Clinical characteristics and outcomes of acute coronary syndrome patients in a PCI-Limited setting: a prospective study from Bhutan

Abstract

Introduction

Coronary artery disease is the most prevalent heart condition and a leading cause of mortality worldwide. Acute coronary syndrome (ACS) encompasses ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA). ACS has become an increasingly concerning health issue in Bhutan. Currently, no baseline data exists on ACS in the country. This study aims to assess the burden of ACS by analyzing the clinical characteristics and outcomes of patients diagnosed with ACS who presented to the National Referral Hospital in Bhutan.

Methods

A prospective cohort study was conducted at the Emergency Department of Jigme Dorji Wangchuk (JDW) National Referral Hospital from October 1, 2022, to September 30, 2023. All patients diagnosed with ACS who presented to the Emergency Department were included in the study. Demographic and clinical presentations were recorded. Electrocardiogram (ECG) recordings were performed for all patients with ACS and categorized into STEMI, NSTEMI, and UA. Appropriate treatments were initiated, and patients were closely monitored. Depending on the severity, patients were either admitted to the medical ward or intensive care unit, while some were discharged home. All data were recorded using a standard pro forma developed for the study. Data analysis was performed using SPSS version 23.

Results

During the study period, 67 patients were diagnosed with ACS. Of these, over 58% (39/67) had NSTEMI, while approximately 33% (22/67) had STEMI. The mean age ± SD of ACS patients was 63.5 ± 16.8 years, with the majority being male (67.2%, 45/67). More than half of the ACS patients presented to the hospital within 24 h of symptom onset, with chest pain (29.7%) and shortness of breath (26.4%) being the most common complaints. Among STEMI patients, over 60% exhibited ST elevation in the anterior and septal leads on ECG, and more than two-thirds required thrombolytic therapy (77.3%, 17/22). Among thrombolytic agents, alteplase was the most commonly used (70%), followed by streptokinase (17.6%). Of the 67 ACS patients, over 46% (31/67) developed complications, with more than one-fourth experiencing heart failure (26.9%). Complications were significantly more common in STEMI patients compared to those with NSTEMI (p < 0.001). The majority (61.2%, 41/67) were discharged home after improvement, while one-third required referral overseas for cardiac interventions. Older age (≥ 60 years) was independently associated with ACS (OR 9.5, 95% CI 1.1–86.9, p = 0.046). Other medical conditions, including hypertension, diabetes, dyslipidemia, and smoking, increased the likelihood of ACS; however, these associations were not statistically significant (p > 0.05).

Conclusion

Among the cases of acute coronary syndrome, 58% were classified as NSTEMI and 33% as STEMI. A majority of patients presented to the hospital within 24 h, expressing complaints of chest pain and shortness of breath, and received essential thrombolytic therapy. Approximately 48% of these patients developed complications, and over one-third were referred overseas for additional treatment. This study indicates that acute coronary syndrome is an emerging public health concern in Bhutan, underscoring the urgent necessity for the establishment of percutaneous coronary intervention (PCI) within the country to mitigate the need for overseas referrals.

Introduction

Acute coronary syndromes (ACS) encompass a range of conditions, including patients who present with recent changes in signs and symptoms, with or without electrocardiogram (ECG) alterations, and with or without acute elevations in cardiac troponin-T enzyme levels [1].

ACS is classified into ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA) [2].

The diagnosis of ACS is based on the patient’s presentation, clinical assessment, ECG changes, and elevation of biochemical markers of myocardial necrosis [3]. UA is defined as the presence of ischemic symptoms without elevations in cardiac biomarkers and transient, if any, ECG changes. The term myocardial infarction (MI) is used when there is evidence of myocardial necrosis in acute myocardial ischemia. STEMI is differentiated from NSTEMI by persistent ECG findings of ST-segment elevation [4, 5].

ACS remains a major cause of mortality and morbidity worldwide. STEMI and NSTEMI incidence rates are 77 and 132 per 100,000, respectively [6]. A Coronary Events Registry showed the rate of STEMI is 42% and NSTEMI of 58% [7].

