Jeffrey A. Leppo

ACC/AHA Guideline Update for Perioperative Cardiovascular Evaluation for Noncardiac Surgery—Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery)

These guidelines represent an update of those published in 1996 and are intended for physicians who are involved in the preoperative, operative, and postoperative care of patients undergoing noncardiac surgery. They provide a framework for considering cardiac risk of noncardiac surgery in a variety of patient and surgical situations. The overriding theme of these guidelines is that preoperative intervention is rarely necessary simply to lower the risk of surgery unless such intervention is indicated irrespective of the preoperative context. The purpose of preoperative evaluation is not simply to give medical clearance but rather to perform an evaluation of the patient’s current medical status; make recommendations concerning the evaluation, management, and risk of cardiac problems over the entire perioperative period; and provide a clinical risk profile that the patient, primary physician, anesthesiologist, and surgeon can use in making treatment decisions that may influence short- and long-term cardiac outcomes. The goal of the consultation is to identify the most appropriate testing and treatment strategies to optimize care of the patient, provide assessment of both short- and long-term cardiac risk, and avoid unnecessary testing in this era of cost containment. ### A. Development of Guidelines These guidelines are based on an update of a Medline, EMBASE, Cochrane library, and Best Evidence search of the English literature from 1995 through 2000, a review of selected journals, and the expert opinions of 12 committee members representing various disciplines of cardiovascular care, including general cardiology, interventional cardiology, noninvasive testing, vascular medicine, vascular surgery, anesthesiology, and arrhythmia management. As a result of these searches, more than 400 relevant new articles were identified. In addition, draft guidelines were submitted for critical review and amendment to the executive officers representing the American College of Cardiology (ACC) and the American Heart Association (AHA). A large proportion of the data used to develop these guidelines are …

Dipyridamole-thallium-201 scintigraphy in the prediction of future cardiac events after acute myocardial infarction

To evaluate the safety and usefulness of serial thallium scanning immediately after intravenous dipyridamole, we studied 51 patients recovering from acute myocardial infarction. Eight patients experienced angina during the procedure, but there were no serious complications. Patients were followed for a mean period of 19 months after hospital discharge. Eleven of 12 patients who died during follow-up or had another infarction had shown transient defects (redistribution) on their predischarge scan, as had 22 of the 24 patients who needed readmission for management of angina. Among all the other clinical or scintigraphic criteria tested, the presence of redistribution on the dipyridamole-thallium scan was the only significant predictor of these serious cardiac events. Twenty-six patients were also given a submaximal exercise test before discharge, of whom 13 subsequently had serious cardiac events. The exercise test had been positive in only 6 of these 13 patients, whereas the dipyridamole-thallium scan had shown a redistribution pattern in 12 (P less than 0.001). We conclude from this preliminary study that dipyridamole-thallium scintigraphy after myocardial infraction is relatively safe. It appears to be a more sensitive predictor of subsequent cardiac events than a submaximal exercise test and may therefore prove useful in evaluating patients after recovery from a myocardial infarction.

Annexin-V imaging for noninvasive detection of cardiac allograft rejection

Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.

Serial thallium-201 myocardial imaging after dipyridamole infusion: diagnostic utility in detecting coronary stenoses and relationship to regional wall motion.

After a 4-minute i.v. dipyridamole infusion, 0.14 mg/kg/min, serial thallium-201 scans were obtained in 60 patients undergoing cardiac catheterization. Forty patients had significant (> 50% stenosis) coronary artery disease (CAD), and 20 patients had normal coronary arteries or trivial lesions. The images were graded qualitatively for thallium activity by three observers. Sensitivity was 93% (37 of 40) and specificity was 80% (16 of 20). The sensitivity and specificity of the thallium-201 study were not affected by the extent of CAD, the presence of Q waves, or propranolol therapy. Twenty-seven of 37 patients who had initial defects (73%) had complete thallium redistribution of one or more defects. Patient-by-patient analysis using a regression model of all patients showed that the fate of a segmental thallium defect predicted abnormal wall motion by angiography better than ECG Q waves. The presence of propranolol therapy or collaterals did not significantly affect the thallium redistribution results.We conclude that qualitative interpretation by multiple observers of thallium images after dipyridamole infusion is a highly sensitive and specific test for CAD. After dipyridamole, as with exercise stress, the extent of thallium redistribution is related to the degree of myocardial wall motion abnormality.

Noninvasive evaluation of cardiac risk before elective vascular surgery.

