High Detectability of Prehospital 12-Lead Electrocardiogram in Diagnosing Spasm-Induced Acute Coronary Syndrome

Abstract

Background: The importance of prehospital (PH) electrocardiograms (ECG) recorded by emergency medical services (EMS) for diagnosing coronary artery spasm-induced acute coronary syndrome (CS-ACS) remains unclear.

Methods and Results: We enrolled 340 consecutive patients with ACS who were transported by EMS within 12 h of symptom onset. According to Japanese Circulation Society guidelines, CS-ACS (n=48) was diagnosed with or without a pharmacological provocation test (n=34 and n=14, respectively). Obstructive coronary artery-induced ACS (OC-ACS; n=292) was defined as ACS with a culprit lesion showing 99% stenosis or >75% stenosis with plaque rupture or thrombosis observed via angiographic and intravascular imaging. Ischemic ECG findings included ST-segment deviation (elevation or depression) and negative T and U waves. In CS-ACS, the prevalence of ST-segment deviation decreased significantly from PH-ECG to emergency room (ER) ECG (77.0% vs. 35.4%; P<0.001), as did the prevalence of overall ECG abnormalities (81.2% vs. 45.8%; P<0.001). Conversely, in OC-ACS, there was a similar prevalence on PH-ECG and ER-ECG of ST-segment deviations (94.8% vs. 92.8%, respectively; P=0.057) and abnormal ECG findings (96.9% vs. 95.2%, respectively; P=0.058). Patients with abnormal PH-ECG findings that disappeared upon arrival at hospital without ER-ECG or troponin abnormalities were more frequent in the CS-ACS than OC-ACS group (20.8% vs. 1.0%; P<0.001).

Conclusions: PH-ECG is valuable for detecting abnormal ECG findings that disappear upon arrival at hospital in CS-ACS patients.

Coronary artery spasm is a major etiology of acute coronary syndrome (ACS) and is characterized by transient myocardial ischemia due to epicardial coronary artery spasms. The early diagnosis and therapeutic management of coronary artery spasm-induced ACS (CS-ACS) are required because patients occasionally develop serious cardiac complications, such as sudden cardiac death, myocardial infarction, and ventricular arrhythmias.^1,2 However, it is sometimes challenging because of the short duration of the attack.³ Chest pain in CS-ACS often resolves on its own, and sometimes ischemic electrocardiogram (ECG) changes cannot be detected upon arrival at the emergency department.

To date, prehospital 12-lead ECG (PH-ECG) systems developed by emergency medical service (EMS) personnel at the site of first medical contact (FMC) have been introduced in several countries. PH-ECG is useful for reducing door-to-balloon time and mortality in patients with ACS,⁴ and performing PH-ECG and notifying the emergency care service in advance are Class I recommendations in the American College of Cardiology/American Heart Association and European Society of Cardiology guidelines.^5,6 However, previous studies mainly focused on the early reperfusion therapy or the prognosis of ACS; the benefits of PH-ECG in the early diagnosis of CS-ACS remain unclear.

We hypothesized that PH-ECGs performed by EMS personnel would be effective in diagnosing CS-ACS. This study aimed to assess the clinical utility of PH-ECGs in the early diagnosis of CS-ACS.

Methods

Patients and Protocols

This retrospective study was performed at Yokohama City University Medical Center. Patients suspected of ACS within 12 h of onset transported from the field by ambulance were screened (n=707). ACS was defined as ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation ACS. STEMI was defined as chest pain lasting at least 30 min with new ST-segment elevation and elevated troponin I concentrations above the 99^th percentile of a normal reference population.⁷ All patients were treated according to the current guidelines of the Japanese Circulation Society (JCS).⁸

Definitions of CS-ACS and Obstructive Coronary Artery-Induced ACS (OC-ACS)

CS-ACS was defined as cases of ≤75% coronary stenosis without plaque rupture or thrombosis formation observed via angiographic and/or intravascular ultrasound or optical coherence tomography and confirmed coronary artery spasm according to the guidelines provided by the JCS for diagnosing and treating patients with coronary spastic angina.^1,9 Obstructive coronary OC-ACS was defined as cases of a culprit lesion with ≥75% stenosis with plaque rupture or thrombosis formation observed via angiographic and/or intravascular ultrasound or optical coherence tomography. The percutaneous coronary intervention (PCI) operator identified the culprit lesion of the ACS at the time of angiography based on angiographic lesion morphology and ECG and echocardiographic findings.

