ICUS Weekly News Monitor 3-27-2009

1.  Business Wire,  Mar 25, 2009,    Lantheus Medical Imaging to Present New Cardiac Imaging Data at the American College of Cardiology 58th Annual Scientific Sessions in Orlando

2.  NHS East Cheshire (UK), Radiology Bulletin,   Tue, 24 March 2009,    Diagnostic Ultrasound Combined With Glycoprotein IIb/IIIa-Targeted Microbubbles Improves Microvascular Recovery After Acute Coronary Thrombotic Occlusions Circulation.
By Xie, Feng MD; Lof, John MS; Matsunaga, Terry PhD; Zutshi, Reena PhD; Porter, Thomas R.





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Business Wire
Mar 25, 2009

Lantheus Medical Imaging to Present New Cardiac Imaging Data at the American College of Cardiology 58th Annual Scientific Sessions in Orlando
ACC.09 Annual Scientific Session Exposition

N.BILLERICA, Mass.--(BUSINESS WIRE)--Lantheus Medical Imaging, Inc., a worldwide leader in diagnostic imaging, today announced that new data for the company’s echocardiography contrast agent DEFINITY® Vial For (Perflutren Lipid Microsphere) Injectable Suspension and its novel fluorine 18-labeled Positron Emission Tomography (PET) agent for myocardial perfusion imaging, BMS747158, will be presented in two separate poster presentations at the American College of Cardiology 58th Annual Scientific Session on March 29-31, 2009, in Orlando, Florida.

New data on survival in an intensive care unit population undergoing transthoracic echocardiography with and without perflutren containing ultrasound contrast agents will be presented. The retrospective study includes more than 39,000 propensity matched cases in patients undergoing transthoracic echocardiography with and without contrast agents. The majority of the perflutren cases used DEFINITY®, which is the market-leading product in ultrasound echocardiography contrast agents in the U.S. Additionally, Phase I data regarding the human safety, dosimetry, biodistribution, and myocardial perfusion imaging characteristics under rest and stress conditions of Lantheus’ new PET agent BMS747158 will be presented.

“We look forward to presenting data at the upcoming American College of Cardiology annual meeting,” said Don Kiepert, president and CEO, Lantheus Medical Imaging, Inc. “The new DEFINITY® data expand on findings published in December 2008 that showed that the use of DEFINITY® for enhancing suboptimal resting echocardiography exams was associated with a 26 percent lower risk of mortality when compared with echocardiography performed without a contrast agent. Additionally, the PET agent data further demonstrate Lantheus’ ongoing commitment to developing new agents for the diagnosis and management of cardiovascular disease.”

The schedule, location and abstract information for the poster presentations are as follows:

Presentation Number:
       1027-265  
Abstract Title:
   Survival in an Intensive Care Unit Population Undergoing Transthoracic Echocardiography With and Without Perflutren Containing Ultrasound Contrast Agents: Results in 39,189 Propensity Matched Cases  
Presentation Time:
   Sunday, March 29, 2009, 3:30 p.m. - 4:30 p.m.  
Topic:
   Contrast Echocardiography  
Presenter:
   Michael L. Main M.D., associate professor of medicine, University of Missouri-Kansas City and director, echocardiography laboratory, Saint Luke’s Mid America Heart Institute, Kansas City, Missouri  
Location:
   Orange County Convention Center, West Hall D  
      
Presentation Number:
   1054-263  
Abstract Title:
   Phase 1 Human Safety, Dosimetry, Biodistribution, and Rest/Stress Myocardial Imaging Characteristics of F-18 Labeled BMS747158  
Presentation Time:
   Tuesday, March 31, 2009, 9:30 a.m. -10:30 a.m.  
Topic:
   Nuclear Cardiology/PET  
Presenter:
   Jamshid Maddahi, M.D., F.A.C.C., professor of molecular and medical pharmacology (nuclear medicine) and medicine (cardiology) at David Geffen School of Medicine at UCLA  
Location:
   Orange County Convention Center, West Hall D  

About DEFINITY®

Since its launch in 2001, activated DEFINITY® Vial For (Perflutren Lipid Microsphere) Injectable Suspension has been administered to over two million patients.1 In patients with suboptimal echocardiograms, DEFINITY® enables physicians to visualize the borders of the heart more clearly.2,3

In 2008, Lantheus announced the initiation of CaRES (Contrast Echocardiography REgistry for Safety Surveillance), the first multi-center Phase IV observational registry that will further evaluate the safety profile of DEFINITY® in patients with suboptimal echocardiograms and provide safety information on the use of ultrasound contrast agents in routine clinical practice. The open-label, non-randomized registry is being conducted in 15 clinical sites in the United States and will include at least 1,000 patients. The study will gather data on patient characteristics and demographics, indication for DEFINITY®’s use, results of safety monitoring of patients during and after DEFINITY® administration, and the nature and frequency of any adverse events that may occur.

