Ian P. Clements

A Platelet-Inhibitor-Drug Trial in Coronary-Artery Bypass Operations: Benefit of Perioperative Dipyridamole and Aspirin Therapy on Early Postoperative Vein-Graft Patency

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in th placebo group. This benefit in graft patency persisted in each of over 50 subgroups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation.

Effect of Dipyridamole and Aspirin on Late Vein-Graft Patency after Coronary Bypass Operations

To study the prevention of occlusion of aortocoronary-artery bypass grafts, we concluded a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun two days before operation) plus aspirin (begun seven hours after operation) with placebo in 407 patients. Results at one month showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. At vein-graft angiography performed in 343 patients (84 per cent) 11 to 18 months (median, 12 months) after operation, 11 per cent of 478 vein-graft distal anastomoses were occluded in the treated group, and 25 per cent of 486 were occluded in the placebo group. The proportion of patients with one or more distal anastomoses occluded was 22 per cent of 171 patients in the treated group and 47 per cent of 172 in the placebo group. All grafts were patent within a month of operation in 94 patients in the placebo group and 116 patients in the treated group; late development of occlusions was reduced from 27 per cent in the placebo group to 16 per cent in the treatment group. The results show that dipyridamole and aspirin continue to be effective in preventing vein-graft occlusion late after operation, and we believe that such treatment should be continued for at least one year.

Estimates of myocardium at risk and collateral flow in acute myocardial infarction using electrocardiographic indexes with comparison to radionuclide and angiographic measures.

OBJECTIVES This study sought to determine the accuracy of the initial 12-lead electrocardiogram (ECG) in predicting final infarct size after direct coronary angioplasty for myocardial infarction and to examine which physiologic variables known to be determinants of outcome the ST segment changes most closely reflect. BACKGROUND Myocardium at risk, collateral flow and time to reperfusion have been shown to be independent physiologic predictors of infarct size in animal and clinical models. However, such measurements may be difficult to perform on a routine basis in patients with myocardial infarction. The standard 12-lead ECG is inexpensive and readily available. METHODS Sixty-seven patients with acute myocardial infarction, ST segment elevation and duration of chest pain < 12 h had an initial injection of technetium-99m sestamibi. Tomographic imaging was performed 1 to 8 h later (after direct coronary angioplasty), and the images were quantified to measure perfusion defect size (myocardium at risk) and severity (a measure of collateral flow). Contrast agent injection and tomographic acquisition were repeated at hospital discharge to measure infarct size. The ST segment elevation score was calculated for each patient according to infarct location and using previously described formulas. RESULTS ST segment elevation score correlated closest with the radionuclide measure of collateral flow (r = -0.44, p < or = 0.0001), as well as an angiographic measure of collateral flow (r = -0.38, p = 0.05). Although ST segment elevation score correlated weakly with the magnitude of myocardium at risk by technetium-99m sestamibi, it was not as strong as infarct location alone in predicting myocardium at risk ([mean +/- SD] anterior 51 +/- 13% left ventricle vs. inferior 17 +/- 10% left ventricle, p < 0.0001). ST segment elevation score was weakly associated with final infarct size (r = 0.34, p = 0.005). A multivariate ECG model was constructed with infarct location as a surrogate for myocardium at risk, ST segment elevation score as a surrogate for estimated collateral flow, and elapsed time to reperfusion from onset of chest pain. All three variables were independently associated with infarct size. CONCLUSIONS The initial standard 12-lead ECG can provide insight into myocardium at risk and, to a greater extent, collateral flow and can consequently provide some estimate of subsequent infarct size. However, the confidence limits for such predictors are wide.

