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Hepatocyte growth factor (HGF) has been shown to have anti-fibrotic, pro-angiogenic, and cardioprotective effects; however, it is highly unstable and expensive to manufacture, hindering its clinical translation. Recently, a HGF fragment (HGF-f), an alternative c-MET agonist, was engineered to possess increased stability and recombinant expression yields. In this study, we assessed the potential of HGF-f, delivered in an extracellular matrix (ECM)-derived hydrogel, as a potential treatment for myocardial infarction (MI). HGF-f protected cardiomyocytes from serum-starvation and induced down-regulation of fibrotic markers in whole cardiac cell isolate compared to the untreated control. The ECM hydrogel prolonged release of HGF-f compared to collagen gels, and in vivo delivery of HGF-f from ECM hydrogels mitigated negative left ventricular (LV) remodeling, improved fractional area change (FAC), and increased arteriole density in a rat myocardial infarction model. These results indicate that HGF-f may be a viable alternative to using recombinant HGF, and that an ECM hydrogel can be employed to increase growth factor retention and efficacy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

New therapies are needed to prevent heart failure after myocardial infarction (MI). As experimental treatment strategies for MI approach translation, safety and efficacy must be established in relevant animal models that mimic the clinical situation. We have developed an injectable hydrogel derived from porcine myocardial extracellular matrix as a scaffold for cardiac repair after MI. We establish the safety and efficacy of this injectable biomaterial in large- and small-animal studies that simulate the clinical setting. Infarcted pigs were treated with percutaneous transendocardial injections of the myocardial matrix hydrogel 2 weeks after MI and evaluated after 3 months. Echocardiography indicated improvement in cardiac function, ventricular volumes, and global wall motion scores. Furthermore, a significantly larger zone of cardiac muscle was found at the endocardium in matrix-injected pigs compared to controls. In rats, we establish the safety of this biomaterial and explore the host response via direct injection into the left ventricular lumen and in an inflammation study, both of which support the biocompatibility of this material. Hemocompatibility studies with human blood indicate that exposure to the material at relevant concentrations does not affect clotting times or platelet activation. This work therefore provides a strong platform to move forward in clinical studies with this cardiac-specific biomaterial that can be delivered by catheter.

Background: Obtaining cardiac output (CO) measurements noninvasively during routine blood pressure recording can improve hypertension management. A new method has been developed that estimates cardiac output using pulse-waveform analysis (PWA) from a brachial cuff sphygmomanometer. This study evaluates the ability of PWA to track changes in CO as derived by Doppler ultrasound during dobutamine stimulation., Hypothesis: This study aims to validate the PWA CO estimation over a wide CO range as would be obtained by dobutamine stimulation during Doppler ultrasound evaluation., Method: A total of 48 patients undergoing standard dobutamine stress echocardiography testing for accepted clinical indications were enrolled. Among them, 44 patients (age 36-83, 18 females, 26 males) with good waveform data for analyses provided estimates of CO in this study. Noninvasive measurements of CO were performed using both Doppler ultrasound recordings and PWA techniques simultaneously at each stage of dobutamine infusion., Results: A total of 207 simultaneous pulse-waveform analyses and Doppler measurements were taken during dobutamine stress on 44 cardiac patients. Linear regression analysis revealed good intra-patient correlation between pulse-waveform analysis and Doppler at different dobutamine-induced CO with coefficients from r = 0.69 to 0.98 (p < 0.05). Analysis of all patients yielded an overall correlation of r = 0.82 (p < 0.001, bias = 0.4 L/min, standard deviation = 1.8 L/min)., Conclusion: The CO measured noninvasively from a sphygmomanometer using this PWA method correlates well with those of Doppler through a range of dobutamine-stimulated levels. The CO by PWA should be useful for monitoring hemodynamic changes in hypertensive and cardiac patients during routine blood pressure measurement.

Rationale and Objectives: In myocardial contrast echocardiography (MCE), power Doppler imaging is more sensitive to contrast agent (microbubble) than gray-scale B-mode imaging; however, no data exist regarding the optimal contrast dose in power Doppler imaging. This study examined the optimal dose of contrast agent for power Doppler in assessing coronary stenosis., Methods: Three grades of coronary stenosis were produced in 6 open-chest dogs. MCE was performed with gray-scale and power Doppler during continuous infusion of 0.2 mL/min FS-069. Thereafter, MCE was repeated with power Doppler during continuous infusion of 0.1 mL/min FS-069., Results: Although the videointensity in the stenosed bed with power Doppler (214 +/- 14) was greater than gray scale (35 +/- 17) during 0.2 mL/min FS-069 infusion (P < 0.0001), power Doppler failed to identify milder coronary stenoses because videointensity in stenosed bed was quickly saturated with contrast agent. The videointensity in the stenosed bed with power Doppler (127 +/- 49) during 0.1 mL/min FS-069 infusion was greater than gray scale (35 +/- 17) during 0.2 mL/min FS-069 infusion (P < 0.0001), and all levels of stenosis were identified with power Doppler, even though the dose of contrast agent was half of that of gray scale imaging. The correlation between videointensity and myocardial blood flow was better in the case of power Doppler at 0.1 mL/min FS-069 infusion (r = 0.77, P < 0.0001) than in the case of gray scale imaging at 0.2 mL/min FS-069 infusion (r = 0.66, P < 0.01)., Conclusions: These data support the need for a lower dose of contrast agent for power Doppler than for gray scale to detect milder coronary stenosis and avoid saturation of imaging fields.

