Gender differences and temporal trends in clinical characteristics, stress test results and use of invasive procedures in patients undergoing evaluation for coronary artery disease.

OBJECTIVES: This study examined gender differences and temporal changes in the clinical characteristics of patients referred for nuclear stress imaging, their imaging results and subsequent utilization of coronary angiography and revascularization. BACKGROUND: Gender bias may influence resource utilization in patients with coronary artery disease (CAD). No study has analyzed gender differences and time trends in patients referred for noninvasive testing and subsequent use of invasive procedures. METHODS: Between January 1986 and December 1995, 14,499 patients (5,910 women and 8,589 men) without established CAD underwent stress myocardial perfusion imaging. The clinical characteristics, imaging results, coronary angiograms and revascularization outcomes were compared in women and men over time. RESULTS: The mean pretest probability of CAD was lower in women (45%) than in men (70%) (p < 0.001). More women (69%) than men (42%) had normal nuclear images (p < 0.001). Men (17%) were more likely than women (8%) to undergo coronary angiography (p < 0.001). Male gender was independently associated with referral for coronary angiography (multivariate model: chi-square = 16, p < 0.001) but was considerably weaker than the imaging variables (summed reversibility score: chi-square = 273, p < 0.001). Revascularization was performed in more men (46% of the population undergoing angiography) than women (39%) (p = 0.01), but gender was not independently associated with referral to revascularization. There were no significant differences in clinical, imaging or invasive variables between the genders over time. CONCLUSIONS: There was little evidence for a bias against women in this study. Women were somewhat less likely to undergo coronary angiography but were referred for stress perfusion imaging more liberally. Practice patterns remained constant over this 10-year period.

Assessment of the exercise electrocardiogram in women versus men using tomographic myocardial perfusion imaging as the reference standard.

The exercise electrocardiogram (ECG) is widely believed to be less accurate in women, primarily due to a high prevalence of false-positive tests. The purpose of this study was to examine the relative accuracy of the exercise ECG in women versus men in 8,671 patients (3,213 women, 5,458 men) using myocardial perfusion imaging as the reference standard. More women (14%) than men (10%) had a false-positive ECG (p <0.001), but the absolute difference was relatively small. The false-negative rate was considerably lower in women (17% vs 32%, p <0.001). Compared with men, women had lower test sensitivity (30% vs 42%, p <0.001) and positive predictive value (34% vs 70%, p <0.001) but higher specificity (82% vs 78%, p = 0.002), negative predictive value (78% vs 52%, p <0.001), and accuracy (69% vs 58%, p <0.001). In patients with a false-negative exercise ECG, "high-risk" scans were less prevalent in women (12% vs 19%, p <0.001). In the smaller subset of patients referred for coronary angiography (205 women, 838 men), the false-positive electrocardiographic rate was again higher in women (13% vs 7%, p = 0.003), but neither specificity (69% vs 74%, p = NS) nor accuracy (60% vs 66%, p = NS) was different between the sexes. Thus, the percentage of patients with a false-positive exercise ECG was higher in women than men but low in absolute terms (<15%) for both sexes. Test specificity was not lower in women. These results suggest that gender should not be a major determinant for selecting stress imaging over standard treadmill testing.

Comparison of acute myocardial infarct size to two-year mortality in patients <65 to those > or =65 years of age.

Older patients have higher in-hospital and longer term mortality after myocardial infarction. To determine if larger infarct size correlates with this observation, myocardium at risk was measured on arrival to the hospital in 347 patients with acute myocardial infarction, and final infarct size was measured at hospital discharge in a subset of 274 of these patients. Myocardium at risk and final infarct size were quantified by tomographic technetium-99m sestamibi imaging. Statistical analyses examined the associations between age, myocardium at risk, final infarct size, and both in-hospital and postdischarge mortality. Median value for age was 64 years, and myocardium at risk was 24% and final infarct size was 12% of the left ventricle. There was no correlation between age and myocardium at risk (r = 0.04, p = NS) or final infarct size (r = 0.06, p = NS). In-hospital mortality was 4% overall and was 2% for patients <65 years old versus 6% for those > or =65 years old (chi-square 11.3, p<0.001). In-hospital mortality was not associated with myocardium at risk (chi square <1, p = NS). For the subset of 274 patients in whom final infarct size was measured, the subsequent 2-year mortality rate was 3% and was independently associated with both age (chi-square 15.6, p<0.001) and final infarct size (chi-square 9.7, p = 0.002). Survival was excellent for patients who were either <65 years old (2-year mortality 1%) or had an infarct size <12% (2-year mortality 0%). For patients > or =65 years old with infarct size > or =12%, 2-year mortality was 13%. These results demonstrate that older patients do not have larger infarcts. Advanced age is associated with higher in-hospital and postdischarge mortality, independent of infarct size.

