Real-time, volumetric echocardiography: usefulness of volumetric scanning for the assessment of cardiac volume and function.

BACKGROUND: A novel imaging system has been introduced which uses a dedicated two-dimensional echo probe for rapid beam forming to scan a pyramidal volume in real time. Real-time volumetric echocardiography has the potential to determine accurate cardiovascular anatomy, volume and function in the beating heart without reconstructions. The results of animal and human studies using volumetric echocardiography are evaluated for the potential for clinical applications. IMAGING METHODOLOGY: A new type of ultrasound imaging, high-speed volumetric scanning based on phased array principles permits real-time three-dimensional, volumetric echocardiography (real-time 3-DE). The system requires no off-line reconstruction techniques, thus enabling dynamic three-dimensional visualization and quantification of the heart in real time using a transthoracic approach. Real-time 3-DE uses a 2-D matrix phased array transducer. Image formation employs 16:1 parallel processing to scan a pyramidal volume composed of multiple steering directions in the azimuth dimension and in the elevation dimension. The finished transducer is mounted in a hand-held case with a circular aperture of 16 mm diameter. The array consists of approximately 1,600 elements, operating at 2.5 MHz. Real-time 3-DE permits simultaneous, multiple plane display of two sector arcs (B-scans) and C-scan (parallel to the transducer face or inclined) on a single monitor, conveying the three-dimensional nature of the ultrasound data. This system also allows these planes to be angled for extra diagnostic flexibility. The motion of all the structures during the cardiac cycle can be evaluated in dynamic mode. METHODS: Real-time 3-DE was assessed for accuracy of volume measurement by measuring the volume of balloons of different size and shape, and the hearts of 15 closed chest dogs with myocardial contrast enhancement, and compared to the volumes measured by left ventricular angiography in the dogs. Real-time 3-DE was used to evaluate the endocardial border determination of the entire left ventricle by injecting contrast agent in 12 patients. The endocardial border determination of each segment was scored, and the endocardial border score index calculated. Both real-time 3-D images and cine magnetic resonance imaging (MRI) were performed in 16 patients to assess the accuracy of volume measurement of the left ventricle in humans. The endocardial border of the left ventricle was manually traced, and the volumes calculated by Simpson's rule. RESULTS: The volumes measured by real-time 3-DE correlated well with the true volumes for different sizes of balloon and for asymmetric balloons. The end-diastolic volume and end-systolic volume linear correlation of real-time 3-DE versus angiography measurements using manual tracing in vivo also gave a good correlation (r = 0.97, p < 0.001; r = 0.92, p < 0.01). Fifty-eight of 192 segments were rated as good at baseline and 143 rated as good after Levovist injection. Endocardial border determination was improved by Levovist injection in 100 of 137 segments (74.6%). The endocardial border score index was significantly higher after Levovist administration than at baseline (p < 0.003). The end-diastolic volume and end-systolic volume of the left ventricle measured by real-time 3-DE in humans correlated well with those measured by MRI (end-diastolic volume: r = 0.97, p < 0.001; end-systolic volume: r = 0.96, p < 0.001). CONCLUSIONS: Transthoracic real-time, volumetric echocardiography opens a new and exciting field of echocardiography. The results of these studies demonstrate that this system can accurately measure the ventricular volume and function without use of geometric assumptions. This volumetric mode or V-mode scanning is a new imaging modality that provides a practical methodology to investigate important clinical and research questions.

Fenfluramine and phentermine and cardiovascular findings: effect of treatment duration on prevalence of valve abnormalities.

