Oi Ling Kwan

Quantitative assessment of mitral regurgitation by doppler color flow imaging: Angiographic and hemodynamic correlations

This study was performed to test the hypothesis that measurements of jet area by Doppler color flow imaging can predict the angiographic severity and hemodynamic consequences of mitral regurgitation. Doppler color flow imaging was performed in 47 patients undergoing cardiac catheterization and left ventriculography. The jet area was measured as the largest clearly definable flow disturbance in the parasternal and apical views, and expressed as the maximal jet area, the mean of the largest jet area (average jet area) in two views or as the ratio of these measures to left atrial area. Correlation of all Doppler color flow measurements with angiographic grades of mitral regurgitation were comparable, maximal jet area being closest at r = 0.76. A maximal jet area greater than 8 cm2 predicted severe mitral regurgitation with a sensitivity of 82% and specificity of 94%, whereas a maximal jet area less than 4 cm2 predicted mild mitral regurgitation with a sensitivity and specificity of 85% and 75%, respectively. All patients with an average jet area greater than 8 cm2 manifested severe mitral regurgitation. However, jet area measurements showed limited correlation with regurgitant volume and fraction (r = 0.55 and 0.62, respectively) for maximal jet area, and were not predictive of hemodynamic abnormalities, including those of pulmonary wedge pressure, stroke volume or ventricular volumes. Thus, in patients with mitral regurgitation, maximal jet area from Doppler color flow imaging provides a simple measurement that predicts angiographic grade, but manifests a weak correlation with regurgitant volume and does not predict hemodynamic dysfunction.

Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction

A hydrogel derived from myocardial extracellular matrix mitigates negative left ventricular remodeling and improves heart function after myocardial infarction in pigs. Healing Biomaterial Delivered to Heart Repairing a broken heart takes more than just time—it may also take a special hydrogel material derived from the heart itself. After a heart attack, cells die and are replaced by a thick scar, which cannot pump blood like normal tissue. This results in total heart failure and death in these patients that survive the initial heart attack. In response, Seif-Naraghi and colleagues have developed a biomaterial that can be injected into the heart to prevent scar formation and help the heart to heal and function as it normally would. The authors used a pig model to study the effects of a myocardial extracellular matrix (ECM)–derived biomaterial on heart healing after myocardial infarction (MI). Two weeks after MI, the material was delivered via catheter to the target region of the heart—much like it would in a real clinical trial with patients. Control animals received either no injection or saline only. After 3 months, tests were performed to see if the heart had healed, if it functioned properly, and if the material caused any irritation to the heart tissue. Seif-Naraghi et al. reported improvements in heart function in the matrix-injected animals and worsening of function in the controls. Their data suggest that the matrix can prevent post-MI negative left ventricular remodeling by improving systolic function and contractility. Other than function, the material appeared to encourage healthy muscle and blood vessel formation in the infarcted areas, whereas tissue from control animals was thin and fibrotic. This myocardial matrix material did not damage peripheral tissues, such as the lungs and liver, or disrupt cardiac rhythm in pigs. Even with direct injection into the left ventricle lumen in rats, there was no inflammation, edema, or hemorrhage. These data in a large animal show that the myocardial ECM–derived material not only improves functional outcome after a heart attack but also is safe and nontoxic, thus making the material ready to move forward toward clinical tests in people. 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.

Effects of aging on left atrial reservoir, conduit, and booster pump function: a multi-institution acoustic quantification study

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.

Comparative accuracy of two-dimensional echocardiography and Doppler pressure half-time methods in assessing severity of mitral stenosis in patients with and without prior commissurotomy.

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)

Left heart opacification with peripheral venous injection of a new saccharide echo contrast agent 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)

Comparative Value of Dobutamine and Adenosine Stress in the Detection of Coronary Stenosis With Myocardial Contrast Echocardiography

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.

Superior intensity and reproducibility of SHU-454, a new right heart contrast agent

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.

Regurgitant jet size by transesophageal compared with transthoracic Doppler color flow imaging.

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)

Correlation of continuous wave doppler velocities with cardiac catheterization gradients: An experimental model of aortic stenosis

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)

Accuracy of combined two-dimensional echocardiography and continuous wave Doppler recordings in the estimation of pressure gradient in right ventricular outlet obstruction

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.