Chest pain is one of the most common causes of presentation at hospital emergency departments (EDs) and general practice.¹ some patients presenting with chest pain will have serious acute illness with a high short-term risk of mortality, which can be excluded in most patients.

In the absence of trauma, the primary focus should be exclusion of four fatal conditions: acute coronary syndrome (ACS), pulmonary embolism, aortic dissection and spontaneous pneumothorax. ACS is the most common of these.² the latter three may be accurately excluded by rapid diagnostic testing (predominantly imaging).  ACS is more challenging as it cannot be readily excluded with an acceptable level of accuracy on initial clinical evaluation or with a single investigation.³

According to the previous studies, about 50-70% of the patients with chest pain are admitted or observed in the EDs out of which only 10% are diagnosed with acute coronary syndromes and about 2 – 8% of ACS are missed on initial presentation.¹,³

Electrocardiography (ECG) is a useful tool for risk stratification of patients who present to the ED with chest pain. Studies have revealed that low-risk patients presenting with chest pain can be identified by clinical evaluation plus ECG at the time of ED presentation.⁴  ECG is unreliable in this regard, due to its limited ability to detect ischemia in the distribution of the left circumflex coronary artery, in the true posterior left ventricular region, and in patients with prior AMI.⁵,⁶ ECG evidence of ischemia may also be transient.⁷,⁸

Studies have shown that ECG’s sensitivity for acute MI was 68%, the specificity was 97%, and the diagnostic odds ratio (DOR) was 104.⁹

Hence other standard tests should be performed to rule out ACS before a patient is safely discharged from the hospital. Troponin-I, echocardiography, coronary angiography are considered as the standard investigations and can identify an ECG negative chest pain to be ACS.

Here, in this study, a focus has been given on assessment of patients with possible cardiac chest pain with a normal ECG, cardiac biomarkers, non invasive imaging and the role of scoring systems for risk stratification in the safe discharge of those patients. Also by establishing a step wise approach, this study would help all the clinicians who regularly assess patients with undifferentiated chest pain.

OBJECTIVES

To assess the incidence of Acute Coronary Syndrome (ACS) among patients presenting with chest pain and a normal initial electrocardiogram (ECG).

To evaluate the diagnostic value of cardiac biomarkers (e.g., Troponin-I) in detecting ACS in patients with normal initial ECG.

To determine the role of non-invasive imaging (e.g., echocardiography, stress testing) in identifying underlying ischemia.

To analyze the effectiveness of clinical scoring systems (e.g., TIMI, HEART score) for risk stratification and safe discharge planning in these patients.

To establish a stepwise diagnostic approach to improve the early identification of ACS and reduce missed diagnoses in patients with non-diagnostic ECG findings.

Study Setting:

The present study was conducted in the Department of Emergency Medicine, Pushpagiri Institute of Medical Sciences and Research Center, Thiruvalla, Kerala.

Study Design:

Cross-sectional and hospital-based follow-up observational study.

Ethics Approval and Consent:

Ethics approval was obtained from the Pushpagiri Institute Research and Ethics Committee. A written informed consent (in native language) was obtained by every subject (or next of kin) participating in the study.

Sample Size with Justification:

The sample size was calculated from a similar previous study by Turnipseed et al., who evaluated 1741 patients with chest pain and normal ECG on initial presentation. Assuming that the prevalence of ACS among patients with chest pain and normal ECG to be 16%, along with an absolute precision of 6% and an alpha error of 5%, the sample size is 149.

Formula used:

n = 4 × p × q / d²

Where,

p = expected prevalence or proportion agreeing with initial diagnosis

q = 100 – p

d = absolute precision

Substituting the values in the formula:

n = 4 × 16 × 84 / 6 × 6 = 149

Study Population:

Patients above the age of 30 years presenting with chest pain of acute onset and a normal ECG to the Emergency Department.

Study Period:

18 months from the date of clearance by the ethical committee; from March 2017 – August 2018.

Sampling Method:

Consecutive sampling.

