CD&D Contributing Editor

ORLANDO, Florida — The cardiovascular device market covers a broad array of product segments, ranging from stents and catheters to heart rhythm management devices, patient monitoring, imaging systems, heart assist devices, cardiac markers, devices for repair of heart defects, and emerging sectors such as cellular therapies for heart and vascular disease. The latest developments in all those segments were highlighted at the 2009 annual scientific sessions of the American College of Cardiology (ACC, Washington), held here in late March.

As demonstrated by the level of coverage given the topic at the conference, device-based treatments for heart failure are attracting growing interest among cardiologists since drug therapies have failed to produce a significant improvement in outcome for most patients, and the prevalence of the disease continues to increase. As shown in Table 1 on page 2, the number of hospitalizations for heart failure in the U.S. and prevalence of the disease have both increased substantially over the past 10 years.

Surgical approaches to treat heart failure also are being investigated, and the outcome of the most recent clinical study using surgical ventricular reconstruction in an attempt to improve heart failure outcomes was presented at the ACC conference.

In the long term, new approaches to treating heart failure using cell therapy and tissue engineering could become important, although at present it is clear that a considerable amount of development will be required before the technology will prove clinically useful.

Another tactic for reducing the severity of heart failure following myocardial infarction was described at the conference which involves protection of the heart and coronary vessels when re-opening a blockage, thereby reducing infarct size and the related tissue damage.

Other advances were described at the conference in the areas of heart assist devices, improved diagnostic technologies for heart disease, disease prevention, and enhanced approaches for therapy guidance.

Expanding range of HF therapies

An example of an emerging device-based treatment for heart failure which was spotlighted at the ACC conference is Cardiac Contractility Modulation (CCM), which employs the Optimizer III system under development by Impulse Dynamics (Curacao, Netherlands Antilles). A clinical trial involving 428 patients with New York Heart Association Class III and IV heart failure has been performed with the device to obtain data in support of a regulatory approval filing in the U.S.

Some 90% of patients included the trial had NYHA Class III heart failure, and the remaining 10% were in NYHA Class IV. The primary endpoint for the trial was an improvement in anaerobic threshold as measured in exercise testing, a new parameter which the FDA recommended be used for the evaluation of the device.Other conventional parameters such as ejection fraction and peak VO2 also were tracked. The patients all had a narrow QRS interval and thus were not candidates for cardiac resynchronization therapy (CRT).

In all, 215 patients were treated with the Optimizer III plus optimal medical therapy, and 213 were treated with optimal medical therapy alone. At six-month follow-up, there was no significant difference in anaerobic threshold between the groups, although there was a trend favoring CCM. There was, however, a significant benefit in VO2, as well as a large benefit in quality of life. In addition, patients with Class III (moderate) disease and an ejection fraction of 25-35% showed a statistically significant benefit for all three parameters including anaerobic threshold. The degree of improvement was equal to that seen with CRT in other trials.

In discussing the results at an ACC press conference, William Abraham, MD, of Ohio State University (Columbus) said that CCM has been shown to provide benefit for a subgroup of patients with moderate heart failure, while those with the most severe disease may not benefit.

The Optimizer III resembles a defibrillator, and is implanted in the same way. Recharging of the battery-operated device is performed using a transcutaneous recharger, enabling patients to recharge the battery at home rather requiring an invasive procedure in the hospital. Abraham also concluded that the study shows anaerobic threshold is of limited value for assessing heart failure.

Another positive device trial in heart failure was reported by Gaetano De Ferrari, MD, of Policlinico San Matteo (Pavia, Italy). De Ferrari evaluated the CardioFit device from BioControl Medical (Yehud, Israel), a chronic vagus nerve stimulation device. Vagal nerve activity is known to be decreased in heart failure, so stimulation could in principle be beneficial, as has previously been shown in animal studies.

The CardioFit was evaluated in a first-in-man safety and feasibility study involving 32 patients with an average ejection fraction of 22.5%. At six-month follow-up, a reduction in heart rate from 82 to 76 was observed, and average ejection fraction increased to 26.6%. There was evidence of remodeling, and significant increases in six-minute walk time as well as a one-class improvement in NYHA status were noted.

Adverse events included pain, cough, and dysphonia, as well as two device-related events resulting in device replacement. There were three deaths and 11 hospitalizations for heart failure during the follow-up period, but none of those events were device-related. The CardioFit device received a CE mark in January.