Since 2010, EMS personnel in Yokohama City have been instructed by the Yokohama City Medical Control Council to record a PH-ECG in an ambulance for hospital selection (triage) if ACS is suspected. All EMS personnel followed the same field protocols throughout the study period. The first ECG acquired upon arrival at the emergency room (ER) was defined as the ER-ECG. The following ECG devices were used: for PH-ECG, ECG3350 or ECG2250 (both Nihon Kohden, Tokyo, Japan); for ER-ECG, Cardiostar FX-7542 (Fukuda Denshi, Tokyo, Japan). The time between the PH-ECG and ER-ECG, the time from symptom onset to PH-ECG, the time from symptom onset to ER-ECG, ACS characteristics, and vital signs at FMC were compared between the CS-ACS and OC-ACS groups.

ST-segment elevation was defined as ST-elevation at the J-point in 2 contiguous leads with a cut-off point ≥1 mm in all leads other than leads V2–V3, where the following cut-off points apply: ≥2 mm in men aged ≥40 years, ≥2.5 mm in men aged <40 years, or ≥1.5 mm in women regardless of age.⁷ ST-segment depression was diagnosed if the ST-segment was horizontal or downward sloping, and the depression was ≥0.5 mV in 2 contiguous leads.⁷ Reciprocal ST-segment depression associated with ST-segment elevation was not considered an ischemic ECG change. A negative T wave was defined as T wave inversion >1 mm in 2 contiguous leads with a prominent R wave or R/S ratio >1.⁷ A negative U wave was defined as a discrete negative deflection of >0.05 mV within the TP segment. In addition to PH-ECG and ER-ECG, we corrected ECG data during the spasm provocation test. Because ST-segment depression and negative T and U waves do not always clearly reflect the ischemic area, we focused on evaluating ST-segment elevation in the ECG during the provocation test. Based on JCS guidelines,⁸ we classified ST-segment elevation into anterior (V1–V6), inferior (II, III, aVF), and posterior (I, aVL) patterns.

Each risk factor (hypertension, diabetes, and dyslipidemia) was defined according to JCS guidelines.⁸ The severity of chest pain severity was measured upon arrival at the ER using a 10-point scale, with 0 representing no pain and 10 representing the worst pain between onset and presentation to hospital. Killip classification was provided by the cardiologist at the ER during the initial evaluation, according to the JCS guidelines.⁸

We collected data on medication prescribed prior to admission, including nitroglycerin sublingual tablets, nicorandil, long-acting nitrates, and calcium channel blockers. We could not accurately determine the precise timing of the use of nitroglycerin sublingual tablets, so it was defined as any use between the onset of symptoms and the EMS call. The use of nicorandil, long-acting nitrates, and calcium channel blockers was determined based on patient self-reports, assuming they were taking the medications on a regular schedule.

Biochemical analyses were performed using venous blood samples obtained from all enrolled patients upon admission. Troponin I concentrations were measured on admission, with cut-off values for positivity set according to manufacturer recommendations using the 99^th percentile as the criterion. During the study period, the definition of troponin I positivity changed because of a change in the reagent. On August 4, 2020, our hospital switched from Chemiluminescent Troponin I Ultra (Siemens, Erlangen, Germany; 99^th percentile 0.040 ng/mL, maximum 50 ng/mL) to Chemiluminescent hs Troponin (Siemens; 99^th percentile 0.047 ng/mL, maximum 25 ng/mL). The in-house correlation between these 2 assays (n=42) was strong (y=0.79x+0.12; r=0.99). The cut-off for positivity was 0.040 ng/mL before August 3, 2020, and 0.047 ng/mL thereafter.