Prevention of late ventricular dilatation after acute myocardial infarction by successful thrombolytic reperfusion

To examine the sequential changes in left ventricular volume after thrombolytic therapy for acute myocardial infarction, gated radionuclide ventriculography was performed within 12 hours of thrombolysis and at 1 and 6 weeks in 34 consecutive patients who received intravenous thrombolytic therapy in the Thrombolysis in Myocardial Infarction Trial. Angiographic confirmation of immediate reperfusion (mean 5.6 hours after onset of symptoms) that persisted at 24 hours was noted in 24 patients; 10 patients were not reperfused. A small (9.5%), but significant (p = 0.05), increase in end-diastolic volume index was noted in the reperfused group between 1 and 6 weeks; however, a marked degree of dilatation (35%) was noted in the non-reperfused group (p = 0.01). The change in left ventricular volume between 1 and 6 weeks differed in the 2 groups for both end-diastolic volume index and end-systolic volume index (p = 0.01 and p = 0.02, respectively). By 6 weeks, both end-diastolic volume index and end-systolic volume index were greater in the nonreperfused group (p less than 0.05). Between the acute and 6-week studies, definite increases in end-diastolic volume index (p less than 0.05) and end-systolic volume index (p less than 0.01) occurred commonly in the nonreperfused group but rarely in the reperfused group. Compared to the nonreperfused group, the reperfused group also had significantly higher ejection fractions at both 1 and 6 weeks (p less than 0.05). The change in end-diastolic volume index between 1 and 6 weeks correlated significantly and inversely with the ejection fraction at 1 week (r = -0.60, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive identification of severe coronary artery disease using exercise radionuclide angiography

The ability of exercise radionuclide angiography to predict the risk of having significant left main or three vessel coronary artery disease was examined in 681 patients who underwent both radionuclide and coronary angiography. There were significant differences in multiple variables between patients with or without such disease. Logistic regression analysis identified seven variables as independently predictive of the presence of left main or three vessel disease. Using these variables, low, intermediate and high probability groups could be identified. The four most important variables--the magnitude of exercise ST segment depression, peak exercise ejection fraction, peak exercise rate-pressure product and sex of the patient--can provide practical estimates of the risk of having left main or three vessel disease. Exercise radionuclide angiography can provide a clinically useful noninvasive estimate of the risk of having significant left main or three vessel disease.

Residual flow to the infarct zone as a determinant of infarct size after direct angioplasty.

BackgroundIn acute myocardial infarction, residual flow to the infarct zone either through antegrade flow in the infarct-related coronary artery or collateral flow from the non-infarct-related arteries is often present before reperfusion therapy. The purpose of this study was to assess the influence of antegrade flow in the infarct-related artery and/or collateral flow to the infarct zone before successful direct angioplasty on infarct size and myocardial salvage in patients with acute evolving myocardial infarction. Methods and ResultsSixty patients with acute evolving myocardial infarction underwent direct successful angioplasty without prior thrombolytic therapy. The myocardium at risk of infarction, the final infarct size, and myocardial salvage were measured by tomographic perfusion imaging with “Tc sestamibi. Antegrade flow in the infarct-related artery before intervention was graded according to the Thrombolysis in Myocardial Infarction (TIMI) study group classification. Collateral flow to the infarct zone before angioplasty was also graded (0 through 3, 0 being no collateral flow). The presence of even minimal antegrade flow before angioplasty (TIMI grade 1) in the infarct-related artery compared with absent flow was associated with a significant reduction in final infarct size (9±17% versus 23±19% of left ventricle, P=.02) and a significant increase in myocardial salvage (23±16% versus 14±13% of left ventricle, P=.05) after angioplasty. When antegrade flow in the infarct-related artery was absent before angioplasty, the presence of collateral flow before angioplasty resulted in a significantly smaller final infarct size (P=.01) and more myocardial salvage (P=.05) after angioplasty. Both antegrade infarctrelated artery flow and collateral flow to the infarct zone had significant independent ability to predict infarct size after angioplasty. When collateral grade and TIM grade were added to provide an estimate of residual flow, a model including residual flow, myocardium at risk, and the interaction of residual flow and infarct site explained 83% of the variability in infarct size after angioplasty. ConclusionsThe presence of antegrade flow in the infarct-related artery and/or collateral flow to the infarct zone before direct angioplasty in acute evolving infarction results in a smaller infarct size after direct successful angioplasty.

Noninvasive identification of myocardium at risk in patients with acute myocardial infarction and nondiagnostic electrocardiograms with technetium-99m-Sestamibi.

