CDU Contributing Editor
NEW ORLEANS, Louisiana The annual scientific sessions of the American College of Cardiology (ACC; Bethesda, Maryland), held here in early March, and attended by about 27,000 physicians, researchers and exhibitors, provided a forum for presentation of the latest developments in interventional cardiology techniques and a window on the future of cardiovascular disease diagnosis and therapy. Drug-eluting stents, which in less than one year on the market in the U.S. have become the most widely used modality for coronary revascularization, now are being employed for an increasingly wide range of patients with conditions that in some cases would have required bypass surgery in the past. Promising results are now being reported with carotid artery stenting, an application that is likely to create additional growth in the vascular device market. In addition, a race is now on to develop percutaneously implanted heart valves, opening up yet another major new market segment for suppliers in the interventional device market.
The trend toward increased use of less-invasive therapies is being extended to cardiac surgery. The latest studies of minimally invasive coronary artery bypass grafting (CABG) show that outcomes may now be better than those achieved with traditional on-pump surgery. Other procedures, such as closure of congenital heart defects, are also being rapidly converted from open surgery to the use of transcatheter technologies. Progress also is continuing in the use of cell-based therapy for heart failure, albeit at a slow rate because of the still-developing knowledge base in tissue engineering, as well as the lack of widespread intellectual property positions in the field. Somewhat paradoxically, as the ability to treat cardiovascular disease has improved, physicians have begun to focus on prevention, with growing interest in technologies that can detect disease at an early stage, and that can pre-emptively treat patients before they develop serious conditions.
According to James Ferguson, MD, of St. Luke's Episcopal Hospital (Houston, Texas), drug-eluting stents (DES) have moved to the top of the list of hot topics in interventional cardiology, displacing distal protection devices, which were last year's No. 1 focus. Other hot topics for this year include peripheral vascular intervention, cell injection therapy for heart failure, percutaneous valves and distal protection devices, vs. last year's list, which included inflammation, drug-eluting stents and peripheral vascular intervention.
DES expand scope of interventional therapy
The market for drug-eluting coronary stents is now one of the most rapidly growing segments within the medical device arena, as shown in Table 1. The market is growing not only because of the higher average unit selling prices for drug-eluting stents, but also because the average number of stents per patient is increasing in the DES era, and because of an expansion in the range of indications for stenting resulting from the ability to treat more complex lesions with good results. As discussed by Greg Stone, MD, of the Cardiovascular Research Foundation (CRF; New York), at a CRF-sponsored symposium held prior to the ACC sessions, the use of drug-eluting stents is now expanding beyond the original indication in 2.5 mm to 3.75 mm de novo coronary lesions to include treatment of chronic total occlusions, bifurcation lesions, and treatment of in-stent restenosis in bare metal stents. Long-term results for the group of patients who first received drug-eluting stent implants continue to demonstrate that outcomes are durable with devices such as the Cypher stent from the Cordis unit (Miami Lakes, Florida) of Johnson & Johnson (New Brunswick, New Jersey). Data presented by Eduardo Sousa of the Institute Dante Pazzanese of Cardiology (Sao Paulo, Brazil) at the CRF session on the first 30 patients to receive the Cypher stent in Brazil demonstrates that the improvement in lumen diameter is preserved out to four years, with no toxic effects and complete vascular healing observed. Data from the SIRIUS trial, the pivotal large-scale trial of the Cypher stent in the U.S., also supports the contention that drug-eluting stents offer a long-term solution for patients with short, focal lesions, with a 5.8% target vessel revascularization (TVR) rate observed at two years. Furthermore, registries such as e-CYPHER, a worldwide registry that will have collected data on 15,000 Cypher patients in 367 sites around the world by this summer, demonstrates that data from the randomized trial can be reproduced in routine clinical practice. At six months, the TVR in the e-CYPHER registry patients is only 1.5%, in a patient population that includes significant numbers of restenotic lesions (13.6%) and chronic total occlusions (about 10%).
