Abnormal ST Segment Response Research Articles

Heart rate adjustment of exercise-induced ST-segment depression identifies men who benefit from a risk factor reduction program.

Whether subjects identified as being at increased risk of coronary heart disease (CHD) death by heart rate adjustment of exercise-induced ST-segment depression will benefit from therapy aimed at reducing risk factors has not been examined. Exercise ECGs were performed in 11,880 men from the Usual Care (UC) and Special Intervention (SI) groups of the Multiple Risk Factor Intervention Trial. UC men were referred to customary sources of care in the community; SI men received counseling on smoking cessation and dietary reduction of cholesterol, and stepped-care therapy for hypertension. An abnormal ST-segment response to exercise was defined according to standard criteria as > or = 100 microV of additional horizontal or downsloping ST-segment depression and by an ST-segment/heart rate (ST/HR) index >1.60 microV/bpm. After 7 years of follow-up, CHD mortality was significantly lower in SI than UC men with an abnormal ST/HR index (2.4%, 19/786 versus 5.3%, 39/729, P=.005) but was comparable in SI and UC men with a normal ST/HR index (1.6%, 84/5154 versus 1.3%, 70/5211, P=NS). Risk reduction in SI men with an abnormal ST/HR index was independent of age and other cardiac risk factors. In contrast, there was no significant difference in CHD death rate between the smaller groups of SI and UC men with an abnormal test by standard criteria (3.6%, 7/192 versus 2.7%, 5/186, P=NS). An abnormal ST/HR index identifies men in whom therapy aimed at reducing CHD risk factors reduces the risk of CHD death by 61%. These findings support the application of heart rate adjustment of ST depression for screening of asymptomatic subjects at increased risk of CHD to identify those who will benefit most from risk factor-reduction programs.

Prognostic value of heart rate adjustment of exercise-induced ST segment depression in the multiple risk factor intervention trial

Objectives.We sought to assess the effect of heart rate adjustment of ST segment depression on risk stratification for the prediction of death from coronary artery disease.Background.Standard analysis of the ST segment response to exercise based on a fixed magnitude of horizontal or downsloping ST segment depression has demonstrated only limited diagnostic sensitivity for the detection of coronary artery disease and has variable test performance in predicting coronary artery disease mortality. Heart rate adjustment of the magnitude of ST segment depression has been proposed as an alternative approach to increase the diagnostic and prognostic accuracy of the exercise electrocardiogram (ECG).Methods.Exercise ECGs were performed in 5,940 men from the Usual Care Group of the Multiple Risk Factor Intervention Trial at entry into the study. An abnormal ST segment response to exercise was defined according to standard criteria as ≥ 100 μV of additional horizontal or downsloping ST segment depression at peak exercise. The ST segment/heart rate index was calculated by dividing the change in ST segment depression from rest to peak exercise by the exercise-induced change in heart rate. An abnormal ST segment/heart rate index was defined as >1.60 μV/beats per min.Results.After a mean follow-up of 7 years there were 109 coronary artery disease deaths. Using a Cox proportional hazards model, a positive exercise ECG by standard criteria was not predictive of coronary mortality (age-adjusted relative risk [RR] 1.5,95% condence interval [CI] 0.6 to 3.6, p = 0.39). In contrast, an abnormal ST segment/heart rate index significantly increased the risk of death from coronary artery disease (age-adjusted RR 4.1, 95% CI 2.7 to 6.0, p < 0.0001). Excess risk of death was confined to the highest quintile of ST segment/heart rate index values, and within this quintile, risk was directly related to the magnitude of test abnormality. After multivariate adjustment for age, diastolic blood pressure, serum cholesterol and cigarettes smoked per day, the ST segment/heart rate index remained a significant independent predictor of coronary death (RR 3.6, 95% CI 2.4 to 5.4, p < 0.001).Conclusions.Simple heart rate adjustment of the magnitude of ST segment depression improves the prediction of death from coronary artery disease in relatively high risk, asymptomatic men. These findings strongly support the use of heart rate-adjusted indexes of ST segment depression to improve the predictive value of the exercise ECG.

