a b s t r a c t

Aims: The aims of this study were (a) to determine the prehospital prevalence of electrocardiographic signs of Acute myocardial ischemia in patients with Suspected acute coronary syndrome and (b) to describe the relationships between the various ECG patterns and the diagnosis of acute myocardial infarction (AMI) and outcomes.

Methods: Prospective cohort study using data from an interventional trial in acute chest pain patients transported by the emergency medical services. These patients were classified into 3 groups: patients with ECG showing signs of acute myocardial ischemia, patients with ECG showing other Abnormal changes (bundle-branch block, pacemaker rhythm, Q-wave or T-wave inversion) and patients without significant Pathologic findings. All P values are age-adjusted.

Results: Among 1546 patients, 312 (20%) had ECG signs of acute myocardial ischemia. Of them, 57% had a final diagnosis of AMI versus 26% of those with other Abnormal ECGs and 12% of those with ECG without significant pathologic findings (P b .0001). In all, 53% of all AMI cases involved patients without ECG signs of acute myocardial ischemia. Although ECG signs of acute myocardial ischemia predicted heart failure and Ventricular tachyarrhythmias both prior to and after hospital admission, there was no significant difference in 30-day mortality between the 3 patient groups (4.3%, 3.7%, and 1.2%, respectively, P = .11).

Conclusion: Among patients with a clinical suspicion of AMI in the prehospital setting, the prevalence of ECG signs suggesting AMI was low, as was the ability to identify AMI patients using ECG findings only. We therefore need better instruments in the prehospital triage of patients with acute chest pain.

(C) 2014

Introduction

Acute chest pain (ACP) is one of the most common symptoms among non-trauma patients calling for the emergency medical service (EMS) and it is given the highest emergency priority [1]. The early identification in the prehospital setting of patients suffering from an acute coronary syndrome (ACS) will shorten the delay to the delivery of effective treatment and thereby improve the likelihood of a successful outcome [2,3].

? State conflicts of interest and source funding: None declared.

?? Bjorn W Karlson is an employee of AstraZeneca.

? This study was funded by the University of Boras, the Health & Medical Care

Committee of the Regional Executive Board, the Vastra Gotaland Region, Sparbanks- stiftelsen Sjuharad, Sweden, and the Laerdal Foundation.

* Corresponding author. Tel.: +46 31 3427548; fax: +46 31 827375.

E-mail address: [email protected] (N.D. Thang).

In previous studies, 20% of calls to the dispatch center were due to chest pain [4]. The diagnosis of acute myocardial infarction (AMI) in the prehospital setting was correct in 45% of cases with suspected ACS, while the corresponding figure at the emergency department was 78% [5]. The prediction of AMI and complications including death from the electrocardiogram (ECG) in the pre- hospital setting has been described previously [6,7]. However, there has been an increase in the number of patients contacting EMS for ACP during the last few decades, thus resulting in a decrease in the proportion of AMI [8] and the pattern of ECG findings in this population thus needs to be re-evaluated. Against this background, the aims of this study were: (a) To determine the prehospital prevalence of ECG signs of acute myocardial ischemia in patients with suspected ACS and (b) to describe the relationships between the various ECG patterns and the diagnosis of AMI and outcomes.

http://dx.doi.org/10.1016/j.ajem.2014.03.006

0735-6757/(C) 2014

Materials and methods

This is a prospective cohort study which involved data from another interventional trial performed by the EMS in the Vastra Gotaland Region and the City of Halmstad in Sweden [9]. The EMS consists of 15 ambulance stations staffed by some 500 nurses, 60 vehicles, and 1 EMS boat and it serves 1.6 million inhabitants in an area of 79000 km² in western Sweden. The staff of each ambulance includes a nurse who has an education in prehospital care and the delegation to give various medications in the prehospital setting.

In Sweden, health care including the use of EMS is available for every citizen without the requirement of any insurance. For an Ambulance transport, the patient has to pay a fee of 200 Swedish kronor.

