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The ability of the heart to maintain resting coronary flow constant when perfusion pressure changes is generally referred to as “coronary autoregulation.” This mechanism is essential because even a modest reduction in resting flow (10% to 20%) is associated with significant contractile

Biofeedback is a self-regulation therapy by which the patient learns how to optimize the functioning of his autonomic nervous system. It has been applied to patients with various cardiovascular disorders. The purpose of this study was to investigate the practical feasibility and the psychophysiological effects of biofeedback applied to heart rate variability (HRV biofeedback) in order to increase cardiac coherence in coronary artery disease (CAD) patients participating in a cardiac rehabilitation programme.In this randomised and controlled study, 31 CAD patients were randomly assigned to an experimental or to a control group. The experimental group participated in a programme of 10 sessions of cardiac coherence biofeedback training, in addition to the rehabilitation programme. The control group participated in the usual cardiac rehabilitation programme only. Physiological variables (systolic and diastolic blood pressure, SDNN) and psychosocial variables (anxiety, depression, type D personality) were measured at the start and at the end of the programme in both groups. Statistical comparisons assessed the inter and intra group differences. The small sample size precludes any firm conclusions concerning the effect of cardiac coherence biofeedback on physiological or psychological variables. However, we observed a significant increase of the percentage of cardiac coherence, in relation with an increased SDNN index.Our study demonstrated the practical feasibility of cardiac coherence biofeedback training in CAD patients. Further research is desirable to investigate the potential benefit of cardiac coherence biofeedback as an adjunct to stress management in cardiac rehabilitation.

BACKGROUND: Positron emission tomography scanners with retractable septa allow both 3-dimensional (3D) and 2-dimensional (2D) acquisition modes. The study aim was to directly compare 2D and 3D acquisition modes for the evaluation of absolute myocardial blood flow (MBF) over a wide range of flow values. METHODS AND RESULTS: Instrumentation was used in 4 dogs to reduce the left circumflex artery lumen by greater than 75%. During infusion of adenosine, MBF was measured with both 2D and 3D dynamic acquisition and both oxygen 15 water and nitrogen 13 ammonia. Injected activities were 333 MBq and 111 MBq for 2D acquisition and 3D acquisition, respectively. Data were reconstructed by analytic methods, and MBF was assessed by use of an 18-segment model. MBF values ranged from 0.4 to 5.8 mL x g(-1) x min(-1) with O-15 water and from 0.3 to 3.9 mL x g(-1) x min(-1) with N-13 ammonia. No significant differences were observed in absolute MBF values obtained with the 2 acquisition modes, regardless of the flow tracer used. Two-dimensionally and three-dimensionally derived MBF values were significantly strongly correlated by use of both O-15 water (y = 0.98x + 0.18, r = 0.87, P < .001) and N-13 ammonia (y = 0.99x + 0.09, r = 0.95, P < .001). CONCLUSION: Quantification of MBF in dogs with 3D positron emission tomography provides results similar to those obtained with the 2D technique, despite a lower activity being injected.

BACKGROUND: After heart transplantation, the transplanted denervated heart displays both an exaggerated chronotropic and an exaggerated inotropic response to circulating catecholamines. This study assessed whether denervated transplanted hearts also display an exaggerated energetic response when challenged with dobutamine. METHODS AND RESULTS: A total of 18 heart transplant recipients and 14 normal volunteers underwent measurements of myocardial oxygen consumption (MVO2), external work (EW), and pressure-volume area (PVA), at rest and during infusion of dobutamine. At rest, calculated myocardial (PVA/MVO2) and mechanical (EW/MVO2) efficiencies were similar among transplant recipients and normal volunteers. During low-dose dobutamine infusion (8 microg/kg/min), transplant recipients exhibited a larger increase in heart rate (to 126 +/- 14 vs 87 +/- 26 beats/min, p < 0.001) and MVO2 (to 269 +/- 43 vs 233 +/- 19 J/min/100g, p < 0.05) and a smaller increase in EW (64 +/- 18 vs 72 +/- 13 J/min/100g, p < 0.05) and PVA (70 +/- 16 vs 81 +/- 13 J/min/100g, p < 0.05) than did normal volunteers. As a result, both myocardial (26 +/- 4 vs 35 +/- 4%, p < 0.05) and mechanical (23 +/- 4 vs 30 +/- 4%, p < 0.001) efficiencies were lower during dobutamine infusion in transplant recipients than in normal volunteers. During the infusion of a higher dose of dobutamine (19 microg/kg/min), the chronotropic and inotropic responses of heart transplant recipients were even more exaggerated. The fall in myocardial efficiency induced by dobutamine correlated with the increase in heart rate (r = -0.58) and could be reproduced in normal volunteers by coadministration of atropine. CONCLUSIONS: Transplant recipients exhibit a larger fall in contractile efficiency and a larger oxygen-wasting effect during dobutamine infusion than do normal volunteers. Because normal volunteers pre-medicated with atropine presented with a similar increase in heart rate and a similar fall in efficiency, the exaggerated energetic response of transplanted hearts to dobutamine likely resulted from the same mechanisms as their chronotropic supersensitivity, i.e., the loss of inhibitory parasympathetic innervation.

It is now widely accepted that patients with chronic coronary artery disease can experience prolonged regional ischemic dysfunction that does not necessarily arise from irreversible tissue damage and, to some extent, can be reversed by restoration of blood flow. Recent clinical and experimental data suggest that this form of chronic but reversible left ventricular dysfunction represents a complex, progressive, and dynamic phenomenon. The initial stages of dysfunction are probably caused by chronic stunning. They are characterized by normal resting perfusion but reduced flow reserve, mild myocyte alterations, maintained membrane integrity (allowing the transport of both thallium and glucose), preserved capacity to respond to an inotropic stimulus, and no or little tissue fibrosis. After revascularization, functional recovery will probably be rapid and complete. On the other hand, the more advanced stages of dysfunction likely correspond to chronic hibernation. They usually are associated with reduced rest perfusion; increased tissue fibrosis; more severe myocyte alterations (degeneration[?], apoptosis); and a decreased ability to respond to inotropic stimuli. Nonetheless, membrane function and glucose metabolism may long remain preserved. After revascularization, functional recovery, if any, will probably be quite delayed and mostly incomplete.