Other registries, including MATRIX and Siro-ISR, will evaluate real-world results for patients with bifurcation lesions and in-stent restenosis who are treated with drug-eluting stents. The MATRIX registry will evaluate 3,500 patients with bifurcation lesions treated with the CRUSH technique developed by Antonio Colombo, MD, of the Center Cuore Columbus (Milan, Italy), which uses two stents and kissing balloon implantation to guarantee coverage of the ostium of the side branch. Siro-ISR already has collected data on 332 patients with 436 in-stent restenosis lesions, with a 0.6% six-month TLR. While the total revascularization rate increased to 14.8% at 12 months, the results nevertheless represent an improvement over results achievable with other modalities to treat in-stent restenosis. Studies such as the SISR trial will compare drug-eluting stents to intravascular brachytherapy for the treatment of in-stent restenosis later this year.
In addition to the expansion of the patient population that can be treated with percutaneous techniques, the DES arena is also characterized by an expansion of the number of available devices. With the early March FDA marketing clearance of the Taxus Express2 stent from Boston Scientific (Natick, Massachusetts), a head-to-head battle has been joined between Cordis and Boston Scientific in the global market for drug-eluting coronary stents. Two-year results from the TAXUS trials demonstrate stable vessel volume, and comparisons of the TAXUS IV trial with results from SIRIUS, albeit not a statistically valid comparison, show a slightly lower TLR rate of 3% for TAXUS vs. 4.1% in SIRIUS, according to Stephen Ellis, MD, of the Cleveland Clinic Foundation (Cleveland, Ohio).
One factor complicating comparisons of outcome is that implantation techniques have evolved, particularly with the Cypher stent, as more experience has been gained with drug-eluting stents in actual practice. In particular, longer stents now are being used to ensure complete lesion coverage, and more care is being taken to avoid trauma at the edges of the stent. One patient group that may prove to be a particularly good target for the Taxus stent is diabetics, based on results presented by Ellis, which may prove important as the percentage of diabetics in the PCI patient population is continuing to increase, and is now at 39% at the Cleveland Clinic.
Patrick Serruys, MD, of the Thoraxcenter (Rotterdam, the Netherlands), also has performed an extensive comparison between Cypher and Taxus in the RESEARCH registry, which includes 2,453 drug-eluting stent patients (1,218 Cypher and 1,235 TAXUS). The patient characteristics indicate the "real-world" nature of the registry: 68% of the patients would not have met the inclusion criteria for the Cypher and Taxus randomized clinical trials. In RESEARCH, 2.2 to 2.3 drug-eluting stents were used per patient, vs. 1.9 for patients treated with bare-metal stents prior to the start of the registry in April 2002, indicating one of the factors that may drive market expansion. Freedom from TLR at six months is essentially the same for the two devices at 96.7% for Taxus and 98.6% for Cypher. The value of drug-eluting stents in complex lesions was described by Colombo at the CCF symposium, where a group of 1,362 patients with high prevalence of diabetes, chronic total occlusions and bifurcation lesions have been treated with either Cypher or Taxus stents. While rates of TLR and adverse events are typically high in such patients, Colombo has observed a definite improvement in that group of patients as compared to previous experience with bare-metal stents.
As a result of the benefits of DES, the percentage of stent procedures in which the devices are used has been rising rapidly. Based on data from the STENT Group registry, which includes information for 1,057 patients treated at six centers in the U.S. and is being maintained by a group led by Charles Simonton, MD, of Carolinas Heart Institute (Charlotte, North Carolina), about 60% of percutaneous interventions employed drug-eluting stents during the period since the Cypher stent was approved in the U.S. in May 2003, about 33% used bare-metal stents, and about 6% used both. Some U.S. centers, however, are using drug-eluting stents in 95% of all PCI cases, and in Europe some are at a 100% utilization rate. According to Serruys, drug-eluting stents are likely to entirely replace bare-metal stents by 2010.
