Prehospital ECG signs of acute coronary occlusion are associated with reduced one-year mortality

International Journal of Cardiology 168 (2013) 3594–3598

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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard

Prehospital ECG signs of acute coronary occlusion are associated with reduced one-year mortality Annica Ravn-Fischer a,⁎, Thomas Karlsson a, Per Johanson a, Johan Herlitz b a b

Institution of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Göteborg, Sweden The Centre of Prehospital Research in Western Sweden, University College of Borås and Sahlgrenska University Hospital, Göteborg, Sweden

a r t i c l e

i n f o

Article history: Received 26 October 2012 Received in revised form 3 April 2013 Accepted 4 May 2013 Available online 30 May 2013 Keywords: Acute coronary syndrome Prehospital triage Coronary care unit Mortality

a b s t r a c t Background: We wanted to evaluate predictors of direct admittance to a coronary care unit (CCU) and predictors of death in patients with suspected acute coronary syndromes (ACS). Methods: During 2004–2007, all consecutive prehospitally triaged patients with suspected ACS were prospectively included. Prehospital and emergency data were collected at point of care. Data from medical records, ECG-, echocardiography- and laboratory databases was collected retrospectively. Results: In all, 2757 patients were included. Out of these 858 were directly admitted to the CCU or cath/lab. Predictors for direct admittance to the CCU were ST-segment elevation on the initial ECG; odds ratio (OR) 46.11, left bundle branch block; OR 3.30, ongoing symptoms; OR 2.90, current smoking; OR 2.18 and ST-segment depression; OR 2.05. Independent predictors for 1-year mortality were cardiogenic shock; OR 14.40, increasing age OR (per year) 1.08, diabetes; OR 2.09 and chronic heart failure; OR 1.67. ST-segment elevation was associated with a lower 1-year mortality rate; OR 0.52. Conclusions: Among patients with a suspected ACS, prehospital ECG-signs indicating an acute coronary occlusion were not only a predictor for direct admission to acute coronary care but also a predictor for increased survival. To improve future outcome in acute ischemic heart diseases we must find and treat not only the STEMI's but also the high-risk NSTEMIs that otherwise would have a poor prognosis. © 2013 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Cardiovascular disease is a major cause of death worldwide. In Sweden 2010 the incidence of myocardial infarction was; 571/100,000 for men and 379/100,000 for women [1]. However, despite new definitions of myocardial infarction and despite new sensitive biomarkers the incidence is decreasing over time. In the last decade in Sweden the age-standardized incidence of myocardial infarction has been reduced by almost 25% for both men and women [1]. Furthermore, mortality due to myocardial infarction has also decreased considerably during the last decade and the 28-day mortality is now about 13% for hospitalized patients [1]. This pleasant progress is presumably depending on both primary preventive factors as smoking habits, physical activity and healthy diets [2] and an improved adherence to guidelines for interventions, acute treatment and secondary prevention factors [3]. Despite this reduction in incidence of myocardial infarction, chest pain patients still are very common in the emergency departments. ⁎ Corresponding author at: Department of Cardiology, Sahlgrenska University Hospital, SE 413 45 Göteborg, Sweden. Tel.: +46 31 342 7585. E-mail address: annica.ravn-fi[email protected] (A. Ravn-Fischer). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.05.064

Only in the municipality of Göteborg approximately 10,000 patients with chest pain seek emergency care, every year [4]. It takes a great effort for the health care system to handle this large volume of patients and it is important to optimize the care of these patients from both economical- and a health care perspective. In patients with chest pain/presumed acute coronary syndrome (ACS) it is of greatest importance to reduce delay times to treatments and investigations in order to reduce myocardial damage [5]. The whole chain of care, including the emergency medical service (EMS) system and the emergency department, must be optimized for best outcome. This has given rise to a need for prehospital triage-methods and telemedical connections between the ambulance crew and the nurses and cardiologists at the Coronary Care Unit (CCU). In this study we investigate a large population of patients who underwent such prehospital triage, and describe differences between those who were directly admitted to the CCU or catheterization laboratory and those who were not. Furthermore we describe factors of importance for survival in the overall population of prehospitally triaged patients with a suspected ACS. The main purpose of the study is to identify factors of importance for survival in this patient cohort in order to improve and optimize the early triage and long-term outcome.