Indications

Activated DEFINITY® (Perflutren Lipid Microsphere) Injectable Suspension is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. The safety and efficacy of DEFINITY® with exercise stress or pharmacologic stress testing have not been established. For full prescribing information, please visit www.lantheus.com.

Important Safety Information About DEFINITY®

WARNING: Serious Cardiopulmonary Reactions

Serious cardiopulmonary reactions, including fatalities, have occurred during or following perflutren-containing microsphere administration.

Assess all patients for the presence of any condition that precludes DEFINITY® administration (see CONTRAINDICATIONS).
In patients with pulmonary hypertension or unstable cardiopulmonary conditions, monitor vital sign measurements, electrocardiography and cutaneous oxygen saturation during and for at least 30 minutes after DEFINITY® administration (see WARNINGS).
Always have resuscitation equipment and trained personnel readily available.
Do not administer DEFINITY® to patients with known or suspected cardiac shunts (right-to-left, bi-directional or transient right-to-left), or hypersensitivity to perflutren. Do not administer DEFINITY® by intra-arterial injection.

In postmarketing use, uncommon but serious reactions observed during or shortly following perflutren-containing microsphere administration included fatal cardiac or respiratory arrest, loss of consciousness, convulsions, symptomatic arrhythmias (atrial fibrillation, supraventricular tachycardia, ventricular tachycardia or fibrillation), hypotension, respiratory distress or cardiac ischemia (see ADVERSE REACTIONS). The risk for these reactions may be increased among patients with pulmonary hypertension or unstable cardiopulmonary conditions (acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, serious ventricular arrhythmias or respiratory failure, including patients receiving mechanical ventilation). In the absence of these underlying conditions, observe patients closely during and following DEFINITY® administration.

Always have cardiopulmonary resuscitation personnel and equipment readily available prior to DEFINITY® administration and monitor all patients for acute reactions.

About BMS747158

BMS747158 is a fluorine 18-labeled agent that binds to the mitochondrial complex 1 (MC-1) inhibitor and was designed to be a novel myocardial perfusion PET imaging agent.

Preclinical studies have demonstrated the unique potential of BMS747158 to serve as a new class of PET agent for myocardial perfusion imaging. The agent demonstrates high, rapid and sustained cardiac uptake which is proportional to myocardial perfusion over a wide range of blood flow rates. The agent also exhibits high target to non-target uptake ratios, perfusion defect recognition, and very high image quality in multiple species.


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NHS East Cheshire (UK), Radiology Bulletin
Tue, 24 March 2009

Diagnostic Ultrasound Combined With Glycoprotein IIb/IIIa-Targeted Microbubbles Improves Microvascular Recovery After Acute Coronary Thrombotic Occlusions Circulation.
By Xie, Feng MD; Lof, John MS; Matsunaga, Terry PhD; Zutshi, Reena PhD; Porter, Thomas R.

Status published online before print, 2 March 2009
Abstract
Background-: The high mechanical index (MI) impulses from a diagnostic ultrasound transducer may be a method of recanalizing acutely thrombosed vessels if the impulses are applied only when microbubbles are channeling through the thrombus.Methods and Results-: In 45 pigs with acute left anterior descending thrombotic occlusions, a low-MI pulse sequence scheme (contrast pulse sequencing) was used to image the myocardium and guide the delivery of high-MI (1.9 MI) impulses during infusion of either intravenous platelet-targeted microbubbles or nontargeted microbubbles. A third group received no diagnostic ultrasound and microbubbles. All groups received half-dose recombinant prourokinase, heparin, and aspirin. Contrast pulse sequencing examined replenishment of contrast within the central portion of the risk area and guided the application of high-MI impulses. Angiographic recanalization rates, resolution of ST-segment elevation on ECG, and wall thickening were analyzed. Pigs receiving platelet-targeted microbubbles had more rapid replenishment of the central portion of the risk area (80% versus 40% for nontargeted microbubbles; P=0.03) and higher epicardial recanalization rates (53% versus 7% for prourokinase alone; P=0.01). Replenishment of contrast within the risk area (whether with platelet-targeted microbubbles or nontargeted microbubbles) was associated with both higher recanalization rates and even higher rates of ST-segment resolution (82% versus 21% for prourokinase alone; P=0.006). ST-segment resolution occurred in 6 pigs (40%) treated with microbubbles who did not have epicardial recanalization, of which 5 had recovery of wall thickening.Conclusions-: Intravenous platelet-targeted microbubbles combined with brief high-MI diagnostic ultrasound impulses guided by contrast pulse sequencing improve both epicardial recanalization rates and microvascular recovery.