Advanced age, obesity, family history of coronary artery disease, Diabetes mellitus, dyslipidemia, smoking, and hypertension are the independent risk factors for ACS [8].

The patient presents with acute chest discomfort, usually expressed as pain, tightness, heaviness, or burning, and is often described as dyspnea, epigastric pain, and pain felt in the left or right arm, neck, or jaw. This prompts the clinical diagnosis of ACS. Prompt assessment of vital signs and acquisition of initial ECG is recommended to diagnose ACS and eliminate differential diagnoses. The resting 12-lead ECG is the first-line diagnostic tool for ACS. Based on the ECG findings, ACS is classified as STEMI and NSTEMI [1]. A cardiac biomarker, high-sensitivity cardiac troponins play a complementary role in diagnosing ACS and are recommended in all patients suspected of ACS. In case of uncertainty regarding the diagnosis of ACS, transthoracic echocardiography is useful in identifying signs suggestive of ongoing ischemia and ruling out other etiologies of chest pain [1].

A patient with ACS is initially treated with oxygen supplementation, sublingual nitrate, intravenous opioids, intravenous beta-blockers, antiplatelets, and anticoagulant drugs. Patients with STEMI should be triaged for immediate thrombolytic therapy if reperfusion is not possible within 120 min of diagnosis, and those with NSTEMI should be considered for early invasive angiography within 24 h. However, the anticoagulants are the mainstay of treatment [1].

ACS is a disease of growing concern in Bhutan. Over the past several years, advancements have been made in managing ACS. However, little is known about the overall profile and the outcomes of patients with ACS since no research has been conducted. This study aimed to evaluate the clinical characteristics and outcomes of patients diagnosed with ACS from a PCI-limited setting, who presented to the Emergency Department of the National Referral Hospital, Bhutan.

Materials and methods

Study design

Prospective cohort study.

Study setting

This study was conducted at the Emergency Department (ED) of Jigme Dorji Wangchuk (JDW) National Referral Hospital in Bhutan. The ED provides emergency care to patients of all ages and serves as the first point of contact for all emergencies.

The department is staffed 24 h a day with three emergency specialists, eight emergency medicine residents, and thirteen medical officers. Upon arrival, all patients presenting to the ED undergo triage. Those requiring immediate attention are taken to the resuscitation room, where they are promptly evaluated by a doctor. After resuscitation and stabilization, patients who cannot be discharged are admitted to the respective wards or Intensive Care Units (ICU) after consulting with the appropriate specialist.

Patients suspected of acute coronary syndrome (ACS) are evaluated in the emergency department (ED), where a 12-lead ECG is performed, and cardiac markers—troponin-I, troponin-T, and creatine kinase MB are obtained. Transthoracic echocardiography (TTE) is conducted for suspected ACS patients to assess regional wall motion abnormalities (RWMA).

Based on the identified type of ACS, appropriate therapies are administered. Due to the lack of percutaneous coronary intervention (PCI) services in Bhutan, all patients with ST-Elevation Myocardial Infarction (STEMI) receive thrombolytic therapy. Patients with Non-ST-Elevation Myocardial Infarction (NSTEMI) and Unstable Angina (UA) are treated with anticoagulants, low molecular weight heparin, and antiplatelet agents, including aspirin and clopidogrel.

Additionally, some ACS patients are referred overseas for advanced cardiac evaluation and intervention.

Study period

One year from 1st October 2022 to 30th September 2023.

Study population

All those patients diagnosed with ACS presented to the ED of JDW National Referral Hospital during the study period.

Inclusion criteria

All ACS cases presenting to the emergency department (ED) were included in the study. However, patients with ACS who were admitted to wards or the ICU, as well as those who developed ACS during their stay in other hospital wards, were excluded from the study.

Study power calculation and sampling methods

A post hoc power analysis was conducted using G*Power 3.1.9.7 software with the following parameters: Test family– χ² tests; Statistical test– Goodness-of-fit tests for contingency tables; Type of power analysis– post hoc to compute achieved power at an α level of 5%, an effect size of 0.4, and a degree of freedom of 2, based on the sample size of the study (n = 67). The study power was determined to be 84.3%, which is sufficient to draw reliable inferences from the findings.