The FMC was defined as the point at which the EMS personnel arrived to assist the patient. Door time was defined as when the patient arrived at the hospital. Patients meeting any of the following criteria were excluded: no PH-ECGs (n=150), conditions precluding the evaluation of ST-segment changes on ECG (i.e., complete left or right bundle branch block, left ventricular hypertrophy, ventricular pacing, or receiving drugs with potential effects on ST-T changes; n=121), no ER-ECGs (n=16), diagnosis unknown (n=21), Type II myocardial infarction triggered by non-coronary etiologies (n=6),⁷ previous myocardial infarction (n=41), spontaneous coronary artery dissection (n=3), and previously diagnosed coronary spasm (n=9); the final study group consisted of 340 patients (Figure 1). All patients underwent invasive coronary angiography and/or multislice coronary computed tomography after admission to confirm the diagnosis. Of the 340 patients included in the study, 48 were diagnosed with CS-ACS and 292 were diagnosed with OC-ACS.

Figure 1.

Study flowchart. ACS, acute coronary syndrome; ECG, electrocardiogram; ER-ECG, ECG in the emergency room; PH-ECG, prehospital ECG.

Ethical Considerations

The study protocol was approved by the Institutional Review Board of Yokohama City University. Because the study was retrospective in nature, the requirement for written informed consent was waived. This study adhered to the Declaration of Helsinki and the ethical standards of the Committee on Human Experimentation.

Statistical Analyses

All continuous data are expressed as the mean±SD or percentage of patients or median with interquartile range (IQR) according to their distribution, and categorical variables are expressed as frequencies and percentages. Student’s t-test or the Mann-Whitney U test, as appropriate, was used to determine the significance of differences in continuous variables between groups. For categorical variables, Fisher’s exact test or the Chi-squared test was used. Bowker’s test was used to detect changes in the frequency of abnormal ECG findings between the PH-ECG and ER-ECG. Statistical significance was defined as a 2-sided P<0.05. All data analyses were performed using JMP Pro^® 17 (SAS Institute Inc., Cary, NC, USA).

Results

Diagnostic Process for CS-ACS

During hospitalization, a spasm provocation test was performed on 36 patients. The median time from admission to the provocation test was 5 days (IQR 3–7 days), with 34 of 36 tests yielding positive results. Of the 2 patients who were negative on the provocation test, 1 had an organic coronary artery lesion and was diagnosed with OC-ACS. The other patient showed a 90% focal stenosis in Lesion #11 induced by acetylcholine but without significant ischemic ECG changes. Nevertheless, the patient was diagnosed with CS-ACS due to ST-segment elevation observed on the PH-ECG. The decision to perform spasm provocation testing was determined by the heart team. Patients with CS-ACS who did not undergo a spasm provocation test (n=14) were diagnosed according to JCS guidelines based on clinical symptoms, ECG findings, and response to nitroglycerin;⁹ all 14 patients had ischemic ECG changes, 11 showed ST elevation, and 3 showed ST depression. In the CS-ACS group, 2 of 48 patients underwent PCI for atherosclerotic coronary stenosis. In the OC-ACS group, 288 of 292 patients underwent PCI or coronary artery bypass grafting.

Of the 34 patients who underwent the spasm provocation test, 33 showed ST-segment elevation during the test. One patient without ST-segment elevation showed ST depression during the provocation test and PH-ECG. Of the 33 patients with ST-segment elevation during the provocation test, 16 showed ST-segment elevation on PH-ECG, and 12 of these 16 (75%) patients had a similar ST-segment elevation pattern to that seen in ECGs during the provocation tests.

Patient Characteristics

Patient characteristics are presented in the Table. The CS-ACS group was younger and had a greater proportion of patients with diabetes and smokers than the OC-ACS group. The chief symptom in most patients in both groups was chest pain. The chest pain scale score at arrival was significantly lower in the CS-ACS than OC-ACS group (median 2 [IQR 0–5] vs. 8 [IQR 5–10]; P<0.001). There was no significant difference in the frequency of nitroglycerin sublingual tablet use between the CS-ACS and OC-ACS groups (4/48 [8%] vs. 8/292 [3%] patients, respectively; P=0.073). However, significantly more patients in the CS-ACS than OC-ACS group used nicorandil or long-acting nitrates (5/48 [10%] vs. 5/292 [2%] patients, respectively; P<0.001). There was no significant difference in the frequency of calcium channel blocker use between the CS-ACS and OC-ACS groups (15/48 [31%] vs. 81/292 [28%] patients, respectively; P=0.616).

Table.