ICUS Weekly News Monitor 3-20-2009

1.  HealthImaging.com,  Mar 10, 2009,    Update: Shockwaves Subside from the FDA's Echo Contrast Warning     By Justine Cadet    

2.  British Journal of Anaesthesia,  Mar 13, 2009,  Ultrasound-guided paravertebral puncture and placement of catheters in human cadavers: an imaging study
By Luyet, C., Eichenberger, U., Greif, R., Vogt, A., Szucs Farkas, Z., Moriggl, B.

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HealthImaging.com
Mar 10, 2009

Update: Shockwaves Subside from the FDA's Echo Contrast Warning
By Justine Cadet    

Views of the heart taken from the apex of the ventricles to visualize parts of the left- and right-sided chambers. Top, without contrast, bottom, with contrast. Source: Lantheus Medical Imaging Since the FDA placed a black-box warning on echocardiography contrast agents in October 2007, the market for the agents dropped tremendously. But there is good news for the echo contrast agent market and patients as the pendulum is swinging back again. The subsequent movement to educate both regulators and providers has led to a modification of the agency’s contraindications and may have generated a resurgence in their use—along with a better understanding of their clinical value.

Regulatory action

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In October 2007, the FDA changed the product labeling for perflutren cardiac ultrasound agents due to reports of about “200 serious adverse events shortly following administration of the products,” including seven deaths, which were mainly attributed to allergic reactions. The cardiac or pulmonary complications included cardiac arrest, heart rhythm problems, hypotension and hypoxemia.

“The approach that the FDA took in contraindicating contrast agents in various disease states was probably not the best approach”, says Michael L. Main, MD, of the Mid-America Heart Institute in Kansas City, Mo. “Since that time, we were able to demonstrate how patients with these disease states are the very patients who are most likely to benefit from the administration of contrast.”

Specifically, Main says, “patients with acute coronary syndrome [ACS], heart failure and respiratory failure are somewhat tenuous cases, but these are the patients in whom an accurate diagnostic study is most needed.”

Two products are available on the U.S. market: Definity from Lantheus Medical Imaging and Optison from GE Healthcare. In Europe, Luminity (European name for Definity) and Optison are approved, but only SonoVue from Bracco Diagnostics is currently being marketed.

The FDA labeling change also included a recommendation to monitor all patients for at least 30 minutes following administration of the agents. But when acute reactions occur—about one in every 10,000 cases—they generally happen within the first five to 10 minutes after injection. “Monitoring patients for 30 minutes does not prevent or help us manage acute reactions,” Main says.

Researchers presented several studies at the American College of Cardiology (ACC) annual meeting in March 2008 supporting the clinical benefits of the contrast agents. Melda Dolan, MD, from St. Louis University School of Medicine, presented findings based a dual-center assessment of nearly 8,000 patients, revealing no death or serious adverse events within 30 minutes of contrast use. At 24 hours, there were three nonfatal myocardial infarctions and one death, none of which the researchers attributed to the ultrasound contrast agents. “The warning placed on ultrasound contrast agents was issued without formal examination of the risks and benefits of using them,” Dolan says.

Advocates of echocardiography gathered forces and worked to educate the FDA and the general cardiovascular community about contrast agent safety. Additionally, a new cross-disciplinary professional society—the International Contrast Ultrasound Society (ICUS)—was formed.

The efforts paid off. In May 2008, the FDA revised several of its warnings and contraindications because the agency said it “determined that, in some patients, the benefits from the diagnostic information that could be obtained through the use of Definity or Optison may outweigh the risk for serious cardiopulmonary reactions, even among some patients at particularly high risk for the reactions.”

