Prognostic value of myocardial ischemia and viability in patients with chronic left ventricular ischemic dysfunction.

BACKGROUND: Previous studies showed that thallium scintigraphy and dobutamine echocardiography were accurate, noninvasive ways of predicting contractile recovery after revascularization in patients with left ventricular (LV) dysfunction. However, the prognostic impact of such methods remains uncertain. METHODS AND RESULTS: We prospectively studied 137 consecutive patients with coronary disease and LV dysfunction who underwent exercise-redistribution-reinjection thallium scintigraphy and dobutamine echocardiography to identify myocardial ischemia and viability. A total of 94 patients subsequently underwent revascularization, and 43 underwent medical treatment. The primary endpoint was cardiac mortality, and mean follow-up was 33+/-10 months. Twenty-four patients died of cardiac causes. By Cox's regression analysis, long-term survival was related to the extent of coronary disease, the presence of diabetes, type of treatment, the presence of ischemic myocardium as determined by thallium scintigraphy, and the presence of viable myocardium as determined by both tests. Three-year survival was greater in patients with ischemic myocardium (as determined by thallium scintigraphy) or viable myocardium (as determined by both tests) who underwent revascularization than in the other groups (P=0.018 with thallium; P<0.001 with dobutamine). Subgroup analyses indicated that among patients with 1- or 2-vessel disease, only those with ischemic or viable myocardium improved survival after revascularization, whereas in patients with 3-vessel or left main diseases, revascularization always improved survival, albeit more in the presence of ischemic or viable myocardium. CONCLUSIONS: Among the parameters commonly available in patients with LV ischemic dysfunction, the presence of ischemic myocardium (as determined by thallium scintigraphy) and that of viable myocardium (as determined by dobutamine echocardiography) are independent predictors of subsequent mortality. These observations may be useful in the preoperative selection of patients for revascularization.

Microvascular obstruction and left ventricular remodeling early after acute myocardial infarction.

BACKGROUND: The presence of microvascular obstruction (MO) within infarcted regions may adversely influence left ventricular (LV) remodeling after acute myocardial infarction. This study examined whether the extent of MO directly alters the mechanical properties of the infarcted myocardium. METHODS AND RESULTS: Seventeen dogs underwent 90 minutes of balloon occlusion of the left anterior descending coronary artery, followed by reperfusion. Gadolinium-enhanced perfusion MRI and 3D-tagging were performed 4 to 6 and 48 hours (8 animals) and 10 days (9 animals) after reperfusion. Early increase in LV end-diastolic volume (from 42+/-9 to 54+/-14 mL, P<0.05) between 4 to 6 and 48 hours after reperfusion was predicted by both extent of MO (r=0.89, P<0.01) and infarct size (r=0.83, P<0.01), defined as MRI hypoenhanced and hyperenhanced regions, respectively. Multivariate analysis demonstrated that extent of MO had better and independent value to predict LV volume than overall infarct size. A strong inverse relationship existed between magnitude of first principal strain (r=-0.80, P<0.001) and relative extent of MO within infarcted myocardium. Also, infarcted myocardium involved by extensive areas of MO demonstrated reductions of circumferential (r=-0.61, P<0.01) and longitudinal (r=-0.53, P<0. 05) stretching. Furthermore, significant reductions of radial thickening (9+/-6% versus 14+/-3%, P<0.01) occurred in noninfarcted regions adjacent to infarcts that had increased (>35%) amounts of MO. CONCLUSIONS: In the early healing phase of acute myocardial infarction, the extent of MO in infarcted tissue relates to reduced local myocardial deformation and dysfunction of noninfarcted adjacent myocardium. Such strain alterations might explain the increased remodeling observed in patients with large regions of MO.

Relation between Gd-DTPA contrast enhancement and regional inotropic response in the periphery and center of myocardial infarction.