We sought to propose a simplified method to measure flow velocity based on ultrasonic microbubble destruction, and investigated the effect of microbubble shell fragility on such measurement. Acoustic density (AD) from the second harmonic short axis image of flow was obtained at variable velocities (2 to 73 mm/s) in an in vitro model during long (1000 ms) and short (33 ms) interval ultrasound (US) pulsing, allowing complete and partial microbubble replenishment between pulses, respectively. Microbubbles with shell elastic modulus of 0.4 MPa and 16 MPa were tested. By shortening pulsing interval, AD diminished gradually, rather than abruptly, to a plateau level for both microbubbles. The extent of AD decay was greater for the fragile than the strong microbubbles. A linear relationship existed between the magnitude of AD decay and flow velocity only in the higher and lower velocity range for the fragile and the strong microbubbles, respectively. Thus, difference in contrast intensities during long and short pulsing intervals, respectively, allowing complete and partial replenishment may provide for velocity measurement, in which choice of optimal microbubble fragility for the range of velocity to measure may increase the accuracy.

Objectives: We sought to validate the ability of real-time myocardial contrast echocardiography (MCE) measures of opacification defect and contrast refilling parameters to estimate risk area (RA) and infarct area (IA) during coronary occlusion and reperfusion., Background: No data exist establishing the accuracy of MCE in determining RA and IA size. We hypothesized that in the setting of coronary occlusion, MCE should identify RA as a perfusion defect early after bubble destruction, collateral flow to viable myocardium as opacification late during refilling and IA as absent opacification., Methods: Three hours of coronary occlusion and reperfusion were each produced in 11 dogs in which real-time MCE was performed during intravenous infusion of Sonovue (Bracco). Real-time contrast echocardiography was performed at baseline, during occlusion and reperfusion. Early (BEGIN) and end (END) images from a FLASH refilling sequence were acquired, as well as late refilling images (LATE) 1 min after FLASH. Real-time contrast echocardiography defect size and quantitative refilling parameters were compared with RA and IA determined by tissue staining., Results: During occlusion, defect size varied with refilling time; defects from BEGIN images correlated best to RA and those from LATE images to IA. Refilling parameters, but not LATE peak intensity, did not predict the IA size during occlusion. During reperfusion, defects from BEGIN images were well correlated to RA and END images to IA, whereas peak plateau intensity and refilling slope parameters predicted IA size., Conclusions: Real-time contrast echocardiography defect size varies throughout microbubble refilling. Appropriately selected defect sizes and refilling parameters provide estimates of RA and IA during coronary occlusion and reperfusion.

Real-time myocardial contrast echo (MCE) provides the potential to assess myocardial blood flow from time-intensity refilling curves after high-energy bubble destruction. This study validated the accuracy of this approach and the effect of specific examination variables and instrument settings on results. The effects of examination depth and angle as well as dynamic range, pulse repetition frequency, and line density were assessed with the use of in vitro incremental flow rates produced in an in vitro tissue phantom. In vivo recordings of real-time imaging with an infusion of a contrast agent (Optison) were obtained in 7 open-chest dogs with graded left anterior descending artery stenosis at baseline and during adenosine hyperemia, and were compared with flow probe measurements. After bubble destruction, time-intensity data were fitted to an exponential function, and the rate of intensity increase (b) and peak plateau intensity (A) were derived from refilling curves. In vivo real-time values for b, but not A, correlated closely with flow probe measures (r = 0.93). A similar correlation for b was observed in vitro (r = 0.98). The correlation between flow rate and b was influenced by several examination variables, including depth, angle, and instrument settings. Real-time MCE provides accurate quantification of coronary flow by assessing the rate of microbubble refilling. However, this parameter may be affected by several examination and instrument variables. Therefore, real-time MCE refilling measures are best applied by comparing baseline values with those of stress studies.

Background: Controversy continues as to whether adenosine or dobutamine is the superior pharmacological stress agent for myocardial contrast echocardiography (MCE)., Methods and Results: We compared real-time MCE refilling curves and wall thickening during adenosine and dobutamine stress in 14 open-chest dogs with left anterior descending and left circumflex coronary artery stenoses that reduced hyperemia by 40% to 60% and 70% to 90% (mild and severe non-flow-limiting stenosis, NFLS) and resting flow by 10% to 30% and 35% to 50% (mild and severe flow-limiting stenosis, FLS). MCE was performed with low-energy imaging during Optison infusion. After high-energy bubble destruction, time-intensity data from risk beds were fitted for an exponential function as y=A(1-e(-)(bt)), from which the rate of intensity increase (b) and maximal plateau intensity (A) were derived. Although severe NFLS and greater stenoses decreased b with both dobutamine and adenosine, with mild NFLS it was reduced in 58% of animals with dobutamine versus 8% with adenosine. The absolute decrease in b, however, was greater for adenosine than dobutamine with FLS. The A parameter was decreased with both adenosine and dobutamine only with the most severe FLS. Wall thickening was decreased with dobutamine in 33% of animals with severe NFLS and in all animals with any FLS; with adenosine, in all with severe FLS., Conclusions: Both dobutamine and adenosine significantly reduce MCE refilling rates in the setting of severe stenosis and in the absence of contractile abnormalities. Dobutamine decreases refilling rate and wall thickening at a less reduced flow grade than adenosine, but adenosine produces a greater magnitude of change than dobutamine.

