CDU Contributing Editor

SAN DIEGO, California The 39th annual meeting of the Society of Thoracic Surgeons (STS; Chicago, Illinois), held here in early February, along with the STS/AATS Tech-Con conference, provided a window to the changing role of surgery in the treatment of cardiovascular disease. The mainstay of cardiothoracic surgery procedures, coronary artery bypass graft surgery, is exhibiting a decline in utilization due to continued conversion to minimally invasive coronary angioplasty and stent therapy. As shown in Table 1 on page 2, which presents the most recent data from the National Hospital Discharge Survey, coronary stent procedures are continuing to rise rapidly while coronary artery bypass graft (CABG) surgery is in a slow decline. In 2001, the number of patients discharged with a CABG procedure dropped to the lowest level since 1991.

Another important procedure for the cardiothoracic surgeon, heart valve repair and replacement, also has not exhibited significant growth over the past five years, and in fact has shown some evidence of a decline in volume recently. In response to the growing incursion of coronary stent therapy, surgeons are working to change their techniques to make surgery a more attractive option for patients, and are focusing more attention on valve procedures, where minimally invasive technologies have so far had a limited impact.

So far, however, the adoption of minimally invasive heart surgery has been slow to occur, with the proportion of total procedures performed in the U.S. using less-invasive coronary bypass techniques stalled at 15% for now. But efforts are continuing to develop improved devices that will enhance patient outcome while minimizing the trauma and adverse effects of surgery. Robotics is one emerging technology that may help to improve surgical intervention, and two of the major suppliers of surgical robots exhibited technologies applicable to cardiothoracic surgery at the STS meeting. Development of technologies for use in less-invasive valve surgery is another focus in the industry, and one surgeon now predicts that more than 50% of valve procedures will be performed using percutaneous techniques by 2005.

As surgeons look to the future, some see a fundamental change that will result in a growing involvement of their specialty in minimally invasive therapy, with increased use of hybrid procedures employing both percutaneous intervention and surgery, greater use of off-pump surgery, and migration to some emerging procedures such as heart remodeling, implantation of mechanical hearts and the use of stem cells for myocardial restoration. The adoption of endovascular grafts to treat thoracic aortic aneurysms is attracting increased attention among surgeons, as are new approaches to treating congestive heart failure including use of prosthetic implants for destination therapy. The treatment of atrial fibrillation is yet another area where cardiothoracic surgeons can play an important role, and potentially have a major positive impact on long-term outcome of patients with cardiovascular disease.

Less-invasive surgery, more durable outcomes

During the 35 years since CABG surgery was introduced, there have been continued advancements in surgical techniques as well as in the technologies used. Bypass surgery has been shown to prolong life expectancy for many patient subgroups, an advantage that has not been demonstrated for other forms of coronary revascularization. The Achilles' heel of CABG surgery, as it was initially implemented, is degeneration of the saphenous vein grafts used for bypass, a shortcoming that results in a high failure rate by 10 years after treatment. Recently, the greater utilization of arteries such as the internal mammary and radial arteries for bypass has significantly reduced graft failure rates, a move that some experts view as a direct response to concerns that CABG is being replaced by percutaneous intervention. To further improve the attractiveness of bypass surgery, surgeons are now exploring a number of new technologies to reduce the invasiveness of the procedure while improving long-term outcomes. Reduced invasiveness is probably the more important factor in increasing the number of patients who opt for surgery, since many patients are willing to accept a poorer long-term outcome (such as a shorter interval before re-intervention is needed) in order to have a less invasive procedure. However, there also is a need to improve the durability of CABG surgery, since the patients who are now being referred for surgery rather than percutaneous therapy tend to have more complex and serious disease.

