Background: The exercise ECG (ETT) is a cost-effective, non-invasive method that provides valuable data in assessment and risk stratification of coronary artery disease (CAD). This study aims to demonstrate the importance of using this testing modality in evaluating patients with CAD.

Methods: This analytical cross-sectional study was conducted among 3000 patients who were referred for ETT at the cardiology unit of Colombo South Teaching Hospital, Sri Lanka between November 2018 and February 2020. ETT was done using classical Bruce protocol and majority of ETT positive patients were referred for Coronary Angiogram (CA). Follow up was conducted up to 2 years post enrollment.

Results: Among the 3000 patients, 797(26.6%) positive, 1896 (63.2%) negative and 307 (10.2%) inconclusive ETT outcomes were found. 698 (23.3%) patients were referred for a CA in which 338 (48.4%) underwent the procedure. The frequent indication of ETT was chest pain (67.1%). Hypertension, Dyslipidemia, Diabetes Mellitus, chronic kidney disease (CKD), and Smoking were the risk factors present in the population with 57.3%, 62.3%, 34.2%, 1.7% and 4.9% respectively.

Conclusion: Among the positive ETT outcome, majority were males 421(52.8%) and older (≥41years) and NSTEMI was the common clinical pattern. Dyslipidemia was the commonest risk factor in the study population. Past history of CAD was not significant in positive ETT population. Majority of patients on beta blocker achieved the target heart rate. Exercise induced ST depression mainly demonstrated in inferolateral leads which was not significant in localizing ischemia. Outcome of CA showed CAD in majority and Triple Vessel Disease (TVD) was most common.

• Exercise ECG

• ST Segment Depression

• CAD

• Dyslipidemia

• Diabetes Mellitus

Faslur Rahuman MB, Senevirathne N, Rathnayake C, Westlly N, Theivendram D, et al. (2024) Regulate Exercise ECG program- Role of Exercise ECG in the assessment of Coronary Artery Disease in a Tertiary Care Hospital in Sri Lanka. J Cardiol Clin Res. 12(1): 1199.

Coronary artery disease (CAD) remains a substantial cause of morbidity and mortality across the globe, despite significant advancements in therapy. In Sri Lanka, CAD is a burgeoning cause of hospital deaths, and has accounted for 10% of all hospital deaths in the past 10 years thus making it the leading cause of mortality [1]. In low and middle-income countries, the burden of cardiovascular diseases is on the rise [2], and has reached 16% of all disability-adjusted life years (DALYs) in 2019 [3]. The burden is much higher in Sri Lanka with 29% DALYs in the same year [3].

Healthcare in a developing nation such as Sri Lanka has limited resources and the demand for Exercise ECG is on the rise in tertiary care hospitals. Exercise ECG is a non-invasive, rapid and cost-effective tool that does not use ionizing radiation and can aid in diagnosing CAD, assessing exercise tolerance, evaluating prognosis in CAD patients, and monitoring response to therapy. Its specificity ranges from 85% to 90% in identifying obstructive CAD, which is similar to well-established stress imaging methods like nuclear myocardial perfusion imaging, echocardiography, or magnetic resonance perfusion [4-6]. The guidelines set forth by the American College of Cardiology and the American Heart Association propose exercise ECG as the primary diagnostic test for individuals with moderate pretest risk and readable resting ECG outcomes [7].

The Ex ECG is still used as a standard initial investigation across many developing countries since the procedure is widely available, less resource intensive and convenient. Exercise- induced ST-segment depression is a strong predictor of adverse cardiac events [8].

While there are perceptions that exercise stress testing alone is insufficient for detecting CAD, its sensitivity increases with the number of diseased coronary arteries [9], and a negative stress test can help avoid angiography [10]. Careful patient selection is crucial to prevent exposing individuals with low likelihood of the condition to unnecessary procedures, or causing delays in high-risk patients. The optimal candidate for a stress ECG test conducted to diagnose CAD is an adult with a low to moderate pretest probability of CAD, determined by factors such as age, gender, and symptoms.

