Low levels of high-density lipoprotein cholesterol are associated with vascular remodeling in cardiac transplant recipients.

BACKGROUND: Early atherosclerosis may be associated with compensatory vessel enlargement, termed positive remodeling. Enlarged brachial artery diameter has been reported in patients with risk factors for atherosclerosis and in individuals with coronary atherosclerosis, indicating that brachial artery enlargement is a marker for the presence of atherosclerotic changes. Cardiac transplant recipients often have abnormal lipid levels, but the effect of specific lipid abnormalities on vascular remodeling in this population has not been evaluated. This study examined the relationship between lipid levels and brachial artery diameter in cardiac transplant recipients. METHODS: Thirty-five stable cardiac transplant recipients underwent high-resolution brachial artery ultrasound to evaluate resting brachial artery diameter. Levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were determined and the presence of other cardiac risk factors was assessed. RESULTS: Brachial artery diameter was larger (4.3 +/- 0.1 mm) in subjects with low levels of HDL-C (< 40 mg/dL, n = 11) compared to subjects with high HDL-C (> or = 40 mg/dL, n = 24), who had a mean brachial artery diameter of 3.7 +/- 0.1 mm (P = .006). Neither high LDL-C (> or = 100 mg/dL) nor high triglycerides (> or = 200 mg/dL) were associated with differences in brachial artery diameter. Multivariate analysis demonstrated that the relationship between low HDL-C and increased brachial artery diameter was independent of body surface area or statin use. CONCLUSIONS: Low levels of HDL-C are an independent predictor of brachial artery enlargement in stable cardiac transplant recipients. These findings suggest that suboptimal HDL-C levels may be associated with the development of vascular remodeling and atherosclerosis in this population.

Noninvasive testing for coronary artery disease in women.

Coronary artery disease is a major cause of morbidity and mortality for women in North America and Europe. Given the significance of coronary disease as a public health problem among women, accurate diagnosis of this condition is of great importance. Several noninvasive testing modalities are available for the diagnosis of coronary heart disease. An understanding of gender-based differences related to noninvasive cardiac testing is useful in order to optimally utilize these tests and improve detection and clinical outcomes in women.

Selective activation of the K(+)(ATP) channel is a mechanism by which sudden death is produced by low-energy chest-wall impact (Commotio cordis).

BACKGROUND: Sudden death due to relatively innocent chest-wall impact has been described in young individuals (commotio cordis). In our previously reported swine model of commotio cordis, ventricular fibrillation (with T-wave strikes) and ST-segment elevation (with QRS strikes) were produced by 30-mph baseball impacts to the precordium. Because activation of the K(+)(ATP) channel has been implicated in the pathogenesis of ST elevation and ventricular fibrillation in myocardial ischemia, we hypothesized that this channel could be responsible for the electrophysiologic findings in our experimental model and in victims of commotio cordis. METHODS AND RESULTS: In the initial experiment, 6 juvenile swine were given 0.5 mg/kg IV glibenclamide, a selective inhibitor of the K(+)(ATP) channel, and chest impact was given on the QRS. The results of these strikes were compared with animals in which no glibenclamide was given. In the second phase, 20 swine were randomized to receive glibenclamide or a control vehicle (in a double-blind fashion), with chest impact delivered just before the T-wave peak. With QRS impacts, the maximal ST elevation was significantly less in those animals given glibenclamide (0.16+/-0.10 mV) than in controls (0.35+/-0.20 mV; P=0.004). With T-wave impacts, the animals that received glibenclamide had significantly fewer occurrences of ventricular fibrillation (1 episode in 27 impacts; 4%) than controls (6 episodes in 18 impacts; 33%; P=0.01). CONCLUSIONS: In this experimental model of commotio cordis, blockade of the K(+)(ATP) channel reduced the incidence of ventricular fibrillation and the magnitude of ST-segment elevation. Therefore, selective K(+)(ATP) channel activation may be a pivotal mechanism in sudden death resulting from low-energy chest-wall trauma in young people during sporting activities.