A consecutive sampling method was employed to enroll all study participants.

Study procedure

Administrative clearance from the Ministry of Health and ethical clearance from the Institutional Review Board, Khesar Gyalpo University of Medical Sciences of Bhutan, were obtained prior to the study. Patients presenting to the emergency department (ED) of JDW National Referral Hospital were triaged, and those diagnosed with ACS were included in the study. Written informed consent was obtained from clinically stable participants, while consent for critically ill patients was provided by their immediate family members.

Demographic variables (age and gender), presenting symptoms (chest pain, shortness of breath, nausea, vomiting, sweating, left arm pain, epigastric pain, giddiness, syncope, abdominal pain, and palpitation), and risk factors for ACS (hypertension, diabetes, dyslipidemia, smoking, and chronic obstructive lung diseases) were recorded using a standard research questionnaire (supplementary file) developed for the study.

An ECG was performed on all ACS patients, and based on clinical evaluations, patients were categorized as STEMI, NSTEMI, or UA. Appropriate treatments were initiated in the ED, and unstable or critically ill patients were admitted to the ICU or wards, depending on their clinical condition. Details regarding ECG changes (ST elevation in anterior, septal, inferior, lateral, and posterior leads) and thrombolytic agents used (alteplase, streptokinase, and tenecteplase) were also recorded.

All patients included in the study were closely monitored. During follow-up, in-hospital complications such as myocardial reinfarction, heart failure, cardiogenic shock, bleeding, stroke, and death were documented. Daily follow-up and recording of complications continued until the patients were discharged after improvement or referred overseas for further treatment.

Study tool

A research questionnaire was used for data collection (Supplementary file). The questionnaire has three sections. Section - A contains demographic (age and gender); section - B consists of clinical characteristics including presenting symptoms (chest pain, shortness of breath, nausea vomiting, sweating, left arm pain, epigastric pain, giddiness, syncope, abdominal pain, and palpitation), risk factors for ACS (hypertension, diabetes, dyslipidemia, smoking, and chronic obstructive lung diseases), ECG changes (ST elevation in anterior, septal, inferior, lateral, and posterior leads), thrombolytic agents (alteplase, streptokinase, and tenecteplase) used, and section - C consists of outcomes of patients (discharged, referred out, myocardial reinfarction, heart failure, cardiogenic shock, stroke, and major bleeding episode).

Data management

Confidentiality is maintained, and identifiable variables were not collected for the study. The principal investigator cross-checked the collected data for completeness. Data collected using the research questionnaire was kept in a secure locker, accessible only to the principal investigator. The data will be preserved for 5 years, after which it will be destroyed. All data were anonymized before scientific dissemination.

Data analysis

Data were double-entered and validated using EpiData (Version 3.1 for data entry and Version 2.2.2.183 for analysis, EpiData Association, Odense, Denmark). The data were then exported and analyzed using SPSS (Version 23).

The Kolmogorov-Smirnov test was used to assess the normality of the study data. Normally distributed continuous variables, including demographic and clinical characteristics, were compared using a t-test, while non-normally distributed variables were analyzed using the Mann-Whitney test and expressed as medians with interquartile ranges (IQR).

Categorical variables were analyzed using the Chi-square or Fisher’s exact test and presented as frequencies and percentages. Multivariate regression analysis was conducted to identify factors associated with individual subtypes of acute coronary syndrome. The odds ratio (OR) and 95% confidence interval were calculated to determine the strength of associations, with a p-value < 0.05 indicating statistical significance.

Ethical clearance

Administrative clearance was granted by the Ministry of Health, while site clearance was obtained from the JDW National Referral Hospital. Ethical approval was provided by the Institutional Research Board (IRB) of the Khesar Gyalpo University of Medical Sciences of Bhutan (IRB/Approval/PN/2022-012/946).