Inclusion Criteria:

Patients with age 30 years or more

Patients with chest pain

Criteria of normal ECG:

1. a) Normal sinus rhythm with a heart rate of 60–100 beats/min
2. b) Normal ST segment and QRS complexes
3. c) Normal T wave morphology

Exclusion Criteria:

Chest pain due to musculoskeletal and respiratory causes

Pathological Q waves

Non-specific ST-T wave abnormalities

Any ST depression

Discrepancies in the axis of T wave and QRS

Study Tools:

Structural questionnaire

Examination

ECG

Echocardiography

Methodology:

1. Patients satisfying the inclusion criteria were enrolled into the study after an informed consent. The treating physician will begin his assessment, stabilization, and workup of the patient and the investigator will be informed. The investigator performs the physical examination and records the ECG findings. Patients with a normal initial ECG at presentation who meet the inclusion criteria will be further evaluated for elevated cardiac biomarker (high sensitivity troponin I), and the investigator also performs a bedside echocardiography to identify the presence of any regional wall motion abnormality (RWMA), systolic dysfunction, and the presence or absence of mitral regurgitation (MR), which would indicate ACS. Patients will also be subjected to repeat ECGs to look for the appearance of new changes.
2. HEART score was calculated in the included study subjects and risk assessment was done. Patients with intermediate and high risk will be admitted based on the clinical findings, and final diagnosis will be made on the basis of dynamic changes in ECG, troponin I, echocardiography, and chest X-ray by an expert physician.

Study Design (Clinical Workflow):

All the patients presenting to the emergency department with chest pain were evaluated with an ECG within 10 minutes of presentation and the ECG was assessed by the investigator. Patients meeting the inclusion criteria were taken up for the study. High sensitivity troponin I (HS trop-I) was assessed in these patients. They were also subjected to repeated ECGs and HS troponin-I. Patients in whom HS trop-I was positive were taken as NSTEACS. Among patients with no dynamic changes in ECG and with a negative HS trop-I, risk stratification using HEART score was done and patients in the intermediate and high-risk categories were admitted based on the investigator’s clinical suspicion of cardiac pain. These patients were reassessed by an expert physician (cardiologist), and a final diagnosis of unstable angina (UA) was made based on the expert clinician’s opinion, stress test, and coronary angiography done in patients.

Questionnaire Used in the Study:

Date

Name

Age

Sex

Occupation (sedentary or healthy lifestyle)

Address

Socioeconomic Status: Upper / Upper middle / Lower Middle / Upper lower / Lower

Risk Factors (Yes/No):

History of smoking

Hypertension

Diabetes

Dyslipidemia

Coronary artery disease

Deep venous thrombosis

Malignancy

Positive family history

Obesity (BMI >30)

Symptom:

Onset (0–3 hours / 3–6 hours / >6 hours)

Duration (<20 min / >20 min)

Character of pain

Aggravation with exercise

Associated autonomic symptoms

Physical Examination and Evaluation:

Systolic murmur

ECG

Trop-I (<ULN / 1–3 times ULN / >3 times ULN)

HEART score

Echocardiography (RWMA, MR, systolic dysfunction)

Dynamic ECG

Trop-I at 3 hrs

Dynamic echocardiography

Final diagnosis

Statistical Methods:

All data was entered into MS EXCEL 2016 and then analyzed with the help of SPSS (Statistical Package for Social Sciences) version 20.0. After tabulation of baseline clinico-social parameters, HEART score and final diagnosis was tabulated. Prevalence (95% confidence interval) of ACS among ECG-negative patients with chest pain was found. Association of final diagnosis and baseline variables was found using Chi-Square and t-tests. The results obtained are depicted in the form of tables, figures, and diagrams wherever necessary. A p-value of <0.05 was taken as statistically significant.

Age and gender distribution in study sample:

The study sample included 160 subjects who met the inclusion criteria. The sample population analyzed consisted of both males and females, of which 97 were males and 63 were females. The minimum age included in the study was 30 years and maximum age was 95 years. The mean age of the study sample was 55.62 with a standard deviation of 13.410. 

Llifestyle distribution in the study sample:

Out of the 160 patients who met the inclusion criteria, 40 patients (25%) had a sedentary lifestyle and 120 patients (75%) had a non sedentary lifestyle.

Baseline Vital Parameters – Distribution of Heart rate, Respiratory Rate, Systolic Blood Pressure, and SpO2 among Study Sample

Table 1: Baseline Vital Parameters – Distribution of Heart rate, Respiratory Rate, Systolic Blood Pressure, and SpO2 among Study Sample.

Distribution of smoking in the study sample:

History of smoking within the past 3 months was documented among the study sample. Out of 160 patients included in the study, 54 patients had a history of smoking. 106 study subjects had no history of smoking within past 3 months.

