BMJ Open. Medical consumption compared for TIMI and HEART score chest pain patients at the emergency department

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1 BMJ Open Medical consumption compared for TIMI and HEART score chest pain patients at the emergency department Journal: BMJ Open Manuscript ID bmjopen-0-00 Article Type: Research Date Submitted by the Author: -Nov-0 Complete List of Authors: Nieuwets, Astrid; Maastricht University Poldervaart, Judith; Julius Center for Health Scienced and Primary Care, Reitsma, Johannes; University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care Buitendijk, Susanne; Gelderse vallei, Emergency medicine Six, Alfred; Zuwe Hofpoort Hospital, Cardiology Backus, Barbra; Medical Center the Hague Bronovo, Emergency medicine Hoes, Arno; Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht Doevendans, Pieter; University of Utrecht, The Netherlands <b>primary Subject Heading</b>: Health economics Secondary Subject Heading: Diagnostics, Cardiovascular medicine Keywords: Adult cardiology < CARDIOLOGY, Myocardial infarction < CARDIOLOGY, HEALTH ECONOMICS, Risk management < HEALTH SERVICES ADMINISTRATION & MANAGEMENT BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

2 Page of BMJ Open Medical consumption compared for TIMI and HEART score chest pain patients at the emergency department A Nieuwets a, JM Poldervaart b, JB Reitsma b, S Buitendijk c, AJ Six d, BE Backus e, AW Hoes b, PA Doevendans f a Maastricht University, Maastricht, The Netherlands b Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands c Department of Emergency Medicine, Gelderse vallei Hospital, Ede, The Netherlands d Department of Cardiology, Zuwe Hofpoort Hospital, Woerden, The Netherlands e Department of Emergency Medicine, Medical Center Haaglanden, Den Haag, The Netherlands f Department of Cardiology, University Medical Center, Utrecht, The Netherlands BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

3 BMJ Open Page of ABSTRACT Objective: We investigated which risk score (TIMI score or HEART score) identifies the largest population of low-risk patients at the emergency department (ED). Furthermore, we retrospectively calculated which score resulted in the largest decrease in medical consumption if patients would have been discharged from the ED. Methods: We performed analyses in two hospitals of the multicenter prospective validation study of the HEART score. Chest pain patients presenting to the ED were included and information was collected on major adverse cardiac events (MACE) and on hospital admissions and diagnostic procedures within weeks. The TIMI and HEART score were calculated. Results: We analysed 0 patients (% male, mean age of 0, cumulative incidence of MACE %). An estimated total of, was spent during follow-up on hospital admission and diagnostic procedures. (0%) patients had a HEART score of 0 to and were considered low-risk, a total of,0 was spent on diagnostic procedures and hospital admission after initial presentation in this group. In comparison, 0 (%) patients with TIMI score of 0 were considered low-risk, with a total of,0 spent on diagnostic procedures and initial hospital admission costs. Conclusions: The HEART score identifies more patients as low-risk compared to the TIMI score, which may lead to a larger reduction in diagnostic procedures and costs in this low-risk group. Future studies should prospectively investigate whether adhering to the HEART score in clinical practice and early discharge of low-risk patients is safe and leads to a reduction in medical consumption. Strengths: We focused on the low-risk patients, in whom the diagnostic dilemma for physicians lies. Reported MACE incidence in this study largely corresponds with existing literature. Limitations: Decision-making for performing diagnostics and admission was left up to the clinician. Possible selection bias. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

4 Page of BMJ Open BACKGROUND Each year, an estimated % of presentations at emergency departments (ED) are attributed to symptoms suspicious of acute coronary syndrome (ACS),. Of all these patients, the majority has chest pain due to non-cardiac causes and only -0% of patients have an ACS. Differentiating between low and high-risk patients for ACS remains a diagnostic challenge, since a normal electrocardiogram (ECG) and initially negative biomarkers do not exclude ACS. Therefore, the majority of low-risk patients are currently admitted to the hospital to undergo stress testing, regardless of low pre-test probability. However, often results of these performed tests are normal. The question remains whether this conservative approach leads to better clinical outcomes for patients and there is discussion on optimal management in patients who are deemed safe to discharge from the ED. Several risk stratification tools and prediction models have been developed over time. Currently, international cardiac guidelines recommend the use of a risk score for risk stratification. The current study investigates two of these risk scores, namely the TIMI score and the HEART score. Firstly, the Thrombosis In Myocardial Infarction (TIMI) risk score is used to stratify risk in chest pain patients admitted to the cardiac care unit (CCU) and can be used to predict 0-day outcomes of mortality, myocardial infarction (MI) and severe recurrent ischemia requiring urgent revascularization. The TIMI score is composed of elements as shown in Table. It is one of the two risk scores that are implemented in current international guidelines and well-known by most clinicians 0. Secondly, the HEART score was developed in 00 and has been validated to stratify the risk of short-term adverse cardiac events in chest pain patients at the ED. The HEART score is an acronym for History, ECG, Age, Risk factors and Troponin. These components can be rated 0, or points each and results in a total HEART score between 0 and 0, as shown in Table. It has been specifically developed for chest pain patients and previous prospective studies indicated the HEART score as valid for patient stratification. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