A. Ravn-Fischer et al. / International Journal of Cardiology 168 (2013) 3594–3598 2. Methods 2.1. Study design This is a study, including all patients with suspected ACS in whom an ambulanceelectrocardiogram (ECG) was recorded and telemedically transmitted to the CCU at a tertiary centre, in the municipality of Göteborg (Sweden), during a 4-year period 2004–2007.

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model, using forward stepwise selection with p b 0.01 for both entering and staying in the model. Due to the retrospective design of the study there is some amount of missing data. Some of the missing data have been analyzed using statistical imputation methods (i.e. expectation–maximization algorithm). All tests are two-sided and p-values below 0.01 were regarded as statistically significant. All analyses were performed using SAS version 9.1 for Windows.

2.2. Ethics

3. Results

The Göteborg Ethical Review Board approved this study. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

In all there were 3238 visits made by 2834 patients in this survey. For patients with multiple visits one was chosen by random. There were 77 patients excluded because of missing data concerning direct admission to CCU/Ward/emergency department or 1-year mortality, thus resulting in 2757 patients included in the analyses. Out of these 858 (31%) were directly admitted to the CCU or catheterization laboratory. Of all patients directly admitted to the CCU 31% were women. Patients directly admitted to the CCU were younger than those who were not and smoking was more common. Ongoing symptoms, pain localized in chest or arms, and ST-segment elevation on ECG were more common among patients directly admitted. A previous history of myocardial infarction, heart failure, percutaneous coronary intervention and coronary artery bypass grafting was more common in the group not directly admitted to the CCU. Previous history of diabetes, myocardial infarction or heart failure was more common among those not alive after 1 year as were Killip class ≥ III, dyspnea and vertigo on admission. It was much more common with a final STEMI-diagnosis in the direct admission to the CCU-group. Subsequently, reperfusion therapy was more common and there were shorter delays to this treatment in the direct admission group. Higher levels of serum creatinine, CRP and plasma glucose were more common among those who died during the first year after admission, as were lower frequency of coronary angiography and percutaneous coronary intervention.