A number of technologies aimed at reducing the invasiveness and adverse side effects of coronary artery bypass surgery, and thus increasing its adoption, were described at the STS conference. The CORx System from CardioVention (Santa Clara, California) is one of the new devices now available for performing stopped-heart surgery while minimizing the adverse effects of the cardiopulmonary support system. The CORx system consists of three components: the CORx IOS, the CORx A/V Loop, and the CORx PowerBase Console. The PowerBase Console is not yet available in the U.S. The CORx IOS integrates air removal, oxygenation and pumping into a single, compact module with a blood contact surface area of less than 1.4 square meters. According to Dr. Mark Groh, MD, of Asheville, North Carolina, that is at least one-third the area for conventional cardiopulmonary bypass circuits. The small contact area translates to reduced exposure of the patient's blood to foreign surfaces, in principle minimizing Systemic Inflammatory Response Syndrome (SIRS), a common complication of conventional bypass surgery. The CORx A/V Loop allows bypass to be performed with little or no hemodilution due to its small internal volume. That feature results in a one-third or greater reduction in blood product usage, and halves the cost for blood products. The PowerBase provides flow control and transmits data on pressure and temperature to a display screen. A key feature of the CORx IOS disposable is the AirVac Active Venous Air Removal System, which incorporates an integrated sensor to actively remove air that inadvertently enters the circuit. The AirVac eliminates the need for a venous reservoir and the associated added surface area, air/blood interface, and exposure to chemical antifoam agents. The CORx system was cleared for marketing in the U.S. in April 2002.

Another new system that shows promise for reducing the adverse effects of coronary artery bypass procedures, the PhysioHeart system, was exhibited by Merce V. Electromedicina (Valencia, Spain). The PhysioHeart uses a balloon system mounted at the base of the oxygenator as a blood pump, and allows the perfusionist to set beat frequency and stroke volume. Studies with the device in animals have shown a complete eradication of necrosis in the liver and lungs that is observed using other bypass methods. The balloon pump mimics the action of the human heart, producing improved capillary perfusion as compared to other types of pumps.

Jostra AG (Hirrlingen, Germany), one of the leading suppliers of cardiopulmonary bypass devices, including the Bentley oxygenator line acquired from Edwards Lifesciences (Irvine, California), has recently introduced the MECC minimal extracorporeal circulation system, a new miniaturized cardiopulmonary bypass system that provides a low priming volume (500 ml) and includes all the required components (oxygenator, pump, arterial filter, and heat exchanger) in a compact package. As with the CardioVentions CORx system, a goal of the MECC design is to minimize the surface area exposed to blood and reduce prime volume, as well as to minimize blood exposure to silicone. FDA clearance was obtained for the MECC system in December. A new version, the MECC II, is under development that will offer a more integrated package and a sufficiently low prime volume to allow bypass to be performed at normal hematocrit, as in the CardioVentions system. Although the cost for the MECC system is higher than for conventional bypass devices, the savings in transfusion costs and blood product usage more than offset the added expense.

Cognitive defects occurring as a result of CABG surgery are one of the concerns surrounding the procedure. Typical rates for stroke following CABG surgery are 2%, while 6% to 10% of patients exhibit encephalopathy. Manipulation of the aorta including clamping is believed to be a primary source of emboli that can cause neurological deficits and stroke. Guidant (Indianapolis, Indiana) has introduced a new device, the HeartString Proximal Seal System, which eliminates the need for clamping of the aorta. The HeartString consists of a plug formed from thread that maintains a seal in the anastomotic hole while sutures are applied. Before the last suture is inserted, the device is removed by pulling the thread. More than 130 cases have been performed with the device so far, with only one complication reported. The HeartString was cleared by the FDA in June 2002.

There is some question as to the true extent of adverse effects associated with CABG surgery. A study published in the Jan. 30 issue of the New England Journal of Medicine, authored by the members of the Octopus study group in the Netherlands, compared on-pump and off-pump coronary bypass surgery in low-risk patients and found no significant differences in death, stroke, myocardial infarction, health-related quality of life, or coronary reintervention at one year, although costs of treatment were about 14% higher for on-pump surgery. The study did not, however, address changes in cognitive capability, and also did not investigate high-risk patients. Data from the Society of Thoracic Surgeons registry shows a lower incidence of stroke in high-risk patients after off-pump surgery, indicating that there may be benefits in addition to cost savings for off-pump surgery in that patient group. A study presented at the STS conference by Ola Selnes of Baltimore, Maryland, that assessed cognitive changes after CABG surgery and compared 142 surgical patients against a group of 92 nonsurgical controls found no significant differences at three months and 12 months. However, as with the study conducted by the Octopus group, the results may not apply to high-risk patients, who are likely to be more susceptible to stroke and other adverse events. Furthermore, the cost advantages of off-pump surgery may justify its use in place of on-pump surgery. The key to achieving greater use of off-pump surgery in the future will be the development of improved technologies that make procedures less technically challenging while maintaining, and ideally improving, its cost advantages.