Patient Characteristics

	CS-ACS (n=48)	OC-ACS (n=292)	P value
Age (years)	57±11	65±13	<0.001
Male sex	41 (85)	244 (83)	0.746
Body mass index (kg/m2)	24±4	24±3	0.149
Chief complaint was chest pain	47 (97)	274 (93)	0.493
Onset time between 00:00–05:59 hours	12 (25)	53 (18)	0.263
Chest pain scale at admission (0–10)	2 (0–5)	8 (5–10)	<0.001
Killip ≥II	6 (12)	60 (20)	0.239
Current smoker	24 (50)	90 (30)	0.009
Hypertension	20 (41)	144 (49)	0.325
Diabetes	5 (10)	135 (46)	<0.001
Dyslipidemia	23 (47)	159 (54)	0.400
Nitroglycerin sublingual tablets	4 (8)	8 (3)	0.073
Nicorandil or long-acting nitrates	5 (10)	5 (2)	<0.001
Calcium channel blocker	15 (31)	81 (28)	0.616
Family history of CAD	5 (10)	51 (17)	0.294
At first medical contact
Japan coma scale score ≥1	6 (12)	34 (11)	0.864
Heart rate (beats/min)	73±18	75±20	0.604
Systolic blood pressure (mmHg)	136±38	138±36	0.804
Diastolic blood pressure (mmHg)	84±21	85±23	0.787
SpO2 (%)	98 [97–99]	98 [97–99]	0.694
Respiratory rate (/min)	24 [18–28]	23 [20–26]	0.772
At admission
Hemoglobin (g/dL)	14.2±1.8	14.4±1.8	0.397
eGFR (mL/min/1.73 m2)	72±17	67±19	0.102
BNP (pg/mL)	18.9 [6.2–33.7]	35.7 [14.5–88.7]	<0.001
Troponin I (ng/mL)	0.018 [0.004–0.073]	0.151 [0.028–1.217]	<0.001
Positive troponin I	22 (45)	207 (70)	<0.001
Exceeding the upper limit of troponin I	2 (4)	200 (68)	<0.001
Peak creatine kinase during hospitalization (IU/L)	138 [90–255]	2,054 [949–3,513]	<0.001
Invasive CA during hospitalization	44 (91)	292 (100)	<0.001
Computed tomography CA during hospitalization	4 (8)	0 (0)	<0.001
No. diseased vessels	0 (0–0)	2 (1–2)	<0.001
PCI during hospitalization	2 (4)	278 (95)	<0.001
Coronary artery bypass grafting	0 (0)	10 (3)	0.368
Time between PH-ECG and ER-ECG (min)	26 [21–33]	24 [20–28]	0.106
Time between symptom onset and PH-ECG (min)	41 [26–62]	56 [33–108]	0.003
Time between symptom onset and ER-ECG (min)	65 [54–96]	80 [58–135]	0.007

Unless indicated otherwise, data are shown as the mean±SD, median [interquartile range], or n (%). BNP, B-type natriuretic peptide; CA, coronary angiography; CAD, coronary artery disease; CS-ACS, coronary spasm-induced acute coronary syndrome; eGFR, estimated glomerular filtration rate; ER-ECG, electrocardiogram in the emergency room; FMC, first medical contact; OC-ACS, obstructive coronary artery-induced acute coronary syndrome; PCI, percutaneous coronary intervention; PH-ECG, prehospital electrocardiogram.

The time between PH-ECG and ER-ECG tended to be longer in the CS-ACS than OS-ACS group (median 26 [IQR 21–33] vs. 24 [IQR 20–28] min; P=0.106). However, the time from symptom onset to PH-ECG (median 41 [IQR 26–62] vs. 56 [IQR 33–108] min; P=0.003) or ER-ECG (median 65 [IQR 54–96] vs. 80 [IQR 58–135] min; P=0.007) was significantly shorter in the CS-ACS than OC-ACS group.

Changes in ECG Findings in CS-ACS vs. OC-ACS

Figure 2 shows differences in the prevalence of ischemic ECG findings between the PH-ECG and ER-ECG. ST-segment deviation included ST-segment elevation and depression. All ECG abnormalities included ST-segment elevation, ST-segment depression, and negative T and U waves.

Figure 2.

