Mona R. Hopfenspirger

Immediate Angioplasty Compared with the Administration of a Thrombolytic Agent Followed by Conservative Treatment for Myocardial Infarction

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.

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.

Myocardium at risk and infarct size after thrombolytic therapy for acute myocardial infarction: Implications for the design of randomized trials of acute intervention☆

OBJECTIVES The purpose of this study was to estimate the effect of an improved reperfusion therapy for acute myocardial infarction on myocardial salvage and ventricular function for anterior and inferior infarctions and to ascertain the sample size required to detect such an effect. BACKGROUND There are significant differences in myocardium at risk between anterior and inferior infarctions that affect the benefit of reperfusion therapy. METHODS We studied 58 patients with acute myocardial infarction (24 anterior, 34 inferior) treated with intravenous recombinant tissue-type plasminogen activator and angioplasty when necessary. Tomographic imaging with technetium-99m sestamibi was performed to measure myocardium at risk, final infarct size and myocardial salvage and to estimate the beneficial effects of an improved therapy. RESULTS A new therapy that was 30% more effective than existing therapy (with respect to salvage) would increase salvage (and reduce mean infarct size) by 5.2% of the left ventricle and increase late ejection fraction by only 0.012 (95% confidence interval [CI] 0.009 to 0.015) in inferior infarction and by 0.038 (95% CI 0.027 to 0.047) in anterior infarction. If anterior and inferior infarctions occurred with equal frequency, a sample size of 140 patients in each treatment group would be required to detect such a change with 80% power. In a trial of interior infarctions alone, a sample size of 236 patients in each treatment group would be required compared with only 98 patients in a trial of anterior infarctions alone. CONCLUSIONS The anticipated mean benefit from an improved reperfusion therapy in individual patients with inferior infarction is very small and of questionable clinical significance. The anticipated benefit in anterior infarction is greater and easier to detect. Future randomized trials should be stratified for infarct location and should consider the greater absolute benefit of treatment in anterior infarction.

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.

Time to reperfusion with direct coronary angioplasty and thrombolytic therapy in acute myocardial infarction

An analysis was performed of the Mayo Clinic randomized trial of direct percutaneous transluminal coronary angioplasty and tissue-type plasminogen activator (t-PA) to determine the time required to achieve reperfusion with direct coronary angioplasty. Because patients in the Mayo trial assigned to t-PA did not undergo protocol coronary angiography, reperfusion rates from the Thrombolysis in Myocardial Infarction (TIMI) I trial in which patients underwent coronary angiography 30, 60 and 90 minutes after thrombolytic therapy were used for comparison. TIMI perfusion grade 2 or 3 flow in the infarct artery was considered to represent reperfusion after thrombolysis. In the 56 patients assigned to t-PA, the mean time from randomization to initiation of the t-PA infusion was 20 minutes. Twenty minutes were therefore added to the previously reported 30-, 60- and 90-minute reperfusion rates to express these in terms of time from randomization (50, 80 and 110 minutes). In the 48 patients who had direct angioplasty, the mean time from randomization to arrival in the cardiac catheterization laboratory was 45 minutes; it took a mean of 6 additional minutes for patients to be prepared and draped and arterial access obtained, and a mean of 27 additional minutes to complete angiography and achieve reperfusion. At 50, 80 and 110 minutes after randomization, the reperfusion rates for direct coronary angioplasty were 12, 54 and 83%, similar to previously reported TIMI reperfusion rates with t-PA (24, 57 and 71%, respectively, p = NS) but significantly greater at 80 and 110 minutes than was reported for streptokinase (8, 23 and 31%, respectively, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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

BackgroundBoth thallium 201 and technetium 99m sestamibi have been used to quantitate infarct size at rest. Exercise201Tl 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 of201Tl and99mTc sestamibi and to correlate these measurements with left ventricular ejection fraction in patients after acute myocardial infarction.Methods and ResultsThe study group consisted of 20 patients who underwent low-level201Tl stress studies with reinjection and99mTc sestamibi resting studies within 4 days. Acute reperfusion was attempted in 18 of 20 patients. For99mTc 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 delayed201Tl 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 with99mTc sestamibi was 12%±13% of the left ventricle, which was significantly smaller than either method with201Tl: threshold method, 29%±18% of left ventricle; polar map method, 25%±17% of left ventricle (both201Tl estimates,p<0.0001 vs99mTc sestamibi;201Tl, 70% threshold vs201Tl polar map,p=0.04). There was a significant correlation between infarct size with99mTc sestamibi and that with201Tl (r=0.72 to 0.73;p<0.001). Infarct size with99mTc sestamibi, however, provided the closest correlation with ejection fraction (r=0.81;p<0.001), with the two201Tl quantitative methods providing very similar correlations (r=0.69;p<0.001).ConclusionsInfarct size with reinjection201Tl imaging correlates significantly with resting infarct size with99mTc 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 with99mTc sestamibi may be slightly more accurate.

Comparison of acute myocardial infarct size to two-year mortality in patients <65 to those ≥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.

Sinus node deceleration during dobutamine perfusion scintigraphy as a marker of inferior ischemia.

Abstract Traditional electrocardiographic markers of exerciseinduced ischemia include ST-segment depression or elevation, U-wave inversion, ventricular ectopy, and chronotropic incompetence. Miller et al1 recently described sinus node deceleration, defined as an initial increase and subsequent decrease in heart rate with progressive exercise, as a marker of atherosclerotic narrowing of the right coronary artery. For patients unable to perform treadmill exercise, dobutamine thallium imaging has emerged as an alternative stress method for the detection of coronary artery disease.2,3 The purpose of this study was to determine if sinus node deceleration occurs during dobutamine perfusion scintigraphy and whether it is a marker of inferior wall ischemia.

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.