Researchers in the U.K. believe that an investigative echocardiography contrast agent could soon be used to replace nuclear cardiography stress exams for the initial detection of coronary artery disease.
The preliminary results of two trials presented at the recent American Heart Association (AHA) scientific sessions in Orlando, FL, suggest that perfusion stress echocardiography is as accurate as nuclear stress testing for detecting coronary artery disease.
Adding the new perfusion functionality to stress echocardiography would be easy to implement in the clinical setting, where the modality is already ubiquitous, and could potentially answer a wide range of questions about the patient in a single test, said lead investigator Dr. Roxy Senior, director of cardiology at London's Imperial College School of Medicine.
"If you look at the scenario of assessing heart disease in patients, echo is the most widely used technology today," Senior told AuntMinnie.com in an interview. "It's available bedside and it's cheap, but (previously) could only assess structure and function -- echo could never assess perfusion."
Analysis of myocardial perfusion could add this third functionality to echocardiography with the aid of the contrast agent Imagnify, a trade name for what developer Acusphere of Watertown, MA, describes as a synthetic biodegradable ultrasound contrast agent consisting of perflubutane polymer microspheres (PPM) for injectable suspension.
To test the agent in a clinical setting, the multicenter phase III Real-time Assessment of Myocardial Perfusion Imaging (RAMP)-1 and RAMP-2 trials aimed to determine if the PPM agent could assess myocardial perfusion and detect coronary artery disease in patients undergoing evaluation for inducible ischemia. At 28 international sites, the RAMP-1 and RAMP-2 trials examined 285 patients (125 or 44% disease-positive) and 377 patients (220 or 58% disease-positive), respectively, with PPM echocardiography, both real-time and triggered.
A total of 662 patients also underwent technetium-99m (Tc-99m) quantitative myocardial perfusion imaging at rest and dipyridamole stress, the researchers wrote. The images were examined for the presence of wall motion and/or perfusion defects by independent readers blinded to the results (three echocardiographers and one to three nuclear readers for each study), according to the study team. Finally, disease was defined by quantitative coronary angiography as 70% or greater stenosis, if available, or 90-day outcome with clinical history and nuclear assessment. No-inferiority and superiority analysis were used to evaluate the results.
The same readers interpreted all the studies at a single center, Boston's Massachusetts General Hospital.
According to the results in the RAMP-1 and RAMP-2 trials, six of six echocardiography readers were noninferior to stress echo for accuracy, four of six were noninferior for sensitivity, and six of six were noninferior for specificity. In addition, two of three echocardiography readers demonstrated superiority for specificity, and three of three showed superiority for sensitivity.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Table shows accuracy, sensitivity, and specificity (left column, top to bottom) in RAMP-1 and RAMP-2 trials compared to nuclear perfusion dipyridamole stressor agent. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
"PPM echo was well-tolerated and has similar diagnostic performance compared to nuclear perfusion in chest pain patients being evaluated for inducible ischemia," the authors concluded.
Dr. Michael Picard, director of echocardiography at Massachusetts General Hospital, wrote in a statement that PPM echo "represents an exciting and easy-to-use technique."
"While the currently available echo technology can detect wall-motion abnormalities, one of the hallmarks of coronary artery disease, the detection of a patient's myocardial blood flow would add a critical piece of the diagnostic puzzle when evaluating patients," he stated. The trial results suggest that PPM "will enable assessment of wall motion and blood flow, which when combined, is a stronger predictor of coronary artery disease than either finding alone, he added.
The quality of echocardiography images is operator-dependent, and the echo readers in the study were all highly experienced, Senior noted, but said the results demonstrated that good echo images using the agent are simply not that difficult to acquire.
"Ninety-nine percent of the images were diagnostic at 28 centers, so it cannot be that difficult," Senior said. As for the possibility of CT angiography replacing some of the nuclear stress testing for coronary artery disease assessment, he considers the idea impractical.
On the other hand, the latest CORe study results for 64-slice CT angiography (CTA) presented at the AHA meeting yielded a negative predictive value of only 83% for CTA -- meaning that in 17% of CTA patients, angiography is required to rule out coronary artery disease, Senior said, adding that less than 1% of patients are unable to undergo echocardiography.
"So I don't think there's any comparison between stress perfusion and CTA, because stress echo gives you the functional significance of the lesion, and it is evaluable in more than 99% of the patients, while CTA gives you the anatomic lesion evaluation in 80%," Senior said.
"The accuracy of diagnosis is as good as the nuclear technique," he concluded. "Now we have a technique that can be used at bedside, it's widely available, every hospital has an echo machine, (it is) low-cost, and can rapidly assess cardiac structure, function, and perfusion at one sitting.
Dr. Joseph Schoepf, director of CT research at the Medical University of South Carolina in Charleston, agreed with Senior's assessment that stress echo is a completely different modality compared to CTA, but said he sees CT's contributions in a more positive light.
"Echo, nuclear myocardial perfusion imaging, and MRI are physiological imaging studies that evaluate the myocardium and the functional sequelae of ischemia on function and perfusion," Schoepf wrote in an e-mail to AuntMinnie.com. "CTA is different and unique, as it is the only noninvasive test that looks directly at coronary artery morphology. Thus, these tests are not competitive, but complementary. The relatively low negative predictive value found in the CORe 64 study is surprising and disappointing, but it should not be used to justify the use of echocardiography over CTA, as those two tests evaluate very different aspects of coronary artery disease."
By Eric Barnes
AuntMinnie.com staff writer
November 22, 2007
Related Reading
Report: Radiology, cardiology PACS still worlds apart, November 6, 2007
Echocardiography reliable for management of end-stage heart failure patients, October 30, 2007
Left ventricular dyssynchrony after MI predicts ventricular remodeling October 25, 2007
Report: Nuclear medicine patient visits drop in 2006, October 16, 2007
Heart disease in women often eludes angiography, February 2, 2006
Copyright © 2007 AuntMinnie.com