Diagnosis of constrictive pericarditis by two-dimensional echocardiography: studies in a new experimental model and in patients.

The purpose of this study was to determine the value of two-dimensional echocardiography in detecting constrictive pericarditis. Serial two-dimensional echocardiography was performed in eight closed chest conscious dogs with experimental constrictive pericarditis, using a new model that creates constrictive pericarditis by the introduction of a pericardial irritant mixture. Constrictive pericarditis was confirmed in these dogs by cardiac catheterization and pathologic examination. Four patients with constrictive pericarditis and three patients with restrictive cardiomyopathy (amyloidosis) were also studied. Analysis of short-axis two-dimensional echocardiograms was performed to determine the frame by frame change in left ventricular cavity areas throughout diastole. Curves of diastolic left ventricular cavity area change versus percent duration of diastole were constructed for each animal and human subject. Pericardial thickness was measured at various gain settings on two-dimensional and M-mode echocardiograms and at post-mortem examination. In dogs with constrictive pericarditis, the echocardiograms seriously overestimated and correlated poorly with pathologic measurements of pericardial thickness. In dogs after constrictive pericarditis developed, 69 +/- 11% (mean +/- SD) (range 50 to 84) of cavity area change occurred in the initial 30% of diastole compared with 35 +/- 7% (range 20 to 45) in control two-dimensional echocardiograms (p less than 0.001). Four patients with constrictive pericarditis showed similar accelerated cavity expansion in early diastole, but three patients with cardiac amyloidosis showed more variable left ventricular diastolic expansion rates. It is concluded that two-dimensional echocardiograms can demonstrate characteristic diastolic filling abnormalities in constrictive pericarditis, but cannot accurately measure pericardial thickness.

Contrast echocardiography in acute myocardial ischemia. III. An in vivo comparison of the extent of abnormal wall motion with the area at risk for necrosis.

To define the in vivo relation between abnormal wall motion and the area at risk for necrosis after acute coronary occlusion, 11 open chest dogs were studied. Five dogs underwent left anterior descending coronary artery occlusion and six underwent left circumflex artery occlusion. Area at risk was defined at five short-axis levels (mitral valve, chordal, high and low papillary muscle and apex) using myocardial contrast echocardiography. Wall motion was measured in the cycles preceding injection of contrast medium. Two observers used two different methods to measure wall motion. In method A, end-diastolic to end-systolic fractional radial change for each of 32 endocardial targets was determined. The extent of abnormal wall motion was then calculated using three definitions of wall motion abnormality: akinesia/dyskinesia, fractional inward endocardial excursion of less than 10%, and fractional inward endocardial excursion of less than 20%. In method B, the information from the entire systolic contraction sequence was analyzed and correlated with a normal contraction pattern. The best linear correlation between area at risk (AR) and abnormal wall motion (AWM) was achieved using method B and expressed by the following linear regression: AWM = 0.92 AR + 3.0 (r = 0.92, p less than 0.0001, SEE = 1.7%). Of the three definitions of abnormality used in method A, the best correlation was achieved between area at risk and less than 10% inward endocardial excursion and was expressed by the following polynomial regression: AWM = -0.01 AR2 + 1.5 AR -0.14 (r = 0.92, p less than 0.001, SEE = 1.7%). These data demonstrate that there is a definite relation between area at risk and abnormal wall motion but that this relation varies depending on the method used to analyze wall motion. However, wall motion during acute ischemia is also influenced by the loading conditions of the heart. Because these may vary in a manner that is independent of the ischemic process, measurement of both risk area and abnormal motion may provide a more comprehensive assessment of cardiac function in myocardial ischemia than is provided by the measurement of either alone.

Left ventricular diastolic collapse in regional left heart cardiac tamponade. An experimental echocardiographic and hemodynamic study.