Automated anastomosis devices have been an important development focus for a number of companies recently. St. Jude Medical (St. Paul, Minnesota) has introduced the Symmetry Bypass Connector worldwide for attachment of saphenous vein grafts to the aorta without using sutures. The device also allows the surgeon to avoid cross clamping. An initial evaluation of the Symmetry in 26 patients resulted in two procedural failures and three cases of stenosis at one-year follow-up, but no patients experienced any symptoms of ischemia and all grafts remained patent. Another product, the Enclose anastomosis assist device from Novare Surgical Systems (Cupertino, California), also is on the market in the U.S. The Enclose has been designed specifically to avoid the need for partial clamping of the aorta. It is priced at $450. Coalescent Surgical (Sunnyvale, California) markets the U-Clip Anastomotic Device for use in performing distal coronary anastomoses. The U-Clip has been used in over 35,000 procedures worldwide, and is being employed not only in coronary procedures but also in peripheral vascular surgery, AV access, transplant and general surgery. A key feature of the U-Clip is that the cross-sectional area of the anastomosis is larger compared to that obtained with conventional continuous suture techniques. The U-Clip technique does not perform an anastomosis in one step, but uses individual, self-deploying nitinol clips (eight to 12 for a typical coronary anastomosis) costing $15 each. A U-Clip anastomosis can be performed in four minutes, significantly less than one performed using continuous sutures, and studies have shown improved patency. The use of individual clips in the procedure also avoids the drawstring effect associated with continuous sutures, resulting in improved flow. Perhaps most importantly, the clips allow an anastomosis to be performed without the use of a side-binding clamp. U-Clips have also been used in robotic surgery. Coalescent is now developing the Spider device, which autofires the U-Clips. A device to perform A-V fistula procedures is under development that promotes faster maturation of the fistula and produces a higher success rate (90% vs. 70%), addressing a major problem in dialysis access.

One of the key barriers to increased adoption of minimally invasive cardiac surgery is the complexity of the procedures, and in particular the difficulties associated with performing precise manipulations using existing endoscopic devices. Medcanica (Miami, Florida) is a venture-funded firm that has developed a tremor reduction port (the Instrument Damping Port) for endoscopic surgery. The device uses a spring to stabilize the tip of an endoscopic tool. The device is placed between the ribs in an endoscopic CABG procedure and effectively acts to dampen motion at the tip of the endoscopic tool.

More sophisticated approaches using robotics are under development. Robotic surgery is beginning to emerge as a viable technology in cardiothoracic surgery, and has attracted considerable interest in Europe. Robotics may allow cardiac surgery procedures to be performed with minimally invasive techniques that are beyond the capabilities of surgeons using manual methods. Intuitive Surgical (Sunnyvale, California) and Computer Motion (Goleta, California) are the two leading companies in the field. Computer Motion has introduced the Endo-ACAB program, which provides equipment and accessories along with training, research opportunities, and assistance in marketing of robotic surgery to physicians. The Endo-ACAB procedure uses 5 mm ports and videoscopic techniques to perform all the preparatory steps for a LIMA-LAD anastomosis, including harvesting of the internal mammary artery, opening the pericardium, locating and stabilizing the target vessel, and clipping and ligating the IMA. The remainder of the bypass procedure is performed using conventional off-pump techniques, and requires a four-centimeter anterior thoracotomy. Intuitive exhibited its da Vinci robotic surgery system at the STS conference, and is focusing on hybrid procedures combining surgical and interventional treatment as a key application. The da Vinci robot is priced at $1 million to $1.3 million depending on options, and the amortized cost of the reusable endoscopic tools used in the procedure is about $1,500. One application that has been demonstrated is endoscopic repair of atrial-septal defects, and in January Intuitive reported it had received FDA clearance of the da Vinci system for that application. FDA clearance already had been received for use in thorascopically-assisted cardiotomy procedures such as mitral valve repair.

