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J Am Coll Cardiol, 2009; 53:32-38, doi:10.1016/j.jacc.2008.08.066
© 2009 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: CARDIAC IMAGING

Safety and Efficacy of Commercially Available Ultrasound Contrast Agents for Rest and Stress Echocardiography

A Multicenter Experience

Melda S. Dolan, MD*,*, Simil S. Gala, MD*, Saritha Dodla, MD{dagger}, Sahar S. Abdelmoneim, MD{ddagger}, Feng Xie, MD{dagger}, David Cloutier, MS{dagger}, Michelle Bierig, MPH, RDCS, RDMS*, Sharon L. Mulvagh, MD, FACC, FRCP{ddagger}, Thomas R. Porter, MD, FACC, FASE{dagger} and Arthur J. Labovitz, MD, FACC, FACP, FCCP, FASE*

* Division of Cardiology, Saint Louis University Hospital, St. Louis, Missouri
{dagger} Section of Cardiology, University of Nebraska Medical Center, Omaha, Nebraska
{ddagger} Division of Cardiology, Mayo Clinic, Rochester, Minnesota

Manuscript received May 16, 2008; revised manuscript received August 14, 2008, accepted August 25, 2008.

* Reprint requests and correspondence: Dr. Melda S. Dolan, Division of Cardiology, Saint Louis University, 3635 Vista Avenue, 14th Floor, St. Louis, Missouri 63110-0250 (Email: melda{at}tetranet.net).

Objectives: The authors sought to define the risks versus benefits of ultrasound contrast agents in patients undergoing stress echocardiography.

Background: The Food and Drug Administration recently placed a "black box" warning on the ultrasound contrast agents Definity (Bristol-Myers Squibb Medical Imaging, Billerica, Massachusetts) and Optison (GE Healthcare, Princeton, New Jersey) after their use was temporally related to 4 deaths. The safety of contrast has not been systematically evaluated.

Methods: We retrospectively analyzed 42,408 patients at 3 different institutions who had baseline suboptimal images and/or underwent myocardial perfusion imaging and received contrast agents; 18,749 of these underwent stress echocardiography. The outcomes (death and myocardial infarction [MI]) within 30 min, 24 h, and during long-term follow-up were recorded.

Results: No deaths or MIs were observed within 30 min; 1 death and 5 nonfatal MIs were observed within 24 h. This was not different from a matched cohort of 15,989 patients not receiving contrast. At 1 h and at 30 days after contrast administration, no significant differences in death rates or MIs were observed between patients who did and did not receive contrast during their stress echocardiogram. Endocardial border visualization in patients with suboptimal images resulted in comparable sensitivity (81% vs. 73%, p = NS) and diagnostic accuracy (82% vs. 77%, p = NS) for wall motion analysis compared with patients with optimal image quality. At long-term follow-up, abnormal wall motion and/or myocardial perfusion predicted adverse outcomes (20.6%) when compared with patients with normal studies (3.7%).

Conclusions: Despite recent warnings regarding echocardiographic contrast, our findings indicate it is a safe and useful diagnostic tool in assessment of patients suspected of having coronary artery disease.

Key Words: echocardiography • contrast • safety • stress

Abbreviations and Acronyms
  CAD = coronary artery disease
  DSE = dobutamine stress echocardiography
  EF = ejection fraction
  ESE = exercise stress electrocardiography
  FDA = Food and Drug Administration
  LV = left ventricular
  MI = myocardial infarction
  MP = myocardial perfusion
  MPI = myocardial perfusion imaging
  RT-MCE = real time-myocardial contrast echocardiography
  UCA = ultrasound contrast agent
  WM = wall motion


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