Objective: To assess the feasibility of measuring left atrial (LA) function with acoustic quantification (AQ) and then assess the effects of age and sex on LA reservoir, conduit, and booster pump function., Patients and Setting: 165 subjects without cardiovascular disease, 3-79 years old, were enrolled by six tertiary hospital centres., Interventions: Continuous LA AQ area data were acquired and signal averaged to form composite waveforms which were analysed off-line., Main Outcome Measures: Parameters of LA performance according to age and sex., Results: Signal averaged LA waveforms were sufficiently stable and detailed to allow automated analysis in all cases. An age related increase in LA area was noted. LA reservoir function did not vary with age or sex. All parameters of LA passive and active emptying revealed a significant age dependency. Overall, the passive emptying phase accounted for 66% of total LA emptying ranging from 76% in the youngest to 44% in the oldest decade. LA contraction accounted for 34% of atrial emptying in all subjects combined with the older subjects being more dependent on atrial booster pump function. When adjusted for atrial size, there were no sex related differences in LA function., Conclusions: LA reservoir, conduit, and booster pump function can be assessed with automated analysis of signal averaged LA area waveforms. As LA performance varies with age, establishment of normal values should enhance the evaluation of pathologic states in which LA function is important.

Our goal was to establish normal values for quantitative color kinesis indexes of left ventricular (LV) wall motion over a wide range of ages, which are required for objective diagnosis of regional systolic and diastolic dysfunction. Color-encoded images were obtained in 194 normal subjects (95 males, 99 females, age 2 mo to 79 yr) in four standard views. Quantitative indexes of magnitude and timing of systolic and diastolic function were studied for age- and gender-related differences. Normal limits of all ejection and filling indexes were in a narrow range (< or =25% of the mean), with no major gender-related differences. Despite invariable ejection fractions, both peak filling and ejection rates decreased with age (30 and 20%, correspondingly) with a concomitant increase in mean filling and ejection times, resulting in five- and twofold increases in the late to early filling and ejection ratios, correspondingly. Diastolic asynchrony increased with age (from 4.7 +/- 2.0 to 6.4 +/- 3.2 from the 2nd to 7th decade). The normal values of color kinesis indexes should allow objective detection of regional LV systolic and diastolic dysfunction.

To demonstrate the feasibility and quantify the intensity of right ventricular (RV) myocardial opacification by myocardial contrast echocardiography (MCE), we analyzed MCE produced by intravenous injection of 0.15 ml/kg of QW7437 in 8 closed-chest dogs. MCE could produce visual opacification of the RV wall similar in time course to that of the left ventricular wall, and the data supported the potential role of MCE in evaluating RV hypertrophy, contraction, and perfusion abnormalities.

Intermittent ultrasound transmission during contrast echocardiography, so-called transient response imaging (TRI), amplifies contrast intensity. This effect of TRI is attributed to decreased microbubble destruction by reduced exposure time to ultrasound energy. The present study examined the hypothesis that the signal amplification produced by TRI is related to the baseline intensity present in the image and the velocity of flow. We performed second harmonic (2.5/5.0 MHz) imaging during both continuous (frame rate 55 Hz) and electrocardiogram-triggered TRI mode. Contrast images produced by perfluorohexane microbubbles (AF0150) in a steady flow model were obtained every minute throughout the decay phase at transit velocities of 8.1, 6.2, 3.4, 1.9, and 0.7 cm/sec. The decay of videointensity over time could be fitted to a sigmoid curve for both imaging modes with r > 0.99 for individual velocities. The intensity with TRI was greater than that with continuous imaging (CI) at any time and velocity. The mean increase in intensity between modes throughout decay was 8.2 +/- 3.7, 12.8 +/- 4.2, 25.7 +/- 5.8, 49.5 +/- 8.0, and 64.0 +/- 14.4 gray levels for the respective velocity levels studied (p < 0.0001). Although varying with baseline intensity at early and late phases, the TRI amplification plateaued during middecay, and within the intensity range of 16 to 143 gray levels for CI and 67 to 186 gray levels for TRI, it showed no overlap among the different velocity levels. Thus the ability of TRI to enhance contrast opacification is much greater at low flow velocities, which has implications regarding the mechanism of TRI effect and preferential visualization of intramyocardial coronary arteries by this agent. Although this effect was influenced by the baseline intensity, it was relatively constant for each velocity level within an optimal intensity range during middecay, providing the basis for flow velocity measurement by contrast echo.

An enhanced method for determining cardiac output using Doppler color flow imaging techniques to measure mitral orifice diameter was developed and validated in an experimental model and in clinical patients. In an in vitro circuit model, color jet width correlated well with actual orifice dimension from 12 to 24 mm (r = 0.99). In the clinical application, mitral valve area was calculated as a X b X pi/4 where a and b represent the width of the color flow stream in the mitral orifice just distal to the annulus in apical long-axis (short-diameter) and 4-chamber (90 degrees rotated, long-diameter) views, respectively. Cardiac output was then computed as the product of mitral valve area and time-velocity integral of transmitral flow from the same site. Cardiac output was also measured by thermodilution and conventional echocardiographic methods using diameters and time-velocity integrals from the left ventricular outflow tract. In 30 patients with nonvalvular heart disease, cardiac output measured by thermodilution ranged from 3.40 to 8.40 L/min. Cardiac output was determined in 28 of 30 patients (93%) by the Doppler color flow imaging technique; it ranged from 3.00 to 8.36 L/min and correlated well with thermodilution: y = 0.90x + 0.63, r = 0.91. Cardiac output was determined in 24 of 30 patients by the conventional left ventricular outflow method (80%). The cardiac output measured by the conventional method correlated less closely with thermodilution (r = 0.84), although there was no statistical difference in correlation coefficiencies between the 2 methods. These results indicate that the Doppler color flow imaging technique can be used to enhance the determination of cardiac output by echocardiography, particularly when the conventional method has resulted in technically inadequate recordings.

