Janine R. Shapiro

Intravenous contrast echocardiography with use of sonicated albumin in humans: Systolic disappearance of left ventricular contrast after transpulmonary transmission☆

The transmission of echocardiographic contrast medium and the cyclic changes in left ventricular videodensity during transpulmonary contrast echocardiography were investigated in nine adult volunteers with the use of intravenous injections of sonicated albumin (microbubble size 5.2 +/- 2.6 microns). Right and left ventricular and myocardial contrast were quantitated by videodensitometric analysis. The injections caused no symptoms, and no hemodynamic or electrocardiographic changes were observed. All injections resulted in right ventricular contrast. Mean peak right ventricular videodensity was 75 +/- 48 at end-diastole and 61 +/- 36 gray scale U/pixel at end-systole (p less than 0.05). Seventy-eight percent of injections resulted in left ventricular contrast with a mean peak videodensity of 21 +/- 33 gray scale U/pixel. Early systole was associated with a rapid decrease in left ventricular contrast intensity with near total disappearance of contrast by end-systole (from 23 +/- 33 and 17 +/- 23 U/pixel at end-diastole to 6 +/- 10 and 3 +/- 2 at end-systole at the left ventricular base and apex, respectively; p less than 0.05). None of the injections resulted in myocardial contrast enhancement by visual or quantitative analysis. Thus, left ventricular contrast echocardiography can be achieved after intravenous injections of sonicated albumin. Transpulmonary left ventricular contrast echocardiography is associated with near total disappearance of contrast during systole. This may be secondary to the destruction of microbubbles by the high left ventricular systolic pressure. These findings may help explain the limited success of this technique thus far for myocardial perfusion imaging.

Quantitative assessment of the immediate results of coronary angioplasty by myocardial contrast echocardiography.

A low pressure gradient across the residual lesion and a minimal percent residual stenosis are markers of a successful coronary angioplasty. A more physiologic method of assessing the results of coronary angioplasty would involve assessment of myocardial perfusion in the affected coronary bed. Contrast two-dimensional echocardiography provides information about regional myocardial perfusion. To assess the correlation between pre- to postcoronary angioplasty changes in gradient or percent stenosis and the increase in peak contrast intensity, 23 consecutive patients were studied during coronary angioplasty. In 19 of the 23 patients, the coronary angioplasty was successful and in 15 (79%) of the 19, an adequate echocardiographic study was obtained. Mild and transient side effects of echo contrast were observed in 3 of the 15 patients. The gradient across the residual lesions decreased from 52 +/- 12 to 11 +/- 4 mm Hg (mean +/- SD), the diameter of the stenotic lesion decreased from 89 +/- 10 to 25 +/- 16% and corrected peak contrast intensity (peak contrast - baseline contrast in gray level U/pixel) increased from 15 +/- 16 to 50 +/- 26. All these differences were significant at the p less than 0.001 level. Corrected peak contrast intensity correlated exponentially with the decrease in pressure gradient (r = 0.82, p less than 0.001). The correlation curve had a greater increase in peak contrast intensity at gradient decreases greater than 45 mm Hg. Corrected peak contrast intensity did not correlate with decrease in diameter of the stenotic lesion (r = 0.19).

Reproducibility of quantitative myocardial contrast echocardiography

To determine whether myocardial contrast echocardiography is quantitatively reproducible, repeated intracoronary injections of sonicated albumin (5%) were performed in eight open chest dogs. Paired injections were performed at baseline, during ischemia produced by ligation of a coronary artery, and during hyperemia induced by intravenous infusion of 0.75 mg/kg body weight of dipyridamole. Contrast washout curves were generated for the left anterior descending coronary artery territory (ischemic area) and left circumflex coronary artery territory (nonischemic area) by beat per beat analysis of frozen end-diastolic frames of left ventricular short-axis views. Peak contrast intensity, contrast washout half-time and area under the curve were derived from these curves. A total of 75 contrast washout curves were analyzed for the study of interinjection, intraobserver and interobserver reproducibility. The correlation coefficients between measurements obtained from paired injections of the echocardiographic contrast agent (interinjection reproducibility) ranged from 0.78 for peak contrast intensity to 0.87 for area under the curve. Percent error varied between 14.7% and 24.7%. The intraobserver variability in measurements was less than the interinjection variability, with a cumulative mean percent error of 17.8% and correlation coefficients of 0.72 (peak contrast intensity), 0.95 (area under the curve) and 0.96 (washout half-time). Interobserver correlation for all indexes was high (r = 0.92 to 0.96). It is concluded that peak contrast intensity, contrast washout half-time and the area under the curve derived from myocardial contrast washout curves can be measured reproducibly from videotapes. In addition, the variability between two injections attempted under identical conditions is greater than reader variability from videotapes.

