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(Chest. 2001;120:1287-1292.)
© 2001 American College of Chest Physicians

Contrast Microbubbles Improve Diagnostic Yield in ICU Patients With Poor Echocardiographic Windows*

Thanh T. Nguyen, DO; Milind R. Dhond, MD; Raju Sabapathy, MD and William J. Bommer, MD

* From the University of California, Davis Medical Center, Sacramento, CA.

Correspondence to: William J, Bommer, MD, Division of Cardiovascular Medicine, Ambulatory Care Center, 4860 Y St, Suite 2800, Sacramento, CA 95817


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objective: To determine the value of contrast echocardiographic studies in patients admitted to ICUs who have poor echocardiographic windows secondary to COPD, ventilator use, or inability to obtain optimal positioning for the echocardiogram.

Design: A prospective comparison study of technically difficult patients in the ICU.

Outcome measure: The total scores for the left ventricle (LV) in the two-chamber and four-chamber views were calculated at baseline and following injection of 1 to 2 mL of a contrast agent. The mean numbers of segments visualized in all patients at baseline and after injection of contrast agent were compared to assess the effect on improved visualization.

Results: Forty consecutive patients underwent echocardiography in the ICU for evaluation of LV function. Of these, 25 patients (63%) had poor visualization of the endocardium and required IV contrast agent. In these 25 patients, the average baseline segmental score was 4.5, compared to 11.6 in patients who received an IV contrast agent. Nineteen patients had an average baseline segmental score of 3.9 and were deemed to have a nondiagnostic study. After administration of IV contrast, all patients converted to a diagnostic study, with an average score of 11.6 segments visualized.

Conclusions: Use of echocardiographic contrast agents in selected patients with poor baseline echocardiographic windows in the ICU setting significantly enhances segmental LV visualization and yielded 100% conversion from nondiagnostic to diagnostic studies.

Key Words: contrast agent • echocardiogram • ICU • IV


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Echocardiography has been widely used as a noninvasive diagnostic tool in cardiovascular medicine. It offers a quick, accurate, and inexpensive method to assess left ventricular (LV) volumes, the severity of valvular disease, and LV function.1 2 3 4 5 The assessment of LV function can provide valuable diagnostic and prognostic information in patients with cardiovascular disease and may be useful in managing patients in an ICU setting. However, poor visualization of endocardial borders due to suboptimal echocardiographic windows in certain individuals may reduce the value of the test. Intubated patients who have COPD or cannot be positioned adequately tend to have poor echocardiographic images.6 7 8 These comprise a significant number of patients found in the ICU setting. Therefore, an agent that can enhance the visualization of the endocardium would be a useful adjunct to standard transthoracic echocardiography in the ICU.

With the aid of IV contrasts agent, LV opacification and visualization of endocardial borders are improved.9 10 11 12 However, it is not known whether a contrast agent used in patients in the ICU will significantly enhance the assessment of LV function. The purpose of this study was to determine if an IV contrast agent would enhance the visualization of the endocardium for the assessment of LV function in ICU patients.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patient Selection
Patients were selected from those undergoing echocardiography for LV function and who were currently in an ICU setting at the time of the study. To be excluded, patients had to have diagnostic LV endocardial border delineation, defined as a good visualization of nine or greater endocardial segments in the apical two-chamber and four-chamber views; a history of hypersensitivity to albumin; or failure to achieve IV access for contrast injection. Endocardial segments were assigned based on previously established methodology,10 12 whereby the two-chamber and four-chamber views of the LV were divided into 12 segments. This offered a simpler and more practicable approach than the more complex 16-segment model used by the American Society of Echocardiography.13

Study Design
This was a prospective study to determine if a contrast agent (Optison; Mallinckrodt Medical; St. Louis, MO) would enhance LV opacification in ICU patients with poor echocardiographic images. The principal objective of the study was to compare the visualization scores of routine vs contrast-enhanced echocardiograms in ICU patients. The study evaluated LV opacification, the number of LV endocardial border segments visualized, and the conversion rate from nondiagnostic to diagnostic echocardiograms. The primary teams were blinded to the results of the contrast echocardiograms.

Contrast Agent
Optison is a suspension of perfluoropropane-filled albumin microspheres with a mean concentration of 5.0 to 8.0 x 108 microspheres per milliliter and a mean diameter of 2.0 to 4.5 µm. Optison comes prepackaged in 3-mL vials and is prepared for injection by rotating the vial for 30 s.

Contrast Injection
After routine echocardiography was performed, 1 mL of contrast agent was injected through an IV line followed immediately by 5 mL of normal saline solution flush. If the LV was not opacified within 30 s, an additional 1 mL of contrast agent was administered through the same route, followed by another 5 mL of normal saline solution flush. During noncontrast and contrast studies, heart rate, BP, ECG, and oxygen saturation were monitored.

