a patent foramen ovale was found in the present echocardiographic study as well as our previous nec- ropsy study.8 In the present study, we found a po- tential source of cardiovascular embolism in 41 of 45 patients (91%) with FOMA. These included se- vere atherosclerosis of the ascending aorta and the aortic arch, which was present in 22% of patients (10 of 45) with FOMA, a finding not examined in a study that has reported a higher prevalence of lone FOMA.” In our study, lone FOMA was present in 9% of patients (4 of 45) with FOMA and in 3% of the entire group studied. Of the 4 patients with lone FOMA, 1 had a long aortic valve strand, a finding of uncertain significance.

The incidence of patent foramen ovale in our pa- tients with cerebrovascular embolic events is lower than that previously reported by others.‘-3~5~6~9~10 This may represent the overall higher mean age of our patients, 1,3,9~10 and the difference in the definition of FOMA used in our study compared with previous reports, many of which used a cut-off value of 2 15 mm oscillation of the membrane,‘*4s5*9 included the width of the basal portion of the aneurysm in their definition,‘*2~4~5~9 or did not distinguish between FOMA and aneurysm of the entire atria1 septum.”

Our findings indicate that FOMA is frequently found in older patients with cardioemholic cerebral ischemic events, is often associated with other ab- normalities with embolic potential, particularly patent foramen ovale, and is rarely identified as an isolated finding.

1. Pearson AC, Labovitz AJ, Tatineni S, Gomez CR. Superiority of transesoph- ageal echocardiography in detecting cardiac source of embolism in patients with cerebral ischemia of uncertain etiology. JAm Coil Cardiol 1991;17:66-72.

2. Pearson AC, Nagelhout D, Castello R, Gomez CR, Labovitz L. Atrial septal aneurysm and stroke: a tramesophageal echocardiographic study. J Am Co11 Cardiol 1991;18:1223-1229. 3. Cabanes L, Mas JL, Cohen A, Amarenco P, Cabanes PA, Oubary P, Chedru F, Guerin F, Bousser MG, de Recondo J. Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. A study using transesophageal echocardiography. Stroke 1993;24:1865-1873. 4. Comess KA, DeRook FA, Beach KW, Lytle NJ, Golby AJ, Albers GW. Transesophageal echocardiography and carotid ultrasound in patients with ce- rebral &hernia: prevalence of findings and recurrent stroke risk. .I Am Coil Cardiol 1994;23:1598- 1603. 5. Albers GW, Comess KA, DeRook FA, Bracci P, Atwood JE, Bolger A, Hotson J. Transesophageal echocardiographic findings in stroke subtypes. Stroke 1994;25:23-28. 6. Labovitz AJ, Camp A, Caste110 R, Martin TJ, Ofili EO, Rickmeyer N, Vaughn M, Gomez CR. Usefulness of tramesophageal echocardiography in unexplained cerebral ischemia. Am J Cardiol 1993;72:1448-1452. 7. Silver MD, Dorsey JS. Aneurysms of the septum primum in adults. Arch Path01 Lab Med 1978;102:62-65. 8. Shirani J, Zafari AM, Roberts WC. Morphologic features of fossa ovalis membrane aneurysm in the adult and its clinical significance. JAm Co11 Cardiol 1995;26:466-471. 9. Schneider B, Hanrath P, Vogel P, Meinertz T. Improved morphologic char- acterization of atria1 septal aneurysm by tramesophageal echocardiography: re- lation to cerebrovascular events. JAm Coil Cardiol 1990;16:1000-1009. 10. Mugge A, Daniel WG, Angernxxm C, Spes C;Khandheria BK, Kronzon I, Freedberg RS, Keren A, Dennig K, Engberding R, Sutherland GR, Vered Z, Erbel R, Visser CA, Lindert 0, Hausmann D, Wenzlaff P. Atria1 septal aneurysm in adult patients. A multicenter study using transthoracic and transesophageal echocardiography. Circulation 1995;91:2785-2792. 1 I. Stone DA, Hawke MW, LaMonte M, Kittner SS, Acosta J, Corretti M, Sample C, Price TR, Plotnick GD. Ulcerated atherosclerotic plaques in the tho- racic aorta are associated with cryptogenic stroke: a multiplane transesophageal echocardiographic study. Am Heart J 1995;130:105-108. 12. Khatibzadeh M, Mitusch R, Stierle U, Gromoli B, Sheikhzadeh A. Aortic atherosclerotic plaques as a source of systemic embolism. J Am Coil Cardiol 1996;27:664-669. 13. Freedberg RS, Goodkin GM, Perez JL, Tunick PA, Kronzon I. Valve strands are strongly associated with systemic embolization: a tramesophageal echocar- diographic study. JAm Co21 Cardiol 1995;26:1709-1712. 14. Cujec B, Polasek P, Voll C, Shuaib A. Transesophageal echocardiography

in the detection of potential cardiac source of embolism in stroke patients. Stroke 1991;22:727-733, 15. Belkin RN, Waugh RA, Kiss10 J. Interatrial shunting in atrial septal aneu- rysm. Am J Cardiol 1986;57:310-312. 16. Rahko PS, Xu QB. Increased prevelance of atria1 septal aneurysm in mitral valve prolapse. Am J Cardiol 1990;66:235-237.

