Functional tests for myocardial ischemia.

Functional tests for myocardial ischemia are numerous. Most depend upon a combination of either exercise or pharmacologic intervention with analysis of the electrocardiogram, of regional perfusion with radionuclide imaging, or of regional wall motion with radionuclide imaging or echocardiography. While each test has unique features, especially at the research level, they are generally quite similar in clinical practice, so the clinician is advised to concentrate on one or two in which local expertise is high.

Prognostic value of predischarge low-level exercise thallium testing after thrombolytic treatment of acute myocardial infarction.

Low-level exercise thallium testing is useful in identifying the high-risk patient after acute myocardial infarction (AMI). To determine whether this use also applies to patients after thrombolytic treatment of AMI, 64 patients who underwent early thrombolytic therapy for AMI and 107 patients without acute intervention were evaluated. The ability of both the electrocardiogram and thallium tests to predict future events was compared in both groups. After a mean follow-up of 374 days, there were 25 and 32% of cardiac events in the 2 groups, respectively, with versus without acute intervention. These included death, another AMI, coronary artery bypass grafting or angioplasty with 75% of the events occurring in the 3 months after the first infarction. The only significant predictors of outcome were left ventricular cavity dilatation in the intervention group and ST-segment depression and increased lung uptake in the nonintervention group. The sensitivity of exercise thallium was 55% in the intervention group and 81% in the nonintervention group (p less than 0.05). Therefore, in patients having thrombolytic therapy for AMI, nearly half the events after discharge are not predicted by predischarge low-level exercise thallium testing. The relatively weak correlation of outcome with unmasking ischemia in the laboratory before discharge may be due to an unstable coronary lesion or rapid progression of disease after the test. Tests considered useful for prognostication after AMI may not necessarily have a similar value if there has been an acute intervention, such as thrombolytic therapy.

Usefulness of semiquantitative analysis of dipyridamole-thallium-201 redistribution for improving risk stratification before vascular surgery.

Preoperative dipyridamole-thallium-201 scanning is sensitive in identifying patients prone to ischemic cardiac complications after vascular surgery, but most patients with redistribution do not have an event after surgery. Therefore, its positive predictive value is limited. To determine which patients with thallium redistribution are at highest risk, dipyridamole-thallium-201 images were interpreted semiquantitatively. Sixty-two consecutive patients with redistribution on preoperative dipyridamole-thallium-201 planar imaging studies were identified. Each thallium scan was then analyzed independently by 2 observers for the number of myocardial segments out of 15, the number of thallium views out of 3 and the number of coronary artery territories with redistribution. Seventeen patients (27%) had postoperative ischemic events, including unstable angina pectoris, ischemic pulmonary edema, myocardial infarction and cardiac death. Thallium predictors of ischemic operative complications included thallium redistribution greater than or equal to 4 myocardial segments (p = 0.03), greater than or equal to 2 of the 3 planar views (p = 0.005) and greater than or equal to 2 coronary territories (p = 0.007). No patient with redistribution in only 1 view had an ischemic event (0 of 15). Thus, determining the extent of redistribution by dipyridamole-thallium-201 scanning improves risk stratification before vascular surgery. Patients with greater numbers of myocardial segments and greater numbers of coronary territories showing thallium-201 redistribution are at higher risk for ischemic cardiac complications. In contrast, when the extent of thallium redistribution is limited, there is a lower risk despite the presence of redistribution.

Prognostic utility of predischarge dipyridamole-thallium imaging compared to predischarge submaximal exercise electrocardiography and maximal exercise thallium imaging after uncomplicated acute myocardial infarction.

The prognostic value of predischarge dipyridamole-thallium scanning after uncomplicated myocardial infarction was determined by comparison with submaximal exercise electrocardiography and 6-week maximal exercise thallium imaging and by correlation with clinical events. Two endpoints were defined: cardiac events and severe ischemic potential. Of the 40 patients studied, 8 had cardiac events within 6 months (1 died, 3 had myocardial infarction and 4 had unstable angina requiring hospitalization). The finding of any redistribution on dipyridamole-thallium scanning was common (77%) in these patients and had poor specificity (29%). Redistribution outside of the infarct zone, however, had equivalent sensitivity (63%) and better specificity (75%) for events (p less than 0.05). Both predischarge dipyridamole-thallium and submaximal exercise electrocardiography identified 5 of the 8 events (p = 0.04 and 0.07, respectively). The negative predictive accuracy for events for both dipyridamole-thallium and submaximal exercise electrocardiography was 88%. In addition to the 8 patients with events, 16 other patients had severe ischemic potential (6 had coronary bypass surgery, 1 had inoperable 3-vessel disease and 9 had markedly abnormal 6-week maximal exercise tests). Predischarge dipyridamole-thallium and submaximal exercise testing also identified 8 and 7 of these 16 patients with severe ischemic potential, respectively. Six of the 8 cardiac events occurred before 6-week follow-up. A maximal exercise thallium test at 6 weeks identified 1 of the 2 additional events within 6 months correctly. Thallium redistribution after dipyridamole in coronary territories outside the infarct zone is a sensitive and specific predictor of subsequent cardiac events and identifies patients with severe ischemic potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Combining clinical and thallium data optimizes preoperative assessment of cardiac risk before major vascular surgery.