OBJECTIVE—To determine whether myocardial contrast echocardiography (MCE) following intravenous injection of perfluorocarbon microbubbles permits identification of resting myocardial perfusion abnormalities in patients who have had a previous myocardial infarction. PATIENTS AND INTERVENTIONS—22 patients (mean (SD) age 66 (11) years) underwent MCE after intravenous injection of NC100100, a novel perfluorocarbon containing contrast agent, and resting 99mTc sestamibi single photon emission computed tomography (SPECT). With both methods, myocardial perfusion was graded semiquantitatively as 1 = normal, 0.5 = mild defect, and 0 = severe defect. RESULTS—Among the 203 normally contracting segments, 151 (74%) were normally perfused by SPECT and 145 (71%) by MCE. With SPECT, abnormal tracer uptake was mainly found among normally contracting segments from the inferior wall. By contrast, with MCE poor myocardial opacification was noted essentially among the normally contracting segments from the anterior and lateral walls. Of the 142 dysfunctional segments, 87 (61%) showed perfusion defects by SPECT, and 94 (66%) by MCE. With both methods, perfusion abnormalities were seen more frequently among akinetic than hypokinetic segments. MCE correctly identified 81/139 segments that exhibited a perfusion defect by SPECT (58%), and 135/206 segments that were normally perfused by SPECT (66%). Exclusion of segments with attenuation artefacts (defined as abnormal myocardial opacification or sestamibi uptake but normal contraction) by either MCE or SPECT improved both the sensitivity (76%) and the specificity (83%) of the detection of SPECT perfusion defects by MCE. CONCLUSIONS—The data suggest that MCE allows identification of myocardial perfusion abnormalities in patients who have had a previous myocardial infarction, provided that regional wall motion is simultaneously taken into account. Keywords: myocardial contrast echocardiography; NC100100; single photon emission computed tomography; perfusion

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.

OBJECTIVES: This study was designed to analyze the effects of acute angiotensin-converting enzyme (ACE) inhibition on myocardial blood flow (MBF) in control and ischemic regions. BACKGROUND: Although animal studies indicate an improvement of MBF to ischemic regions after ACE inhibition, this effect has not been conclusively demonstrated in patients with coronary artery disease. METHODS: Myocardial blood flow was analyzed in ischemic and nonischemic regions of 10 symptomatic patients with coronary artery disease using repetitive [15O] water positron emission tomography at rest and during maximal dobutamine stress before and after ACE inhibition with quinaprilat 10 mg IV. To exclude the possibility that repetitive ischemia may cause an increase in MBF, eight patients underwent the same protocol without quinaprilat (placebo patients). RESULTS: Rate pressure product in control and quinaprilat patients was comparable. In placebo patients, repetitive dobutamine stress did not change MBF to ischemic regions (1.41 ± 0.17 during the first stress vs. 1.39 ± 0.19 ml/min/g during the second stress, p = 0.93). In contrast, MBF in ischemic regions increased significantly after acute ACE inhibition with quinaprilat during repetitive dobutamine stress (1.10 ± 0.13 vs. 1.69 ± 0.17 ml/min/g, p < 0.015). Dobutamine coronary reserve in ischemic regions remained unchanged in placebo patients (1.07 ± 0.11 vs. 1.10 ± 0.16, p = 0.92), but increased significantly after quinaprilat (0.97 ± 0.10 vs. 1.44 ± 0.14, p < 0.002). Total coronary resistance decreased after ACE inhibition (123 ± 19 vs. 71 ± 10 mm Hg · min · g/ml, p < 0.02). CONCLUSIONS: Angiotensin-converting enzyme inhibition by quinaprilat significantly improves MBF to ischemic regions in patients with coronary artery disease.

Cardiovascular mortality is falling in most industrialised nations. Primarily responsible for this encouraging trend are preventive measures such as risk-factor modification but improved medical and surgical management have helped too. Clinical decision making in the patient with coronary heart disease demands techniques that not only describe coronary anatomy but also provide functional indices for early detection and to monitor the severity and extent of disease. Nuclear medicine methods can characterise non-invasively myocardial function, perfusion, and metabolism. Novel radiopharmaceuticals, improvements in imaging equipment, and extensive validation have contributed to the growing clinical acceptance of these techniques and to their cost-effective integration in the workup of patients with cardiovascular disease.

Although exercise intolerance is a cardinal symptom of patients with dilated cardiomyopathy (DC) and heart failure, the factors that limit exercise capacity in these patients remain a matter of debate. To assess the contribution of left ventricular (LV) diastolic filling to the variable exercise capacity of patients with DC, we studied 47 patients (60 +/- 12 years) with DC in stable mild-to-moderate heart failure with a mean LV ejection fraction of 28%. Exercise capacity was measured as total body peak oxygen consumption (VO2) during symptom-limited bicycle (10 W/min) and treadmill (modified Bruce protocol) exercise. LV systolic function and diastolic filling were assessed at rest before each exercise by M-mode, Doppler echocardiography, and radionuclide ventriculography. As expected, treadmill exercise always yielded higher peak VO2 than bicycle exercise (21 +/- 6 vs 18 +/- 5 ml/kg/min, range 12 to 35 and 7 to 30 ml/kg/min, respectively, p

Dipyridamole single-photon emission computed tomography (SPECT) has a high negative predictive value for perioperative cardiac events, but events are infrequent in patients with a positive test. In contrast, dipyridamole echocardiography is more selective for detection of multivessel disease and thus may have a greater specificity for cardiac events. We therefore compared the ability of dipyridamole SPECT and echocardiography to predict perioperative and long-term cardiac events in 133 patients referred for vascular surgery, The group was also evaluated based on clinical features and election fraction. Four patients had surgery cancelled because of high risk and were excluded from further analysis. Among the 129 remaining patients, 21 had coronary revascularization (n = 12) or an early cardiac end point (n = 9). The sensitivity of SPECT for the prediction of early events (90%) was not significantly different from that of echocardiography (66%, p = NS). The specificity of SPECT (68%) was less than that of echocardiography (88%, p < 0.001%), as was the accuracy (72% vs 84%, p = 0.02). These findings were replicated after exclusion of patients with treatment end points. During long-term follow-up, 12 patients experienced greater than or equal to 1 event: 6 died from cardiac causes, 4 underwent revascularization, and 3 had myocardial infarction. Thus, the specificity of SPECT and echocardiography for late events were 58% and 80%, respectively (p < 0.001). The 3-year survival of patients without ischemia during echocardiography or at SPECT was not different (93% vs 94%, p = NS). (C) 1998 by Excerpta Medica, Inc.