5 BMJ Open Page of Although both risk scores have been validated, they are mostly not yet actively used 0 ; that is, no policy decision is made based on the individual risk score of a patient. Furthermore, none of these previous studies mentioned secondary outcome measurements such as clinical course or medical consumption. A pilot study of patients by Six et al. analysed medical consumption of chest pain patients with a HEART score at the ED. It concluded that, if the HEART score would be routinely applied on chest pain patients, diagnostic pathways for low-risk patients could be shortened which could lead to cost reduction. However, these were small numbers in a small non-academic hospital. Our goal is to investigate the medical consumption in the low-risk TIMI and HEART score categories. Furthermore, we assessed which risk score is more efficient in identifying the largest number of low-risk patients, without compromising safety. METHODS Study population This is an additional analysis of 0 patients in two hospitals, using the data of a multicenter prospective validation study in 0 hospitals of the HEART score, which included a total of, patients between 00 and 00. The ethics committees of all participating hospitals approved the study. Since it was an observational study and patients received standard care, at that time informed consent procedures were waived. Patients were informed of the registration of data and the followup policy and data was processed anonymously. Any patient with acute chest pain admitted to the (cardiac) ED was eligible, regardless of age or pre-hospital suspicion. Patients with ST-elevation myocardial infarction (STEMI) were immediately taken to the coronary intervention room, and therefore excluded. Two hospitals were chosen for this sub analysis on diagnostic procedures as it was anticipated that for these hospitals patient information of sufficient quality would be available. The first is a general hospital with a large specialised cardiology department, the second an academic BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

6 Page of BMJ Open hospital. Both are intervention centres and perform percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG). Calculation of the TIMI and HEART score ED residents of participating hospitals were instructed to fill out the Case Record Form (CRF), which consisted of patient history, cardiovascular risk factors, medication, physical examination and past medical history. Laboratory results, including conventional Troponin I or T, and the admission ECG were added to the CRF. The ECG was blindly classified afterwards by independent, experienced cardiologists. The HEART score was developed in 00 and predicts the -week incidence of major adverse cardiac events (MACE), stratifying patients into a low-risk (HEART score 0-), intermediate-risk (-) and high-risk (-0) group. The incidence of MACE in the previous validation studies has been.% in low-risk patients,.% in intermediate-risk patients, and 0.% in high-risk patients. The classification into the different risk categories can be used to make a direct clinical decision for further patient evaluation. In the current study, the HEART score was calculated by the resident at the ED, without actively using the score for further management. Each of the elements in the HEART score were given 0, or points, resulting in a score between 0 and 0, see Table. The TIMI score was developed in 000 for prediction at the CCU for 0-day outcomes of mortality, myocardial infarction (MI) and severe recurrent ischemia requiring urgent revascularization, with the following occurrence rates:.% for TIMI 0/,.% for,.% for,.% for,.% for and 0.% for -. Only a TIMI score of 0 seems to identify patients to be safely discharged home from the ED without further testing 0. In the current study, an algorithm was devised to calculate for the TIMI score automatically from admission data, without interpretation by the investigators and blinded for the outcome. The score consists of elements, and each of the elements was given 0 or point, resulting a total score between 0 and, see Table. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

7 BMJ Open Page of Outcome measures -week occurrence of MACE Information on the primary outcome of MACE was already collected during the original study. The definition of MACE consisted of AMI, PCI, CABG, stenosis managed conservatively, and death due to any cause. The duration of follow-up was six weeks in all patients. The diagnosis of AMI was diagnosed by an adjudication committee according to the applicable guidelines at that time 0. Further information on definition and assessment of MACE can be found in the main publication. Occurrence of MACE in low-risk group Since we were particularly interested in the low-risk population, low-risk was defined as missed MACE in less than % of all patients with MACE in each total score. For the HEART score this resulted in a low-risk group of patients with a score from 0 to. For the TIMI score this low-risk group consisted of patients with a TIMI score of 0. Admission, re-admission, ED revisits, out-patient clinic visits and diagnostic procedures Additionally, information on whether or not patients were admitted after the initial presentation, length of admission, re-admissions, ED revisits, out-patient clinic visits and diagnostic procedures within six-weeks after initial presentation was collected. All information was retrieved from electronic patient files. Information on the following diagnostic procedures was collected: bicycle stress testing with exercise ECG, myocardial scintigraphy, cardiac MRI, coronary computed tomography angiography (CCTA) and coronary angiography (CAG). Standard (thoracic) CT-scans were not included, since these were mostly requested in the context of pulmonary disease. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

8 Page of BMJ Open Costs Costs of diagnostic procedures were based on rates as provided by a university medical centre. These costs were up to date as of January st, 0. Costs of hospital admission and ED visits were based on Dutch guidelines for medical cost analysis. Statistical analysis Continuous variables are presented as means (± standard deviation, SD) or medians (interquartile range, IQR), while categorical variables are presented as numbers (percentage). From contingency tables, the incidence of MACE and distribution of the use of health care resources were extracted. Of the incidence of MACE the corresponding % confidence intervals (CI) were calculated. All analyses were performed using Statistical Package for the Social Sciences for Windows 0.0 (SPSS Incl. Chicago, Illinois). RESULTS Study population The current study included 0 patients of two hospitals (.% of the initial study population). Attempts were made to track down follow-up data for patients receiving their follow-up in different hospitals than the study hospitals, however, in patients (.%) we were unsuccessful and thus these patients were lost to follow-up. Additionally, (.%) patients were included twice in the original study and we considered only their first presentation. For an overview of patient selection with inclusion and exclusion, see Figure. Eventually, 0 patients remained for analysis. Mean age was 0 years and % was male. Baseline characteristics are depicted in Table. -week occurrence of MACE A total of 0 (.%) patients out of the 0 were diagnosed with MACE. Figure and Table give an overview of the distribution of the different conditions within MACE. Most common was the BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