Many contraindications were removed, including worsening or clinically unstable congestive heart failure, acute MI, ACS, serious ventricular arrhythmias or high risk of arrhythmias. And several remained, including the monitoring of patients at high-risk of pulmonary hypertension or unstable cardiopulmonary conditions for at least 30 minutes post-administration of the agents.

Safe and cost-effective

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Studies proving the efficacy of echo contrast agents began appearing in 2001. They have demonstrated that up to a third of the images taken without contrast are often inadequate. They also have demonstrated that medical management of patients is significantly improved when contrast agents are used. When patients bypass contrast-enhanced echo, they invariably are referred to nuclear tests, which are more costly.

William A. Zoghbi, MD, president of the American Society of Echocardiography (ASE), says that the appropriate use of contrast is extremely cost-effective, since the improved accuracy of echocardiographic studies in difficult-to-image patients impacts patient management and decreases downstream utilization of more invasive—and more costly—procedures, such as nuclear scans, transesophageal echocardiography (TEE) or cardiac catheterization. In particular, he cites a study, conducted by Leslee J. Shaw, MD, et al, which found that contrast agents were cost-efficient (Ultrasound Con Agents 2001).  

Yongqi Yong, MD, from Baylor College of Medicine in Houston, and colleagues also found that contrast echo was cost-effective compared with TEE in determining regional and global ventricular function, with a cost saving of 3 percent and 17 percent, respectively (Am J Cardiol 2002;89:711–718).

The consensus is, and the evidence suggests, that when the correct diagnosis is made the first time with the help of contrast agents, the hospital saves money, says Main. He also acknowledges serious adverse events with contrast agents are quite rare in daily practice. Additionally, new data have emerged indicating that side effects occur at a very low level.

Main et al conducted a study seeking to assess any mortality difference in patients undergoing echocardiography while hospitalized, with (12,475 cases) and without (6,196 cases) contrast enhancement (Definity) (JACC 2008;51:1704-1706). They found that 0.4 percent of hospitalized patients died within 24 hours of the echo, but found no increased mortality risk associated with Definity, “despite evidence for higher clinical acuity and more co-morbid conditions in patients undergoing contrast studies.”     

Main says that the 0.4 percent mortality rate is “due to the fact that this patient population is very sick. We suggest that the adverse events, previously attributed to the echo contrast agents, might be pseudo-complications, due to their underlying disease.”

Main et al published a seperate retrospective study in December 2008 in the American Journal of Cardiology that found the administration of a contrast agent (Definity) was associated with a 24 percent decreased risk of mortality. Researchers examined nearly 60,000 contrast-enhanced studies and more than 4 million unenhanced studies.

Mustafa Kurt, MD, and colleagues from the Methodist DeBakey Heart and Vascular Center Imaging Institute in Houston recently found that the utilization of contrast echo in technically difficult cases improves endocardial visualization and impacts cardiac diagnosis, resource utilization and patient management. The study was published online Feb. 11, 2009 in the Journal of the American College of Cardiology.

Kurt et al prospectively enrolled 632 consecutive patients with technically difficult echocardiographic studies, who received contrast (Definity). They found that the percent of uninterpretable studies decreased after contrast administration from 11.7 to 0.3 percent and technically difficult studies decreased from 86.7 to 9.8 percent. A significant impact of contrast echo on management was observed: additional diagnostic procedures were avoided in 32.8 percent of patients and drug management was altered in 10.4 percent, with a total impact (procedures avoided, change in drugs, or both) observed in 35.6 percent of patients, according to the investigators. The impact of contrast increased with worsening quality of nonenhanced study, the highest being in intensive care units.

A cost-benefit analysis showed that the use of contrast resulted in a $122 saving per patient. “In these technically difficult-to- image patients, a rapid, simple, inexpensive, and safe test that results in accurate information is desirable,” Kurt says.

Charles A. Herzog, MD, of the echocardiography laboratory at Hennepin County Medical Center in Minneapolis, found that from February 1998 to February 2002, 3,051 patients received Optison with no adverse events recorded. From February 2002 to October 2007, 12,974 received Definity and 20 events were recorded, four of which were serious (JAMA 2008;299(17):2023-2025). The adverse event rate overall was 0.12 percent.