Background —Microvascular obstruction within an area of myocardial infarction indicates worse functional recovery and a higher risk of postinfarction complications. After prolonged coronary occlusion, contrast-enhanced MRI identifies myocardial infarction as a hyperenhanced region containing a hypoenhanced core. Because the time course of microvascular obstruction after infarction/reperfusion is unknown, we examined whether microvascular obstruction reaches its full extent shortly after reperfusion or shows significant progression over the following 2 days. Methods and Results —Seven dogs underwent 90-minute balloon occlusion of the left anterior descending coronary artery (LAD) followed by reflow. Gadolinium-DTPA–enhanced MRI performed at 2, 6, and 48 hours after reperfusion was compared with radioactive microsphere blood flow (MBF) measurements and myocardial staining to define microvascular obstruction (thioflavin S) and infarct size (triphenyltetrazolium chloride, TTC). The MRI hypoenhanced region increased 3-fold during 48 hours after reperfusion (3.2±1.8%, 6.7±4.4%, and 9.9±3.2% of left ventricular mass at 2, 6, and 48 hours, respectively, P r =0.99 and thioflavin S, r =0.93). MRI hyperenhancement also increased (21.7±4.0%, 24.3±4.6%, and 28.8±5.1% at 2, 6, and 48 hours, P r =0.92). The microvascular obstruction/infarct size ratio increased from 13.0±4.8% to 22.6±8.9% and to 30.4±4.2% over 48 hours ( P =0.024). Conclusions —The extent of microvascular obstruction and the infarct size increase significantly over the first 48 hours after myocardial infarction. These results are consistent with progressive microvascular and myocardial injury well beyond coronary occlusion and reflow.

Purpose: Heart failure is the final common pathway for most forms of heart disease, and is characterized by a reduced energy status. Myocardial oxygen consumption (MV02) is closely related to the main determinants of systolic function (heart rate, pressure and contractility). The aim of the study was to compare myocardial blood flow, metabolism and mechanical efficiency in rapid pacing induced heart failure in dogs. Methods: 5 dogs were paced for 3 weeks at 240 bpm, with regular follow up of hemodynamic characteristics. Coronary blood flow and oxidative metabolism were evaluated with [15O] water and [11C]acetate clearance respectively, in baseline conditions (B) and after 3 weeks of rapid pacing (3 wk RP) using positron emission tomography. Results: Three weeks of rapid pacing in a dog model resulted in a severely depressed left ventricular function (LV dP/dtmax 3698 ± 314 mmHg (B) vs. 1365 ± 103 mmHg (3 wk RP)). On the contrary myocardial blood flow 1.29 ± 0.11 ml/min/g (B) vs. 1.05 ± 0.07 ml/min/g (3 wk RP) and oxidative metabolism 0.178 ± 0.1 min-1 (B) vs. 0.161 ± 0.1 min-1 (3 wk RP) remained essentially unchanged, indicating a reduced efficiency and a change in O2 utilization. Conclusions: Heart failure induced by rapid ventricular pacing in dogs provokes a clearly reduced mechanical efficiency, illustrating the occurrence of a metabolic remodeling in heart failure induced by rapid pacing.

Objective: Our objective was to investigate the influence of preoperative myocardial ultrastructure and metabolism on recovery of contractile function after coronary artery bypass grafting in patients with coronary artery disease and left ventricular dysfunction. Methods: Dynamic positron emission tomography with 13N-ammonia and 18F-deoxyglucose was used to assess myocardial perfusion and glucose uptake in 53 patients scheduled for coronary revascularization because of coronary artery disease and left ventricular dysfunction. The degree of tissue fibrosis and the presence of potentially reversible alterations of cardiomyocytes (loss of myofilaments and accumulation of glycogen) were quantified from transmural biopsy specimens. These were harvested from the center of the dysfunctional area during the operation and analyzed with a light microscope. The recovery of contractile performance was assessed from the changes in left ventricular function at contrast ventriculography or echocardiography before and 6 months after the operation. Results: According to postoperative changes in regional wall motion, left ventricular function was considered to have improved in 34 patients, whereas dysfunction persisted in 19 patients. In patients with improved wall motion, ejection fraction rose by 12% and end-systolic volume decreased by 28%. By contrast, in patients with persistent dysfunction, ejection fraction decreased by 6% and end-systolic volume increased by 25%. Before revascularization, myocardium with reversible dysfunction displayed higher levels of absolute myocardial blood flow, higher myocardial glucose uptake, less tissue fibrosis, and more altered cardiomyocytes than myocardium with persistent dysfunction. Significant correlations were found between regional blood flow and the surface of the biopsy specimen covered by fibrosis, as well as between glucose uptake and the density of altered cardiomyocytes. Conclusion: In patients with left ventricular ischemic dysfunction, the recovery of regional and global left ventricular function after surgical revascularization is associated with higher preoperative blood flow and glucose uptake, with less tissue fibrosis and a higher amount of viable cardiomyocytes in the dysfunctional area. The current study thus confirms the value of noninvasive preoperative metabolic imaging for identification of residual viable myocardium and for prediction of the functional outcome after revascularization. (J Thorac Cardiovasc Surg 1997;113:379-89)

Background Previous work has documented that dysfunctional noninfarcted collateral-dependent myocardium, a condition typical of myocardial hibernation, exhibited almost normal resting perfusion. The present study was designed to test whether these observations could be extended to unselected patients with chronic dysfunction and a previous infarction. Methods and Results Dynamic positron emission tomographic imaging with [ 13 N]ammonia and [ 18 F]fluorodeoxy-glucose (FDG) to assess myocardial perfusion and glucose uptake was performed in 39 patients with chronic anterior wall dysfunction undergoing coronary revascularization. Left ventricular function was evaluated by echocardiography before (at rest and during low-dose dobutamine infusion) and 5 months after revascularization. At follow-up, wall motion was improved in 24 patients and unchanged in 15 patients. Before revascularization, absolute myocardial blood flow was higher (84±27 versus 60±26 mL·min − 1 ·100 g − 1 , P =.007) in reversibly compared with persistently dysfunctional segments. In segments with reversible dysfunction, values of myocardial blood flow were similar to those in the remote segments of the same patients or in anterior segments of normal volunteers. During glucose clamp, FDG uptake was higher (69±17% versus 49±18%, P − 1 ·100 g − 1 , P =NS) in reversibly compared with persistently dysfunctional segments. A flow-metabolism mismatch was present in 18 of 24 reversibly injured but absent in 10 of 15 persistently dysfunctional segments. With dobutamine, wall motion improved in 17 of 24 reversibly dysfunctional segments and did not change in 13 of 15 segments with persistent dysfunction. Conclusions This study indicates that chronic but reversible ischemic dysfunction is associated with almost normal resting myocardial perfusion, with maintained FDG uptake, and with recruitable inotropic reserve. These data support the contention that chronic hibernation is not the consequence of a permanent reduction of transmural myocardial perfusion at rest.

