Exercise Stress Testing in Patients with Chest Pain and Normal Coronary Arteriography: With Review of the Literature

Eighty of 654 patients studied because of chest pain were found to have normal coronary arteriography. Fifty of these completed submaximal treadmill exercise studies. The purpose of this study was to determine whether treadmill electrocardiography could obviate the need for coronary arteriography in the evalution of patients with undiagnosed chest pain. Of patients studied, 22% had typical angina pectoris, while 78% had atypical chest pain. The resting electrocardiogram was normal in 58% of patients, while 42% showed repolarization abnormalities. Submaximal treadmill testing was normal in 64%, incomplete in 12%, and demonstrated classic ischemic S-T depression in 24%. Our findings of 24% positive studies in patients with normal vessels and 12% incomplete tests suggest that stress electrocardiography may be of limited value in predicting the morphologic state of the coronary arteries in patients with undiagnosed chest pain.     

The influence of early repolarization variant on the exercise electrocardiogram: a correlation with coronary arteriograms

Sixteen adult patients with S-T segment elevation in their resting electrocardiograms characteristic of early repolarization variant (ERV) and chest pain syndromes of possible myocardial ischemia were evaluated with both treadmill exercise electrocardiography and coronary arteriography. Of 14 patients with normal coronary arteriograms, 13 had their resting S-T elevation return (“normalize”) to the isoelectric baseline with physical exercise, while one patient with normal arteriograms and normal left ventricular contractility but moderately elevated left ventricular end-diastolic pressure of unknown etiology developed significant S-T depression with exercise. Two patients with significant coronary atherosclerotic occlusive lesions developed “ischemic” S-T depression during treadmill testing. Symptoms developed during treadmill exercise did not distinguish patients with coronary artery disease from those without. Thus, while ERV at rest may be “normalized” by graded physical exercise in the absence of significant coronary atherosclerosis, the presence of ERV does not prevent the usual electrocardiographic manifestations of exercise-induced myocardial ischemia.     

Normal coronary arteriogram. An avoidable test?

Between 10 and 20% of coronary arteriograms in patients with chest pain show normal vessels, often in association with a history of "atypical" angina. Conventional non-invasive tests are inaccurate in this group of patients compared with those with classical angina. This study prospectively evaluates combined 12 lead exercise electrocardiography and thallium-201 scintigraphy as a screening test in patients with atypical angina in order to determine whether normal arteriograms are avoidable in this important subgroup of patients presenting with chest pain. Sixty seven consecutive patients with atypical angina underwent both maximal exercise testing and thallium scintigraphy before coronary arteriography. Chest pain during exercise was a poor predictor of coronary disease in this group. Eleven (16%) had abnormal arteriography, with the sensitivity of exercise and thallium tests being 45% and 73%, respectively. When both tests were applied the predictive accuracy for normal coronary arteries was 96% (54/56) and that for the presence of coronary disease was 82% (9/11). If coronary arteriography was withheld in patients in whom both the exercise test and thallium scintigraphy were negative, the number of normal coronary arteriograms could be reduced with only a very small risk of failing to detect individuals with coronary disease.     

Gastroesophageal reflux in patients with angiographically normal coronary arteries: an uncommon cause of exertional chest pain.

OBJECTIVES--To investigate the association between exertional chest pain and gastroesophageal reflux in patients with normal coronary angiograms and in controls by measuring oesophageal pH during treadmill exercise tests and to compare the results with routine ambulatory monitoring. DESIGN--Case control study. SETTING--Tertiary referral cardiac unit. PATIENTS--50 consecutive patients with chest pain and completely normal coronary angiograms and 16 controls with coronary artery stenoses. MAIN OUTCOME MEASURES--Episodes of acid reflux and chest pain during treadmill exercise; a symptom index expressing the percentage of episodes of pain related to acid reflux during ambulatory monitoring. RESULTS--Four (8%) patients and two (12%) controls had reflux during treadmill exercise (NS). 32 (64%) and 16 (100%) reported chest pain, but only three (6%) and two (12%) had coincident reflux (NS). Reflux was as frequent before, during, and after treadmill exercise (five (8%) v six (9%) v two (3%)) in the 66 subjects; (NS). 19 (38%) patients and three (19%) controls had abnormal reflux on ambulatory monitoring (NS). Eight (16%) and three (19%) had a symptom index > 50%, but six and two of these reported pain without coincident reflux during treadmill exercise. CONCLUSION--There are many potential causes of chest pain in patients with angiographically normal coronary arteries. Although gastroesophageal reflux is commonly implicated and many patients have a high incidence of spontaneous reflux during ambulatory monitoring, it rarely occurs during exertion and the association with chest pain is poor.     