In an analysis, Paul Grayburn, MD, from Cardiology Consultants of Texas, said that the four deaths cited by the FDA occurred over a six-year period, in which two million doses were administered, indicated that the fatal event rate was approximately one in 500,000. Grayburn wrote that the rate “is far less than the fatal event rate of a treadmill exercise test (one in 2,500) or a transesophageal echocardiogram (one in 10,000)” (Am J Cardiol 2008;101(6):892-893).

The market drop-off

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Despite the recent studies and modification of the contraindications, the remaining black-box warning seems to have scared off providers from using the agents. In fact, the use of contrast for echocardiography declined 22 percent in the second quarter of 2008, compared to usage in the same quarter of 2006, according to research from Arlington Medical Resources (AMR), which provides market analysis for the pharmaceutical and diagnostic imaging industries. AMR collected data from a random sampling from several hundred facilities throughout the U.S. and Europe.

Analyst Anna Fisher says the role of ultrasound contrast agents continues to be important in the overall echocardiography market because it enhances imaging quality for interpretation. For fear of liabilities, however, many facilities, especially community hospitals, are performing more cases with saline instead of contrast. Experts say that saline is not as efficacious in imaging the heart as contrast agents. “The contrast agents allow us to look at the left side of the heart chambers to help us indentify the function of the left chamber of the heart. Agitated saline does not cross the lungs,” says Steven B. Feinstein, MD, director of echocardiography at Rush University Medical Center in Chicago.

It is hoped that supportive clinical studies, the International Contrast Ultrasound Society and other echo contrast proponents will continue to spread the word that these agents can increase the efficacy and cost-effectiveness of echocardiography.


Ultrasound-guided paravertebral puncture and placement of catheters in human cadavers: an imaging study
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British Journal of Anaesthesia
Mar 13, 2009

Ultrasound-guided paravertebral puncture and placement of catheters in human cadavers: an imaging study
By Luyet, C., Eichenberger, U., Greif, R., Vogt, A., Szucs Farkas, Z., Moriggl, B.

Background

During paravertebral block, the anterolateral limit of the paravertebral space, which consists of the pleura, should preferably not be perforated. Also it is possible that, during the block, the constant superior costotransverse ligament can be missed in the loss-of-resistance technique. We therefore aimed to develop a new technique for an ultrasound-guided puncture of the paravertebral space.

Methods

We performed 20 punctures and catheter placements in 10 human cadavers. A sonographic view showing the pleura and the superior costotransverse ligament was obtained with a slightly oblique scan using a curved array transducer. After inline approach, injection of 10 ml normal saline confirmed the correct position of the needle tip, distended the space, and enabled catheter insertion. The spread of contrast dye injected through the catheters was assessed by CT scans.

Results

The superior costotransverse ligament and the paravertebral space were easy to identify. The needle tip reached the paravertebral space without problems under visualization. In contrast, the introduction of the catheter was difficult. The CT scan revealed a correct paravertebral spread of contrast in 11 cases. Out of the remaining, one catheter was found in the pleural space, in six cases there was an epidural, and in two cases there was a prevertebral spread of contrast dye.

Conclusions

We successfully developed a technique for an accurate ultrasound-guided puncture of the paravertebral space. We also showed that when a catheter is introduced through the needle with the tip lying in the paravertebral space, there is a high probability of catheter misplacement into the epidural, mediastinal, or pleural spaces

ICUS Weekly News Monitor 2-27-2009

1.  MedPage Today,  Feb 24, 2009,    ASA: Ultrasound-Activated Microbubbles Boost Clot-Busting Action of tPA      By Crystal Phend

2.  Business Wire,  Feb 24, 2009,   (Press Release)  New Study Published in Journal of the American College of Cardiology Finds Utilization of Contrast Echocardiography with DEFINITY® Improves Patient Diagnosis and Management

3.  World Journal of Gastroenterology,  Feb 15, 2009,  Signet-ring cell carcinoma of ampulla of Vater: Contrast-enhanced ultrasound findings     By Gao JM, Tang SS, Fu W, Fan R.


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MedPage Today
Feb 24, 2009

ASA: Ultrasound-Activated Microbubbles Boost Clot-Busting Action of tPA
By Crystal Phend, Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.  
 
Using ultrasound-stimulated microspheres with tissue plasminogen activator (tPA) could speed up recanalization in acute ischemic stroke and enhance recovery, researchers found.Action Points  
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Explain to interested patients that microbubble agents (Definity, Optison) are FDA approved only for patients with suboptimal echocardiograms and to improve the delineation of the left ventricular endocardial borders.

Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Recanalization after administration of tPA tended to take half as long with the addition of ultrasound-boosted microspheres (P=0.054), Andrei V. Alexandrov, M.D., of the University of Alabama at Birmingham, and colleagues reported here at the American Stroke Association International Stroke Conference.

The lower 1.4-ml dose of perflutren microspheres used in the dose-ranging study appeared safe -- there were no intracerebral hemorrhages -- while more than doubling the rate of good functional outcome (P=0.0424).

Used alone, the micron-sized spheres of gas covered in a lipid shell -- used for decades as contrast agents for diagnostic ultrasound -- haven't been seen to have any effect on tPA therapy, Dr. Alexandrov said.

But when hit with a pressure wave from ultrasound, the microspheres oscillate, stirring the tPA in the target vessel and adding a mechanical grinding or sanding action to break down the fibrin clot causing the stoke, he said.

Following on earlier success in the CLOTBUST trial, Dr. Alexandrov's group conducted the multicenter phase I-II Transcranial Ultrasound in Clinical Sonothrombolysis (TUCSON) trial.

The trial randomized acute ischemic stroke patients to open-label treatment with the standard 0.9 mg/kg dose of intravenous tPA with saline placebo and intermittent transcranial Doppler monitoring or the tPA with microspheres plus 90 minutes of continuous 2-MHz transcranial Doppler ultrasound.

For the primary endpoint of sustained complete recanalization at 120 minutes, there was a signal for benefit with the lowest microbubble dose but no significant trend (P=0.221).

The rates of recanalization were:

67% among the 12 patients treated with the 1.4-ml microsphere dose
46% among the 11 patients treated with the 2.8-ml dose
33% among the 12 controls

Other recanalization outcomes likewise tended to be best with the lowest microsphere dose, including complete recanalization (67% versus 46% with 2.8-ml dose and 33% with placebo, P=0.177).

Median time to any recanalization, though, was equally fast with the two doses (30 minutes for both versus 60 with placebo, P=0.054).

Clinical outcomes at three months uniformly favored the 1.4-ml microsphere group, including a significantly higher rate of favorable outcome defined by a modified Rankin Scale 0 of 1 (75% versus 50% with the 2.8 ml dose and 36% in controls, P=0.0424 for 1.4 ml versus placebo).

Other findings included a tendency toward more patients with "dramatic early clinical recovery" (42%, 27%, 17%, respectively, P=0.396) and with a modified Rankin score of 2 or less (83%, 60%, and 55%, P=0.297).

Mortality was seen only in the 2.8-ml dose group (30% versus 0% in the other two groups, P=0.022).

They noted also an excess of symptomatic intracerebral hemorrhage events in the higher microsphere dose group (27% versus 0% in the other two groups, P=0.028).

Post-hoc analysis revealed significantly higher stroke severity in this group (P=0.047 versus the lower dose group) and uncontrolled hypertension in all three symptomatic hemorrhage cases.

"The rate of symptomatic intracerebral hemorrhage observed in the second dose tier may have been related to excessive blood pressures while lower recanalization and recovery rates could be due to greater stroke severity at baseline," they said.

But, "alternatively, bleeding with the higher microsphere dose could be related to greater mechanical stress to the endothelium and tissues," Dr. Alexandrov's group said.

They cautioned, however, that the study included a relatively small sample size in every group without the ability to extend enrollment.

The study was sponsored by ImaRx Therapeutics.

Dr. Alexandrov reported clinical trial-related grant support from the National Institute of Neurological Disorders and Stroke and served as consultant for ImaRx Therapeutics. Co-authors reported conflicts for ImaRx Therapeutics and NINDS.


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Business Wire
Feb 24, 2009

(Press Release)
New Study Published in Journal of the American College of Cardiology Finds Utilization of Contrast Echocardiography with DEFINITY® Improves Patient Diagnosis and Management
Study Finds Decrease in Percentage of Uninterpretable and Technically Difficult Studies with Contrast Echocardiography

Lantheus Medical Imaging, Inc., a worldwide leader in diagnostic imaging, today recognizes and comments on a paper published online in the February 2009 issue of the Journal of the American College of Cardiology that reinforces the clinical use and impact of its echocardiography contrast agent DEFINITY® Vial For (Perflutren Lipid Microsphere) Injectable Suspension in hospitalized and critically ill cardiac patients. New data from a prospective, single center, cohort study of over 600 hundred patients find the use of contrast echocardiography with DEFINITY® in technically difficult cases improves endocardial visualization and significantly impacts cardiac diagnosis, resource utilization and patient management decisions. The study authors include Dr. William A. Zoghbi, M.D., F.A.C.C., and his colleagues at Cardiovascular Imaging Institute, The Methodist DeBakey Heart and Vascular Center in Houston, Texas.

