Jean-Marie R. Detry

Optimal use of dobutamine stress for the detection and evaluation of coronary artery disease: combination with echocardiography or scintigraphy, or both?

OBJECTIVES This study was conducted to examine the efficacy of dobutamine stress two-dimensional echocardiography and perfusion scintigraphy for the detection of coronary artery disease in routine practice, to establish the causes of erroneous results and to derive appropriate criteria for the selection of either or both tests. BACKGROUND Dobutamine stress combined with echocardiography or perfusion scintigraphy may be used to detect coronary artery disease. Although both imaging approaches have demonstrated similar levels of accuracy, it is not known whether there may be particular indications for the use of one or the other technique or a rationale for their combination. METHODS Two hundred seventeen patients without previous infarction were studied prospectively with dobutamine stress echocardiography and technetium-99m methoxy isobutyl nitrile (sestamibi) single-photon emission computed tomography at the time of diagnostic coronary angiography. The presence of coronary stenoses of > or = 50% diameter was compared with the presence of rest or stress-induced abnormalities of perfusion and regional function. The extent of these abnormalities was correlated with an equivalent score of extent of angiographic disease. RESULTS Significant coronary artery disease was found in 142 patients; 102 (72%) were identified by dobutamine echocardiography and 108 (76%, p = NS) by perfusion imaging. In 75 patients without significant disease, the specificity of dobutamine echocardiography was 83% compared with 67% for scintigraphy (p = 0.05). Echocardiographic sensitivity was lower in patients unable to complete the test because of side effects (n = 64) than in the remainder (59% vs. 77%, p = 0.02); this influence was less apparent with scintigraphy (71% vs. 78%, p = NS). Selective use of scintigraphy in the 31 patients with a negative submaximal stress echocardiogram led to a sensitivity of 80% for this combination. Patients with left ventricular hypertrophy accounted for most of the difference in specificity between echocardiography and scintigraphy (94% vs. 59%, p = 0.02). Their respective accuracies were 76% and 73%. CONCLUSIONS Dobutamine stress echocardiography and perfusion scintigraphy have equivalent accuracy. In patients with left ventricular hypertrophy, echocardiography appears to be the test of choice. Selective use of sestamibi scintigraphy in patients with a negative submaximal echocardiogram enhances the accuracy of stress echocardiography alone.

Diagnostic value of history and maximal exercise electrocardiography in men and women suspected of coronary heart disease.

Coronary arteriographic data have been compared in 278 patients (231 males and 47 females) with the ECG response to a maximal exercise test and with the history (myocardial infarction - MI, typical or atypical angina pectoris - AP). The sensitivity and specificity of exercise ECG were similar in males and females. False negative ECG responses were frequent in males (40%) and false positive ECG responses were frequent in females (38%). This difference between sexes was essentially due in our patients to the higher prevalence of CHD in males (80%) than in females (43%). In the absence of a previous MI, a history of typical AP was associated with coronary heart disease (CHD) in 94% of males and 62% of females. Atypical AP was rarely associated with CHD (18% in males; 11% in females). When typical AP was associated with an abnormal exercise ECG, CHD was highly probable in males (98%) and present in 75% of females. In presence of atypical AP with a normal exercise ECG, CHD was unlikely in males (11%) and in females (8%). We conclude that exercise ECG has limited value for the diagnosis of CHD. In men with typical AP, exercise ECG often confirms the diagnosis but a negative ECG exercise does not rule out CHD because of the high incidence of fales negative responses. In males and females with atypical AP, an abnormal response to exercise is difficult to interpret owing to a high incidence of false positive responses.

How accurate is dobutamine stress electrocardiography for detection of coronary artery disease? Comparison with two-dimensional echocardiography and technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion scintigraphy.