Application and safety of outpatient ergonovine testing in accurately detecting coronary spasm in patients with possible variant angina

We analyzed the results of 61 consecutive outpatient ergonovine provocation tests to determine the safety and efficacy of such outpatient testing for detecting coronary artery spasm (CAS). Criteria for outpatient testing included: clinical history suggestive of variant angina, noncritical coronary artery disease documented by coronary arteriography, normal exercise treadmill test, no symptomatic arrhythmias, and no history of recent myocardial infarction. All antianginal medications were tapered and stopped. Ergonovine maleate was given as a bolus at 3-minute intervals in consecutive doses of 0.05, 0.10, and 0.25 mg. A positive test was defined as chest pain accompanied by > 0.1 mV ST segment elevation on 12-lead ECG. If pain and ST-segment elevation occurred, intravenous and sublingual nitroglycerin were immediately administered for rellef of myocardial ischemia. Of the 61 patients studied, 10 had positive tests; there were no complications. Follow-up of the 51 patients with negative studies has not revealed cardiac etiology for their chest pain. We conclude that outpatient ergonovine testing is a safe and accurate diagnostic test for identifying CAS in a highly selected population of patients with possible variant angina when performed under carefully controlled conditions.     

Spectrum of exercise thallium-201 myocardial perfusion imaging in patients with chest pain and normal coronary angiograms.

Twenty-seven consecutive patients with chest pain and no significant obstructive coronary lesions on arteriography were studied with thallium-201 myocardial imaging during exercise and at rest. Fifteen of the patients had typical and 12 atypical angina pectoris. All underwent treadmill exercise electrocardiographic testing; the results were abnormal in 10 patients (37 percent), normal in 14 (52 percent) and uninterpretable in 3 (11 percent). The exercise and resting thallium-201 myocardial images were normal in 23 patients (85 percent); the results of exercise testing were normal in 12 of these patients, abnormal in 8 and uninterpretable in 3. Four patients had a perfusion defect on exercise thallium-201 myocardial imaging; the defect filled in by 4 hours in two patients but persisted in the other two. In contrast, when thallium-201 myocardial imaging was performed in 28 consecutive patients with angiographic coronary artery disease, only 5 patients (16 percent) had normal exercise and resting thallium-201 myocardial images. Therefore, thallium-201 myocardial imaging offers a more effective means of identifying patients with chest pain and no obstructive coronary artery disease than the clinical history or the exercise electrocardiographic test, or both. However, 15 percent of these patients will have abnormal exercise thallium-201 myocardial images because of factors that have not yet been identified.     

Symptomatic and silent myocardial ischaemia in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE--To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN--Cross sectional study. SETTING--University department of medical cardiology. PATIENTS--90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. INTERVENTIONS--48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary arteriography (n = 35). RESULTS--43 patients had at least one episode of ST segment depression on ambulatory electrocardiographic monitoring. The median number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2 to 17) min. Over 90% of these episodes were clinically silent. 26 patients had positive exercise electrocardiography and 48 patients had reversible thallium perfusion defects despite chest pain during exercise in only five patients. 18 of the 35 patients who had coronary arteriography had important coronary artery disease. Seven of these patients gave no history of chest pain. CONCLUSIONS--Symptomatic and silent myocardial ischaemia are common in hypertensive patients with left ventricular hypertrophy, even in the absence of epicardial coronary artery disease.     