9 BMJ Open Page of performance of PCI in patients (.%). A diagnosis of AMI was made in patients (.%), patients received a CABG (.%) and patients (.%) had a stenosis on CAG that could be managed conservatively. One patient died (0.%), with a HEART score of 0 and a TIMI score of. This -year old male with NSTEMI was managed conservatively because of high age and comorbidity, however developed new cardiac ischemia and died shortly after. Occurrence of MACE across risk score categories A patient was defined as low-risk when MACE cumulative incidence of missed MACE was less than % of all 0 patients with MACE (Table ). This resulted in a low-risk group of patients with a HEART score of 0 to (n=, cumulative MACE incidence in this low-risk group:.%; % CI: 0. to.0%) or TIMI score of 0 (n=0, cumulative MACE incidence in this low-risk group: 0%; % CI: 0 to.%). Admission, re-admission, ED revisits and diagnostic procedures A total of patients (%) were admitted to the hospital after presentation at the ED, a total of patients (%) were re-admitted and patients (%) revisited the ED within weeks. In total exercise ECG tests were performed, myocardial scintigraphies, cardiac MRIs, CCTAs, and CAGs. Within the low-risk TIMI group, patients (%) were admitted after ED presentation, compared to patients (%) in the low-risk HEART group. Furthermore, within weeks 0 patients (0%) revisited the ED times within the low-risk TIMI group and patients (%) from the low-risk HEART group revisited the ED times. Within the low-risk TIMI group, exercise ECG tests (%), myocardial scintigraphies (%), cardiac MRI (%), CCTA (%), and no CAGs were administered. In the low-risk HEART group 0 bicycle stress tests (%), myocardial scintigraphies (%), cardiac MRIs (%), CCTAs (%), and CAGs (%) were performed. Further information on use of health care resources is found in Table and Table. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

10 Page of BMJ Open Costs In total an estimated, was spent during the weeks of follow-up on 0 patients, of which, (%) on hospital admission and re-admission costs and, (%) on diagnostic procedures (Table ). This, consisted of admissions at initial ED visit by patients being admitted for a total of, days. The total costs of diagnostic procedures consisted of costs for the bicycle stress tests (,; %), myocardial scintigraphy (,; %), cardiac MRI (,; %), CCTA (,00; %), and CAG (,; %). Concerning the costs in the low-risk population, in the low-risk HEART patients, a total of, was spent on diagnostic procedures and an additional 0, on admission during initial presentation, resulting in a total cost of,0 (.% of the mentioned total costs of,). On the other hand, in the low-risk TIMI patients, a total of, was spent on diagnostic procedures and, on hospital admission, resulting in potential savings of,0 (.% of total costs). DISCUSSION This additional analysis on medical consumption in 0 chest pain patients shows that admission, readmission and ED revisit rates increase with higher TIMI and HEART scores. Diagnostic procedure rates were similar between HEART and TIMI within low-, intermediate- and high-risk groups. Only the use of bicycle stress tests declined as TIMI and HEART increased whereas use of CAG increased with increasing scores. However, the HEART score with a score between 0 and identifies more low-risk patients at the ED than the TIMI score with a score of 0. In the current study, 0% of chest pain patients received a low HEART score of 0 to, with a cumulative incidence of MACE of.%. It remains unsure whether diagnostic procedures with limited predictive values are going to detect this.% population. In this specific group with a low pre-test probability, reduction of diagnostics could diminish patient burden and hospital costs. The same goes for the low-risk TIMI group, however in this group the reduction of diagnostics is limited as only 0 (%) patients with TIMI 0 are considered low-risk. This is due to the conservative nature of the TIMI BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

11 BMJ Open Page 0 of score, resulting in a MACE incidence of 0% in its low-risk group. When including TIMI scores of into the low-risk group, the number of patients will increase, however, the occurrence of MACE will increase as well. It is to be debated what is an acceptable yet achievable missed event rate for chest pain patients in our current health care system with ED overcrowding. Our findings are consistent with other studies in terms of demonstrated safety of the HEART score for risk-stratification and its possible use in determining further policy to reduce medical consumption, especially in low-risk patients. However, literature discussing TIMI and its incidence of MACE shows some discrepancy with our results. The TIMI low-risk group in this study consisted of patients with TIMI 0 and had an incidence of MACE of 0% within weeks of follow up. Several studies found that even with a TIMI score of 0, patients did experience a risk of MACE up to.%. Chest pain patients often receive multiple diagnostic tests, with a risk of iatrogenic damage and furthermore are prone to false-positive or false-negative results, especially the exercise ECG test. Especially low-risk patients are a group in which medical consumption could be reduced. In our study, a total of, could have been saved on diagnostic procedures alone and an additional 0, could have been saved if patients with a HEART score of 0 to had been reassured and discharged early from the ED. The possible total cost reduction amounted to,0 (.% of the mentioned total costs of,). If the TIMI score would have been used to stratify risk categories and the low-risk TIMI group be discharged with reassurance, a total of, would have been saved in diagnostic procedures and another, in hospital admission costs, resulting in potential savings of,0 (.% of total costs). Extrapolating our results from two hospitals with a total of,0 beds to all hospitals in the Netherlands (with a total of,000 beds ), the implementation of the HEART score as a risk stratifying tool could result in savings of,,, which is more than a fourfold increase compared to the TIMI score, which could reduce costs in the Netherlands with,0. 0 BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