Higher profile for valve repair, replacement

Valve repair and replacement is in fact growing in importance in cardiothoracic surgery as CABG procedure volume continues to decline. New mechanical valve technologies, as well as advances in tissue valves, are helping to drive heightened interest among cardiac surgeons. According to suppliers of heart valves, more than 250,000 patients worldwide undergo open-heart valve replacement operations each year. As shown in Table 2 on page 5, a number of new heart valve products have been introduced recently, and more are under development. About two-thirds of all heart valves implanted in the U.S. are mechanical valves, based on data from the National Center for Health Statistics (Bethesda, Maryland) for 2001. Leading suppliers such as Medtronic estimate that 90,000 mechanical heart valves are implanted in the U.S. annually. According to presenters at the STS conference, durability is one of the primary reasons for choosing a mechanical valve. However, patients with mechanical valves must take anti-coagulants regularly, leading to a requirement for frequent monitoring, creating a major inconvenience for patients. Control of anticoagulation parameters is often not optimal because of the difficulty of testing. One factor that may help to improve outcomes for patients with mechanical valves is the recent implementation of Medicare reimbursement for coagulation self-testing, which may stimulate use of more frequent monitoring and improved control of hemostasis for heart valve patients. However, the current reimbursement framework does not provide a strong incentive to adopt self-testing.

While tissue valves are not presently employed as often as mechanical valves, the tissue valve segment is growing more rapidly. Two types of tissue valves stented and stentless are commonly employed for heart valve replacement. Most implants today use stented valves; according to suppliers, only about 5,000 patients per year receive a stentless valve in the U.S. A key issue with most existing types of stentless valves is the difficulty of surgical implantation, due to the poor handling characteristics of the devices, which lack a scaffold to provide mechanical support. But the latest generation of stentless valves has some desirable features that may increase their use in the future, including improved handling characteristics and optimized fluid flow. Benefits of stentless valves include a low incidence of mismatch between the patient and the valve, and better hemodynamic properties including laminar flow, potentially leading to better long-term outcomes for patients receiving stentless valve implants. Some recent studies have shown that exercise performance is improved for patients with stentless valves, and some small-scale studies indicate that patient survival is improved, but large, long-term randomized trials have yet to be performed to substantiate those results.

One of the most unique new valve replacement products under development is the 3F Aortic Bioprosthesis from 3F Therapeutics (Lake Forest, California). The 3F device uses a tubular design and equine pericardium as the base material, and employs a computer-aided process to cut the valve leaflets to optimize the fit of each component. 3F also is pursuing a long-term strategy to develop minimally invasive technologies for valve repair. The existing device can be deployed without the need for sutures, and for future versions the company is targeting a minimally invasive on-pump approach, to be followed by development of off-pump techniques and, eventually, transcatheter delivery.

Tissue-processing technologies are now playing a significant role in heart valve devices to reduce thrombosis and thromboembolism. For example, the Medtronic (Minneapolis, Minnesota) Mosaic valve is a third-generation device that is fabricated using the company's alpha amino oleic acid (AOA) anti-mineralization treatment combined with the Medtronic Physiologic Fixation process. The processes help to maintain the natural leaflet structure of the valve and reduce the potential for calcification of the tissue. St. Jude Medical (St. Paul, Minnesota) also is developing a valve that is fabricated with a special treatment process to inhibit mineralization. Another advance is the addition of scaffold materials to stentless valves to improve their handling characteristics during the implant procedure. Shelhigh (Millburn, New Jersey), for example, has incorporated a delrin framework in its stentless valve to provide support during the attachment procedure.