Modern therapy of coronary artery disease (CAD) increasingly involves interventional strategies aimed at restoring blood flow to the ischemic myocardium. The emergence of coronary artery bypass surgery, percutaneous transluminal coronary angioplasty, and more recently thrombolytic therapy, has helped to change the natural course of ischemic heart disease and contribute to the overall reduction in the mortality from both acute myocardial infarction and chronic CAD. Presumably, the beneficial effects of revascularization result from improving blood supply to dysfunctional but viable regions with subsequent improvement in regional and global left ventricular function. Over the past decade, several approaches have been proposed to predict the reversibility of left ventricular dysfunction after coronary revascularization. For the most part, these methods rely on assessment of basic cellular mechanisms that are known to play a central role in the recovery of systolic function after coronary revascularization. These include sufficient resting perfusion to provide metabolic fuels and to allow wash-out of toxic metabolites, maintain membrane integrity (which includes the ability to generate transmembrane ionic gradients and to transport energy providing substrates), preserve metabolic machinery (to allow glucose, fatty acid and oxygen consumption), and recruitable inotropic reserve. Among the available modalities, thallium imaging, positron emission tomography, and low-dose dobutamine echocardiography are currently the most frequently used in the clinical setting. All allow prediction of reversible dysfunction with a high degree of sensitivity (greater than 80%). They seem to vary, however, in terms of specificity, thallium imaging showing the lowest (50-55%) and dobutamine echocardiography the highest (80-85%) specificity. New promising modalities, such as FDG or MIBI SPECT imaging, contrast echocardiography and integrated backscatter imaging are just ahead and will likely strengthen further our ability to identify jeopardized but viable myocardium.

Background Both thallium imaging and low-dose dobutamine echocardiography have been proposed to predict the reversibility of left ventricular (LV) dysfunction in patients with coronary disease. The present study was designed to evaluate whether the use of these techniques during the preoperative assessment of coronary patients with depressed LV function can improve our ability to identify those likely to have improved LV function after surgery. Methods and Results Forty consecutive patients (age, 60±10 years) with coronary disease and an ejection fraction ≤35% underwent dobutamine echocardiography (10 μg/kg per minute) and exercise-redistribution-reinjection thallium single photon emission computed tomography (SPECT) before coronary revascularization by bypass surgery (n=33) or angioplasty (n=7). Recovery of LV function was evaluated by echocardiography 5.3±2.4 months after revascularization. According to the changes in end-systolic volume and ejection fraction after revascularization, the patients were categorized into groups with (n=19) and without (n=21) postoperative functional improvement, defined as a >5% increase in ejection fraction and >10 mL decrease in end-systolic volume. Before revascularization, patients with improved postoperative function had smaller end-diastolic volume and less wall motion abnormalities than those with persistent dysfunction. They also showed greater improvement of wall motion score with dobutamine (6.1±2.4 versus 1.8±4.2 grades, P P =.04). Discriminant analysis selected the improvement in wall motion score with dobutamine and baseline end-diastolic volume as independent predictors of postoperative recovery. Consideration of both parameters allowed prediction of functional outcome in 84% of the patients with and 81% of those without postoperative improvement. Conclusions Among the parameters commonly available before surgery in coronary patients with depressed LV function, the maintenance of significant inotropic reserve, the severity of LV remodeling, and the magnitude of the perfusion defect after exercise can predict the reversal of LV dysfunction after revascularization.

The contribution of PET viability studies to the understanding of recoverable ischemic left ventricular dysfunction cannot be overemphasized. However, it is uncertain whether FDG used with PET will continue to play a pivotal role in the clinical evaluation of all patients with poor function. Several competitive approaches became available over the recent years, perhaps equally effective. Currently, no data from appropriate prospective studies comparing cost, effectiveness and impact on patient prognosis of the different approaches are available.

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.

Glucose metabolism has been studied in the auditory cortex of human subjects with deafness of early onset, and compared to normal subjects with ears plugged. The metabolism in the auditory cortex and in the association auditory cortex was higher in deaf subjects than in normal subjects. This result is compared to similar observations that we made previously in the visual cortex of human subjects with blindness of early onset.

OBJECTIVES. This study was conducted to examine the efficacy of dobutamine stress two-dimensional echocardiography and perfusion scintigraphy for the detection of coronary artery disease in routine practice, to establish the causes of erroneous results and to derive appropriate criteria for the selection of either or both tests. BACKGROUND. Dobutamine stress combined with echocardiography or perfusion scintigraphy may be used to detect coronary artery disease. Although both imaging approaches have demonstrated similar levels of accuracy, it is not known whether there may be particular indications for the use of one or the other technique or a rationale for their combination. METHODS. Two hundred seventeen patients without previous infarction were studied prospectively with dobutamine stress echocardiography and technetium-99m methoxy isobutyl nitrile (sestamibi) single-photon emission computed tomography at the time of diagnostic coronary angiography. The presence of coronary stenoses of > or = 50% diameter was compared with the presence of rest or stress-induced abnormalities of perfusion and regional function. The extent of these abnormalities was correlated with an equivalent score of extent of angiographic disease. RESULTS. Significant coronary artery disease was found in 142 patients; 102 (72%) were identified by dobutamine echocardiography and 108 (76%, p = NS) by perfusion imaging. In 75 patients without significant disease, the specificity of dobutamine echocardiography was 83% compared with 67% for scintigraphy (p = 0.05). Echocardiographic sensitivity was lower in patients unable to complete the test because of side effects (n = 64) than in the remainder (59% vs. 77%, p = 0.02); this influence was less apparent with scintigraphy (71% vs. 78%, p = NS). Selective use of scintigraphy in the 31 patients with a negative submaximal stress echocardiogram led to a sensitivity of 80% for this combination. Patients with left ventricular hypertrophy accounted for most of the difference in specificity between echocardiography and scintigraphy (94% vs. 59%, p = 0.02). Their respective accuracies were 76% and 73%. CONCLUSIONS. Dobutamine stress echocardiography and perfusion scintigraphy have equivalent accuracy. In patients with left ventricular hypertrophy, echocardiography appears to be the test of choice. Selective use of sestamibi scintigraphy in patients with a negative submaximal echocardiogram enhances the accuracy of stress echocardiography alone.