Impact of echocardiographic left ventricular mass on mechanistic implications of exercise testing parameters

Electrocardiographic left ventricular (LV) hypertrophy has long been known to be associated with an abnormal ST-segment response to exercise; this association has been considered to represent a false-positive finding. There is a paucity of data relating echocardiographic LV mass to exercise ST-segment responses and other exercise parameters. As part of a routine evaluation, 1,408 men and 1,618 women from the Framingham Heart Study who were free of clinical cardiac disease underwent echocardiography and exercise treadmill testing according to the Bruce protocol at the same clinic visit. Abnormal ST-segment responses were defined both by standard criteria and the ΔT/heart rate index. LV mass was calculated from M-mode echocardiography. Echocardiographic LV hypertrophy was associated with an abnormal ΔST/heart rate index (in men, odds ratio [OR] 1.78, 95% confidence interval [CI] 1.05 to 3.01, p = 0.03; in women, OR 2.13, 95% CI 1.31 to 3.44, p = 0.002) but not with an abnormal response according to standard criteria. Echocardiographic LV hypertrophy was also associated with a lower likelihood of achieving an age-predicted target heart rate (in men, OR 0.45, 95% CI 0.31 to 0.65, p < 0.001; in women, OR 0.53, 95% CI 0.37 to 0.76, p < 0.001) and with a lower exercise capacity. Despite these associations, echocardiographic LV hypertrophy was associated with a higher peak heart rate-systolic blood pressure double product. In conclusion, echocardiographic LV hypertrophy is associated with an abnormal ST-segment response, a lower likelihood of achieving target heart rate, decreased exercise capacity, and an increased double product, which is a reflection of myocardial oxygen demand.

The long-term predictive value of an exercise thallium-201 scintigraphy for patients with acute chest pain but without myocardial infarction

Patients who are hospitalized because of chest pain and suspected acute myocardial infarction, but in whom the diagnosis is ruled out, are at high risk for subsequent cardiac events (cardiac death or nonfatal acute myocardial infarction). Risk stratification was done for 158 such patients who underwent exercise thallium-201 scintigraphy at the time of discharge. Thirty-eight patients (24%) were women, and all patients were followed for 7 years. The diagnostic sensitivity, specificity, and predictive value of thallium scintigraphy for the identification of patients having subsequent cardiac events during follow-up was calculated. A cardiac event occurred in 41 patients during the follow-up period. Presence of both transient and permanent defects and abnormal ST-segment responses during thallium scintigraphy were significantly associated with an impaired prognosis (P < 0.0001). The highest sensitivity (85%) was achieved by the combination of transient defect with or without persistent defect and with or without abnormal ST-segment response. The highest specificity was provided by a transient defect (90%), and the predictive value of a positive test result was 60%. Seventeen of 29 patients with a transient defect had a cardiac event during follow-up. Patients with normal test results had excellent prognoses; 93% of 82 patients were free of cardiac events during follow-up. Exercise thallium-201 scintigraphy is suitable for long-term risk stratification in patients with chest pain and suspected but unconfirmed myocardial infarction, because high- and very low-risk subsets can be identified at the time of discharge.

Can serial exercise testing improve the prediction of coronary events in asymptomatic individuals?

An abnormal ST segment response to treadmill exercise has a low predictive value for future coronary events (angina pectoris, nonfatal myocardial infarction, or cardiac death) in apparently healthy individuals. To determine whether the conversion from a normal to an abnormal ST segment response might identify individuals at high risk for a future coronary event, we analyzed the results of serial exercise tests performed at 2-4-year intervals in 726 male and female volunteers, aged 22-84 years (mean, 55.1 years), from the Baltimore Longitudinal Study of Aging (BLSA). All subjects were free of cardiovascular disease at entry by history, physical examination, and resting 12-lead electrocardiogram. Over a mean overall follow-up of 7.4 years, coronary events occurred in 34 of 178 (19.1%) of those with an abnormal ST response to exercise versus 30 of 548 (5.5%) in those with a normal response (p = 0.001). Angina pectoris was the most common presenting coronary event regardless of ST segment exercise response. Among individuals with an abnormal ST segment response, the incidence of events was virtually identical between those with an initially abnormal response (group 1) and those who converted from a normal to an abnormal response (group 2), 19.8% versus 18.5%. After adjustment for standard coronary risk factors by proportional hazards regression analysis, the risk of a coronary event relative to subjects with persistently normal ST segment responses (group 3) remained nearly identical in the two groups, 2.72 in group 1 (p less than 0.003) and 2.80 in group 2 (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