The prospective study was designed to evaluate the impact of echocardiographic contrast utilization on patient diagnosis and management. While contrast echocardiography (CE) has improved left ventricular opacification and delineation of endocardial borders, its impact on physician decision making has not been evaluated in a large study.

“This large clinical study, conducted by Dr. Zoghbi and his collaborators, involved 65 practicing clinicians and reinforces the impact of DEFINITY® echocardiography among hospitalized and intensive care unit patients. The study found that the physicians’ ability to help their patients was positively impacted by the appropriate use of DEFINITY® contrast,” said Mark Hibberd, M.D., Ph.D., senior medical director, global medical affairs, Lantheus Medical Imaging, Inc. “This study confirms the important clinical use of DEFINITY® and that better left ventricular opacification and endocardial border delineation allows physicians to significantly improve left ventricular functional assessments and the detection of left ventricular thrombus. In doing so, other more costly tests were avoided and drug therapies were better tuned to patient needs. The impact of the appropriate use of DEFINITY® contrast was largest in critical care settings, where other diagnostic options are limited.”

A total of 632 consecutive patients (545 hospitalized inpatients and 87 outpatients) with technically difficult studies who underwent a rest echocardiogram and received DEFINITY® for endocardial enhancement from June to October 2007 were enrolled in the study. A technically difficult study was defined as a study in which > 2 myocardial segments were not visualized at baseline from any imaging window. Quality of the studies, number of left ventricular (LV) segments visualized, estimated left ventricular ejection fraction (LVEF), the presence, absence or suspicion of apical thrombus, and management decisions were compared before and after contrast.

The study found that the percent of uninterpretable studies decreased from 11.7% to 0.3% and the number of technically difficult studies decreased from 86.7% to 9.8% (p<0.0001) after contrast echocardiography. An LV thrombus was suspected in 35 patients and was definite in three patients before CE. After contrast, only one patient had a suspected thrombus, and five additional patients with thrombus were identified (p<0.0001).

A significant impact of CE on management was observed. In particular, additional diagnostic procedures were avoided in 32.8% of patients and drug management was altered in 10.4%, with a total impact (procedures avoided, change in drugs, or both) observed in 35.6% of patients. The impact of contrast increased with worsening quality of baseline non-enhanced study, the highest being in intensive care units. Lantheus did not provide funding for the study.

“These findings further support the benefit-risk profile of DEFINITY® and underscore the importance of ultrasound contrast with DEFINITY® in hospitalized patients, and especially in critically ill cardiac patients,” said Don Kiepert, president and CEO, Lantheus Medical Imaging, Inc. “These data provide the medical community with important, new clinical evidence of how DEFINITY® can significantly impact clinical decisions and improve the usefulness of their echocardiograms. Lantheus remains committed to providing important clinical and safety information on the use of DEFINITY® in routine clinical practice.”

Online copies of the article can be found at:

Journal of the American College of Cardiology: “Impact of Contrast Echocardiography on Evaluation of Ventricular Function and Clinical Management in a Large Prospective Cohort,” by Mustafa Kurt, M.D., et al. http://content.onlinejacc.org/cgi/content/full/j.jacc.2009.01.005v1
About DEFINITY®

Since its launch in 2001, activated DEFINITY® Vial For (Perflutren Lipid Microsphere) Injectable Suspension has been administered to over two million patients.1 In patients with suboptimal echocardiograms, DEFINITY® enables physicians to visualize the borders of the heart more clearly.2,3

In 2008, Lantheus announced the initiation of CaRES (Contrast Echocardiography REgistry for Safety Surveillance), the first multi-center Phase IV observational registry that will further evaluate the safety profile of DEFINITY® in patients with suboptimal echocardiograms and provide safety information on the use of ultrasound contrast agents in routine clinical practice. The open-label, non-randomized registry is being conducted in more than 10 clinical sites in the United States and will include at least 1,000 patients. The study will gather data on patient characteristics and demographics, indication for DEFINITY®’s use, results of safety monitoring of patients during and after DEFINITY® administration, and the nature and frequency of any adverse events that may occur.

