Validity of exercise treadmill test in diagnosis of coronary artery disease

Background: Exercise is commonly used as a physiological test to determine cardiovascular disorders not appearing at rest and to assess the functional status of the heart. It is a widely used non-invasive test for assessment of suspicious or proved cardiovascular disorders. It is mainly performed to clarify the prognosis and to assess the functional capacity, the possibility and severity of coronary artery disease (CAD), and the efficacy of treatment. Coronary angiograprhy is the standard method for diagnosis of coronary artery disease (CAD), and it determins the type of therapy according to severity of coronary involvement wether by medical therapy, percutanous coronary intervention (PCI), or coronary artery bypass grafting (CABG) surgery in patients with CAD. Aim: To estimate the sensitivity, specificity, positive and negative predictive values and accuracy of exercise treadmill test in diagnosis of coronary artery disease. Methods: Exercise treadmill test and coronary angiography were performed on 77 consecutive patients (men and women), age range between 30-70 years, they were evaluated at Basrah Cardiac Center (February-June-2012). Both examinations were performed primarily for diagnostic reasons. All clinical data and results of ECG and exercise treadmill test were collected before coronary angiography. Results: The total number of patients included in the study was 77; mean age was 56.9 ± 8.9 years. The mean age for men was 57.0 ± 8.7 years (n= 53), women had a mean age of 56.0 ± 9.5 years (n=24), 90.9% of patients had CAD risk factors. Hypertension was the frequent risk factor present in 72% of patients. Exercise test was positive in 75.3%, negative in 20.8%, pseudonormalization in 3.9%. The sensitivity and positive predictive value of the test were 88% and 79% respectively, while its specificity, negative predictive value and accuracy were 46%, 63% and 75%


INTRODUCTION
he diagnosis of coronary artery disease can be obtained usually by history taking and functional tests.Exercise treadmill test is a relatively safe, not expensive and can be easily performed and interpret. [1]The appropriateness of exercise test for a patient depends on his symptoms, presence of significant illnesses, drug therapy, and physical activity. [2]The report of the test includes the achieved level of exercise, maximal heart rate, electrocardiographic changes, arrhythmias, vital signs and symptoms. [2]Interpretation of the exercise test should include the capacity of exercise obtained, the extent of ST segment deviation and hemodynamic and clinical responses to exercise. [3]The exercise test alone and in combination with other non-invasive tests can be considered as an essential test due to its high functional, diagnostic and prognostic informations.The coronary angiography is considered as the gold standard test for diagnosis of CAD.Understanding exercise physiology and pathophysiology in addition to expertise in electrocardiography is essential for interpretation of exercise test result. [4]There are many protocols used for performing exercise test, of which the Bruce protocol is the commonest on. [5]ST segment depression during exercise testing wether horizontal or down sloping is the most reliable sign of ischemia. [6]he result of exercise test includes positive, negative, equivocal and uninterpretable, and in case of equivocal and uninterpretable results, further investigations are indicated to confirm the diagnosis of CAD. [2]e Aim: To estimate the sensitivity, specificity, positive and negative predictive values and accuracy of exercise test in diagnosis of coronary artery disease.

Exercise
treadmill test and coronary angiography were performed on 77 consecutive patients (men and women) aging 30-70 years in a cross-sectional study.All attending patients were evaluated at Basrah Cardiac Center from February-June-2012.This study was performed primarily for diagnostic reasons to confirm the presence of coronary artery disease.The coronary angiography was considered as the gold standard method for diagnosis of coronary artery disease.Patients with stable angina, unstable angina, non ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI) were included in this study.The presenting symptoms of patients were either typical chest pain (retrosternal, exertional and relieved by rest or sublingual nitroglycerine) or angina equivalent (palpitation, easy fatiguability, dyspnea on exertion, nausea and vomiting).All patients were underwent exercise treadmill test according to standard Bruce protocol.Coronary angiograms were performed by standard Judkin technique (via femoral artery) or Sons technique (via Brachial artery), they were interpreted independently by the catheterizing cardiologist.Only patients with ≥ 50% stenosis in at least one of the three major arteries (left anterior descending artery, left circumflex artery, and right coronary artery) or their first-order branches was considered as a positive coronary angiography.The data were analysed by using SPSS version 16.The results of all quantitative data were expressed as mean ± SD.Sensitivity, specificity, positive and negative predictive values and accuracy were calculated.All clinical data and results of exercise tests were collected before coronary angiography and were evaluated without knowledge of the results of coronary angiography.