Results

Characteristics and risk factors of patients with acute coronary syndrome

The study involved 67 patients with acute coronary syndrome, primarily NSTEMI (58.2%, n = 39), followed by STEMI (32.8%, n = 22) and UA (8.9%, n = 6). The mean age was 63.5 ± 16.8 years, with older patients in the STEMI (59.1%) and NSTEMI (69.2%) groups compared to younger (< 60 years) UA patients (83.3%). Most participants were male (67.2%) and non-smokers (66.7%), with few reporting a family (97.1%) or personal history of cardiovascular disease. Common symptoms included chest pain (29.7%), shortness of breath (26.4%), and nausea/vomiting (17.0%). More than half presented to the emergency department within 24 h, and the time from symptom onset to hospital arrival was significantly shorter for STEMI patients (3.5 h) compared to NSTEMI patients (36 h, p = 0.005). The details are shown in Table 1.

Table 1 Clinical characteristics and risk factors of acute coronary syndrome presenting at emergency department, National referral hospital, Bhutan, 2022–2023

Types of acute coronary syndrome

The majority of patients with acute coronary syndrome had NSTEMI (58.2%, 39 out of 67), followed by STEMI (32.8%, 22 out of 67) and UA (8.9%, 6 out of 67), as shown in Fig. 1.

Fig. 1

Pie chart illustrating the distribution of different types of acute coronary syndrome

ECG changes and the treatment of STEMI with thrombolysis

Out of 67 patients diagnosed with acute coronary syndrome, over 33% (22 patients) had STEMI. Most of the STEMI patients exhibited ST elevations in the anterior (31.0%), septal (31.0%), and inferior (21.4%) leads on their ECG. More than two-thirds of the STEMI patients required thrombolysis, with 77.3% (17 out of 22) needing this treatment. Among the thrombolytic agents administered, the majority were treated with alteplase (70.6%, 12 out of 17), followed by streptokinase (as shown in Table 2).

Table 2 Types of ST elevation and the treatment of the patients with STEMI with the thrombolytic agents

Complications of acute coronary syndrome

Out of 67 patients with ACS, over 46% (31 out of 67) experienced complications or major adverse cardiovascular events (MACE). Among these complications, more than a quarter of the patients, specifically 26.9% (18 out of 67), developed heart failure, followed by cardiac arrhythmias, which occurred in 13.4% (9 out of 67) of the patients. A significant number of complications were observed in patients with STEMI compared to NSTEMI (p < 0.001). Further details are provided in Table 3 below.

Table 3 In-hospital outcome and major adverse cardiovascular events (MACE) in patients admitted to the National referral hospital of Bhutan, 2022 to 2023

Outcomes

As shown in Table 4, of the 67 patients diagnosed with ACS, more than 61% (41 out of 67) were discharged home after their condition improved. In contrast, just over one-third required referrals to other facilities. Additionally, there was one in-hospital mortality case in the NSTEMI group, representing 1.5% (1 out of 67).

Table 4 The overall outcomes of the patients with acute coronary syndrome admitted to the National referral hospital of Bhutan, 2022 to 2023

Factors associated with acute coronary syndrome

Age 60 years or older is a significant risk factor for unstable angina, with an odds ratio of 9.5 (95% CI 1.1–86.9, p = 0.046). Additionally, medical conditions such as hypertension, diabetes, and dyslipidemia, along with smoking, contribute to the risk of acute coronary syndrome, although their associations lack statistical significance (p > 0.05).

Patients who present to the emergency department with symptoms of ACS more than 24 h after the onset of symptoms are significantly more likely to experience STEMI, with an odds ratio of 3.8 (95% CI 1.2–11.8, p = 0.020). Factors associated with ACS are shown in Table 5.

Table 5 Factors associated with acute coronary syndrome in patients reported to the emergency department, National referral hospital, 2022–2023

Discussion

A total of 67 patients diagnosed with ACS presented to the emergency department at the national referral hospital in Bhutan between 2022 and 2023. Among these patients, over 58% were diagnosed with NSTEMI, approximately 33% with STEMI, and about 9% with unstable angina. Similar rates of NSTEMI, STEMI, and unstable angina were reported in an audit conducted by the National Health Service (NHS) in the UK, as well as in other studies from Nepal and Sri Lanka [7, 9,10,11]. This indicates that NSTEMI is the most common form of ACS compared to STEMI and unstable angina. Conversely, a prospective study that analyzed registry data from 89 centers across 10 regions and 50 cities in India, which enrolled 20,937 patients, revealed that over 60% of ACS cases were STEMI [12].