Indications

Activated DEFINITY® (Perflutren Lipid Microsphere) Injectable Suspension is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. The safety and efficacy of DEFINITY® with exercise stress or pharmacologic stress testing have not been established. For full prescribing information, please visit www.lantheus.com.

Important Safety Information About DEFINITY®

WARNING: Serious Cardiopulmonary Reactions

Serious cardiopulmonary reactions, including fatalities, have occurred during or following perflutren-containing microsphere administration.

Assess all patients for the presence of any condition that precludes DEFINITY® administration (see CONTRAINDICATIONS).
In patients with pulmonary hypertension or unstable cardiopulmonary conditions, monitor vital sign measurements, electrocardiography and cutaneous oxygen saturation during and for at least 30 minutes after DEFINITY® administration (see WARNINGS).
Always have resuscitation equipment and trained personnel readily available.
Do not administer DEFINITY® to patients with known or suspected cardiac shunts (right-to-left, bi-directional or transient right-to-left), or hypersensitivity to perflutren. Do not administer DEFINITY® by intra-arterial injection.

In postmarketing use, uncommon but serious reactions observed during or shortly following perflutren-containing microsphere administration included fatal cardiac or respiratory arrest, loss of consciousness, convulsions, symptomatic arrhythmias (atrial fibrillation, supraventricular tachycardia, ventricular tachycardia or fibrillation), hypotension, respiratory distress or cardiac ischemia (see ADVERSE REACTIONS). The risk for these reactions may be increased among patients with pulmonary hypertension or unstable cardiopulmonary conditions (acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, serious ventricular arrhythmias or respiratory failure, including patients receiving mechanical ventilation). In the absence of these underlying conditions, observe patients closely during and following DEFINITY® administration.

Always have cardiopulmonary resuscitation personnel and equipment readily available prior to DEFINITY® administration and monitor all patients for acute reactions.

About Lantheus Medical Imaging, Inc.

Lantheus Medical Imaging, Inc., a worldwide leader in diagnostic medicine for the past 50 years, is committed to advancing the field of diagnostic imaging. The company’s proven success in discovering, developing and marketing innovative medical imaging agents provides an unparalleled platform from which to bring forward breakthrough new tools for the diagnosis and management of disease. The company is home to leading diagnostic imaging brands, including Cardiolite® (Kit for the Preparation of Technetium Tc99m Sestamibi for Injection), DEFINITY® Vial For (Perflutren Lipid Microsphere) Injectable Suspension, and TechneLite® (Technetium Tc99m Generator) and has nearly 700 employees worldwide with headquarters in North Billerica, Massachusetts, and offices in Puerto Rico, Canada, and Australia. For more information, visit www.lantheus.com.

1 Source: The Echocardiography Monthly Monitor: United States, October 2001-September 2007, Arlington Medical Resources, Inc., Malvern, PA.

2 Kitzman DW et al. Efficacy and safety of the novel ultrasound contrast agent perflutren (definity) in patients with suboptimal baseline left ventricular echocardiographic images. AM J Cardiol. 2000; 86: 669-674.

3 Data on file, Lantheus Medical Imaging, Inc.

Contacts
Lantheus Medical Imaging, Inc.
Jocelyn Polk, 978-671-8854
Mobile: 978-618-7670
or
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Michele Rozen, 617-730-8284
Mobile: 617-953-2214


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World Journal of Gastroenterology
Feb 15, 2009

Signet-ring cell carcinoma of ampulla of Vater: Contrast-enhanced ultrasound findings
By Gao JM, Tang SS, Fu W, Fan R.

Department of Ultrasound, Shengjing Hospital of China University, 36 Heping Street, Sanhao District, Shenyang 110004, Liaoning Province, China. This email address is being protected from spambots. You need JavaScript enabled to view it.

Signet-ring cell carcinoma (SRCC) of ampulla of Vater is extremely uncommon, and less than 15 cases have been reported so far in literature. It mainly occurs in elderly people (median age 57 years). We report a rare case of SRCC of the ampulla of Vater in a 38-year-old woman who presented with a small tumor at the Vater, discovered by the contrast-enhanced ultrasound (CEUS). Histopathological examination showed prominent signet-ring features. We also describe the imaging features of SRCC of ampulla of Vater in CEUS.

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