Patients and data collection

From March 1, 2008, to December 31, 2010, all patients who were transported to hospital by the EMS due to ACP were evaluated for inclusion in a 2 x 2 factorial design intervention study evaluating the impact of a special prehospital emergency cardiac care course for EMS nurses, as well as the addition of an anxiolytic drug (midazolam) to the standard prehospital medical treatment of chest pain. The study was registered in the www.clinicaltrials.gov Protocol Registration System (registration number 151: 2008/4564). The inclusion criteria for this interventional trial were pain or discomfort (feeling of weight, dyspnea or the like) in the chest, with an intensity of at least 4 on a colour analogue scale, graded from 0 to 10, where 0 means no pain at all and 10 the worst imaginable pain, on EMS arrival. When the patient did not understand the scale, he/she could be included if the pain or discomfort was described as being of at least medium severity, with a simultaneous clinical suspicion of ACS [10,11]. Exclusion criteria for the initial trial were age b 18 years, secondary transpor- tation from a clinic (if pain treatment had been commenced), trauma, alcohol influence, drug abuse, dementia, disorientation, communica- tion difficulties, and systolic blood pressure below 100 mmHg.

In the current sub-study, one further exclusion criterion is no prehospital ECG recording available for interpretation.

In eligible patients, a 12-lead Standard ECG was recorded just after EMS arrival and was transmitted to the research center. The final diagnosis and Cardiovascular complications were retrospectively recorded from the database of the health-care system by specially trained monitoring nurses. It is recommended that the clinical diagnosis of AMI should be based on a dynamic serial elevation of troponin T, troponin I or CK-MB, plus at least one further criterion (eg, typical chest pain or ECG signs of acute myocardial ischemia) [12,13]. In our study, the final diagnosis of AMI (primary endpoint) was based on the assessment of the responsible physician. In order to give a full clinical picture in addition to AMI development and death during 30 days, the following complications prior to and after admission to hospital were also analyzed: heart failure, hypotension, supraventric- ular tachyarrhythmias, ventricular tachyarrythmias, and atrioventric- ular block (secondary endpoints). These complications were defined according to the judgment of and treatment by the responsible health care provider.

In the present sub-study, the ECG definition of acute myocardial ischemia in the absence of Left bundle branch block , right bundle-branch block, and pacemaker rhythm was new ST elevation at the J point in 2 contiguous leads with the cut-off points of >=1 mm (0.1 mV) in all leads other than leads V₂-V₃, where the cut-off points of >=2 mm (0.2 mV) in men aged >=40 years, >=2.5 mm (0.25 mV) in men aged b 40 years and >=1.5 mm (0.15 mV) in women apply. In cases of ST-segment depression, those regarded as manifestations of acute myocardial ischemia were a down-sloping ST segment with a J-point depression of >=0.5 mm (0.05 mV) in at least 2 contiguous leads. “Contiguous leads” refer to anterior leads (V₁-V₆), inferior leads (II, III, aVF) or lateral/apical leads (I, aVL) [12,13].

Other abnormal ECG signs included LBBB, right bundle-branch block, pacemaker rhythm and T-wave inversion or Q-wave in at least two leads. All ECGs were interpreted by the same physician.

Mortality during 30 days after hospital admission was analyzed. Date of death or confirmation of survival was obtained from the Swedish National Population Registry.

Statistical analysis

According to the ECG definition above, eligible patients were classified into 3 groups: patients with ECG showing signs of acute myocardial ischemia, patients with ECG showing other abnormal changes and patients with ECG without significant pathologic findings. Except for age, where an unadjusted Mann-Whitney U test was used, all comparisons between groups were made using logistic regression for dichotomous variables, a stratum-adjusted Kruskal- Wallis test for continuous variables and Cox’s proportional hazards model for mortality to calculate age-adjusted p-values. All tests were 2-sided and P values for any difference between the 3 patient groups below .05 were considered statistically significant. If a statistically significant difference was obtained as above, we performed pairwise group comparisons and the significance level for these comparisons was set at .015. All analyses were performed using SAS 9.3 software.

Study ethics

Approval for this study was given by the Research Ethics Committee at Gothenburg University, Guldhedsgatan 5A, SE-413 20 Gothenburg, Sweden.