Competition in the DES space is likely to be intense, with two major players now in the market and a number of new entrants developing next-generation products. Boston Scientific, along with many security analysts who follow the interventional cardiology segment, believes it will quickly capture the leadership position based on the greater ease of use of the Taxus stent vs. Cypher, and on its recent track record in markets outside the U.S. However, Cordis has countered with the announcement of a new strategic alliance with Guidant (Indianapolis, Indiana). Guidant was the leading supplier in the coronary stent market until the introduction of drug-eluting stents, with a 39% share of the global market in calendar year 2002. The alliance effectively doubles the size of the Cypher sales force. The coupling of Guidant's strong presence in interventional cardiology with the Cypher stent should help Cordis in its efforts to retain market share in the U.S. The agreement also provides for immediate settlement of patent disputes between Guidant and Cordis, allowing both to focus more resources on competing in the market.
In addition, a technology sharing and product development partnership will allow development to begin immediately on a next-generation product based on Guidant's Multi-Link Vision Stent Delivery System, a move that could help to counter the key advantage of the Taxus stent vs. Cypher. The two companies also will share in the development and commercialization of a new bioabsorbable stent technology. Boston Scientific is not waiting to be surpassed by Cordis with a next-generation stent, however. A successor to Taxus, the Liberte, already under development, will include a balloon with a five-way fold, built-in protection of the stent edge, improved flexibility (15% greater than the Express platform used in Taxus) for dealing with tortuous vessels while maintaining high radial strength, and .038" struts vs. the .052" struts of Taxus. The device also will be available in three versions (small vessel, workhorse and large vessel), improving the ability to match stent characteristics to the vessel being treated.
Drug-eluting stents under development include an everolimus stent from Guidant, the biolimus A9-eluting device from Biosensors International Pte Ltd. (Singapore), the Endeavor stent from Medtronic (Minneapolis, Minnesota), an ABT-578 eluting stent from Abbott Vascular Devices (Redwood City, California), the Unistar and Costar stents from Conor Medsystems (Menlo Park, California), the EPC Capture R-Stent from Orbus Medical Technologies (Fort Lauderdale, Florida), the AMS Absorbable Metal Stent from Biotronik (Berlin, Germany), and additional devices from Sorin Biomedica (Saluggia, Italy), Terumo Medical (Tokyo), Blue Medical Devices (Helmond, the Netherlands) and Translumina GmbH (Hechingen, Germany).
The Guidant stent features the company's proprietary Champion polylactic acid bioabsorbable polymer, which degrades to carbon dioxide and water in a series of steps, reducing the potential for adverse tissue reactions to the drug-eluting matrix. Deliverability of the device is equivalent to that of the bare-metal Multi-Link Vision, according to Campbell Rogers, MD, of the Cardiovascular Research Foundation, with equivalent angiographic visibility. The Biosensors stent uses a drug (biolimus) that is very similar to sirolimus in its mechanism of action but is released more rapidly from the stent and absorbs more rapidly in the vessel wall. Two platforms are under development, Challenge and the S-Stent platform, the latter using a biodegradable polylactic acid coating. Both the Medtronic and Abbott stents use the same drug, ABT-578, which has properties similar to those of sirolimus. The Medtronic device will use the Driver stent platform plus a phosphorylcholine drug-eluting coating. Abbott's version of the ABT-578 stent will use the TriMax stent platform acquired in the company's purchase of the BioDivysio product line from Biocompatibles (Farnham, UK), along with a phosphorylcholine coating.