To test the ability of ketone bodies to inhibit myocardial fatty acid oxidation in vivo, the myocardial clearance kinetics of [1–11C]palmitate was assessed with positron emission tomography in six fasted volunteers and six instrumented dogs, studied repeatedly before and during infusion of 3-hydroxybutyrate (17 mumol.kg-1 x min-1). With the use of multiexponential fitting of tissue time-activity curves, the size, half time (T1/2), and index of the early rapid phase of 11C myocardial clearance, reflecting palmitate oxidation, were calculated. In humans, the relative size (-28%, P < 0.001) and index (-37%, P < 0.01) of the early rapid phase decreased significantly during infusion of 3-hydroxybutyrate, consistent with decreased fatty acid oxidation. Paradoxically, T1/2 decreased from 10.1 +/- 1.6 to 7.4 +/- 1.1 min (P < 0.01). To elucidate possible mechanisms, multiple coronary arteriovenous samples were obtained from the dogs to assess the efflux of oxidized and nonmetabolized tracer. Infusion of 3-hydroxybutyrate resulted in decreased myocardial [11C]CO2 production (-40%, P < 0.05) and reduced palmitate retention (-38%, P < 0.05). In three dogs, the arteriovenous difference in radiolabeled palmitate became negative 10 min after injection, indicating backdiffusion of nonmetabolized tracer from the myocardium. Thus a steady-state infusion of 3-hydroxybutyrate, resulting in physiological plasma levels, alters [1-11C]palmitate kinetics in vivo by decreasing myocardial long-chain fatty acid oxidation and by increasing backdiffusion of nonmetabolized tracer.

BACKGROUND The mechanisms of action of exercise-simulating and vasodilator stressors support their combination with imaging techniques that evaluate left ventricular function and perfusion, respectively. However, reported accuracies of either pharmacological stress together with two-dimensional echocardiography (2DE) or single photon emission computed tomography (SPECT) of myocardial perfusion are similar. The purpose of this study was to establish the optimal stress for each imaging technique by comparing the results of digitized 2DE and 99mTc-methoxyisobutyl isonitrile (MIBI) SPECT using both dobutamine and adenosine stresses in the same patients and conditions. METHODS AND RESULTS Ninety-seven consecutive patients without evidence of previous infarction undergoing coronary angiography for clinical indications were studied prospectively. Dobutamine was infused during clinical, ECG, and echocardiographic monitoring in dose increments from 5 to 40 micrograms.kg-1.min-1. Adenosine was infused under the same conditions in doses of 0.10, 0.14, and 0.18 mg.kg-1.min-1. For each protocol, the end points were achievement of peak dose, development of severe ischemia, or intolerable side effects. At peak stress, 20 mCi of MIBI was injected, and SPECT imaging was performed 2 hours later; abnormal poststress images were compared with resting SPECT: Digitized 2DE images were compared qualitatively before, during, and after stress in a cine-loop display. Significant coronary disease (n = 59 patients) was defined by the quantification of > 50% stenosis in a major epicardial vessel. The sensitivity of adenosine 2DE was 58%, less than those of adenosine MIBI (86%, p = 0.001), dobutamine 2DE (85%, p = 0.001), and dobutamine MIBI (80%, p = 0.01). Their respective specificities were 87%, 71%, 82%, and 74% (p = NS). The accuracy of adenosine 2DE was 69%, compared with 80% for adenosine MIBI (p < 0.001), 84% for dobutamine 2DE (p = 0.001), and 77% for dobutamine MIBI (p = 0.005); the latter three did not differ significantly in either sensitivity or accuracy. CONCLUSIONS This prospective, direct comparison of alternative pharmacological stresses in patients without myocardial infarction shows vasodilator stress scintigraphy and dobutamine stress echocardiography and scintigraphy to share equivalent levels of sensitivity. All three are significantly more sensitive than adenosine stress echocardiography. Dobutamine stress may be used for wall motion or perfusion imaging, but adenosine stress is best combined with perfusion scintigraphy.

As a result of improved anesthetic, surgical, and myocardial protection techniques, the surgical risks of performing coronary artery bypass graft (CABG) in these patients have decreased significantly between 11 and 16%, to less than 6%. Myocardial revascularization has subsequently become a valid treatment option in selected patients with observed survival benefits compared to medical therapy, and in some cases, improvement in symptoms and functional status.

BACKGROUND Diagnostic accuracy of the exercise electrocardiogram in women has been shown to be limited for the detection of coronary artery disease. New diagnostic methods based on computer analysis of the exercise electrocardiogram and multivariate analysis have improved the diagnostic value of exercise testing in male subjects. The aim of the present study was to assess whether the diagnostic value of exercise testing can be enhanced in women by using multivariate analysis of exercise data. METHODS AND RESULTS Between 1978 and 1984, 135 infarct-free women underwent exercise testing and coronary angiography. Significant coronary artery disease was present in 41% of the patients. In this first group, maximal exercise variables were submitted to a stepwise logistic analysis. Work load, heart rate, and ST60X were selected to build a diagnostic model. The model was tested in a second group of 115 catheterized women (significant coronary artery disease in 47%) and of 76 volunteers. We compared the present model with conventional analysis of the exercise electrocardiogram, with ST changes adjusted for heart rate, and with a previously described analysis. In both groups, sensitivity was better with the present model (66% and 70%) than by conventional (68% and 59%) and by the previously described analysis (57% and 44%) without a loss of specificity (85% and 93%). Receiver-operator characteristic curves showed also a better diagnostic accuracy with the present model. CONCLUSIONS In women, logistic analysis of exercise variables improves the diagnostic value of exercise testing. It yields a significantly better sensitivity without a loss of specificity.

