25june2010 ARDMS NEWS

Ultrasound May Add to Cardiovascular (CV) Risk Prediction

Ultrasound imaging of the heart and the main artery to the brain may paint a dramatically different picture of cardiovascular health in women thought to be at low risk by traditional factors, researchers found.

Despite being judged at low cardiovascular event risk by the widely-used Framingham risk score, ultrasound imaging of a small cohort of women (most obese or with metabolic syndrome) revealed abnormalities in the carotid artery, in left ventricular or left atrial size, or in diastolic function, Danya L. Dinwoodey, MD, of Massachusetts General Hospital, Boston, and colleagues reported here at the American Society of Echocardiography meeting.

These results suggest that traditional risk factors may not be enough to guide preventive treatment and counseling for these women, said Dinwoodey.

"These things we were looking at have been shown in previous studies to confer poor cardiovascular outcomes," Dinwoodey said. "Just by doing a simple ultrasound we're finding that they are actually much higher risk for cardiovascular events."

The researchers recommended screening women diagnosed with obesity or metabolic syndrome using selected ultrasound imaging to help further risk-stratify such patients.

Full echocardiograms may be too expensive for primary prevention screening, Dinwoodey cautioned, but a couple of ultrasound views of key areas of the heart, along with measuring carotid intima media thickness (IMT), may be feasible for clinical use.

The role of echocardiography among other screening modalities still needs to be determined, Dinwoodey added. "There are a lot of potential candidates for better risk stratifying," she said. "At this point, it's not clear what the best way to do this is ... but it's clear that what's currently available is not working. It's not accurately predicting a woman's true risk for cardiovascular disease."

To search for better ways to assess risk, Dinwoodey and her team analyzed baseline data from the Heart Awareness and Primary Prevention in Your Neighborhood (HAPPY Heart) trial, designed as a lifestyle intervention trial.

In the study cohort, the researchers analyzed complete ultrasound data for 43 asymptomatic, low-income Caucasian or Hispanic women (mean age 50.7) who had at least two traditional cardiac risk factors but a normal left ventricular ejection fraction.

Among the women, 67% were obese and 74% had metabolic syndrome. Yet all had a Framingham risk score predicting less than a 10% cardiovascular risk over 10 years.

While 67% of the women had an abnormal ultrasound finding at baseline, among the 32 women with metabolic syndrome, 75% had an abnormal ultrasound, and 79% of the 29 obese women had abnormal ultrasounds.

The most common ultrasound abnormality was elevated IMT -- defined as over 75% of predicted for age and race or at least 1.2 mm of carotid plaque. It showed problems in 37% of women overall and in 45% of the obese women and 41% of those with metabolic syndrome.

Diastolic dysfunction appeared in 37% overall, with a slightly higher rate in obese women (38%) and metabolic syndrome cases (41%).

Echocardiography showed an enlarged left atrial volume index of more than 34 mL/m2 in 30% of women overall (38% in obese women and 34% in metabolic syndrome) but none had elevated left ventricular wall mass of greater than 89 g/m2.

Although the diagnosis of metabolic syndrome requires at least three of the five components of the disorder -- abdominal obesity, insulin resistance, low HDL cholesterol, high triglycerides, and high blood pressure -- women with more components appeared to carry greater risk of an abnormal echocardiography finding.

Ultrasound imaging may have a side benefit in helping women recognize the need for risk reduction, Dinwoodey said. She explained that in the intervention portion of the study she had seen women take charge of their risk factors and prepare to make healthy lifestyle changes after seeing the state of their carotid arteries and heart.

At the same time, Dinwoodey cautioned that the pilot study was limited by its small sample size.
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Article written by staff at medpagetoday.com and adapted for the purposes of this newsletter.
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Philips Hopes Ultrasound Unlocks Potential of Gene Therapy
An experimental therapy that offers hope for treating disease by shutting off targeted genes might work if controlled with ultrasound pulses, according to Philips Healthcare.

Last week, Andover, Mass-based Philips inked a deal with biomed company RXi Pharmaceuticals to research using ultrasound to activate the therapy, known as RNA interference, or RNAi, which could help block genes implicated in several diseases.
The agreement is part of Philips' effort to move beyond diagnosis to therapy planning and image-guided intervention, the company told DOTmed News.