Changes in ischemic 12-lead electrocardiogram (ECG) findings between prehospital (PH) and emergency room (ER) ECGs in patients with coronary artery spasm-induced acute coronary syndrome (CS-ACS) and obstructive coronary artery-induced acute coronary syndrome (OC-ACS). Frequencies of (A) ST-segment deviation and (B) overall ECG abnormalities. P values were calculated using Bowker’s test. ST-segment deviation included ST-segment elevation and ST-segment depression. All ECG abnormalities included ST-segment elevation, ST-segment depression, negative T wave, and negative U wave.

In the CS-ACS group, significant differences in the frequency of ST-segment deviations (from 77.0% to 35.4%; P<0.001) and overall ECG abnormalities (from 81.2% to 45.8%; P<0.001) were observed between PH-ECGs and ER-ECGs. In contrast, in the OC-ACS group, ST-segment deviations (from 94.8% to 92.8%; P=0.057) and overall ECG abnormalities (from 96.9% to 95.2%; P=0.058) were similar on PH-ECGs and ER-ECGs. Figure 3 shows a representative case of CS-ACS that presented ECG changes between the PH-ECG and ER-ECG.

Figure 3.

Representative case of a patient with coronary artery spasm-induced acute coronary syndrome (CS-ACS) who presented with electrocardiogram (ECG) changes between the prehospital and emergency room ECGs. Chest pain in CS-ACS often resolves independently, and ischemic ECG changes are sometimes not detected upon arrival at the emergency department.

Figure 4 shows detailed changes in the ischemic ECG findings. The frequency of ST-segment elevation was significantly reduced from PH-ECG to ER-ECG in the CS-ACS group (from 56.2% to 18.7%; P<0.001) but not in the OC-ACS group (from 83.5% to 81.8%; P=0.131). The frequency of ST-segment depression, negative T, and negative U waves between the PH-ECG and ER-ECG did not differ significantly between the 2 groups.

Figure 4.

Differences in detailed ischemic 12-lead electrocardiogram (ECG) findings between prehospital (PH) and emergency room (ER) ECGs in patients with coronary artery spasm-induced acute coronary syndrome (CS-ACS) and obstructive coronary artery-induced acute coronary syndrome (OC-ACS). P values were calculated using Fisher’s exact tests or Chi-squared tests.

Next, we investigated the frequency of patients who presented abnormal ECG findings on the PH-ECG but normal ECG findings on the ER-ECG, indicating that the ECG abnormality resolved before arrival at hospital (Figure 5). The frequency of patients with abnormal PH-ECG but normal ER-ECG findings was significantly higher in the CS-ACS than OC-ACS group (37.5% vs. 2.0%, respectively; P<0.001). There was a significantly higher proportion of patients who presented abnormal ECG findings on the PH-ECG, normal ECG findings on the ER-ECG, and troponin I concentrations within the normal range at admission in the CS-ACS than OC-ACS group (20.8% vs. 1.0%; P<0.001).

Figure 5.

Proportions of patients with abnormal prehospital (PH) but normal emergency room (ER) electrocardiograms (ECGs) in the coronary artery spasm-induced acute coronary syndrome (CS-ACS) and obstructive coronary artery-induced acute coronary syndrome (OC-ACS) groups. (A) Proportion of patients with an abnormal PH-ECG but normal ER-ECG. (B) Proportion of patients with abnormal PH-ECG, normal ER-ECG, and negative troponin at admission. P values were calculated using Fisher’s exact tests or Chi-squared tests.

Patients with CS-ACS were divided into 2 groups: those in whom the diagnosis was based on a positive pharmacological spasm provocation test (n=34) and those in whom the diagnosis was based on ECG changes and normal coronary angiography without a provocation test (n=14). We compared the frequency of ischemic ECG findings between the PH-ECG and ER-ECG in patients with CS-ACS diagnosed with and without a pharmacological spasm provocation test (Figure 6). In both groups, the frequency of ST-segment deviations and all ECG abnormalities decreased significantly from the PH-ECG to ER-ECG.

Figure 6.

Frequency of ischemic 12-lead electrocardiogram (ECG) findings between prehospital (PH) and emergency room (ER) ECGs in patients with coronary artery spasm-induced acute coronary syndrome (CS-ACS) and obstructive coronary artery-induced acute coronary syndrome (OC-ACS). Frequency of (A) ST-segment deviation and (B) overall ECG abnormalities. P values were calculated using Bowker’s test. ST-segment deviation included ST-segment elevation and depression. All ECG abnormalities included ST-segment elevation, ST-segment elevation depression, negative T wave, and negative U wave.