Clinical determinants of hemodynamic and symptomatic responses in 2,000 patients during adenosine scintigraphy.

OBJECTIVE: To determine whether subsets of patients referred for a clinically indicated radionuclide adenosine stress study respond differently to a standard infusion of adenosine. MATERIAL AND METHODS: We assessed multiple clinical and hemodynamic variables in the first 2,000 patients who underwent adenosine perfusion studies in our laboratory. A relevant clinical variable was defined as one that was significantly associated with changes in heart rate and blood pressure during adenosine infusion. Relevant clinical variables that were most significantly related to hemodynamic variables included age, gender, rhythm (atrial fibrillation), diabetes, and left ventricular function. These variables were then related to symptomatic responses (adverse effects) to adenosine infusion. To determine whether the different peripheral responses to adenosine reflected clinically important differences in coronary vasodilatation, we compared perfusion imaging with coronary angiographic findings in the 408 patients who underwent both studies within 6 months of each other. RESULTS: The decrease in systolic blood pressure was greater and the reflex tachycardia was less in patients 70 years of age or older and in those with insulin-dependent diabetes in comparison with younger patients and those without type 1 diabetes. Men had smaller decreases in blood pressure and smaller increases in heart rate than did women. Patients with atrial fibrillation and those with left ventricular ejection fraction less than 40% had smaller decreases in blood pressure and smaller increases in heart rate than did those in sinus rhythm or those with an ejection fraction of 40% or more. Age 70 years or older, male gender, atrial fibrillation, and left ventricular ejection fraction less than 40% were associated with fewer symptoms and less severe chest pain in comparison with patients without these variables. For patients with coronary angiograms, the relationship between coronary artery disease evident on angiography and perfusion abnormalities noted on scintigraphy was not different for any of the relevant clinical variables. CONCLUSION: Common clinical patient subsets are associated with different peripheral hemodynamic and symptomatic responses to infusion of adenosine. Despite these observations, however, the ability to detect coronary artery disease with perfusion imaging is not obviously altered.

Prognosis in patients with spontaneous chest pain, a nondiagnostic electrocardiogram, normal cardiac enzymes, and no evidence of severe resting ischemia by quantitative technetium 99m sestamibi tomographic imaging.

BACKGROUND: There are limited data addressing the outcome of patients with normal or near normal myocardial perfusion during chest pain at rest. The purpose of this study was to determine the prognosis of patients with spontaneous chest pain, a normal or nondiagnostic electrocardiogram, no enzymatic evidence of myocardial infarction, and no evidence of severe resting ischemia by quantitative technetium 99m (99mTc) sestamibi imaging. METHODS: In the study, 111 patients who fulfilled the above criteria were injected with 99mTc sestamibi during resting chest pain and were followed for a median 2.7 years. Of the patients in the study group, 58% had coronary artery disease that was documented by clinical history or coronary angiography. Tomographic 99mTc perfusion images were interpreted with a quantitative threshold technique initially developed to detect severely hypoperfused myocardium. The images were also interpreted qualitatively to detect patients with milder degrees of hypoperfused myocardium. RESULTS: During follow-up 3 patients had cardiac deaths, 5 had nonfatal myocardial infarctions, and 21 underwent revascularization procedures (13 within 3 months and 8 more than 3 months after the sestamibi study). At 3 years, survival free of cardiac death was 97%, survival free of cardiac death or myocardial infarction was 91%, and survival of cardiac death, myocardial infarction, or late revascularization was 82%. Quantitative analysis of the scans revealed that 100% of patients without fixed defects had 3-year survival free of cardiac death versus 76% of patients who had fixed defects (p < 0.001). Mild to moderate resting ischemia by qualitative interpretation of the scans was present in 20% of patients, but this did not predict outcome. CONCLUSIONS: Patients with spontaneous chest pain and nonischemic quantitative 99mTc sestamibi images were at reasonably low risk for hard cardiac events although some patients (18%) required revascularization.

Infarct size after acute myocardial infarction measured by quantitative tomographic 99mTc sestamibi imaging predicts subsequent mortality.