BACKGROUND: Gd-DTPA contrast-enhanced (CE) MRI identifies patterns of early hypoenhancement and delayed hyperenhancement in acute myocardial infarction, but their clinical significance for the prediction of myocardial viability remains controversial. Therefore, we closely examined the relationship between these CE patterns and regional inotropic response to low-dose dobutamine infusion at a regional level. METHODS AND RESULTS: Thirteen dogs underwent CE and tagged MRI at rest and during 5 microg. kg(-1). min(-1) dobutamine 48 hours after MI. CE patterns and 3D regional strains were measured in 96 segments per animal. Segments were categorized as being normofunctional (n=828) if resting circumferential shortening was within the range of remote myocardium, or dysfunctional (n=420) if not. Inotropic response in resting dysfunctional segments was assessed according to CE patterns. Significant improvement of radial thickening (from +12+/-1% [mean+/-SEM] to +22+/-2%, P<0.05) and circumferential shortening (from +1+/-1% to -5+/-1%, P<0.05) strains occurred in dysfunctional myocardium with normal CE pattern but not in myocardium with early hypoenhancement. Delayed hyperenhanced myocardium displayed a more complex behavior. Circumferential stretching improved in the peripheral regions (from +4+/-1% to -2+/-2%, P<0.05), where the infarct was nontransmural (38+/-3% transmurality), but not in centrally hyperenhanced regions (from +4+/-1% to +1+/-1% P=NS), where the infarct was 66+/-3% transmural. CONCLUSIONS: Inotropic reserve was confined to dysfunctional myocardium with normal contrast enhancement but not to myocardium with early hypoenhancement. Inotropic response in delayed hyperenhanced myocardium is influenced by transmurality of necrosis. These observations support the use of CE MRI for the clinical detection of myocardial viability.

Destruction of contrast microbubbles by ultrasound: effects on myocardial function, coronary perfusion pressure, and microvascular integrity.

BACKGROUND: Recent experimental data indicate that ultrasound-induced destruction of ultrasound contrast microbubbles can cause immediate rupture of the microvessels in which these microbubbles are located. METHODS AND RESULTS: To examine the functional and morphological significance of these findings in the heart, isolated rabbit hearts were perfused retrogradely with buffer containing ultrasound contrast agents and were insolated at increasing levels of acoustic energy with a broadband transducer emitting at 1.8 MHz and receiving at 3.6 MHz and operated in the triggered mode (1 Hz). At the end of each experiment, the hearts were fixed in glutaraldehyde and examined with light microscopy. Neither exposure to ultrasound alone or to contrast alone affected left ventricular developed pressure. By contrast, simultaneous exposure to contrast and ultrasound resulted in a reversible, transient mechanical index (MI)-dependent decrease in left ventricular developed pressure (to 83+/-5% of baseline at an MI of 1.6) and a transient MI-dependent increase in coronary perfusion pressure (to 120+/-6% of baseline at an MI of 1.6). Myocardial lactate release also showed significant increases with increasing MIs. Macroscopically, areas of intramural hemorrhage were identified over the beam elevation in hearts exposed to both contrast and high-MI ultrasound. Light microscopy revealed the presence of capillary ruptures, erythrocyte extravasation, and endothelial cell damage. The mean percentage of capillaries ruptured at an MI of 1.6 was 3.6+/-1.4%. CONCLUSIONS: Simultaneous exposure of isolated rabbit hearts to ultrasound and contrast agents results in an MI-dependent, transient depression of left ventricular contractile function, a rise in coronary perfusion pressure, an increase in lactate production, and limited capillary ruptures.

Salvage of ischemic myocardium by prostacyclin during experimental myocardial infarction.

The effects of prostacyclin (PGI2) on infarct size and regional myocardial blood flow were studied in 28 anesthetized dogs subjected to 5 hours of coronary occlusion. A region of myocardial hypoperfusion was defined by injection of dye into the left atrium just before sacrifice. Infarct size was determined by planimetry of left ventricular slices after incubation in triphenyl tetrazolium chloride. The animals received either PGI2 in Tris buffer solution (20 to 40 ng/kg per min, n = 14) or Tris buffer alone (control, n = 14) beginning 10 minutes after anterior descending coronary artery occlusion. During PGI2 infusion, mean arterial pressure decreased by 8%, but heart rate was unchanged. Infarct size was significantly less (p less than 0.005) in PGI2-treated dogs compared with the control group, both as percent of left ventricle (8.1 versus 17.7%) and as percent of the hypoperfused zone (39.8 versus 77.3%). No significant changes in regional myocardial blood flow occurred over the 5 hour infusion period in either group. Thus, under the conditions of this study, prostacyclin appeared to protect ischemic myocardium by a direct flow-independent mechanism.

Exercise echocardiography is an accurate and cost-efficient technique for detection of coronary artery disease in women.