STUDY OBJECTIVE: To determine whether clinical markers and preoperative dipyridamole-thallium imaging are both useful in predicting ischemic events after vascular surgery. DESIGN: Retrospective, observational study. SETTING: University medical center. PATIENTS: Two hundred fifty-four consecutive patients referred to a nuclear cardiology laboratory before surgery. Forty-four patients had surgery cancelled or postponed after clinical evaluation and dipyridamole-thallium imaging. Surgery was not confirmed for ten. Two hundred patients receiving prompt vascular surgery were the study group. MEASUREMENTS AND MAIN RESULTS: Thirty patients (15%) had early postoperative cardiac ischemic events, with cardiac death in 6 (3%) and nonfatal myocardial infarction in 9 (4.5%). Logistic regression identified five clinical predictors (Q waves, history of ventricular ectopic activity, diabetes, advanced age, angina) and two dipyridamole-thallium predictors of postoperative events. Of patients with none of the clinical variables (n = 64), only 2 (3.1%; 95% CI, 0% to 8%) had ischemic events with no cardiac deaths. Ten of twenty (50%; 95% CI, 29% to 71%) patients with three or more clinical markers had events. Eighteen of one hundred sixteen (15.5%; 95% CI, 7% to 21%) patients with either 1 or 2 clinical predictors had events. Within this group, 2 of 62 (3.2%; 95% CI, 0% to 8%) patients without thallium redistribution had events compared with 16 events in 54 patients (29.6%; 95% CI, 16% to 44%) with thallium redistribution. The multivariate model using both clinical and thallium variables showed significantly higher specificity at equivalent sensitivity levels than models using either clinical or thallium variables alone. CONCLUSIONS: Preoperative dipyridamole-thallium imaging appears most useful to stratify vascular patients determined to be at intermediate risk by clinical evaluation. For patients with one or two clinical predictors, thallium redistribution correlates with substantial change in probability of events. For nearly half the patients, however, thallium imaging may have been unnecessary because of very high or low cardiac risk predicted by clinical information alone.

Simultaneous low level treadmill exercise and intravenous dipyridamole stress thallium imaging.

Intravenous dipyridamole-thallium imaging unmasks ischemia in patients unable to exercise adequately. However, some of these patients can perform limited exercise, which, if added, may provide useful information. Treadmill exercise combined with dipyridamole-thallium imaging was performed in 100 patients and results compared with those of 100 other blindly age- and sex-matched patients who received dipyridamole alone. Exercise began after completion of the dipyridamole infusion. Mean +/- 1 standard deviation peak heart rate (109 +/- 19 vs 83 +/- 12 beats/min, p less than 0.0001) and peak systolic and diastolic blood pressure (146 +/- 28/77 +/- 14 vs 125 +/- 24/68 +/- 11 mm Hg, p less than 0.0001) were higher in the exercise group compared with the nonexercise group. There was no difference in the occurrence of chest pain, but more patients in the exercise group developed ST-segment depression (26 vs 12%, p less than 0.0001). The exercise group had fewer noncardiac side effects (4 vs 12%, p less than 0.01) and a higher target (heart) to background (liver) count ratio (2.1 +/- 0.7 vs 1.2 +/- 0.3; p less than 0.01), due to fewer liver counts. There were no deaths, myocardial infarctions or sustained arrhythmias in either group. Combined treadmill exercise and dipyridamole testing is safe, associated with fewer noncardiac side effects, a higher target to background ratio and a higher incidence of clinical electrocardiographic ischemia than dipyridamole alone. Therefore, it is recommended whenever possible.

The aetiology and course of isolated severe aortic regurgitation: a clinical, pathological, and echocardiographic study.