In the current study, the mean age of patients with ACS was 63.5 years, with the majority (61%) falling into the older age groups of 60 years and above. Similar findings have been reported in the literature, indicating that ACS is more prevalent among older individuals than younger ones [13]. additionally, ACS is more common in men than in women. In this study, approximately 67% of the patients with ACS were male, compared to 33% who were female. A similar predominance of males was noted in analyses of the ACS registry in India [12]. Traditionally, it has been believed that women experience fewer cases of ACS due to the protective effects of the sex hormone estrogen. Estrogen is known to inhibit platelet aggregations, decrease the plasma levels of procoagulant factors, and stimulate the production of prostacyclin and nitric oxide, leading to significant antiplatelet effects [14].

In the current study, patients frequently reported symptoms such as chest pain (29.7%), shortness of breath (26.4%), nausea and vomiting (17.0%), and sweating (9.3%). These symptom presentations align with findings from the existing literature, where ACS is typically associated with one or more of these symptoms [11, 13].

Patients with ACS usually arrive at the emergency department promptly, often due to severe chest pain. This study revealed that more than half of the patients sought medical attention within 24 h of their symptoms appearing. Additionally, the time taken to report to the emergency department was significantly shorter for patients with STEMI compared to those with NSTEMI or unstable angina.

Many patients with ACS still arrive at the hospital late. This delay may stem from a lack of awareness regarding the significance of their symptoms, coupled with strong cultural influences on health-seeking behavior in our population. Typically, individuals tend to visit hospitals only after they have completed their rituals and traditional home remedies. In Bhutan, a Buddhist country, people often perform rituals for various ailments, and it is only when their condition worsens that they seek medical assistance at a hospital.

There are well-established risk factors for ACS, which can be categorized into modifiable and non-modifiable factors. In our study, the most common modifiable risk factors identified were hypertension, diabetes mellitus, and dyslipidemia. Additionally, COPD ranked among the top five risk factors for ACS. Hypertension is the primary risk factor for ACS, a finding that aligns with existing literature. The PURE study, a multinational prospective cohort study that enrolled 155,722 participants over 11 years from high-, middle-, and low-income countries, reported that hypertension is the most significant risk factor for cardiovascular disease [15].

Non-modifiable risk factors include family history and a history of coronary artery disease (CAD). It is generally accepted that the development of atherosclerotic CAD or death from CAD in a first-degree relative before the age of 55 for males and 65 for females indicates a significant family history.

Data from the 2011 to 2014 NHANES survey and the 2017 AHA heart and stroke statistics indicated that 12.2% of adults have a biological parent or sibling who experiences a heart attack or angina before turning 50 [16]. However, this study did not demonstrate a significant association between non-modifiable risk factors and ACS. This lack of association may be attributed to the relatively recent advancements in modern medicine in our country, as part generation may not have had access to the medical technologies necessary for diagnosing and treating such cases.

In the STEMI subtype, anterior and septal wall infarctions were the most common, accounting for 31% of cases, followed by inferior wall infarctions at 21.4%. These findings are consistent with a study conducted in India. A one-year prospective observational cohort study involving 651 patients reported that, in the STEMI subtype, anterior wall involvement was more prevalent than inferior wall myocardial infarctions [17].

Thrombolytic agents are the only treatment options available in our setting. Our study revealed that 77.3% of STEMI cases received thrombolytic agents as their primary reperfusion therapy. This rate of thrombolytic use is comparable to findings from Western studies, such as the TRACE registry, which reported that 78% of patients received thrombolytic therapy [18]. In contrast, the CREATE registry from India reported a slightly lower rate, indicating that only 66.5% of patients received thrombolytic therapy. However, it is important to note that those studies included both thrombolytic agents and primary PCI as reperfusion therapy options [12]. Another treatment modality available for ACS is dual antiplatelet therapy (DAPT). DAPT is the preferred treatment for ACS, alongside PCI, as it reduces mortality and helps prevent recurrent thrombotic complications. A prospective study on DAPT demonstrated significantly lower rates of hospitalization for cardiovascular reasons (7.9%), acute myocardial infarction (2.3%), stent thrombosis (1.3%), and target-vessel revascularization (4.2%) [19]. In Bhutan, DAPT is not currently available. Instead, clopidogrel in combination with aspirin is used for the management of ACS patients.