OBJECTIVES: This study compared the accuracy and cost implications of using exercise echocardiography and exercise electrocardiography for detection of coronary artery disease in women. BACKGROUND: The specificity of exercise electrocardiography in women is lower than in men. Exercise echocardiography accurately identifies coronary artery disease in women, but its utility in place of exercise electrocardiography is unclear. METHODS: One hundred sixty-one women without a previous Q wave infarction underwent exercise echocardiography and coronary angiography. Positive findings were a new or worsening wall motion abnormality on the exercise echocardiogram and ST segment depression > 0.1 mV at 0.08 s after the J point on the exercise electrocardiogram (ECG). RESULTS: Coronary artery stenosis > 50% diameter narrowing was present in 59 patients; the sensitivity (mean +/- SD) of exercise echocardiography was 80 +/- 3%. In 48 patients with an interpretable ECG, the sensitivity of exercise echocardiography was 81 +/- 4%, and that of the exercise ECG was 77 +/- 3% (p = 0.50). In 102 patients without coronary artery disease, the overall specificity of exercise echocardiography was 81 +/- 4%. In 70 patients with an interpretable ECG, the specificity of exercise echocardiography (80 +/- 3%) exceeded that of the exercise ECG (56 +/- 4%, p < 0.0004). The accuracy of exercise echocardiography was also greater than exercise electrocardiography (81 +/- 5% vs. 64 +/- 6%, p < 0.005). Exercise echocardiography stratified significantly more patients of intermediate (20% to 80%) pretest disease probability into the high (> 80%) or low (< 20%) posttest probability group. In women without a previous exercise ECG, the specificity of exercise echocardiography continued to exceed that of exercise electrocardiography (80 +/- 3% vs. 64 +/- 3%, p = 0.05). Exercise echocardiography had the best balance between accuracy and cost for the diagnosis of coronary artery disease in women. CONCLUSIONS: Exercise echocardiography is more specific than exercise electrocardiography for diagnosis of coronary artery disease in women and is a cost-effective approach to the diagnosis of coronary artery disease because of the avoidance of inappropriate angiography.

Head-to-head comparison of exercise-redistribution-reinjection thallium single-photon emission computed tomography and low dose dobutamine echocardiography for prediction of reversibility of chronic left ventricular ischemic dysfunction.

OBJECTIVES: We sought to directly compare the diagnostic value of exercise-redistribution-reinjection thallium single-photon emission computed tomography (SPECT) and low dose dobutamine echocardiography for prediction of contractile recovery after revascularization. BACKGROUND: Both thallium SPECT and dobutamine echocardiography have been proposed to predict the reversibility of left ventricular dysfunction after revascularization. Although both techniques permit differentiation of viable from nonviable myocardium, few studies have directly compared their accuracy in the same patients. METHODS: Seventy-three consecutive patients (mean [+/- SD] age 59 +/- 9 years) with coronary disease and regional left ventricular dysfunction underwent exercise-redistribution-reinjection thallium SPECT and dobutamine echocardiography before revascularization. Recovery of function was evaluated with echocardiography 5.5 +/- 2.5 months after revascularization. For analysis, the left ventricle was divided into 16 segments, in which percent thallium uptake was quantitated using circumferential profiles, and regional wall motion was graded semiquantitatively (normal = 1; akinetic = 3). RESULTS: The diagnostic performance of the two tests was investigated both for individual patients and for individual segments. Individual patient analysis showed that left ventricular ejection fraction improved > 5% after revascularization in 43 patients, whereas 30 showed no change. Receiver operating characteristic curves were used to select optimal criteria for prediction of functional recovery after revascularization. According to a mean thallium uptake > 54% at reinjection, SPECT had a sensitivity of 72%, a specificity of 73% and an overall accuracy of 73%. Similarly, according to an improvement in wall motion score > 3.5 grades during doubutamine echocardiography, echocardiography had a sensitivity of 88%, a specificity of 77% and an overall accuracy of 84% (p = NS vs. thallium). Segmental analysis showed that SPECT and dobutamine echocardiography had similar sensitivity (77% and 75%, respectively), but SPECT had lower specificity (56% vs. 86%, p < 0.01). CONCLUSIONS: Quantitative exercise-redistribution-reinjection thallium SPECT and dobutamine echocardiography have comparable accuracy for prediction of reversibility of global left ventricular dysfunction after revascularization. However, dobutamine echocardiography has greater specificity than thallium imaging for prediction of functional recovery on a segmental basis.

How accurate is dobutamine stress electrocardiography for detection of coronary artery disease? Comparison with two-dimensional echocardiography and technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion scintigraphy.