OBJECTIVES: This study was designed to describe the hemodynamic abnormalities associated with the appearance of left ventricular diastolic collapse in the setting of regional left heart cardiac tamponade. BACKGROUND: Cardiac tamponade after heart surgery is frequently associated with localized pericardial effusion. Although right ventricular diastolic collapse and right atrial collapse are reliable echocardiographic findings in patients with circumferential pericardial effusion and tamponade, they are often not present in postoperative patients with localized pericardial effusion and regional left heart tamponade. Left ventricular diastolic collapse has been described in such patients, but the degree of hemodynamic alteration that exists with this finding is not known. METHODS: Acute regional left heart tamponade was produced 14 times in seven spontaneously breathing anesthetized dogs by infusing fluid into an isolated compartment created in the pericardial space adjacent to the left ventricular free wall. Continuous echocardiographic imaging and hemodynamic monitoring of left ventricular, systemic arterial, right atrial, pulmonary capillary wedge and pericardial pressures were performed. Measurements at baseline were compared with those made at the onset of left ventricular diastolic collapse and at decompensated tamponade. RESULTS: Left ventricular diastolic collapse was noted in all 14 episodes of regional tamponade. It occurred when pressure in the left pericardial compartment exceeded left ventricular diastolic pressure by 3.0 +/- 1.9 mm Hg. At the onset of left ventricular diastolic collapse, cardiac output and mean arterial pressure were significantly reduced from the control value (p < 0.05). Systolic hypotension was noted only twice at this stage, respiratory variation in systolic pressure > 10 mm Hg only once. The appearance of this sign was also associated with elevated left heart filling pressures. CONCLUSIONS: Left ventricular diastolic collapse is a reliable sign of regional left ventricular tamponade and is associated with a reduction in cardiac output. This echocardiographic finding usually occurs before the development of arterial hypotension and pulsus paradoxus. Thus, left ventricular diastolic collapse is potentially more reliable than hypotension or pulsus paradoxus in the diagnosis of regional left ventricular tamponade.

Contrast echocardiography in acute myocardial ischemia: I. In vivo determination of total left ventricular "area at risk".

Myocardial contrast echocardiography has been shown recently to accurately assess the "area at risk" for necrosis after acute coronary occlusion in the experimental model. Risk area quantitation, however, has been studied primarily from single tomographic planes. Because the three-dimensional extent of myocardial necrosis depends on the total volume of myocardium at risk, the total left ventricular "area at risk" was determined in 11 dogs (Group A) with either left anterior descending or left circumflex artery occlusion using contrast echocardiography and compared with risk area determined by technetium autoradiography. An excellent correlation was found between the two methods (r = 0.96%, y = 0.91x + 1.5, p less than 0.001, SEE = 3.17). A comparison of risk area for individual levels of the left ventricle using both methods, however, showed some variation in the degree of correlation, with the poorest fit being apparent at the apex. To identify the source of the variation, errors caused by data registration were minimized in six additional dogs (Group B) by implanting epicardial markers at a single level and measuring "area at risk" at this level using both methods. When no registration error was present, the correlation between the two methods was excellent (r = 0.99, y = 0.92x + 2.6, p less than 0.001, SEE = 0.55). In conclusion, the "area at risk" for infarction after acute coronary occlusion can be determined accurately for the entire left ventricle as well as for a single tomographic slice using myocardial contrast echocardiography. This was validated using technetium autoradiography, which is an established method of determining "area at risk" in the experimental setting.

Delineation of extended lengths of coronary arteries by multiplane transesophageal echocardiography.

