M. John Williams

Exercise echocardiography is an accurate and cost-efficient technique for detection of coronary artery disease in women

OBJECTIVES This study compared the accuracy and cost implications of using exercise echocardiography and exercise electrocardiography for detection of coronary artery disease in women. BACKGROUND The specificity of exercise electrocardiography in women is lower than in men. Exercise echocardiography accurately identifies coronary artery disease in women, but its utility in place of exercise electrocardiography is unclear. METHODS One hundred sixty-one women without a previous Q wave infarction underwent exercise echocardiography and coronary angiography. Positive findings were a new or worsening wall motion abnormality on the exercise echocardiogram and ST segment depression > 0.1 mV at 0.08 s after the J point on the exercise electrocardiogram (ECG). RESULTS Coronary artery stenosis > 50% diameter narrowing was present in 59 patients; the sensitivity (mean +/- SD) of exercise echocardiography was 80 +/- 3%. In 48 patients with an interpretable ECG, the sensitivity of exercise echocardiography was 81 +/- 4%, and that of the exercise ECG was 77 +/- 3% (p = 0.50). In 102 patients without coronary artery disease, the overall specificity of exercise echocardiography was 81 +/- 4%. In 70 patients with an interpretable ECG, the specificity of exercise echocardiography (80 +/- 3%) exceeded that of the exercise ECG (56 +/- 4%, p < 0.0004). The accuracy of exercise echocardiography was also greater than exercise electrocardiography (81 +/- 5% vs. 64 +/- 6%, p < 0.005). Exercise echocardiography stratified significantly more patients of intermediate (20% to 80%) pretest disease probability into the high (> 80%) or low (< 20%) posttest probability group. In women without a previous exercise ECG, the specificity of exercise echocardiography continued to exceed that of exercise electrocardiography (80 +/- 3% vs. 64 +/- 3%, p = 0.05). Exercise echocardiography had the best balance between accuracy and cost for the diagnosis of coronary artery disease in women. CONCLUSIONS Exercise echocardiography is more specific than exercise electrocardiography for diagnosis of coronary artery disease in women and is a cost-effective approach to the diagnosis of coronary artery disease because of the avoidance of inappropriate angiography.

Prognostic value of dobutamine echocardiography in patients with left ventricular dysfunction

OBJECTIVES This study sought to establish the prognostic implications of ischemic and viable myocardium identified by dobutamine echocardiography in patients with left ventricular dysfunction. BACKGROUND Recent studies have suggested that in patients with viable myocardium identified by positron emission tomography, medical treatment is associated with recurrent cardiac events. Dobutamine echocardiography has been used to identify viable myocardium in patients with left ventricular dysfunction, but the prognostic significance of this test is undefined. METHODS One hundred thirty-six consecutive patients (mean [+/- SD] age 67 +/- 7.9 years; 104 men) with moderate or severe left ventricular dysfunction (left ventricular ejection fraction 30 +/- 5%) undergoing dobutamine echocardiography were included in the study. Dobutamine was administered using a standard incremental protocol (5 to 40 micrograms/kg body weight per min intravenously in 3-min stages) with additional atropine (1 mg intravenously) as required. Standard body weight echocardiographic views were digitized on-line and compared using a side-by-side display. Viable myocardium was identified by enhancement of regional function at low dose (< 10 micrograms); scar was diagnosed by akinesia at rest or dyskinesia without change and ischemia as new or worsening dysfunction. One hundred thirty patients (95%) were followed up for 16 +/- 8 months after the original study for major cardiac events (cardiac death, myocardial infarction or severe unstable angina requiring late myocardial revascularization). RESULTS No significant complications occurred during dobutamine echocardiography. Viable myocardium was detected in 26 patients (19%), ischemia in 23 (17%), both viability and ischemia in 13 (10%) and scar in 74 (54%). Of 108 patients treated medically, 46 had viable or ischemic myocardium, and 62 had scar only. There were no significant differences in age or other clinical characteristics, stress response, left ventricular dimensions and ejection fraction between the two groups. Cardiac events occurred in 26 medically treated patients (24%): 18 died of cardiac-related causes; 4 had a nonfatal myocardial infarction; and 4 had late revascularization because of unstable angina. The event rate was greater in patients with viable or ischemic myocardium than those with scar (43% vs. 8%, p = 0.01 by log-rank test). In a Cox regression model, the presence of viable or ischemic myocardium was found to predict subsequent events (relative risk 3.51, p = 0.02) independently of ejection fraction and age. CONCLUSIONS Viable or ischemic myocardium detected at dobutamine echocardiography in patients with left ventricular dysfunction is associated with an adverse prognosis, independent of age and ejection fraction.