Usefulness of Combined Color Doppler/Contrast in Providing Complete Delineation of

Left Ventricular Cavity Gopal Agrawal, MD, Edward G. Cape, PhD, Joel S. Raichlen, MD, Conny Tirtaman, MD,

Eric T. Lee, MS, PoHoey Fan, MD, and Navin C. Nanda, MD

T his study addresses the hypothesis that contrast-en- hanced color Doppler (CECD) will provide im-

proved assessment of left ventricular (LV) cavity size. Because of the low signal-to-noise ratio, it is often dif- ficult to assess cavity size using B-mode echocardi-

From the Heart Station/Echocardiography Laboratories, Division of Cardiology, University of Alabama at Birmingham, Birmingham, Al-

abama; Cardiac Dynamics Laboratory, Children’s Hospital of Pitts- burgh, Universi of Pittsburgh, Pittsburgh, Pennsylvania; and the Di- vision of Cardio ogy, Thomas Jefferson University, Philadelphia, Penn- “i

sylvania. Dr. Nando’s address is: University of Alabama at Birmingham, Heart Station SWB/S102, 620 South 19th Street, Bir- mingham, Alabama 35233. Manuscript received October 28, 1996; revised manuscript received and accepted March 3, 1997.

ography without contrast enhancement. After injection of contrast it can be difficult to distinguish endocardial borders because the borders and the contrast-enhanced blood pool appear similar (i.e., both are represented by relatively high-intensity B-mode pixels). With gain augmentation in CECD, color pixels should approach the endocardial borders but will be clearly different, i.e. one is color (the blood pool) and the other is B mode (the endocardial border). This “contrast” of col- ors should facilitate simpler measurement of the cham- ber boundaries in practice. This study compares delin- eation of the LV chamber by use of contrast-enhanced 2dimensional echocardiography (CE2D), color Dopp- ler (CD), and CECD.

98 6 1997 by Excerpta Medico, Inc. All rights reserved.

0002-9149/97/S 17.00 PII SOOO2-9149(97)00296-g

i

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 PATIENT NO.

B

p 90

!!. 80

CDC ._

__

1 3 5 7 PiTIEN:‘NO.

13 15 17 19 21

FIGURE 1. Contrast-enhanced color Do B

pler flow mappin 1

(CDC) resulted in complete fillin 3,

of the left ventricular (LV) cavity in bath end-diastole [Aj and en -s stole (B] in 20 o 21 patients studied. Contrast-en

l anced 2-dimensional echo-

cardiography (2~C) and color Doppl er ow mapping without contrast enhancement (CD) resulted in only partial filling of the LV cavity.

Twenty-one patients (13 men and 8 women; mean consent was obtained from each patient. Indications age 57 years, range 37 to 84) received intravenous for contrast injection were delineation of LV endo- injection of 3 g of a disaccharide agent (Levovist, cardial border (17 patients, 2 of these were also Berlex Laboratories, Inc., Wayne, New Jersey).’ checked for thrombus versus artifact in the LV apex) This study was approved by the institutional review and assessment of mitral regurgitation severity (4 pa- boards of each institution, and appropriate informed tients).

BRIEF REPORTS 99

FIGURE 2. Apical d-chamber view in 1 of the tie&. Contrast-enhanced B-mode ex- amination (Aj shows incomplete filling of the eft ventricular (Lv) cavity by contrast sig- r nals. However, when color Doppler was turned on, complete opacification of the LV cavity occurred 16). IA = left atrium; RA = right atrium; RV = right ventricle.

All patients underwent a medical history, phys- ical examination, electrocardiography, biochemi- cal screen, and blood count. This clinical evaluation was repeated 0.5 and 24 hours after the contrast study. Heart rate, blood pressure, and respiratory rate were measured before and 5 minutes after contrast injection. Continuous electrocardiographic monitor- ing was maintained during the contrast study. Pa- tients were also monitored for development of ad- verse symptoms or effects.

Patients were imaged from the apex in the left lateral decubitus position using a 2.5-MHz trans- ducer interfaced to a commercially available CD sys- tem (Acuson, 128XP-10, Mountain View, Califor-

100 THE AMERICAN JOURNAL OF CARDIOLOGY@’ VOL. 80

nia, 9 patients; Hewlett-Packard, Sonos 1000 or 1500, Andover, Massachusetts, 12 patients). The pulse repetition frequency was held constant for each study, yielding Nyquist velocities of 32 to 58 cm/s for the range of studies, as required for image opti- mization in each study. Studies were stored on S- VHS videotape.

The percentage of LV cavity filled with CE2D, CD, and CECD was separately calculated using pla- nimetry in both end-diastole and end-systole. The end-diastolic frame was chosen as that with the max- imum size of the LV cavity, whereas the end-systolic frame represented the smallest LV cavity. Similar measurements of the CD pixels were obtained (re-

JULY 1, 1997

placing B-mode contrast signals) in both end-dias- tole and end-systole. The duration of complete con- trast opacification of the LV cavity with CECD was measured in each patient.