OBJECTIVES: The purpose of this study was to evaluate the utility of multiplane transesophageal echocardiography in assessing the coronary artery tree. BACKGROUND: Evaluation of coronary disease with single-plane and biplane transesophageal echocardiography is limited to the very proximal vessels. The numerous views provided by multiplane imaging may enhance visualization of coronary arteries and detection of their abnormalities. METHODS: Intraoperative multiplane transesophageal echocardiography was performed in 45 consecutive adults who had recently undergone angiography. Recordings were reviewed in blinded manner. RESULTS: We describe the coronary segments visualized with the different imaging planes and define new views. The left main coronary artery with its bifurcation was visualized in all 45 patients. Sensitivity and specificity for detection of coronary narrowings were 100% when results were compared with angiographic data. Visualization of proximal, mid and distal segments of the left anterior descending coronary artery was possible in 69%, 31% and 16% of patients, respectively. Among patients in whom the proximal segment was visualized, sensitivity and specificity for detection of significant narrowings were 80% and 100%. Proximal, mid and distal portions of the left circumflex coronary artery were visualized in 80%, 51% and 20% of patients. Among patients in whom the proximal portion was well seen, sensitivity and specificity were 89% and 100%. The proximal, mid and distal portions of the right coronary artery were visualized in 84%, 16% and 11% of patients. Among patients in whom the proximal segment was visualized, sensitivity and specificity were 82% and 100%. Color Doppler examination was less useful because it detected only 52% of all patients with proximal stenosis. CONCLUSIONS: Multiplane transesophageal echocardiography allows enhanced visualization of extended lengths of coronary arteries and the reliable identification of coronary artery abnormalities.

Delineation of site, relative size and dynamic geometry of atrial septal defects by real-time three-dimensional echocardiography.

OBJECTIVES: This study attempted to determine the site, relative size and dynamic geometry of atrial septal defects using dynamic three-dimensional echocardiography. BACKGROUND: Recent studies have demonstrated the feasibility of dynamic three-dimensional echocardiography. Images are acquired from computerized reconstruction of sequential, tomographic ultrasound "slices" of the heart. Ultrasound images can be obtained by linear progression of a transducer within a transesophageal imaging probe. In small infants and children the large transducer size has not allowed transesophageal placement, and the probe has been placed on the thorax or in the subcostal position. Other scanning devices, housed in plastic containers, acquire images in a rotational format and can also be placed in a transthoracic or subcostal position. METHODS: Specially designed transesophageal probes and a dedicated computer unit were used for two-dimensional image retrieval and reconstruction of three-dimensional images. Sixteen patients with atrial septal defects were studied (median age 18 months, range 1 day to 18 years). In one patient, images were obtained by transesophageal probe placement; in the other 15 patients, the probe was placed in the transthoracic or subcostal position. RESULTS: A dynamic three-dimensional echocardiogram of the atrial septal defect could be obtained in 13 of the 16 patients. The distinguishing features of the atrial septal defects and their spatial orientation could be visualized in unique three-dimensional views. CONCLUSIONS: Dynamic three-dimensional imaging could be applied to the specific evaluation of atrial septal defects. Unique views of the heart allowed for spatial comprehension of the defects, rendering potentially important clinical information.

Effect of lidocaine and bretylium on energy requirements for transthoracic defibrillation: experimental studies.

The purpose of this study was to determine the effect of the antiarrhythmic drugs lidocaine and bretylium on the minimal energy requirement for transthoracic defibrillation--the defibrillation threshold. Closed chest dogs were anesthetized with chloralose or pentobarbital; lidocaine was administered at varying rates for 2 hours and defibrillation threshold periodically redetermined. Similar protocols were followed for bretylium. Serum lidocaine levels from therapeutic to toxic ranges were obtained, and up to a 60% (p less than 0.05) increase in defibrillation threshold in the pentobarbital-anesthetized dogs was demonstrated. In chloralose-anesthetized dogs the lidocaine effect was modest, with only a 10 to 20% rise in defibrillation threshold (p = NS) despite similar increases in serum lidocaine levels. Thus, lidocaine increases the minimal energy requirements for transthoracic defibrillation, but this effect is in part anesthesia-related, indicating a lidocaine-pentobarbital interaction. When phentolamine was administered to chloralose-anesthetized dogs receiving lidocaine, defibrillation threshold rose 13% (p less than 0.05); this suggests that alpha-adrenergic receptor blockade is at least in part the mechanism of the pentobarbital-lidocaine interaction on defibrillation threshold. Bretylium with either anesthetic had no significant effect on defibrillation threshold.

Endothelium-dependent pulmonary artery responses in chronic heart failure: influence of pulmonary hypertension.