Functional status and quality of life in patients with heart failure undergoing coronary bypass surgery after assessment of myocardial viability

OBJECTIVES The aim of this study was to evaluate whether preoperative clinical and test data could be used to predict the effects of myocardial revascularization on functional status and quality of life in patients with heart failure and ischemic LV dysfunction. BACKGROUND Revascularization of viable myocardial segments has been shown to improve regional and global LV function. The effects of revascularization on exercise capacity and quality of life (QOL) are not well defined. METHODS Sixty three patients (51 men, age 66+/-9 years) with moderate or worse LV dysfunction (LVEF 0.28+/-0.07) and symptomatic heart failure were studied before and after coronary artery bypass surgery. All patients underwent preoperative positron emission tomography (PET) using FDG and Rb-82 before and after dipyridamole stress; the extent of viable myocardium by PET was defined by the number of segments with metabolism-perfusion mismatch or ischemia. Dobutamine echocardiography (DbE) was performed in 47 patients; viability was defined by augmentation at low dose or the development of new or worsening wall motion abnormalities. Functional class, exercise testing and a QOL score (Nottingham Health Profile) were obtained at baseline and follow-up. RESULTS Patients had wall motion abnormalities in 83+/-18% of LV segments. A mismatch pattern was identified in 12+/-15% of LV segments, and PET evidence of viability was detected in 30+/-21% of the LV. Viability was reported in 43+/-18% of the LV by DbE. The difference between pre- and postoperative exercise capacity ranged from a reduction of 2.8 to an augmentation of 5.2 METS. The degree of improvement of exercise capacity correlated with the extent of viability by PET (r = 0.54, p = 0.0001) but not the extent of viable myocardium by DbE (r = 0.02, p = 0.92). The area under the ROC curve for PET (0.76) exceeded that for DbE (0.66). In a multiple linear regression, the extent of viability by PET and nitrate use were the only independent predictors of improvement of exercise capacity (model r = 0.63, p = 0.0001). Change in Functional Class correlated weakly with the change in exercise capacity (r = 0.25), extent of viable myocardium by PET (r = 0.23) and extent of viability by DbE (r = 0.31). Four components of the quality of life score (energy, pain, emotion and mobility status) significantly improved over follow-up, but no correlations could be identified between quality of life scores and the results of preoperative testing or changes in exercise capacity. CONCLUSIONS In patients with LV dysfunction, improvement of exercise capacity correlates with the extent of viable myocardium. Quality of life improves in most patients undergoing revascularization. However, its measurement by this index does not correlate with changes in other parameters nor is it readily predictable.

Comparison of exercise echocardiography with an exercise score to diagnose coronary artery disease in women.

