MIS in Cardiovascular: The Last Best Hope

Now it is appropriate to ask whether, for product companies in particular, cardiovascular represents the final and full realization of MIS' promise-or another bumpy ride with disappointment the only certain endpoint. Sidebar: Angioplasty and the MISThreat: The advent of MIS resurrects the historic rivalry between interventional cardiology and cardiac surgeons.

After failing to fulfill its promise in laparoscopy, minimally-invasive surgery is hot again—this time in cardiovascular. Is MIS about to flower again? Or is there still reason to be cautious?

by David Cassak

• Interest in using minimally-invasive techniques in cardiovascular surgery is growing today, driven by patients, payers, and an eager surgeon community.

• Many clinicians believe MIS could revolutionize revascularization, but others think the adoption curve could be slow because of the difficulty of the procedure.

• Technology will play a role in making MIS more predictable and more widely disseminated, as cardiovascular and general surgical instrument companies battle for the new marketplace.

• Some clinicians worry about a hype factor which could lead patients, payers, and even some product suppliers wondering what happened to MIS’ potential in cardiovascular.

On March 4, Heartport Inc. , a small California medical device company, filed for an IPO that placed a tentative market cap on the company of $252 million. Three days earlier another California startup, CardioThoracic Systems Inc. ,filed for its IPO. Tentative market cap: $237 million, fully diluted.

What could possibly justify such rich valuations? Believe it or not, minimally-invasive surgery (MIS). After the early boom-and-bust experience of MIS in gall bladder removal (laparoscopic cholecystectomy)—which saw dozens of small and large companies come up empty—many industry executives thought MIS’ star had faded. They shouldn’t have.

Even during the heyday of laparoscopic cholecystectomy, many clinicians and industry executives believed MIS’ most promising opportunities would come in cardiovascular and thoracic surgery. If surgeons could use minimally-invasive techniques in procedures such as coronary artery bypass and valve repair and replacement, to access the heart without having to crack the patient’s chest open, the benefits of MIS—faster recovery and higher comfort for patients, improved economics for payers—would be obvious.

Still, as MIS gears up for its second boom, the questions that dogged its earlier rise and fall in GI remain: how far will minimally-invasive approaches penetrate the wide range of cardiovascular procedures? And what role will technology play in furthering this next major wave—in particular, technology offered by innovative small companies as opposed to large cardiovascular and surgical instrument suppliers? Perhaps it is now, when enthusiasm for MIS in cardiovascular is reaching a crescendo, that it is appropriate to ask whether, for product companies in particular, cardiovascular represents the final and full realization of MIS’ promise—or another bumpy ride with disappointment the only certain endpoint.

Lining Up to Do Them

Though performed on only about 1,000 patients around the world to date, chances are you’ve already heard of minimally-invasive cardiac bypass surgery (MICAB), the first of the major cardiovascular procedures to be done minimally-invasively. Over the past several months, hospital PR departments—and some product suppliers—have been working overtime to publicize the advent of this new procedure. Reports of what is sometimes called MIDCAB, for minimally-invasive direct cardiac artery bypass, or PACAB for port-access cardiac artery bypass, have appeared widely in daily newspapers and been profiled on some national television news programs.

Such reports belie the very preliminary nature of the procedure. Dr. James Fonger of Johns Hopkins School of Medicineand Sinai Hospital in Baltimore, one of the early adopters, estimates that “there are probably a half a dozen centers doing this in a serious fashion and another dozen centers starting to get some experience at the present time.” Adds one industry observer, “It gets to the point where everybody wants to be the first on their block to do this. As soon as they do, they issue a press release that makes it seem like this is appropriate for and available to everyone. The reality is, this is a difficult procedure to do.”

Still, interest in the procedure is hot. Despite the fact that surgeons tend to be a conservative group, skeptical of new technologies and new procedures until they’ve seen a lot of safety and efficacy data and peer reviewed articles, MIS was “the talk of the recent Society for Thoracic Surgeons’ meeting in Orlando,” notes Terry Shepherd, president of the Valve Division of bypass, but without the sternotomy, a highly traumatic procedure to the patient.

As with MIS in other procedures, patients experience less pain and discomfort and are able to resume work and other daily functions sooner. Employers and other payers like it because recovery times are faster and productivity losses are cut. Indeed, many industry observers believe consumer and payer demand will lead the charge. Perhaps most important, MIS often produces clinical as well as economic benefits. “It’s axiomatic to say minimally-invasive techniques will gain favor because of costs,” says Glenn Nelson, MD, vice chairman of Medtronic Inc. “But they’ll also be adopted because of clinical outcomes. Through MIS, we disrupt the normal anatomy to a lesser degree and that will lead to better outcomes.”