Results

Of 1826 patients included in the original interventional study, 280 (15%) were excluded from participation in the present study, as no prehospital ECG recording was available. As a result, 1546 patients were eligible. Of them, 312 (20%) had ECG signs of acute myocardial ischemia, 427 (28%) had other abnormal ECG patterns, and 807 (52%) had ECG without significant pathologic findings, as previously defined. The mean age of the patients in the 3 groups was 72, 75, and 67 years, respectively (P b .0001), and the percentage of females was 42, 36, and 50%, respectively (P b .0001).

Final diagnosis, duration of hospitalization and survival (Table 1)

Patients with ECG signs of acute myocardial ischemia had a final diagnosis of AMI in 57.3% of cases versus 25.9% in those with other abnormal ECGs and 11.7% in the group with ECG without significant pathologic findings (P b .0001).

The proportion of hospitalized patients in the 3 groups was 96.7%, 88.9%, and 76.1%, respectively (P b .0001). The median duration of hospitalization for patients with ECG signs of acute myocardial ischemia and patients with other abnormal ECGs was longer than in those without these ECG signs. There was a non-significant trend towards a difference in 30-day mortality between the 3 study groups.

Final diagnosis of AMI in relation to the prehospital ECG pattern (Table 2, Table 3)

As shown in Table 2, 3 quarters of patients with ST elevation developed a confirmed AMI and patients with LBBB or ST depression had a rate of AMI development of around 40%. A lower risk of infarct development was found in patients with no ischemic ECG changes (12%), but almost a quarter of patients with a final diagnosis of AMI were still recruited from this group. Only 27% of patients with a confirmed AMI had ST-elevation myocardial infarction according to the prehospital ECG.

Table 1

Final diagnosis, duration of hospitalization and survival

ECG with signs of ischemia (n = 312)

ECG with other abnormal changes^a (n = 427)

ECG without significant P^b

pathologic findings (n = 807)

Final diagnosis (12/14/65)c Confirmed AMI	172 ( 57.3)A, B	107 (25.9)A, C	87 (11.7)B, C	b.0001
Angina pectoris	21 (7.0)A, B	60 (14.5)A	105 (14.2)B	.002
Pulmonary embolism	0 (0.0)	3 (0.7)	4 (0.5)	.43
Pleuropneumonia	8 (2.7)	9 (2.2)	20 (2.7)	.63
Gastric ulcer etc.	6 (2.0)	9 (2.2)	25 (3.4)	.51
Pericarditis	1 (0.3)	0 (0.0)	5 (0.7)	.83
Hepatobiliary disease	1 (0.3)	3 (0.7)	13 (1.8)	.08
Musculoskeletal pain	2 (0.7)	9 (2.2)	17 (2.3)	.25
Psychogenic pain	1 (0.3)	3 (0.7)	8 (1.1)	.67
Non-specified chest pain	22 (7.3)A, B	114 (27.6)A, C	319 (43.0)B, C	b.0001
Atrial fibrillation/flutter	34 (11.3)A, B	28 (6.8)A	25 (3.4)B	.0001
Heart failure	4 (1.3)A	24 (5.8)A	14 (1.9)	.02
Other	28 (9.3)	44 (10.7)	100 (13.5)	.21
Admitted to a hospital ward (8/4/25)	294 (96.7)A, B	376 (88.9)A, C	595 (76.1)B, C	b.0001
Days in hospitald (median, (25th, 75th percentile)) All patients (9/9/38)	5 (2.8)A, B	4 (2.7)A, C	2 (1.4)B, C	b.0001
Only those admitted to hospital ward (1/5/3)	5 (3.8)B	4 (2.8)C	3 (2.5)B, C	b.0001
Discharged alive or not admitted (9/4/25) 30-day mortalitye	296 (97.7)	412 (97.4)	776 (99.2)	.27
All patients (1/0/3)	13 (4.3)	14 (3.7)	9 (1.2)	.11
AMI patients (1/0/0)	8 (4.7)	7 (7.1)	3 (3.6)	.96
Non-AMI patients (0/0/2)	5 (4.1)	6 (2.2)	5 (0.8)	.20

Data presented as n (%), unless otherwise stated.

^{A, B, C} Pairwise comparisons, groups with same letter differ significantly.

