Stephen A. Abraham

Positron emission tomographic measurements of absolute regional myocardial blood flow permits identification of nonviable myocardium in patients with chronic myocardial infarction

OBJECTIVES This study tested the hypothesis that nonviable myocardium can be identified by quantitative measurements of regional myocardial blood flow obtained using positron emission tomography in conjunction with a mathematical model of nitrogen-13 (N-13) ammonia tracer kinetics. BACKGROUND Under steady state basal conditions there is a minimal level of blood flow required to sustain myocardial viability. Therefore, the hypothesis predicts that regions with flow below a certain threshold are likely to be composed primarily of scar. METHODS Studies were conducted in 26 patients with chronic myocardial infarction. Positron emission tomographic measurements of basal regional myocardial blood flow (N-13 ammonia) and fluorine-18 (F-18) fluorodeoxyglucose uptake were made and correlated with information about coronary anatomy and regional wall motion to assess myocardial viability. RESULTS In patients with chronic myocardial infarction, normal zone blood flow (0.81 +/- 0.32 ml/min per g [mean +/- SD]) was greater (p < 0.02) than that of border zones (0.59 +/- 0.29 ml/min per g), which in turn exceeded (p < 0.001) that of infarct zone flow (0.27 +/- 0.17 ml/min per g). Good correlation was noted between relative F-18 fluorodeoxyglucose uptake and relative regional myocardial blood flow in all zones (r = 0.63, p < 0.001). Mismatch between blood flow and F-18 fluorodeoxyglucose uptake, with a single exception, was not observed in any segment with blood flow < 0.25 ml/min per g. All dyskinetic segments (n = 5) also had blood flow < 0.25 ml/min per g. In contrast, 43 of 45 myocardial segments (23 patients) with normal contraction or only mild hypokinesia had flow > or = 0.39 ml/min per g (average flow 0.78 +/- 0.35 ml/min per g). CONCLUSIONS In patients with chronic myocardial infarction, myocardial viability is unlikely when basal regional myocardial blood flow is < 0.25 ml/min per g. Average basal flow in segments with normal or nearly normal wall motion is 0.78 +/- 0.35 ml/min per g. Thus, positron emission tomographic measurement of regional myocardial blood flow is helpful in identifying nonviable myocardium in these patients.

Usefulness of dipyridamole-thallium scanning for preoperative evaluation of cardiac risk for nonvascular surgery

The ability to stratify cardiac risk before nonvascular surgery using clinical markers and dipyridamole-thallium scanning (DTS) was assessed for patients with known or suspected coronary artery disease unable to exercise. Of 100 consecutively studied patients who proceeded to nonvascular surgery, 9 (9%) experienced greater than or equal to 1 perioperative cardiac ischemic event, including death in 2 patients (2%) and nonfatal myocardial infarction in 2 (2%). Logistic regression identified 2 clinical predictors (age greater than 70 years and history of heart failure), and 1 DTS (thallium redistribution) predictor of events. Of 45 patients with neither clinical variable, none (0%; 95% confidence intervals [CI] 0 to 8%) had events. Of 55 patients with greater than or equal to 1 clinical marker, 9 (16.4%; 95% CI 7 to 26%) had events. Within this subgroup, 1 of 31 patients (3.2%; 95% CI 0 to 16%) without thallium redistribution had events compared with 8 of 24 (33.3%; 95% CI 14 to 52%) with redistribution. An algorithm combining 5 independent clinical and 2 DTS predictors, derived previously in vascular surgery patients, was validated in the 100 nonvascular surgery patients. It is concluded that preoperative planar DTS is most useful to stratify selected nonvascular surgery patients at intermediate or high risk by clinical assessment. However, for almost half of those patients with known or suspected coronary artery disease, DTS may be unnecessary because of sufficiently low predictive value based on simple clinical descriptors.

Coronary risk of noncardiac surgery

ORONARY ARTERY disease is the number one cause of death in the United States, often progressing silently until severe disease is present. It is also one of the most frequent causes of death after noncardiac surgery. Therefore, risk stratification of patients with suspected or known coronary artery disease should be performed at the time of presentation for noncardiac surgery. Occasionally, a patient’s condition will necessitate modification of the planned surgical approach or deferment in favor of a trial of medical therapy. Appropriately selected patients will benefit from preoperative coronary interventions, primarily coronary artery bypass surgery (CARG), before undergoing noncardiac surgery. This review will describe the epidemiologic aspects of perioperative myocardial infarction (MI) and cardiac death. Various methods of risk stratification will be discussed, including exercise treadmill testing with and without adjunctive radionuclide imaging, studies of left ventricular function, dipyridamole thallium scintigraphy, silent ischemia monitoring, and transesophageal echocardiography. We will also present a summary of the impact of medical and interventional therapy of coronary artery disease on perioperative cardiac complications. Finally, a general patient management strategy will be outlined.