BioControl is now initiating a multi-center pivotal clinical trial of the device at centers in the U.S. and Europe.

A surgical treatment for heart failure, surgical ventricular reconstruction (SVR), fared less well in clinical trials as reported at ACC. The SVR procedure was evaluated in the Surgical Treatment for Ischemic Heart Failure (STICH) trial, which included 1,000 patients randomized to either CABG plus SVR surgery or CABG alone.

At three-year follow-up, there was no difference in outcome for the two groups in terms of death or hospitalizations due to cardiovascular causes. While SVR produced a reduction in end diastolic volume index of 20% vs. 3% in the CABG group, that change had no effect on major cardiovascular events or hospitalizations. Furthermore, patients who had the SVR procedure required an extra 30 minutes of OR time, and accumulated an additional $14,000 in treatment cost, with no attendant benefit.

Robert Jones, MD, of Duke University Medical Center (Durham, North Carolina), who discussed the results at the ACC sessions, stated that there is no segment of heart failure patients who should have the SVR procedure in addition to CABG.

Device-based therapy employing CRT and ICD-CRT devices remains an important treatment modality for heart failure, although growth in that segment of the market has slowed to 5% to 6% worldwide on a constant currency basis.

According to supplier estimates, the worldwide market for high-voltage cardiac rhythm management devices totaled $7 billion in 2008, and mid-single digit growth is projected for 2009. The market is driven by population demographics, in particular the size of the 60-and-older population at highest risk for heart rhythm disorders and heart failure, as well as by replacements of previously implanted devices and expansion of indications for use.

The opportunity for growth is greatest in developing regions, particularly the BRIC countries (Brazil, Russia, India and China). In fact, according to data from St. Jude Medical (St. Paul, Minnesota), now the No. 2 player in cardiac rhythm management with a 24% share of the ICD market and a 28% share in pacemakers in 2008, year-to-year growth in the population age 60 and older in the BRIC countries is projected at about 3.2% for 2009 versus about 2% in the developed countries, and by 2013 the growth rates are projected to be about 4% and less than 2% respectively.

In 2009, the total population age 60 and older in the BRIC countries was 298.5 million, compared to 166.5 million in the U.S., Japan, and the Big 5 European countries combined. Consequently, one avenue for growth in the market is to stimulate increased implant rates in the BRIC countries. For example, ICD implant rates in 2007 were almost nil in the population age 60 and older in China vs. 3,500 per million inhabitants in the U.S. and between 400 and 1,300 per million in Europe.

Another route for growing the market is expansion of indications, particularly in the large population of patients with less severe disease who currently do not receive implants. Two clinical trials described at the ACC sessions evaluated the benefit of ICD and CRT (biventricular pacemaker) therapy in such patients, the Immediate Risk Stratification Improves Survival (IRIS) and Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trials.

In the IRIS trial, as discussed by Gerhard Steinbeck, MD, of Ludwig Maxmilians University (Munich, Germany), 900 patients with a mean ejection fraction of 35% who had a recent myocardial infarction were randomized to ICD plus optimal medical therapy versus optimal medical therapy alone. The trial was designed to study the impact on mortality of early ICD therapy in patients with mild disease.

At three-year follow-up, there was no difference in mortality between the treatment groups (22.9% mortality for the medical therapy group versus 22.0% for the ICD plus medical therapy group). Sudden cardiac death was clearly reduced in the ICD group compared to medical therapy, indicating that ICD therapy was effective in preventing sudden death, but patients in the ICD group went on to die of other causes over the three-year follow-up period.

The lack of an overall mortality benefit for ICD therapy does not favor a change in guidelines to expand the indications for ICD implantation and recommend earlier implantation after a heart attack, although some patients might benefit by realizing a prolongation of life.

The results of the REVERSE trial, presented at ACC by Jean-Claude Daubert, MD, of CHU de Pontchaillou (Rennes, France), were more favorable for expansion of heart rhythm device utilization. One-year results from the trial were presented at the 2008 ACC sessions, and Daubert provided two-year follow-up data at this year's conference.

The patients enrolled in the trial had mild (NYHA Class I or II) heart failure, an ejection fraction of less than 40%, and an enlarged left ventricle. All patients received a CRT (biventricular pacemaker) implant, but one group of 182 patients had the CRT function turned on, while a comparison group of 80 patients had the function turned off.