BACKGROUND: The combination of fenfluramine and phentermine was a widely used obesity treatment before the withdrawal of fenfluramine for an association with heart valve regurgitation. The prevalence and clinical significance of regurgitation among patients treated with these medications has yet to be fully established. METHODS AND RESULTS: To evaluate the potential association between the duration of treatment and the prevalence of heart valve abnormalities, we examined 1163 patients who had taken fenfluramine-phentermine and 672 control patients who had not taken the drug combination within 5 years. Mild or greater aortic regurgitation was present in 8.8% of treated patients and 3.6% of control patients (P<0.001). Moderate or greater mitral regurgitation was present in 2.6% of treated patients and 1.5% of control patients (P=0.18). The adjusted odds ratio compared with controls of aortic regurgitation of mild or greater severity increased according to duration of treatment: 90 to 180 days, 1.5 (P=0.23); 181 to 360 days, 2.4 (P=0.002); 361 to 720 days, 4.6 (P<0.001); >720 days, 6.2 (P<0.001). CONCLUSIONS: This is the largest study to demonstrate a relation between the length of treatment with fenfluramine-phentermine and the prevalence of valvular abnormalities. These findings suggest that valvular abnormalities in patients who took fenfluramine-phentermine primarily involve those who had taken these medications for >6 months and predominantly results in mild aortic regurgitation. The valve regurgitation identified by this study was not accompanied by significant differences in cardiovascular symptoms nor physical findings other than a higher prevalence of heart murmurs.

Clinical information determines the impact of transesophageal echocardiography on the diagnosis of infective endocarditis by the duke criteria.

BACKGROUND: Although transesophageal echocardiography (TEE) is more sensitive than transthoracic echocardiography (TTE) in detecting echocardiographic evidence of infective endocarditis (IE), the impact of TEE on the clinical diagnosis of IE has not been clearly delineated. METHODS AND RESULTS: We studied 112 patients with 114 suspected episodes of IE over a 6-year period who underwent both TTE and TEE during their diagnostic evaluation. Using the results of these studies along with clinical and microbiologic data, we attempted to determine the incremental value of TEE to the Duke Endocarditis Diagnostic Criteria. Patients were initially classified into a diagnostic category of the Duke criteria with TTE data, and then the diagnostic classification was reconsidered with TEE data. A diagnostic category reassignment occurred in 25 of 114 episodes of IE evaluated when TEE results were incorporated into the evaluation with the Duke criteria (22 patients were reclassified from possible IE to definite IE whereas 3 patients were reclassified from rejected to possible IE). Diagnostic reclassification occurred in 9 (11%) of the 80 episodes of suspected IE with native cardiac valves and 13 (34%) of 34 episodes with prosthetic cardiac valves. Most patients reclassified from possible IE to definite IE with TEE data (19 of 22) had an intermediate clinical likelihood of IE, whereas 92% of patients had negative TTE results. Pathologic examination of valvular tissue in 22 of the 114 episodes of suspected IE revealed that the positive predictive value of the Duke criteria with TEE data for diagnosis of IE was 85% in patients with native valves and 89% in patients with prosthetic valves. CONCLUSIONS: When clinical evidence of IE is present, TEE improves the sensitivity of the Duke criteria to diagnose definite IE. TEE data appears to be especially useful for the diagnostic evaluation of patients with suspected IE who have prosthetic valves.

Real-time 3-dimensional echocardiography evaluation of congenital heart disease.

We evaluated the ability of real-time 3-dimensional (RT3D) echocardiography to diagnose congenital heart defects and its potential for presenting structural abnormalities in novel views. Seventy-five patients with suspected congenital heart defects were examined with the use of RT3D echocardiography. Images were reviewed off-line as multiple slices of the raw data or as volume-rendered images by a blinded observer. Diagnoses made from blinded review of the RT3D images were compared with the clinical report of the 2D echocardiogram obtained at the same visit. Real-time 3D echocardiography identified all structural abnormalities except for small atrial septal defects in 2 patients and coronary artery anatomy in D-transposition of the great arteries. Less than 5 minutes were needed to acquire RT3D images in all cases, and sedation was never required. Unique region-oriented views obtained from the 3D data set can be acquired quickly and have the potential to enhance understanding of complex cardiac anatomy.

Real-time volumetric echocardiography: the technology and the possibilities.

The heart is a dynamic organ with complexities in its shape. As such, it places special demands on three-dimensional techniques for reconstruction. Real-time volumetric echocardiography, which is based on phased array and parallel processing principles to enhance line density within a scan volume, provides rapid image acquisition. We introduce the principle, potential clinical importance, current limitations, and future of volumetric imaging methods.