Lack of Lung Hemorrhage in Humans After Intraoperative Transesophageal Echocardiography with Ultrasound Exposure Conditions Similar to Those Causing Lung Hemorrhage in Laboratory Animals

This study investigated the phenomenon of ultrasonically induced lung hemorrhage in humans. Multiple experimental laboratories have shown that diagnostic ultrasound exposure can cause hemorrhage in the lungs of laboratory animals. The left lung of 50 patients (6 women, 44 men, mean age 61 years) was observed directly by the surgeon after routine intraoperative transesophageal echocardiography was performed. From manufacturer specifications the maximum derated intensity in the sound field of the system used was 186 W/cm2, the maximum derated rarefactional acoustic pressure was 2.4 MPa, and the maximum mechanical index was 1.3. The lowest frequency used was 3.5 MHz. This exposure exceeds the threshold found for surface lung hemorrhage seen on gross observation of laboratory animals. No hemorrhage was noted on any lung surface by the surgeon on gross observation. We conclude that clinical transesophageal echocardiography, even at field levels a little greater than the reported thresholds for lung hemorrhage in laboratory animals, did not cause surface lung hemorrhage apparent on gross observation. These negative results support the conclusion that the human lung is not markedly more sensitive to ultrasound exposure than that of other mammals.

Exercise doppler echocardiography in patients with mitral prosthetic valves

Submaximal supine exercise was done by 17 patients with mitral prostheses. Eleven had Björk-Shiley (BS) and six had Starr-Edwards (SE) valves. In 15 patients with normally functioning prostheses, valve area at rest was 2.4 +/- 0.25 cm2 in the BS patients and 1.8 +/- 0.35 cm2 in the SE group (p less than 0.01). In the SE group, peak and mean gradients increased from 8 +/- 1 and 5 +/- 1 mm Hg, respectively, at rest to 22 +/- 5 and 13 +/- 4 mm Hg at peak exercise (mean +/- 1 SD). In the BS group, peak and mean gradients increased from 10 +/- 3 and 5 +/- 2 mm Hg, respectively, at rest to 16 +/- 3 and 10 +/- 3 mm Hg at peak exercise. Peak pressure gradient at peak exercise and the increase in peak gradient with exercise (exercise-resting gradient) were significantly higher in the SE group (p less than 0.05). By plotting the heart rate versus the transmitral gradient during the recovery period, a heart rate-gradient curve was obtained for each type of prosthesis. Doppler echocardiography with moderate supine exercise can be performed in most patients with mechanical prosthesis. Hemodynamic properties (the occlusive character of the SE prosthesis) were brought out by exercise. Doppler echocardiographic measurements during exercise can provide important information, particularly in patients with borderline measurements at rest.

Myocardial contrast two-dimensional echocardiography: dose-myocardial effect relations of intracoronary microbubbles.

It is controversial whether echocardiographic contrast agents prepared by sonication cause transient myocardial depression beyond that known to occur with contrast agents alone. In nine open chest dogs, contrast injections were made into the left anterior descending coronary artery during two-dimensional echocardiography. One hundred forty-four recordings were analyzed subsequently, by an observer who was unaware of other data, for percent depression of systolic wall thickening, duration of regional wall motion abnormalities, peak contrast enhancement and contrast washout. Two microbubble sizes were obtained by sonicating Renografin-76 (meglumine sodium diatrizoate): mean diameter 12 +/- 3 (SEE) and 20 +/- 6 micron. Four doses (range 0.5 to 3 ml) of each of four agents (12 and 20 micron bubbles in Renografin, nonsonicated Renografin and saline solution) were injected in random order. Significant relations were found between percent depression of systolic wall thickening, duration of regional wall motion abnormalities and contrast washout time versus microbubble size (p less than 0.001) and microbubble dose (p less than 0.01). Little increased contrast effect was found at larger doses or with larger microbubbles compared with the smaller doses and size studied. Injections of nonsonicated Renografin caused less depression of systolic wall thickening (p less than 0.05), faster resolution of wall motion abnormalities (p less than 0.05), less contrast (p less than 0.001) and more rapid contrast washout (p less than 0.001) than did 12 micron bubbles in Renografin. A significant correlation was found between the duration of regional wall motion abnormalities and contrast washout time (r = 0.93, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of the activated coagulation time and heparin dose-response curve for the determination of protamine dosage in vascular surgery