The one-year data had shown no significant difference in worsening of heart failure with CRT therapy, with only a 5% improvement, while at two years 34% of patients worsened in the OFF group vs. only 19% in the ON group. The deterioration in the OFF group occurred primarily in the final six months of follow-up. No symptomatic improvement was observed since the patients were not symptomatic at the outset of the study, but there was a 62% reduction in death and heart failure hospitalizations.

While some complications occurred related to the CRT device implant, primarily related to dislocations of the pacing leads, the benefit of the therapy outweighs its risks, according to Cecilia Linde, MD, PhD, of Karolinska University Hospital (Stockholm, Sweden), who discussed the trial at an ACC press conference.

Evaluation of an imaging agent that shows promise for determining which patients will benefit from ICD therapy was described at the ACC sessions by Arnold Jacobson, MD, PhD, of GE Healthcare (Waukesha, Wisconsin). Adrevue, a nuclear imaging agent approved by the FDA in 2008 for imaging neuroendocrine tumors, was evaluated in the ADMIRE-HF trial for imaging of patients with Class II and III heart failure.

Adrevue (iobenguane 123I), which is not FDA-approved for cardiac imaging, is a radiolabelled norepinephrine analog used in a scintigraphy exam to image the sympathetic nervous system of the heart. Uptake of the agent is correlated with sympathetic nerve function, and is lower in patients with heart cell malfunction as can occur in patients with heart failure. The study analyzed the heart/mediastinum ratio as measured at the outset of the trial from the scintigraphy image, and classified patients as low or high uptake. 83% of patients in the study had NYHA Class II heart failure.

At two-year follow-up, event-free survival was 85% in the high uptake group (ratio>1.6) versus 63% for those in the low uptake group. There were 51 cardiac deaths in the low-uptake group vs. two in the high-uptake group, providing a 98.8% negative predictive value of high uptake for cardiac death.

As discussed by Jacobson, heart imaging with Adrevue adds prognostic information which is not provided by conventional parameters such as ejection fraction, NYHA class, or BNP levels, and could help to select patients who can benefit from ICD therapy.

Cellular therapy and tissue engineering for heart failure treatment is another alternative to CRT that has shown some promise in early-stage trials. Companies involved in development of cellular therapy for heart disease include BioHeart (Sunrise, Florida), Advanced Cell Technology (Los Angeles), Osiris Therapeutics (Columbia, Maryland), Gamida Cell (Jerusalem, Israel), Amorcyte (Hackensack, New Jersey), Cardio3 BioSciences (Braine L'Alleud, Belgium), Aastrom Biosciences (Ann Arbor, Michigan), Aldagen (Durham, North Carolina), Angioblast Systems (New York), BioLine Rx (Jerusalem, Israel), Provascular (Cambridge, Massachusetts), Stemedica Cell Technologies (San Diego), Neuronyx (Malvern, Pennsylvania), Cytori Therapeutics (San Diego), Geron (Menlo Park, California), Capricor (Los Angeles), Baxter Healthcare (Deerfield, Illinois), t2cure (Frankfurt, Germany), and Athersys (Cleveland) in partnership with Angiotech Pharmaceuticals (Vancouver, British Columbia).

A number of companies and clinical researchers are using autologous cells, such as mesenchymal stem cells derived from skeletal muscle, for cardiac tissue regeneration, which has the advantage of avoiding immune rejection of the implanted cells. Others are using allogeneic cells derived from a variety of sources which avoids the need to extract cells from the patient and eliminates concerns that autologous cells may harbor remnant characteristics of the disease process or may be defective in certain traits.

Angioblast Systems, for example, is employing allogeneic adult stem cells derived from healthy young adults, the Revascor therapy, in the Angioblast trial for heart failure treatment. The company recently reported it had achieved a key safety milestone in the first 20-patient low-dose phase of the Phase II trial, with no cell-related adverse events, and is now proceeding with a higher-dose phase.

A total of 60 patients will be enrolled in three groups, including a placebo group as well as low and high-dose groups. The Revascor cells are modified to remove immunogenic moieties, and are delivered to target areas of the heart that have been identified as hibernating myocardium. The cells are delivered via transendocardial injection guided with the NOGA system and catheter from Cordis/J&J (Miami Lakes, Florida), using an 8 Fr sheath for femoral access.