OBJECTIVES: The purpose of this study was to determine whether pulmonary artery responses to acetylcholine are abnormal in patients with chronic heart failure. BACKGROUND: Defective pulmonary artery endothelium-dependent responses have been observed in chronic heart failure models in animals. However, pulmonary artery endothelial responses in humans with chronic heart failure are unknown. METHODS: Twenty-two patients with chronic treated heart failure (12 with secondary pulmonary hypertension, Group I; 10 with normal pulmonary artery pressure, Group II) and 8 control patients constituted the study groups. Intravascular ultrasound measurements of pulmonary artery area just beyond the tip of an 8F infusion sheath were obtained in response to acetylcholine (10(-6), 10(-5) and 10(-4) mol/liter). The 10(-6) mol/liter infusion was repeated after methylene blue infusion. Indomethacin (5 micrograms/ml) was sequentially added to this combination in 17 patients. RESULTS: There were no significant differences among the three groups in vascular area responses to the lowest concentration (10(-6) and 10(-5) mol/liter) of acetylcholine, but the 10(-4) mol/liter infusion resulted in significant constriction in Group II patients (p < 0.05, analysis of variance [ANOVA]). Pretreatment with methylene blue in Group II also resulted in significant pulmonary artery vasoconstriction to even the 10(-6) mol/liter acetylcholine infusion (10.4 +/- 7.8% in Group II vs. 1.7 +/- 3.9% in the control group and 0.1 +/- 4.3% in Group I, p < 0.05, ANOVA). The addition of indomethacin resulted in reversal of the constriction in Group II patients. CONCLUSIONS: These responses indicate that the pulmonary artery endothelium may play a significant role in inhibiting vasoconstriction in patients with chronic heart failure who maintain normal pulmonary artery pressure.

Calculation of aortic regurgitant volume by a new digital Doppler color flow mapping method: an animal study with quantified chronic aortic regurgitation.

OBJECTIVES: The aim of the present study was to quantitate aortic regurgitant volume and regurgitant fraction in a chronic animal model with surgically created aortic regurgitation using a new semiautomated color Doppler flow calculation method. BACKGROUND: The conventional noninvasive methods for evaluating the severity of aortic regurgitation have not been accepted widely nor compared with truly quantitative reference standards. METHODS: Eight to 20 weeks after aortic regurgitation was surgically induced in six sheep, a total of 22 hemodynamic states were studied. Electromagnetic flow probes and meters provided reference flow data. Epicardial color Doppler echocardiographic studies were performed to image left ventricular outflow tract forward and aortic regurgitant blood flows. The new method digitally integrated spatial and temporal color flow velocity data for left ventricular outflow tract forward flow and ascending aortic regurgitant flow. The pulsed Doppler method using the velocity-time integral was also used to obtain regurgitant volumes and regurgitant fractions. RESULTS: Regurgitant volumes and regurgitant fractions by the new method agreed well with those obtained electromagnetically, whereas the pulsed Doppler method overestimated these reference data (mean [+/-SD] difference 0.23 +/- 2.9 ml vs. 11 +/- 5.8 ml, p < 0.0001 for regurgitant volume; mean difference 1.2 +/- 7.6% vs. 19 +/- 13%, p < 0.0001 for regurgitant fraction). CONCLUSIONS: This animal study, using strictly quantified aortic regurgitant volumes, demonstrated that the digital color Doppler method provides accurate aortic regurgitant volumes and regurgitant fractions without cumbersome measurements.

Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation.