OBJECTIVES: This study was designed to establish the appropriate diagnostic criteria for positive dobutamine electrocardiographic (ECG) stress test results and to compare their accuracy with those of dobutamine two-dimensional echocardiography and perfusion scintigraphy. BACKGROUND: Conventional criteria for positive findings on ECG exercise testing may not be appropriate for use with dobutamine ECG stress testing. METHODS: One hundred twenty-nine consecutive patients with an interpretable ECG and without previous myocardial infarction were prospectively studied at the time of coronary arteriography. All completed a standard dobutamine protocol (5 to 40 micrograms/kg body weight per min in 3-min dose increments) without side effects. Significant coronary artery disease, defined as > 50% lumen diameter stenosis of a major epicardial coronary artery on coronary angiography, was present in 83 patients. Empiric receiver operating curves were generated for various ECG criteria derived from computer-averaged signals. RESULTS: The best ECG criterion, with a sensitivity of 42% and a specificity of 83%, was an ST segment shift, relative to baseline, of 0.5 mm 80 ms after the J point. The sensitivity of this criterion was greater than that of the conventional criterion of 1-mm ST segment depression 60 (23%) or 80 (18%) ms after the J point, was comparable to that of chest pain occurring during the test (44%, p = NS) but remained inferior to the sensitivities of technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion (76%) or stress echocardiography (76%, p < 0.001, for both). The specificity of this criterion was not significantly different from that of technetium-99m mibi perfusion tomography (65%) or stress echocardiography (89%) but was superior to that of chest pain (59%, p < 0.025). CONCLUSIONS: We conclude that this new criterion for dobutamine electrocardiography is specific but that an imaging technique is still required to accurately predict coronary artery disease.

Myocardial perfusion and oxygen consumption in reperfused noninfarcted dysfunctional myocardium after unstable angina: direct evidence for myocardial stunning in humans.

OBJECTIVES: To positively establish the diagnosis of myocardial stunning in patients with unstable angina and persistent wall motion abnormalities after reperfusion by coronary angioplasty. BACKGROUND: Although myocardial stunning is thought to occur in several clinical conditions, definite proof of its existence in humans is still lacking, owing to the difficulty of measuring myocardial blood flow (MBF) in absolute terms. METHODS: We studied 14 patients with unstable angina due to proximal left anterior descending coronary artery disease who presented persistent anterior wall motion abnormalities despite revascularization of the culprit lesion by percutaneous coronary angioplasty (PTCA) and who did not have clinical evidence of necrosis. Dynamic positron emission tomography (PET) with [13N]-ammonia and [11C]-acetate was performed 48 h after PTCA to determine absolute MBF and oxygen consumption (MVO2). Regional wall thickening and regional cardiac work were determined using two-dimensional echocardiography. Improvement of segmental wall motion abnormalities was followed for a median of 4 months (1.5 to 14 months). RESULTS: As judged from the changes in segmental wall motion score, regional dysfunction was spontaneously reversible in 12/14 patients and improved from 2.2 +/- 0.3 to 1.2 +/- 0.3 at late follow-up (p < 0.001). With PET, [13N]-ammonia MBF was similar among dysfunctional and remote normally contracting segments (85 +/- 29 vs. 99 +/- 20 ml x min (-1) x 100g(-1), p = not significant [n.s.]), thus demonstrating a perfusion-contraction mismatch. Despite the reduced contractile function, dysfunctional myocardium presented near normal levels of MVO2 (6.5 +/- 4.2 vs. 8.0 +/- 1.9 ml x min (-1)x 100g(-1), p = n.s.). Consequently, the regional myocardial efficiency (regional work divided by MVO2) of the dysfunctional myocardium was found to be markedly decreased as compared with normally contracting myocardium (6 +/- 6% vs. 26 +/- 6%, p < 0.001). CONCLUSIONS: This study demonstrates that human dysfunctional myocardium capable of spontaneously recovering contractile function after unstable angina endures a state of perfusion-contraction mismatch. These data for the first time provide unequivocal direct evidence for the existence of acute myocardial stunning in humans.

Collateral blood flow after coronary occlusion: influence of barbiturate anaesthesia and thoracotomy.

A study was undertaken to determine whether barbiturate anaesthesia, with or without thoracotomy, adversely affects collateral blood flow during acute coronary artery occlusion. Twelve dogs were instrumented with an electromagnetic flow probe and pneumatic occluder on the left circumflex artery; seven days later, in the conscious state, complete coronary artery occlusion was induced for 8 min. Heart rate, mean aortic pressure, and subendocardial and subepicardial blood flow in the ischaemic zone were measured by radioactive microspheres before and 5 min into coronary artery occlusion. Measurements were repeated after pentobarbital 30 mg.kg-1 (n = 7) and after pentobarbital plus thoracotomy (n = 12). Compared with the conscious state, pentobarbital and thoracotomy produced a decrease in endocardial blood flow in the ischaemic zone (0.21(0.04) to 0.15(0.03) ml.min-1.g-1) and a modest redistribution from endocardium to epicardium (ratio of endocardial to epicardial flow 0.55(0.06) to 0.49(0.07) ml.min-1.g-1), coincident with an increase in heart rate from 127 to 178 beats.min-1 but no change in mean arterial pressure. Directionally similar, but smaller, changes occurred during anaesthesia without thoracotomy. To determine the role of tachycardia five of the animals were studied in the conscious state during a 50% increase in heart rate induced by atrial pacing. A similar decrease occurred in coronary blood flows as with anaesthesia. The results indicate that barbiturate anaesthesia and thoracotomy produce a diminution in collateral flow to ischaemic myocardium, together with an accentuation of its transmural maldistribution, and suggest that anaesthetic induced tachycardia is primarily responsible for these flow alterations.

Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve in migraineurs.

BACKGROUND: Migraine drugs can produce adverse cardiac effects. The authors have demonstrated previously that ergotamine can lead to a significant reduction of hyperemic myocardial blood flow, but little is known about the effect of the newer serotonin analogues. Coronary artery constriction caused by serotonin or its analogues is mediated mainly by 5HT2 receptors. The selective 5HT1B/1D agonist naratriptan has no significant activity at 5HT2 receptors; however, like all 5HT1B/1D agonists developed for the acute treatment of migraine, naratriptan could potentially constrict coronary arteries by activation of 5HT1B receptors. METHODS: The effects on myocardial blood flow of subcutaneous naratriptan 1.5 mg compared with placebo were assessed under resting and hyperemic conditions with PET using oxygen-15 labeled water during two separate visits. This study was a randomized, double-blind, placebo-controlled crossover trial in 34 migraine subjects with no evidence of ischemic heart disease, studied outside a migraine attack. RESULTS: Naratriptan did not differ significantly from placebo in its effects on resting myocardial blood flow, but did evoke a small, significant fall in hyperemic myocardial blood flow (-13% versus placebo) and an increase in hyperemic coronary resistance (+19% versus placebo) without any signs or symptoms suggestive of myocardial ischemia. Naratriptan did not significantly affect the coronary vasodilator reserve (hyperemic/resting blood flow) compared with placebo. CONCLUSIONS: These results show that at therapeutic doses, naratriptan exerts only a minor effect on myocardial blood flow, coronary vasodilator reserve, or coronary resistance among subjects with no evidence of ischemic heart disease. These results should not be extrapolated to patients with coronary artery disease, in whom all 5HT1 agonists for migraine are contraindicated.

Quantitative relationship between global left ventricular thallium uptake and blood flow: effects of propranolol, ouabain, dipyridamole, and coronary artery occlusion.

The quantitative relationship between fractional myocardial thallium uptake and radioactive microsphere-determined flow was studied in 33 open chest dogs under baseline conditions during increased coronary flow (dipyridamole), decreased coronary flow (propranolol and coronary artery stenosis), inhibition of Na-K ATPase (ouabain), and regional infarction. Myocardial contents of thallium and microspheres were compared in left ventricular (LV) biopsies taken 5, 10, 15, 30, and 60 min after thallium injection, expressed as fractions of injected dose. Maximal LV thallium uptake occurred 10 min after injection and the 10-min values were therefore used for subsequent comparisons. Combining all dogs, fractional LV thallium content (% injected dose) correlated well with fractional LV blood flow (% cardiac output) (r = 0.95). However, for fractional LV flows in the low, normal, or moderately elevated range (LV flow/cardiac output less than 9%), thallium content consistently exceeded flow by about 15%. This relationship was not altered by ouabain or regional ischemia or infarction. For greatly elevated fractional LV flows (greater than 9%), thallium content was not significantly different from flow. To explain these differences, myocardial and systemic extraction fractions for thallium were determined in eight dogs with a dual tracer method. At baseline, myocardial extraction fraction was significantly greater than systemic (88 +/- 0.4% compared with 75 +/- 1%, p less than 0.001). During dipyridamole, myocardial extraction fraction decreased and myocardial and systemic values were no longer significantly different (82 +/- 1% compared with 79 +/- 1%). These results show that the fraction of injected thallium dose taken up by the LV myocardium exceeds the delivered fraction of cardiac output over a wide range of LV flows, and is not altered by ouabain-induced inhibition of sodium-potassium ATPase or regional myocardial infarction. This difference is explained by a greater myocardial than systemic extraction fraction for thallium. During high LV flows produced by dipyridamole, fractional LV thallium uptake and flow become similar as myocardial and systemic extraction fractions equalize.

Accumulation of polymorphonuclear leukocytes in reperfused ischemic canine myocardium: relation with tissue viability assessed by fluorine-18-2-deoxyglucose uptake.