Operating on a Beating Heart

Indeed, Nelson argues, MIS holds something for everyone: cost savings for employers, better results for patients, and more clinical freedom for surgeons. “There are things you can do closed that you can’t do open.”

Such advantages notwithstanding, there is, even among MIDCAB’s strongest advocates, a note of caution, if not about the procedure itself, at least about the surgeons who are lining up to try it. Notes Dr. Thomas Burdon of Stanford University Medical Center,who is working on the HeartPort approach to MIS, “The same thing happened in laparoscopic and thorascopic surgery. There’s an initial surge of activity as everyone tries it.” But he goes on, “There are a lot of people out there who have no real idea what they’re doing, are not scrutinized by the FDA, and haven’t ever been in an animal lab. They’re the wrong people to be doing this.” Adds Michael Mack of Dallas Medical City, another cardiovascular MIS pioneer, “We’ve been down this road with thoracoscopy and you see what happens—mistakes get made, accidents happen. You can see surgeons feeling pressure to do something just to keep up. And surgeons shouldn’t feel that pressure. There’s a fine line between innovation and progress on one side and creating chaos on the other.”

The ability to access the heart and harvest the internal mammary artery through small incisions is critical to minimally-invasive bypass. But what makes minimally-invasive bypass truly innovative, at least in its first iterations, is that it eliminates not just the sternotomy, but also the use of artificial cardiopulmonary bypass and operates directly on the heart. Indeed, the procedure is called minimally-invasive directbypass because the surgeon is both directly looking at and operating on a beating heart.

The procedure was first developed in the US around two years ago. One of the earliest adopters was Dr. Valavanur A. Subramanian of New York’s Lenox Hill Hospital. “1992-93 was the time of the stent trials,” Subramanian recalls, which underscored the problems catheter-based therapies such as angioplasty had with restenosis. “We were seeing a lot of new technologies such as lasers and roto-blators, but the restenosis rate was still high,” he explains.

At the same time, Subramanian and his colleagues had begun to do pericardial drainage through small incisions. “Every time we made a small incision, we saw the LAD and left IMA right there, and it soon occurred to us we could use this [minimally-invasive] technique for other things.” Under his approach, the heart is beating, though it has been slowed down.

Subramanian is not only an early adopter, but also one of the first to report on the success of the procedure. In early 1995, he joined with three other facilities, two in Italy and one in Argentina, for a multi-center study that by November of last year had reported on 188 cases. Subramanian himself has performed 80 minimally-invasive procedures, including 15 double bypasses and one triple bypass.

Around the same time that Subramanian was developing his approach in New York, across the country, other surgeons had begun to explore MIS’ potential. In Dallas, a team led by Drs. Michael Mack and Tea Acuff were working on minimally-invasive coronary artery bypass with a slightly different twist. Drawing on their experience as lung surgeons in thoracoscopy, Acuff and Mack developed a technique in which they make three incisions on the left side of the chest put a scope in and harvest the internal mammary artery, says Mack. “We then make another access incision and sew it onto a beating heart.”

An Arrested Heart

For many clinicians, it is the ability to avoid the risks of the heart-lung machine, rather than the trauma of the sternotomy, that is the key to minimally-invasive coronary artery bypass. “Putting the patient on the heart-lung machine is the most deleterious thing we can do,” says VA Subramanian. “We want to avoid that as much as possible.” Adds Michael Mack, “If I had to have an operation and could eliminate either the sternotomy or the cardiopulmonary bypass, I’d eliminate the bypass.”

MIDCAB advocates note that though the heart is beating, the arteriotomy site, where the anastomosis is being done, has, for the most part, been immobilized. But not everyone agrees that the ability to do bypasses directly on a beating heart is the best approach. Working exclusively with HeartPort’s endo-aortic clamp technology, Thomas Burdon is part of a team of researchers at Stanford, led by Dr. Bruce Reitz, that have begun to do bypasses on hearts that have been put on cardiopulmonary bypass and then stopped, exactly as is done in open CABs. (Because of their pending IPO, HeartPort executives declined to be interviewed for this article.)

Indeed, while other surgeons argue for the benefit of eliminating the heart-lung machine, Burdon argues that putting the patient on cardiopulmonary bypass is safer because it builds off 10 to 15 years of advances in cardiovascular surgery.

Burdon notes that arresting the heart allows surgeons to use the same principles in MIS that they’ve been using in open procedures. “We’re operating on an artery that is one to three millimeters in diameter, and the way we’ve been trained to do it [in open procedures] is on the arrested heart,” he argues. “All of the advances that have been made have enabled the mortality and morbidity rates to approach less than 1% in large series of first-time coronary operations. That’s almost as good as gall bladder surgery and it’s been because, with the aid of cardiopulmonary bypass, we’ve arrested the heart when doing the operation.”