"Recovery Only" ST-Segment Depression and the Predictive Accuracy of the Exercise Test

To clarify the predictive value of exercise-induced ST-segment depression occurring in recovery only, and to determine whether the addition of recovery data improves the interpretation of the exercise test. Retrospective analysis of data collected during exercise testing and coronary angiography. A 1000-bed Veterans Affairs Medical Center. The study included 328 male patients who had had both a sign- or symptom-limited treadmill test and coronary angiography. Of the 168 patients who had abnormal ST-segment responses, 26 had such responses only during recovery. The positive predictive value of this pattern for significant angiographic disease (84%) was not statistically different from the predictive value of ST depression occurring during exercise (87%). Inclusion of ST depression during recovery significantly increased the sensitivity of the exercise test from 50% to 59% (P = 0.01) without a change in predictive value. In addition, ST-segment depression occurring only during exercise is usually associated with less-severe angiographic coronary artery disease. The occurrence of ST-segment depression during the recovery period only, does not generally represent a "false-positive" response. The inclusion of findings from this period increases the diagnostic yield of the exercise test. Previously proposed exercise test scores, as well as exercise electrocardiography (ECG) analysis done in conjunction with scintigraphy, have a falsely lowered sensitivity that could be increased by considering ST-segment changes occurring in recovery.

Effect of estrogen replacement therapy on the ST-segment response to postural and hyperventilation stimuli

It is widely recognized that exercise-induced ST-segment abnormalities often occur in women with normal coronary arteries. False-positive exercise responses from 14 to 67% have been reported. 1 The high frequency of ST-segment abnormalities at rest and in response to exercise in premenopausal women may be explained by their elevated plasma estrogen levels. Although direct testing of this hypothesis is difficult, the effect of estrogen on the ST-segment response to hyperventilation and postural shifts may provide insight into this question. These frequently used preexercise maneuvers are believed to provoke ST-segment shifts independent of myocardial ischemia. We designed this study to compare the frequency of abnormal ST-segment responses to sitting, hyperventilation and standing in postmenopausal women receiving estrogen replacement therapy versus those not receiving it.

Usefulness of thallium-201 Scintigraphy in predicting the development of angina pectoris in hypertensive patients with left ventricular hypertrophy

Hypertension and left ventricular (LV) hypertrophy are independent risk factors for the development of coronary artery disease. To determine whether patients at higher risk for coronary artery disease can be identified, 40 asymptomatic hypertensive men with LV hypertrophy were prospectively studied using exercise thallium-201 scintigraphy and exercise radionuclide angiography. Endpoints indicative of coronary artery disease were defined as the subsequent development of typical angina pectoris, which occurred in 8 patients during a median follow-up of 38 months, or myocardial infarction, which did not occur. The exercise electrocardiogram was interpreted by standard ST-segment criteria and by a computerized treadmill exercise score. Abnormal ST-segment responses were present in 16 of the 40 hypertensives (40%), whereas the treadmill score was positive in 8 of those same 40 patients (20%). Scintigraphic perfusion defects assessed both visually and semiquantitatively were observed in 8 of 40 (20%) patients. An abnormal ejection fraction response to exercise was present in 40% (16 of 40) of patients, and 3 of 40 (7.5%) developed new wall motion abnormalities during exercise. Six of 8 patients with either perfusion defects or abnormal treadmill score developed typical angina during follow-up. All 5 patients with concordant positive exercise scintigrams and treadmill score developed chest pain during follow-up and had coronary artery disease confirmed by coronary angiography. However, only 7 of 16 (44%) patients with positive ST changes or abnormal ejection fraction responses during exercise developed chest pain during follow-up. In contrast, of 32 patients with negative scintigrams only 2 developed atypical chest pain syndromes, and significant coronary artery disease was excluded by angiography in 1 patient. Thus, both thallium-201 scintigraphy and treadmill score accurately detect coronary artery disease in asymptomatic hypertensive patients with LV hypertrophy and predict the future development of angina symptoms.