Polymorphonuclear leukocytes may participate in reperfusion injury. Whether leukocytes affect viable or only irreversibly injured tissue is not known. Therefore, we assessed the accumulation of 111In-labeled leukocytes in tissue samples characterized as either ischemic but viable or necrotic by metabolic, histochemical, and ultrastructural criteria. Six open-chest dogs received left anterior descending coronary occlusion for 2 hr followed by 4 hr reperfusion. Myocardial blood flow was determined by microspheres and autologous 111In-labeled leukocytes were injected intravenously. Fluorine-18-2-deoxyglucose, a tracer of exogenous glucose utilization, was injected 3 hr after reperfusion. The dogs were killed 4 hr after reperfusion. The risk and the necrotic regions were assessed following in vivo dye injection and postmortem tetrazolium staining. Myocardial samples were obtained in the ischemic but viable, necrotic and normal zones, and counted for 111In and 18F activity. Compared to normal, leukocytes were entrapped in necrotic regions (111In activity: 207 +/- 73%) where glucose uptake was decreased (26 +/- 15%). A persistent glucose uptake, marker of viability, was mainly seen in risk region (135 +/- 85%) where leukocytes accumulation was moderate in comparison to normal zone (146 +/- 44%). Thus, the glucose uptake observed in viable tissue is mainly related to myocytes metabolism and not to leukocytes metabolism.

Delineation of myocardial viability with PET.

UNLABELLED: Relative flow and metabolic imaging (the "mismatch pattern") with PET have been proposed to identify the presence of viable myocardium in patients with ischemic left ventricular dysfunction. Yet, optimal criteria to identify dysfunctional but viable myocardium and predict significant functional improvement have not been fully defined. METHODS: Dynamic PET imaging with 13N-ammonia and 18F-deoxyglucose to assess absolute myocardial perfusion and glucose uptake was performed in 25 patients (20 men, 5 women; mean age 57 +/- 12 yr, range 30-72 yr) scheduled for coronary revascularization because of coronary artery disease, anterior wall dysfunction and mildly depressed left ventricular ejection fraction (49% +/- 11%). Global and regional left ventricular function was evaluated by contrast left ventriculography at baseline and after revascularization. RESULTS: As judged from the changes in end-systolic volume and resting anterior wall motion before and after revascularization, 17 patients with improved wall motion score and decreased end-systolic volume were considered to have viable myocardium, whereas 8 patients with either no change in regional wall motion or increased end-systolic volume were considered to have nonviable myocardium. Before revascularization, viable myocardium showed higher absolute myocardial blood flow (77 +/- 20 versus 51 +/- 9 ml (min.100 g)-1, p = 0.004) and absolute regional myocardial glucose uptake (36 +/- 14 versus 24 +/- 11 mumole (min.100 g)-1, p = 0.04) than nonviable myocardium. CONCLUSION: This study identified absolute myocardial blood flow and normalized glucose extraction as the most powerful predictors of the return of contractile function after coronary revascularization in patients with ischemic anterior wall dysfunction.

Nitrogen-13-ammonia and oxygen-15-water estimates of absolute myocardial perfusion in left ventricular ischemic dysfunction.

UNLABELLED: Measurements of resting myocardial blood flow (MBF) in patients with chronic left ventricular ischemic dysfunction by 15O-water with 13N-ammonia and PET have yielded conflicting results. The aim of this study was to perform a head-to-head comparison of both tracers in the same patient population and to answer the question of whether distinctive tracer properties account for differences in estimates of MBF in chronically dysfunctional myocardium by both tracers. METHODS: A total of 30 patients with chronic dysfunction of the anterior myocardial wall due to significant left anterior descending coronary artery disease underwent PET measurements of absolute MBF in the anterior wall by use of 15O-water and 13N-ammonia before coronary revascularization by either coronary artery bypass graft (n = 24) or percutaneous transluminal coronary angioplasty (n = 6). Improvement of regional contractile function was assessed by two-dimensional echocardiography at a mean of 7.5 +/- 2.1 mo after revascularization. As judged from the changes in anterior myocardial wall motion after revascularization, patients were considered to have either reversibly (n = 16) or persistently (n = 14) dysfunctional myocardium. Estimates of MBF by 15O-water and 13N-ammonia, obtained in every patient before revascularization, were compared among the two patient groups by use of previously validated methods. RESULTS: With 13N-ammonia, resting regional MBF was significantly higher in reversibly as opposed to persistently dysfunctional segments [84 +/- 8 versus 48 +/- 6 ml (min x 100 g)(-1), mean +/- s.e.m., p < 0.01]. By contrast, no such difference was found when using 15O-water to measure MBF [74 +/- 6 versus 86 +/- 9 ml (min x 100 g)(-1), p = ns]. This was mainly due to the fact that the perfusable tissue fraction (PTF), a fitted parameter of the 15O-water model, was significantly higher in reversibly as opposed to persistently dysfunctional segments (0.63 +/- 0.03 versus 0.50 +/- 0.03, p < 0.05). As a consequence, the 15O-water perfusable tissue index (PTI), which is the ratio of the PTF to the anatomical tissue fraction, was greater in reversibly dysfunctional as opposed to persistently dysfunctional segments (1.07 +/- 0.07 versus 0.79 +/- 0.05, p < 0.01). CONCLUSION: This study demonstrates significant differences in MBF estimates between 15O-water and 13N-ammonia in chronically dysfunctional ischemic myocardium. Our results indicate that the 15O-water method yields higher absolute MBF values than the 13N-ammonia approach. Our results also support the use of PTI as a marker of myocardial tissue viability.