OBJECTIVES This study was designed to establish the appropriate diagnostic criteria for positive dobutamine electrocardiographic (ECG) stress test results and to compare their accuracy with those of dobutamine two-dimensional echocardiography and perfusion scintigraphy. BACKGROUND Conventional criteria for positive findings on ECG exercise testing may not be appropriate for use with dobutamine ECG stress testing. METHODS One hundred twenty-nine consecutive patients with an interpretable ECG and without previous myocardial infarction were prospectively studied at the time of coronary arteriography. All completed a standard dobutamine protocol (5 to 40 micrograms/kg body weight per min in 3-min dose increments) without side effects. Significant coronary artery disease, defined as > 50% lumen diameter stenosis of a major epicardial coronary artery on coronary angiography, was present in 83 patients. Empiric receiver operating curves were generated for various ECG criteria derived from computer-averaged signals. RESULTS The best ECG criterion, with a sensitivity of 42% and a specificity of 83%, was an ST segment shift, relative to baseline, of 0.5 mm 80 ms after the J point. The sensitivity of this criterion was greater than that of the conventional criterion of 1-mm ST segment depression 60 (23%) or 80 (18%) ms after the J point, was comparable to that of chest pain occurring during the test (44%, p = NS) but remained inferior to the sensitivities of technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion (76%) or stress echocardiography (76%, p < 0.001, for both). The specificity of this criterion was not significantly different from that of technetium-99m mibi perfusion tomography (65%) or stress echocardiography (89%) but was superior to that of chest pain (59%, p < 0.025). CONCLUSIONS We conclude that this new criterion for dobutamine electrocardiography is specific but that an imaging technique is still required to accurately predict coronary artery disease.

Amlodipine reduces transient myocardial ischemia in patients with coronary artery disease: Double-blind circadian anti-ischemia program in Europe (CAPE trial)

OBJECTIVES This study was carried out to determine the effect of the once-daily calcium channel blocking agent amlodipine (half-life 35 to 50 h) on the circadian pattern of myocardial ischemia in patients with chronic stable angina. BACKGROUND Myocardial ischemia during normal daily life, both symptomatic and asymptomatic, has been associated with increased risk of cardiovascular morbidity and mortality, and the circadian pattern parallels that for myocardial infarction and sudden death. METHODS The Circadian Anti-Ischemia Program in Europe (CAPE) was a large, 10-week international (63 sites), double-blind, parallel study. After a 2-week, single-blind placebo phase, during which stable doses of antianginal treatment were maintained (beta-adrenergic blocking agents in 65% of patients), patients with chronic stable angina with at least three attacks of angina per week, with at least four ischemic episodes or > or = 20 min of ST segment depression in 48 h of Holter monitoring, were randomized to receive treatment with either 5 mg/day of amlodipine or placebo (2:1 randomization). The dose was increased to 10 mg/day after 4 weeks. During week 7 of treatment, 48-h ambulatory ECG monitoring was repeated. RESULTS Three hundred fifteen of 1,160 patients screened were eligible, and 250 had complete evaluable data. Compared with placebo, amlodipine significantly reduced both the frequency of ST segment depression episodes (60% for amlodipine vs. 44% for placebo, p = 0.025) and total integrated ST ischemic area (62% mm-min vs. 50% mm-min, p = 0.042). Amlodipine reduced ischemia over the 24 h with the intrinsic circadian pattern maintained. In addition, diary data showed a significant reduction in angina (70% for amlodipine vs. 44% for placebo, p = 0.0001) and in nitroglycerin consumption (67% vs. 22%, respectively, p = 0.0006). Amlodipine and placebo demonstrated similar safety profiles (adverse events 17.3% for amlodipine and 13.3% for placebo; discontinuation rates due to adverse events were 2% vs. 4.4%, respectively). CONCLUSIONS Once-daily amlodipine, when added to background treatment, significantly reduced both symptomatic and asymptomatic ischemic events over 24 h in patients with chronic stable angina.

Improved identification of coronary artery disease in patients with left bundle branch block by use of dobutamine stress echocardiography and comparison with myocardial perfusion tomography

This study compared the efficacy of dobutamine stress testing using 2-dimensional echocardiography and perfusion tomography for the noninvasive identification of coronary artery disease (CAD) in patients with left bundle branch block (LBBB). Twenty-four patients with permanent, complete LBBB (11 with previous myocardial infarction) were studied prospectively with dobutamine echocardiography and perfusion tomography. The presence of > 50% luminal diameter coronary stenosis was compared with the presence of dobutamine-induced fixed or reversible perfusion defects, and with resting or dobutamine-induced abnormalities of wall thickening. For each test, the left anterior coronary artery territory was compared with the circumflex and/or right coronary artery. Significant CAD was found in the left anterior descending coronary artery in 12 patients; all (100%) were identified by perfusion imaging, and 10 (83%, p = NS) by 2-dimensional stress echocardiography. In the 12 patients without left anterior descending CAD, scintigraphy was also positive in all (specificity: 0%), and echocardiography in only 1 (specificity: 92%, p < 0.01). The diagnostic accuracy was 50% and 87% (p < 0.05), respectively. This low specificity of perfusion tomography was improved by requiring an associated apical defect to indicate left anterior descending CAD and was corrected by restricting the diagnosis of coronary disease to those patients with partially reversible defects. In the circumflex and/or right coronary artery territory, sensitivity and specificity were similar using both techniques. We conclude that dobutamine-stress echocardiography is a specific and accurate test for the noninvasive identification of CAD, even in the left anterior descending artery territory of patients with LBBB.