OBJECTIVES: The goal of this study was to examine the effect of heart failure etiology on peripheral vascular endothelial function in cardiac transplant recipients. BACKGROUND: Peripheral vascular endothelial dysfunction occurs in patients with heart failure of either ischemic or nonischemic etiology. The effect of heart failure etiology on peripheral endothelial function after cardiac transplantation is unknown. METHODS: Using brachial artery ultrasound, endothelium-dependent, flow-mediated dilation (FMD) was assessed in patients with heart failure with either nonischemic cardiomyopathy (n = 10) or ischemic cardiomyopathy (n = 7), cardiac transplant recipients with prior nonischemic cardiomyopathy (n = 10) or prior ischemic cardiomyopathy (n = 10) and normal controls (n = 10). RESULTS: Patients with heart failure with either ischemic cardiomyopathy or nonischemic cardiomyopathy had impaired FMD (3.6 +/- 1.0% and 5.1 +/- 1.2%, respectively, p = NS) compared with normal subjects (13.9 +/- 1.3%, p < 0.01 compared with either heart failure group). In transplant recipients with antecedent nonischemic cardiomyopathy, FMD was markedly higher than that of heart failure patients with nonischemic cardiomyopathy (13.0 +/- 2.4%, p < 0.001) and similar to that of normal subjects (p = NS). However, FMD remained impaired in transplant recipients with prior ischemic cardiomyopathy (5.5 +/- 1.5%, p = 0.001 compared with normal, p = 0.002 vs. transplant recipients with previous nonischemic cardiomyopathy). CONCLUSIONS: Peripheral vascular endothelial function is normal in cardiac transplant recipients with antecedent nonischemic cardiomyopathy, but remains impaired in those with prior ischemic cardiomyopathy. In contrast, endothelial function is uniformly abnormal for patients with heart failure, regardless of etiology. These findings indicate that cardiac transplantation corrects peripheral endothelial function for patients without ischemic heart disease, but not in those with prior atherosclerotic coronary disease.

Impact directly over the cardiac silhouette is necessary to produce ventricular fibrillation in an experimental model of commotio cordis.

OBJECTIVES: In an experimental model of sudden death from chest wall impact (commotio cordis), we sought to define the chest wall areas important in the initiation of ventricular fibrillation (VF). BACKGROUND: Sudden death can result from an innocent chest blow by a baseball or other projectile. Observations in humans suggest that these lethal blows occur over the precordium. However, the precise location of impact relative to the risk of sudden death is unknown. METHODS: Fifteen swine received 178 chest impacts with a regulation baseball delivered at 30 mph at three sites over the cardiac silhouette (i.e., directly over the center, base or apex of the left ventricle [LV]) and four noncardiac sites on the left and right chest wall. Chest blows were gated to the vulnerable portion of the cardiac cycle for the induction of VF. RESULTS: Only chest impacts directly over the heart triggered VF (12 of 78: 15% vs. 0 of 100 for noncardiac sites: p < 0.0001). Blows over the center of the heart (7 of 23; 30%) were more likely to initiate VF than impacts at other precordial sites (5 of 55; 9%, p = 0.02). Peak LV pressures generated instantaneously by the chest impact were directly related to the risk of VF (p < 0.0006). CONCLUSIONS: For nonpenetrating, low-energy chest blows to cause sudden death, impact must occur directly over the heart. Initiation of VF may be mediated by an abrupt and substantial increase in intracardiac pressure. Prevention of sudden death from chest blows during sports requires that protective equipment be designed to cover all portions of the chest wall that overlie the heart, even during body movements and positional changes that may occur with athletic activities.

Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease.

OBJECTIVES: We studied whether assessment of endothelium-dependent vasomotion (EDV) with brachial artery ultrasound (BAUS) imaging predicts the presence or absence of coronary artery disease (CAD) as defined by exercise myocardial perfusion imaging (ExMPI). BACKGROUND: Abnormalities in EDV can be detected in arteries before the development of overt atherosclerosis, and its presence may predict poor long-term prognosis. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral EDV. METHODS: Clinically-indicated ExMPI along with BAUS were performed in 94 subjects (43 women, 51 men). Coronary artery disease was defined by myocardial ischemia or infarction on single photon emission computed tomography images. Flow-mediated dilation (FMD) after upper arm occlusion was defined as the percent change in arterial diameter during reactive hyperemia relative to the baseline. RESULTS: Subjects with CAD by ExMPI (n = 23) had a lower FMD (6.3 +/- 0.7%) than those without CAD by ExMPI (n = 71) (10.5 +/- 0.6%; p = 0.0004). Flow-mediated dilation was highly predictive for CAD with an odds ratio of 1.32 for each percent decrease in FMD (p = 0.001). Based on a receiver-operator analysis, an FMD of 10% was used as a cut-point for further analysis. Twenty-one of 23 subjects who were positive for ExMPI had an FMD < 10% (sensitivity 91%), whereas only two of 40 subjects with an FMD > or =10% were ExMPI-positive (negative predictive value: 95%). There was a correlation between the number of cardiac risk factors and FMD. Individuals with an FMD < 10% exercised for a shorter duration than those with an FMD > or =10% (456 +/- 24 vs. 544 +/- 31 s, respectively; p = 0.02). CONCLUSIONS: Assessment of EDV with BAUS has a high sensitivity and an excellent negative predictive value for CAD and, thus, has the potential for use as a screening tool to exclude CAD in low-risk subjects. Further standardization of BAUS is required, however, before specific cut-points for excluding CAD can be established.