To determine the effects of a moderately prolonged exercise on left ventricular systolic performance, 23 healthy male subjects, aged 18 to 51 yr (mean 37 yr) were studied. The subjects exercised first on a treadmill (brief exercise) and completed, on a separate day, a 20-km run. M-mode, two-dimensional, and Doppler echocardiography, as well as calibrated carotid pulse tracings, were obtained at rest and immediately on completion of both brief and prolonged exercise. Left ventricular systolic function was assessed by end-systolic stress-shortening relationships. Heart rate increased similarly after brief and prolonged exercise (+30%). Mean arterial pressure decreased from 99 +/- 7 to 92 +/- 8 mmHg (P less than 0.001) after prolonged exercise, but it remained unchanged after brief exercise. Left ventricular end-diastolic volume was decreased after prolonged exercise (130 +/- 23 vs. 147 +/- 18 ml at rest, P less than 0.01). Both ejection fraction and rate-adjusted mean velocity of fiber shortening decreased after prolonged exercise [from 67 +/- 5 to 60 +/- 6% (P less than 0.001) and from 1.12 +/- 0.2 to 0.91 +/- 0.2 cm/s (P less than 0.001), respectively] despite a lower circumferential end-systolic wall stress (133 +/- 23 vs. 152 +/- 20 g/cm2). The relationship between ejection fraction (or mean velocity of fiber shortening adjusted for heart rate) and end-systolic wall stress was displaced downward on race finish (P less than 0.05). These changes were independent of the changes in left ventricular end-diastolic volume and hence those in preload. The data suggest that moderately prolonged exercise may result in depressed left ventricular performance in healthy normal subjects.

A prospective study of 111 patients who underwent repeat coronary angiography and exercise thallium-201 scintigraphy 6 ± 2 months after complete revascularization by percutaneous transluminal coronary angioplasty was performed to assess whether clinical, procedure-related and postangioplasty exercise variables yield independent information for the prediction of angiographic restenosis after angioplasty. Complete revascularization was defined as successful angioplasty of one or more vessels that resulted in no residual coronary lesion with >50% diameter stenosis. Restenosis was defined as a residual stenosis at the time of repeat angiography of >50% of luminal diameter. Restenosis occurred in 40% of the patients.The 111 patients were randomly subdivided into a learning group (n = 84) and a testing group (n = 27). A logistic discriminant analysis was performed in the learning group and the logistic model was used to estimate a logistic probability of restenosis. This probability of restenosis was validated in the testing group. In the learning group of 84 patients univariate analysis of 39 factors revealed 8 factors related to restenosis: recurrence of angina (p < 0.0001), postangioplasty abnormal finding on exercise thallium-201 scintigram (p < 0.0001), exercise thallium-201 scintigram score (p < 0.0001), difference between exercise and rest ST segment depression (p < 0.001), postangioplasty exercise ST segment depression (p < 0.001), absolute postangioplasty stenosis diameter (p < 0.003), postangioplasty exercise work load (p < 0.03) and postangioplasty exercise heart rate (p < 0.05).Multivariate analysis revealed four factors independently related to increased risk of restenosis in the following order of importance: recurrence of angina (p < 0.0001), abnormal finding on exercise thallium-201 scintigram (p < 0.001), absolute postangioplasty stenosis diameter (p < 0.002) and exercise ST segment depression (p < 0.01). With use of a logistic model these predictors of restenosis were weighed into a restenosis probability score (high, intermediate and low risk) that was validated in the testing group. The predictive value for restenosis in the high risk group (probability >80%) was 100% and the predictive value for no restenosis in the low risk group (probability

To determine whether exercise testing and thallium scintigraphy provide additional prognostic information in symptomatic patients undergoing catheterization, we studied 432 consecutive male patients without a previous myocardial infarction by means of an exercise test, thallium scintigraphy and catheterization. The follow-up period was 46 +/- 24 months (from 12 to 96). Events were defined as death (27 patients), nonfatal myocardial infarction (occurring in 27 patients) or late (greater than 60 days after test) surgery or dilatation (needed in 45 patients). The 5 year survival rate was 89% and the event-free rate was 72%. History, noninvasive and invasive variables were submitted to a stepwise Cox regression analysis. By multivariate analysis, the significant variables related to death were the number of diseased vessels and exercise workload; the selected variables for all cardiac events were the number of diseased vessels; the score at thallium exercise testing and exercise workload. Among the subgroups of 337 coronary patients, the predictive variables for death were exercise workload and the number of diseased vessels. For all cardiac events, the selected variables were the number of diseased vessels, the score of defects during thallium exercise and exercise workload. Thus, in patients without a previous myocardial infarction, noninvasive variables do provide prognostic information which is not available either from the history or from catheterization.

OBJECTIVE: We determined the value of attenuation correction (AC) of myocardial perfusion estimation with (99m)Tc-MIBI SPECT in overweight patients by comparison of uncorrected (filtered back-projection (FBP) and corrected (an iterative algorithm with a measured attenuation coefficients map (FL-AC)) (99m)Tc-MIBI relative uptake to perfusion data obtained in the same patients with NH3 PET. In addition, the impact of attenuation correction for the assessment of myocardial viability with (99m)Tc-MIBI SPECT was determined using FDG PET as the reference method. METHODS: Thirty consecutive overweight patients (BMI=28+/-4) with left ventricular dysfunction underwent a resting (99m)Tc-MIBI SPECT and a PET study (NH3 and FDG). (99m)Tc-MIBI SPECT scans were reconstructed without attenuation correction (FBP) and with attenuation correction (FL-AC). The left ventricle was divided into 16 segments, in which the relative uptake was quantified using circumferential profiles. A relative uptake > or = 60% was considered consistent with viable myocardium for FDG and MIBI. RESULTS: The absolute difference between (99m)Tc-MIBI SPECT and NH3 PET uptakes was less pronounced in the inferior (12+/-10% vs. 17+/-12%, P

Background: The purpose of this study was to examine the ability of real-time myocardial contrast echocardiography (MCE) with power modulation to quantitate myocardial blood flow (MBF) and to assess its transmural distribution in open-chest dogs undergoing partial or total coronary stenoses. Methods and Results: MBF was measured in 12 dogs instrumented with a cuff occluder around the left anterior descending coronary artery at rest, during partial coronary stenosis (during infusion of adenosine), and during coronary occlusion. The MCE-derived rate of microbubble velocity, beta, and myocardial blood volume, A, were obtained by curve fitting of videointensity versus time plots, after the transient destruction of microbubbles by high-energy ultrasound. The data were compared with MBF measured with radiolabeled microspheres. Significant correlations were found between radiolabeled microsphere-derived MBF and both beta (r = 0.93) and the product of A x beta (r = 0.91). MCE beta reserve also correlated well with microsphere-derived flow reserve. Comparing endocardial/epicardial MCE ratios and microsphere-derived MBF ratios, significant correlation was also found between endomicropsheres/epimicrospheres MBF ratio and both endo/epi beta (r = 0.90) and endo/epi A x beta (r = 0.88). Conclusions: Real-time power modulation MCE allows for an accurate quantification of MBF and of its transmural distribution in open-chest dogs undergoing partial or total coronary stenoses.