In addition, to clarify the effect of medications on ECG findings, we investigated differences in medications between patients with and without abnormal ECG changes. For PH-ECG in CS-ACS patients, there was no significant difference in the use of nitroglycerin sublingual tablets, nicorandil or long-acting nitrates, or calcium channel blockers between patients with and without abnormal ECG changes (Supplementary Table 1). In contrast, for ER-ECG in CS-ACS patients, although there was no significant difference in the use of nitroglycerin sublingual tablets between those with and without abnormal ECG changes, the rates of use of nicorandil or long-acting nitrates and calcium channel blockers were significantly higher in patients with than without abnormal ECG changes (5% vs. 0% [P=0.015] and 13% vs. 2% [P<0.001], respectively; Supplementary Table 2). In the OC-ACS group, there were no significant differences in medication usage rates between patients with and without abnormal ECG changes, whether assessed by PH-ECG or ER-ECG (Supplementary Tables 1,2).

Discussion

This study has 2 key findings. First, in the CS-ACS group, abnormal ECG findings, especially ST elevation, were more frequent on the PH-ECG than ER-ECG. Conversely, in the OC-ACS group, the frequency of abnormal ECG findings was similar on the ER-ECG and PH-ECG. Second, in 20.4% of patients with CS-ACS, the PH-ECG rather than ER-ECG detected abnormalities despite normal troponin concentrations and normal ECG findings on admission, whereas abnormalities were detected in only 1% of patients with OC-ACS. To the best of our knowledge, this is the first study demonstrating the usefulness of PH-ECG for diagnosing CS-ACS.

Role of PH-ECG in Diagnosing CS-ACS

A unique feature of CS-ACS, characterized by transient myocardial ischemia secondary to spontaneous coronary artery spasms, may play a role in the rapid resolution of ECG abnormalities. The chest pain severity scale score on admission was significantly lower in the CS-ACS than OC-ACS group, and the frequency of ST-segment elevation was significantly reduced from the PH-ECG to ER-ECG in the CS-ACS group. These results indicate the difficulty in detecting spontaneous ECG changes during attacks in patients with CS-ACS and suggest the clinical utility of PH-ECG for the accurate and early diagnosis of CS-ACS.

Numerous observational studies have demonstrated that PH-ECG can reduce mortality, total reperfusion time, and door-to-balloon time in patients with STEMI.^4,10,11 In a meta-analysis of 14 studies involving 29,365 patients,⁴ the PH-ECG led to a shorter door-to-balloon time (mean difference in time −26.24 min; 95% confidence interval [CI] −33.46, −19.02; P<0.001) and lower short-term mortality (odds ratio 0.72; 95% CI 0.61–0.85; P<0.001) than the control group. However, apart from a few case reports,¹² the clinical benefits of PH-ECG have not been investigated in patients with CS-ACS.

Our results demonstrate the different roles of PH-ECG in OC-ACS and CS-ACS. In the OC-ACS group, the frequency of ST-segment deviation and overall ECG abnormalities was similar on PH-ECG and ER-ECG, suggesting that PH-ECG provides the least additional information in diagnosing ACS. In contrast, in the CS-ACS group, the ECG findings (especially ST-segment elevation) differed significantly between PH-ECGs and ER-ECGs. In addition, the frequency of abnormal findings detected solely on PH-ECGs, without any abnormalities on ECG or in troponin concentrations at the time of hospital arrival, was higher in the CS-ACS than OC-ACS group. Therefore, PH-ECG, the earliest recorded ECG in ACS, provided valuable information and aided in the diagnosis of ACS in patients with CS-ACS who had less chest pain at admission.

This study also highlights the diagnostic utility of PH-ECG in patients with coronary spasms presenting with ACS. A previous study demonstrated that in 986 patients with coronary spasm confirmed via the ergonovine provocation test, 149 (15.1%) presented with ACS and 847 (84.9%) presented with chronic coronary syndrome.¹³ In that study, multivariable Cox regression analyses showed that cases of coronary spasm presenting with ACS were associated with an increased risk of major adverse cardiac events (hazard ratio 1.65; 95% CI 1.14–2.37; P=0.007) and recurrent myocardial infarction (hazard ratio 2.57; 95% CI 1.35–4.87; P=0.004).¹³ Thus, the possibility of diagnosing CS-ACS with PH-ECG is extremely important because coronary spasm patients presenting with ACS have a worse prognosis than coronary spasm patients with chronic coronary syndromes.