Although the hemodynamic responses to isotonic and isometric exercise are different, few data exist comparing the response to left ventricular (LV) diastolic filling dynamics with these two forms of exertion. Therefore we performed Doppler examination before and at the end of isotonic and isometric exercise in 20 normal volunteers to define the differential responses of LV filling to these two forms of exertion. Transmitral inflow velocity signals from the apical view and phonocardiography were recorded before and at the termination of treadmill exercise (TRD) to 11 METs and handgrip (HG) 50% maximal for 2 minutes). Mean blood pressure (mBP), heart rate (HR), early diastolic (E) and late atrial (A) inflow velocities, mean acceleration rate (ACC) of E wave, time velocity integral of inflow (Ti), and isovolumic relaxation time (IRT) from second heart sound to onset mitral inflow were measured. Absolute changes from baseline were significantly different for the two forms of exertion: TRD versus HG: BP = 11 +/- 9 versus 36 +/- 10 mm Hg, HR = 37 +/- 16 versus 16 +/- 9 beats/min, E = 11.6 +/- 11.3 versus -7.0 +/- 9.4 cm/sec, A = 29.9 +/- 14.5 versus 14 +/- 12 cm/sec, ACC = 164 +/- 151 versus -56 +/- 135 cm/sec2, Ti = 1.9 +/- 3.0 versus -1.7 +/- 1.7 cm, and IRT = -12 +/- 9 versus 9 +/- 10 msec, all p < 0.0001 except for A, p < 0.001). Isotonic treadmill exercise resulted in enhanced early diastolic filling manifested by increases in E and ACC and a decreased in IRT. Conversely, isometric handgrip exercise produced evidence of reduced early filling including decreased E and ACC and slightly increased IRT. Thus the response of LV filling dynamics recorded by Doppler differs for isotonic and isometric exertion and likely reflects the variable pressure and flow alterations induced by these two forms of exertion.

An echocardiographic system has been developed that performs automatic endocardial border detection and instantaneously calculates and displays a waveform of left ventricular cavity area versus time. The purpose of this study was to compare measurements of left ventricular filling dynamics from automatic border detection echocardiography with similar measurements from cineventriculography. Thirty-three patients undergoing cardiac catheterization had automatic border detection echocardiography performed within 45 minutes of cineventriculography. Ten patients had normal catheterization findings and 23 had cardiac disease. The automatic border detection waveforms generated from two echocardiographic views were measured to determine the fraction of filling occurring during the early diastolic rapid filling phase and during the filling phase resulting from atrial contraction. Similar fractions were derived from curves generated from frame-by-frame measurements of cineangiographic volumes. Results were analyzed by correlating echocardiographic and cineventriculographic results, and by a limits of agreement analysis (limits of agreement were +/- 2 standard deviations of the mean difference between echocardiography and cineventriculography). There were significant correlations between echocardiography and cineventriculography for each of the parameters studied. The best results were obtained for the apical four-chamber view (rapid filling fraction r = 0.72, P < 0.0001, atrial filling fraction r = 0.56, P < 0.001). Differences in filling patterns between normal and abnormal patient groups detected by cineventriculography were also detected by automatic border detection echocardiography. However, broad limits of agreement were observed, that may limit the ability of the automatic border detection system to reliably predict cineventriculographic results in an individual patient. Automatic border detection echocardiography can provide information about left ventricular filling dynamics that is similar to that obtained from frame-by-frame analysis of cineventriculograms. However, the variability in the results may limit the application of the technique in individual patients.

Standard two-dimensional echocardiographic image planes are defined by anatomic landmarks and assumptions regarding their orientation when these landmarks are visualized. However, variations of anatomy and technique may invalidate these assumptions and thus limit reproducibility and accuracy of cardiac dimensions recorded from these views. To overcome this problem, we have developed a three-dimensional echocardiograph consisting of a real-time scanner, three-dimensional spatial locater, and personal computer. This system displays the line of intersection of a real-time image and an orthogonal reference image and may be used to assess actual image orientation during standardized two-dimensional imaging when the line-of-intersection display is not observed by the operator. Three hundred forty standard images were assessed from 85 examinations by 11 echocardiographers. Twenty-four percent of the unguided standard images were optimally positioned within +/- 5 mm and +/- 15 degrees of the standard. Of the optimal images, two thirds were parasternal long-axis views. A subsequent study with three-dimensional echocardiography and line-of-intersection guidance of image positioning showed 80% of the guided images to be optimally positioned, a threefold improvement (p < 0.001). Two-dimensional echocardiography does not achieve reasonably consistent optimal positioning of standard imaging views, suggesting that measurements taken from these views are likely to be suboptimal. Three-dimensional echocardiography that uses line-of-intersection guidance improves image positioning threefold and should therefore improve the accuracy and reproducibility of quantitative echocardiographic measurements derived from these images.