Key to the arrested-heart procedure is the HeartPort device developed in collaboration with the Stanford researchers. (Reitz and his team serve as consultants to HeartPort.) Under traditional open bypass, the heart is stopped by clamping the aorta from the outside before the cardioplegic solution is infused into the heart. HeartPort, says Burdon, had to find a way both to clamp the aorta from the inside and be able to deliver the solution.

The HeartPort device works much like an angioplasty balloon, inserted into the femoral artery and then snaked up into the heart. Once there, the balloon is inflated, occluding the aorta. The cardioplegic solution can be delivered and blood drained from the heart to create a bloodless field. At that point, the minimally-invasive aspects of the procedure take place. Three small ports are made in the chest and a small incision is made to remove a portion of the fourth rib, and looking down on the anterior descending artery, the surgeon performs a traditional graft. “Once the heart is stopped, we can do our anastomosis in a controlled fashion,” says Burdon.

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The Heart-Lung Debate

The Stanford team has been working on arrested heart bypasses for three years, having spent much of that time developing the proper instrumentation and experimenting on animals and cadavers. As of early February, the procedure had been tried on approximately 10 people.

The issue in choosing to work on arrested rather than beating hearts, says Burdon, is “basic safety.” “Good, safe cardiopulmonary bypass with the use of the heart-lung machine has really accelerated the development of cardiovascular surgery,” he says.

Burdon acknowledges that heart-lung bypass isn’t risk-free, but, he argues, at least we know what happens when you go on cardio-pulmonary bypass. More to the point, it’s the way 99% of cardiovascular operations are performed today, he argues. “As far as I’m concerned, [operating on an arrested heart] is a safe procedure. I’d have it done on me tomorrow.”

Still, the arrested heart procedure, though only in the early stages of development, has drawn criticism as well, mostly from clinicians who believe that putting patients on heart-lung bypass should be avoided at all costs. Notes Dallas’ Tea Acuff, who is now performing about one-third of his open bypasses off the heart-lung machine, “I don’t think anyone believes putting people on bypass is good. While it’s routinely used in open procedures, it can cause a fair number of problems. If we could just do away with it altogether, we would.”

That means that the HeartPort procedure may prove more appropriate for the next generation of minimally-invasive bypass—those treating multiple vessel disease where putting patients on the heart-lung machine is unavoidable—but less relevant for the kinds of simple, single vessel procedures that constitute the early wave of adoption. Argues Lenox Hill’s Subramanian, the arrested heart procedure is “fine if you’re treating a severely damaged heart. But if only a small part of the heart needs repair, why would you want to stop the whole heart?”

Wishing a Rival Well

“Ask any surgeon whether the ability to do coronary- artery bypass without the heart-lung machine would be better, and the answer is almost universally ‘Yes,’ says Kathleen A. Marshall, vice president of marketing at CTS, which is developing proprietary technology to do MIDCABs. “Intuitively, it’s just clear that [doing the procedure on] a beating heart is better.” Still, CTS officials are quick to make it clear that they don’t see themselves competing with HeartPort. “They have one approach, we have another; we’re just working in different directions,” says CTS’ president Richard Ferrari. Indeed, in some areas, such as valve repair, operating on an arrested heart may be the only way to do the procedure. “We think both approaches will be very successful,” he concludes.

In fact, Ferrari says he wishes HeartPort all the luck in the world, especially with its IPO. (CTS had, at press time, launched its own public offering). “From a selfish point of view, I hope HeartPort does very well because when you have a new industry developing, the last thing you want is for one of the leaders not to succeed.”

Indeed, the real question isn’t whether the procedure should be done on a beating or arrested heart, but what impact MIS will have on cardiovascular surgery broadly speaking. One of the dilemmas that both providers and product suppliers faced in MIS in GI was that after quickly penetrating cholecystectomies, surgeons resisted the spread of MIS to other procedures such as hernia and appendectomies because they were more difficult to do and often took just as long as open procedures.

Stanford’s Burdon argues that 70-80% of the cardiovascular procedures can be done using minimally-invasive approaches. But other industry observers argue that minimally-invasive bypass’ potential is limited to the 5-15% of patients with coronary artery disease who suffer from single vessel disease. A handful of MIDCABs have been done on two vessels and a couple have even been done on three vessels. But today, the vast majority of cases are done on single vessels. Baltimore's James Fonger notes that “patients with single vessel coronary disease are the primary candidates for this procedure,” in particular, those who might have had angioplasty or stents but found the therapy failed “and want to move on to a different approach where [restenosis] may have less chance of occurring.”