Relation of exercise capacity to left ventricular systolic function and diastolic filling in idiopathic or ischemic dilated cardiomyopathy

Although exercise intolerance is a cardinal symptom of patients with dilated cardiomyopathy (DC) and heart failure, the factors that limit exercise capacity in these patients remain a matter of debate. To assess the contribution of left ventricular (LV) diastolic filling to the variable exercise capacity of patients with DC, we studied 47 patients (60 +/- 12 years) with DC in stable mild-to-moderate heart failure with a mean LV ejection fraction of 28%. Exercise capacity was measured as total body peak oxygen consumption (VO2) during symptom-limited bicycle (10 W/min) and treadmill (modified Bruce protocol) exercise. LV systolic function and diastolic filling were assessed at rest before each exercise by M-mode, Doppler echocardiography, and radionuclide ventriculography. As expected, treadmill exercise always yielded higher peak VO2 than bicycle exercise (21 +/- 6 vs 18 +/- 5 ml/kg/min, range 12 to 35 and 7 to 30 ml/kg/min, respectively, p <0.001). Both of these VO2 measurements were highly reproducible (R = 0.98). With univariate analysis, close correlations were found between peak VO2 (with either exercise modalities) and Doppler indexes of LV diastolic filling, as well as with the radionuclide LV ejection fraction. Stepwise multiple regression analysis identified 3 nonexercise variables as independent correlates of peak VO2, of which the most powerful was the E/A ratio (multiple r2 = 0.38, p <0.0001), followed by peak A velocity (r2 = 0.54, p <0.0001) and mitral regurgitation grade (r2 = 0.58, p = 0.024). In conclusion, our data indicate that in patients with DC, peak VO2 is better correlated to diastolic filling rather than systolic LV function.

Coronary artery reperfusion in acute myocardial infarction: assessment by pre- and postintervention thallium-201 myocardial perfusion imaging.

In a randomized trial of intracoronary streptokinase (STK) therapy in acute myocardial infarction, 44 patients (21 control subjects and 23 patients treated with STK) underwent sequential thallium-201 planar imaging before angiography and after 4 hours (redistribution), 4 days and 6 weeks. Patients were classified according to the presence or absence of angiographic reperfusion of the infarct-related artery. The semiquantitative score of myocardial thallium uptake was expressed as percent of maximal defect score. Both in control and in STK-treated groups, thallium defect scores decreased over time, but this decrease was smaller in the control group (before angiography, 33 +/- 4%; redistribution, 29 +/- 4%; 4 days, 25 +/- 4%; and 6 weeks, 22 +/- 4%) than in the STK group (44 +/- 4%, 38 +/- 4%, 26 +/- 4% and 21 +/- 3%, respectively). In patients in whom reperfusion was achieved (20 STK-treated, 6 control subjects), a marked decrease in thallium score was observed (before angiography, 40 +/- 4%; redistribution, 32 +/- 4%; 4 days, 20 +/- 5%; and 6 weeks, 14 +/- 22%) compared with patients in whom reperfusion was not achieved (37 +/- 4%, 36 +/- 5%, 33 +/- 5% and 33 +/- 4%, respectively). These results indicate that serial thallium imaging is an accurate method of assessing changes in myocardial perfusion after acute myocardial infarction. Restoration of thallium uptake was observed after reperfusion of the infarct-related artery whether this recanalization was seen spontaneously or after successful thrombolysis.