Means for load variation during echocardiographic assessment of the Frank-Starling relationship.

Because minimally invasive methods of preload variation are not validated for load-insensitive indexes of cardiac performance, intravenous nitroglycerin (NTG), phenylephrine, and saline solution (VOL) boluses were used in blocked and intact autonomic states to alter load and were compared with vena caval occlusion in the assessment of preload recruitable stroke work relationships between stroke work and left ventricular end-diastolic volume in dogs. In both autonomic states NTG and VOL produced comparable linear relationships. NTG and saline solution were combined with noninvasive measurements of left ventricular pressure and volume to construct echocardiographic relationships between stroke work and left ventricular end-diastolic cross-sectional area; NTG produced linear relationships similar to vena caval occlusion. Therefore NTG and VOL reliably alter load in constructing preload recruitable stroke work relationships, and NTG may be used with noninvasive measurements to provide load-insensitive estimates of cardiac function in a minimally invasive manner.

Real-time, three-dimensional echocardiography: feasibility of dynamic right ventricular volume measurement with saline contrast.

BACKGROUND: The asymmetry and complex shape of the right ventricle have made it difficult to determine right ventricular (RV) volume with 2-dimensional echocardiography. Three-dimensional cardiac imaging improves visualization of cardiac anatomy but is also complex and time consuming. A newly developed volumetric scanning system holds promise of obviating past limitations. METHODS: Real-time, transthoracic 3-dimensional echocardiographic images of the right ventricle were obtained with a high-speed volumetric ultrasound system that uses a 16:1 parallel processing schema from a 2.5 MHz matrix phased-array scanner to interrogate an entire pyramidal volume in real time. The instrumentation was used to measure RV volume in 8 excised canine hearts; dynamic real-time 3-dimensional images were also obtained from 14 normal subjects. RESULTS: Three-dimensional images were obtained in vitro and in vivo during intravenous hand-agitated saline injection to determine RV volumes. The RV volumes by real-time 3-dimensional echocardiography are well correlated with those of drained in vitro (y = 1.26x - 9.92, r = 0.97, P <.0001, standard error of the estimate = 3.26 mL). For human subjects, the end-diastolic and end-systolic RV volumes were calculated by tracing serial cross-sectional, inclined C scans; functional data were validated by comparing the scans with conventional 2-dimensional echocardiographic indexes of left ventricular stroke volume. CONCLUSIONS: These data indicate that RV volume measurements of excised heart by real-time 3-dimensional echocardiography are accurate and that beat-to-beat RV quantitative measurement applying this imaging method is possible. The new application of real-time 3-dimensional echocardiography presents the opportunity to develop new descriptors of cardiac performance.

Assessment of regional wall motion abnormalities with real-time 3-dimensional echocardiography.