冠脉造影正常胸痛患者的病因辨析

胸痛是心血管科常见症状,临床医师常较重视冠心病引起的胸痛而忽略了胸痛的其它原因,造成了一定的误诊.有资料显示一半以上胸痛患者冠脉造影正常,临床明确诊断为冠心病的患者中有10%～30%冠脉造影正常.现就这一问题总结了冠脉造影正常胸痛患者的常见病因,希望为正确的诊断和治疗胸痛患者提供帮助.     

Symptomatic and silent myocardial ischaemia in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE--To assess the prevalence of symptomatic and silent myocardial ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN--Cross sectional study. SETTING--University department of medical cardiology. PATIENTS--90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with left ventricular hypertrophy due to essential hypertension. INTERVENTIONS--48 hour ambulatory ST segment monitoring (all patients), exercise electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary arteriography (n = 35). RESULTS--43 patients had at least one episode of ST segment depression on ambulatory electrocardiographic monitoring. The median number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2 to 17) min. Over 90% of these episodes were clinically silent. 26 patients had positive exercise electrocardiography and 48 patients had reversible thallium perfusion defects despite chest pain during exercise in only five patients. 18 of the 35 patients who had coronary arteriography had important coronary artery disease. Seven of these patients gave no history of chest pain. CONCLUSIONS--Symptomatic and silent myocardial ischaemia are common in hypertensive patients with left ventricular hypertrophy, even in the absence of epicardial coronary artery disease.     

Altered myocardial perfusion in patients with angina pectoris or silent ischemia during exercise as assessed by quantitative thallium-201 single-photon emission computed tomography

The extent of abnormally perfused myocardium was compared in patients with and without chest pain during treadmill exercise from a large, relatively low-risk consecutive patient population (n = 356) referred for quantitative thallium-201 single-photon emission computed tomography (SPECT). All patients had concurrent coronary angiography. Patients were excluded if they had prior coronary angioplasty or bypass surgery. Tomographic images were assessed visually and from computer-generated polar maps. Chest pain during exercise was as frequent in patients with normal coronary arteries (12%) as in those with significant (greater than 50% stenosis) coronary artery disease (CAD) (14%). In the 219 patients with significant CAD, silent ischemia was fivefold more common than symptomatic ischemia (83% versus 17%, p = 0.0001). However, there were no differences in the extent, severity, or distribution of coronary stenoses in patients with silent or symptomatic ischemia. Our major observation was that the extent of quantified SPECT perfusion defects was nearly identical in patients with (20.9 +/- 15.9%) and without (20.5 +/- 15.6%) exertional chest pain. The sensitivity for detecting the presence of CAD was significantly improved with quantitative SPECT compared with stress electrocardiography (87% versus 65%, p = 0.0001). Although scintigraphic and electrocardiographic evidence of exercise-induced ischemia were comparable in patients with chest pain (67% versus 73%, respectively; p = NS), SPECT was superior to stress electrocardiography for detecting silent myocardial ischemia (52% versus 35%, respectively; p = 0.01). The majority of patients in this study with CAD who developed ischemia during exercise testing were asymptomatic, although they exhibited an angiographic profile and extent of abnormally perfused myocardium similar to those of patients with symptomatic ischemia. The prognostic significance of quantified perfusion defects detected by SPECT remains to be assessed.     

Chest pain: relationship of psychiatric illness to coronary arteriographic results

Seventy-four patients with chest pain and no prior history of organic heart disease were interviewed with a structured psychiatric interview immediately after coronary arteriography. The majority of patients with both negative and positive coronary angiographies had undergone previous exercise tolerance tests, but the patients with angiographic coronary artery disease were significantly more likely to have had positive results on a treadmill test. Patients with chest pain and negative coronary arteriograms were significantly younger; more likely to be female; more apt to have a higher number of autonomic symptoms (tachycardia, dyspnea, dizziness, and paresthesias) associated with chest pain, and more likely to describe atypical chest pain. Patients with chest pain and normal coronary arteriographic results also had significantly higher psychologic scores on indices of anxiety and depression and were significantly more likely to meet criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, for panic disorder (43 percent versus 6.5 percent), major depression (36 percent versus 4 percent), and two or more phobias (36 percent versus 15 percent) than were patients with chest pain and a coronary arteriography study demonstrating coronary artery stenosis.     