12 Page of BMJ Open When discharging patients based solely on a score to reduce redundant medical consumption, it remains the question whether the rate of missed MACE is acceptable. In this study, four patients in the low-risk HEART score group experienced MACE within weeks. The first of these patients (HEART score ) had already been scheduled for CABG prior to presentation. The other two patients with a HEART score of, as well as the one patient with HEART, were diagnosed immediately with ACS at the ED and received elective PCIs in a later stage, indicating mild severity of disease in these patients. These cases show that the HEART score should not be blindly followed, but rather be used as a risk stratification tool. Our study may have several limitations. Firstly, any decisions on diagnostic testing and admissions were left to the clinicians. This should be taken into account when interpreting the results. However, because of the observational nature of our research question, this is surmountable. Secondly, since this is a sub analysis, a group of patients was selected from a larger sample, making estimation less definitive, especially in terms of safety. However, all patients who met the initial inclusion criteria were included in the original study, making selection bias less evident. Thirdly, we could have underestimated medical consumption because patients also received follow-up in other hospitals than where they had their initial presentation. However, we assume that most patients mention co-treatment in other hospitals to their physician at the ED, who reports this in the discharge letter, and thus was apparent to us. Lastly, a conventional troponin assay was used, since high-sensitive troponin was not yet introduced during the original study. Our findings support previous studies that the HEART score aids medical decision-making in terms of risk stratification. The HEART score identifies more patients as low-risk compared to the TIMI score, which may lead to a reduction in diagnostic procedures and hospital admission in this low-risk group and thus in possible savings. Future studies should prospectively investigate whether adhering actively to the HEART score with an early discharge from the ED of low-risk patients, is indeed safe and leads to a reduction in the use of health care resources. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

13 BMJ Open Page of Contributorship statement BEB and AJS designed the study. BEB, AJS, JMP, JBR, SB together with all participating hospitals acquired the data. JMP, JBR, AN and SB analyzed the data. JMP, JBR and AN drafted the manuscript. All authors read and approved the final manuscript. Competing interests Authors declare to have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial or notfor-profit sectors. Data sharing statement Technical appendix, statistical code, and dataset are available upon request by the corresponding author. REFERENCES. Goodacre, S.; Cross, E.; Arnold, J.; Angelini, K.; Capewell, S.; Nicholl, J. The health care burden of acute chest pain. Heart 00, (), -0.. Pope, J. H.; Aufderheide, T. P.; Ruthazer, R.; Woolard, R. H.; Feldman, J. A.; Beshansky, J. R.; Griffith, J. L.; Selker, H. P. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 000, (), -0.. Hollander, J. E. Risk stratification of emergency department patients with chest pain: the need for standardized reporting guidelines. Ann Emerg Med 00, (), -0.. Penumetsa, S. C.; Mallidi, J.; Friderici, J. L.; Hiser, W.; Rothberg, M. B. Outcomes of patients admitted for observation of chest pain. Arch Intern Med 0, (), -.. Brace-McDonnell, S. J.; Laing, S. When is low-risk chest pain acceptable risk chest pain? Heart 0, 00 (), Jneid, H.; Anderson, J. L.; Wright, R. S.; Adams, C. D.; Bridges, C. R.; Casey, D. E.. J.; Ettinger, S. M.; Fesmire, F. M.; Ganiats, T. G.; Lincoff, A. M.; Peterson, E. D.; Philippides, G. J.; Theroux, P.; Wenger, N. K.; Zidar, J. P. 0 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-st-elevation myocardial infarction (updating the 00 guideline and replacing the 0 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 0, 0 (), -.. Hamm, C. W.; Bassand, J. P.; Agewall, S.; Bax, J.; Boersma, E.; Bueno, H.; Caso, P.; Dudek, D.; Gielen, S.; Huber, K.; Ohman, M.; Petrie, M. C.; Sonntag, F.; Uva, M. S.; Storey, R. F.; Wijns, W.; Zahger, D.; Guidelines, E. S. C. C. f. P. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 0, (), -0.. Antman, E. M.; Cohen, M.; Bernink, P. J.; McCabe, C. H.; Horacek, T.; Papuchis, G.; Mautner, B.; BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