Transthoracic Echocardiography
Echocardiography was performed (Sonos 5500; Hewlett-Packard; Andover, MA) using a 1.8/3.6-MHz transducer. Each patient was positioned on the left side according to the patient’s ability to move with ECG leads attached. Noncontrast and contrast images were obtained using harmonic imaging. The ultrasound was transmitted at 1.8 MHz and received at twice this frequency (3.6 MHz). Instrument settings were optimized for each patient by the sonographer. Apical two-chamber and four-chamber views were recorded on videotape (super video home system [sVHS] format). The videotape was then replaced, and contrast images were obtained and recorded on a second videotape. The instrument settings were left unchanged except for transmit power, which was lowered to a mechanical index of < 1.0 to reduce apical bubble destruction. Apical two-chamber and four-chamber views of the LV were acquired at a rate of 30 frames per second. Great care was taken to avoid apical foreshortening and to maximize the length from the base to apex.

Image Analysis
Two independent cardiologists with expertise in the field of echocardiography analyzed the sVHS videotapes of the noncontrast and contrast echocardiograms. All observations were made at baseline and after injection of contrast agent in the two-chamber and four-chamber views. In addition, the two-chamber and four-chamber views of the LV were divided into 12 segments, as shown in Figure 1 .



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  		Figure 1.. Two-chamber and four-chamber views of the LV divided into 12 segments. LA = left atrium; RV = right ventricle; RA = right atrium.

 
LV Opacification: LV opacification was a qualitative assessment by both cardiologists. Adequate opacification was defined as opacification of two thirds (8 of 12 segments) or greater of the LV chamber.

Segmental Scoring: A score of 1 was assigned to a wall segment if it was visualized in both systole and diastole. A score of 0 was assigned to the segment if it was not visualized. At the end of each echocardiographic study, the segmental scores were totaled and divided by 12 to represent a mean score for that echocardiographic study.

Diagnostic Yield: The rate of conversion from a nondiagnostic to a diagnostic echocardiogram with contrast was assessed. Patients were considered to have a nondiagnostic echocardiogram if the average score for that specific study was less than six segments visualized. Studies were determined to have become diagnostic after contrast if they improved to more than nine segments visualized. The study was classified as an intermediate diagnostic study if 6, 7, 8, or 9 segments were visualized.

Statistical Analysis
Numerical data are expressed as mean ± SD. A paired two-sample t test was used to test for statistical difference between the noncontrast and contrast studies. Statistical significance was determined at the {alpha} = 0.05 level.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Patient Population
A total of 40 consecutive ICU patients underwent echocardiography to assess LV function. A wide variety of primary diagnoses accounted for the patient population, including pneumonia (n = 15), labile hypertension (n = 1), myocardial infarction (n = 2), respiratory failure (n = 20), and pulmonary embolus (n = 2). Of these patients, 15 patients (37%) had excellent acoustic windows and all myocardial segments were seen in the apical two-chamber and four-chamber views. The remaining 25 patients (63%) had three or more segments not well visualized on noncontrast echocardiograms and therefore formed the study population. The population characteristics are outlined in Table 1 . The mean body mass index for our patients was 29 ± 5 kg/m2. No significant changes in heart rate, oxygen saturation, and BP were detected during the IV administration of the contrast agent. Representative precontrast and postcontrast echocardiograms from a patient in this study are shown in Figure 2 .


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  		Table 1.. Patient Characteristics (n = 25)*

 


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  		Figure 2.. Apical four-chamber (left) and two-chamber (right) views from a single patient. Top: Precontrast, there is poor visualization of the LV endocardial borders. Middle: After injection of 1.0 mL of contrast agent, there is 100% opacification of the LV chamber and complete endocardial delineation. Bottom: The orange outline delineates the endocardial (inner) and epicardial (outer) borders, following the contrast injection. The inner endocardial border is not visible on the precontrast (top) images. However, following contrast injection the endocardial border can be more completely visualized (middle, bottom).

 
Imaging Variables
As seen in Table 1 , ICU patients had numerous factors that have been associated with poor echocardiographic images. Eighteen patients (72%) had a history of COPD. Thirteen patients (52%) were receiving mechanical ventilation. Sixteen patients (64%) could not be positioned in the usual left-lateral recumbent position for the echocardiogram. Sixteen patients (64%) had two of the three contributing factors that lessen the quality of the echocardiographic study. Eight patients (32%) had all three contributing factors.

LV Opacification
After visual assessment of the sVHS-videotape images, all 25 patients (19 patients with nondiagnostic studies and 6 patients with intermediate studies) had achieved >= 8 of 12 segments seen after the injection of contrast. Therefore, adequate LV opacification was achieved at end systole and end diastole in all patients following contrast echocardiography.