Prevalence of coronary artery disease in patients with isolated aortic valve stenosis.

The prevalence of significant coronary artery disease (reduction in luminal diameter by more than 50%) among 88 consecutive patients with aortic stenosis requiring aortic valve replacement at Hammersmith Hospital was examined. Twenty two (34%) patients had significant coronary disease. Nineteen of 42 (45%) patients with typical angina had coronary disease; three of 20 (15%) patients with atypical chest pain had coronary disease, while none of 26 patients free of chest pain had significant coronary disease. Risk factors for coronary disease were equally distributed among patients with and without significant luminal obstruction. Because of the small, but definite, hazard of coronary arteriography and in the interest of cost containment it is suggested that patients with aortic stenosis who are free of chest pain do not require routine coronary arteriography. This applies particularly to patients requiring urgent aortic valve replacement.     

U波异常有助诊断缺血性心脏病—冠脉造影与心电图对照

目的 探讨U波异常在诊断缺血性心脏病中的价值。方法 选择临床拟为冠心病的男性患者52例，排除电解质紊乱，应用常规心电图、运动负荷心电图及冠脉造影，分析ST段缺血性改变、U波异常在诊断缺血性心脏病中的敏感性和特异性。结果 52例临床拟诊冠心病患者，冠脉造影阳性者38例。冠脉造影阳性者中，常规心电图ST段呈缺血性改变者16例，U波异常者8例，其诊断缺血性心脏病的灵敏度分别为42．11％、21．11％(16/38、8/38)；运动试验阳性者26例，运动诱发U波异常者15例，其诊断缺血性心脏病的灵敏度分别为68．42％、39．47％(26/38、15／38)。冠脉造影阴性者(n＝14)中，常规心电图ST段无缺血性改变6例，U波正常13例，特异度分别为42．86％、92．86％(6／14、13／14)5运动负荷时，结果 阴性9例，U波正常14例，特异度分别为64．29％、100％(9／14、14／14)。运动负荷时尚见2例单独U波异常，其冠脉造影证实有病理性狭窄。结论 U波异常在诊断缺血性心脏病中敏感性虽不如ST段下移的高，但U波异常的特异性高，尤其是运动诱发的U波异常更具诊断价值；缺血性U波异常有助诊断冠心病。     

Dobutamine thallium myocardial perfusion tomography

Dobutamine has favorable properties for the pharmacologic manipulation of myocardial oxygen demand in the provocation of ischemia during the investigation of coronary artery disease. The value of dobutamine infusion for thallium myocardial perfusion tomography was assessed in 50 patients with exertional chest pain undergoing coronary arteriography. Dobutamine was infused in 5-min stages at incremental rates from 5 to 20 micrograms/kg per min or until limited by symptoms. The myocardium was divided into nine segments for analysis of perfusion. Thirty-nine of 40 patients with coronary artery disease had a reversible perfusion defect demonstrated by dobutamine thallium tomography (sensitivity 97%) and 8 of 10 patients with normal coronary arteries had normal myocardial perfusion (specificity 80%). These values were significantly better than the sensitivity and specificity of exercise electrocardiography (78% and 44%, respectively; p less than 0.01). There was a significant relation between the mean number of segments with abnormal perfusion and the number of diseased coronary vessels (0.6, 2.6, 4.4 and 6 segments in zero-, one-, two- and three-vessel disease, respectively; p less than 0.001). There was also a significant relation between the maximal tolerated dose of dobutamine and the treadmill exercise time (r = 0.56, p less than 0.001), but a wide range of exercise times was achieved in the 15- and 20-micrograms/kg per min groups, principally because of exercise limitation by noncardiac symptoms. Dobutamine infusion was well tolerated in all patients, including six with asthma. There were no significant arrhythmias or limiting symptoms other than chest pain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of QT dispersion in the interpretation of treadmill exercise electrocardiograms of patients without exercise-induced chest pain or ST-segment depression