Accurate characterization of regional wall motion abnormalities requires a thorough evaluation of the entire left ventricle (LV). Although 2-dimensional echocardiography is frequently used for this purpose, the inability of tomographic techniques to record the complete endocardial surface is a limitation. Three-dimensional echocardiography, with real-time volumetric imaging, has the potential to overcome this limitation by capturing the entire volume of the LV and displaying it in a cineloop mode. The purpose of this study was to assess the feasibility of using real-time 3-dimensional (RT3D) echocardiography to detect regional wall motion abnormalities in patients with abnormal LV function and to develop a scheme for the systematic evaluation of wall motion by using the 3-dimensional data set. Twenty-six patients with high-quality 2-dimensional echo images and at least 1 regional wall motion abnormality were examined with RT3D echocardiography. For 2-dimensional echocardiography, wall motion was analyzed with a 16-segment model and graded on a 4-point scale from normal (1) to dyskinetic (4), from which a wall motion score index was calculated. Individual segments were then grouped into regions (anterior, inferoposterior, lateral, and apical) and the number of regional wall motion abnormalities was determined. The RT3D echocardiogram was recorded as a volumetric, pyramid-shaped data set that contained the entire LV. Digital images, consisting of a single cardiac cycle cineloop, were analyzed off-line with a computerized display of the apical projection. Two intersecting orthogonal apical projections were simultaneously displayed in cineloop mode, each independently tilted to optimize orientation and endocardial definition. The 2 planes were then slowly rotated about the major axis to visualize the entire LV endocardium. Wall motion was then graded in 6 equally spaced views, separated by 30 degrees, yielding 36 segments per patient. A higher percentage of segments were visualized with 2-dimensional versus RT3D echocardiography (97% vs 83%, respectively, P <.001). With the use of the 2-dimensional echocardiographic results as the standard, RT3D echocardiography detected 55 (96%) of 57 regional wall motion abnormalities. Analysis of the RT3D echocardiograms resulted in 3 false-negative and 5 false-positive findings. The total number of regional wall motion abnormalities was correctly classified by RT3D echocardiography in 19 (73%) of 26 patients. RT3D echocardiography detected 11 of 13 anterior, 19 of 20 inferoposterior, 9 of 9 lateral, and 15 of 15 apical wall motion abnormalities. An excellent correlation was found between the 2 techniques for assessment of the regional wall motion score index (r = 0.89, P <.001). This initial clinical study demonstrates the feasibility and potential advantages of RT3D echocardiography for the assessment of regional LV function. Compared with 2-dimensional echocardiography, this new method permits recording of the entire LV in a single beat, allowing the extent and location of the regional wall motion abnormalities to be determined.

Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation.

More than 40 different beta-cardiac myosin heavy chain (beta-MHC) missense mutations have been identified that cause familial hypertrophic cardiomyopathy (FHC). Some of these are recognized to have important clinical manifestations, such as an increased incidence of sudden death. We report that the beta-MHC missense mutation Arg663His causes predominant cardiac morphology and atrial fibrillation. Longitudinal clinical evaluations were performed in a kindred with FHC. The nucleotide sequence of the beta-MHC gene was analyzed to define the causal mutation. A missense mutation in the beta-MHC gene, Arg663His, was identified in 24 individuals. Clinical studies demonstrated modest left ventricular hypertrophy in affected individuals, predominantly localized in the proximal segment of the interventricular septum, which increased (average = 40 +/- 8%) during 7 years of follow-up. Results showed that 47% of Arg663His adults (age > 16 years) with ventricular hypertrophy developed atrial fibrillation, significantly more (p <0.001) than observed in ungenotyped FHC populations. Survival of affected individuals remained near normal. The beta-MHC missense mutation Arg663His causes a characteristic pattern of ventricular hypertrophy. Arg663His individuals have a markedly higher prevalence of atrial fibrillation, compared with a population with ungenotyped hypertrophic cardiomyopathy. The demonstration of phenotype as a direct consequence of genotype further extends the utility of molecular data in clinical medicine. Early identification of Arg663His individuals has the potential to minimize the serious sequelae of this arrhythmia in this FHC group.

Real-time three-dimensional echocardiography for determining right ventricular stroke volume in an animal model of chronic right ventricular volume overload.

BACKGROUND: The lack of a suitable noninvasive method for assessing right ventricular (RV) volume and function has been a major deficiency of two-dimensional (2D) echocardiography. The aim of our animal study was to test a new real-time three-dimensional (3D) echo imaging system for evaluating RV stroke volumes. METHODS AND RESULTS: Three to 6 months before hemodynamic and 3D ultrasonic study, the pulmonary valve was excised from 6 sheep (31 to 59 kg) to induce RV volume overload. At the subsequent session, a total of 14 different steady-state hemodynamic conditions were studied. Electromagnetic (EM) flow probes were used for obtaining aortic and pulmonic flows. A unique phased-array volumetric 3D imaging system developed at the Duke University Center for Emerging Cardiovascular Technology was used for ultrasonic imaging. Real-time volumetric images of the RV were digitally stored, and RV stroke volumes were determined by use of parallel slices of the 3D RV data set and subtraction of end-systolic cavity volumes from end-diastolic cavity volumes. Multiple regression analyses showed a good correlation and agreement between the EM-obtained RV stroke volumes (range, 16 to 42 mL/beat) and those obtained by the new real-time 3D method (r=0.80; mean difference, -2.7+/-6.4 mL/beat). CONCLUSIONS: The real-time 3D system provided good estimation of strictly quantified reference RV stroke volumes, suggesting an important application of this new 3D method.