14 Page of BMJ Open Corbalan, R.; Radley, D.; Braunwald, E. The TIMI risk score for unstable angina/non-st elevation MI: A method for prognostication and therapeutic decision making. JAMA 000, (), -.. Marcoon, S.; Chang, A. M.; Lee, B.; Salhi, R.; Hollander, J. E. HEART score to further risk stratify patients with low TIMI scores. Cric Pathw Cardiol 0, (), Thygesen, K.; Alpert, J. S.; White, H. D.; Jaffe, A. S.; Apple, F. S.; Galvani, M.; Katus, H. A.; Newby, L. K.; Ravkilde, J.; Chaitman, B.; Clemmensen, P. M.; Dellborg, M.; Hod, H.; Porela, P.; Underwood, R.; Bax, J. J.; Beller, G. A.; Bonow, R.; Van der Wall, E. E.; Bassand, J. P.; Wijns, W.; Ferguson, T. B.; Steg, P. G.; Uretsky, B. F.; Williams, D. O.; Armstrong, P. W.; Antman, E. M.; Fox, K. A.; Hamm, C. W.; Ohman, E. M.; Simoons, M. L.; Poole-Wilson, P. A.; Gurfinkel, E. P.; Lopez-Sendon, J. L.; Pais, P.; Mendis, S.; Zhu, J. R.; Wallentin, L. C.; Fernandez-Aviles, F.; Fox, K. M.; Parkhomenko, A. N.; Priori, S. G.; Tendera, M.; Voipio- Pulkki, L. M.; Vahanian, A.; Camm, A. J.; De Caterina, R.; Dean, V.; Dickstein, K.; Filippatos, G.; Funck- Brentano, C.; Hellemans, I.; Kristensen, S. D.; McGregor, K.; Sechtem, U.; Silber, S.; Tendera, M.; Widimsky, P.; Zamorano, J. L.; Morais, J.; Brener, S.; Harrington, R.; Morrow, D.; Lim, M. l.; Martinez- Rios, M. A.; Steinhubl, S.; Levine, G. N.; Gibler, W. B.; Goff, D.; Tubaro, M.; Dudek, D.; Al-Attar, N. Universal definition of myocardial infarction. Circulation 00, (), -.. Six, A. J.; Backus, B. E.; Kelder, J. C. Chest pain in the emergency room: value of the HEART score. Neth Heart J 00, (), -.. Backus, B. E.; Six, A. J.; Kelder, J. C.; Mast, T. P.; van den Akker, F.; Mast, E. G.; Monnink, S. H.; van Tooren, R. M.; Doevendans, P. A. Chest pain in the emergency room: a multicenter validation of the HEART Score. Crit Pathw Cardiol 00, (), -.. Fesmire, F. M.; Martin, E. J.; Cao, Y.; Heath, G. W. Improving risk stratification in patients with chest pain: the Erlanger HEARTS score. Am J Emerg Med 0, 0 (), -.. Mahler, S. A.; Miller, C. D.; Hollander, J. E.; Nagurney, J. T.; Birkhahn, R.; Singer, A. J.; Shapiro, N. I.; Glynn, T.; Nowak, R.; Safdar, B.; Peberdy, M.; Counselman, F. L.; Chandra, A.; Kosowsky, J.; Neuenschwander, J.; Schrock, J. W.; Plantholt, S.; Diercks, D. B.; Peacock, W. F. Identifying patients for early discharge: performance of decision rules among patients with acute chest pain. Int J Cardiol 0, (), -0.. Backus, B. E.; Six, A. J.; Kelder, J. C.; Bosschaert, M. A.; Mast, E. G.; Mosterd, A.; Veldkamp, R. F.; Wardeh, A. J.; Tio, R.; Braam, R.; Monnink, S. H.; van Tooren, R.; Mast, T. P. v. d.; Akker, F.; Cramer, M. J.; Poldervaart, J. M.; Hoes, A. W.; Doevendans, P. A. A prospective validation of the HEART score for chest pain patients at the emergency department. Int J Cardiol 0, (), -.. Six, A. J.; Cullen, L.; Backus, B. E.; Greenslade, J.; Parsonage, W.; Aldous, S.; Doevendans, P. A.; Than, M. The HEART score for the assessment of patients with chest pain in the emergency department: a multinational validation study. Crit Pathw Cardiol 0, (), -.. Six, A. J.; Backus, B. E.; Kingma, A.; Kaandorp, S. I. Consumption of diagnostic procedures and other cardiology care in chest pain patients after presentation at the emergency department. Neth Heart J 0, 0 (), -0.. Leite, L.; Baptista, R.; Leitao, J.; Cochicho, J.; Breda, F.; Elvas, L.; Fonseca, I.; Carvalho, A.; Costa, J. N. Chest pain in the emergency department: risk stratification with Manchester triage system and HEART score. BMC Cardiovasc Disord 0,,.. Mahler, S. A.; Hiestand, B. C.; Goff, D. C.. J.; Hoekstra, J. W.; Miller, C. D. Can the HEART score safely reduce stress testing and cardiac imaging in patients at low risk for major adverse cardiac events? Crit Pathw Cardiol 0, 0 (), de Araujo Goncalves, P.; Ferreira, J.; Aguiar, C.; Seabra-Gomes, R. TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS. Eur Heart J 00, (), -.. Ramsay, G.; Podogrodzka, M.; McClure, C.; Fox, K. A. Risk prediction in patients presenting with suspected cardiac pain: the GRACE and TIMI risk scores versus clinical evaluation. QJM 00, 00 (), -. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