Independent prognostic risk factors for patients referred because of suspected acute myocardial infarction without confirmed diagnosis. Prognosis after discharge in relation to medical history and non-invasive investigations.

Variables associated with risk of cardiac events, i.e. acute myocardial infarction (AMI) or cardiac death after discharge, were studied in patients who had been referred to coronary care units because of suspected AMI due to chest pain, but in whom this was not confirmed. The patients were all under 76 years of age, and were followed from 12 to 24 months, median 14 months. The estimated percentage without a cardiac event in 257 patients after one year was 91.3. On the basis of prognostic and clinical importance the analyzed variables included selected aspects of the medical history, electrocardiogram on admission in all 257 patients, subsequent electrocardiogram at rest, exercise test, thallium scintigraphy, chest X-ray, echocardiography, systolic time intervals and Holter monitoring when possible in 217 patients. Multivariate analysis identified combined electrocardiogram at rest and during exercise as the only variable with independent prognostic information. The presence of ST segment deviation, Q-wave, negative T-wave or intraventricular block in the electrocardiogram at rest or an abnormal ST segment response during exercise, increased the hazard of a cardiac event by a factor of 11.8. It is concluded that patients without confirmed AMI are at risk following discharge. These patients should undergo an exercise test and those with an abnormal electrocardiogram at rest and/or during exercise should be followed closely after discharge.

Comparative electrocardiographic and myocardial blood flow effects of rapid atrial pacing and dipyridamole infusion in dogs with chronic coronary artery occlusion

Altering regional myocardial flow by the use of potent vasodilators as well as increasing oxygen demand by exercise have been employed as diagnostic methods for detecting coronary arterial obstruction. We sought to define the relative capabilities of these two methods to produce abnormal ECG patterns and to alter myocardial blood flow after Ameroid constriction of the left circumflex coronary artery. Atrial pacing to rates of 210 beats/min was performed, followed by intravenous administration of 0.25 and 0.50 mg/kg of dipyridamole. ECGs were recorded to construct body surface isopotential distributions. Flow was measured by serial injections of radiolabelled microspheres. In 15 animals studied after 3 to 5 weeks of Ameroid constriction, pacing increased epicardial flow by 19.14 ± 7.11% but reduced endocardial flow by 35.69 ± 12.32%, with a significant reduction (to less than 0.67) in the endocardial/epicardial flow ratio in 12 (80%) dogs; both endocardial and epicardial flows were significantly lower in the ischemic than in the nonischemic bed. Ten dogs developed abnormal ST segment responses of subendocardial ischemia. In contrast, dipyridamole produced a dose-dependent rise in both endocardial (25.33 ± 8.54% and 55.80 ± 9.22% after 0.25 and 0.5 mg/kg, respectively) and epicardial (29.13 ± 7.49% and 66.33 ± 7.64% after 0.25 and 0.5 mg/kg, respectively) flows without a significant fall in the transmural ratio. These increases were, however, significantly less than those observed in nonischemic bed flow, resulting in a transventricular gradient of blood flow. No dog developed abnormal ECG patterns after dipyridamole infusion. Thus pacing produces both a transmural and a transventricular gradient in blood flow, whereas vasodilation causes only a transventricular flow abnormality. The associated ECG responses are consistent genesis of the ST segment.

Differences in the frequency of ST segment depression during upright and supine exercise: Assessment in normals and in patients with coronary artery disease

Increased utilization of ambulatory ST segment monitoring mandates an appreciation of nonischemic variables that may influence the ST segment. While a greater frequency of ST segment depression has been reported with supine vs upright exercise, the relative false positive rate in both positions is not known. Thus, we compared the frequency of exercise ECG abnormalities during upright and supine bicycle exercise in two groups—17 normals and 46 patients with coronary artery disease. Exercise was performed in combination with radionuclide ventriculographic imaging. Peak exercise heart rate, peak systolic blood pressure, and exercise duration time were all slightly higher in the upright vs supine position ( p < 0.05). Nevertheless, the frequency of positive ST segment responses was more common in the supine position, both in the patients with coronary artery disease (54% vs 30%, p < 0.05) and in the normal subjects (29% vs 6%, p = NS). The corresponding radionuclide ventriculographic responses, however, were normal during upright and supine exercise in 6 of the 11 CAD patients and in all five of the normal subjects with an abnormal ST segment response during supine exercise only. The frequency of exercise-induced chest pain was also similar in the two positions. Thus, we theorize that nonischemic factors may govern some positive ST segment responses in the supine position. This finding is of relevance for understanding the potential sources of physiologic false positive ST segment responses for ambulatory ST segment monitoring.