This study compares the accuracy of the routine exercise electrocardiogram, exercise score, and exercise echocardiography for the diagnosis of coronary artery disease (CAD) in women. Seventy women with a pretest probability of 53 +/- 30% for CAD were stressed using a maximal symptom-limited bicycle exercise protocol. Significant ST-segment change was defined by a depression of > 0.1 mV 0.06 second after the J point. The exercise score was calculated from ST response, heart rate, and workload using an equation derived from a multivariate model. A positive stress echocardiogram was defined by development of a new or worsening wall motion abnormality. The results were compared with the presence or absence of significant (> 50% diameter) stenoses at angiography. Exercise echocardiography identified 29 of the 33 patients (88%) with CAD, compared with 22 (67%) using ST analysis alone, and 20 (61%) using the exercise score (both p < 0.05 vs exercise echocardiography). The specificity of exercise echocardiography (84%) and the multivariate score (73%) were comparable, and exceeded that of the ST analysis (51%) in 37 patients without CAD (p < 0.01). The accuracy of exercise echocardiography (86%) exceeded that of the exercise score (67%, p = 0.01) and ST analysis (59%, p < 0.01). Among all 70 patients, an intermediate (20% to 80%) probability of coronary disease was identified in 21 patients on the basis of exercise echocardiography, in 38 based on the multivariate score, and in 38 based on the ST analysis alone. Exercise echocardiography is more sensitive than the exercise score, and more sensitive and specific than ST-segment analysis for the diagnosis of CAD in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the extent and timing of the coronary hyperemic response to dipyridamole: A study with transesophageal echocardiography and positron emission tomography with oxygen 15 water

Coronary flow reserve may be measured with Doppler-derived coronary blood-flow velocity or scintigraphic assessment of myocardial perfusion. The purpose of this study was to compare coronary flow velocity and perfusion measures of flow reserve with respect to their extent and time course. Coronary flow velocity reserve in the proximal left anterior descending coronary artery measured by pulsed-wave Doppler at transesophageal echocardiography, with measures of perfusion reserve obtained in the corresponding territory, were measured by a standard O15 water technique at positron emission tomography. Eighteen male volunteers underwent both tests on different days in random order, with dipyridamole stress (0.56 mg/kg). After correction of resting flow and perfusion measurements to a standard cardiac workload (to compensate for heterogeneity in hemodynamics between the two studies), coronary flow reserve was calculated as the ratio between dipyridamoleand corrected resting flow. The uncorrected perfusion reserve measured by positron emission tomography was 3.7 +/- 1.2, compared with a corrected perfusion reserve of 2.3 +/- 0.7. This correlated with a corrected flow velocity reserve of 2.9 +/- 1.0 at transesophageal echocardiography (R = 0.92; p < 0.001). The mean difference between these results was 0.58 +/- 0.41; discrepant results occurred at higher flows, in the presence of discordant blood pressure responses to stress, and because of intersubject variations in the timing of the peak coronary flow response, which were detected by continuous monitoring at transesophageal echocardiography. Measurement of coronary flow reserve at transesophageal echocardiography correlates well with measurements at positron emission tomography, and discrepancies are minimized if measurements are taken at the same time after dipyridamole.

Correlation of Preoperative Myocardial Function, Perfusion, and Metabolism With Postoperative Function at Rest and Stress After Bypass Surgery in Severe Left Ventricular Dysfunction

Previous studies of dobutamine echocardiography (DE) and positron emission tomography (PET) showed similar accuracy for predicting improvement in resting wall motion after revascularization, although limited direct comparative data are available. We sought to compare the relative accuracy of detecting contractile reserve, ischemia, perfusion, and myocardial metabolism for predicting functional recovery after coronary bypass surgery in 94 consecutive patients (aged 63+/-11 years) with chronic coronary disease and depressed left ventricular function (ejection fraction 28+/-5%). PET imaging comprised rest and dipyridamole stress myocardial perfusion images, with fluorodeoxyglucose to define metabolism-perfusion mismatch. A standard dobutamine-atropine stress was used, with evaluation of low- and peak-dose echocardiographic responses. Regional function was assessed after 13+/-16 weeks at rest in 68 patients who underwent isolated coronary bypass operation without evidence of perioperative infarction, and at rest and stress in a subgroup of 29 patients. Concordance between methods for evaluating abnormal segments (ischemic, viable, and scar) and accuracy of both tests for predicting improvement in regional function were identified. Concordance between PET and DE for identifying viable or nonviable myocardium was 63% using a 16-segment model. For predicting improved resting function after surgery, the sensitivity of PET (84%) was superior to DE (69%, p<0.001), but DE was more specific (78% vs. 37%, p<0.0001) and more accurate (75% vs. 53%, p<0.001) in predicting recovery at rest. Analysis of postoperative recovery of segmental function during stress also showed the specificity of DE to exceed that of PET (89% vs. 32%, p<0.001). The accuracy of DE was enhanced by evaluation of function during stress (86%, p<0.001), but this was not altered with PET (52%, p = NS). Thus, PET is more sensitive than DE in predicting functional recovery, but DE is more specific than PET. Evaluation of left ventricular functional recovery during stress may be preferable to assessment at rest.

