Using positron emission tomography (PET), the medical isotope 15O-water and cold pressor tests, Japanese researchers reported at the Society of Nuclear Medicine’s (SNM; Reston, Virginia) 53rd annual meeting in San Diego that they were able to detect the beginnings of atherosclerosis – before the disease became clinically evident. This finding, they said, will allow physicians to advise high-risk patients, who show no cardiovascular symptoms, to make lifestyle changes or undergo medical treatment, said Masanao Naya, MD, a physician at Hokkaido University Graduate School of Medicine (Sapporo, Japan).

In addition, researchers determined that elevated levels of interleukin-6 – one of the inflammatory chemicals produced by endothelial cells and that has been associated with an increased risk of heart disease – is “a major determinant” of coronary endothelial dysfunction, especially in individuals with high blood pressure.

Josef Machac, cardiovascular vice chairman of the Program Committee of SNM, in a statement called the findings of the study “quite revolutionary research. By measuring the response of coronary blood flow to stress, these researchers were able to detect atherosclerosis before it became evident clinically,” he said.

Atherosclerosis is a progressive disease that begins with damage to the innermost layer of the artery — the endothelium — and buildup of fatty substances, cholesterol and cellular waste products in the inner linings of arteries, which carry oxygen-rich blood to the heart, brain and other parts of the body. Over time, plaques narrow coronary arteries, allowing less blood to flow to the heart muscle, and rupture of these plaques may result in heart attack and death, said Naya, co-author of “Determinants of Coronary Endothelial Dysfunction in Hypertensive Patients.” Naya explained, “We can select high-risk patients with endothelial dysfunction using blood sample analysis at an early stage of atherosclerosis, then start medical treatment or lifestyle modification.”

Coronary endothelial function is impaired at an early stage of atherosclerosis in hypertensive patients; however, the magnitude of dysfunction differs among individuals, said Naya. “We can assess the endothelial dysfunction in the human heart noninvasively using PET and evaluate factors that can determine endothelial dysfunction,” he added. The researchers examined 27 untreated patients with high blood pressure. Myocardial blood flow was measured both at rest and during stimulation induced by a cold pressor test by using PET with 15O-water. The patient’s feet were immersed in icy water for 4 minutes, and a person’s risk for hypertension or high blood pressure was evaluated by observing blood pressure response.

Additional research needs to be done, said Naya. “We have been enrolling more patients and evaluating the relevance to the prognosis and the effect of medical treatments or life modification,” he noted.

In other SNM meeting news relating to the cardio sector, Digirad (Poway, California), a provider of cardiovascular imaging services and solid-state nuclear medicine imaging products to physician offices, hospitals and imaging centers, reported the release of its new Cardius 3 XPO triple-head cardiac gamma camera. The system introduces new Solidium high-definition solid-state (HDSD) digital detector technology, a new design that allows imaging of patients weighing up to 500 pounds and offers up to 38% faster image acquisition times than conventional dual head systems.

Stem cell use seeks CHF prevention

Researchers at the Minneapolis Heart Institute Foundation have launched a study to examine whether administration of stem cells to first-time heart attack patients can prevent the development of congestive heart failure (CHF).

The study protocol calls for patients with acute myocardial infarctions to be admitted to either the University of Minnesota (Minneapolis) or Abbott Northwestern Hospital (also Minneapolis) – with which the Minneapolis Heart Institute has an affiliation – through its nationally recognized Level 1 heart attack program, which allows patients to undergo immediate angioplasty and stenting. Patients will then undergo bone marrow aspiration and harvesting of their stem cells three to seven days later, which will be followed by an intra-coronary infusion of the isolated stem cells on the same day.

Of the 60 patients in this new study, 45 patients will have their stem cells infused through a catheter in the region of their heart attack, and 15 will receive a placebo. Patients in the placebo group will receive cell therapy six months following their heart attack. The study is intended to look exclusively at patients with moderate to large heart attacks, putting them at risk of developing CHF.

Each year more than 1 million Americans have their first heart attack, putting them at risk of developing CHF as a result of cardiac cell death and scar formation which results in diminished pumping ability of the heart and leads to exercise intolerance and fluid retention. However, researchers believe that patients’ own bone marrow-derived stem cells, which are capable of secreting a variety of growth and survival factors, can improve cardiac function after a heart attack and fend off the development of CHF.

To date, several clinical trials in Europe have demonstrated the safety and feasibility of using adult stem cells for cardiac repair following acute myocardial infarction, but in most of the studies the heart attacks were small and therefore much less likely to lead to the development of CHF.

“Europe and Asia started doing these [types of studies] a couple of years ago ... but there’s been nothing published or completed [on stem cells in CHF], just because the regulatory issues and the hurdles are a little bit higher,” Jay Traverse, MD, a cardiologist with the Minneapolis Heart Institute and principal investigator for the study, told Cardiovascular Device Update.

He also noted that the studies done outside the U.S. were carried out on patients “with pretty small infarcts [and] their ejection fractions were only mildly decreased.” In other words, patients in these trials “were not likely to go on to develop congestive heart failure, which is really the group of patient that needs this type of therapy.”

Traverse noted that this “first-of-its-kind study” in the U.S. is randomized and placebo-controlled, involving 60 patients with moderate to large anterior infarctions who will receive an intra-coronary infusion of their own stem cells or placebo. All patients will receive standard treatment including aspirin, beta-blockers, ACE inhibitors and statins. The study, funded by the Minneapolis Heart Institute Foundation, the Abbott Northwestern Hospital Foundation and the National Institutes of Health (NIH; Bethesda, Maryland), is being conducted following FDA trial approval this past September.