"Our decision to jointly research RNAi-based therapies with RXi is driven by our belief that patient care will ultimately benefit from the combination of novel drugs and advanced medical imaging technologies," Henk van Houten, senior vice president of Philips Research and head of its health care research program, said in a statement.

RNA is a chemical messenger used by DNA to carry out its commands, such as building proteins. In RNA interference, snippets of double-stranded RNA break off and attach to other strands of messenger RNA, stopping them in their tracks and effectively blocking the effects of the genes whose bidding they're doing.

The therapeutic promise of the technique is great since the goal is to shut off genes implicated in diseases such as cancers, Dr. Craig Mello, a professor at University of Massachusetts Medical School in Worcester and a founder of Worcester-based RXi, told DOTmed News.

Mello shared the Nobel Prize in Physiology and Medicine in 2006 with Andrew Z. Fire of Stanford University for his discovery of RNA interference.

"The numbers of possible products are [only] limited by the number of genes there are in the human," he said. RNAi can be developed to knock down genes involved in inflammation, cancer, and neurodegenerative disorders, Mello observed.

However, there is a massive obstacle to bringing the therapy into the clinic: making sure the therapeutic drugs go where they're supposed to go, and nowhere else. "You have to get this into the cell for it to work," Mello said.

If injected, drugs relying on RNAi could deactivate genes throughout the body, and not just at the targeted site such as a tumor.

"So, the challenge for the whole field is delivery," Mello said, "and what Philips brings to this is technology for delivering and releasing drugs in a very precise region."

What Philips and RXI plan to do is research using ultrasound to ensure the drugs get activated only where they're supposed to.
In the planned joint therapy, the specially designed RNAi drug would be injected with micro-bubbles. The clinician would then deliver focused ultrasound pulses at the tumor or other target. The pulses would break up the micro-bubbles, causing them to make micro-tears in the surrounding tissue where the ultrasound pulse was delivered, allowing the drug to get absorbed. The doctors can also use ultrasound to image this action to ensure the drug goes to the right target.

"We can visualize the arrival of the bubbles in the target organ, the focused ultrasound pulse and the subsequent rupturing of the bubbles," said Steve Klink, a spokesman for Philips. "It's a great combination of two technologies, one which is extremely potent at getting the drug into the cell once it contacts the cell; the other one is capable of keeping the drug internalized and releasing it at its target in the body."
Philips said, in the long run, the company is interested in researching cardiology and oncology. "But we are still at this early stage. So at this point, it's not focused on a particular disease yet," Klink said.
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Article written by staff at dotmed.com and adapted for the purposes of this newsletter.
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Carotid Artery Ultrasound an Effective Alternative to More Invasive Coronary Angiography
A study published in the June 2010 issue of the American Heart Journal shows that a noninvasive carotid artery ultrasound of the neck can be used as a preliminary diagnostic tool for coronary artery disease (CAD). This may be an alternative to the standard, expensive and more invasive coronary angiography.

The ultrasound test can also be used to rule out the diagnosis of CAD in patients presenting with reduced heart pump function.

"Our research has identified that carotid artery ultrasound is capable of identifying the presence of severe and extensive coronary artery disease," said Harmony R. Reynolds, MD, Cardiovascular Clinical Research Center, New York University Langone Medical Center, New York, New York. "Based on our findings, physicians might consider using the carotid ultrasound test as an initial screen for CAD in patients with reduced heart pump function and no history of heart attack. If a patient tests positive for plaque buildup in the neck arteries, then it can be followed by angiography of the heart arteries."

Traditional diagnosis of CAD is through coronary angiography. However, this test is an invasive and expensive catheter imaging procedure that is associated with risks from contrast material and radiation exposure.

For the current study, patients underwent the noninvasive carotid artery ultrasound to determine the artery's intima-media thickness and presence or absence of plaque. Researchers concluded that carotid artery ultrasound is a valuable screening tool for diagnosing and excluding CAD when a patient has heart muscle weakness without a known cause.

"Ultrasound of the carotid artery is a very widely available and inexpensive technique," said Glenn I. Fishman, MD, Leon H. Charney Division of Cardiology, NYU Langone Medical Center. "The study, if replicated in a larger population, could change the screening of patients with unexplained decreased heart pump function, and potentially allow them to avoid the need for invasive coronary angiography."