The Role of Exercise Testing in the Identification of Patients with Silent Myocardial ischemia

At present, the role of exercise testing in asymptomatic individuals is limited, and the test should be applied only selectively. Regardless of this, the popularity of wellness programs and the widespread use of exercise testing in asymptomatic groups continue. The preceding discussion presents some guidelines to help improve on the diagnostic accuracy of exercise testing in all patients, with special emphasis on its use in asymptomatic individuals.

Comparison of clinical variables and variables derived from a limited predischarge exercise test as predictors of early and late mortality after myocardial infarction

An exercise test limited to 5 METS or 70% of age-predicted maximal heart rate was performed 1 day before hospital discharge by 225 survivors of acute myocardial infarction, all of whom were subsequently followed up for at least 5 years. The mortality rate was 11.1% during the first year, but averaged only 2.9% per year from the second to fifth year. Over the entire follow-up period, the five variables that predicted mortality by multivariate analysis were QRS score, an exercise-induced ST segment shift, previous infarction, failure to achieve target heart rate or work load and ventricular arrhythmia during the exercise test. Because mortality differed markedly before and after 1 year, Cox regression analyses were performed separately for both of these periods. The factors that were predictive of mortality during the first year were an exercise-induced ST shift (p less than 0.0001, relative risk 7.8), failure to increase systolic blood pressure by 10 mm Hg or more during exercise (p = 0.0039, relative risk 4.3) and angina in hospital 48 hours or longer after admission (p = 0.0046, relative risk 3.4). None of these three variables was predictive of mortality after 1 year. Previous infarction (p = 0.0007), QRS score (p = 0.0042) and ventricular arrhythmia during the exercise test (p = 0.016) were predictive of mortality after the first year. Thus, clinical and exercise test variables are complementary predictors of mortality after myocardial infarction. An abnormal ST segment response during an early limited exercise test and angina in the hospital are common strong predictors of mortality to 1 year, but not thereafter. Late mortality correlates with markers of poor left ventricular function.

The abnormal exercise electrocardiogram in apparently healthy men: a predictor of angina pectoris as an initial coronary event during long-term follow-up.

A group of 916 apparently healthy men between the ages of 27 and 55 years (mean 37) were followed up with serial medical and exercise test evaluations for a period of 8 to 15 years (mean 12.7) to determine (1) the prevalence and specific types of new coronary events observed in subjects with and without abnormal ST segment responses to exercise and (2) the predictive value of a serial conversion to an abnormal ST segment response to exercise for new coronary events. During the initial evaluation there were 23 subjects (2.5%) with an abnormal ST segment response to exercise. During follow-up there were nine (39%) coronary events in this group: eight cases of angina and one of sudden death. With serial testing, an additional 38 subjects (5.1%) experienced conversion to an abnormal ST segment response to exercise. During follow-up there were 12 (32%) coronary events in this group: 10 cases of angina, one of myocardial infarction, and one other. There were 833 subjects with normal ST segment responses to exercise with all tests. In this group there were 44 (5.3%) coronary events: 25 cases of myocardial infarction, seven of sudden death, and 12 of angina. We conclude that in apparently healthy middle-aged men an abnormal ST segment response to exercise is predictive of angina pectoris but not of myocardial infarction or sudden cardiac death as an initial coronary event.

Limitation of exercise-induced R wave amplitude changes in detecting coronary artery disease in asymptomatic men

The exercise electrocardiograms of 255 asymptomatic men were analyzed for changes in R wave amplitude and ST segments. The results were correlated with findings at cardiac catheterization. There were 65 men with coronary artery disease and 190 normal subjects. R wave amplitude changes were evaluated in bipolar leads X, Y and Z. The predictive value of an abnormal ST segment response for detecting disease was only 29%. This value was improved to 42% using R wave amplitude changes with a sensitivity of 28% and specificity of 87%. Exercise-induced R wave amplitude changes enhance the specificity of detecting coronary disease in asymptomatic men over ST segment criteria alone but the sensitivity is poor and the predictive value is not enhanced. Thus, these criteria are limited in adding to the diagnostic accuracy of stress testing.