Intermittent harmonic imaging with contrast is increasingly used to detect perfusion defects in patients with coronary disease. To achieve this, image homogeneity and the ability to visualize segments on the lateral and distal portions of the imaging field are important. The objective of this study was to evaluate whether the use of specific postprocessing algorithms, such as background subtraction with color coding and parametric display, allows for improved image homogeneity compared with conventional intermittent second harmonic imaging. For this purpose, 20 participants who were free of cardiac abnormalities and in whom myocardial perfusion should by definition be homogeneously distributed, underwent contrast echocardiography during the constant intravenous infusion of 1.0 +/- 0.3 mL/min of perfluorocarbon-enhanced sonicated dextrose albumin. End-systolic ECG-triggered images were obtained from the apical 4-chamber view at pulsing intervals of 300-ms 1, 3, 5, and 8 cardiac cycles. For analysis, each set of images was aligned, averaged, background subtracted, and color coded. Pulsing intervals versus videointensity plots were then generated for each pixel in the images and fitted to an exponential function to produce parametric images of beta (an index of microbubble velocity) and A (a measure of myocardial blood volume). The heterogeneity of the contrast effect was evaluated by computing the coefficients of variation in each image. Contrast heterogeneity was >20% with all 4 methods. However, it was greater in gray-scale second harmonic (39 +/- 13%) and color-coded (47 +/- 16%) images than in parametric images of beta and A (24 +/- 14 and 24 +/- 8%, respectively; both P

Background— Functional mitral regurgitation (MR) is common in patients with heart failure and left ventricular (LV) dysfunction, and its severity may vary over time, depending primarily on the loading conditions. Because dynamic changes in the severity of functional MR may affect forward stroke volume, we hypothesized that exercise-induced changes in MR severity influence the stroke volume response of patients with LV dysfunction to exercise, and hence their exercise capacity. Methods and Results— Heart failure patients (n=25; mean age 53±12 years) with LV dysfunction underwent dynamic bicycle exercise at steady-state levels of 30%, 60%, and 90% of predetermined peak V̇ o 2 . During each exercise level, right heart pressures, cardiac output, V̇ o 2 , and MR severity were measured simultaneously. During exercise, MR severity, as evaluated by the ratio of MR jet over left atrium area, increased from 15±8% to 33±15%. Peak V̇ o 2 , exercise-induced changes in stroke volume, and those in capillary wedge pressure correlated with the changes in MR ( r =−0.55, −0.87, and 0.62, respectively, P r =−0.75, P r =−0.72, P r =0.86, P Conclusions— Our data indicate that in patients with LV dysfunction, exercise-induced changes in MR severity limit the stroke volume adaptation during exercise and therefore contribute to limitation of exercise capacity.

P the beneficial effects of revascularization result from restoring blood supply to dysfunctional but viable myocardial regions with subsequent improvement in regional and global left ventricular (LV) function. During the past decade, delineation of viable from nonviable myocardium has been the focus of considerable attention and has fostered the development of several new modalities aimed at predicting the return of LV function after revascularization. Among these modalities, low-dose dobutamine echocardiography has recently emerged as a safe, noninvasive, and accurate means of identification of viable myocardium. Although existing data suggest that low-dose dobutamine echocardiography is useful in predicting outcome in patients with moderately depressed LV function, there are no data regarding the prognostic impact of this modality in patients with severe LV dysfunction (i.e., an ejection fraction 25%). Accordingly, the aim of the present study was to evaluate the prognostic value of low-dose dobutamine echocardiography in patients with severely depressed LV function undergoing coronary bypass grafting (CABG).

Hypothyroidism is often associated with defective memory, psychomotor slowing, and depression. However, the relationship between thyroid status and cognitive or psychiatric disturbances remains unclear. Using psychometric scales, 10 patients who had undergone total thyroidectomy for thyroid carcinoma were evaluated for depression, anxiety, and psychomotor slowing; they were examined both when euthyroid and hypothyroid after thyroid hormone withdrawal. Positron emission tomography was used, with oxygen-15-labeled water and fluorine-18F-labeled 2-deoxy-2fluoro-D-glucose as the tracers, to correlate the regional cerebral blood flow and cerebral glucose metabolism with the mental state in patients. Two different image analysis techniques (regions of interest and statistical parametric maps) were applied. In hypothyroidism, there was a generalized decrease in regional cerebral blood flow (23.4%, P < 0.001) and in cerebral glucose metabolism (12.1%, P < 0.001) and there were no specific local defects. Patients were also significantly more depressed (P < 0.001), anxious (P < 0.001) and psychomotor slowed (P < 0.005) in hypo than in euthyroid status. These results indicate that the brain activity was globally reduced in severe hypothyroidism of short duration without the regional modifications usually observed in primary depression.

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 insonated 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.

Aims To assess the accuracy of positron emission tomography to predict recovery of global cardiac function after revascularization in patients with coronary artery disease.Methods and Results One hundred and seventy-eight patients (157 male, 58 +/- 10 years) with coronary artery disease and left ventricular dysfunction (mean ejection fraction 39 +/- 14%) were enrolled in six European centres. They underwent a common protocol for the assessment of viability using F-18-fluoro-2-deoxyglucose (FDG) positron emission tomography during a standardized euglycaemic hyperinsulinaemic glucose clamp before revascularization by either surgery (n = 140) or angioplasty (n = 38). Seven patients were excluded because of incomplete revascularization of a dysfunctional region. Based on the recovery of global ejection fraction 2-6 months after revascularization, patients were classified into two groups: 82 patients who had a >5% improvement in ejection fraction postoperatively, and 89 patients without postoperative ejection fraction improvement. Optimal cut-off points for postoperative improvement of global cardiac function were computed, using receiver operating curve analysis. The highest sensitivity (79%) and specificity (55%) for predicting postoperative ejection fraction improvement by positron emission tomography was found when three or more dysfunctional segments had a relative FDG uptake >45% of normal remote myocardium (overall accuracy 67%).Conclusions In a large cohort of coronary patients with impaired ejection fraction, FDG positron emission tomography demonstrated high sensitivity and moderate specificity to predict improvement of cardiac function after coronary revascularization.