Recommendations for dual antiplatelet therapy suggest the use of dual antiplatelet therapy in patients presenting with all Acute Coronary Syndrome (ACS) types [11]. Therefore, the exercise stress test can be valuable in the critical analysis of the prescription of dual antiplatelet therapy. Patients on dual antiplatelet therapy are suspected to be having ACS indicating that the patient may suffer from significant occlusions to the coronary circulation. The diagnostic value of the exercise tolerance test provides valuable prognostic information about the five-year risk of death from any cause [12].

Research revealed that the sensitivity and predictive accuracy of conventional ST criteria for exercise-induced ST depression are notably reduced in male patients using β-blockers and failing to achieve the target heart rate. Conversely, in individuals who don’t attain the target heart rate and are not taking β-blockers, the sensitivity and predictive accuracy remain unaffected [13].

This study aims to provide a comprehensive analysis of the exercise ECG findings, the associated factors, management protocols, and outcomes in a tertiary care hospital in Sri Lanka. By highlighting the value of exercise tolerance testing, especially in a developing country, the study aims to emphasize its importance in risk stratification for patients with suspected or diagnosed CAD.

Study Design and Population

The study was conducted at the Colombo South Teaching Hospital, Kalubowila, Sri Lanka between   November   2018 and February 2020. This   analytical   cross-sectional   study was conducted at Cardiology Clinic with 3000 patients of all age groups who were referred for exercise ECG test after being assessed for the likelihood of coronary artery disease by the Cardiologist. The study was initiated after receiving approval from the Institutional Ethics Committee at Colombo South Teaching Hospital, Kalubowila. All the patients were recruited into the study after obtaining a written consent. The data was collected using a predefined standard interviewer administered questionnaire. Questionnaire included patients’ socio-demographic information, previous medical history, family history, co-morbidity, laboratory investigations, current medication, place of referral, and indications for referral of the Ex-ECG test.

Patients were checked for their BMI. Patients   with   a BMI (Body Mass Index) of ≤18.49 kg/m2 were classified as underweight, 18.50 kg/m2 to 24.99 kg/m2 as normal weight, 25 kg/m2 to 29.99 kg/m2 as overweight, and ≥30 kg/m2 as obese. Lifestyle was categorized as active or sedentary based on the patient’s occupation and level of physical activity. Semi-skilled and manual workers were considered to have an active lifestyle, while professionals, technical workers, and clerical staff were categorized as having a sedentary lifestyle.

The presence of a positive family history of ischemic heart disease (IHD) in a first-degree relative was noted. Current medications, including beta blockers, antiplatelet therapy, statins, and calcium channel blockers, were also recorded.

Investigations

Exercise testing was performed utilizing the Quinton Q-Stress TM55 treadmill, overseen by a Cardiologist. The ECG recordings were captured using the Cardiac Science Q-Stress system. ECG readings were taken at each stage, with a frequency of one per minute, both before and after reaching peak exercise, as well as during the recovery phase. The ECG was set to a paper speed of 25 mm/s, where 1 vertical mm represented 0.1 mV. Blood pressure measurements were taken using a mercury sphygmomanometer during the final minute of each stage. The exercise test was halted if exertional hypotension, severe ventricular arrhythmia, notable ST depression (≥3 mm), or constraining chest pain was reported.

An abnormal exercise ST response was characterized as the presence of horizontal or downsloping ST depression (at the J point), or ST segment elevation in leads devoid of pathological Q waves (with the exception of the aVR lead). Other reasons for discontinuing the test were when target heart rate of 85% of maximal predicted heart rate was achieved.

The exercise test followed the classical Bruce protocol, with the duration of exercise and workload measured in METs (metabolic equivalents). METs represent the oxygen consumption of an average individual at rest (3.5 ml oxygen/ kg per minute). Blood pressure changes during exercise and rest were documented. The starting point of the Bruce protocol corresponds to 7 METs, stage 2 ranges from 7 to 10 METs, and stage 3 exceeds 10 METs [14].

Exercise ECG results were interpreted as positive, negative, or inconclusive for ischemia based on symptoms, electrocardiography, and blood pressure changes. Positive results were determined by specific criteria such as significant ST segment depression, U wave inversion, frequent premature ventricular contractions/ ventricular tachycardia, or exertional hypo-tension [15]. Negative results were recorded when the target heart rate was achieved without meeting the criteria for ischemia [15]. Inconclusive results included clinically insignificant arrhythmia, P or T wave morphology changes, failure to achieve the target heart rate, or minor ST depression [15].

