Significant Benefits Seen for Critically Ill Patients Undergoing Contrast-Enhanced Echocardiography

A large, retrospective study has demonstrated that use of contrast-enhanced echocardiography was associated with a significantly improved short-term survival among critically ill, intensive care unit (ICU) patients, when compared with matched patients receiving noncontrast echocardiography.

The study's findings were presented at the 58th annual scientific sessions of the American College of Cardiology held in Orlando, FL, USA, in March 2009. Patients who received contrast exhibited a 26% lower risk of short-term mortality within 48 hours after the exam when compared with patients who received echocardiography without the ultrasound contrast agent. Transthoracic echocardiography, the most common type of echocardiogram, uses a transducer on a person's chest to send high frequency ultrasound waves through the chest wall to the heart to generate images of the heart that physicians can then analyze. A new contrast agent comprised of lipid microspheres was used to improve the images of suboptimal noncontrast echocardiograms.

These recent findings build on a recent multicenter 2008 retrospective study of over four million hospitalized patients that also demonstrated that echocardiography with Definity vial for injectable suspension (perflutren lipid microsphere), developed by Lantheus Medical Imaging, Inc. (North Billerica, MA, USA), was associated with a lower risk of short-term mortality in comparison with patients undergoing non-Definity echocardiograms.

"The data demonstrate a significantly lower risk of short-term mortality among critically ill patients receiving contrast-enhanced echocardiograms and affirm the clinical value of echocardiogram contrast agents as an important diagnostic tool for specialized patient populations," said Michael L. Main, M.D., associate professor of medicine, University of Missouri (Kansas City, USA); director, echocardiography laboratory, Saint Luke's Mid America Heart Institute (Kansas City, MO, USA) and lead author on the study. "Given the limited diagnostic options for critically ill patients, we are encouraged by these results that demonstrate the survival benefit of contrast-enhanced echocardiograms in an ICU setting."

Using the Premier Perspective database, 145,882 adult inpatient records were matched by propensity score for age, race, gender, hospital, and admission type, multiple comorbid conditions, and APR-DRG (All Patient Refined Diagnosis Related Groups) severity of illness. Of these, 39,189 patients were critically ill and in the ICU when the echocardiogram was performed, 19,318 patients received contrast-enhanced studies, approximately 78% of the total population received Definity. A subset of 12,572 patients on mechanical ventilation was also examined. Premier's Perspective database is the largest clinical comparative database in the United States used to track hospital performance in five clinical areas: acute myocardial infarction (AMI); heart failure; community-acquired pneumonia; coronary artery bypass graft (CABG); and hip and knee replacement.

Short-term mortality rates (< 48 hours of echocardiogram) were 2.98% for patients undergoing noncontrast studies and 2.30% for patients undergoing contrast-enhanced examinations. A multivariate logistic regression analysis was used to compare short-term mortality, controlling for case mix and clinical covariates. Critically ill patients undergoing contrast-enhanced echocardiograms had a statistically significant 26% lower risk-adjusted odds ratio for 48-hour mortality than those patients who received only echocardiography without the ultrasound contrast agent. For those patients on mechanical ventilation, 48-hour mortality rates were 6.11% for those undergoing noncontrast exams and 4.59% for individuals with contrast-enhanced examinations, representing a 27% lower mortality rate for the contrast-enhanced group.

"With Definity already widely used in the intensive care unit settings, the results confirm that there is a survival advantage associated with using echocardiogram contrast agents appropriately," said Mark Hibberd, M.D., Ph.D., senior medical director, Global Medical Affairs, Lantheus Medical Imaging, and coauthor on the study. "The contrast-associated survival advantage is important, especially in the mechanically ventilated patients, in whom routine echocardiography without contrast is especially challenging. The current database analysis does not allow us to draw conclusions on the reasons why contrast utilization is associated with a survival advantage. Some possible explanations include more accurate, faster diagnoses leading to better patient management decisions, and/or the avoidance of other potentially higher-risk or invasive tests that become unnecessary after contrast echocardiography. This study follows [another recent study] in which it was demonstrated that echocardiogram image quality was significantly improved in 88% of those studies having suboptimal images without contrast and where the use of Definity significantly changed patient management particularly in ICU/SICU [surgical intensive care] patients. [That] study gives the medical community further clinical evidence of the important role Definity can play in improving the standard of care for patients in the ICU."

Since its launch in 2001, activated Definity has been administered to over two million patients. In patients with suboptimal echocardiograms, Definity enables physicians to visualize the borders of the heart more clearly. In 2008, Lantheus announced the initiation of CaRES (Contrast Echocardiography REgistry for Safety Surveillance), the first multicenter phase IV observational registry that will further evaluate the safety profile of Definity in patients with suboptimal echocardiograms and provide safety information on the use of ultrasound contrast agents in routine clinical practice. The open-label, nonrandomized registry is being conducted in 15 clinical sites in the United States and will include at least 1,000 patients. The study will gather data on patient characteristics and demographics, indication for Definity's use, results of safety monitoring of patients during and after Definity administration, and the nature and frequency of any adverse events that may occur.

Activated Definity is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. The safety and efficacy of Definity with exercise stress or pharmacologic stress testing have not been established.

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