More complex cases, he argues, may be better dealt with using traditional open surgery. “For single vessel disease, this is a very good therapy and is currently being done in all coronary locations around the heart,” he says. “But I doubt if [minimally-invasive bypasses] will achieve the same penetration that laparoscopic cholecystectomies did because a lot of patients present with three and four vessel disease which currently is best handled by conventional surgery.”

Indeed, given that such single vessel disease is often treated with catheter-based interventions—angioplasty and stents—some industry observers argue that minimally-invasive surgery’s greatest impact will be on angioplasty rather than conventional bypass. Notes Dallas’ Tea Acuff, “There are 400,000 PTCAs being done on single vessels, and [MIS] is a very good approach for that. The impact is really going to be on new indications for surgery [i.e., converting catheter-based therapies to surgery] as opposed to taking away from traditional surgeries. We’re still going to be doing surgery for the more complex cases for a long time until we can figure out other ways of doing [multiple vessel cases].” (See sidebar, “Angioplasty and the MIS Threat”, p. 54).

And, in fact, some clinicians report that more and more MIDCABs are being used as primary therapy for single vessel diseases—particularly in those cases where post-angioplasty restenosis is most likely. Still, many believe that, for now at least, until an aggressive push by consumers and payers forces their hand, surgeons are more likely to use MIDCABs as secondary therapy, an alternative where earlier angioplasties failed.

Beyond Bypass

Baltimore’s James Fonger sees another potential, not widely recognized yet, for MIS approaches: the re-operative population. For patients who, for instance, “had a mammary artery and two veins placed on the heart 15 years ago and the vein grafts are now occluding while the mammary artery is fine,” he explains, “this technique provides a focal strategy for fixing a specific area on the heart and then exiting without doing a full-scale cardiac operation.”

Still, while early adopters contemplate the variety of MIS applications, most agree that the complexity of cardiovascular surgery will make rapid adoption of MIS unlikely. “We’re still a long way away from widespread adoption,” says VA Subramanian, primarily because the principle steps, harvesting the mammary, sewing the anastomosis, “take a lot of skill,” adding, “We’re developing new tools and techniques, but we still have a long way to go before we perfect this.”

Indeed, how quickly surgeons in other centers become proficient is a big question. Comparing cardiovascular MIS with laparoscopy, Dallas’ Michael Mack adds, “Both are high volume procedures so there’s a lot of opportunity for surgeons to get good at it. But laparoscopic cholecystectomy is, technically, a very easy procedure to do, and you get over the learning curve very quickly. That’s not the case with bypass surgery, which even in an open situation is a technically very difficult procedure.”

Many surgeons are still intimidated by the simple fact of operating on a beating heart. Even VA Subermanian notes that he can’t, after all his experience, “predict which hearts will beat more aggressively.” Working on approaches, some pharmacological, to slow or quiet the heart, he notes, “It’s still not that comfortable a procedure, even for me and I’ve done a lot of them.”

In particular, resistance is likely to come from older surgeons who believe that learning MIS is more trouble than it’s worth. “As with any new technology, certain people learn it quickly,” notes Thomas Burdon. “There’s a hand-eye coordination that makes [MIS] familiar to the surgeon who’s been trained in thorascopic and laparoscopic techniques. At the same time, if you’re a 55 year old surgeon who has never been trained in these new procedures, you’re likely to resist this.”

Still, notwithstanding such obstacles, nearly everyone agrees that MIDCABs will dramatically change cardiovascular surgery, precisely by bringing the benefits of MIS—faster recovery, less patient discomfort, greater economic benefits—to traditional surgery. “We’ve had a procedure [i.e., open bypass], proven to have a very high success rate after 18 years, and no one wants it,” notes Michael Mack. “They all want angioplasty. Why? Because it’s less invasive. But with this new procedure, we can eliminate the two most invasive aspects [of open surgery]—the sternotomy and the cardiopulmonary bypass.”

And bypass surgery is only the first of many cardiovascular procedures that can be done minimally-invasively. St. Jude’s recent agreement with HeartPort suggests that valve repair and replacement will soon be done minimally-invasively (though valve procedures can only be done on an arrested heart and so will not avoid cardiopulmonary bypass.) Says St. Jude’s Terry Shepherd, “There is probably a group of older surgeons who look at this and think, ‘I’d rather just retire.’ But as the clinical environment becomes more competitive and managed care begins to exert its influence, there are going to be a lot of surgeons saying to themselves, ‘This is the way surgery’s going to be done in the 21st century. I have to be able to do this procedure or I’m going to be out of a job.’” Adds Medtronic’s Glen Nelson, “While there are some who argue that only 10-15% of the patients are candidates [for MIS], a lot of surgeons believe there are a significant number of cases that can be done this way. And that may grow. The current approach is what I would call less invasive, it certainly isn’t minimally-invasive and we’ll see further improvements.”