Morphological and functional characteristics of patent foramen ovale and their embolic implications.

BACKGROUND AND PURPOSE: Transesophageal echocardiography (TEE) has detected a high prevalence of patent foramen ovale (PFO) in stroke patients, but the clinical implications of the distinctive characteristics of this patency are still a matter of debate. METHODS: We studied 350 patients with acute ischemic stroke or transient ischemic attack (TIA) within 1 week of admission. Of these, 101 (29%) were identified by contrast TEE to have a PFO; 86 patients (25%) were cryptogenic stroke patients, and 163 were excluded because of the presence of a definite or possible arterial or clinical evidence of a source of emboli or small-vessel disease. Thirteen PFO subjects without a history of embolism were designated as the control group. All PFO and cryptogenic stroke patients were followed up by neurological visits. RESULTS: Compared with controls, PFO patients with acute stroke or TIA more frequently presented with a right-to-left shunt at rest and a higher membrane mobility (P:<0. 05). Patients with these characteristics were considered to be at high risk. During a median follow-up period of 31 months (range, 4 to 58 months), 8 PFO and 18 cryptogenic stroke patients experienced recurrent cerebrovascular events. The cumulative estimate of risk of cerebrovascular event recurrence at 3 years was 4.3% (95% confidence interval [CI], 0% to 10.2%) for "low-risk" PFO patients, 12.5% (95% CI, 0% to 26.1%) for "high-risk" PFO patients, and 16.3% (95% CI, 7. 2% to 25.4%) for cryptogenic stroke patients (high-risk PFO versus low-risk PFO, P:=0.05). CONCLUSIONS: The association of right-to-left shunting at rest and high membrane mobility, as detected by contrast TEE, seems to identify PFO patients with cerebrovascular ischemic events who are at higher risk for recurrent brain embolism.

Intravascular ultrasound and intracardiac echocardiography: concepts for the future.

Intravascular ultrasound imaging is a catheter-based method that has been shown to be better than contrast angiography in the detailed assessment of coronary and peripheral arterial atherosclerotic lesions, arterial dissections and clots, aortic and pulmonary arterial disorders, and the effects and complications of interventional therapy in various vascular beds. Evaluation of refined ultrasound catheters, combined imaging and therapeutic devices, and off-line 3-dimensional reconstruction capabilities indicates that intravascular ultrasound could provide guidance during various catheter-based therapeutic procedures. Early experience with intracardiac echocardiography suggests that this technique could evolve as a clinically useful method with diagnostic, monitoring, and guidance applications. Future directions for further development include designing of miniaturized imaging devices, "look-forward" imaging devices, low frequency devices for whole heart imaging, multifrequency ultrasound catheters and multifunction ultrasound consoles, and approaches to real-time 3-dimensional imaging, on-line tissue characterization, automated acoustic quantification and tissue characterization, the study of myocardial perfusion, and catheter-based acoustic myocardial biopsy. These developments could lead to the conversion of catheterization laboratories into integrated imaging, monitoring, and therapeutic stations. In addition, continuous monitoring of cardiac function could be possible in the critical care unit and in the operating room as well. Ongoing advances in catheter technology and image processing indicate that these concepts are within the realm of becoming reality.