The temporal variability of color flow jets during regurgitation has not been systematically examined. We therefore analyzed color Doppler images in 52 patients (29 with mitral regurgitation and 23 with aortic regurgitation) for frame-to-frame variability in the size of the regurgitant color jet. Planimetered jet areas varied markedly throughout the flow period, with the difference between the largest and smallest mitral regurgitant jets ranging from 1.1 to 11.9 cm2 in individual patients. Maximal and minimal aortic regurgitant jets varied from 1.5 to 6.6 cm2 between frames. The point during the cardiac cycle at which the largest regurgitant jet area was recorded also varied markedly for mitral and aortic lesions. Mitral regurgitant jets peaked at 51% of systole, with a range from 9% to 100%. The point during diastole at which the maximal aortic regurgitant jet was recorded varied from 2% to 84%, with a mean of 31.2% of the diastolic period. The persistence of the flow disturbance was examined as the percent of systole or diastole during which the maximal jet area remained at least 50% or 75% of its maximal size. Mitral regurgitant jets remained at least one-half maximal size for a mean of 60.7% (range, 20% to 90%) of systole, but remained at 75% of maximal size for a mean of only 39% of systole. Aortic regurgitant jets persisted at over one-half maximal size for a mean of 63.2% (range, 30% to 90%) of diastole, but sustained 75% of maximal size for a mean of only 44% of diastole.(ABSTRACT TRUNCATED AT 250 WORDS)

To confirm whether or not echocardiographic B-color images (temperature, magenta, rainbow) are superior to ordinary gray-scale images, 62 coronary artery disease (CAD) patients (42 men and 20 women) underwent gray-scale and B-color echocardiography and cineangiography within 24 hours. Left ventricular (LV) volume was derived from angiography using the single-plane area-length method and was derived from echocardiography using single-plane modified Simpson's formula. In predicting angiographic volume, the correlations between B-color images and angiography were similar to that between the gray-scale image and angiography. In evaluating LV ejection fraction, the correlation coefficients between B-color images and angiography (temperature r = 0.93, magenta r = 0.93, rainbow r = 0.92) were slightly higher than that between the gray-scale image and angiography (r = 0.85) (p less than 0.05). We conclude that B-color images yield estimates of LV volumes that are of similar accuracy to gray-scale images in patients with CAD.

Combined echocardiography and Doppler color flow mapping from transthoracic imaging windows has become the standard method for the noninvasive assessment of valvular regurgitation. This study compared regurgitant jet areas by Doppler color flow imaging derived from the newer transesophageal approach with measurements obtained from conventional transthoracic apical views. Maximal regurgitant jet area determinations and an overall visual estimate of lesion severity were obtained from 42 patients who underwent color flow examination by both techniques. Seventy-three regurgitant lesions were visualized by transesophageal flow imaging: 34 mitral, 22 aortic, and 17 tricuspid jets. Transthoracic studies in the same patients revealed fewer regurgitant lesions for each valve; 20 mitral, 16 aortic, and 12 tricuspid (p = 0.0009). A comparison of maximal jet areas determined by transesophageal and transthoracic studies showed a good overall correlation (r = 0.85, SEE = 2.8 cm2) and a systematic overestimation by the transesophageal technique (TEE = 0.96 TTX + 2.7). For the subgroup with mitral insufficiency, valve lesions visualized by both techniques were larger by the transesophageal approach (n = 18, 6.0 versus 3.6 cm2, p = 0.008). Semiquantitative visual grading of individual valve lesions by two independent observers revealed a higher grade of regurgitation with more jets classified as mild (38 versus 25), moderate (18 versus 13), and severe (17 versus 10) by esophageal imaging than by transthoracic imaging. Thus, transesophageal color flow mapping techniques yield a higher prevalence of valvular regurgitation than do transthoracic techniques in the same patients. Jet area and the overall estimate of regurgitant lesion severity were also greater by transesophageal color Doppler imaging compared with standard transthoracic imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

The objective of this study was to evaluate the effect of alterations in preload induced by lower body negative pressure on Doppler transmitral filling patterns. Echocardiograms and Doppler recordings were performed in 18 normal young men (aged 23 to 32 years) during various levels of lower body negative pressure (0, -20 and -50 mm Hg). Lower body negative pressure induced a reduction in diastolic velocity integral (from 12.17 +/- 0.79 to 8.42 +/- 0.71 cm, p = 0.0067) and consequently left ventricular diastolic diameter (from 5.11 +/- 0.09 to 4.45 +/- 0.1 cm, p less than 0.0001). There was a significant reflex increase in heart rate from 59.9 +/- 1.9 to 77.1 +/- 2.4 beats/min (p less than 0.0001), but blood pressure was unchanged. This reduction in preload altered Doppler transmittral filling patterns as follows: 1) peak early velocity (E) decreased from 59.2 +/- 3.8 to 39.1 +/- 1.7 cm/s (p less than 0.0001); 2) atrial filing velocity (A) was unchanged (35.58 +/- 1.5 to 33.52 +/- 1.4 cm/s, p = 0.517); 3) E/A ratio decreased from 1.7 +/- 0.13 to 1.19 +/- 0.08 (p = 0.0087); 4) mean acceleration (from 482 +/- 37 to 390 +/- 27 cm/s2, p = 0.03) and mean deceleration (from 327 +/- 31 to 169 +/- 21 cm/s2, p less than 0.001) of the early filling wave were significantly reduced; and 5) peak acceleration (from 907 +/- 42 to 829 +/- 29 cm/s2) and peak deceleration (from 771 +/- 94 to 547 +/- 76 cm/s2) also decreased, but not significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Few data exist regarding the consequences of abnormalities of segmental contraction on intraventricular flow patterns. The development of color Doppler flow imaging has now permitted the visualization of intraventricular blood flow patterns. Therefore, we performed Doppler flow mapping in 41 patients (12 with normal left ventricular contraction, eight with hypokinesis or akinesis, and 21 with dyskinesis) and compared these findings with left ventriculography. Systolic blood flow by Doppler mapping in subjects with normal ventricular contraction was characterized primarily by flow through the left ventricular outflow tract and into the aorta. In patients with dyskinesis, paradoxical systolic flow toward the abnormal segment was present, and persisted for at least 50% of systole in 18 of 21 patients. Mean duration of paradoxical flow in dyskinetic patients was 77% of systole. Paradoxical flow was also observed in two of five patients with akinesis but in no patients with hypokinesis. A good correlation was observed between the duration of paradoxical systolic flow and indexes of regional wall motion (radian shortening of the involved myocardium) (r = 0.77) and global ejection fraction derived from cineangiography (r = 0.79). Correlations between the area of the paradoxical systolic flow stream in midsystole and indexes of left ventricular function were less close, with r equaling 0.57 for both regional wall motion and ejection fraction. Thus, paradoxical systolic flow can be detected in most patients with left ventricular dyskinesis, and correlates with the magnitude of regional and global left ventricular dysfunction by cineangiography.