15 BMJ Open Page of Yan, A. T.; Yan, R. T.; Tan, M.; Casanova, A.; Labinaz, M.; Sridhar, K.; Fitchett, D. H.; Langer, A.; Goodman, S. G. Risk scores for risk stratification in acute coronary syndromes: useful but simpler is not necessarily better. Eur Heart J 00, (), Backus, B. E.; Six, A. J.; Kelder, J. H.; Gibler, W. B.; Moll, F. L.; Doevendans, P. A. Risk scores for patients with chest pain: evaluation in the emergency department. Curr Cardiol Rev 0, (), -.. Pollack, C. V.. J.; Sites, F. D.; Shofer, F. S.; Sease, K. L.; Hollander, J. E. Application of the TIMI risk score for unstable angina and non-st elevation acute coronary syndrome to an unselected emergency department chest pain population. Acad Emerg Med 00, (), -.. Hakkaart-van Roijen, L.; Tan, S. S.; Bouwmans, C. A. M. Handleiding voor Kostenonderzoek; Instituut voor Medical Technology Assesment: Rotterdam the Netherlands, 00.. Mahler, S. A.; Riley, R. F.; Hiestand, B. C.; Russell, G. B.; Hoekstra, J. W.; Lefebvre, C. W.; Nicks, B. A.; Cline, D. M.; Askew, K. L.; Elliott, S. B.; Herrington, D. M.; Burke, G. L.; Miller, C. D. The HEART pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes 0, (), -0.. Mahler SA, Miller CD, Hollander JE, et al. Identifying patients for early discharge: performance of decision rules among patients with acute chest pain. Int J Cardiol. 0;():-0.. Universitair Medisch Centrum Groningen. Tarieven Onderlinge Dienstverlening. (accessed Aug, 0). BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

16 Page of BMJ Open Table. The TIMI (thrombosis in myocardial infarction) score for unstable angina/nstemi Age years 0 risk factors for CAD 0 Known CAD 0 Aspirin use in past days 0 Recent severe angina 0 Elevated cardiac markers 0 ST deviation 0. mm 0 TOTAL 0- CAD: Coronary artery disease, NSTEMI: non-st-segment elevation myocardial infarction BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

17 BMJ Open Page of Table. The HEART score for chest pain patients History Highly suspicious Moderately suspicious Slightly or non-suspicious 0 ECG Significant ST-depression Nonspecific repolarization disturbance Normal 0 Age years >-< years years 0 Risk factors risk factors, or history of atherosclerotic disease or risk factors No risk factors known 0 Troponin x normal limit >-< normal limit Normal limit 0 Total 0-0 ECG: electrocardiogram BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

18 Page of BMJ Open Table. Baseline characteristics Total Patients without MACE Patients with MACE mean/n SD/% mean/n SD/% mean/n SD/% Demographics Study group 0 0 % 0 % Age in years 0.0 Male % % % Vital signs at presentation Heart rate. Systolic blood pressure.0 Diastolic blood pressure. Cardiovascular risk factors Diabetes Mellitus 0 % % % Hypertension % % % Hypercholesterolemia % % 0% Smoking 0 % % 0 % Family history of CVD 0% 0 % % Obesity % 0 0% % History of cardiovascular disease Myocardial infarction % % % CABG 0 % % % PCI % % % CVA % % % PAD % % % Mean HEART score. Mean TIMI score. n: number, SD: standard deviation, CV: cardiovascular, CABG: coronary artery bypass grafting, PCI: percutaneous coronary intervention, CVA: cerebrovascular accident, PAD: peripheral arterial disease, ECG: electrocardiogram. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

19 BMJ Open Page of Table. Components of MACE for each TIMI and HEART score and cumulative frequency of all patients with MACE and all patients in risk group TIMI Components of MACE* Cumulative frequency of all patients with MACE and all patients in risk group N patients AMI PCI CABG CAG cons Death Total patients with MACE Cum. frequency of all patients with MACE Cum. frequency MACE of all patients in risk group Cumulative N patients % 0% %.0% %.% 0 0.% 0.% %.0% 0 0.%.% 0.%.0% %.% 0 Total %.% 0 HEART Components of MACE* Cumulative frequency of all patients with MACE and all patients in risk group N patients AMI PCI CABG CAG cons Death Total patients with MACE Cum. frequency of all patients with MACE Cum. frequency MACE of all patients in risk group Cumulative N patients % 0% % 0% % 0.% %.% %.% %.% 0.%.% 0 0.%.% 0 0.%.0% %.% %.% 0 Total %.% 0 n: number of patients, MACE: major adverse cardiac events, AMI: acute myocardial infarction, PCI: percutaneous coronary intervention, CABG: coronary arterial bypass grafting, CAG cons: CAG conservatively treated. * total components of MACE can exceed the total number of patients with MACE, since patient can have > MACE. on July 0 by guest. Protected by copyright. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from

20 Page of BMJ Open Table. Admission, ED revisit, and re-admission rates compared for low TIMI scores and low HEART scores Patients (n) Initial presentation Re-admissions ED revisits admitted days (sum) patients re-admissions (n) days (sum) patients revisits (n) Low risk TIMI (0) 0 % % 0 0% Not low risk TIMI (-) % 0% 0 % Low risk HEART (0-) % % % Not low risk HEART (-0) % % % Total all patients 0 %, % % Table. Comparison of diagnostic procedures within weeks for low HEART scores and low TIMI scores Patients Diagnostic procedures (n) Stress bicycle test Myocard scintigraphy Coronary CTangiography Cardiac MRI Coronary angiography Low risk TIMI (0) 0 % % % % 0 0% Not low risk TIMI (-) 0 % % % % % Low risk HEART (0-) 0 % % % % % Not low risk HEART (-0) 0 % % 0.% % % Total all patients 0 % % % % % on July 0 by guest. Protected by copyright. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from