Effect of aging on myocardial perfusion reserve.

UNLABELLED: Myocardial perfusion reserve (hyperemic divided by basal myocardial blood flow) describes vasodilator responsiveness of coronary-resistive vessels. The effect of aging and gender on myocardial perfusion reserve remains controversial. METHODS: We studied 56 normal volunteers (21 women, 35 men; aged 50 +/- 20 yr, range 21-86 yr) with 15O-water PET to measure myocardial blood flow during basal and hyperemic states with intravenous dipyridamole (0.56 mg/kg, n = 46) or adenosine (140 micrograms/kg/min, n = 10). For comparative analysis, patients were grouped according to age: < 30 yr (n = 11), 30-49 yr (n = 18), 50-69 yr (n = 15) and > or = 70 yr (n = 12). RESULTS: Overall, basal flow was 1.00 +/- 0.26 ml/min/g and hyperemic flow was 3.31 +/- 1.38 ml/min/g, resulting in a myocardial perfusion reserve of 3.38 +/- 1.35. There was an increase in basal flow with age (r = 0.45, p < 0.025), although hyperemic flow was only lower in patients > or = 70 yr, causing a significant reduction in myocardial perfusion reserve: 3.54 +/- 0.96 in < 30 yr, 4.23 +/- 1.35 in 30-49 yr, 3.51 +/- 1.21 in 50-69 yr and 1.94 +/- 0.46 in > or = 70 yr (p < 0.05 versus all groups < 70 yr). CONCLUSION: Myocardial blood flow during basal and hyperemia conditions are roughly comparable up to 60 yr of age. Above this age, there is significant increase in basal flow associated with an increase in systolic blood pressure. Above 70 yr, there is a significant reduction in hyperemic flow, and thus myocardial perfusion reserve independent of hemodynamic response to vasodilator stress.

Validation of radionuclide cardiac output measurements during exercise.

A nongeometric radionuclide technique with correction for attenuation was used for the determination of cardiac output and stroke volume during exercise in nine normal subjects and in ten hypertensive patients. Simultaneous reference stroke volume (range 48-159 ml) and cardiac output (range 3.6-23.8 l/min) measurements were obtained by the Fick method. Data were collected at rest and during 60 degrees upright exercise, at two or three levels of increasing severity. Three statistical measurements were used for the comparison of both methods: correlation, precision, and accuracy. Radionuclide and Fick cardiac output measurements (n = 67, rest and exercise data) correlated well (r = 0.90). For stroke volume, the correlation was less (r = 0.64); however, the precision or random variability of both methods was similar for stroke volume (radionuclide: 8 ml or 9%; Fick: 16 ml or 16%). The accuracy or systematic error was defined as the mean difference between radionuclide and Fick measurements. The radionuclide method underestimated the Fick measurements. The systematic error was 18 +/- 18 ml for stroke volume and 2.4 +/- 2.4 l/m for cardiac output. A similar comparison of both methods was made on the absolute changes of stroke volume (r = 0.61; range -19 + 70 ml) and cardiac output (r = 0.82; range +1.6 + 16.4 l/m) between rest and exercise. The precision of the two methods was similar; the systematic error was 1.9 +/- 2.2 l/m for cardiac output and 6 +/- 17 ml for stroke volume. Thus, in these two groups of patients, although radionuclide and Fick cardiac output measurements at rest and during exercise correlated well, the radionuclide values were systematically and significantly lower.

Relation of ultrasonic tissue characterization with integrated backscatter to contractile reserve in chronic left ventricular ischemic dysfunction.