Isometric exercise produces well-defined hemodynamic changes in normal and diseased states. However, the effect of isometrics on the degree of valvular regurgitation recorded by color Doppler flow imaging (CDFI) has not been reported. CDFI was therefore used to evaluate changes in valvular regurgitation in 34 patients, mean age 53 +/- 16 years. Data were collected for 43 regurgitant lesions including 20 cases of aortic regurgitation and 23 cases of mitral regurgitation. Isometrics produced a significant increase in heart rate (71 to 83 beats/min) and blood pressure (132/64 to 153/70 mm Hg) in all patients (p less than 0.0001). Regurgitant jet area by CDFI increased significantly in both aortic regurgitation (4.5 to 6.2 cm2, p less than 0.0001) and mitral regurgitation (6.2 to 8.2 cm2, p less than 0.001). Patients taking concurrent vasodilator or angiotensin-converting enzyme inhibitor therapy had similar responses to those not receiving long-term therapy. Thus, CDFI detects an increase in aortic and mitral regurgitant jet area induced by isometric exertion. The change in CDFI jet area with handgrip demonstrates the influence of loading conditions on the size of a regurgitant jet area, and suggests that isometric exertion may increase the magnitude of mitral and aortic regurgitation.

The accuracy of electrocardiography, M-mode echocardiography and two-dimensional echocardiography in predicting left ventricular hypertrophy was compared in 50 patients who came to autopsy within 6 months after the studies were performed. Several methods for determining left ventricular hypertrophy were examined for each of the three techniques. M-mode echocardiography was technically adequate to evaluate the presence or absence of left ventricular hypertrophy more often than either electrocardiography or two-dimensional echocardiography. Measurements from M-mode echocardiography also correlated best with autopsy measurements. Both echocardiographic techniques had a higher sensitivity than electrocardiographic criteria in diagnosing left ventricular hypertrophy. Two-dimensional echocardiography was not shown to improve the M-mode assessment of left ventricular hypertrophy. In an attempt to simplify both M-mode left ventricular mass calculations and the diagnosis of left ventricular hypertrophy for the clinician, a left ventricular mass nomogram was constructed, enabling quick insertion of standard M-mode echocardiographic measurements.

This study was undertaken to compare the accuracies of the two-dimensional echocardiographic (2DE) and Doppler pressure half-time methods for the noninvasive estimation of cardiac catheterization measurements of mitral valve area in patients with pure mitral stenosis both with and without a previous commissurotomy. Data were retrospectively obtained from 74 consecutive patients who underwent cardiac catheterization within a 30 month period for evaluation of mitral stenosis, and who had two-dimensional echocardiograms performed before catheterization. Six patients (8.1%) had technically inadequate 2DE images and their data were excluded from analysis. Two of these patients had undergone commissurotomy, while the remaining four had not. Continuous-wave Doppler echocardiographic examinations were attempted in 45 patients and adequate measurements of pressure half-times were obtained in all patients studied. Mitral valve area by two-dimensional echocardiography was measured as the planimetered area along the inner border of the smallest mitral orifice visualized during short-axis scanning, while pressure half-time was calculated as the interval between the peak transmitral velocity and velocity/square root 2 as measured from the envelope of the Doppler spectral signal. Calculations from catheterization represented the minimal valve area at rest as derived from the Gorlin formula with the use of pressure gradients and thermodilution measurements of cardiac output. Thirty-seven of the patients had had a previous mitral commissurotomy a mean of 11.2 +/- 5.4 years before, while the remaining 37 patients were previously unoperated. Mean valve area as determined at catheterization for the total group of patients ranged from 0.37 to 2.30 cm2 (mean = 1.08 +/- 0.42 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)

Fifteen patients (median age 8.5 years) with fixed right ventricular outflow tract obstruction were evaluated by two-dimensional echocardiographically directed continuous wave Doppler ultrasound within 24 hours of cardiac catheterization. Pulmonary artery blood velocity measurements were determined from a real time spectral display of pulmonary artery flow profile and converted to pressure drop utilizing a modified Bernoulli equation. Use of both parasternal and subcostal imaging permitted more accurate detection of maximal flow velocity than did use of either approach alone. Gradients estimated from Doppler recordings correlated well with those measured at cardiac catheterization (correlation coefficient = 0.95, standard error of the estimate = 7.9 mm Hg) with a trend to slight underestimation of gradient in more severe obstruction. In three patients with combined valvular and subvalvular stenosis and one patient with right ventricular outlet obstruction due totally to a ventricular septal aneurysm, Doppler estimation of gradient provided an accurate assessment of total right ventricular-pulmonary artery gradient. Thus, continuous wave Doppler ultrasound combined with two-dimensional echocardiography provides a reliable noninvasive method of estimating pressure gradient in patients with right ventricular outflow tract obstruction.