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.

Chronic left ventricular (LV) ischemic dysfunction, a condition often referred to as myocardial hibernation, is associated in humans with ultrastructural alterations of the myocytes, including the loss of myofilaments and the accumulation of glycogen. Given the severity of these structural changes, contractile function is unlikely to resume immediately upon revascularization. Therefore, the aim of the present study was to assess the time course of functional improvement after successful revascularization as well as its potential structural correlates. We studied 32 patients with coronary disease and chronic LV ischemic dysfunction who underwent bypass surgery. Dynamic positron emission tomography with N-13 ammonia and F-18 deoxyglucose to assess myocardial perfusion and glucose metabolism was performed in 29 patients. In all patients, a transmural biopsy was harvested from the center of the dysfunctional area, to quantify the increase in extracellular matrix and the presence of structurally altered cardiomyocytes. LV function was serially measured by digitized 2-dimensional echocardiography before and at 10 days, 2 months, and 6 months after revascularization. The time course of recovery of regional function was estimated from the monoexponential decrease in dysfunctional wall motion score. At follow-up, 19 patients had improved LV function, whereas 13 patients showed persistent dysfunction. Before revascularization, reversibly dysfunctional segments had higher myocardial blood flow (82 +/- 29 vs 53 +/- 21 ml. (min. 100 g)(-1), p = 0.044), higher glucose uptake (40 +/- 16 vs 21 +/- 9 micromol. (min. 100 g)(-1), p = 0.001), and less increase in extracellular matrix (25 +/- 15% vs 46 +/- 17%, p = 0.0008) than segments with persistent dysfunction. The extent to which function recovered was positively correlated with myocardial blood flow and negatively correlated with the increase in the extracellular matrix. In patients with reversible dysfunction, the return of segmental function was progressive and followed a monoexponential time course with a median time constant of 23 days (range 6 to 78). The rate of recovery correlated best with the proportion of altered cardiomyocytes in the biopsy. The present study thus indicates that the recovery of regional and global LV function after successful revascularization is progressive and follows a monoexponential time course that is influenced by the extent of the structural changes affecting cardiomyocytes.

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 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.

Dilated cardiomyopathy (DCM) is a major cause of mortality among patients with heart failure. The aim of the present study was to investigate the independent contribution of Doppler-derived left ventricular (LV) filling to the prediction of survival in patients with DCM, of either ischemic or nonischemic origin, and to derive a simple risk stratification score based on easily available clinical and echocardiographic parameters. We followed 197 consecutive patients (159 men, mean age 60+/-13 years) with an echocardiographic diagnosis of DCM (LV end-diastolic dimension >60 mm, fractional shortening

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

Since the pioneering work of Tennant and Wiggers,1 it has been known that total ischemia leads to a prompt cessation of contraction and eventually results in the appearance of cell damage and irreversible myocardial necrosis. Accordingly, in the minds of many cardiologists, the discovery of an abnormal regional contraction in a patient with coronary artery disease has long been equated with the presence of irreversible myocardial necrosis. With the advent of recanalization therapy, however, evidence progressively accumulated that prolonged regional “ischemic” dysfunction did not always arise from irreversible tissue damage and, to some extent, could be reversed by restoration of blood flow.2 3 4 5 These observations have led to the speculation that chronically hypoperfused myocardium, which is often referred to as “hibernating,”2 3 4 5 6 could maintain viability by simply reducing its metabolic demand to match the decreased supply for as long as myocardial perfusion was inadequate. The chronic impairment of contractile function in this setting has been regarded as a protective mechanism by which the heart spontaneously downgrades its myocardial function, minimizes its energy requirements, and prevents the appearance of irreversible tissue damage.2 4 5 The concept of chronic hibernation thus consists of two parts: a unique clinical observation that bears important implications for the management of patients with chronic coronary artery disease2 3 4 5 6 and a pathophysiological hypothesis, yet to be demonstrated, implying that the chronic dysfunction is due to a chronic reduction of resting MBF.4 5 Other aspects that were not included in the original description, ie, the rapidity of mechanical recovery after successful revascularization7 and the response of dysfunctional myocardium to inotropic stimulation, are now also considered to be integral parts of this condition. The purpose of this discussion is to review some of the …

BACKGROUND: The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood. OBJECTIVE: To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period. MATERIALS AND METHODS: Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984-1993). RESULTS: Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n = 18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/ RBS+ abnormalities (n = 10) were most frequently insignificant. CONCLUSION: In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed.

Myocardial imaging with thallium-201 (201T1) has been proposed and extensively used for the assessment of myocardial viability because tracer uptake and retention require tracer delivery through adequate perfusion, sarco-lemmal integrity and intact metabolic function. These three properties have been shown to be important requirements in order to permit recovery of systolic function after restoration of normal perfusion in dysfunctional myocardium. The aim of this chapter is to review the experimental studies providing a rationale for the use of 201T1 for viability studies and the clinical data suggesting that exercise and resting 201T1 imaging provide relevant information for the assessment of dysfunctional myocardium.

Previous reports have suggested that dobutamine stress echocardiography compares favourably with other stress agent-imaging modality combinations for the detection of coronary artery disease. However, in daily clinical practice the value of a test is defined on a probability basis. To study the relative diagnostic contribution of clinical and dobutamine stress test variables, Bayesian analysis was performed in 223 patients with suspected coronary artery disease, who underwent coronary angiography and a high-dose dobutamine stress test in conjunction with electrocardiography, echocardiography and Technetium-99m sestamibi SPECT myocardial perfusion scintigraphy. According to the pre-test (clinical) probabilities, patients were divided into low-, intermediate- and high-risk groups; 155 patients were in the intermediate-visit group. After dobutamine stress echocardiography the number of patients in this intermediate-risk group was reduced to 102 (P