Another development-stage device, based on the Conor Drug-Eluting Stent platform, shows considerable promise for increasing the ability to deliver multiple drugs with different elution profiles. The Conor stent consists of a metal framework with laser-drilled holes that act as drug reservoirs, and a biodegradable polymer coating to control delivery. The drug can be eluted either into the lumen or into the tissue, and up to five different drugs can be eluted from one stent. The Orbus technology is unique in that it does not employ a drug, but rather uses a coating with monoclonal antibodies to CD34, an endothelial progenitor cell-specific antibody. The Genous endothelial progenitor cell capture technology is designed to limit restenosis by quickly covering the stent with a layer of biocompatible endothelial cells and is being evaluated in the HEALING I trial and the HEALING II registry. Biotronik is developing the Lekton Magic Absorbable Metal Stent and has reported no restenosis in eight patients receiving the stent at one month in below-the-knee artery implants, with a worldwide coronary clinical study in the planning stage.
Other advances complement stents
One area of expansion in the scope of applications for interventional cardiology is in the treatment of chronic total occlusions (CTOs). Drug-eluting stents are showing promise for allowing such lesions to be treated with percutaneous intervention with significantly improved rates of restenosis, but the occlusion must first be opened and crossed before a stent can be placed. The SafeCross device, already available from IntraLuminal Therapeutics (Carlsbad, California), features optical coherence reflectometry along with RF ablation to cross and recanalize total occlusions. Another approach, the FrontRunner CTO catheter, using controlled, blunt micro-dissection, has been commercialized by LuMend (Redwood City, California). A technique using acoustic energy to ablate occlusions is under development by OmniSonics Medical Technologies (Wilmington, Massachusetts). However, as discussed by the Thoraxcenter's Serruys at the ACC sessions, all of the existing approaches to CTO recanalization rely on manual manipulation. The potential exists to employ a combination of magnetic navigation, optical coherence tomography (OCT) and radiofrequency ablation to develop a next-generation system for crossing chronic total occlusions. Siemens Medical Solutions (Erlangen, Germany) has developed a stereotaxis system, initially for use in guidance of electrophysiology catheters, that provides magnetically controlled catheter guidance, and that can be combined with OCT technology from LightLabs Imaging (Westford, Massachusetts), a subsidiary of Goodman Co. Ltd. (Tokyo), to enable real-time, automated recanalization of total occlusions.
Another area of intensive development activity within interventional cardiology is distal protection devices such as the PercuSurge GuardWire from Medtronic and related techniques to remove thrombus and debris from the arteries prior to stenting. In theory, such devices could help to minimize embolization during treatment, particularly for patients who have just suffered an acute myocardial infarction, and thereby enhance microvascular reperfusion. However, initial results from the EMERALD trial using the GuardWire, described at the ACC sessions by the Cardiovascular Research Foundation's Stone, have raised questions about the value of distal protection in improving patient outcome in post-myocardial infarction (MI) patients. The trial showed no statistically significant reduction in complications, infarct size or major adverse cardiac events with the use of distal protection compared to controls. While significant debris was captured by the balloon protection system in three-quarters of the patients, there was no significant improvement in blush score (an indication of microvascular flow) or in ST-segment resolution. The results surprised Stone and most other experts, since prevention of downstream embolization due to the typically large amount of thrombus and debris liberated when a thrombotic occlusion is re-opened would seemingly provide some benefits. One factor cited by Stone that may have limited the benefit of distal protection in the trial is the inclusion of patients who had experienced onset of chest pain at up to six hours prior to treatment. It may not be feasible to have an impact on infarct size if treatment is not initiated early. However, it also is possible that flow of debris into side branches of the artery, which is not prevented by balloon occlusion devices such as the PercuSurge, may have compromised the ability to achieve improvement in outcome.