Patients with positive exercise ECG results were referred to the National Hospital or other teaching hospitals for coronary angiogram and results were obtained through telephonic calls. Follow-up was conducted after enrollment, and relevant information was extracted from patient records during clinic visits.

Statistical Analysis

Statistical analyses were executed using SPSS version 25. Continuous data is displayed as mean ± standard deviation, while discrete data is presented as proportions. The two-tailed Student’s t-test was employed to compare the peak significance among age groups and risk factors analysis for continuous variables. Results are considered significant when the p-value is below 0.05.

Baseline Socio-demographic and clinical character- istics by different ETT outcomes

Of the 3000 patients enrolled in the study, majority 2687 (89.6%) belonged to the age group of above 41 years. Among those with positive ETT, it was observed that the highest proportion of patients (603, 75.7%) belonged to the age group 50-70 years (Figure 1).

Figure 1: Age group and ETT outcomes

Most common exercise ECG indication was chest pain 2014 (67.1%) followed by Shortness of breath 665(22.2%). Among the positive outcomes, majority were males 421(52.8%). Almost all the positive outcomes (778, 97.6%) were found in the older population (≥41 years). In the total ETT population, 2361 (78.7%) were overweight or obese which is also reflected in the ETT positive group (608, 76.3%), and 445 (14.8%) were without any risk factor while 1897 (63.2%) had at least one risk factor. Considering BMI, 725 (41.2%) females belonged to the overweight category while 542 (44%) males were having normal BMI. In relation with the BMI and ETT outcomes, positive outcomes were predominant (203, 25.6%) in male population who had normal BMI (Table 1).

Table 1: Socio-demographic & Clinical characteristics by ETT outcomes

Clinical Pattern of Ischemic Heart Diseases

In clinical pattern of IHD, 1246, 41.5% who came for ETT showed history of NSTEMI and STEMI more commonly in males (210, 56.1% and 107, 75.9% respectively) while stable angina and unstable angina were common among females (154, 62.6% and 260, 61% respectively). NSTEMI was the most common clinical pattern as well as the common ACS type among the positive outcomes (176, 47.1%). Age-wise unstable angina was seen to be the most common IHD among both age groups (≥ 41 years 397, 93.1% and ≤ 40 years 29, 6.8 %). The unstable angina (14.2%), and NSTEMI (12.47 %) are the most common clinical patterns of IHD in the overall study population (Figure 2) (Supplementary Table 1).

Figure 2: Type of ischemic heart disease pattern

ECG changes

Considering the ETT results of all the patients, ST depression was found to be the most common cause for ECG change accounting for 690 patients (23%), followed by cases of ST depression and elevation combined in 115 patients (3.8%). ST elevation in 12 patients (0.4%) and arrhythmia in 2 patients (0.06%) were notably very few. Most commonly involved lead was Inferior-lateral (434, 49%) followed by Lateral (228, 34%), Inferior (66, 9%), Antero-lateral (46, 7%), Anterior (8, 1%) while aVR, ST-elevation and Antero-septal leads shows minimum percent (1, <1%) (Figure 3) (Supplementary Table 2).

Figure 3: Positive outcomes, ECG lead classification

Risk factors and ETT outcomes

Among the various risk factors, dyslipidemia plays a major role in the prevalence of CAD, and the majority show CAD positive pattern (179, 83.3%) while only few 36 (16.7%) show normal pattern. 2nd most common risk factor hypertension (HTN) also show CAD positive outcomes. 3rd risk factor is Diabetes Mellitus (DM) where the majority were diseased and only 16 (23.9%) showed a normal angiographic pattern. Smoking has also been a strong predictor of the CAD where only 12 (17.9%) had a normal angiographic pattern and 86 (44.1%) were CAD positive.

Dyslipidemia was the most common risk factor (857, 39.6%) noted in analysis of both the previous history of IHD except STEMI and positive Exercise Tolerance Test (ETT) outcome (530, 37.3%) except STEMI (90, 37.2%). In patients with STEMI, majority had hypertension. Dyslipidemia (1145, 61.3%), diabetes (624, 60.8%) and hypertension (1012, 58.9%) were the most common risk factors among the females, while smoking (139, 94.6%) and Chronic Kidney Disease (CKD) (28, 53.8%) were common among males.