Contrast echocardiography: influence of ultrasonic machine settings, mixing conditions, and pressurization on pixel intensity and microsphere size of Albunex solutions in vitro.

To use Albunex as a blood-flow tracer, the stability and consistency of microspheres under mixing conditions must be known. This study examined the effects of mixing conditions and machine settings on the size and echogenicity of Albunex solutions in vitro. Acoustic power, log compression, time-gain compensation, and transducer frequency were varied as Albunex solutions were imaged after mixing with magnetic stirring and pressurized. Higher acoustic power and lower transducer frequency decreased mean pixel intensity of Albunex solution images over time. Intensity, size, and number of Albunex microspheres were not significantly different between stirring speeds. The echogenicity of the Albunex solutions decreased with pressurization, and the critical pressure necessary to reduce the intensity to half its initial value increased with the logarithm of concentration (r = 0.91; p < 0.001). The microsphere size decreased with pressurization and remained smaller after pressure release (3.66 +/- 2.13 versus 1.47 +/- 0.95 microns; p < 0.01). These data indicate that acoustic power and transducer frequency may affect the physical properties of Albunex microspheres, decreasing mean videointensity. Pressure sensitivity of Albunex caused the decrease of videointensity and microsphere size.

Influences of ultrasonic machine settings, transducer frequency and placement of region of interest on the measurement of integrated backscatter and cyclic variation.

Integrated backscatter and its cyclic variation are potentially important parameters to discriminate normal from diseased myocardium. Cyclic variation of integrated backscatter is expected to be independent of machine settings. Backscatter images of swine hearts were taken using a two-dimensional backscatter system while acoustic power was varied at different time gain control (TGC) settings. Cyclic variation was measured in vivo with various acoustic power and TGC settings using different transducer frequencies. Three different regions were analyzed. For any given TGC setting, the relationship between acoustic power and integrated backscatter in vitro was linear only over a narrow range. In vivo, cyclic variation was present at all regions studied in both long- and short-axis views. However, lower acoustic power (< 15 dB) and TGC (< 20 dB), or excessive settings of acoustic power (> 35 dB) and TGC (> 50 dB), produced minimal cyclic variation. Appropriate acoustic power (20-35 dB) and TGC (30-50 dB) produced larger and more consistent cyclic, variation at the posterior region of the left ventricle. These data indicate that each region has specific, appropriate machine settings to maximize the magnitude of cyclic variation.

Evaluation of the effect of transthoracic cardioversion from ventricular tachycardia to sinus rhythm on left atrial mechanical function.

We measured left atrial function during sinus rhythm before and after ventricular tachycardia was induced in an electrophysiology laboratory, using peak transmitral A-wave velocity from pulsed-Doppler transthoracic echocardiography as a marker of left atrial mechanical function. The results of this prospective study do not support the hypothesis that a transthoracic shock of mild to moderate energy diminishes atrial mechanical function.

Assessment of the Frank-Starling relationship by two-dimensional echocardiography.

The Frank-Starling relationship between left ventricular stroke work and end-diastolic minor-axis cross-sectional area was evaluated as a load-insensitive measure of inotropic state by two-dimensional echocardiography in 10 conscious dogs. Stroke work was calculated as the product of systolic change in cross-sectional area and either (1) beat-to-beat mean arterial pressure or (2) initial systolic blood pressure. Both Frank-Starling relationships were highly linear during preload variation (mean r = 0.96), sensitive to the inotropic state (slope increase with calcium 51% +/- 43% and 62% +/- 53%, respectively), and insensitive to afterload (r < 0.4, slope or x intercept versus afterload). Thus the Frank-Starling relationships derived from two-dimensional echocardiographic images and peripheral arterial pressure may be a useful and practical means of assessing inotropic state with minimally invasive measurements.