2.3. Study population Patients with suspected ACS based on prehospital symptoms and/or clinical signs were retrospectively included. The patients were identified through the tertiary CCU prehospital ECG database. These patients were included regardless of being directly admitted to the tertiary CCU/catheterization laboratory or referred to one of three emergency departments in the Sahlgrenska University Hospital organization. According to the symptoms and the ECG pattern the patient was triaged/given priority for direct admission to the CCU/catheterization laboratory or the emergency department. This triage decision was made by either a CCU-nurse or a physician. All patients, both those who were hospitalized (at a CCU or a general medical ward) and those discharged from the emergency department were included. There were no exclusion criteria. 2.4. Data sources Prehospital and emergency data was telemedically collected, at point of care, by the CCU-nurse for each received ECG. Further, a point of care contact-sheet comprising 41 variables was filled in. Data from medical records, ECG-, echocardiography- and laboratory databases were collected retrospectively. Age, gender, previous history of illness, smoking habits, body mass index, symptoms, ECG-patterns, laboratory parameters, investigations, and final diagnosis at discharge and mortality were collected and entered into a database for subsequent statistical analysis. For ACS-patients, being treated at the CCU, data was also collected from the Swedish National Quality Registry, SWEDEHEART (Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies). The data sampling (after the initial recording by the CCU nurse) was performed by two research nurses, a medical student and one cardiologist, all clearly instructed how to record data. For each variable that was assessed there were strict definitions. Uniformity in data collection was enabled by regular meetings within the research group. 2.5. Outcome measures The primary aim of this study was to identify predictors for 1-year mortality in ACS-patients. Secondary outcome measures were to identify differences among patients that were directly admitted to a CCU/catheterization laboratory compared with those who were primary sent to the emergency department. 2.6. Definition of variables Immediate reperfusion therapy was defined as start of the percutaneous coronary intervention — or the coronary artery bypass grafting procedure within 90 min from time of prehospital ECG. The definition of myocardial infarction was based on the following diagnostic criteria; 1) Laboratory parameters (minimum one troponin value, I or T or CKMb value, above the upper reference level (troponin T ≥ 0.03 μg/L, troponin I ≥ 0.1 μg/L or CKMb ≥ 5 μg/L) and another troponin or CKMb value 6 h later indicating dynamic changes) and at least one of the two conditions 2a) symptoms raising suspicion of myocardial infarction such as; pain or discomfort in chest, arms, neck, jaw, back or abdomen; dyspnea; nausea; and cold sweat or 2b) ECG-findings suggesting ischemia: ST-segment elevation/depression in at least two contiguous leads (ST-segment elevation of ≥0.1 mV in leads aVL, aVF, I, II, III, and V5–V6 or ≥0.2 mV in leads V1–V4, ST-segment depression of ≥0.1 mV) or left bundle branch block [6]. The definition of ACS was a final diagnosis of either myocardial infarction, including ST-elevation myocardial infarction (STEMI), non-st-elevation myocardial infarction (N-STEMI) or unstable angina pectoris. 2.7. Statistical analyses Age was compared using Mann–Whitney U test. All other comparisons between those directly admitted to CCU and those not and between those alive and those dead after 1 year were age adjusted, using logistic regression for dichotomous variables and a stratum adjusted Kruskal–Wallis test for continuous/ordered variables. Proportions and means/medians are presented as crude results, i.e. not adjusted for age. To identify independent predictors of directly admittance to CCU and of 1-year mortality a two-step strategy was used (Tables 3a and 3b.). Firstly, all variables in Table 1 (except delay time) were tested univariately, using Fischer's exact test and Mann–Whitney U test for dichotomous and continuous variables, respectively. In the next step, all variables with a univariate p-value b0.01 were tested for inclusion in a multiple logistic regression

3.1. Comments/clarifications Tables 1 & 2 In these tables there are two columns with headings, “Direct admission to CCU” and “Alive after one year” with subtitles “Yes” or “No”. All patients in the study are presented in both the direct admission column and the column concerning mortality. These columns should be considered as independent of each other. In a multivariate analysis, ST-segment elevation on ECG was identified as a strong predictor for direct admittance to CCU. Other independent predictors for direct admittance identified were; left bundle branch block, ongoing symptoms, pain localizations in chest and arms, cold sweat, smoking-habits and ST-segment depression. Predictors of 1-year mortality were cardiogenic shock, symptoms associated with acute heart failure, high age, previous history of diabetes and chronic heart failure. Presence of ST-elevation on the initial ECG was associated with lower 1-year mortality. 4. Discussion The chest pain patient is one of the most common visitors at our hospitals, and former studies have shown that about 50% of these patients are hospitalized after triage at the emergency department [7]. In the municipality of Göteborg (630,000 inhabitants in Dec. 2011) there are three hospitals offering emergency care for patients with presumed ACS. All these hospitals have a CCU but the hospitals differ in size, number of beds and available resources. Facilities for 24-hour coronary angiography/percutaneous coronary intervention and coronary artery bypass grafting are located in the tertiary center only. This type of organization is not unusual, and such a subdivision of resources results in considerable demands in logistics for the emergency medical system organization as well as for the three emergency departments which in total handle about 10,000 patients with chest pain per year

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Table 1 Baseline characteristics, symptoms and status on admission. Direct admission to CCU