Douglas Losordo, MD, of Northwestern University (Chicago), described promising results with cell therapy for microvascular repair of the heart in patients with heart failure. Based on the well-documented drop in microvessel density that occurs in infarct-damaged heart tissue, Losordo is using CD34+ cells combined with granulocyte colony stimulating factor injection in an attempt to restore heart function in no-option patients. The cells are selected using a separation system from Baxter Healthcare.

At a satellite symposium sponsored by the Texas Heart Institute (Houston), Losordo described results of a 156-patient trial, reporting 12-month safety and six-month efficacy data. The trial involved a placebo group as well as low and high-dose treatment groups. A statistically significant reduction in angina frequency compared to placebo was achieved, and a significant improvement in exercise time was reported (from 69 to 138 seconds). Notably, Losordo consistently found that the lower-dose group had a better response than the high dose group, although both groups responded significantly better than the placebo group.

There were two adverse events related to the therapy in the trial, both due to perforations occurring during transmyocardial injection, one of which resulted in death. But the results were overall more favorable in the treatment group versus controls according to Losordo.

Osiris has one of the most advanced programs in cell therapy for improving heart function following a heart attack. The company reported enrollment of the first patient in a Phase II trial of its Prochymal stem cell therapy for treating post-MI patients in early April. Prochymal employs mesenchymal stem cells specially formulated for intravenous infusion which are derived from the bone marrow of healthy adult donors.

Prochymal also is being evaluated for a variety of other indications including treatment of graft-versus-host disease.

Another trial of cell therapy for chronic ischemic cardiomyopathy employing allogeneic mesenchymal stem cells was described at the Texas Heart symposium by Joshua Hare, MD, of Miller School of Medicine at the University of Miami.

As described by Hare, the Prometheus trial, under the direction of Alan Heldman, MD, is evaluating the ability of cell therapy to reverse the remodeling process in chronic infracted myocardium. Cells are infused in patients who are undergoing heart surgery using an injection system from BiaCardia (San Carlos, California). Eight patients have been treated so far in the trial. In prior studies conducted in pigs, the treatment was shown to produce a significant (30%) reduction in scar size, and remodeling of the heart was observed.

BioLine Rx is developing another approach for reversal of heart remodeling following a myocardial infarction. As described by Shmuel Tuvia at a late-breaking clinical trial session, the BioLine technology employs a bioabsorbable material which is injected into the infarct area. The material, BL-1040, is a calcium cross-linked alginate which is a liquid at room temperature and forms a hydrogel when cross-linked by calcium ions. The material subsequently is bioabsorbed when implanted.

BL-1040 is non-immunogenic and non-thrombogenic, and can be delivered via a catheter. Delivery is targeted in part due to the increased permeability of the capillary bed of the heart in the infarcted region. The primary effect of the injected material is to replace missing extracellular matrix in the infarct area, providing structural support and thereby preventing the dilatation of the heart that is a hallmark of adverse remodeling in post-MI heart failure.

In animal studies with BL-1040, complete prevention of left ventricular remodeling has been observed, and the effects are maintained after resorption of the material. A 50% drop in mitral regurgitation has also been observed at six months in animal studies, as well as a 100% reduction in mortality. A clinical trial of BL-1040 involving 30 patients who have suffered a first MI is underway at nine sites in Europe. At 90 days, follow-up of the first 10 patients has shown a slight drop in left ventricular volume, a two-fold drop in BNP levels, and no safety issues.

Richard Lee, MD, of Brigham & Women's Hospital (Boston), described an emerging technology employing self-assembling peptide nanofibers that can be used to create injectable microenvironments which be engineered to recruit endogenous progenitor cells for tissue repair, including repair of damaged heart tissue. Lee is the founder of Provasculon (Cambridge, Massachusetts), a company that is developing tissue regeneration technologies based on Stromal Cell-Derived Factor-1 (SDF-1).

Studies in animals have shown that nanofiber scaffolds complexed with various compounds such as growth factors and SDF-1 can enable targeted stimulation of growth of cardiac stem cells and cardiomyocytes. Using a construct consisting of self-assembling nanofiber scaffold with attached SDF-1, Lee has demonstrated a doubling of recruitment of progenitor cardiomyocytes, and improved ejection fraction.