21 BMJ Open Page 0 of Table. Overview of the total costs on initial hospital admission and diagnostic procedures for low HEART scores and low TIMI scores Costs of performed diagnostic procedures ( ) Costs of initial admission ( ) Total costs of diagnostic procedures and initial admission ( ) Myocard CCTA Cardiac CAG Total Admission costs scintigraphy MRI Stress bicycle Low risk TIMI (0),,0 00 0,,,0 Not low risk TIMI (-) 0,0,,00,, 0,,, Low risk HEART (0-),,,00,,, 0,, Not low risk HEART (-0) 0,0,00 00,,,,, on July 0 by guest. Protected by copyright. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from 0

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23 BMJ Open Page of Figure Patient flow chart xmm (0 x 0 DPI) BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

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28 BMJ Open Medical consumption compared for TIMI and HEART score chest pain patients at the emergency department: a retrospective cost analysis Journal: BMJ Open Manuscript ID bmjopen-0-00.r Article Type: Research Date Submitted by the Author: 0-Feb-0 Complete List of Authors: Nieuwets, Astrid; Maastricht University Poldervaart, Judith; Julius Center for Health Scienced and Primary Care, Reitsma, Johannes; University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care Buitendijk, Susanne; Gelderse vallei, Emergency medicine Six, Alfred; Zuwe Hofpoort Hospital, Cardiology Backus, Barbra; Medical Center the Hague Bronovo, Emergency medicine Hoes, Arno; Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht Doevendans, Pieter; University of Utrecht, The Netherlands <b>primary Subject Heading</b>: Health economics Secondary Subject Heading: Diagnostics, Cardiovascular medicine Keywords: Adult cardiology < CARDIOLOGY, Myocardial infarction < CARDIOLOGY, HEALTH ECONOMICS, Risk management < HEALTH SERVICES ADMINISTRATION & MANAGEMENT BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

29 Page of BMJ Open Medical consumption compared for TIMI and HEART score chest pain patients at the emergency department: a retrospective cost analysis A Nieuwets a*, JM Poldervaart b, JB Reitsma b, S Buitendijk c, AJ Six d, BE Backus e, AW Hoes b, PA Doevendans f a Maastricht University, Maastricht, The Netherlands b Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands c Department of Emergency Medicine, Gelderse vallei Hospital, Ede, The Netherlands d Department of Cardiology, Zuwe Hofpoort Hospital, Woerden, The Netherlands e Department of Emergency Medicine, Medical Center Haaglanden, Den Haag, The Netherlands f Department of Cardiology, University Medical Center, Utrecht, The Netherlands *Corresponding author BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

30 BMJ Open Page of ABSTRACT Objective: To investigate which risk score (TIMI score or HEART score) identifies the largest population of low-risk patients at the emergency department (ED). Furthermore, we retrospectively calculated the corresponding decrease in medical consumption if these patients would have been discharged from the ED. Methods: We performed analyses in two hospitals of the multicenter prospective validation study of the HEART score. Chest pain patients presenting to the ED were included and information was collected on major adverse cardiac events (MACE) and on hospital admissions and diagnostic procedures within weeks. The TIMI and HEART score were calculated for each patient. Results: We analysed 0 patients (% male, mean age of 0, cumulative incidence of MACE %). An estimated total of, was spent during follow-up on hospital admission and diagnostic procedures. (0%) patients had a HEART score of 0 to and were considered low-risk, a total of,0 was spent on diagnostic procedures and hospital admission after initial presentation in this group. In comparison, 0 (%) patients with TIMI score of 0 were considered low-risk, with a total of,0 spent on diagnostic procedures and initial hospital admission costs. Conclusions: The HEART score identifies more patients as low-risk compared to the TIMI score, which may lead to a larger reduction in diagnostic procedures and costs in this low-risk group. Future studies should prospectively investigate whether adhering to the HEART score in clinical practice and early discharge of low-risk patients is safe and leads to a reduction in medical consumption. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

31 Page of BMJ Open STRENGTHS and LIMITATIONS Strengths: Data from a prospective, multicentre validation study of the HEART score were used including a broad population of patients with chest pain. The overall MACE incidence in our population largely corresponds with existing literature, suggesting that our patient selection is representative for the larger group of chest pain patients. In each patient, both the TIMI and HEART score were calculated leading to a paired analysis which is more valid and more powerful to detect differences. Limitations: This study concerns a retrospective analysis of costs within a prospective study from 00. Another disadvantage is the use of contemporary cardiac troponin instead of the increasingly used highsensitive cardiac troponin. The decision-making process of performing a diagnostic procedure in a patient is a subjective one, that was carried out by different physicians based on their personal opinion or preference. Likewise, both risk scores contain the subjective element of history, which possibly results in interrating variance. By selecting a subsample of a larger cohort study we might have introduced some form of selection bias into our analysis. However, the incidence of the outcome of major adverse cardiac events in our subsample was similar to that the original study population. Our estimates of costs for medical consumption might have been underestimated due to loss to follow up of their further medical consumption. BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