BACKGROUND: 99mTc sestamibi is a recently developed radioisotope that has been used to measure myocardium at risk and infarct size. The relation between these measurements and subsequent patient outcome has not yet been demonstrated. METHODS AND RESULTS: Two hundred seventy-four consecutive patients with acute myocardial infarction underwent tomographic 99mTc sestamibi imaging on arrival at the hospital (to measure myocardium at risk before reperfusion therapy) and at hospital discharge (to measure the amount of salvaged myocardium and final infarct size). Defect size on the sestamibi images was quantified using a threshold value of 60% of peak counts from the circumferential count profile curves generated for five representative slices of the left ventricle. Patients were followed after hospital discharge to evaluate the association between final infarct size and subsequent mortality. The median defect size measured was 27% of the left ventricle at presentation to the hospital (range, 0% to 77%) and was 12% of the left ventricle at hospital discharge (range, 0% to 68%). Almost one half of the patients had a final infarct size of < or = 10%. The median amount of myocardium salvaged was 9% (range, -31% to 75%). During a median duration of follow-up of 12 months, there were 10 deaths (7 cardiac and 3 noncardiac) and 1 resuscitated out-of-hospital cardiac arrest. There was a significant association between infarct size and overall mortality (chi 2 = 8.66, P = .003) and cardiac mortality (chi 2 = 11.89, P < .001). Two-year mortality was 7% for patients whose infarct size was > or = 12% versus 0% for patients whose infarct size was < 12%. There also was a significant association between myocardium at risk and cardiac mortality (chi 2 = 6.87, P = .009). There was no association between myocardium at risk and overall mortality or between amount of myocardium salvaged and either overall mortality or cardiac mortality. CONCLUSIONS: Larger infarct size measured by 99mTc sestamibi imaging after acute myocardial infarction is associated with increased mortality risk during short-term follow-up.

Hemodynamic responses and adverse effects associated with adenosine and dipyridamole pharmacologic stress testing: a comparison in 2,000 patients.

OBJECTIVE: To compare the hemodynamic responses and the adverse effects associated with two coronary vasodilators used for pharmacologic stress testing. DESIGN: We retrospectively studied the results of adenosine and dipyridamole perfusion imaging in a large group of patients who underwent pharmacologic stress radionuclide perfusion imaging. MATERIAL AND METHODS: One thousand patients given dipyridamole between April 1989 and April 1991 (before adenosine became available) were compared with 1,000 patients given adenosine between April 1991 and October 1992. A standard protocol was used to infuse the drugs before myocardial perfusion imaging with 201Tl or 99mTc sestamibi. RESULTS: Peak heart rate was higher (85 versus 83 beats/min; P = 0.02) and systolic blood pressure was lower (129 versus 133 mm Hg; P < 0.0001) with adenosine than with dipyridamole. More patients had a decrease in systolic blood pressure of 30 mm Hg or more with adenosine than with dipyridamole (P = 0.002). Horizontal or downsloping ST-segment depression of 1 mm or more occurred in 9% of patients who received adenosine and in 8% of those who received dipyridamole. Adverse effects occurred in 78% of the adenosine study group and in 50% of the dipyridamole group (P < 0.0001). Chest pain was the most common symptom with both drugs. Atrioventricular block occurred in 76 patients who received adenosine but in none who received dipyridamole. Because of adverse effects, 28% of patients who received dipyridamole required extra monitoring time (mean, 6 +/- 5 minutes beyond the standard protocol). Aminophylline was administered to 163 and 6 patients, respectively, in the dipyridamole and adenosine study groups. CONCLUSION: Adenosine causes slightly greater systemic vasodilation than does dipyridamole. Adverse effects occur less often with dipyridamole but, in comparison with adenosine, are more difficult to manage and necessitate more monitoring time as well as fairly frequent intravenous use of aminophylline for reversal.

Comparison of reinjection thallium 201 and resting technetium 99m sestamibi tomographic images for the quantification of infarct size after acute myocardial infarction.

BACKGROUND: Both thallium 201 and technetium 99m sestamibi have been used to quantitate infarct size at rest. Exercise 201Tl scintigraphy has been shown to have powerful prognostic information after myocardial infarction. A single study using these agents that could provide data on infarct size and prognosis would be of value. The purpose of this study was to compare estimates of infarct size by use of 201Tl and 99mTc sestamibi and to correlate these measurements with left ventricular ejection fraction in patients after acute myocardial infarction. METHODS AND RESULTS: The study group consisted of 20 patients who underwent low-level 201Tl stress studies with reinjection and 99mTc sestamibi resting studies within 4 days. Acute reperfusion was attempted in 18 of 20 patients. For 99mTc sestamibi tomographic imaging, infarct size was quantitated with 60% of maximal counts per slice for five short-axis slices as described in multiple previous studies. The postreinjection delayed 201Tl images acquired 4 hours after stress were quantitated according to the same threshold method. 201Tl patient images were also quantitated with a commercially available polar map program and compared with sex-matched control subjects. Ejection fraction was determined for each patient by radionuclide ventriculography 6 weeks later. Ejection fraction was well preserved for the group: mean 0.53 +/- 0.10. Infarct size with 99mTc sestamibi was 12% +/- 13% of the left ventricle, which was significantly smaller than either method with 201Tl: threshold method, 29% +/- 18% of left ventricle; polar map method, 25% +/- 17% of left ventricle (both 201Tl estimates, p < 0.0001 vs 99mTc sestamibi; 201Tl, 70% threshold vs 201Tl polar map, p = 0.04). There was a significant correlation between infarct size with 99mTc sestamibi and that with 201Tl (r = 0.72 to 0.73; p < 0.001). Infarct size with 99mTc sestamibi, however, provided the closest correlation with ejection fraction (r = 0.81; p < 0.001), with the two 201Tl quantitative methods providing very similar correlations (r = 0.69; p < 0.001). CONCLUSIONS: Infarct size with reinjection 201Tl imaging correlates significantly with resting infarct size with 99mTc sestamibi, although it provides significantly larger estimates. Although both approaches can be combined with a same-day exercise protocol, the closer correlation of infarct size with ejection fraction at 6 weeks suggests that resting infarct size with 99mTc sestamibi may be slightly more accurate.