It has recently been reported that increased QT dispersion seen on standard 12-lead electrocardiograms (ECGs) reflects transient myocardial ischemia. The present study investigates whether increased QT dispersion induced by exercise is a useful indicator for detecting significant coronary stenosis in patients who do not have chest pain or significant ST-segment depression in response to exercise. We studied 135 consecutive patients (mean age +/- SD, 55 +/- 9 years; 97 men and 38 women) who complained of anginal chest pain and who did not have exercise-induced chest pain or significant ST-segment depression during treadmill exercise electrocardiography. Coronary angiography was performed in all of patients. Of the 135 patients, 97 had no significant coronary stenosis, 25 had 1-vessel coronary artery disease (CAD), and 13 had multivessel CAD. QT dispersion immediately after exercise was significantly greater in the group with significant coronary stenosis than without significant coronary stenosis (62 +/- 13 vs 40 +/- 14 ms, p <0.0001). When QT dispersion >/=60 ms immediately after exercise was considered a positive result, this indicator had a sensitivity of 74%, a specificity of 85%, and an accuracy of 81% for the diagnosis of significant coronary stenosis. In conclusion, we have shown that QT dispersion immediately after exercise is useful for detecting significant CAD in patients who do not have exercise-induced chest pain or significant ST-segment depression.     

微血管性心绞痛临床特点研究

目的探讨微血管性心绞痛的临床特征。方法对30例具有典型心绞痛发作患者行常规心电图、24h动态心电图、平板运动试验检查及冠状动脉超影检查。结果静息心电图正常18例,有缺血性ST-T改变10例,冠状动脉造影正常30例,超声心动图正常28例。30例患者心绞痛发作时ST段压低,平板运动试验30例均阳性。结论微血管性心绞痛是由于冠脉微血管内皮功能障碍及微血管结构异常导致的心肌缺血。诊断需结合临床表现、心电图、平板运动试验及冠状动脉造影结果。治疗以硝酸酯类、β受体阻滞剂、尼可地尔疗效显著。临床预后良好。     

Prognostic Value of Dobutamine Stress Echocardiography in Patients Undergoing Diagnostic Coronary Arteriography

There are only a few studies addressing the prognostic value of dobutamine stress echocardiography in patients with suspected coronary artery disease and none have assessed its value compared with coronary arteriography. Accordingly, graded dobutamine stress echocardiography was performed in 121 patients who underwent coronary arteriography based on symptoms and the findings of treadmill exercise electrocardiography. During the follow-up period of mean (SD) months (15 ± 9) there were 41 cardiac events (death [n = 5], acute myocardial infarction [n = 2], unstable angina [n = 29], and congestive heart failure [n = 5]). There were a greater number of patients with inducible wall motion abnormality (88%) on dobutamine stress with cardiac events compared with those without (55%, p <0.001). The wall motion score indexes at rest (1.6 ± 0.6) and at peak stress (2.1 ± 0.8) were worse in patients with cardiac events compared with those without (1.2 ± 0.3, p <0.001 and 1.5 ± 0.6, p <0.001, respectively). When multivariate analysis was performed using clinical, exercise, echocardiographic, and coronary arteriographic data the independent predictors of cardiac events were exercise duration (p = 0.01), presence of inducible wall motion abnormality (p = 0.03), and wall motion score index at peak stress (p <0.001). Thus, dobutamine stress echocardiography is a powerful predictor of future cardiac events in patients undergoing exercise testing and coronary arteriography for evaluation of chest pain and is superior to both exercise electrocardiography and coronary arteriography for the prediction of subsequent cardiac events.