RESULTS
The total number of the patients in this study was 77 patients, 90.9% of them had CAD risk factors, while 9.1% were devoid of CAD risk factors, 72.7% of the patients had hypertension, T 55% had obesity, 39% had sedentary life style, 33% had diabetes, 32% were smokers, 11.5% had family history of premature CAD and 3.9% were heavy alcoholics.The mean age was 56.9 ± 8.9 years, 53 (68.8%) patients were males, mean age 57.0 ± 8.9 years and 24 (31.2%)patients were female, mean age 56.0 ± 9.5 years.Clinically, 65% of patients had stable angina, 16% had unstable angina, 10% had NSTEMI (Non ST Elevation Myocardial Infarction), 9% had STEMI (ST Elevation Myocardial Infarction).Exercise test was positive in 75.3% of patients, negative in 20.8% of patients, Pseudonormalization in 3.9%.False negative in females= 12.5%, false negative in males= 5.6%, false positive in female= 29.4%, false positive in males= 21%, Sensitivity= 88%, Specificity= 46%, Positive predictive value= 79%, Negative predictive value=63%, Accuracy 75%.The sensitivity of exercise test ranges from 61%-73% and specificity ranges from 59%-81% as reported by different studies. [8]A metaanalysis of 58 consecutively published reports including 11,691 patients who underwent exercise test and coronary angiography showed wide variation in specificity and sensitivity with mean sensitivity was 67% and mean specificity was 72%. [8]The sensitivity and specificity of exercise test for detection of CAD are 78% and 70% respectively. [6]It is reported that the sensitivity of exercise test in single-vessel CAD patients ranges from 25%-71%, and patients with multi-vessel CAD the sensitivity and specificity are 81% and 66% respectively, while the sensitivity and specificity of those patients with left main or three-vessel CAD are 86% and 53% respectively. [9]ST-segment depression and exercise induced chest pain are the most important factors in the diagnosis of CAD. [10]ur study showed high sensitivity (88%) comparing to specificity (46%) which may reflect the severity of CAD patients examined in the study as the sensitivity increases as the number of diseased coronary arteries increases.
False negative results are more common in females (12.5%) than males (5.6%) and it is true for false positive result of exercise test which is high (29.41%) in females compared to (21.07%) in males, this made diagnosing coronary artery disease is more difficult in women than men.The sensitivity of exercise test for the diagnosis of CAD is low in women in comparison with men because of lower prevalence of severe CAD in women and most of women are unable to perform maximum aerobic capacity. [8]More than 50% of women assessed for angina pectoris have non-obstructive CAD (microvascular angina or syndrome X) which is proved by coronary angiography. [11]In coexistence of left ventricular hypertrophy resulted from hypertension and valvular heart disease. [8]Pseudonormalization of T-wave (invertion of T-wave at rest and becoming upright at exercise test) is considered as a nondiagnostic sign of CAD, but in rare cases may be a sign of myocardial ischemia in patients with proved CAD. [9]T-wave normalization during exercise test seen in 10-15% of patients with abnormal T-waves on their baseline Electrocardiograms, and it is found that pseudonormalization has low sensitivity and poor positive predictive value for reversible myocardial ischemia. [12]Pseudonormalization noticed in our study in 3 of 77 patients and all of them had history of STEMI concomitantly have significant coronary artery disease on coronary angiography.

CONCLUSION
Exercise test is a relatively safe, non -invasive and valuable test in the diagnosis of CAD in patients with sign and symptoms of this disease, but still considered below the coronary angiography (which is the gold standard method) for the diagnosis of CAD.The sensitivity of the test increases as the number of diseased coronary arteries increases as in left main and three vessel disease.ST segment depression in women with abnormal resting ECGs is probably of less diagnostic value than in men.False positive and false negative results were more common in women than men.Pseudonormalization during exercise test in patients with ischemic heart disease may indicate severely obstructed coronary arteries and these patients should be treated on an urgent bases.

Limitations
This study was limited by its small sample size (77 patients).It also lacks information about heart rate variability and hemodynamic evaluations such as blood pressure.We combined existing data from several different hospitals and exercise treadmill test clinics.

Table 2 . The results of exercise treadmill test and coronary angiography.
elderly age group, the prevalence of severe CAD is high and exercise test in this age group is slightly of high sensitivity in comparison with younger age group, but slightly lower specificity due to