Distribution of hypertension, diabtes, dyslipidemia in the study sample:

Out of a total 160 study subjects, 61 had hypertension and 99 subjects were not known hypertensives.  64 of the included study subjects had diabetes on medications and 96 were not having diabetes. 81of the included study subjects had dyslipidaemia on medications and 79 were not having dyslipidaemia.

Distribution of Coronary artery disease, DVT, Malignancy

Out of the 160 study subjects included, 15 patients had prior coronary artery disease and 145 patients had no prior history of coronary artery disease. 9 of the total included subjects had a present or past history of deep venous thrombosis and 151 subjects had no DVT. 6 patients out of the 160 study subjects included had malignancy. And 154 patients had no malignancy in the present or past.

Distribution of positive family history of CAD:

Out of 160 study subjects included, 15 patients had a positive family history and 145 patients had no family history of coronary artery disease.

Distribution of obesity:

Body mass index (BMI) was calculated in the study subjects and any patient with a BMI of ≥30 was considered as obese. Out of 160 study subjects included, 16 patients were obese.

Distribution of risk factors in the study sample:

Table 2: Distribution of risk factors in the study sample.

Distribution of echocardiographic findings in study sample:

At the initial assessment of the patients, echocardiography was done and the presence of RWMA, MR or Systolic dysfunction was documented. 5 patients had RWMA, 4 patients had MR and 3 patients had systolic dysfunction.

HEART score in the study sample:

HEART scores were observed in study sample. 92 patients (57.5%) had a score of low risk (HEART score 0-3), 59 patients (36.9%) had intermediate risk (HEART score 4-6), 9 patients (5.6%) had high risk (HEART sore 7 & 8).

Distribution of acute coronary syndrome in the study sample:

Out of  160 subjects included in the study, 46 patients (28.8%) were admitted into the hospital and out of them, 26 patients (16.3%) were diagnosed to have ACS and 134 patients were non ACS. 9 patients(5.6%) had NSTEACS and 17 patients(10.6%) had unstable angina.

The present study was a cross-sectional and hospital-based follow-up observational study conducted on patients attending the Emergency Department of Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla, Kerala. The study included 160 subjects presenting with chest pain and a normal initial ECG. The duration of the study was 18 months, starting from the clearance date by the ethical committee.

Age and Gender Distribution:

The mean age of participants in this study was 54.74 years (SD: 13.414). This finding is similar to a study by Turnipseed et al., 10 which reported a mean age of 54.6 ± 12.1 years. Another study by Moy et al. 11 found a higher mean age distribution of 62.82 ± 15.34 years, indicating that the patients in our study were younger on average compared to that cohort.

In terms of gender, 97 patients (60.6%) were male, and 63 (39.4%) were female, showing a male predominance in the study population. This finding is consistent with other studies, such as one by Khesroh et al., 12 which reported a male predominance of 66% in patients with acute coronary syndrome.

Prevalence of Acute Coronary Syndrome (ACS):

Among the 160 patients with chest pain and a normal initial ECG, 26 patients (16.3%) were diagnosed with acute coronary syndrome (ACS). This prevalence is similar to that reported by Turnipseed et al.10 which found an incidence of ACS in 17% of chest pain patients with a normal ECG. 25 of the 160 patients had positive troponin-I levels (above the upper limit of normal) at presentation, further supporting the diagnosis of ACS in these patients.

These findings suggest that despite a normal initial ECG, a significant proportion of patients presenting with chest pain may still have underlying acute coronary syndrome, highlighting the need for comprehensive evaluation and risk stratification in such cases.

The current study highlights the importance of a comprehensive diagnostic approach in patients presenting with chest pain and a normal initial ECG. Despite normal ECG findings, a significant proportion of patients (16.3%) were diagnosed with acute coronary syndrome (ACS), emphasizing the need for further investigation using cardiac biomarkers and non-invasive imaging techniques. The use of troponin-I as a diagnostic tool was crucial in identifying ACS in these patients, and echocardiography provided additional insights into regional wall motion abnormalities and systolic dysfunction. Risk stratification using the HEART score proved effective in identifying patients at intermediate and high risk, guiding clinical decision-making regarding admission and further management. Our findings underline the significance of combining clinical evaluation, biomarker analysis, and imaging to reduce the risk of missed diagnoses. Therefore, a stepwise approach, incorporating serial ECGs, cardiac biomarkers, and imaging, is essential for safe discharge planning and improving patient outcomes in the emergency department.

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