Another technique targeting the same objective, i.e., elimination of debris and thrombus in acute myocardial infarction (AMI) patients prior to stenting, is being evaluated by Possis Medical (Minneapolis, Minnesota), using its AngioJet catheter in the 480-patient AIMI trial. Data from the study has not yet been analyzed. Rather than capturing thrombus and debris by occlusion of the vessel and subsequent aspiration, the AngioJet uses rheolytic thrombectomy to macerate and aspirate a blood clot. A single-center randomized controlled trial has already shown some benefit for using the AngioJet in AMI patients. Bench studies conducted by Possis have shown that the AngioJet can capture thrombus left behind by the PercuSurge system, due in part to the much lower evacuation forces generated by the PercuSurge device vs. the AngioJet. However, users of the AngioJet have observed that distal embolization still can occur in 11% of cases and are consequently favoring combined use of the device along with a filter protection system. The considerable added cost involved in such an approach could limit utilization significantly, unless major improvements in outcome are demonstrated. Many physicians already use the Boston Scientific FilterWire along with the Export catheter from Medtronic to help prevent distal embolization during stent and angioplasty procedures, but most users believe that improved devices are needed.
Among the more promising new devices under development are the Rubicon Filter from Rubicon Medical (Salt Lake City, Utah), the CardioPath Debulking System from Pathway Medical Technologies (Redmond, Washington), the TriActiv Balloon Protected Flush Extraction System from Kensey Nash (Exton, Pennsylvania), the Interceptor filter capture device from Medtronic, the Emboshield from Abbott Vascular and the KEPT and Rinspiration devices from Kerberos (Mountain View, California). The Rubicon filter is in clinical trials in Germany and will be launched in Europe in late spring of this year and in the U.S. in 2005 pending FDA clearance. Rubicon Medical is in the process of being acquired by Boston Scientific. As compared to that company's FilterWire, the Rubicon filter has a smaller profile (2.4 Fr vs. 3.0 Fr) and is configured as a single guidewire with a small centerwire that is pulled back to deploy the filter. The CardioPath system consists of an aspirating pathectomy catheter that expands during the procedure to provide a 100% increase in lumen cross-sectional area over the device's initial size. In vitro studies show the device can remove 97% of all debris, with the remaining particles having a mean diameter of less than 5 microns. The device is designed to remove not only thrombus and loose debris, but also calcific plaque, while protecting the artery or vein from distal embolization. CardioPath's first application is treatment of diseased saphenous vein grafts. Clinical trials are under way outside the U.S., and in the U.S. under a Phase I investigational device exemption. Pathway also is preparing to begin a randomized trial for use in AMI patients. The KEPT system consists of a guide catheter with an occlusion balloon, plus a rinse catheter that can be placed inside the guide catheter lumen. A low-pressure rinse is used to create turbulence to enhance aspiration of thrombus and debris. The Rinspiration system is a more advanced device that uses a single catheter to rinse and aspirate simultaneously. The device has received 510(k) clearance for peripheral vascular applications but is not presently on the market pending completion of a successful search for a marketing partner.
Another advanced approach for the treatment of AMI patients is under development by TherOx (Irvine, California), in partnership with Boston Scientific. The TherOx technology is based on the delivery of aqueous oxygen to ischemic tissues via transcatheter techniques. The TherOx device has been evaluated in the AMIHOT trial, which involved treatment of myocardial infarction patients in 10 U.S. centers. The device has already received regulatory approval in Europe. Thirty-day results from AMIHOT, however, did not demonstrate any clinical benefit of the therapy in the total study population, although some benefit was observed in patients with anterior MI.
Continued advances in coronary stents and ancillary technologies such as devices for CTO treatment and distal protection will help drive an ongoing expansion of the types of patients with occlusive coronary artery disease who can be successfully treated with interventional techniques. As a result, further declines in the use of bypass surgery are likely. In addition, some cardiologists are beginning to investigate methods for early detection of conditions leading to an acute coronary event, such as vulnerable plaque detection, including the possibility of prophylactic interventions in cases where the risk is sufficiently high. Collectively, trends in interventional technology favor continued growth in the market, and promise opportunities for both established suppliers as well as technology-based start-ups.