Composite major adverse cardiovascular events (MACE) occurred in over 46% of patients, with complications significantly higher in the STEMI subtype compared to NSTEMI. Heart failure was predominant in both subtypes, affecting 36.4% of the STEMI patients and 25.6% of the NSTEMI patients. This finding aligns with a study conducted in India, which reported higher in-hospital MACE rates in the STEMI group (23.9% compared to 11.4% in the NSTEMI subtype) [17]. Overall, the MACE rate in our study was comparable to contemporary registries from Saudi Arabia, such as the SPACE registry, which utilized a similar definition of MACE. A prospective registry study conducted across 17 hospitals in Saudi Arabia included 5,055 patients over two years [7].

During our one-year study period, there was one death in the NSTEMI subtype, resulting in a mortality rate of 1.5%. However, since our facility lacked the capability to perform coronary angiograms during this time, most patients with STEMI and some with NSTEMI were referred to facilities outside the country. Unfortunately, we were unable to follow up with these referred patients, which means that the low mortality rate reported in this study may not accurately reflect the actual mortality rate. The overall in-hospital mortality rate of 1.5% is comparable to data from developed countries and some Arabian Gulf nations, but it is lower than rates observed in underprivileged communities in India [7, 12].

The coronary angiogram is the primary diagnostic tool for identifying coronary artery disease (CAD). During the one-year study period, a total of 25 patients (37.3%) were referred to India for further evaluation and treatment. Among these patients, the STEMI subtype accounted for the majority of referrals, making up 86.4%. Additionally, 15.4% of patients from the NSTEMI subtype were also referred to India. Notably, no patients from the unstable angina subtype were referred.

Among patients with ACS, more than 61% were discharged from the hospital after demonstrating improvement with treatment. Of these patients, over 82% were classified as NSTEMI and 14% as STEMI. Additionally, all patients diagnosed with unstable angina were treated and subsequently discharged home.

In patients diagnosed with various subtypes of ACS, being 60 years of age or older was found to be independently associated with unstable angina. Additionally, medical conditions such as hypertension, diabetes, and dyslipidemia, along with a history of smoking, were more common among those who developed ACS, although this association was not statistically significant for each subtype. Furthermore, a family history of CAD was not linked to ACS in our study.

One of the major limitations of this study is that we did not follow up with patients who were referred out, particularly those with STEMI subtypes, which have a worse prognosis. Additionally, we did not follow patients after their discharge from the hospital. Ideally, all patients should have been monitored for a month to determine the true outcomes, especially the incidence of major adverse cardiovascular events (MACE) in our population. The lack of assessment regarding long-term outcomes after discharge further contributes to the limitations of this study.

One limitation of this study is that we did not record psychosocial factors, stress levels, or protective factors, such as moderate to high-intensity physical exercise and the consumption of fruits and vegetables, which have been included in similar studies conducted elsewhere. This omission may have affected our understanding of the overall risk factors associated with ACS in our setting.

Another limitation is that we did not document out-of-hospital events, which may have resulted in an underestimation of the actual mortality rates related to ACS.

Conclusion

A study of 67 patients with acute coronary syndrome demonstrates that males outnumber females and that the condition predominantly affects the elderly population. NSTEMI emerged as the most prevalent subtype, followed by STEMI and unstable angina. Most STEMI patients presented within the critical thrombolytic therapy window and received appropriate treatment. Age 60 years and older is unequivocally linked to an increased risk of ACS, which has a notable mortality rate of 1.5%. Alarmingly, over 80% of STEMI patients who face a significantly worse prognosis were referred abroad for care. These findings underscore the urgent need to recognize ACS as a rising public health concern in Bhutan, necessitating the immediate establishment of PCI to administer appropriate treatment and to mitigate morbidity and mortality associated with this condition.