BackgroundPatients who have chest pain without electrocardiographic ST elevation are not candidates for thrombolytic therapy in most clinical trials. This study examined the value of technetium-99m-Sestamibi tomographic imaging to assess myocardial perfusion in patients during chest pain without ST elevation. Methods and ResultsTc-99m-Sestamibi was injected in 14 patients who had chest pain without ST elevation, who subsequently developed enzymatic evidence of myocardial infarction within 24 hours. Tomographic imaging was performed 1–6 hours after injection. Thirteen of 14 patients showed significant perfusion defects indicative of acute myocardial infarction consistent with absent perfusion (20±15% of the left ventricle; range, 2–53%); one patient had normal images. Because of the absence of definitive electrocardiographic changes, only five patients received reperfusion therapy within 6 hours of the onset of chest pain. Regional wall motion abnormalities were present in nine of nine patients undergoing contrast ventriculography and correlated with the location of the Tc-99m-Sestamibi perfusion defect. At the time of subsequent coronary angiography, total arterial occlusion was present in 11 of the 14 patients. The infarct-related artery could be identified in 13 of the 14 patients. In six of these 13 patients, the left circumflex was the infarct-related artery. ConclusionsPatients who have chest pain without electrocardiographic ST elevation may have arterial occlusion and significant myocardium at risk. Tc-99m-Sestamibi imaging may be of benefit in identifying these patients early so that they can be considered for acute reperfusion therapy.

Gender-related differences in cardiac response to supine exercise assessed by radionuclide angiography.

This study examines the recently reported gender differences in cardiac responses to exercise. The study group consisted of 192 men and 67 women with a low probability of coronary artery disease who underwent supine exercise radionuclide angiography. Men had a lower rest ejection fraction than that of women (0.63 versus 0.66, p = 0.02) and greater increases in ejection fraction with exercise (0.08 versus 0.02, p = 0.0001). The slope relating ejection fraction to metabolic equivalents of exercise (METs) was greater (p = 0.004) for men, even after adjustment for differences in rest ejection fraction and end-diastolic volume index. Compared with men, women had a smaller rest end-diastolic volume index (87 versus 97 ml/m2, p = 0.003) and a greater increase in end-diastolic volume index with exercise (6 versus -2 ml/m2, p = 0.002). The slope relating end-diastolic volume to METs was greater for women, even after adjustment for differences in rest end-diastolic volume index and peak work load. There are clear gender differences in the supine exercise response of ejection fraction and end-diastolic volume that are not explained by differences in exercise capacity.

Cardiac Involvement in Lyme Disease: Manifestations and Management

Cardiac involvement in Lyme disease may manifest as atrioventricular block, myopericarditis, and left ventricular dysfunction. Diagnosis depends on recognition of the systemic nature of Lyme disease, including cardiac involvement, and its natural history. Serologic tests that are both sensitive and specific may aid in diagnosis. Although current recommendations for the treatment of Lyme disease with carditis include antibiotics and salicylates or corticosteroids, these types of therapy have not been unequivocally demonstrated to alter the natural history of cardiac involvement. Supportive therapy may necessitate temporary transvenous cardiac pacing in symptomatic patients.

Reproducibility of noninvasive tests of peripheral occlusive arterial disease

We studied the reproducibility of four tests of peripheral occlusive arterial disease in 54 subjects, 32 of whom had this disease. We found that the reproducibility of systolic blood pressures obtained at rest from the thighs, calves, and ankles approximated that of arm systolic and diastolic blood pressures, as did the ankle-to-arm systolic blood pressure ratios. The average of the tenth and ninetieth percentile ranges of the resting systolic blood pressure ankle-to-arm ratios was +/- 0.10. Systolic blood pressures from the fingers were somewhat less reproducible, and those from the toes were even more variable. Systolic blood pressure ankle-to-arm ratios measured after the patient had exercised were less reproducible than resting ratios. The average of the tenth and ninetieth percentile ranges of the 1-, 3-, 5-, and 10-minute ratios after exercise was -0.13 to +0.16. Skin temperatures from the fingers and toes were approximately as reproducible as systolic blood pressures from the arms and legs and as the resting ankle-to-arm blood pressure ratios. Pulse-volume recordings from the thighs, calves, ankles, feet, toes, and fingers were very poorly reproducible. We conclude that information on the reproducibility of these measurements is essential in the evaluation of noninvasive arterial tests that are used to determine the course of peripheral occlusive arterial disease.