Graded dobutamine stress echocardiography was performed in 121 patients undergoing diagnostic coronary arteriography for suspected coronary artery disease based on symptoms and findings of exercise electrocardiography. Stepwise Cox regression analysis using clinical, exercise electrocardiographic, echocardiographic, and coronary arteriography variables revealed that wall motion score index at peak stress (p <0.001), inducible ischemia (p = 0.03), and exercise duration (p = 0.04) were the only independent predictors of cardiac events.     

平板运动试验阳性而冠脉造影正常的胸痛患者72例分析

目的：分析平板运动试验（TET）阳性而冠脉造影（CAG）正常的胸痛患者的临床特征．增强对TET假阳性及其临床意义的认识．提高冠心病（CAD）的诊断准确率。方法：对我科近3年因胸痛住院行TET检查结果阳性而CAG正常的72例患者的临床特征进行回顾性分析。结果：TET阳性而CAG阴性的患者以女性多见（61．1％）,心绞痛症状多不典型（63．9％）,心脏彩超检查可以正常（57．1％）。结论：TET阳性且有典型心绞痛症状,但冠脉造影正常的高血压患者,其发病机制应考虑为冠脉微血管病变所致;而心绞痛症状不典型者、或仅以心律失常为表现者、女性患者,若不伴或极少伴有CAD危险因素．临床诊断CAD更应慎重。     

One-year psychosocial follow-up of patients with chest pain and angiographically normal coronary arteries

As many as 30% of patients with chest pain symptoms who are referred for arteriography are found to have normal coronary arteries. Research has shown that patients with anginal symptoms and normal coronary arteries score higher on neuroticism measurements (anxiety, depression and somatic concerns) at the time of catheterization than patients with anginal symptoms who have coronary artery disease. Research examining the cardiac course of chest pain patients with normal coronary arteries indicates that this is a nonprogressive disorder. Although follow-up studies of these patients report continued chest pain and diminished physical activity, these studies have ignored the psychologic status of the patients. Thus, it is not known whether their higher neuroticism scores at the time of catheterization persist following angiography or whether such elevated indexes of neuroticism are transient phenomena associated with precatheterization anticipatory stress. The present study examined 48 Veterans Administration Medical Center patients: 24 with anginal symptoms and normal coronary arteries and 24 with documented coronary artery disease. The patients completed a structured clinical interview and a set of psychologic inventories on the day before catheterization and 1 year later. The findings established continued high neuroticism scores among patients with anginal symptoms only and supported the findings of other investigators regarding continuing chest pain and restricted physical activity. The knowledge alone of benign coronary artery status resulted in virtually no change in the psychosocial status of these patients. Alternative treatment methods are discussed.     

Long-term clinical course of patients with angina and angiographically normal coronary arteries

In 88 of 103 consecutive patients with angina and normal coronary arteries, follow-up data could be achieved 6-11 years (9.2 +/- 1.2 years) after diagnostic left heart catheterization. Three of these patients died during follow-up (two noncardiac deaths and one death with no identifiable etiology). One patient suffered a documented myocardial infarction. In 40 patients (47%) chest pain diminished, while symptoms were unchanged in 20 (24%) or even worse in 25 (29%). Resolution or persistence of chest pain could not be predicted either by the character of pain (typical vs. atypical), the presence of hypertension, a left bundle-branch block, a positive exercise electrocardiogram or pathological pulmonary artery pressures during exercise, documentation of myocardial bridges, local wall motion abnormalities, or a left ventricular end-diastolic pressure greater than or equal to 13 mmHg. However, continuing chest pain was significantly more common in patients who revealed a 'slow-flow phenomenon' at initial coronary arteriogram. Thus, in patients with angina and normal coronary arteries the long-term course regarding frequency of morbid cardiac events is benign. However, more than half of the patients reported chest pain to be similar or even worse than at catheterization. Most clinical and invasive results at initial evaluation had no predictive value for the persistence of symptoms. The impact of 'slow-flow' in coronary arteriography, which was a phenomenon almost exclusive to patients with constant or even worse chest pain at follow-up, should be evaluated in larger patient populations.