Hemodynamic Determinants of Exercise ST-Segment Depression in Coronary Patients

Eight patients with coronary heart disease were studied during two periods of exercise separated by 30 min of rest; workload was increased in a stepwise fashion every minute of exercise up to a level that produced limiting symptoms of angina, fatigue, or dyspnea. The magnitude of ST-segment depression and the central aortic pressure were measured during exercise and recovery periods, and myocardial oxygen requirements were estimated by the pressure-time index (systolic aortic pressure × heart rate × ejection time).Seven of the eight patients exhibited a close relationship (r ranged from 0.74 to 0.98) between magnitude of exercise ST-segment depression and indices expressing myocardial oxygen requirements; heart rate, blood pressure, and ejection time were also related to magnitude of exercise ST-segment depression. These relationships were reproducible during two consecutive exercises. Like onset of angina, magnitude of exercise ST-segment depression is usually related to hemodynamic factors influencing myocardial oxygen needs. Consequently, comparisons of exercise-induced ST depression before and after therapy (drugs, physical training, and surgery) are valid only if ECG findings are compared at the same level of myocardial oxygen requirements.In contrast, absence of such a relationship during recovery suggests an important difference in mechanisms of the post-exercise electrocardiogram.

Risk stratification in patients with dilated cardiomyopathy: contribution of Doppler-derived left ventricular filling

Dilated cardiomyopathy (DCM) is a major cause of mortality among patients with heart failure. The aim of the present study was to investigate the independent contribution of Doppler-derived left ventricular (LV) filling to the prediction of survival in patients with DCM, of either ischemic or nonischemic origin, and to derive a simple risk stratification score based on easily available clinical and echocardiographic parameters. We followed 197 consecutive patients (159 men, mean age 60+/-13 years) with an echocardiographic diagnosis of DCM (LV end-diastolic dimension >60 mm, fractional shortening <25%) over an average period of 62+/-13 months. The presumed etiology of DCM was ischemic in 52% of the patients. During follow up, 69 patients died of cardiac causes and 41 required transplantation. At 5 years, overall cardiac event-free survival was 55% and freedom from death or heart transplantation was 43% (compared with 86% for the 5-year age- and sex-adjusted survival rate in our country). Kaplan-Meier survival curves generated for different thresholds of the peak E velocity and the E/A ratio indicated significant worsening of prognosis with increasing values of these parameters in both ischemic and nonischemic patients. Using Cox stepwise regression analyses, age (chi-square to remove 24.4; p <0.001), peak E velocity (chi-square to remove=18.9; p <0.001), LV ejection fraction (chi-square to remove 6.4; p <0.011), and systolic blood pressure (chi-square to remove 4.5; p=0.034) independently predicted cardiac deaths, whereas New York Heart Association (NYHA) functional class (chi-square to remove 48.5; p < 0.001), LV ejection fraction (chi-square to remove 19.1; p <0.001), E/A ratio (chi-square to remove 10.8; p <0.001), and systolic blood pressure (chi-square to remove 5.8; p <0.016) were independently associated with cardiac death or need for transplantation. Based on these parameters, a risk score was elaborated, which allowed appropriate classification of each individual patient into low- (5-year survival rate of 72%), intermediate- (46% survival rate), and high-risk groups (11% survival rate). In conclusion, our data show that among the noninvasive parameters commonly available in patients with either ischemic or nonischemic DCM, age, the NYHA functional class, the LV ejection fraction, the systolic blood pressure, the peak E velocity, and the E/A ratio provide relevant and independent information regarding the risk of cardiac death or the need for heart transplantation.

Trimetazidine European Multicenter Study Versus Propranolol in Stable Angina-pectoris - Contribution of Holter Electrocardiographic Ambulatory Monitoring

The major objective of the Trimetazidine European Multicenter Study (TEMS) was to compare in a double-blind trial the anti-ischemic effects of trimetazidine (20 mg 3 times daily) with those of propranolol (40 mg 3 times daily). The inclusion criteria were based on an abnormal response to a multistage exercise test. After 3 months of treatment the improvements noted in all exercise testing data were similar in the trimetazidine and propranolol groups; similar data were obtained for the grades and severity of anginal attacks during daily life (from patient diaries). A 24-hour Holter monitoring was performed at entry and at the end of the study, but an abnormal Holter monitoring (1-mm ST-segment depression during at least 1 minute) was not an inclusion criterion. This explains why at entry only 50% of the patients in both groups had an abnormal Holter recording. After 3 months of treatment, there were no significant differences between the 2 groups, but we observed a trend toward a decrease in ambulatory ischemia in the trimetazidine group and a trend toward an increase in ambulatory ischemia in the propranolol group. These data in the propranolol group are in total disagreement with the available literature on beta blockers, which was due to a totally erratic behavior pattern in 2 patients in the propranolol group. When we excluded these 2 erratic cases from the propranolol group and extended our analysis to all available paired comparisons (day -14 to day 30 and day 0 to day 90), we were able to compare 44 and 60 observations, both off therapy and on either propranolol or trimetazidine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)