In our study population, Dyslipidemia (p= 0.015), hypertension (p= 0.001), Diabetes (p=0.001) and smoking (p= 0.010) show significance among the positive outcomes while previous IHD doesn’t show significance (Figure 4).

Figure 4: Risk factors and ETT outcomes

METS and ETT outcomes

In patients with METS<7, a positive ET result was observed in the majority. As METS increased, a more negative ET result was noted (Figure 5).

Figure 5: Overall Management

Management

Findings as per the management follow-up of ETT patients suggested that 782 (26.1%) were discharged. 1477 patients accounting for 49.2% were advised   medical   management and another 698 (23.3%) patients were referred to coronary angiogram (CA). Others were advised to undergo Dobutamine stress echocardiogram (7 patients), Holter Monitoring (11 patients) and Computed tomography angiography (25 patients) (Figure 6).

Figure 6: METS and ETT Outcomes

Medical Management: Among 797 patients with a positive ETT, 329 (41.2%) didn’t have any previous ischemic events. Among the positive outcomes, majority 389 (48.8%) were on dual antiplatelet while 169 (26.49%) were on aspirin alone and 46 (24.6%) were on clopidogrel alone. Analysis shows that, 374 (12.5%) patients with a history of NSTEMI were on dual antiplatelet (352, 94%), statins (354, 95%) and beta blockers (277, 74%). Among the patients on dual antiplatelets, 389 (41.3%) had a positive ETT, while 469 (49.7%) and 85 (9.0%) patients had a negative and inconclusive ETT respectively. Out of 187 (6.2%) patients who were on clopidogrel alone, 113 (60.4%) patients had no previous history of IHD, while 70 (37.4%) had previous history of IHD, and 4 (2.1%) were already with PCI. Among the positive outcomes, 30% were with IHD and 20.35% were without IHD (Table 2).

Table 2: Medical Treatment and different ETT outcomes

Coronary Angiogram: Among the CA referred patients (698); 338(48.4%) underwent coronary angiogram, 203 (29.1%) didn’t undergo angiogram, 157(22.5%) could remained unavailable for a telephonic interview. The reasons for undone coronary angiogram are mentioned in Figure 7.

Figure 7: Reasons for not undergoing coronary angiogram

This study conducted with a population of three thousand (3000) patients referred to the cardiology clinic comprised of a majority 2687(89.57%) lying above the age group of 40 years. 58.9% of the population were females among which majority presented with atypical chest pain. Studies show that women experience ischemia in the absence of significant coronary blockade. On the contrary, it has been noticed that these individuals exhibit heightened coronary vascular tone, microvascular disease, endothelial dysfunction, and diffuse disease. These factors could potentially lead to ischemia or angina [16]. The existence of these vessel irregularities is linked with comparable cardiovascular complications as those seen in patients with blocked coronary arteries, as demonstrated in coronary angiography [16].

The most common age group who had the highest probability of having a positive exercise tolerance test was between 50 to 70 years. A study done by Acharya H et al., showed somewhat similar findings where the age group of 41-50 years had 75% of positive Treadmill test (TMT) and the age group 51-60 years had 66.66% of positive TMT test [17]. Almost all the positive outcomes were found in older population (≥41years) compared to the younger population (≤ 40 years). Among the positive outcomes, majority were males 421(52.8%). Most common indication was chest pain 2014(67.1%) followed by Shortness of breath 665(22.2%). The previously mentioned study done by Acharya H et al., showed 44% of patients had typical angina chest pain and 16% of patients had atypical chest pain [17].

Dyslipidemia was seen to be the most common risk factor among the total population which was also reflected in the female population (61.3%), followed by hypertension (57.3%) and diabetes (34.2%). In similar studies done previously, hypertension was seen as the prevalent risk factor. Smoking and CKD were common amongst the male population [18,19]. Considering the risk factor correlation to ETT outcome, among the positives, 530 (66.5%) presented with dyslipidemia, 515(64.62%) presented with hypertension, 329(41.28%) presented with diabetes while 32(4.02%) and 15(1.88%) presented with smoking and CKD respectively.