Negative predictive value of the Duke criteria for infective endocarditis.

With use of new Duke criteria, 405 episodes of suspected endocarditis were previously classified as "definite," "possible," or "rejected" endocarditis. To determine the negative predictive value of the Duke clinical criteria for the classification of suspected endocarditis, chart review and follow-up were performed for the 52 episodes in which the diagnosis of endocarditis was rejected. Three of 52 episodes were reclassified to possible endocarditis; 49 episodes in 48 patients met the criteria for rejected endocarditis. Of these 49 episodes, 31 (63%) had a firm alternate diagnosis other than endocarditis, 17 (35%) had resolution of the clinical syndrome leading to the suspicion of endocarditis with < or = 4 days of antibiotics, and 1 patient had no evidence of endocarditis at surgery. Echocardiograms recorded in 3 patients with rejected endocarditis had evidence of oscillating valvular masses, and blood cultures were positive in 13 episodes; none of these patients had evidence of endocarditis at follow-up. Follow-up or outcome information was available in all 49 episodes. Excluding the 5 in-hospital deaths, mean duration (+/- SD) of follow-up was 39.9 +/- 28.8 months (range 0.5 to 108.0); in living patients, mean time to final follow-up was 56.2 +/- 25.2 months (range 25.0 to 108.0). One patient had possible infective endocarditis at autopsy. No patient in our series whose diagnosis of endocarditis had been rejected had proven endocarditis. Therefore, the negative predictive value of the Duke clinical criteria for endocarditis is at least 92%.

Intraoperative echocardiography during congenital heart operations: experience from 1,000 cases.

BACKGROUND: This article provides an overview of the application of intraoperative echocardiography during repair of congenital heart defects based on our experience with 1,000 patients. METHODS: The patients in this study all underwent repair of a congenital heart defect between 1987 and 1994 at Duke University Medical Center. Echocardiography was performed on all patients in the operating room both before and after repair using epicardial or transesophageal imaging (or both). Hospital costs and outcome data were obtained for all patients. RESULTS: Overall, 44 patients (4.4%) underwent intraoperative revision of their repair based on echocardiographic findings. There was an initial learning phase during which 8.5% of repairs needed to be revised. With experience, the number of revisions fell to as low as 3% to 4%, but need for revision continued to occur throughout the series. Thirty-nine patients (88.6%) had a successful revision. It was not possible for the surgeon to predict the need for a revision based on his confidence in the repair: in 2.6% of patients thought by the surgeon to have a good repair, intraoperative echocardiography revealed the need for operative revision. The average cost for patients who return to the operating room during their hospitalization for revision of a repair is significantly greater than for those whose repairs are revised before they leave the operating room ($94,180.28 +/- $33,881.63 versus $21,415.79 +/- $8,215.74). There were no significant complication attributable to intraoperative echocardiography. CONCLUSIONS: In an era where complete repair of congenital heart defects is emphasized, intraoperative echocardiography provides information that can guide successful operative revision so that babies leave the operating room with optimal results.

Three-dimensional flow images by reconstruction from two-dimensional vector velocity maps.

A method for constructing three-dimensional images of flow is described. The technique involves the acquisition of numerous closely spaced planes, each comprised of a map of the two-dimensional velocities measured in that plane. Each such vector velocity map is formed by tracking the motion of small regions of ultrasonic speckle between two ultrasonic acquisitions separated by a short time interval. In contrast to current Doppler velocity methods, this technique measures both the axial and lateral components of flow and is not subject to aliasing. The resulting series of two-dimensional vector velocity maps is then combined into a three-dimensional data set, which can be manipulated with appropriate software to yield quantitative three-dimensional displays of the flow within the interrogated volume. In this article we present such images obtained from measurements of in vitro laminar flow in a vessel, as well as a free jet phantom. The results allow comprehensive visualization of the three-dimensional flow characteristics, indicating promise for more complete and quantitative clinical assessment of blood flow.