Advances in heart-assist devices

Another segment of the market for device-based treatment of heart failure is heart-assist devices. The market for heart assist and heart replacement devices totaled approximately $354 million worldwide in 2008 as shown in Table 2.

Examples of products in the heart assist device segment include the HeartMate II Left Ventricular Assist System from Thoratec (Pleasanton, California), the Impella from Abiomed (Danvers, Massachusetts), the TandemHeart PTVA System from CardiacAssist (Pittsburgh), the DeBakey VAD Child from MicroMed Technology (Houston), the INCOR implantable LVAD from Berlin Heart (Berlin, Germany), and the CardioWest temporary Total Artificial Heart from SynCardia Systems (Tucson, Arizona).

A number of other devices are under development, as shown in Table 3.

An important trend in the segment is the development of smaller, less-invasive LVADs which promise to expand the target patient population. An example is the Synergy Pocket Micro-Pump under development by CircuLite. As discussed in a late-breaking clinical trial session at ACC by Daniel Burkhoff, MD, of Columbia University (New York), the Synergy is a partial circulatory support device designed for use in NYHA Class IIIb and IVa patients, and employs a patented pump that is implanted subcutaneously in a pacemaker-like pocket.

The pump, which is the size of a AA battery, is connected to an inflow cannula placed in the left atrium and an outflow graft attached to the subclavian artery. The device is powered by an external dual battery pack and controller weighing 3.3 pounds, connected to the pump via a percutaneous lead that enters the body in the abdominal area. The batteries can power the system for 16-18 hours.

Because the pump provides only partial support, battery or controller failure is not life-threatening. The Synergy is designed for long-term use to provide up to three liters per minute of flow, increasing total cardiac output and allowing the heart to rest, potentially enabling recovery of heart function. In a feasibility study involving 16 patients with an average ejection fraction of 20%, a significant increase in mean arterial pressure was observed at 10 weeks post-implant, and a reduction in wedge pressure was also observed. Peak VO2 increased from 9.6 to 14.1 ml/kg/min.

Using the initial version of the device, eight patients had device failures due to thrombus formation in the rotor compartment. However, CircuLite has resolved that problem by incorporating a larger rotor. According to Burkhart, the results of the feasibility study indicate that partial cardiac support may interrupt progressive deterioration in heart failure, improving quality of life and enabling patients to tolerate more aggressive drug therapy. The minimally invasive nature of the Synergy device may also lower the bar to LVAD implantation, enabling a broader spectrum of patients to receive the therapy.

VentraCor is developing the VentrAssist device, a centrifugal VAD that employs hydrodynamic suspension of the pumping element to eliminate wear and improve efficiency. The newest version, the LVA4, is only 3 mm in diameter. The device is already on the market outside the U.S., and the company has completed a bridge-to-transplant trial in the U.S.

Initial trials with the VentrAssist involving 138 patients who received implants, described by Andrew Boyle, MD, of the University of Minnesota, demonstrated a 78.6% success rate, defined as remaining on support for 180 days. Failure was defined as death or discontinuation of support. Adverse event rates were similar to those for other VADs such as the HeartMate II, except for a higher rate of thrombosis in the VentrAssist patients.

The company has modified the inflow cannula design to reduce the thrombosis rate. Development is on hold at present, however, due to an inability of the company to obtain funding, and VentraCor was placed under Voluntary Administration in Australia in March. Although the company remains solvent and reported sales of $12.7 million in 1H09, continued commercialization of the VentrAssist will depend on a successful outcome of the administration.

Thoratec, the current leader in the heart-assist device market with a worldwide share exceeding 60%, also is developing new heart assist technologies. The company's development-stage CentriMag device is a new system that employs bearingless magnetically levitated motor technology, and can be used for up to six hours for temporary support in severe heart failure patients during cardiac surgery.

Thoratec also is performing studies with its HeartMate II LVAD, which already is approved for bridge-to-transplant, with a goal of expanding device indications to include destination therapy.

Newer LVADs that can be implanted with percutaneous techniques provide cardiologists with an enhanced capability for cardiac support compared to conventional intra-aortic balloon pump devices, and are expected to play an increasingly important role in post-MI patients, according to Carmela Milano, MD, of Duke University Medical Center. The devices enable support of patients for 48 to 72 hours, allowing additional time for diagnosis and treatment, including percutaneous interventions. In addition, the devices appear to have value in patients with less severe heart failure by off-loading the heart to enable it to recover its pumping ability.