Preserving the Familiar

Indeed, for now, the primary obstacle to MIS in cardiovascular seems to be one of developing tools and techniques that make it possible for procedures now requiring great skill to be done more easily and with predictable and reproducible results by a large number of surgeons. Says James Fonger, “I think the early surgeons doing this technique feel some responsibility to minimize the learning curve for others. Certainly we want anyone who decides to do this to take a serious attitude toward learning it—to learn how to do it well and to follow up their results so they know exactly what the results are in their programs.”

Still, for all of the talk about MIS’ potential in cardiovascular, the key to this putative revolution rests on preserving much of traditional bypass procedures even as it introduces minimally-invasive techniques. Describing how his approach differs from other techniques, Michael Mack notes, “In any MIS procedure, one of the cardinal principles is that you duplicate the procedure as it’s done in the open situation. You can’t compromise the procedure just to do it by a less invasive approach, and we feel [the other approach] compromises the internal mammary artery by not harvesting the same way that you do in an open situation.”

Indeed, there is a tension in discussions about minimally-invasive cardiovascular surgery between promoting the new and preserving the traditional. Even HeartPort’s approach preserves what Stanford surgeons argue is a critical feature of traditional bypass: working on a still heart. Says Mack, “The revolution isn’t necessarily in making a new operation, but in making the current operation more patient friendly.”

For product suppliers, the challenge is to provide technology that is both innovative and mainstream at the same time. Thus, notes CTS’ Kate Marshall, “The quality of the bypass is directly related to the surgeon’s ability to create the anastomosis. Our objective is to allow him to do that in a minimally-invasive fashion without changing how they do it now.” Adds St. Jude’s Terry Shepherd, “What a lot of companies are doing isn’t revolutionizing cardiovascular surgery, they’re simply making traditional surgery possible through minimally-invasive techniques.”

Developing New Tools

Indeed, St. Jude officials argue that MIS will introduce a new paradigm in cardiovascular surgery. “We’re going to see that we can get at the heart in a totally different way, using different protection and access methodologies from what has historically been the case,” Shepherd explains. “Instead of traumatizing the patient with a traditional median sternotomy, we’ll go in wherever we need to with minimal trauma.”

But the paradigm preserves as much as it changes. Shepherd acknowledges that, for now at least, what’s different about minimally-invasive valve replacement isn’t the valve, it’s the instrumentation. “At some point, we can envision new valve designs that will come from this new approach,” he says. “But right now, [the clinical investigators] are using the same gold standard valve they would with open replacements. And that goes back to the notion that you want to change as few things as possible in the early stages as the procedure is emerging and everyone is getting comfortable with it.”

And the importance of preserving established approaches means that while few of the companies looking to profit from this phenomenon doubt the potential of MIS in cardiovascular, many are having trouble getting a handle on what precisely the paradigm shift means for them and what new opportunities, if any, will emerge.

The analogy with MIS in GI is apt. Many industry executives note that like the trocars, insufflators, and clip appliers that made laparoscopic cholecystectomy possible, the widespread proliferation of minimally-invasive approaches in cardiovascular will, to a large degree, be driven by the availability of new technology, an in particular technology that standardizes the procedure, making it easier to do and thus more widespread, and with more predictable results, argues Lenox Hill’s VA Subermanian, who is on CTS’ scientific advisory board. “We want to make this procedure available to as many patients as possible,” he says. “With the right technology, we’ll see 90% of the patients having this done easily with good results. Without it, we’ll never get to that.”

Indeed, argues Subramanian, developing new tools is the “most important factor in realizing the potential of this procedure. This technique won’t be widely practical without the development of specialized technology.” Even established MIS suppliers recognize the need. Leon Hirsch, chairman of US Surgical Corp.,argues that minimally-invasive bypass is currently a limited opportunity because “right now the only ones who can do this are a handful of truly skilled surgeons,” he says. “For a broader application, we’re going to need a significant addition to the armamentarium. The products currently available aren’t adequate to allow the average surgeon to do minimally-invasive bypasses.” Hence, US Surgical is working on a host of new products, he says, not just updates or intensive marketing of its current line.

Some industry executives go on to argue that the development of new, innovative products for CV MIS will reshape other current technology. Says CTS’ Rich Ferrari, “This is a complete shift in the way revascularization is going to be performed in the future and its impact on future treatment strategies will be significant.”