Age (year); mean ± sd Women (%) Previous history (%) Diabetes Hypertension Smoking Myocardial infarction Heart failure PCI CABG Stroke BMI; median ± sd Ongoing symptoms (%) Pain localization Chest Neck Arms Back Abdomen Other symptoms (%) Dyspnea Cold sweat Nausea Vomiting Vertigo Arrhythmia Cardiac arrest Cardiogenic shock ECG pattern (%) ST elevation ST depressiona LBBB Pacemaker b 1 Decision by nurse Direct admission to CCU Status on admission (median ± sd) Heartrate; bpm Systolic BP; mm Hg Diastolic BP; mm Hg Rales of the lungs; % (Killip III) Cardiogenic shock; % (Killip IV) Onset of symptoms to arrival in hospital; hours:min, median (94/846)

Alive after 1 year

Yes (n = 858)

No (n = 1899)

P1

Yes (n = 2316)

No (n = 441)

P1

65.6 ± 13.1 31

70.8 ± 15.7 44

b0.0001 b0.0001

67.2 ± 15.2 38

79.6 ± 9.6 48

b0.0001 0.91

15 37 35 23 7 12 8 8 26.5 ± 4.3 93

18 41 20 40 18 14 15 13 26.3 ± 4.6 78

0.12 0.95 b0.0001 b0.0001 b0.0001 0.009 b0.0001 0.07 0.11 b0.0001

15 38 27 31 12 14 13 10 26.5 ± 4.5 83

27 49 19 52 32 11 14 17 25.0 ± 4.0 81

b0.0001 0.45 0.03 b0.0001 b0.0001 0.37 0.82 0.33 0.14 0.29

87 11 33 9 4

68 7 15 9 6

b0.0001 0.02 b0.0001 0.62 0.008

75 9 22 9 5

68 6 14 7 7

0.13 0.24 0.02 0.17 0.14

14 35 23 9 9 4 2 1

22 17 14 5 9 4 b1 b1

0.0004 b0.0001 b0.0001 0.001 0.41 0.34 0.0006 0.001

18 23 18 7 10 4 b1 b1

29 21 12 4 5 4 1 2

0.0003 0.20 0.04 0.15 0.007 0.50 0.12 0.06

77 14 7 4 50 100

9 21 14 0.0002 45 0

b0.0001 0.001 0.001 3 0.09 –

33 18 10 4 47 33

20 24 22 0.74 43 19

0.008 0.35 0.0002

78 ± 26 136 ± 27 82 ± 17 4 2 1:58

83 ± 27 141 ± 30 81 ± 16 3 1 2:37

0.0003 0.0003 0.81 0.002 0.007 b0.0001

81 ± 27 141 ± 28 82 ± 16 2 b1 2:15

86 ± 28 131 ± 33 77 ± 17 9 7 2:30

0.53 0.01 0.001 b0.0001 b0.0001 b0.0001 b0.0001 0.40

BMI: body mass index; CABG: coronary artery bypass grafting; LBBB: left bundle branch block; PCI: percutaneous coronary intervention. P1 age adjusted p-value (except for age itself). All patients in the study are presented in both the direct admission column and the column concerning mortality. These columns should be considered as independent of each other. a Not available for 2004.

[4]. For this considerable quantity of patients it is important that everyone arrives at the right level of care as soon as possible to avoid unnecessary delay times to investigations and treatments. In this study we have focused on predictors for direct admittance to a CCU with full access to timely invasive measures, and on predictors of 1-year mortality in order to understand the use of our triage mechanisms. Optimization of the early chain of care will directly lead more patients to the right level of care without delay. Over the years, our attention directed to early identification of the STEMI group has grown very successfully and these patients are more often primarily directed to the CCU or catheterization laboratory and thus timely treated with immediate revascularization in accordance to national [8] and international guidelines [9]. This is reflected in the current study. Our results show that ST-segment elevation on the ECG is the most important predictor for direct admittance, and that ST-segment elevation actually is associated with a lower long-term mortality as compared to patients who do not have such changes; maybe due to the fact that patients with a presumed STEMI get such high priority for acute care.

