (33.4%) were due to musculoskeletal and/or rheumatological disorders and 45 visits (14.5%) were due to psychosomatic disorders ( As shown in Table 2, ED visits made by repeated chest pain ED visitors were less likely to have an underlying cardiac (18.6% vs. 39.7%) or musculoskeletal/ rheumatologic disorder (28.8% vs. 34.5%) but were more likely to have a psychosomatic disorder (33.9% vs. 9.9%) as a cause.
Cardiac causes for chest pain varied between the two groups: in the repeated group, these ED visits were either caused by a hypertensive crisis (6 visits; 54.5%) or cardiac arrhythmias (5 visits; 45.5%); none was due to a myocardial infarction. In the control group, most frequent cardiac causes for ED visits due to chest pain were myocardial infarction (23%), hypertensive crisis (22%), arrhythmia (19%) and cardiac decompensation (17%).
Sixty-eight (21.9%) of the 311 ED visitors arrived by emergency medical services. All chest pain ED patients were assessed upon arrival using the ESI. In both study groups, patients were mostly triaged as ESI 3 ( Table 2).

Incidence of acute myocardial infarction
AMI was diagnosed in 23 of the 311 individual ED visits due to chest pain (7.4%).
The incidence for having an AMI during an ED visit after 4 Chronic kidney failure, n (%) 31  All results were reported as mean (standard deviation) or median (25 th -75 th percentile) ED: Emergency Department; BMI: Body Mass index and musculoskeletal disorder (occurring twice).
Outcome Table 4 presents outcome parameters of the individual ED visits. On average, repeated chest pain ED visitors spent 60 minutes less in the ED (219 vs. 279.5 minutes), but waited similarly until they were seen by an emergency physician (12.5 vs. 7 minutes). Repeated chest pain ED visitors were less likely to be admitted to the hospital (15.3% vs. 41.7%). All 39 in-house admissions to special care units occurred in the control group. One repeated chest pain ED visitor had to be intubated for cardioversion; no cardiopulmonary resuscitation was necessary in either group. Table 5a shows diagnostic tests done during the ED stay. ED: Emergency Department; ESI: Emergency Severity Index * defined as Atrial Fibrillation (AF), Atrial Flutter (AFL) and tachycardia