The activated coagulation time (ACT) can be used to construct a two-point heparin dose-response curve (HDRC) from the ACT values at baseline and 5 minutes after heparin administration. The ACT value at any subsequent time interval can then be used to estimate the residual heparin activity from the HDRC. The protamine dose is calculated to be the amount of residual heparin multiplied by a correction factor (1.3 was suggested for cardiac surgery). In vascular surgery, heparin and protamine dosing remain empirical, ACT monitoring is not standard, and use of the HDRC has not been previously investigated. Forty-five patients were prospectively randomized to one of three groups. ACT was measured before heparinization (1 mg/kg, 1 mg = 100 U), 5 minutes later, and then every 30 minutes until just prior to and after protamine administration. Group I received 1 mg/kg of protamine. In Groups II and III the residual heparin activity was interpolated from the HDRC and multiplied by 1.3 or 1.0, respectively, to derive the protamine dosage. Randomization created balanced groups with respect to demographic data. The individual peak effect of heparin ranged from 177% to 401% of control. The ACT returned to control after protamine in all groups. The protamine dose was significantly less when the HDRC was used (P < 0.05). Group III received the least protamine (0.64 +/- 0.07 mg/kg, P < 0.05). No adverse protamine reactions or postoperative bleeding occurred. It is concluded that ACT monitoring and use of the HDRC provides a safe and easy method to individualize protamine dosage in vascular surgery.

Digital Subtraction Myocardial Contrast Echocardiography: Design and Application of a New Analysis Program for Myocardial Perfusion Imaging

Myocardial contrast echocardiography may provide important physiologic information on myocardial perfusion. Most current analysis programs use manual frame grabbing and selecting of the area of interest. This is time-consuming and not highly reproducible. A system for automatic analysis of myocardial contrast echocardiographic studies was developed and evaluated. The program acquires an electrocardiographically gated sequence of end-diastolic images with a frame grabber in a personal computer. The baseline image is subtracted and the videodensity versus time contrast curve parameters are calculated on-line. Fast color-coded analysis is done automatically with a running square window that covers the entire image. A second mode of contrast analysis allows manual selection of multiple regions of interest. The program was evaluated with contrast echo data from open-chest dogs and two demonstrative patients. This myocardial contrast analytic package is an inexpensive, rapid, flexible, convenient, and reproducible on-line method that facilitates myocardial contrast echocardiographic analysis.

Bidirectional glenn shunt surgery using lepirudin anticoagulation in an infant with heparin-induced thrombocytopenia with thrombosis.

There are few reports of the management of pediatric patients with heparin-induced thrombocytopenia (HIT) requiring cardiac surgery using currently available anticoagulants. We report a case of an infant with HIT requiring a bidirectional Glenn shunt who was successfully managed using lepirudin (r-hirudin, Refludan; Aventis, Bridgewater, NJ). Dosing and monitoring of anticoagulation were difficult, and we suggest caution in the use of lepirudin for cardiac surgery unless reliable monitoring of the degree of anticoagulation becomes available.

Contrast agents for myocardial perfusion studies

Twenty years after Gramiak and Shah at the University of Rochester reported the echocardiographic contrast effect [1], the uses and applications of contrast echocardiography are still growing. The need for new and more standardized contrast agents with superior reproducibility and capillary transmission capability has been felt for years [2]. Meltzer et al. [3] and Armstrong et al. [4] reported on commercially prepared contrast agents in the early 1980s. Feinstein et al. [5] introduced the use of ultrasonic energy (sonication) to create smaller microbubbles. Current knowledge and future prospects about mechanisms of the ultrasound contrast effect and the new contrast agents are summarized in this chapter.