Increased left ventricular cavity size, not wall thickness, potentiates myocardial ischemia

Left ventricular (LV) hypertrophy increases the vulnerability of the myocardium to ischemia. The purpose of this study was to determine whether LV diameter or wall thickness was the principal determinant of the effect of LV mass on the development of ischemia, measured by exercise thallium perfusion imaging, in a population with coronary artery disease (CAD). We studied 109 patients with CAD but no prior myocardial infarction who underwent exercise thallium imaging within 1 year of coronary angiography. Thallium perfusion defects were present in 76% of patients. LV mass index was associated with thallium perfusion abnormalities (odds ratio 2.09 for 50 gm increments), an association that persisted after adjusting for extent of CAD. LV end-diastolic diameter had a strong correlation with a thallium defect (odds ratio 3.7 for 10 mm increments), but LV wall thickness had no correlation (odds ratio 1.0 for 5 mm increments). In a stepwise regression model that included extent of CAD and other potential clinical variables, LV end-diastolic diameter was the strongest predictor of thallium defects (adjusted odds ratio 4.5). This study confirms the association of LV hypertrophy with ischemia in patients with CAD, specifically in patients with eccentric hypertrophy.

901-54 Exercise Echocardiography is More Cost Efficient than Exercise ECG as an Initial Test for Evaluation of Cardiac Symptoms in Women

Although exercise echo (ExE) has been shown to be more accurate and specific than exercise electrocardiography (ExECG) in women, the clinical and cost implications of incorporating ExE in the evaluation of suspected coronary artery disease (CAD) in women has not been well resolved. The aim of this study was to assess the accuracy, angiography rate. and cost of various diagnostic strategies in women. A consecutive group of 161 female patients (age 60 ± 9 yrs) underwent ExECG, ExE and coronary angiography. Positive ExECG was defined as g 0.1 mV ST depression, and positive ExE was defined by a new or worsening wall motion abnormality. Sensitivity (sens) and specificity (spec) were calculated by comparison of ExE (sens 79%, spec 81%) and ExECG (sens 77%, spec 56%) with angiography(significant stenosis g 50%). Pre-test CAD probability (44 ± 33%) was calculated from age and symptoms. Seven different strategies (see table) involving angiography, ExECG ExE, selective combination (ExE for nondiagnostic ExECG), stepwise combination (ExE for positive or nondiagnostic ExECG), and Bayesian approaches (all high pre-test CAD probability pts undergoing angiography, intermediate probability pts undergoing angiography, if ExE or ExECG positive); Strategy Cost/pt (

Relative efficacy of medical therapy and revascularization for improving exercise capacity in patients with chronic left ventricular dysfunction

) Angio(%) Negative angio (%) FalseNeg% I Angiography 1.434 100 63 0 II Exercise ECG 1,023 69 56 11 III Exercise Echo 828 41 29 13 IV Selective ECG/echo 836 51 44 14 V Stepwise ECG/echo 663 31 26 22 VI Bayesian ECG 745 37 27 25 VII Bayesian ExEcho 641 51 48 29 Use of ExE in all pts, with angiography only with positive ExE (III) involved less angiography and was less expensive at a similar level of accuracy to I and II. Strategy IV is least expensive but would lead to an unacceptable number of false negatives. The Bayesian approaches are compromised by the limitations of clinical stratification of women into high and low probability groups based on symptoms. Conclusion The greater spec of ExE in women avoids inappropriate angiography. Use of ExE as an initial test for CAD in women is justifiable on cost grounds.