Medtronic’s Glen Nelson agrees. As the instrumentation evolves, he notes, “the presence of certain kind of instruments may change product design and, in fact, engender new products.”

Medtronic executives even agree that putting patients on cardiopulmonary bypass can be problematic. “We’re probably more aware than anyone that it has traumatic effects,” Nelson goes on. “If you asked anyone here what they believe is the ideal approach [to surgery], the answer would be to avoid artificial bypass. And if we could find a means of doing that, we’d move to it in a minute.” Medtronic still believes cardiopulmonary bypass is the only way to do certain cardiovascular procedures. But Nelson continues, “If there’s a way of improving it, we’re not about to stand by and let someone else do that. We spend a significant amount of R&D dollars trying to minimize the trauma of bypass.”

The growth of minimally-invasive cardiovascular surgery underscores the problem that as procedures and technology change, some companies stand to lose as much as they gain. The issue can cause a kind of blind resistance. “Sometimes companies try to protect a franchise they have with an element of denial about change,” says Nelson. “I think successful companies recognize that when things are changing in a field where they’re providing products, they need to try to understand what’s happening and whether they need to adapt their product to meet the new demands.”

Sometimes the changes obsolete established technologies altogether, he says. Medtronic’s approach, he argues, is to look at each of these changes as an opportunity to diversify rather than a threat.”

Indeed, Nelson sees minimally-invasive techniques, broadly speaking, requiring a host of new technology platforms. “This is all part of a trend toward less invasive medical therapy and diagnosis,” he says. “It’s not limited to laparoscopy or cardiovascular, but runs the complete gamut” of medical applications. Medtronic’s own recent efforts in interventional neurology are, in many respects, part of the company’s response to the minimally-invasive phenomenon.

Do We Really Need Something New?

Still, he notes, not all of those opportunities will lend themselves to Medtronic’s strengths, and that will dictate Medtronic’s strategy. “I think our success in the past has come from the fact that we haven’t tried to reach too far. We try to build off technology platforms and customer contacts where we really understand the therapies we’re providing and can realistically assess where the market is going.”

US Surgical and Medtronic aren’t the only large suppliers looking at the opportunity in cardiovascular MIS; so are cardiovascular giants Boston Scientific Corp. and St. Jude, to name just two, while Johnson & Johnson executives are tracking the potential not through their cardiovascular business, JJ Interventional Systems, but through US Surgical’s chief rival in MIS, Ethicon Endo-Surgery. Says one JJIS executive, “We’re going to leave it to [Ethicon Endo-Surgery], though we’ll be there to help them if they need our help.”

Indeed, BSC is one of CTS’ investors, though CTS officials insist BSC’s role doesn’t entitle them to the technology, while Medtronic and US Surgical have funded much of the work of Acuff and Mack in Dallas. (HeartPort reportedly sought funding support from a number of large device companies, including Ethicon and Medtronic, but couldn’t come to terms.)

Given the early focus on surgical instrumentation to make access possible, it’s less clear what kind of opportunity MIS represents to cardiovascular companies. St. Jude officials acknowledge that while they’re interested in any advance in the treatment of valve disease, they’re not likely to use MIS as a springboard into the surgical instrumentation business. Medtronic executives agree. Says Nelson, “Whether a firm that provides therapeutic products needs to vertically integrate into instrumentation is open to question. I don’t think it’s mandatory.”

US Surgical’s Hirsch argues that the key to product development in CV MIS isn’t just to create access, as it was in laparoscopy, but to deal with issues such as perfusion and the ability to sew anastomosis that weren’t present in the first wave of MIS. “Coronary artery bypass is a lot more complex than gall bladder surgery,” he says. “And the things that make it more complex are the kinds of things, independent of the surgery itself, that you don’t find in gall bladder surgery. Trying to do an anastomosis on a beating heart is like trying to make love in a hammock.”

Lenox Hill’s VA Subramanian argues that better technology will help to standardize the procedure and make it widely available. He cites an analogy with open bypass surgery. “In the late 1960s and ’70s, there were people doing [open bypasses], but there weren’t a lot of them.” Open bypasses, he argues, “didn’t become widespread until the tools and techniques were developed that made it easier to do. Today, we do 485,000 bypasses every year, without it we’d probably do something like 10,000.”

Moreover, he argues, advances in technology will help move MIDCAB well beyond single vessel bypass. Such optimism notwithstanding, however, to date, the vast majority of MIDCABs have been done using technology that already exists in the market, and there are some who question whether new, specialized technology is really necessary. Says one industry executive, “I’ve looked at this very closely and asked surgeons and still can’t figure out what new devices or instrumentation surgeons want.”