Discussion
In this study, the overall prevalence of AMI was 7.4%, but no AMI occurred in repeated ED visitors with chest pain. The repeated chest pain ED visitor tended to be male, around 50 years old and suffered mostly from psychosomatic or musculoskeletal disorders, followed by hypertensive crisis or arrhythmia that were the only cardiovascular etiologies for chest pain. The overall risk of having an AMI after the index ED visit was 2.2% in the entire study population whereas it was 0% for the repeated ED visitors.
None of the reviewed articles has specifically analysed the AMI rate in repeated ED visitors with chest pain. Our results are novel, and we used the rate of AMI during a defined follow-up period after an index ED visit due to chest pain as a reference. The periods of follow-up have been individually set in each study, for example 30 days [43] or up to 180 days [64]. The risk of having an AMI in low-risk patients with chest pain during follow-up visits ranges from 0 to 0.4% while follow-up periods varied    In the current study, the overall prevalence of AMI (7.4%) in chest pain patients was lower compared to the range (15-25%) described in the literature [4][5][6]. This can be mostly explained by the restrictive inclusion criteria and focus on the subgroup of recurrent ED patients for this current study. Additionally, it is partly explained by the Swiss Health Care System. In case of an acute event, e.g. a STEMI, timely diagnostics and therapy are standardized in Switzerland according to the European Society of Cardiology guidelines [67]. The difference to other countries is that Swiss patients, when suffering from stable chest pain, have a wider and faster access to elective cardiac diagnostic tests and may receive earlier interventions (e.g. stenting) if needed. Thus, underlying coronary artery diseases are excluded by advanced and early accessible diagnostic tests. Almost 20% of the control group experienced an AMI. Most of the AMIs (19 of 23) occurred during the first ED visit and patients immediately received a coronary angiography for therapy of coronary ischemia. This rate is clearly lower compared to the literature about AMI due to cardiac causes of chest pain (40-60%) and reflects the wide and fast availability of elective cardiac diagnostic tests in Switzerland in stable patients [68].
While only four of all 23 cases of AMI occurred during a secondary ED visit, one may argue clear warning signs could have been missed during the index ED visit. Schull et al. reported a similar rate of missed AMI (2%) in chest pain patients discharged from the ED [69]. They defined an AMI as "missed", if a patient with AMI had had a previous ED visit up to 7 days before the incident or if an alternative ED discharge diagnosis had been determined masking the AMI due to typical or atypical presentations (e.g. "angina", "abdominal pain", "gastritis", "syncope", "shortness of breath") or the patient was not admitted to the hospital [69]. In our study, all four patients with an AMI during the second ED visit had had a complete and negative diagnostic ischemia testing done on the index visit. Furthermore, these AMIs occurred within 8 to 222 days after the index ED visit. Therefore, one can argue that no case of AMI was missed during the index ED visit in this current study population.
Interestingly, only few of the reviewed articles have analysed non-ischemic causes of chest pain in repeated ED visitors [39,66,[68][69][70]. Generally, 20-60% of chest pain is of non-cardiac origins [70]. 50-90% of patients with non-cardiac chest pain show mainly symptoms of gastrooesophageal reflux and 5-30% of musculoskeletal problems [71]. In our study, non-cardiac disorders were the cause for chest pain in more than 60% of all ED visits. Our analysis showed that chest pain was caused in a third of all repeated ED visits by a psychosomatic origin. Identically to our study, anxiety was shown to be one of the main reasons for repeated ED visits in patients with low-risk chest pain [39]. Furthermore, the current study showed a cardiac cause for chest pain in about 20% of repeated ED visits. However, none of these visits were due to cardiac ischemia, but due to hypertensive crisis or cardiac arrhythmias. These results are similar to the literature which shows that all nonischemic cardiac causes are responsible for 10 to 20% of chest pain cases [68,72]. Common causes of non-ischemic cardiac chest pain in the literature were aortic dissection, acute pericarditis, heart failure, mitral valve prolapse and post-stent insertion chest pain [72]. However, chest pain was not a common symptom of hypertensive crisis [73]. No studies were found that primarily investigated cardiac arrhythmias as the specific cause of chest pain.
In our study, patients of the repeated group had a lower number of troponin-T testing performed at ED admission when compared to the control group. No data in the literature are available on investigating the rates of troponin-T-testing in chest pain patients. Therefore, a comparison of our results with the literature was not possible. In twelve of the 59 repeated ED visits (20.3%) no testing of troponin-T levels was performed. These 12 visits were performed by seven patients of the repeated group. Five of these seven patients had a known psychosomatic disorder without any other cardiovascular diseases or risk factors and therefore, a troponin-T testing was not indicated. Patients' age also seemed to be a relevant factor. The younger the patient, the less likely a testing of troponin-T levels was performed. Five of the 12 visits were performed by patients younger than 30 years of age. Final reasons for chest pain in these 12 visits in the repeated group were musculoskeletal disorders (five visits), psychosomatic disorders (three visits), hypertensive crisis (one visit), cardiac arrhythmia (one visit), gastroesophageal reflux (one visit) and respiratory infection (one visit). Furthermore, in nine of these 12 visits, an ECG was performed without any signs of cardiac ischemia. All three visits in which no ECG was performed were made by one patient with chest pain. This was a 20-year-old man who had suffered from a pneumothorax the year before. In each of his ED re-visits, the cause of the chest pain was of musculoskeletal etiology.
In only 17 of the 252 ED visits performed by the control group, no testing of troponin-T levels was performed (6.7%). This higher performance of the troponin-T tests in the control group was mostly due to sicker patients suffering more frequently from cardiovascular risk factors and needing therefore more often a troponin-T testing. However, these 17 visits that did not receive troponin-T testing showed similar characteristics compared to the repeated group. Hence, the factor age also seemed to be a relevant indicator: five and nine of these 17 ED visits were performed by patients aged ≤ 30 years and ≤ 40 years respectively. Nine visits were due to musculoskeletal, four to psychosomatic, two to hypertensive crisis, one to gastrointestinal and one to pulmonary disorders. While in 13 of these 17 visits, an ECG was performed (all with normal findings). In these four visits without an ECG, patients' age varied from 26 to 74 years and musculoskeletal or psychosomatic disorders (twice each) were found to be the causes for chest pain.
No data were found in the literature investigating the rate of in-hospital ischemia testing in repeated ED patients with chest pain. In two of the nine repeated ED patients who were admitted to the hospital, a cardiac ischemia testing (coronary angiography and stress-testing once each) was performed during the hospital stay. Both patients were male and had a known history of two-vessel cardiac artery disease (CAD). They were 47 and 64 years old, had normal ECGs and troponin-T levels and had a final diagnosis of hypertensive crisis and psychosomatic disorder respectively. These two patients were the only ones with a known history of CAD in the repeated group. In the remaining seven admitted cases in which no inhospital cardiac ischemia testing was performed, the final reasons for chest pain were pulmonary embolism, atrial fibrillation, supraventricular tachycardia (once each) and thoracic pain syndrome (four times). During all of these visits, a negative ECG had been performed and the levels of troponin-T were always negative with the exception of a slight elevation in the case of atrial fibrillation.

Strengths and Limitations
One of the strengths of this study is its low selection bias within the repeated chest pain patients with the only exclusion criteria being under 18 years of age and having less than two ED visits due to chest pain within one year. Since the USZ has an interventional cardiologist on call 24/7, many patients with chest pain were primarily assigned to the USZ by the paramedics. Therefore, the study sample is well represented and the results are generalizable.
A limitation is that this study is a single-centre-study. It is likely that recurrent ED visits to other nearby hospitals by these patients were not registered. Up to 58% of repeated ED patients are known to visit more than one ED [74]. Furthermore, as a result of the retrospective design, there is a possibility of incomplete data. However, since the cardiac workup was mostly done in-house, the data of the primary and secondary endpoints were complete.

Conclusions
No AMI in the repeated ED visitors presenting recurrently due to chest pain were missed. Chest pain in repeated ED visitors was mostly caused by psychological, musculoskeletal or rheumatologic disorders. If the cause was of cardiac origin, it was either due to hypertensive crisis or cardiac arrhythmia. Nevertheless, repeated ED visitors with chest pain must be seriously investigated each time at presentation and cardiac causes need to be excluded.