Complications of exercise and pharmacologic stress tests: differences in younger and elderly patients.

BackgroundAge characteristics of patients undergoing various types of stress tests are important because of differences in clinical background and exercise performance between the young and elderly. Adverse effects of pharmacologic agents are known to be more common in the elderly, who are less able to perform vigorous exercise stress testing. We investigated the clinical background, performance characteristics, and complication rate of various stress tests in younger (≤75 years old) and elderly (>75 years old) patient populations.MethodsA total of 3412 patients (2796 younger, 616 elderly) underwent 5 types of stress tests with (1) technetium-99m sestamibi (MIBI) single photon emission computed tomography: symptom-limited exercise (Ex, 1598 younger, 173 elderly), (2) dipyridamole infusion (0.14 mg/kg/min, 4 minutes) without exercise (D, 260 younger, 114 elderly), (3) with exercise (DEx, 339 younger, 112 elderly), (4) adenosine infusion (0.14 mg/kg/min, 5 minutes) without exercise (A, 253 younger, 101 elderly), and (5) with exercise (AEx, 346 younger, 116 elderly).ResultsSixty-seven percent of patients in the younger population were able to achieve 85% of the maximum predicted heart rate, whereas 54% of the elderly reached this level of exercise. No patient had life-threatening complications. In both the younger and elderly groups, chest discomfort, feelings of impending syncope, flushing, and fall in blood pressure occurred less frequently in DEx than D and in AEx than A. Sinus bradycardia occurred less frequently in AEx than A in the younger (1.2% vs 4.3%, P<.05) and elderly groups (0.9% vs 6.9%, P<.05). Atrioventricular block was less frequent in AEx than A in the younger group (3.2% vs 7.9%, P<.05) but not so in the elderly group (13.0% vs 17.8%, not significant). The frequency of ischemic electrocardiographic changes in DEx and AEx was very similar to that of Ex in both the younger and elderly groups, although ischemic electrocardiographic changes in D and A are known to be less frequent.ConclusionOf the elderly group who were judged to be fit to exercise to 85% of maximum predicted heart rate, nearly half failed to reach this level. In contrast, the younger patients were able to achieve this level in 67% of tests. Supplementation with modest exercise reduced most of the pharmacologically related adverse effects. The elderly group was not protected from atrioventricular block as effectively as the younger group by additional exercise in the adenosine stress test. Ischemic electrocardiographic changes in the pharmacologic stress test were as frequent as in the exercise stress test when modest supplementary exercise was added to the pharmacologic protocol. There were no deaths, myocardial infarction, or other major complications. These observations suggest that exercise and pharmacologic stress tests are safe in the elderly, including those patients more than 75 years old.

Factors Influencing Regional Myocardial Contractile Response to Inotropic Stimulation Analysis in Humans With Stable Ischemic Heart Disease

BACKGROUND We hypothesized that the response of a myocardial segment to maximal dobutamine reflects not only maximal blood flow but also tethering, metabolic, and beta-blocker status. METHODS AND RESULTS Patients with stable ischemic heart disease (n = 27) had positron emission tomographic measurement of blood flow at rest and with adenosine, and echocardiography at rest and with dobutamine. Positron emission tomographic measurement of [18F]fluorodeoxyglucose myocardial distribution also was made. Adenosine blood flow in segments that contracted normally at peak dobutamine was similar to that of segments that became hypokinetic (1.06 +/- 0.72 versus 1.02 +/- 0.77 mL.g-1.min-1). Segments that became akinetic failed to augment blood flow (0.68 +/- 0.30 mL.g-1.min-1). Fluorodeoxyglucose-blood flow mismatch was more common in segments with abnormal wall motion at peak dobutamine (24 of 59, 41%) versus those that contracted normally (63 of 269, 23%; chi 2, 7.40; P < .01). In patients off beta-blockers, segments that contracted normally at peak dobutamine increased blood flow with adenosine (0.70 +/- 0.31 to 0.86 +/- 0.46 mL.g-1.min-1; P < .05), whereas those that became abnormal did not (0.63 +/- 0.24 to 0.65 +/- 0.19 mL.g-1.min-1; P = NS). Segments of patients on beta-blockers that contracted normally at peak dobutamine increased blood flow with adenosine (0.78 +/- 0.31 to 1.10 +/- 0.70 mL.g-1.min-1; P < .05), as did segments that became abnormal (0.74 +/- 0.34 to 1.06 +/- 0.82 mL.g-1.min-1; P = NS). However, segments adjacent to ones with abnormal wall motion at rest had higher frequency of abnormal response at peak dobutamine in groups on (48% versus 16%; chi 2, 14.1; P < .001) and off (51% versus 21%; chi 2, 10.9; P < .01) beta-blockers. CONCLUSIONS Augmented contraction at maximal dobutamine depends not only on increased myocardial blood flow but also on tethering, metabolic, and beta-blocker status. Furthermore, impaired flow reserve does not preclude a normal response to maximal dobutamine, since blood flow need not increase greatly to meet demand.