In previous studies, indicator-dilution curves obtained by videodensitometry of contrast two-dimensional echocardiograms have shown close correlation with measurements of blood flow in vitro. In this study the technique was extended and contrast indicator-dilution curves obtained in vivo were correlated with simultaneous cardiac output measurements determined by thermodilution in eight dogs. Two-dimensional echocardiograms of the left ventricle were performed with the transducer on the myocardium during left atrial-pulmonary vein injection of 10 cc of a 1 X 10(-4) concentration of 30 mu diameter microballoons. A total of 148 injections were performed at 37 levels of cardiac output (1.70 to 7.90 liters/min) induced by alterations of left ventricular preload, isoproterenol and propranolol. Indicator-dilution curves were obtained from recordings of the analog signal of a linear videodensitometer focused on the left ventricle. Linear regression analysis between total area of the indicator-dilution curves and cardiac output yielded correlation coefficients (r) of 0.77 to 0.96 (mean 0.90) for individual dogs, and 0.65 for all cardiac output determinations in all dogs. Analysis of indicator-dilution curve area by the forward triangle-exponential decay method yielded enhanced individual coefficients of 0.90 to 0.97 (mean 0.94) with cardiac output and 0.61 for the group of animals. It is concluded that echographic indicator-dilution curves obtained from uniform size microballoons and videodensitometry may be obtained in vivo and correlate with cardiac output measurements.

The purpose of this study was to compare estimates of pressure gradients obtained from continuous-wave (CW) Doppler recordings with direct pressure measurements derived from cardiac catheterization in patients with aortic stenosis. Forty patients who underwent cardiac catheterization for evaluation of aortic stenosis were prospectively studied with CW Doppler spectral recordings of the aortic valve prior to catheterization. Thirty-three patients underwent a second Doppler examination simultaneously with pressure recordings in the catheterization laboratory. Nineteen of the patients had catheterization pressures measured using high-fidelity, micromanometer-tip catheters. Doppler and pressure tracings were digitized using a microprocessor-based computer with a software program which allowed for calculation of maximal instantaneous, mean, and peak-to-peak gradients, plus ejection and acceleration times. Maximal instantaneous gradient by CW Doppler showed an excellent correlation with maximal instantaneous catheterization gradient (r = 0.93, SEE = 9 mm Hg). The correlation of maximal instantaneous Doppler gradient with peak-to-peak catheterization gradient was also linear (r = 0.85, SEE = 12 mm Hg), but there was a consistent overestimation of peak-to-peak gradient in 38 of 40 cases (mean = 17 mm Hg). Mean gradient as calculated by the two techniques correlated best of all measurements performed (r = 0.95, SEE = 6 mm Hg). When patients were grouped into subsets of mild (0 to 25 mm Hg), moderate (25 to 50 mm Hg), and severe (greater than 50 mm Hg) levels of stenosis, the correlation of maximal instantaneous Doppler and peak-to-peak catheterization gradients were r = 0.22, 0.44, and 0.77, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to use a canine preparation of experimental aortic stenosis to compare estimates of pressure gradient derived from continuous wave Doppler ultrasound with gradients measured directly by catheterization. Aortic stenosis was created in six mongrel dogs by placing an elastic band around the aorta. Eighty-eight different pressure gradients, ranging from 5 to 160 mm Hg, were produced by variable tightening of the aortic band. Pressure gradients were measured by micromanometer-tipped catheters placed in the left ventricle and aorta. Doppler spectral signals were simultaneously obtained using a 2.0 MHz nonimaging transducer placed directly on the surface of the ascending aorta. Doppler and pressure recordings were analyzed using a custom-designed software program to measure maximal instantaneous, mean and peak to peak gradients, as well as ejection and acceleration times. Maximal instantaneous Doppler gradient showed an excellent linear correlation with maximal instantaneous catheterization gradient (r = 0.98, SEE = 5.3 mm Hg). The correlation of Doppler-estimated maximal gradient to peak to peak catheterization gradient was also linear (r = 0.97, SEE = 6.2 mm Hg) but resulted in a systematic overestimation of pressure drop (mean overestimation = 9.0 mm Hg). Measurement of the Doppler gradient at mid-systole resulted in a more accurate correlation with the peak to peak catheterization gradient (r = 0.98, SEE = 6.1 mm Hg) and eliminated the problem of overestimation.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous injection of a variety of fluids has been shown to produce right heart contrast by ultrasound, but the intensity and reproducibility achieved are variable. Thus, a new polysaccharide agent being developed for commercial distribution, SHU-454, was quantitatively compared for intensity and variability with agitated saline solution, indocyanine green, carbon dioxide and hydrogen peroxide. Videodensitometry was used to measure peak and total opacification of the right ventricle after peripheral intravenous contrast administration. One hundred eighty injections were performed in nine closed chest dogs while two-dimensional echograms were recorded. SHU-454 yielded the highest peak (p less than 0.001) and total (p less than 0.005) intensity values when compared with the standard agents. In addition, SHU-454 yielded the lowest coefficient of variation between injections (p less than 0.04) in producing this contrast effect. There were no biologically significant changes in heart rate, blood pressure or arterial blood gases during injection of any of the substances used. A newly developed agent, SHU-454, is superior to standard agents in the ability to reliably produce right heart contrast after venous injection in dogs.