The prognostic utility for predicting cardiac events was determined for dipyridamole-thallium scintigraphy, exercise stress testing (when possible; n = 69) and multiple clinical variables in 100 consecutive patients admitted for elective surgical repair of peripheral vascular disease. After initial noninvasive evaluation, 11 patients were referred for coronary angiography and the remaining 89 patients had surgery without further cardiac studies. Fifteen patients (17%) had a postoperative myocardial infarction, one of which was fatal. Of these 15 patients, 14 had thallium redistribution and 3 had positive ST segment depression during stress testing. Among the many variables tested, the presence of redistribution on serial dipyridamole-thallium images was the most significant predictor of serious cardiac events. All 11 patients who had coronary angiography had both redistribution and multivessel coronary artery disease. Four of these 11 patients died during follow-up and 6 had coronary artery bypass surgery. It is concluded that dipyridamole-thallium imaging has significant prognostic utility in predicting postoperative myocardial infarction and death in patients with severe peripheral vascular disease, and is superior to exercise testing or clinical variables in determining cardiac risk. The odds for a serious cardiac event were 23 times greater in a patient with thallium redistribution than in a patient without redistribution, strongly suggesting that myocardial imaging may be used as a primary screening test before elective vascular surgery.

ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery - Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to update the 1996 guidelines on perioperative cardiovascular evaluation for noncardiac surgery)

Table of ContentsI. IntroductionA. Development of GuidelinesB. General ApproachC. Preoperative Clinical EvaluationII. Further Preoperative Testing to Assess Coronary RiskA. Clinical MarkersB. Functional CapacityC. Surgery-Specific RiskIII. Management of Specific Preoperative Cardiovascular Condition

Dipyridamole thallium 201 scintigraphy to detect coronary artery disease before abdominal aortic surgery

Dipyridamole thallium 201 scintigraphy (DTS) was used to screen 116 consecutive patients referred for aortic reconstructive surgery for coronary artery disease (CAD). Thallium redistribution was found to have the best statistical correlation with postoperative myocardial infarction (MI). No MIs occurred after aortic operations among 60 patients with normal scans compared with 8 of 31 patients with abnormal ones. The odds of a patient with abnormalities found by DTS having a postoperative MI were 12 times greater than for those with a normal scan. No symptom or combination of symptoms of CAD was as good as an abnormal DTS in identifying patients at risk. The incidence of MI was 7.0% for patients with symptomatic CAD and 8.5% for those who were asymptomatic. Cardiac complications gradually declined as surgeons gained confidence in the use of DTS, to the point where no postoperative MIs occurred during the final year of the study. DTS approaches the ideal preoperative test for CAD in patients with peripheral vascular disease. The test does not require exercise, is minimally invasive, safe, and of sufficient sensitivity to detect myocardial ischemia in the absence of symptoms. Furthermore, it is cost-effective; only those patients with an abnormal scan and an imperative need for aortic surgical treatment need further cardiac evaluation.

Safety of dipyridamole testing in 73,806 patients: The Multicenter Dipyridamole Safety Study

BackgroundDipyridamole imaging is widely used as an alternative to exercise testing to identify and risk stratify patients with coronary artery disease. Safety data on intravenous dipyridamole stress testing has been derived largely from individual institutional data.Methods and ResultsData were collected retrospectively by 85 coinvestigators from 73,806 patients who underwent intravenous dipyridamole stress imaging in 59 hospitals and 19 countries to determine the incidence of major adverse reactions during testing. The dose of dipyridamole infused was 0.56 mg/kg in 64,740 patients, 0.74 mg/kg in 6551 patients, and 0.84 mg/kg in 2515 patients. Combined major adverse events among the entire 73,806 patients included seven cardiac deaths (0.95 per 10,000), 13 nonfatal myocardial infarctions (1.76 per 10,000), six nonfatal sustained ventricular arrhythmias (0.81 per 10,000) ((ventricular tachycardia in two and ventricular fibrillation in four), nine transient cerebral ischemic attacks (1.22 per 10,000), (with speech or motor deficit), one stroke, and nine severe bronchospasms (1.22 per 10,000) (one intubation and eight near intubations). In addition to the safety data, detailed demographic, peripheral hemodynamic, side effect, and concomitant drug data were examined in a subgroup of 3751 patients. End points from subsets of patients were compared with those of the group as a whole. Multivariate analysis revealed that dipyridamole-induced chest pain was more common in patients less than 70 years old (p = 0.0017), those with a history of coronary revascularization (p = 0.002), or patients taking aspirin (p = 0.0001). Minor noncardiac side effects were less frequent among the elderly (p = 0.0053) and more frequent in women (p = 0.0001) and patients taking maintenance aspirin (p = 0.0034). When a patient was judged on the basis of the adequacy of hemodynamic response to be a dipyridamole “nonresponder” (< 10 mm Hg drop in systolic blood pressure and 10 beats/min increase in heart rate), the only significant predictor was angiotensin-converting enzyme inhibitor intake (p = 0.0025). Inferoposterior hypoperfusion was significantly more frequent in patients with dipyridamole-induced hypotension: 57% (44/77) (p < 0.0001) of those who had hypotension and 89% (8/9) (p = 0.0076) who had severe symptomatic bradyarrhythmias displayed inferoposterior defects on thallium scanning. Caffeine levels were determined in 391 consecutive patients: levels greater than 5 mg/L were observed in only eight patients (2%), suggesting that methylxanthine levels sufficients to alter the hemodynamic response to dipyridamole resulting in suboptimal hyperemic stress are unlikely when patients take nothing by mouth after midnight.ConclusionThe risk of serious dipyridamole-induced side effects is very low and is comparable to that reported for exercise testing in a similar patient population.