Future developments in the field of heart valve surgery are likely to include the increased use of minimally invasive implant techniques, extending to transcatheter methods for performing valve procedures. For example, as discussed by presenters at the STS conference, surgical valvotomy is now effectively an obsolete procedure as a result of the widespread adoption of balloon valvuloplasty, performed with the Inoue double balloon catheter manufactured by Toray Medical (Tokyo). However, when valve disease cannot be successfully treated with valvuloplasty, open surgical repair is indicated. Efforts are now under way to develop new catheter-based methods that will replace even those surgical procedures. Percutaneous repair of mitral valves was described at the STS conference by Dr. Ottavio Alfieri of Milan, Italy. The leading supplier of tissue valves, Edwards Lifesciences, is performing Phase I studies on animals of beating heart mitral valve repair. The existing technique uses a suture device plus a vacuum-driven component that captures the valve leaflets and approximates them. In Phase II, plans call for the device to be miniaturized to allow it to be deployed in a 9 F catheter, allowing use of a percutaneous approach. The delivery system includes a guide wire, a guide catheter and a therapy catheter that is used to cut and suture the leaflets. Potential candidates for the procedure include patients with edge-to-edge defects, those with localized defects, and those who are not candidates for surgery because of the presence of risk factors. Research also is under way to develop percutaneous techniques for pulmonic valve repair.

Endovascular grafts attract growing interest

In addition to implementing less-invasive approaches to cardiac surgery, cardiothoracic surgeons are also becoming increasingly interested in using endovascular therapy as an alternative to surgery. According to presenters at the STS conference, surgeons can now share reimbursement with interventionalists when endovascular procedures are performed. Endovascular grafts have now been adopted in many treatment centers worldwide for repair of abdominal aortic aneurysm, with more than 32,000 devices implanted as shown in Table 3 on page 7. While the devices have encountered some issues related to long-term performance including migration and endoleaks, endovascular grafts have generally proven to be a major advance in aneurysm treatment, providing lifesaving therapy for many patients who were poor candidates for surgical aneurysm treatment because of risk factors. Thoracic aortic aneurysm (TAA) treatment is an attractive application for endovascular grafts, since surgical treatment is associated with a high rate of morbidity and mortality. According to Michael Dake, MD, of Stanford University Medical Center (Palo Alto, California), there are now about 15 centers worldwide with significant experience in using endovascular grafts for TAA treatment. As discussed by Craig Miller, MD, also of Stanford, at the STS conference, development of endografts for TAA applications has been under way for at least five years, initially using prototype devices fashioned from peripheral vascular stents covered with Dacron and a relatively large (24 F to 28 F) delivery system. The technology for device deployment has proven to be a difficult barrier to overcome. However, Miller's early studies produced encouraging results, including a stroke rate in treated patients of 7% vs. rates in surgical series ranging from 5% to 13%, and a lower (3%) rate of paraplegia following the procedure than anticipated. Paraplegia is a concern with TAA devices because of the potential for blocking of blood vessels feeding the lower limbs.

Manufacturers of endovascular grafts, including Guidant, Medtronic and W.L. Gore (Flagstaff, Arizona), have developed refined versions of their devices that are suitable for TAA therapy, and clinical studies are under way. Some devices now are being implanted for compassionate use in patients who are not surgical candidates. The devices are a major improvement over earlier prototypes, according to Miller, and in a Phase I trial with the Gore Excluder for TAA the acute outcome included a 4% death rate, and no strokes or paraplegia in 27 patients. At one year, the death rate rose to 18.5%, but there were no device-related complications. Applications include treatment of aortic dissections including trauma-induced dissections, treatment of aneurysms, and treatment of penetrating ulcers. There has been greater use of the devices outside the U.S. For example, Enio Buffolo, MD, of Sao Paulo, Brazil, has performed 1,366 endovascular procedures for TAA treatment using a device manufactured by Braile Biomedica (Sao Jose do Rio Preto, Brazil). The Braile device consists of a stainless steel Z-stent covered with polyester, implanted using a 20 F to 24 F delivery system. Case volume increased from 16 in 1987 to 163 in 2002 in Buffolo's center. In the past year, about 60% of all patients referred to the center for TAA treatment received endovascular therapy, while only 40% were treated with conventional surgery.

The number of patients who require treatment for TAA is considerably smaller than the number requiring AAA treatment. About 13,000 patients were discharged from U.S. hospitals in 2000 with any diagnosis of thoracic aortic aneurysm, according to the National Center for Health Statistics, vs. 123,000 with AAA. However, suppliers estimate that up to 60% of TAA patients may be candidates for endovascular treatment, vs. 20% to 25% of AAA patients, due to the greater trauma of TAA surgery. As a result, the introduction of a viable TAA endovascular product should drive a significant new increment in growth in the endovascular graft market.