We need to consider the prevalence of CS-ACS in the present study to align our findings with current clinical practices for ACS. Our research focused exclusively on patients with ACS who were transported by ambulance and in suitable condition for evaluating ST-segment changes on ECG. Nakayama et al. reported a 20% prevalence of coronary spasms in non-ST-elevation ACS patients.¹⁴ Their study differs from the present study in that they excluded ST-elevation ACS patients and included patients who were not transported by EMS and in suitable condition for evaluating ST-segment changes on ECG. Despite the differences in study populations between the present study and that of Nakayama et al., their reported CS-ACS prevalence is comparable to the 14% observed in the present study. Therefore, although it is challenging to determine whether the 14% prevalence of CS-ACS in our study is high or low, these figures are comparable to previous research findings.

The results of this study indicate the importance of the widespread use of PH-ECG in ACS, even though the use of PH-ECG is not widespread in Japan. A report from the Japanese nationwide survey of 69 fire departments in 2016 found that the actual PH-ECG usage rate was only 49.3%.¹⁵ Because CS-ACS is more common in Japan than in other countries,^16,17 the widespread use of PH-ECG in Japan is desirable. Further prospective studies are required to investigate whether PH-ECG performed by EMS can improve the diagnostic performance and prognosis of patients with CS-ACS.

Study Limitations

This study has several limitations. First, this was a single-center retrospective observational study. Therefore, a potential selection bias could not be completely excluded. Second, although obstructive atherosclerotic ACS was confirmed through coronary angiography or intravascular imaging, the possibility of coexisting CS-ACS was not entirely ruled out in the OC-ACS group. Third, the time from symptom onset to PH-ECG was shorter in the CS-ACS than OC-ACS group, although the exact reason for this is unclear. However, there are several possible explanations. Considering patients’ backgrounds, patients with CS-ACS were younger and had a higher prevalence of tobacco use and a lower incidence of diabetes. These factors are reported to be associated with reduced hospital delays.^18,19 In addition, CS-ACS patients had higher vasodilator prescription rates compared with OC-ACS patients (Table), which may indicate that these patients were instructed to seek immediate care if they experienced severe chest pain, because recognition of symptoms as cardiac in origin has been reported to be associated with early calls to emergency services.¹⁸ Finally, prior medication may have affected ECG changes in our study. In CS-ACS patients, the rates of use of nicorandil or long-acting nitrates and calcium channel blockers were significantly higher in those with abnormal ER-ECG changes, suggesting these vasodilators may impact ER-ECG findings. Nevertheless, these results do not decrease the clinical significance of our study, which demonstrates the utility of PH-ECG in the early diagnosis of CS-ACS.

Conclusions

PH-ECG is the earliest assessment of ACS and is clinically useful for detecting ECG abnormalities in patients with CS-ACS. Further prospective studies are required to investigate whether PH-ECG performed by EMS can improve the diagnostic performance and prognosis of patients with CS-ACS.

Acknowledgments / Sources of Funding

None.

Disclosures

M. Kosuge is a member of Circulation Journal’s Editorial Board. The remaining authors have no conflicts of interest to disclose.

IRB Information

This study was approved by Yokohama City University (Reference no. F240100009) and the ethics committees of the respective hospitals.

Data Availability

Individual deidentified participant data will be shared. All analyzable datasets related to the study will be shared, as will the study protocol and statistical analysis plan. The data will be available immediately following publication and ending 10 years after publication. The data will be shared with anyone wishing to access the data, for any purpose. The data will be shared as Excel files via email.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-24-0485