Valve repair, heart failure technologies
Another hot topic addressed in numerous sessions at the ACC conference was the use of interventional techniques to treat valve disease. A number of promising percutaneous valve repair and replacement devices are under development, as shown in Table 2. The devices will address a target population of at least 94,000 patients who undergo heart valve surgery annually in the U.S. That number is expected to grow with the introduction of percutaneous valves, since many patients with valve disease are not suitable for surgical treatment. Most devices are at an early stage of development and typically require a large (24 Fr to 25 Fr) catheter for implantation. One of the most advanced technologies is being developed by eValve (Redwood City, California) a transcatheter system used to correct valve regurgitation via the Alfieri technique, which involves stitching of the valve leaflets. The eValve device uses a clip rather than sutures to join the leaflets and can be deployed without stopping the heart.
Edwards Lifesciences (Irvine, California), the leading supplier of biological heart valves, also has initiated a program for percutaneous valve development, via the acquisition of Percutaneous Valve Technologies (PVT; Fort Lee, New Jersey). An initial study using the PVT device in 44 patients achieved 90% procedural success and positive outcomes. The procedure can be performed either with a retrograde or antegrade approach, although the retrograde approach is preferred since less manipulation is required and procedure times are shorter (one hour vs. about 80 minutes if the antegrade approach is used).
Jena Carditec (Jena, Germany), a unit of Jena Optics, is a new entrant in the percutaneous valve field. The company is focusing on reducing the diameter of its self-expanding valve, which currently is 24 mm in diameter and requires a 25 Fr catheter for deployment. The device is designed to treat both aortic stenosis and aortic insufficiency. At present, developers are focusing on treatment of high-risk patients who are not suitable for surgical therapy, and who thus have no other therapeutic options except percutaneous treatment. In the future, improved versions of today's percutaneously implantable valves are expected to allow a large percentage of invasive valve surgeries to be replaced by interventional techniques, creating a new, high-growth segment of the interventional cardiology device market.
Cell transplant therapy for heart failure is another emerging technology that attracted considerable attention at the ACC sessions. Researchers have begun to implement a variety of techniques designed to ensure that an adequate number of cells are implanted into the proper location in the heart. One approach, described by Tomasz Siminiak of the University School of Medical Sciences District Hospital (Poznan, Poland), uses the TransAccess Catheter System from Medtronic, a technology acquired via the acquisition of the assets of TransVascular (Palo Alto, California) in August 2003. Ten patients with post-MI heart failure have been treated with the device in the POZNAN trial by delivery of autologous skeletal myoblast stem cells to an infarcted region. The cells are extracted via biopsy, cultured outside the body, and then reinfused using the TransAccess catheter, which includes on-board intravascular ultrasound (IVUS) imaging, to direct the cells to the desired location in the heart. Up to 200 million myoblast cells were delivered to each patient. All patients showed improvement in symptoms (New York Heart Association class), and ejection fraction improved in four of the 10 patients at six-months follow-up. Ventricular tachycardia, a condition that has plagued a number of efforts to use cell implants for heart failure therapy, was observed in one patient. The use of catheter-based techniques for cell delivery has the advantage of reduced invasiveness as well as improved access to the heart tissue as compared to open surgery.
GenVec (Gaithersburg, Maryland) also is developing skeletal myoblast implant technology for heart failure treatment. Studies conducted by Frances Pagani, MD, of the University of Michigan Health System (Ann Arbor, Michigan), and Nabil Dib, MD, of the Arizona Heart Institute (Phoenix, Arizona), using the GenVec BioBypass myoblast cell transplantation system were highlighted at the ACC meeting. Dib described studies in 22 patients who received surgical myoblast injections. The procedure involves biopsy to obtain 2 grams to 5 grams of skeletal muscle cells followed by three to five weeks of cell culture and injection into the heart. Although the study did not employ controls, a dose-response effect was observed as more cells were delivered. Two patients had episodes of ventricular tachycardia, one of which was symptomatic. Nevertheless, the therapy appears safe, according to Dib, and plans call for moving to catheter-based delivery, with a trial already under way in Europe. GenVec has established a partnership with Cordis to use the Nogastar and Myostar catheters for guidance and delivery of cell implants.