In our study population, among the total population, 47.1% of patients with a past history of NSTEMI were positive amongst which majority were males. Study by McNeer et al., inferred that unstable angina was the most common IHD which had the highest prevalence amongst the male population [20].

Another aspect analyzed was the use of clopidogrel in the population with chest pain. According to our study, 187 (6.2%) patients were on clopidogrel alone and 943(31.4%) were on dual antiplatelets. In case of patients who were on clopidogrel alone, 113 patients were without any previous history of IHD, 70 had a history of IHD, and 4 were already with PCI. Positive outcome showed that, 46 (5.8%) were on clopidogrel alone and majority 389 (48.8%) were on dual antiplatelets. 30% with IHD and 20.35% without IHD were positive.

Majority (52.8%) of the positive outcomes were present among the male population. The reason could be that most of the females have a poor exercise tolerance due to their sedentary life style as well as high BMI. Study by Abdul Wajid Khan Faisal et al., explain that the male patients with a strongly positive, symptom- limited ETT are likely to have a true positive treadmill test result compared to females [21].

Patients with limited exercise capacity (<4 METs) constitute a group at high risk, particularly when ischemic ECG alterations are observed during this modest exertion. In contrast, individuals with a robust exercise capacity (>10 METs) frequently exhibit a favourable outlook, regardless of the extent of anatomical CAD. It’s approximated that with each 1 MET increase in exercise capacity, the survival rate improves by 12%. Notably, failing to achieve 85% of the predicted exercise capacity was significantly linked to an elevated risk of myocardial infarction, unstable angina, the need for coronary revascularization, and mortality [22-25]. In our study, among the patients with poor exercise tolerance (METs <7), majority 40.21% (312) of total were noted to be positive, patients with moderate (METS 7-10) and good (METS >10) exercise tolerance were markedly negative. Patients with inconclusive results frequently complained of leg pain, wheezing, fatigue, giddiness, shortness of breath, high BP, development of bundle branch blocks, arrhythmia or maximum heart rate before adequate workload achieved. Similar findings were noted in the study conducted by Peterson PN et al., [22].

ST-segment responses and Lead distribution during the exercise treadmill testing plays a major role in screening for patients with and without CAD. The ST-segment response, exercise duration, and maximum heart rate achieved were employed to forecast the presence and degree of substantial coronary artery disease. In this study, majority of positive lead changes (ST depression) were noted for Infero-Lateral (II, III, aVF, V5, V6) leads (49%) followed by Lateral (I, aVL, V5-V6) (34%) and inferior (II, III, aVF) (9%). Anterior (V1-V4) (1%) and Anterolateral (I,aVL, V1-V6) (7%) leads were least frequent. Study Guiteras Val et al., demonstrated that Leads I and aVL were the least sensitive, followed by leads V1 and V2 and leads II, III, aVF and V3[26].

The coronary angiogram results depicted a correlation between patients with risk factors and positive CAD. Triple Vessel Disease (TVD) (51.5%) was more common among CAD positive patients compared to Double Vessel Disease (DVD) (17.5%), Single Vessel Disease (SVD) (15.4%) and minor CAD (2.0%). All the risk factors seem to be associated with a high frequency of TVD compared to other CAD sub-classifications. (SVD, DVD, minor CAD). The study by Samson et al., had similar findings where TVD was the common type of CAD among their cohort of patients. Risk factors such as CKD and smoking were predominant in Samson’s study, but dyslipidemia and DM was seen to be more common in our study.

Patients diagnosed with CAD who undergo PCI involving stent placement are administered dual antiplatelet therapy [27]. This approach is crucial to effectively prevent subsequent ischemic incidents following an ACS [28]. In our study, 41.3% patients on dual antiplatelets had a positive ETT, 49.7 % had a negative ETT and 9.0% had an inconclusive ETT. Increasing evidence has emerged suggesting that a more tailored approach to antiplatelet therapy should be considered according to a patient’s ischemic and bleeding risk profile [29].