Three-dimensional echocardiography: clinical relevance and application.

Three-dimensional (3D) echocardiography has recently become a practical reality. It is now practicable to perform 3D echocardiography using transthoracic and transesophageal acoustic windows both in adults and children. The unique image projections that 3D echocardiography yields appear to have enormous potential for displaying intracardiac anatomy in exquisite detail. An important aspect of 3D echocardiography is its ability to supply accurate quantitative data without the use of geometric assumptions. In particular, coupled to contrast ultrasound agents, 3D echocardiography could be valuable in the assessment of myocardial perfusion abnormalities. Early clinical experience suggests that 3D echocardiography is likely to play a valuable role in the evaluation of various cardiac disorders, especially in cardiac surgery. In this section, we will review the use of volume-rendered 3D echocardiography in the diagnosis and assessment of cardiac disorders with particular emphasis on the clinical application of this new methodology.

Simulation of intraoperative visualization of cardiac structures and study of dynamic surgical anatomy with real-time three-dimensional echocardiography.

Most prior efforts of 3-dimensional (3-D) reconstruction of echocardiographic images have focused on quantitation of ventricular size and function. The resulting images have been displayed in the wire mesh format. Recently, a method for 3-D transesophageal echocardiography using a computer-controlled probe that acquires parallel tomographic slices has been described. This technique provides dynamic 3-D volume-rendered images of the heart. This study was designed to determine if surgical visualization of intracardiac anatomy could be simulated using this imaging system. Data acquired from 8 patients with congenital and acquired heart disease were analyzed. Real-time 3-D images of the cardiac chambers and valves were obtained. Images of the cardiac pathology including fibrocalcific nodules on the aortic valve, mitral valve endocarditis, rheumatic mitral stenosis, and an ostium secundum atrial septal defect were displayed in 3 dimensions that simulated surgical exposure of these structures. These 3-D representations of cardiac anatomy were in some ways superior to standard intraoperative visualization in that they demonstrated the heart as a dynamic structure, as opposed to the empty, nonbeating heart observed while on cardiopulmonary bypass. In conclusion, 3-D images of cardiac structures as seen by the surgeon intraoperatively can be provided using a computer-driven tomographic transesophageal echocardiographic probe. This imaging system can be potentially useful in the planning and evaluation of cardiac surgery. Technical improvements such as 3-D representation of flow jets, the ability to manipulate images to simulate cardiac surgery, and on-line reconstruction can make this a powerful tool in the future.

Determination of cardiac output using acoustic quantification in critically ill patients.

The reliability of automated acoustic quantification (AQ) in yielding real-time left ventricular (LV) area, volume, and ejection fraction has been validated. The purpose of this study was to explore the potential of AQ in providing accurate immediate determination of cardiac output in critically ill patients. A total of 48 patients were studied. One group consisted of 37 critically ill patients with indwelling Swan-Ganz catheters. In these patients, cardiac output by AQ, manual tracing of end-diastolic and end-systolic frames of 2-dimensional images, and thermodilution were measured. AQ was also compared with Doppler calculation of flow through the left and right ventricles in 11 additional patients. Adequate data for calculation of cardiac output with AQ were obtained in 78% of critically ill patients. There was an excellent correlation between AQ and off-line manual analysis for LV volumes (r = 0.94 and 0.91 for end-diastole and end-systole), ejection fraction (r = 0.85), and cardiac output (r = 0.93). AQ also correlated well with Doppler analysis (r = 0.97) and thermodilution technique (r = 0.95) in the determination of cardiac output. However, AQ slightly underestimated thermodilution measurements, with rather wide limits of agreement (-0.3 +/- 1.1 liter/min). There was a similar underestimation of cardiac output with manual analysis when compared with thermodilution. Given the absence of significant differences between AQ and manual analysis, this observation suggests that the bias is related to the echocardiographic determination of stroke volume, and not to errors from the automated border detection. It is concluded that AQ, besides providing information on LV volumes and ejection fraction, also can yield rapid measurements of cardiac output in most patients who are acutely ill.