In 10 patients, CD imaging was activated just af- ter observing the peak contrast effect in CE2D. These images were used for analysis. In 4 patients, CD and CECD were performed without CE2D. In 7 patients, separate injections were given for B-mode and CD examinations. The second injection (for CD) was given after the B mode had returned to baseline. In these cases, no change in the clinical situation of any patient was noted between injections.

A simple linear regression analysis was per- formed to test the correlation coefficient. Data are expressed as mean ? SD. The difference between 2 means was analyzed by Student’s t test. Interob- server variability was tested by comparing 2 observ- ers’ measurements, whereas intraobserver variability was tested by comparing measurements from the same observer after a 3-month period.

The results obtained using CE2D, CD, and CECD are shown in Figure I. CD, and CE2D only partially filled the LV chamber in end-diastole and end-sys- tole. CECD produced marked improvement in filling of the left ventricle when compared with CD (p <O.OOOl) and CE2D (p <O.OOOl). CECD com- pletely filled the LV cavity in all patients except 1 at both end-diastole and end-systole (p <O.OOOl) (Figure 2). Both inter- and intraobserver reproduci- bility were found to be excellent (r = 0.96, SEE = 0.05 cm’, and r = 0.97, SEE = 0.04 cm2, respec- tively).

For all 21 patients, the duration of increased CD signal intensity for complete opacification of the LV cavity in end-diastole and end-systole was long (mean 193.67 seconds, range 68 to 380; or a mean of 276.48 cycles, range 95 to 800). Digital extraction of color pixel magnitudes after injection showed higher average intensities for peak diastole versus peak systole (p = 0.017).

The 4 patients who were studied for assessment of mitral regurgitation had good delineation of the LV endocardial border as determined by CE2D. In these patients, we found identical values of LV cav- ity size by CD with contrast compared with LV cav- ity size by 2D echocardiography alone in end-dias- tole and end-systole (8 observations, r = 1.0).

The disaccharide contrast agent was very safe and produced no side effects during the test and follow- up periods. Only 1 patient in the study had local redness, swelling, and tenderness at the injection site in the right arm, which recovered after a few days. No clinically relevant changes were observed in heart rate, blood pressure, electrocardiogram, and blood chemistry.

In this study we investigated 3 media that “fill” the chamber and are displayed on a 2D image. By measuring the boundary of this medium we approx-

imate the interior of the chamber. Injection of con- trast agent improved the 2D image but was limited in producing better measurements of LV area since streaming and areas of stagnation cause nonuniform distribution of contrast agent. The resulting improve- ment of the image may be inconsistent throughout, or not improved at all, in certain segments.

CD was also useful for delineation of the wall/ blood pool interface because, due to swirling effects, few locations within the LV chamber have zero ve- locity. Because of the wall filter that is imposed in cardiac imaging, however, a specific range of low velocities is not imaged. Because some regions of flow stagnation will exist and velocities immediately adjacent to a wall will have velocities equaling those of the wall, CD alone must embody some fraction of underestimation.

Combining contrast enhancement and CD imag- ing eliminates the pitfalls each technique has alone. By increasing the apparent gain of the color flow imager, contrast agents increase the sensitivity of CD to low-velocity regions, providing a more complete delineation of the LV cavity.

Higher average intensities of color pixel magni- tudes after contrast injection during peak diastole compared with peak systole mainly reflect the angle of bulk outflow tract velocity to the 4-chamber view- ing plane. The 4-chamber view, which includes the mitral inflow plane, must deviate to some extent from the outflow tract, so that systolic CD frames include relatively stagnant regions of flow.

Use of contrast to enhance CD imaging increases the possibility of bleeding of color into the LV walls, which could potentially produce overestimation of chamber size. Care must be taken to ensure this does not occur, as contrast enhancement effectively in- creases the instrument gain by increasing the ampli- tude of returning ultrasound signals. Ongoing im- provements in instrumentation by ultrasound manufacturers to optimize contrast imaging will help solve this potential problem.

CE2D improves delineation of LV endocardial borders, but difficulties still arise due to incomplete filling of the LV cavity2.” and similar 2D appearance of the contrast-enhanced blood pool and the endo- cardial surfaces.

CECD results in complete delineation of the LV endocardium in almost all patients, and this should facilitate more accurate determination of LV vol- ume and ejection fraction.

1. Aggrawal KK, Gatewood RP, Nanda NC, Chopra KL. Improved TEE as- sessment of significant proximal narrowing of the left anterior descending and left circumflex coronary arteries using echo contrast enhancement. Am J Car&d 1994:73:1131-1133. 2. Keller MW, F&stein SB, Watson DD. Successful left ventricular opacifi- cation following peripheral venous injection of sonicated contrast agent: an experimental evaluation. Am HearrJ 1987;114:570-575. 3. Smith MD, Elion JL, McClure RR, Evans OL, DeMaria AN. Opacification with peripheral venous injection of a new sacchtide echo contrast agent in dogs. JAm Co11 Cardiol 1989;13:1622-1628.

BRIEF REPORTS 101