Severity and response of chest pain during thrombolytic therapy for acute myocardial infarction: a useful indicator of myocardial salvage and infarct size.

OBJECTIVES: The purpose of this study was to determine noninvasively whether chest pain severity is predictive of the amount of myocardium at risk and whether the response of pain during thrombolysis is associated with myocardial salvage during acute myocardial infarction. BACKGROUND: The perception of chest pain and response to reperfusion therapy during acute myocardial infarction may provide important information for treatment benefit. Previous studies have been limited by the inability to measure myocardium at risk and myocardial salvage. METHODS: Sixty-two patients with acute myocardial infarction received an injection of technetium-99m sestamibi before thrombolysis and again at hospital discharge. Tomographic imaging was performed 1 to 6 h later. Myocardium at risk, infarct size and absolute myocardial salvage were derived from these images using previously described techniques and were expressed as a percent of the left ventricle. Salvage index was calculated by dividing myocardial salvage by the myocardium at risk. Chest pain severity was graded before thrombolysis as none, mild, moderate or severe. Chest pain response during thrombolytic therapy was graded as none, partial or completely resolved. RESULTS: There was no association between chest pain severity and myocardium at risk, but there was a weak trend toward greater myocardial salvage and salvage index (p = 0.09 and p = 0.12, respectively) for patients with more severe symptoms. Patients without chest pain at the start of thrombolysis still demonstrated significant salvage (11 +/- 11% of the left ventricle, p = 0.009). There was a significant association between chest pain response to therapy and both myocardial salvage (p = 0.03) and salvage index (p = 0.01). By multivariate analysis, chest pain severity and response of chest pain during thrombolysis were significant independent predictors of myocardial salvage, salvage index and infarct size. Thrombolysis was most effective in the 20 patients (32%) with moderate or severe chest pain and complete resolution of symptoms during thrombolysis (salvage of 79% to 89% of the area at risk). In the remaining 32 patients with chest pain, salvage of the area at risk was only 32%. CONCLUSIONS: These findings suggest that the assessment of chest pain before and after thrombolytic therapy is a readily available, useful indicator of the efficacy of the therapy.

Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. The Mayo Coronary Care Unit and Catheterization Laboratory Groups.

BACKGROUND: Immediate angioplasty and the administration of a thrombolytic agent followed by conservative treatment are two approaches to the management of acute myocardial infarction, but these methods have not been compared prospectively. METHODS: We enrolled 108 patients with acute myocardial infarction in a randomized trial designed to test the hypothesis that immediate angioplasty (without previous thrombolytic therapy) may result in greater myocardial salvage than the administration of a thrombolytic agent followed by conservative treatment. The primary end point was the change in the size of the perfusion defect as assessed at admission and discharge by tomographic imaging with technetium-99m sestamibi, a myocardial perfusion agent that can measure myocardium at risk and final infarct size. RESULTS: End-point data were available for 56 patients randomly assigned to receive tissue plasminogen activator (mean [+/- SD] time to start of infusion, 232 +/- 174 minutes after the onset of chest pain) and 47 patients randomly assigned to receive angioplasty (first balloon inflation at 277 +/- 144 minutes). In the case of anterior infarction, myocardial salvage as assessed by imaging with technetium-99m sestamibi was 27 +/- 21 percent of the left ventricle for 22 patients in the thrombolysis group, as compared with 31 +/- 21 percent for 15 patients in the angioplasty group. For infarcts in all other locations, myocardial salvage was 7 +/- 13 percent for 34 patients in the thrombolysis group and 5 +/- 10 percent for 32 patients in the angioplasty group. After adjustment for infarct location, the difference in mean salvage between groups was 0 (P = 0.98), with a 95 percent confidence interval of +/- 6 percent of the left ventricle. CONCLUSIONS: In patients with acute myocardial infarction, immediate angioplasty does not appear to result in greater myocardial salvage than the administration of a thrombolytic agent followed by conservative treatment, although a small difference between these two therapeutic approaches cannot be excluded.