Indeed, with HeartPort’s technology exclusively used at Stanford and CTS’s still a year away at least from the market, it is general surgical companies like Ethicon Endo-Surgery and, most notably, US Surgical who stand to benefit most from the early interest in cardiovascular MIS.

For now, many industry executives believe that small companies have an edge because of the need to be flexible in developing new technology in an emerging market. CTS officials argue that CV MIS is “not yet at the stage where big company resources are typically useful,” as Kate Marshall puts it. “The technical development that has to follow clinical developments are still very early, and that’s not a stage at which large companies are typically pioneers.” Adds Rich Ferrari, “We don’t believe big is better, we believe better is better. What’s critical is moving quickly, and in my experience, entrepreneurial companies have that advantage. The fastest way to get something done is through a start-up company that’s completely focused on an area and has invested all of their life blood in that area. That’s what we’ve done; we are the beating heart company.”

Terry Shepherd of St. Jude agrees. “Early in the adoption period, I think technology is going to win. The people that are there early, can execute quickly, can make course corrections early—because there are going to be a lot of course corrections as the methodologies evolve—those are going to be the winners in the short term. At this point in the game, I think there’s no reason to believe the small company won’t be the innovators and be highly successful.”

But, longer term, some industry executives question whether small companies can fully realize MIS’ potential opportunity. In laparoscopy, dozens of small companies, with the most innovative of new approaches, stumbled because US Surgical and Ethicon tied up distribution channels. These larger players may not have been the innovators themselves, often acquiring or licensing technology from small companies, but they created the market.

And there are those who argue that, particularly as the market matures and competitors flood the market, big companies have advantages over smaller players. “We’ve been in this business for years,” says Leon Hirsch, explaining why US Surgical is well-positioned to tap MIS’ potential in cardiovascular. “What to us is second nature is to other companies a new learning curve.”

US Surgical first began developing new instruments for cardiovascular around three years ago, says Hirsch, taking advantage of an extensive network of relationships with clinicians both in the US and abroad. (Last fall, US Surgical announced its first minimally-invasive bypass working with a team of surgeons in France.) “We have a very solid understanding of what surgeons need and the technical ability to deliver that,” says Hirsch.

Hirsch goes on to argue that small companies will find it difficult marshaling the resources necessary to tap the opportunity, including a breadth of in-house R&D and technical expertise, and extensive relationships in the medical community. “For a lot of reasons—research, testing, and particularly the regulatory process—you’re going to have to have extensive contacts among providers,” he says.

Control of distribution and marketing channels is also an issue, though in the short term, not as significant as it was in laparoscopy. US Surgical has been calling on vascular surgeons for over 10 years, mostly to sell their clip appliers. But, says Hirsch, it’s only been in the last couple of years that the company has had a wide range of products to sell to the cardiovascular market.

Hirsch argues that perhaps most important issue is training—again an area where big companies have an edge. (CTS officials claim they, too, have begun to create programs to train surgeons.) “We don’t want to have happen [in cardiovascular] what happened in gall bladder surgery where a lot of surgeons were doing this early who shouldn’t have been. That’s dangerous enough when it’s a gall bladder; it’s a catastrophic when you’re operating on the heart.”

Technology Creates a Market

Medtronic’s Glen Nelson notes another advantage large companies have: broad technology platforms that give them the ability to be flexible and adaptable simply because they are not invested completely in one technology. “You get an internal dialogue that offers different perspectives and approaches to the same condition,” he says. “Look at Medtronic, we provide multiple means of treating coronary disease. If it all goes to angioplasty, we’re in that business. If MIS becomes predominant, we’ll play on the surgical side. Our business is really to provide disease therapy rather than specific technology approaches.”

And that suggests the biggest advantage big companies have: the ability to invest great resources and simply wait out the development of the market. US Surgical executives know that opportunity in MIS will take some time to emerge. Still, says Leon Hirsch, “the risk/reward ratio is good. We’ve invested substantial resources in developing these instruments, but we think what we’ll get out of it is even more substantial.”

And as issues like marketing clout and critical mass become more important, CTS officials see the possibility of alliances with larger suppliers to give them skills small companies don’t typically possess. “We believe the key to gaining market share will be the ability to produce better products faster,” says Rich Ferrari. “At the same time, we are looking at strategic alliances in which we may join with another player to bring other products to the table so we can compete for large contracts.”