Seventy two consecutive patients with severe isolated aortic regurgitation were evaluated by preoperative echocardiographic and angiographic assessment of the aortic root. Biopsy specimens of the aortic wall were taken at operation. Two major groups of patients were found: those with cusp derangement but normal aortic roots and those with normal cusps but dilated aortic roots. Of the 42 cases of abnormal cusps, 20 were rheumatic, 15 were infective, and six were bicuspid. One patient had a tear in an otherwise normal cusp. Of the 30 cases of abnormal roots but normal cusps, six had inflammatory changes (syphilis, Reiter's disease, giant cell aortitis) and 24 had root dilatation caused by non-inflammatory destruction of elastic laminae. Echocardiographic measurement of the aorta at the level of the top of the commissures predicted the findings at pathology. In 37 of 39 patients with cusp disease the measurement was less than 37 mm. In 27 of 33 patients with root disease the measurement was greater than or equal to 37 mm. This difference was statistically significant. There was no difference in the sizes of the prosthesis used in each group, suggesting that it was the diameter of the junction of the aorta with the sinuses rather than the junction of the sinuses with the ventricle that was important in aortic regurgitation. Clinical progression in patients with non-inflammatory aortic root disease is slower than in patients with infective disease but faster than in those with rheumatic cusp disease.

Safety of intravenous dipyridamole for stress testing with thallium imaging.

Cardiac and noncardiac side effects were studied in 293 consecutive patients referred for nonexercise stress thallium imaging with intravenous dipyridamole. Six minutes after the initiation of infusion, there was a mean 9-beat/min increase in heart rate and a mean 12-mm Hg decrease in systolic blood pressure. The largest increase in heart rate exceeded 20 beats/min in only 13% of patients and the largest decrease in systolic blood pressure exceeded 20 mm Hg in 31%. Noncardiac side effects were headache (11%), lightheadedness or dizziness (5%) and nausea (4%). Only 9 patients required intravenous aminophylline for relief of noncardiac side effects: severe headache in 7 and nausea in 2. Cardiac side effects included chest pain in 76 patients (26%), of whom 70% were given aminophylline for relief of symptoms. Sixty patients (20%) had ischemic ST-segment depression and 56 (19%) had arrhythmias (ventricular in 50 and atrial in 6). There were no deaths, myocardial infarctions or sustained arrhythmias due to dipyridamole administration. Among 62 patients also undergoing cardiac catheterization, side effects except for arrhythmias were unrelated to the number of vessels with coronary artery disease. Intravenous dipyridamole is safe for nonexercise stress testing and has few serious side effects. However, the possibility of ischemia requires careful selection of patients and monitoring of vital signs and the electrocardiogram during the test.

Exercise thallium scans: patterns of use and impact on management of patients with known or suspected coronary artery disease.

Physicians' ordering patterns and subjective assessments of the management impact of 345 exercise thallium studies at a tertiary care hospital were evaluated. Exercise thallium tests were ordered to obtain functional information (60%), to detect myocardial ischemia (29%), for routine follow-up (6%) and for screening for coronary artery disease (CAD) (5%). Exercise thallium testing was ordered instead of exercise electrocardiography alone because of an interest in assessing the size of an ischemic or infarcted area (37%), a belief that the exercise electrocardiogram was likely to be nondiagnostic (35%) or that exercise thallium was a better test (23%). In 20% of cases physicians said that thallium imaging results were helpful or pivotal in major management decisions, such as those regarding catheterization or surgery. In most cases, no further tests were ordered and antianginal therapy or activity prescription was changed after exercise thallium testing. Exercise thallium images also helped to stratify patients into low and high probability of CAD categories better than exercise electrocardiographic results alone did. Our data suggest that physicians are using exercise thallium testing to obtain functional information more often than simply to detect CAD and that physicians consider the test to be of considerable value.

Comparison of exercise electrocardiography and quantitative thallium imaging for one-vessel coronary artery disease.