Quantitative PET Measurements of Regional Myocardial Blood Flow: Observations in Humans with Ischemic Heart Disease

This review focuses on several related issues concerning positron emission tomography measurements of regional myocardial blood flow using 13-N-ammonia in humans. The effect of partial volume correction on estimates of K1, the model parameter describing myocardial blood flow, is considered. In addition a new method for computing K1 images of myocardial flow distribution is briefly described and compared to a standard method. Potential differences between K1 and equilibrium levels of 13-N-ammonia in the myocardium for estimation of myocardial blood flow are discussed also. The issue of heterogeneity of myocardial blood flow and flow reserve in normal volunteers is considered from the clinical point of view in terms of evaluation of patients with ischemic heart disease. Finally, the use of absolute measurement of adenosine-stimulated myocardial blood flow to assess physiological significance of coronary artery stenoses is addressed.

Evidence of reduced resting blood flow in viable myocardial regions with chronic asynergy

OBJECTIVES We tested the hypothesis in patients (n = 24) with ischemic heart disease that chronic contractile dysfunction occurs in myocardial regions with true reduction in rest blood flow. BACKGROUND Whether viable myocardial regions with chronic contractile dysfunction have true reduction in rest myocardial blood flow is controversial. METHODS Positron emission tomography (PET) 13N-ammonia was used to measure myocardial blood flow in combination with 18F-fluorodeoxyglucose (18FDG) to assess myocardial viability. Viability also was assessed by dobutamine echo and recovery of function after coronary artery bypass grafting (CABG). Segments (n = 252) were selected based on PET measured reduced resting blood flow and rest asynergy on echo. RESULTS Regional myocardial viability was present in 20 of 23 patients by PET, 13 of 23 by dobutamine echo and 10 of 11 by postrevascularization criteria. Rest blood flow in normal regions was 1.14+/-0.52 ml/min/g and by definition exceeded (p < 0.005) that in both viable (0.48+/-0.15; n = 8 patients) and nonviable (0.45+/-0.14; n = 8 patients) regions (post-CABG criteria), which did not differ. Correction of rest myocardial blood flow in viable asynergic segments, only, for fibrosis and incomplete tracer recovery raised the level to 0.67+/-0.21 (p < 0.005 vs. normal). Finally, evidence of both stunning (rest asynergy with normal flow) and hibernation was present in 15 of 23 (65%) patients. CONCLUSIONS Reduced rest blood flow in viable myocardial regions with chronic asynergy is common and cannot be accounted for by partial volume effect. Thus, hypotheses concerning physiologic mechanisms underlying chronic contractile dysfunction should consider the role played by chronic reduction of basal myocardial blood flow.

Preoperative cardiac risk assessment for noncardiac surgery

Patients presenting for noncardiac surgery should receive careful preoperative cardiac risk stratification. This has implications not only for the perioperative period, but also for long-term survival. After an initial clinical evaluation, certain patients will be referred for noninvasive testing. Those without significant inducible ischemia at a high workload have a low risk for perioperative cardiac complictions. Patients who are unable to exercise adequately may require alternative forms of testing, of which dipyridamole thallium scintigraphy is the most thoroughly studied and validated option. Patients with either high-risk clinical profiles or significant thallium redistribution merit consideration for preoperative coronary angiography. Treatment options for high-risk patients include: (1) Proceeding with surgery as planned along with aggressive perioperative monitoring and anti-ischemic therapy, (2) coronary angiography with subsequent myocardial revascularization as appropriate before elective surgery, (3) selecting an alternative, lower risk surgical approach, and (4) cancellation of surgery in lieu of a trial of conservative therapy.