Recent data from our national registry SWEDEHEART shows that out of all MIs in Sweden in 2011 the STEMI group constitutes 30% compared with the LBBB group 6% and the NSTEMI-group 64% [10]. The NSTEMI/ LBBB patients are older, have more co-morbidities and multi-vessel disease than the STEMI group [11]. Therefore we might question ourselves: Why are NSTEMI patients, diabetics and patients with acute heart failure not directly admitted to a CCU/catheterization laboratory as often as the younger and “healthier” STEMI group is? According to previous studies we know that elderly ACS patients are a high risk group with more significant treatment benefits than younger patients but even so they are not admitted to the CCU in the same extent [12,13]. Furthermore, current guidelines recommend earlier invasive strategies for NSTEMI-patients with high clinical risk, for instance evaluated by the GRACE-score [14]. Directing NSTEMI-patients to hospitals without facilities for coronary angiographies may preclude such early intervention, and we have previously presented that patients admitted to CCUs without angiography in-house do have longer delay-times [4]. Longer delay-times to revascularization will increase myocardial damage which could result in impaired heart function [15].

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Table 2 Treatments, investigations and laboratory parameters. Direct admission to CCU

Immediate reperfusion (%) Trombolysis PCI CABG Coronary angiography (only) Arrival in hospital to immediate reperfusion therapy (hours:min); median Coronary angiography % In total Primary/rescue PCI Later during hospital stay PCI (%) During hospital stay CABG % Primary CABG During hospital stay Left ventricular function Normal (≥50%) Mildly depressed (40–49%) Moderately depressed (30–39%) Markedly depressed (b30%) Laboratory values (median) Max troponin-T (μg/L) Max troponin-I (μg/L) Max CKMB (μg/L) Max p-glucose (mmol/L) Max s-creatinine (μmol/L) Max CRP (mg/L) Min Hb (g/L) Final diagnosis (%) STEMI NSTEMI Unstable angina Mortality (%) In hospital 30-day mortality 1-year mortality

Alive after 1 year

Yes (n = 858)

No (n = 1899)

P1

Yes (n = 2316)

No (n = 441)

P1

b1 63 2 7 0:20

b1 3 b1 1b0.0001 1:30

0.65 b0.0001 0.0004 3 b0.0001

b1 25 b1 4 0:24

b1 10 b1 0.08 0:25

0.65 0.0002 0.82

84 75 9

14 5 8

b0.0001 b0.0001 0.59

40 30 9

20 15 4

0.0002 0.003 0.09

68

7

b0.0001

29

13

b0.0001

4 2

b1 1

b0.0001 0.67 0.15a

2 2

b1 b1

0.57 0.39 b0.0001a

56 24 13 7

56 18 12 14

59 26 11 8

26 19 26 29

0.52 4.8 40 7.0 81 5 140 64 8 4 4.5 5.5 9.8

0.92

0.01 0.1 3 6.7 88 7 135

b0.0001 b0.0001 b0.0001 0.005 0.001 b0.0001 0.21

0.03 0.1 4 6.7 82 5 139

0.09 0.3 5 8.0 112 20 123

0.002 0.0005 0.65 b0.0001 b0.0001 b0.0001 b0.0001

7 14 3

b0.0001 0.003 0.45

26 10 3

19 19 2

0.36 0.01 0.17

0.14 0.20 0.01

0 0 0

31.3 39.9 100

– – –

5.2 6.8 18.8

CABG: coronary artery bypass grafting PCI: percutaneous coronary intervention. P1 age adjusted p-value. All patients in the study are presented in both the direct admission column and the column concerning mortality. These columns should be considered as independent of each other. a Ordered value of left ventricle function used in p-value calculation.