The relative value of exercise electrocardiography and computer analyzed thallium-201 imaging was compared in 124 patients with 1-vessel coronary artery disease (CAD). Of these, 78 had left anterior descending (LAD), 32 right and 14 left circumflex (LC) CAD. In patients with no previous myocardial infarction (MI), thallium imaging was more sensitive than the electrocardiogram (78% vs 64%, p less than 0.01), but in patients with previous MI, sensitivity was similar. Further, thallium imaging was more sensitive only in LAD and LC disease. Redistribution was compared with ST-segment depression as a marker of ischemia. Only in patients with prior MI (76% vs 44%, p less than 0.01) and only in LC and right CAD did redistribution occur more often than ST depression. Thallium imaging was more accurate in localizing stenoses than the electrocardiogram (p less than 0.001), but did not always correctly predict coronary anatomy. Septal thallium defects were associated with LAD disease in 84%, inferior defects with right CAD in 40% and posterolateral lesion defects with LC CAD in 22%. The results indicate the overall superiority of thallium imaging in 1-vessel CAD compared with exercise electrocardiography; however, there is a wide spectrum of extent and location of perfusion defects associated with each coronary artery. Thallium imaging complements coronary angiography by demonstrating the functional impact of CAD on myocardial perfusion.

Prognostic value of exercise thallium-201 imaging in patients presenting for evaluation of chest pain.

Accurate prognostic information is important in determining optimal management of patients presenting for evaluation of chest pain. In this study, the ability of exercise thallium-201 myocardial imaging to predict future cardiac events (cardiovascular death or nonfatal myocardial infarction) was correlated with clinical, coronary and left ventricular angiographic and exercise electrocardiographic data in 139 consecutive, nonsurgically managed patients followed-up over a 3 to 5 year period (mean follow-up, 3.7 +/- 0.9), using a logistic regression analysis. Among patients without prior myocardial infarction (100 of 139), the number of myocardial segments with transient thallium-201 defects was the only statistically significant predictor of future cardiac events when all patient variables were evaluated. Among patients with myocardial infarction before evaluation (39 of 139), angiographic ejection fraction was the only significant predictor of future cardiac events when all variables were considered. This study suggests an approach to evaluate the risk of future cardiac events in patients with possible ischemic heart disease.

Differentiation of transiently ischemic from infarcted myocardium by serial imaging after a single dose of thallium-201.

Myocardial 201Tl uptake and regional blood flow by the microsphere technique were determined in anesthetized dogs undergoing either 20 min of coronary occlusion and 100 min of reperfusion (N = 10) or 120 min of occlusion (N = 4). In both groups, 201Tl was injected intravenously after 10 min of occlusion. In transiently occluded dogs, regional flow at the time of 201Tl administration was reduced to 8 +/- 3% of normal flow in endocardial layers of the central ischemic zone. After 100 min of reperfusion, flow values were not significantly different from normal. 201Tl activity after reperfusion rose to 56 +/- 5% of normal, demonstrating that redistribution of the radionuclide occurred during the reflow period. In animals with persistent occlusion, there was a significant relationship between 201Tl uptake and flow (r = 0.95) and no evidence of redistribution of 201Tl during the two hour occlusion period. In another five dogs receiving 201Tl, serial gamma camera images obtained during reperfusion showed increasing uptake of the tracer in apical defects which returned to normal by 4 hours of reflow. Thirteen patients with stable angina received 2 mCi of 201Tl intravenously at peak exercise, and multiple gamma camera images obtained serially. All demonstrated zones of diminished 201Tl uptake 10 min after exercise. Defects which partially or completely disappeared within 1-6 hours postexercise corresponded to areas supplied by coronary arteries with significant stenoses. Persistent defects were present in regions of old myocardial infarction. Six additional patients with acute myocardial infarction demonstrated 201Tl myocardial defects which showed no significant change over 6 hours. Thus, redistribution of 201Tl into ischemic myocardium was demonstrated during transient coronary occlusion in dogs and after exercise stress in man. Sequential imaging after a single dose of 201Tl at the time of exercise may provide a means for distinguishing between transient perfusion abnormalities or ischemia and myocardial infarction of scar.

Improvement in myocardial function and coronary blood flow in ischemic myocardium after mannitol.

The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery. Mannitol significantly improved the depressed ventricular function curves which occurred with left anterior descending coronary artery occlusion. Mannitol also significantly lessened the S-T segment elevation (epicardial electrocardiogram) occurring during myocardial ischemia in the isovolumic hearts and this reduction was associated with significant increases in total coronary blood flow (P < 0.005) and with increased collateral coronary blood flow to the ischemia area (P < 0.005).THUS, INCREASES IN SERUM OSMOLALITY PRODUCED BY MANNITOL RESULT IN THE FOLLOWING BENEFICIAL CHANGES DURING MYOCARDIAL ISCHEMIA: (a) improved myocardial function, (b) reduced S-T segment elevation, (c) increased total coronary blood flow, and (d) increased collateral coronary blood flow.