References

• 1.   Hokimoto S, Kaikita K, Yasuda S, Tsujita K, Ishihara M, Matoba T, et al. JCS/CVIT/JCC 2023 guideline focused update on diagnosis and treatment of vasospastic angina (coronary spastic angina) and coronary microvascular dysfunction. Circ J 2023; 87: 879–936.
• 2.   Takagi Y, Takahashi J, Yasuda S, Miyata S, Tsunoda R, Ogata Y, et al. Prognostic stratification of patients with vasospastic angina: A comprehensive clinical risk score developed by the Japanese Coronary Spasm Association. J Am Coll Cardiol 2013; 62: 1144–1153.
• 3.   Takagi Y, Yasuda S, Takahashi J, Tsunoda R, Ogata Y, Seki A, et al. Clinical implications of provocation tests for coronary artery spasm: Safety, arrhythmic complications, and prognostic impact: Multicentre registry study of the Japanese Coronary Spasm Association. Eur Heart J 2013; 34: 258–267.
• 4.   Nakashima T, Hashiba K, Kikuchi M, Yamaguchi J, Kojima S, Hanada H, et al. Impact of prehospital 12-lead electrocardiography and destination hospital notification on mortality in patients with chest pain: A systematic review. Circ Rep 2022; 4: 187–193.
• 5.   O’Connor RE, Brady W, Brooks SC, Diercks D, Egan J, Ghaemmaghami C, et al. Part 10: Acute coronary syndromes: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2010; 122(18 Suppl 3): S787–S817.
• 6.   Steg PG, James SK, Atar D, Badano LP, Lundqvist CB, Borger MA, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569–2619.
• 7.   Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol 2018; 72: 2231–2264.
• 8.   Kimura K, Kimura T, Ishihara M, Nakagawa Y, Nakao K, Miyauchi K, et al. JCS 2018 guideline on diagnosis and treatment of acute coronary syndrome. Circ J 2019; 83: 1085–1196.
• 9.   JCS Joint Working Group. Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2013): Digest version. Circ J 2014; 78: 2779–2801.
• 10.   Ortolani P, Marzocchi A, Marrozzini C, Palmerini T, Saia F, Baldazzi F, et al. Usefulness of prehospital triage in patients with cardiogenic shock complicating ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Am J Cardiol 2007; 100: 787–792.
• 11.   Matsuzawa Y, Kosuge M, Fukui K, Suzuki H, Kimura K. Present and future status of cardiovascular emergency care system in urban areas of Japan: Importance of prehospital 12-lead electrocardiogram. Circ J 2022; 86: 591–599.
• 12.   Singh A, Nguyen L, Everest S, Bhandari M. Coronary vasospasm presenting as ST-elevation myocardial infarction. Cureus 2022; 14: e22205.
• 13.   Cho SW, Park TK, Gwag HB, Lim AY, Oh MS, Lee DH, et al. Clinical outcomes of vasospastic angina patients presenting with acute coronary syndrome. J Am Heart Assoc 2016; 5: e004336.
• 14.   Nakayama N, Kimura K, Endo T, Fukui K, Himeno H, Iwasawa Y, et al. Current status of emergency care for ST-elevation myocardial infarction in an urban setting in Japan. Circ J 2009; 73: 484–489.
• 15.   Otani H, Tanaka H, Maki A, Takyu H, Harikae K, Ueta H, et al. The utilization of pre-hospital 12 lead electrocardiogram by emergency life-saving technicians and its education. J Jpn Soc Emerg Med 2017; 20: 703–711.
• 16.   Mizuno Y, Harada E, Morita S, Kinoshita K, Hayashida M, Shono M, et al. East Asian variant of aldehyde dehydrogenase 2 is associated with coronary spastic angina: Possible roles of reactive aldehydes and implications of alcohol flushing syndrome. Circulation 2015; 131: 1665–1673.
• 17.   Pristipino C, Beltrame JF, Finocchiaro ML, Hattori R, Fujita M, Mongiardo R, et al. Major racial differences in coronary constrictor response between Japanese and Caucasians with recent myocardial infarction. Circulation 2000; 101: 1102–1108.
• 18.   Perkins-Porras L, Whitehead DL, Strike PC, Steptoe A. Pre-hospital delay in patients with acute coronary syndrome: Factors associated with patient decision time and home-to-hospital delay. Eur J Cardiovasc Nurs 2009; 8: 26.
• 19.   Ogushi A, Hikoso S, Kitamura T, Nakatani D, Mizuno H, Suna S, et al. Factors associated with prehospital delay among patients with acute myocardial infarction in the era of percutaneous coronary intervention: Insights from the OACIS registry. Circ J 2022; 86: 600–608.