Prinzmetal’s variant angina: Electrocardiographic and angiographic correlations

Thirty patients with variant angina pectoris (VAP) were analyzed for electrocardiographic features during episodes of VAP. Twenty-nine of these patients had cardiac catheterization, and an autopsy study was performed in one. The patients showed predominantly concave upright T-waves during pain. An increase of R wave amplitude (expressed as delta R) of more than 10% was seen in 17/30 patients (57%). The primary ST-T changes produced by the VAP episodes were conspicuous in two patients with pre-existent complete left and right bundle branch block. Serious dysrhythmias, including ventricular fibrillation (VF), ventricular tachycardia (VT), ventricular premature beats (VPBs) (more than five/min, multifocal and R on T phenomenon), and 2 degrees atrioventricular block were found in thirteen patients (43%). The development of dysrhythmias was related to the duration of VAP episodes. The average time to onset of dysrhythmias was 3.54 min. The dysrhythmias were not contingent upon pre-existing coronary artery anatomy (defined by Friesinger's coronary score), left ventricular ejection fraction or left ventricular segmental abnormalities. The location of the ST-segment elevation and the presence of dysrhythmias during the episodes of VAP (A-V blocks, ventricular tachycardia and fibrillation) were not predictive factors of the coronary anatomy. Eight patients (27%) developed myocardial infarction (MI). Five of them had nontransmural MIs and three developed transmural MIs. The development of MI was not related to the severity of the VAP attacks (appreciated by the magnitude of ST-segment elevation and R wave changes) but showed a relation to the development of an unstable pattern which preceded the infarction. Sixteen patients underwent exercise testing. In eight of them, the coronary arteriograms were normal (Group I); in the remaining eight, significant proximal coronary artery obstructive disease was found (Group II). Group I patients displayed a normal ST-segment response and functional aerobic capacity (FAI = 4.4 +/- 14) as well as normal heart rate (HR) and double product (SBP X HR) responses (HR = 154 +/- 21; SBP X 21; SBP X HR = 290 +/- 71). During exercise, a normal delta R was observed. With one exception, Group II patients showed an abnormal ST-segment response with an overall low exercise capacity (FAI = 57 +/- 17) and decreased hemodynamic response (HR = 27; SBP X HR = 130 +/- 40). FAI, HR, SBP X HR Group I vs. Group II = P less than .005/less than .02/less than .005. The abnormal ST-segment response included elevation in four patients and depression in three. During exercise, Group I with ST-elevation displayed a normal (negative) delta R response; while Group II with ST-depression displayed an abnormal delta R response (positive or no change). There was no difference in the coronary score between Group II patients with ST-segment elevation or depression.

Rest and exercise electrocardiograms and radionuclides in patients presenting for cardiac rehabilitation.

The rest and exercise ECG, 201thallium myocardial scintigram (201T1), and radionuclide ventriculography are noninvasive procedures which can be used to evaluate myocardial damage and ischemia. To compare these procedures and to obtain baseline information, 85 male patients with coronary heart disease were evaluated prior to beginning an exercise program. Findings at rest included Q waves or bundle branch block in 54%; 47% had 201T1 redistribution defects and 33% an abnormal ejection fraction (EF). Of the 39 patients with normal ECGs, 31 had no 201T1 defects and only of these 31 (3%) had an abnormal EF. Abnormal EF or 201T1 redistribution defects did not occur in patients without a history of myocardial infarction. Abnormal resting EF occurred in 63% of patients with abnormal versus 7% of those with normal 201T1 redistribution scans. Exercise test results included an abnormal ST-segment response in 80%, an abnormal EF response in 65%, and a 201T1 ischemic defect in 37%. Twenty patients had exercise-induced ST elevation, and this phenomenon was more related to ventricular aneurysms than to ischemia. 201Thallium imaging, radionuclide ventriculography, and the ECG provide results regarding myocardial damage that agree by more than chance, while the exercise induced ST-segment changes did not agree with the radionuclide indications of exercise-induced ischemia.