Previous studies have shown that viable but stunned myocardium displays contractile reserve and exhibits cardiac cycle-dependent variations of integrated backscatter, whereas infarcted myocardium does not. The present study was designed to evaluate whether integrated backscatter imaging could be useful in identifying segments with recruitable inotropic reserve in patients with chronic left ventricular (LV) ischemic dysfunction. We studied 15 patients (mean age 59 +/- 10 years) with chronic coronary artery disease, anterior or inferior wall dysfunction, and depressed LV ejection fraction (35 +/- 12%), and 6 noncardiac control subjects (mean age 49 +/- 18 years). Cardiac cycle-dependent variations of integrated backscatter were measured in anterior and inferior segments during transesophageal echocardiography and compared with the contractile response (% wall thickening) of these segments to low doses of dobutamine (5 to 10 microg/kg/min). The average magnitude of cardiac cycle-dependent variations of integrated backscatter was greater among normally contracting segments of both patients and controls (5.67 +/- 0.88 and 5.64 +/- 2.26 dB, respectively, p = NS) than among dysfunctional segments (2.77 +/- 3.05 dB, p <0.01 vs control and remote segments). Dysfunctional segments were further categorized into those with and without dobutamine-induced contractile reserve. At baseline, systolic wall thickening was similar among segments responding to dobutamine than among those that did not (3.6 +/- 2.3% vs 2.9 +/- 1.6%, p = NS). During dobutamine, systolic wall thickening increased only in segments showing improvement in wall motion score (to 24.5 +/- 4.7%), whereas it remained unchanged in segments not responding to dobutamine (to 2.0 +/- 3.7%, p <0.01). The magnitude of resting cardiac cycle-dependent variations of integrated backscatter was larger in segments responding to dobutamine than in those with persistent dysfunction (5.31 +/- 2.06 vs 0.23 +/- 0.94 dB, p <0.01) and correlated significantly (r = 0.74, p <0.01) with systolic wall thickening during dobutamine. Our data demonstrate that resting cardiac cycle-dependent variations of integrated backscatter closely parallel contractile reserve in patients with chronic LV ischemic dysfunction. This suggests that tissue characterization with integrated backscatter could be a useful adjunct to the delineation of myocardial viability in these patients.

Effect of intracoronary thrombolytic therapy on exercise-induced ischemia after acute myocardial infarction.

Intracoronary streptokinase (SK) therapy increases vessel patency rate after acute myocardial infarction (AMI) and thus may lead to a greater exercise-induced myocardial ischemia. This hypothesis was tested in 39 patients enrolled in an angiographically randomized trial of intracoronary SK (19 treated with SK and 20 control subjects); all patients underwent thallium-201 scintigraphy at rest before acute angiography, as well as at rest and during stress 5 to 6 weeks after AMI. The patients were classified into 2 groups based on the presence (n = 13) or absence (n = 26) of complete obstruction of the infarct-related coronary artery at the end of the acute angiography. Semiquantitative score of myocardial thallium uptake was expressed as percent of maximal defect score. Thallium defect score at rest between admission and 5 to 6 weeks' study decreased from 10 +/- 16% units in the control group and from 23 +/- 14% units in the SK group (p = 0.01). This decrease was related to opening of the infarct-related artery (opening 23 +/- 16% vs occlusion 5 +/- 10%). The change in exercise-induced defect score was significantly (p = 0.01) larger in patients in the SK group (11 +/- 6% units) than in those in the control group (5 +/- 7% units). The perfusion defect during exercise was larger (p = 0.006) in patients with incomplete obstruction or reperfusion (10 +/- 6% units) than in patients with complete obstruction (3 +/- 7%). This difference was independent of the number of diseased coronary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved identification of coronary artery disease in patients with left bundle branch block by use of dobutamine stress echocardiography and comparison with myocardial perfusion tomography.

This study compared the efficacy of dobutamine stress testing using 2-dimensional echocardiography and perfusion tomography for the noninvasive identification of coronary artery disease (CAD) in patients with left bundle branch block (LBBB). Twenty-four patients with permanent, complete LBBB (11 with previous myocardial infarction) were studied prospectively with dobutamine echocardiography and perfusion tomography. The presence of > 50% luminal diameter coronary stenosis was compared with the presence of dobutamine-induced fixed or reversible perfusion defects, and with resting or dobutamine-induced abnormalities of wall thickening. For each test, the left anterior coronary artery territory was compared with the circumflex and/or right coronary artery. Significant CAD was found in the left anterior descending coronary artery in 12 patients; all (100%) were identified by perfusion imaging, and 10 (83%, p = NS) by 2-dimensional stress echocardiography. In the 12 patients without left anterior descending CAD, scintigraphy was also positive in all (specificity: 0%), and echocardiography in only 1 (specificity: 92%, p < 0.01). The diagnostic accuracy was 50% and 87% (p < 0.05), respectively. This low specificity of perfusion tomography was improved by requiring an associated apical defect to indicate left anterior descending CAD and was corrected by restricting the diagnosis of coronary disease to those patients with partially reversible defects. In the circumflex and/or right coronary artery territory, sensitivity and specificity were similar using both techniques. We conclude that dobutamine-stress echocardiography is a specific and accurate test for the noninvasive identification of CAD, even in the left anterior descending artery territory of patients with LBBB.