Opacification of the left heart chambers after venous injection of echo contrast agents with transpulmonary capabilities has been difficult to achieve because of a lack of availability of a biodegradable nontoxic agent that produces uniformly small microbubbles. SHU-508 is a new saccharide echo contrast agent that produces bubble sizes from 2 to 8 microns in diameter, capable of traversing the pulmonary capillary bed and resulting in left heart contrast. The echo intensity produced by this agent was compared with that of agitated saline solution, indocyanine green and SHU-454 (another experimental saccharide agent for right-sided contrast) during 136 injections in eight dogs. Videotaped two-dimensional echographic images were digitized and analyzed with the use of videodensitometry for peak right and left ventricular intensity, pulmonary transit times and time of persistence of contrast. The highest right ventricular intensity value (3,594 +/- 1,393) was achieved with SHU-508 (p less than 0.05 compared with the other agents). The right ventricular contrast seen with SHU-508 also persisted for a longer period (22.8 +/- 12 s) than with the standard agents (p less than 0.001). Left ventricular contrast with SHU-508 was visually evident in all 42 injections, whereas the peak left ventricular intensity was 35% as bright as that produced in the right ventricle by the same agent. Peak left ventricular intensity values from SHU-508 were compared with those from agitated saline solution injected from the pulmonary capillary wedge position in four dogs. SHU-508 produced brighter left ventricular intensity (1,281 +/- 607) compared with that obtained with the saline-wedge technique (p les than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

No data exist regarding the ability of magnetic resonance imaging to assess cardiac size and performance in human beings. Therefore, measurements of cardiac dimensions by magnetic resonance imaging were compared with those obtained by two-dimensional echocardiography in 21 normal subjects. Magnetic resonance transverse cardiac sections were obtained during electrocardiographic gating using a spin echo pulse sequence. In normal subjects, magnetic resonance imaging yielded a range of values for cardiac dimensions having a similar standard deviation as that of two-dimensional echocardiography. Diastolic measurements of the aorta, left atrium, left ventricle and septum obtained by magnetic resonance imaging correlated well with those obtained by two-dimensional echocardiography (r = 0.82, 0.78, 0.81 and 0.75, respectively). The correlation coefficient of r = 0.35 observed for the posterior wall thickness was not surprising in view of the narrow range of normal values. Only a general correlation (r = 0.53) existed for the right ventricular diastolic dimension; this was probably related to the difficulty in obtaining representative measurements due to the complex geometry of this chamber. Failure of systolic dimension measurements by magnetic resonance imaging to correlate with those obtained by echocardiography is probably related to limitations of electrocardiographic gating, especially of determining the exact end-systolic frame. Although technically complex at present, magnetic resonance imaging does provide an additional noninvasive technique for measurement of cardiac size.

Time-intensity curves can be obtained from contrast echocardiography of the left ventricle. The purposes of this study were: 1) to verify whether these curves conform to the basic principles of indicator-dilution theory; and 2) to derive indexes of left ventricular ejection fraction from curve analysis. In seven closed chest dogs, 31 doses of the polysaccharide agent SHU-454 were injected into the left ventricular cavity during apical four chamber two-dimensional echocardiography. Data were obtained at different levels of ejection fraction, which were induced by changes in preload, afterload and contractility, and measured by single plane Simpson's rule analysis of digital subtraction left ventriculograms. In a subset of two dogs, eight incremental doses (from 1 to 8 ml) of SHU were injected in the basal state. Contrast echocardiograms were digitized off-line, the mean gray level/pixel of a region of interest inside the left ventricular cavity was measured, and the average value for three systolic frames of each beat was used to obtain time-intensity curves. A good correlation was observed between the peak of the time-intensity curve and the quantity of contrast injected (correlation coefficient r = 0.91 by a logarithmic fit). The echo intensities observed in each animal were subsequently transformed in quantity of contrast according to these functions and their natural logarithm was calculated both with and without background subtraction. All curves relating time and the natural logarithm of the corrected intensity exhibited a descending rectilinear portion (washout) in which the correlation was very good (r = 0.97 +/- 0.02 = mean +/- SD) and which was not significantly affected by background subtraction. The validity of this fit was also unaffected by heart rate (55 to 158 beats/min) and angiographic ejection fraction (22 to 74%), and only minimally influenced by duration of contrast washout (3.3 to 14.6 seconds). Ejection fraction was calculated by an algorithm derived from indicator-dilution theory: ejection fraction = [1 - e(-bd)] X 100, where b = slope of the curve and d = cardiac cycle duration. Linear regression analysis between values of ejection fraction derived by angiography and contrast echo yielded r = 0.73. A second index, based on b and d, was derived by multiple regression analysis. Linear regression analysis of this index and angiographic ejection fraction yielded a correlation of r = 0.87.(ABSTRACT TRUNCATED AT 400 WORDS)