Segmental Score
The baseline echocardiograms in 25 patients had an average total score of 4.5 segments visualized (range, 2 to 8 segments). The IV contrast agent was used in all 25 patients. Twenty-one patients (84%) needed only 1 mL of contrast agent for the study. Four patients (16%) needed an additional 1 mL of contrast agent for the study. The average amount of contrast agent used in this study per patient was 1.2 mL. After contrast injection, the average segmental score was increased to 11.6 segments (range 9 to 12 segments) visualized for all patients (Fig 3 ).



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  		Figure 3.. The number of LV segments visualized before (precontrast) and after (postcontrast) are shown in open and solid bars. There is a statistically significant increase in segments visualized with contrast agent for patients with nondiagnostic studies, for patients with intermediate studies, and for all patients.

 
Diagnostic Yield
The rate of conversion from a nondiagnostic to a diagnostic echocardiogram was evaluated with each study based on the wall segment scores. All of the patients (n = 19) who had a nondiagnostic echocardiogram converted to a diagnostic study. In patients who converted from a nondiagnostic to a diagnostic study, the average score was 3.9, increasing to 11.6 endocardial segments visualized after contrast. The remaining six intermediate studies had a baseline echocardiogram with an average of 6.3 segments visualized. After contrast, all of the intermediate studies converted to diagnostic studies with an average score of 11.4 segments visualized. Thus, the contrast studies converted all nondiagnostic and intermediate studies to diagnostic studies with excellent visualization.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
LV function and regional wall motion assessment are important clinical variables in managing patients, especially those in an ICU setting. Patients who are admitted into the ICU tend to have more difficult echocardiographic images for a variety of reasons. These include mechanical ventilation, inability of appropriate positioning for the echocardiograhic study, and higher incidence of COPD. Although echocardiography is an excellent tool to assess LV function, regional wall motion, and valvular disease, it has limited usefulness in patients with poor echocardiographic images. With the use of contrast agents, patients with poor echocardiographic images (and therefore nondiagnostic studies) can be converted to diagnostic studies yielding more accurate data. By using harmonic imaging, it is possible to detect ultrasound energy resulting from the resonance or destruction of microbubbles. The increased signal-to-noise ratio detection by harmonic imaging will result in an increase in the video intensity, resulting in a greater success rate of LV opacification after injection of contrast agent.

Our study was not designed to analyze the cost-effectiveness of using a contrast agent in ICU patients with poor echocardiographic windows. However, by improving diagnostic capabilities of echocardiograms, cost-effectiveness may improve secondary to the decrease of repetitive testing in patients with initially nondiagnostic studies. Shaw et al14 15 have shown that in a selected patient cohort, the use of myocardial contrast echocardiography results in improved diagnostic accuracy and cost-effectiveness.

Rationale for Using Contrast Agents in the ICU
The small size of the microspheres allows them to pass through the pulmonary circulation. The low diffusion rate of the high-molecular-weight gas (188 g/mol) delays the disappearance of the microspheres and permits full opacification of the left-heart chambers. Studies8 10 12 have shown the use of microbubbles improved endocardial border visualization and wall motion assessment in patients with suboptimal echocardiographic studies. We chose Optison because, to our knowledge, it is currently the only commercially available transpulmonary contrast agent in the United States. Most ICU patients in our institution have poor windows for an echocardiographic study. They tend to have poor echocardiographic windows due to factors mentioned previously. The information from these studies may not be interpreted accurately, and some studies would even be considered nondiagnostic. Currently, there are few studies in the literature assessing the usefulness of contrast echocardiography in patients in an ICU setting. This study was designed to demonstrate the usefulness of utilizing a contrast agent in patients admitted to an ICU. We demonstrated that a more accurate assessment of global and regional LV function could be achieved using a contrast agent.

The ability to provide a better diagnostic study allows physicians in the ICU to optimize management of patients with LV dysfunction. Since the use of contrast-enhanced echocardiography improves the diagnostic yield of the study, it allows more accurate assessment of LV function and aids the clinician in differentiating patients with normal vs reduced LV function. This may be most valuable in patients with ejection fractions < 40% in whom medical management differs greatly when compared to patients with preserved ejection fraction.16 17 18 19 20 It is important to note that contrast echocardiography is very useful in patients without adequate visualization of endocardial borders, as defined previously, in the two-chamber and four chamber views on baseline echocardiogram in the ICU. Currently, there are no data to support the use of contrast echocardiogram in patients in the ICU in whom all segments can be clearly seen on the baseline echocardiogram.

Study Limitations
All of the patients in the study were in sinus rhythm. None of the patients had frequent ventricular ectopy or atrial fibrillation. It is not known whether contrast echocardiography would be as accurate in a patient population with arrhythmias.

Conclusions
Contrast echocardiography in ICU patients with limited echocardiographic windows provides LV opacification and significantly improves wall segment analysis. This should significantly enhance the assessment of LV function in these critically ill patients.


   Footnotes
 
Abbreviations: LV = left/ventricle/left ventricular; sVHS = super video home system

Received for publication January 6, 2000. Accepted for publication March 1, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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