^a ECG with left bundle branch block or Right bundle branch block or pacemaker rhythm or T-wave and/or Q-wave in at least any two leads.

^b Age-adjusted p-value for any difference between the 3 groups.

^c Number of patients with missing information in the 3 groups respectively.

^d From day of initial alarm (value was zero for those not admitted to hospital ward).

^e Kaplan-Meier estimate, only First visit included for those with multiple visits (n = 303/382/748).

Sensitivity, specificity, negative, and positive predictive values of various prehospital ECG patterns for a final AMI diagnosis are shown in Table 3.

Cardiovascular complications prior to hospital admission and in hospital (Table 4)

In the prehospital setting, we found a significant difference in heart failure and ventricular arrhythmias between the 3 groups. This difference was also found after hospital admission, where there was also a significant difference in terms of hypotension, and supraven- tricular arrhythmias.

Discussion

We found that, among patients with chest pain of at least medium severity and raising a suspicion of ACS as judged by the EMS crew, about 1 in 5 had ECG signs of acute myocardial ischemia [14].

Table 2

Prehospital ECG patterns

	All patients	Patients with a final diagnosis
	(n = 1546)	of AMI (n = 366)
Left bundle branch block (1)a	103 (7)	40 (11)
Right bundle branch block (7)	107 (7)	28 (8)

Pacemaker rhythm (0) 46 (3) 5 (1)

ST-elevation (7) 143 (9) 100 (27)

ST-depression (5) 169 (11) 72 (20)

There was no significant difference in 30-day mortality between the 3 groups of patients with different ECG patterns. This is unexpected, as myocardial damage is supposed to be more extensive among patients with signs of acute myocardial ischemia [15-17], as well as among patients with other abnormal ECG patterns [18], compared with patients without these signs. However, due to the small number of events, one could assume the power to detect significant differences in mortality to be low, but no formal Power calculation was performed.

The longer duration of hospitalization among patients with ECG signs of acute myocardial ischemia or other abnormal ECGs was expected. This was most probably related to the higher frequency of infarct development and to the higher rate of complications in these patient cohorts.

More than half the patients with ECG signs of acute myocardial ischemia fulfilled the criteria for a confirmed AMI. For patients with ST elevation this figure was even higher. This emphasizes the value of a 12-lead standard ECG in the prehospital setting [19-21], however, almost one third of the patients with these ECG signs did not have a final diagnosis of either AMI or angina pectoris. This finding highlights the challenging difficulty involved in predicting AMI, together with the need for further improvement in the prehospital diagnostic work- up among patients with ACP and a clinical suspicion of ACS. A recent study suggests that a relatively high proportion of patients with a final

Table 3

Sensitivity, specificity, NPV and PPV for a final AMI diagnosis, with 95% confidence intervals

Data presented as n (%).

^a Number of patients for whom information on final diagnosis is missing.

^b T-wave inversion in at least (any) two leads.

^c Q-wave in at least (any) two leads.

or ST-depression

ST-elevation only	36 (23.32)	92 (95.98)	69 (78.82)	74 (66.80)
Any ECG abnormality	76 (72.80)	60 (57.63)	88 (86.90)	39 (36.43)

NPV: negative predictive value; PPV: positive predictive value.

T-wave inversionb (2) Q-wavec (4)	55 (4) 116 (8)	10 (3) 24 (7)		Sensitivity	Specificity	NPV	PPV
Remaining patients (65)	807 (52)	87 (24)	ST-elevation and/	47 (42.52)	71 (86.90)	74 (81.85)	57 (52.63)