32 BMJ Open Page of BACKGROUND Each year, an estimated % of presentations at emergency departments (ED) are attributed to symptoms suspicious of acute coronary syndrome (ACS).[, ] Of all these patients, the majority has chest pain due to non-cardiac causes and only -0% of patients have an ACS.[] Differentiating between low and high-risk patients for ACS remains a diagnostic challenge, since a normal electrocardiogram (ECG) and initially negative biomarkers do not exclude ACS. Therefore, the majority of low-risk patients are currently admitted to the hospital to undergo stress testing, regardless of low pre-test probability. However, often results of these performed tests are normal.[] The question remains whether this conservative approach leads to better clinical outcomes for patients and there is discussion on optimal management in patients who are deemed safe to discharge from the ED.[] Several risk stratification tools and prediction models have been developed over time. Currently, international cardiac guidelines recommend the use of a risk score for risk stratification.[, ] The current study investigates two of these risk scores, namely the TIMI score and the HEART score. Firstly, the Thrombosis In Myocardial Infarction (TIMI) risk score is used to stratify risk in chest pain patients admitted to the cardiac care unit (CCU) and can be used to predict 0-day outcomes of mortality, myocardial infarction (MI) and severe recurrent ischemia requiring urgent revascularization.[, ] The TIMI score is composed of elements as shown in Table. It is one of the two risk scores that are implemented in current international guidelines and well-known by most clinicians.[0] Secondly, the HEART score was developed in 00 and has been validated to stratify the risk of short-term adverse cardiac events in chest pain patients at the ED.[, -] The HEART score is an acronym for History, ECG, Age, Risk factors and Troponin. These components can be rated 0, or points each and results in a total HEART score between 0 and 0, as shown in Table. It has been specifically developed for chest pain patients and previous prospective studies indicated the HEART BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

33 Page of BMJ Open score as valid for patient stratification, especially in identifying a low-risk group of patients without compromising safety. Such a low-risk group can then be considered for early discharge from the ED.[,,,, -] In a previous study by Mahler et al. the HEART score identified 0% (% CI %) as low-risk (HEART score or lower) with a corresponding sensitivity of % (% CI 00%) for ACS.[] A recent study suggests that a TIMI score of 0 and HEART score of less than or equal to with high-sensitivity troponin I could achieve a negative predictive value greater than or equal to.% while identifying more than 0% of patients as suitable for immediate discharge.[0] Although both risk scores have been validated, they are mostly not yet actively used; that is, no policy decision is made based on the individual risk score of a patient. Furthermore, none of these previous studies mentioned secondary outcome measurements such as clinical course or medical consumption. A pilot study of patients by Six et al. analysed medical consumption of chest pain patients with a HEART score at the ED.[] It concluded that, if the HEART score would be routinely applied on chest pain patients, diagnostic pathways for low-risk patients could be shortened which could lead to cost reduction. However, these were small numbers in a small non-academic hospital. Our goal is to investigate the medical consumption in the low-risk TIMI and HEART score categories. Furthermore, we assessed which risk score is more efficient in identifying the largest number of low-risk patients, without compromising safety. METHODS Study population This is an additional analysis of 0 patients in two hospitals, using the data of a multicenter prospective validation study in 0 hospitals of the HEART score, which included a total of, patients between 00 and 00.[] The ethics committee of the University Medical Centre Utrecht approved the study. Since it was an observational study and patients received standard care, at that time informed consent procedures were waived. Patients were informed of the registration of data BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.

34 BMJ Open Page of and the follow-up policy and data was processed anonymously. Any patient with acute chest pain admitted to the (cardiac) ED was eligible, regardless of age or pre-hospital suspicion. Patients with ST-elevation myocardial infarction (STEMI) were immediately taken to the coronary intervention room, and therefore excluded. Two hospitals were chosen for our additional study on diagnostic procedures as it was anticipated that for these hospitals patient information of sufficient quality would be available. The first one is a general hospital with a large specialised cardiology department, the second one an academic hospital. Both are intervention centres and perform percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG). Calculation of the TIMI and HEART score ED residents of participating hospitals were instructed to fill out the Case Record Form (CRF), which consisted of patient history, cardiovascular risk factors, medication, physical examination and past medical history. Laboratory results, including contemporary Troponin I or T, and the admission ECG were added to the CRF. The ECG was blindly classified afterwards by independent, experienced cardiologists. The HEART score was developed in 00 and predicts the -week incidence of major adverse cardiac events (MACE), stratifying patients into a low-risk (HEART score 0-), intermediate-risk (-) and high-risk (-0) group.[,, ] The incidence of MACE in the previous validation studies has been.% in low-risk patients,.% in intermediate-risk patients, and 0.% in high-risk patients.[] The classification into the different risk categories can be used to make a direct clinical decision for further patient evaluation. In the current study, the HEART score was calculated by the resident at the ED, without actively using the score for further management. Each of the elements in the HEART score were given 0, or points, resulting in a score between 0 and 0, see Table. The TIMI score was developed in 000 for prediction at the CCU for 0-day outcomes of mortality, myocardial infarction (MI) and severe recurrent ischemia requiring urgent revascularization, with the BMJ Open: first published as 0./bmjopen-0-00 on June 0. Downloaded from on July 0 by guest. Protected by copyright.