A number of other groups are using stem cells from bone marrow as the source for autologous cells for implantation in the heart. Victor Zhau, MD, in a plenary lecture at the ACC sessions, described the use of gene therapy in combination with bone-marrow derived stem cell implants to repopulate an infarcted region with cells rendered more resistant to ischemia by insertion of the Hypoxia Responsive Element (HRE) gene. Emerson Perin, MD, of Pro-Cardiaco Hospital (Rio de Janeiro, Brazil), described using bone marrow that was filtered to produce a mixture containing about 10% cardiomyocyte precursor cells for injection. The Cordis Biosense (Diamond Bar, California) NOGA catheter was used for guidance. Importantly, the study evaluated objective measures of cardiac function, such as oxygen consumption and exercise time, in 12 patients. VO2 max increased about 40% on average in the treated patients, although it remained well below normal at one-year follow-up. There was no evidence of an increase in arrhythmias. Overall, the results of studies of cell transplantation therapy for heart failure indicate that the treatment is safe, at least when low doses are used. The next step in clinical studies will be to increase dose levels and to perhaps add methods to stimulate growth of the implanted cells, since the degree of improvement observed in the trials to date is far from a cure for heart failure.
Early detection, preventive therapy
Although continuing advances in treatment for advanced cardiovascular disease are resulting in better outcomes, many cardiologists believe that even greater benefit can be derived by improving the ability to detect disease at an early stage and employing preventive treatment to avoid progression to the point at which drug-eluting stents, replacement heart valves and cell implants become necessary. One of the most vexing problems, as discussed by presenters at a symposium sponsored by the Association for the Eradication of Heart Attack (AEHA; Houston, Texas), is the large number of deaths from cardiovascular disease, estimated at 19 million a year by the World Health Organization (Geneva, Switzerland), in patients who do not have elevated risk factors. In the view of experts presenting at the symposium, including Eugene Brunwald, MD, of Harvard Medical School; Valentine Fuster, MD, of Mt. Sinai Hospital (New York), Serruys and Douglas Zipes, MD, of Indiana University School of Medicine (Indianapolis, Indiana), more emphasis needs to be placed on improving the ability to identify such high-risk asymptomatic individuals prospectively to allow preventative measures to be taken. While sudden cardiac death and acute MI in previously asymptomatic persons was believed to be unexplainable and unavoidable only 15 years ago, most of those cases are now known to have links to pre-clinical disease and either classical, or novel but identifiable, risk factors. New technologies such as EBCT, a high-sensitivity imaging modality from GE Healthcare (Waukesha, Wisconsin), high-sensitivity CRP testing, vulnerable plaque imaging using IVUS palpography and optical coherence tomography are beginning to improve the ability to detect and categorize disease at an early stage.
The cost of widespread testing for early heart disease detection represents a major barrier to implementation, however, since there are more than 140 million people in the U.S. alone over the age of 35 who are potential candidates for testing. In addition, plaque is so prevalent in most Western populations that a search for patients with vulnerable plaque may prove fruitless. There are needs, according to a panel convened at the AEHA session, for a triaged approach to screening that starts with biomarkers, ideally using tests that can be performed at the point of care, and progresses to non-invasive imaging using techniques such as computed tomography, EBCT and magnetic resonance imaging, and then, in the highest-risk patients, to invasive techniques such as IVUS or OCT. Based on existing data, about 40% of individuals would qualify as low risk, 50% would qualify as intermediate risk and require more testing and 10% would be categorized as high risk and qualify for intensive risk reduction, perhaps involving provisional stenting or bypass surgery.
A substantial market now exists for products used to screen for lipid levels as early markers of cardiovascular disease at the point of care, as shown in Table 3, with strong growth projected as increasing focus is placed on early detection. Significant opportunities also are emerging for diagnostic modalities for use in intermediate and high-risk patients.