Real-Time Myocardial Contrast Echo May Identify Patients Who Need Revascularization

Reed Miller

November 12, 2012

LOS ANGELES — Real-time myocardial contrast echocardiography (RTMCE) to detect coronary disease yields more abnormal studies and is more likely to detect multivessel coronary disease than regular stress echocardiography, results of the Prospective Randomized Comparison of Conventional Stress Echocardiography with Real Time Perfusion Stress Echocardiography in Predicting Clinical Outcome (POISE) study show [1].

Dr Thomas Porter (University of Nebraska-Omaha) presented results from POISE last week at the American Heart Association 2012 Scientific Sessions. "Potentially here what we're seeing is a test that can identify the high-risk patient and modify their outcomes," Porter told heartwire .

Low-power ultrasound imaging systems with microbubble contrast solution can detect wall-motion abnormalities and also analyze myocardial perfusion without the radiation dose of radionuclide myocardial imaging, Porter explained. But it is not clear if this additional information improves patient outcomes over and above the wall-motion data provided by conventional stress echocardiography. So POISE randomized 2063 patients with intermediate pretest probability to either RTMCE or conventional echo during a stress exam.

Definity, a microbubble contrast agent developed by Lantheus Medical, was continuously infused in all of the RTMCE patients to examine both myocardial perfusion and wall motion, while the same contrast agent was injected in the conventional-stress-echo patients only in the 46% of cases where the endocardial border delineation on the image was inadequate without more contrast.

A total of 2014 patients were studied at a median follow-up of 2.5 years. The only difference in the patient groups was that the patients randomized to RTMCE had slightly lower ejection fractions and higher frequency of prior revascularization. Abnormal studies were more frequent with RTMCE than with conventional stress echo (p<0.001) and more frequently abnormal in a multivessel myocardial territory (p<0.005).

About 27% of the abnormal studies identified by RTMCE led to a revascularization, compared with only 16% of those identified by conventional echo, but overall event-free survival in patients with positive or negative studies was the same for the RTMCE and conventional-stress-echo groups. "You'd think that an abnormal study by either test would lead to revascularization, but it seemed like the real-time contrast echo was more accurate at predicting who was going to need revascularization, and that may be one of the reasons why a positive study had an equivalent outcome," Porter told heartwire . "In other words, real-time myocardial contrast echo better detected those at high risk and those who would require revascularization, and therefore those patients ended up having the same outcome as with an abnormal conventional-stress echo."

The only multivariate predictor of outcome in either group was the identification of a resting wall-motion abnormality with RTMCE, irrespective of whether those patients were revascularized or not. That was not a predictor in the conventional-stress-echo group. "One possible explanation for that is that these patients were . . . coming to the echo lab to rule out coronary disease, so some of them probably had unstable coronary syndromes," he said. "If you identify a resting wall-motion abnormality in that patient, they are very likely to be at risk for having an adverse event."

To examine the importance of the interpreter's experience, the studies were given to either an experienced reviewer in perfusion imaging or four level-3 reviewers with basic training in perfusion imaging. The predictive value of a positive study was the same with either type of echocardiography when interpreted by the more experienced reviewers but not for the less experienced reviewers. So reviewer experience is critical for the optimal use of contrast in echo, either with conventional imaging or RTMCE, the POISE investigators concluded.

Could RTMCE Identify High Risk Patients?

In the future, Porter's group plans to study the potential for real-time myocardial contrast echo to identify patients at high risk for coronary adverse events. In POISE, RTCME appeared to be better than conventional echo at identifying the patients who need revascularization, so a future study will randomize patients with a resting wall-motion abnormality on RTCME to revascularization or optimal medical therapy alone.

"Revascularization can't just be done on everybody because we know it isn't helpful if we do it on everybody, but we know there are subsets that really do need this, and this is a way to identify those patients," Porter said. "It's a bedside technique that doesn't require radiation, and it's very inexpensive compared with other perfusion-imaging techniques."

Porter reports grant support from NuvOx Pharma, Astellas Pharma, Lantheus Medical Imaging, and Philips Healthcare and equipment support from Philips Healthcare; he serves as an advisor to Lantheus Medical Imaging and Acusphere.