Improving diagnosis, monitoring, guidance

Remote monitoring of patients with heart failure and heart rhythm disorders is being employed for a growing proportion of the population as another strategy for improving outcomes and reducing hospitalization rates. Patients with implantable cardiac rhythm devices such as ICDs, ICD-CRT, and CRT devices are now widely monitored via RF telemetry which connects the implanted device to a receiver in the home that is in turn linked via modem or an Internet connection to a monitoring center.

Changes in reimbursement have been one factor driving adoption. Reimbursement for a routine 90-day check-up is now 30% to 40% higher for a remote electronic visit vs. an in-clinic visit according to suppliers. About one of every four patients with an implanted device from St. Jude Medical, or about 40,000 patients, have RF-equipped devices according to the company.

Data on device performance, event history, and parameters related to device integrity are automatically transmitted to the St. Jude Merlin@home station, and then forwarded to the company's monitoring center.

Suppliers such as Boston Scientific (Natick, Massachusetts) predict that all pacemakers and ICDs will have remote monitoring capability within two years. Remote monitoring for patients without implanted devices ialso is expanding rapidly.

HeartEvent (Palmetto Bay, Florida), a provider of ambulatory/remote ECG monitoring services, introduced a new disposable patient monitor at the ACC exhibition which the company believes will make monitoring easier to implement and thereby expand the number of monitored patients. The company also introduced a new contract structure for cardiologists that enables the physician to bill for global reimbursement, not just the professional component as is the case with most other remote monitoring services.

The device provides two-lead ECG monitoring along with automatic capture of heart arrhythmias such as atrial fibrillation and ventricular fibrillation events. Patients also can actuate recording of an event by pushing a button on the device. HeartEvent operates a 24-hour call center in Miami for monitoring of patient data, and charges $200 for a two-week monitoring cycle.

Vitaphone (Mannheim, Germany), a major provider of remote cardiac monitoring services outside the U.S. with 12 call centers in operation worldwide, has just entered the U.S. market with its cellular telephone-based ECG monitor, and is beginning to recruit patients. The company has established a call center in Las Vegas to serve the U.S. market.

New developments in imaging technology were described at the conference which promise to improve guidance of interventional cardiology procedures. John Carroll, MD, of the University of Colorado (Boulder), described clinical use of a new 3-D angiography system under development by Philips Medical (Best, the Netherlands). The system employs rotational angiographic image acquisition along with computerized reconstruction to automatically generate a 3-D rendering of the coronary arteries, including rendering of images of implanted stents and other devices. Images can be acquired in as little as seven seconds, reducing the need for contrast injection and lowering radiation exposure.

The system helps to mitigate the key disadvantages of conventional angiography, which include lack of a 3-D perspective, leading to inaccurate measurements of lesion length, inability to fully assess vessel tortuosity to determine if a lesion can be accessed, and a lack of a good perspective of the working area.

Using the new 3-D imaging system, Carroll demonstrated the ability to accurately measure and characterize the lesion and surrounding blood vessels, as well as four-dimensional road mapping to guide interventions. The Philips 3-D angiography system is still in development, and is not yet commercially available.

Moshe Flugelman of MediGuide (Haifa, Israel), now a unit of St. Jude Medical, described the company's gMPS medical positioning system at an emerging technology symposium at the ACC sessions. The gMPS system provides real-time tracking of a catheter tip during an interventional procedure, and enables construction of a 3-D roadmap to allow precise guidance to a target lesion. A feature called Smart Trace provides a real-time indication of foreshortening of stents as they are deployed with an accuracy of 1%.

Flugelman described applications in gMPS-enabled guidance of transcatheter valve implants and stent placement. The gMPS can be integrated with conventional angiographic imaging systems including the Axiom from Siemens Healthcare (Munich, Germany) and the Allura from Philips Medical.

The gMPS has been installed in three sites so far, with plans to expand the range of compatible angiography systems. gMPS uses sub-millimeter size sensors on a catheter tip and proprietary electromagnetic tracking to determine 3-D position and orientation, and graphically projects device position on a 2-D or 3-D image of the area of interest.

In addition to fluoroscopic imaging, the gMPS technology can be used with CT, ultrasound, and other imaging modalities.