Patients with ongoing symptoms raising suspicion of a threatening myocardial infarction and ECG without ST elevation or left bundle branch block ought to qualify to CCU care. We know that the CCU, with cardiologists and heart specialized nurses, offers the best evaluation for ischemic heart disease [16] and the oldest patients with the most severe illness would probably benefit from a higher attention instead of being down-prioritized due to lack of indication for immediate reperfusion treatment. The CCU care also includes follow up by cardiologists and secondary prevention rehab programs that we know are beneficial for the

patient [17]. ACS patients not admitted to the CCU unfortunately often miss these rehab programs and there is an under-utilization of cardiac rehab especially among the elderly [17]. In order to improve acute cardiac care in the future the cardiology services must be well organized, efficient and appropriately resourced. It is also important to better define the role of the CCU since such high level care is expensive [18]. Despite the existing severe financial climate, the CCU capacity might be allowed to expand to prepare for larger volumes of patients. This could make it possible to take care, not only of the STEMI group, but also of the older patient with multiple illnesses suffering from heart disease.

Table 3a Predictors for direct admission to the CCU. Table 3b Predictors of 1-year mortality.

OR (95% C.I.) Ongoing symptoms Pain localization Chest Arms Other symptoms Cold sweat ECG-pattern ST-segment elevation ST-segment depression Left bundle branch block Previous history Smoking (ongoing)

2.90 (1.74,4.83) 1.84 (1.24,2.72) 1.61 (1.13,2.29)

p b 0.0001 p = 0.002 p = 0.009

2.33 (1.66,3.28)

p b 0.0001

46.11 (32.34,65.74) 2.05 (1.36,3.08) 3.30 (2.06,5.26)

p b 0.0001 p = 0.0006 p b 0.0001

2.18 (1.55,3.06)

p b 0.0001

OR (95% C.I.) Age (per year) ECG-pattern ST-segment elevation Status on admission Systolic blood pressure (per mm Hg) Rales of the lungs (Killip III) Cardiogenic shock (Killip IV) Previous history Diabetes Chronic heart failure

1.082 (1.066,1.097)

p b 0.0001

0.52 (0.36,0.76)

p = 0.0006

0.988 (0.983,0.993) 2.87 (1.57,5.23) 14.40 (3.24,63.96)

p b 0.0001 p = 0.0006 p = 0.0005

2.09 (1.52,2.86) 1.67 (1.22,2.28)

p b 0.0001 p = 0.001

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4.1. Limitations This study is retrospective and there is some amount of missing data due to the design. This study comprises a large amount of tests that raise the risk for false statistical significances, even though 0.01 was used as significance level. Since different persons were performing the data collection we cannot entirely rule out the possibility of any data collection bias, even if a standardized manner of collection was used. The data collectors were clearly instructed to maintain the data collection as uniform as possible, however no assessment of inter-data collector validity was performed.

4.2. Clinical implications Among patients having symptoms, which require an ECG to be recorded and sent to the CCU, STEMI patients have become a relatively low risk group, most likely explained by early reperfusion. The present challenge to health care providers is to find appropriate early treatment for the “new” high risk group i.e. patients with a suspected ACS but without ST-elevation on the ECG.

5. Conclusions The strongest predictor for direct admittance to a CCU was a prehospital ECG suggesting acute occlusion of a coronary vessel. Interestingly, these patients actually had lower 1-year mortality compared with other patients. Patients with conditions predicting mortality, such as increasing age, diabetes and chronic heart failure, might be wrongly down-prioritized in the initial triage and might benefit from direct admittance and care at a CCU. To improve future outcome in acute ischemic heart diseases we must find and treat not only the STEMI's but also the high-risk NSTEMI that otherwise would have a poor prognosis.

Acknowledgements I want to express my sincere thanks to Stefan Kihlgren, Margaretha Sjölin and Homa Rashed for great support during data collection. This study was supported by grants from the Laerdal Foundation in Acute Medicine in Norway.

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