Comparative early and late cardiac morbidity among patients requiring different vascular surgery procedures

PURPOSE The evaluation of coronary artery disease (CAD) in patients undergoing vascular surgery can provide information with respect to perioperative and long-term risk for CAD-related events. However, the extent to which the required surgical procedure itself imparts additional risk beyond that dictated by the presence of CAD determinants remains in question. The purpose of this study was to quantify the relative contributions of specific vascular procedures and CAD markers on perioperative and long-term cardiac risk. METHODS The study cohort comprised 547 patients undergoing vascular surgery from two medical centers who underwent clinical evaluation, dipyridamole thallium testing, and either aortic (n = 321), infrainguinal (n = 177), or carotid (n = 49) vascular surgery between 1984 and 1991. Perioperative and late cardiac risk of fatal or nonfatal myocardial infarction (MI) was compared for the three procedures before and after adjustment for the influence of comorbid factors. These adjusted estimates may be regarded as the component of risk because of type of surgery. RESULTS Perioperative MI occurred in 6% of patients undergoing aortic and carotid artery surgery, and in 13% of patients undergoing infrainguinal procedures (p = 0.019). Significant (p < 0.05) predictors of MI were history of angina, fixed and reversible dipyridamole thallium defects, and ischemic ST depression during testing. Although patients undergoing infrainguinal procedures exhibited more than twice the risk for perioperative MI compared with patients undergoing aortic surgery (relative risk: 2.4[1.2 to 4.5, p = 0.008]), this value was reduced to insignificant levels (1.6[0.8 to 3.2, p = 0.189]) after adjustment for comorbid factors. There was little change in comparative risk between carotid artery and aortic procedures before (1.0[0.3 to 3.6, p = 0.95]) or after (0.6[0.2 to 2.3, p = 0.4]) covariate adjustment. The 4-year cumulative event-free survival rate was 90% +/- 2% for aortic, 74% +/- 5% for infrainguinal, and 78% +/- 7% for carotid artery procedures (p = 0.0001). Predictors of late MI included history of angina, congestive heart failure, diabetes, fixed dipyridamole thallium defects, and perioperative MI. Patients undergoing infrainguinal procedures exhibited a threefold greater risk for late events compared with patients undergoing aortic procedures (relative risk: 3.0[1.8 to 5.1, p = 0.005]), but this value was reduced to 1.3(0.8 to 2.3, p = 0.32) after adjustment. Long-term risk among patients undergoing carotid artery surgery was less dramatically altered by risk factor adjustment. CONCLUSION In current practice, among patients referred for dipyridamole testing before operation, observed differences in cardiac risk of vascular surgery procedures may be primarily attributable to readily identifiable CAD risk factors rather than to the specific type of vascular surgery. Thus the cardiac and diabetic status of patients should be given careful consideration whenever possible, regardless of surgical procedure to be performed.

Intracoronary Doppler assessment of moderate coronary artery disease: comparison with 201Tl imaging and coronary angiography. FACTS Study Group.

BACKGROUND Coronary angiography may not reliably predict whether a stenosis causes exercise-induced ischemia. Intracoronary Doppler ultrasound may enhance diagnostic accuracy by providing a physiological assessment of stenosis severity. The goal of this study was to compare intracoronary Doppler ultrasound with both 201Tl imaging and coronary angiography. METHODS AND RESULTS Fifty-five patients with 67 stenotic coronary arteries underwent coronary angiography with intracoronary Doppler ultrasound and had exercise 201Tl testing within a 1-week period. Coronary flow reserve was measured, and analyses were performed by independent core laboratories. The mean stenosis was 59+/-12%; 51 of 67 stenoses were intermediate in severity (40% to 70%). A coronary flow reserve < 1.7 predicted the presence of a stress 201Tl defect in 56 of 67 stenoses (agreement=84%; kappa=0.67; 95% CI=0.48 to 0.86). In the patients who achieved 75% of their predicted maximum heart rate, the Doppler and 201Tl imaging data agreed in 46 of 52 stenoses (agreement=88%; kappa=0.77; 95%CI=0.57 to 0.97). Scatter was evident when angiography was compared with coronary flow reserve (r=.43), and the angiogram did not reliably predict the results of the 201Tl stress test (kappa=0.21; agreement=57% to 63%). CONCLUSIONS Doppler-derived coronary flow reserve accurately predicts the presence of exercise-induced ischemia on stress 201Tl imaging, and coronary angiography does not reliably assess the physiological significance of an intermediate coronary stenosis.