Traverse said that investigators for the trial – which has enrolled six patients since it began back in November – hope to get at least a “several percent retention” of the stem cells in the heart, which could add up to a “couple million cells setting up shop in the area of the infarct.”

While he said that the best way found thus far to get the cells into the heart has been a direct injection via a needle at the end of a catheter (studies have shown at least a 10% retention of cells with this method), that was not a viable option in the case of the patients involved in this study. The problem is that everyone was a bit anxious about sticking a needle into an area that has already had an infarct. He said the more direct injection approach has only been used on chronic ischemia patients who have already undergone bypass and angioplasty with a scarred over infarct that have no other options.

The use of what Traverse called a “true placebo,” something not found in most of the European and Asian studied, is another important aspect of this study. “I think we’ve learned over the years ... that if you don’t have a placebo you tend to get patients who know they got the drug and say they feel a lot better,” but who have in fact not really improved all that much at all. Placebo patients undergo the same procedure including the aspiration and harvesting procedures and have a solution that looks fairly identical to the stem cells infused into their artery.

“What we’re hoping is that these stem cells will help salvage a lot of the cells that were injured from the infarction that would normally go on to die.” As for possible cell regeneration, he noted that while the issue “is still up in the air,” he said European studies that have started with a superior patient ejection fraction (EF) showed close to a 10% improvement in that clinical measurement. “We’re starting out with an average EF of about 40%. It would be great if patients’ ejection fractions would improved up to 50% or so, but we don’t know if that’s going to be possible or not.” The patients will be followed for two years following treatment, with MRI used to determine if the therapy reduces scarring and improves cardiac function.

Combined scans improve PE assessment

Physicians could improve their ability to accurately diagnose pulmonary embolism, which kills about 600,000 Americans a year, if they would extend the commonly used chest computed tomography (CT) to the legs and combined it with the physician’s own clinical assessment of the patient, according to a new study funded by the National Heart, Lung, and Blood Institute (NHLBI) of the NIH. The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II study of 824 patients is the largest study ever conducted to assess the role of contrast-enhanced multidetector CT angiography for diagnosing pulmonary embolism, the institute said. The study was published in the June 1 issue of the New England Journal of Medicine.

“What brought this particular investigation to mind is the fact that people are using CT angiography to make the diagnosis, but literature had been a little bit unclear – had been a lot unclear – as to how accurate is the diagnosis,” Paul Stein, MD, lead author of the paper, director of research education at St. Joseph Mercy Oakland Hospital (Pontiac, Michigan), and professor of medicine at Wayne State University (Detroit), told CDU.

Although small studies had been done at individual hospitals or even groups of hospitals, Stein said “there had never been any tests with a sufficient number of patients to be certain.” Also, he said that most of the studies that were published were conducted using “first-generation CT scanners, and we needed to know the accuracy with more up-to-date CT scanners.” The PIOPED II study researchers reported in the NEJM that chest CT angiography alone detects suspected pulmonary embolism (PE) in only 83% of patients. In contrast, combined results of the chest CT angiogram and the leg CT scan detect clots in 90% of patients.

The researchers recommend that physicians consider additional test results before ruling out PE in patients whose scan does not detect clots but whose clinical assessment suggests a high likelihood of PE, i.e., the extension of CT scans to the legs. According to Stein, PE in 90% of patients originates from blood clots in the leg veins, or what is commonly known as deep vein thrombosis. When these clots in the legs travel to the lungs through the right chambers of the heart, into the artery and then into the lungs, the “clot gets caught” there because the “veins taper off” in the lungs, he said.

The extension of the CT scan to the legs would only take about an additional two to three minutes of both the patient’s and the technicians’ time, and it would require only one injection of a contrast agent that ultimately will travel to the legs after leaving the chest area, Stein said. It would necessitate only the moving down of the scanner over the legs, and the patient is already lying on the X-ray table.

“The patient does get more radiation, and we have ways of reducing that, but there is a radiation burden to it,” Stein said. There would also likely be an additional “reading fee” by the radiologist by adding the legs, and the hospitals that own the scanners might charge an extra fee, he said.

In PIOPED II, researchers compared the accuracy of three ways to diagnose blood clots in 824 patients suspected of having pulmonary embolism; chest CT angiogram alone; chest CT angiogram with venous-phase imaging, or leg CT; and chest CT angiogram with an objective clinical assessment known as the Wells Score. Overall, the sensitivity, or the ability to detect clots, of the combined chest CT and leg CT was 90%, compared to 83% sensitivity of the chest CT angiogram alone. The specificity, or the ability to rule out the presence of clots, of the chest CT alone compared to the chest CT and leg CT combined was similar, or about 95%. A high clinical probability combined with positive chest CT correctly indicated PE in 96% of study participants. However, in patients with a high clinical probability, a negative chest CT result did not “confidently” rule out a diagnosis of PE, the researchers said.

“I hope that [the study] calls to physicians’ attention that contrast CT is, in fact, a good study, and generally accurate,” Stein told CDU. “It’s more accurate if done in combination with the leg studies. My [sense of it] is more people are identified [with leg studies] because one might see the clot in the legs before they get to the lung or see something in the leg that would be causing problems ...”

Stein said that the study used multidetector CT scans including those by Siemens Medical Solutions (Malvern, Pennsylvania) and GE Healthcare (Waukesha, Wisconsin).