Table 4

Complications prior to hospital admission and in hospital

Prior to hospital admission In hospital

ECG with signs

ECG with other

ECG without

p^a ECG with signs

ECG with other

ECG without P^a

	of ischemia	abnormal changes	significant pathologic		of ischemia	abnormal changes	significant pathologic
	(n = 312)	(n = 427)	findings (n = 807)		(n = 312)	(n = 427)	findings (n = 807)
Heart failure	9 (2.9)B	11 (2.6)	4 (0.5)B	.03	57 (19.1)B	82 (19.5)C	42 (5.4)B, C	b.0001
(5/2/12/13/7/26)b Hypotension	8 (2.6)	4 (0.9)	12 (1.5)	.21	26 (8.7)A, B	15 (3.6)A	20 (2.6)B	b.0001
(6/2/12/13/7/26)
AV block/	2 (0.7)	2 (0.5)	0 (0.0)	.07	10 (3.4)	9 (2.1)	13 (1.7)	.37
bradyarrhythmia
(5/2/12/14/7/25) Supraventricular	5 (1.6)	5 (1.2)	6 (0.8)	.55	37 (12.3)A	23 (5.5)A	27 (3.5)A, B	b.0001
tachyarrhythmias
(7/2/13/12/7/25) Ventricular	3 (1.0)B	0 (0.0)	0 (0.0)B	.005	10 (3.3)B	8 (1.9)	5 (0.6)B	.01
tachyarrhythmias
(6/4/12/13/9/26)

Data presented as n (%).

AV block: atrioventricular block.

^{A, B, C} Pairwise comparisons; group with same letter differs significantly.

^a Age-adjusted p-value for any difference between the 3 groups.

^b Number of patients with missing information in the 3 groups respectively, prior to hospital admission and in hospital.

diagnosis of AMI can be detected prior to hospital admission with new biochemical markers [22].

The opportunity to predict AMI among patients with ACP and LBBB is a further challenge. In our study, more than one third of the patients with LBBB had a final diagnosis of AMI. This finding highlights the high frequency of AMI among ACP patients with LBBB. It could be either a first infarction leading to LBBB or a re-infarction with LBBB due to an old myocardial infarction. In addition, the high prevalence of cardiovascular complications in this patient group emphasizes the fact that patients with ACP and LBBB should be given high priority.

Our study shows that a high proportion of patients with a confirmed AMI are recruited from patients whose ECG does not show any signs of acute myocardial ischemia. Although this is well known in the hospital setting [23,24], it has not previously been as clearly addressed in the prehospital setting.

Overall 24% of all patients in the study cohort fulfilled criteria for AMI and only 6% had ST elevation myocardial infarction when related to the prehospital ECG. Thus only a minority are candidates for transport to Catheterization laboratory.

In this study, patients with ECG signs of acute myocardial ischemia had a higher risk of heart failure prior to hospital admission than those with normal ECGs. Furthermore, after hospital admission, hypoten- sion and supraventricular arrhythmias were more frequent in patients with ECG signs of acute myocardial ischemia than in the other two ECG groups. Arrhythmias and systolic myocardial dysfunction are known to be the main causes of cardiac death in patients who suffer an AMI [25]. These findings highlight the well-known association between acute myocardial ischemia and electrical and mechanical instability in the early phase of AMI [26]. There is a known relationship between the extent of myocardial damage and the risk of complications [15]. Patients with ECG signs of myocardial ischemia are expected to develop more myocardial damage [16,17].

Strengths and limitations of the study

One strength of this study is that we evaluated a large patient cohort in terms of ECG recording, symptom evaluation and compli- cations in the prehospital setting. Another strength is that all the ECGs were interpreted by the same physician, who was blinded to the patients’ outcome.

Limitations: Secondary analyses of data, for which the current study was not designed is a potential limitation. We only evaluated

patients with suspected ACS and medium to severe pain. More than one sixth of the patients were excluded from the analyses because ECG recordings were not available for interpretation. These patients might have had less Typical symptoms. This represents a significant source of bias. Due to exclusion criteria in the original interventional study, patients who were transported from a clinic and furthermore patients who had hypotension on admission of the EMS could not be included. The lack of access to previous ECG tracings on patients is a limitation, but it reflects the clinical reality in the prehospital setting [27]. Another limitation is that the final diagnosis of AMI is based on the official clinical judgement. We also lacked information about the background population with chest pain who called for the EMS.

Conclusions

Among patients with a clinical suspicion of AMI in the prehospital setting, the prevalence of ECG signs suggesting AMI was low, as was the ability to identify AMI patients using ECG findings only. We therefore need better instruments in the prehospital triage of patients with ACP.

Acknowledgments

The authors would like to thank the EMS organizations and their staff in the Vastra Gotaland Region and in the City of Halmstad in Sweden.

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