The major limitation of our study is that the negative and inconclusive results of patients who were put on medical management were not further intervened, and only the patients with positive ETT outcome were followed up for further analysis out of which 22.5% was lost to follow up to reveal CA findings, thus this may have potentially affected the sensitivity and the specificity of the study. Also, the dosage of beta blockers was not noted in patients who had used them prior to the exercise test hence this may have affected the target heart rate. Moreover, a major limitation is that this is a single centric study conducted only among the patients who visited Colombo South Teaching Hospital; therefore, the results could show considerable variation geographically. The most valuable exercise ECG parameter for identifying coronary artery disease is still the ST segment shift. However, regrettably, it doesn’t provide as much assistance in pinpointing the exact location of myocardial ischemia. Despite territorial changes in ECG, predominately demonstrated in inferolateral and lateral leads in positive ETT outcomes, it did not reveal in coronary angiography outcomes as majority were TVD.

Majority of the exercise ECG carried out were negative. Among the positive outcomes, majority were males 421(52.8%). Almost all the positive outcomes were found in older population (≥41years) compared to the younger population. Dyslipidemia, hypertension, and diabetes were common among females while smoking played a major role among the male population. Majority of the patients with a past history of NSTEMI were on dual antiplatelet, statins and beta blockers. Dyslipidemia was the most common risk factor for coronary artery disease.

Our study among 3000 population reveals that, male population of 51-70 had the highest prevalence of positive ETT outcomes. Most common indication was chest pain and majority of females presented with atypical chest pain. Unstable angina is most common clinical pattern among the elder and younger population. NSTEMI was the most common clinical pattern as well as the most common ACS type among the positive outcomes. The past history of ischemic heart disease was not significant (P<0.05) in the positive ETT population. Patients on Dual antiplatelets (48.8%) had a high positive outcome compared to clopidogrel or aspirin alone. Majority of the patients on beta blockers had achieved the target heart rate (82.36%) which was significant. Majority ST-depressions presented in the Exercise ECG were noted in the inferolateral leads (49%) which were not significant in localizing the ischemia in angiography. Outcomes of CA showed CAD in majority and TVD was the most common among those. Those who had TVD had Dyslipidemia as one of the major risk factors.

We acknowledge the team members of Cardiology Unit, Colombo South Teaching Hospital, Sri Lanka where the study was conducted.

The exercise ECG (ETT) is non-invasive, inexpensive method to yield substantial data for risk stratification of CAD.

This modality of testing carries significance in the evaluation of patients suspected or already diagnosed with CAD.

The ETT is still used as a standard initial investigation across many developing countries since the procedure is widely available, less resource intensive and convenient.

Informed Consent/Consent to publish: Given.

Data Availability Statement: Data available on request from the authors.

Ethics approval (for case reports/original research): Institutional ethics committee has approved the research protocol and written informed consent has been obtained

Author contributions (for original research):

Conceptualisation: Dr. M.B.F.Rahuman,

Data curation: Dr. M.B.F.Rahuman, Dr. Noeline Westley, Dr.Dushanth Theivendram

Formal analysis: Dr. M.B.F.Rahuman, Dr. Pubudu De Silva, Dr. Amanda Nawaratna

Funding acquisition: Dr. M.B.F.Rahuman,

Investigation: Dr. M.B.F.Rahuman, Dr. Nadeeja Senevirathne, Dr. Chamara Rathnayake

Methodology: Dr. M.B.F.Rahuman, Dr. Nadeeja Senevirathne, Dr. Chamara Rathnayake

Project administration: Dr. M.B.F.Rahuman, Dr. Nadeeja Senevirathne, Dr. Chamara Rathnayake

Resources: Dr. M.B.F.Rahuman

Software: Dr. M.B.F.Rahuman,

Supervision: Dr. M.B.F.Rahuman,

Validation: Dr. M.B.F.Rahuman,

Visualisation: Dr. M.B.F.Rahuman,

Writing – original draft preparation: Dr. M.B.F.Rahuman, Dr. Noeline Westley, Dr. Dushanth Theivendram, Dr. Amanda Nawaratna, Dr. Pubudu De Silva,

Writing – review & editing: Dr. M.B.F.Rahuman, Dr. Noeline Westley, Dr. Dushanth Theivendram, Dr. Amanda Nawaratna, Dr. Pubudu De Silva,

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