Whether small company technology or big company clout wins, the key to the opportunity for suppliers is to keep the procedure familiar. “You’ve got to make it familiar enough that you’re not asking surgeons to jettison every piece of training they’ve ever had and learn a whole new approach,” says St. Jude’s Terry Shepherd. “It’s important that you not tell them they have to re-invent the wheel.”

One of the difficulties of predicting MIS’ potential, particularly for bypass surgery, is the complexity of cardiovascular therapy. While gall bladder and hernia repair are fairly straightforward, the variety of options available to treat coronary artery disease—from angioplasty to open CABs, minimally-invasive CABs to new therapies now under development—make the adoption model slippery. Still, it’s hard to find anyone currently working in cardiovascular MIS who doesn’t think its potential is enormous. Not only are new cost and consumer pressures making the benefits of minimally-invasive surgery compelling, but cardiovascular surgeons themselves seem, say many industry observers, ready to embrace new ways of doing things. Says Dallas’ Tea Acuff, “Right now every surgeon is starting to ask, ‘What am I doing and why am I doing it?’ If you’d come in five years ago with a new technology, they’d have said, ‘Why do we need to?’ But right now, everyone is thinking about how they can change, and that makes the field very fertile now. Before, there wasn’t any place for the seeds to start.”

But there are two distinct schools of thought about the nature and timing of that potential. For the most enthusiastic, the combination of familiar techniques and the benefits of minimal-invasiveness will make the adoption curve steep. Thus, VA Subramanian talks of a new paradigm for cardiovascular surgery and argues that the only thing holding the field back is the availability of new technology.

And in important ways, the technological advances of small companies like CTS and HeartPort will significantly fuel the boom. Until someone comes along with an alternative technology, bypass on arrested heart is impossible without HeartPort’s endo-aortic clamp, while CTS’ system holds the promise of finally allowing surgery off cardiopulmonary bypass, a long-desired goal. Says CTS’ Kate Marshall, “This procedure is not going to become revolutionary until there are the tools that make it so easy that any surgeon can do it. That’s what CTS is all about—providing the tools and technology that will allow surgeons to do this procedure without having to develop surgical skills that are significantly different from those they already have.”

Comparing the opportunities in MIS in cardiovascular with those in an early generation of GI procedure, CTS’ Rich Ferrari notes, “We’re not trying to propose that the whole world is going to go to MIS thoracic surgery. However, the difference between [CV and GI] is that we started with procedures we know can be done but simply didn’t have the tools to make them available to a large group of surgeons. There’s no question that having this technology available will make this procedure widespread; that’s not the same as saying just because you could use one set of instruments to take out a gall bladder, you can also use them to repair hernias and do appendectomies.”

In valve replacement, in particular, where access may actually be easier when done minimally-invasively, Terry Shepherd says, “I would be surprised if by the year 2000, 75-80% of the patients who are candidates for this procedure weren’t getting it.” Indeed, he goes on, the question surgeons will face is, why not do it this way? “It saves time and money, with no side effects. I think in time we’ll get to the point where people will say, ‘Why didn’t we always do it this way?’ ”

The Hype Factor

Product suppliers have and will do much to create the buzz around MIS in CV. “We were quietly doing this procedure without much fanfare, until HeartPort issued a press release on this in mid-1995,” notes Baltimore’s James Fonger.

Still, others are sounding a note of caution. Dallas’ Michael Mack believes the potential of MIS is real, but, he argues, more as a long term play. “I think that there’s a lot of hype about it right now by the media and by people trying to make money off of the opportunity.”

That worries Mack who anticipates in the short term a backlash against minimally-invasive procedures as the reality fails to meet expectations. “A lot of people are going to be disappointed and it could stall the whole field,” he says.

Mack argues that MIS’ roll-out has to be “in a slow, orderly progression” because particularly in the early stage, the techniques involved will be difficult for many surgeons to master. He compares the roll-out of minimally-invasive bypasses to mitral valve repair, a technique that’s been around for 10 to 15 years, but has only been incorporated into the general cardiac surgeon’s armamentarium in the last five. “The technique [for valve repair] had to be developed,” he argues. “And I think we’ll see the same thing in [CV MIS]. This is a 10 to 15 year roll- out, not a six-month roll-out. There’s a lot about this technique that can be done fairly easily. But to go from a totally open microvascular anastomosis to a totally endoscopic microvascular anastomosis in one fell swoop, which is what some people are pushing, is just too much to ask.”

Moreover, many clinicians are waiting for hard data to confirm MIS’ safety and efficacy. Says James Fonger, “I think the focus of the early investigators has to be to convincingly demonstrate the performance of these bypass grafts one year after surgery to confirm that we have, in fact, the quality and results we assume we’re getting.” Indeed, Fonger is currently developing a real-time world-wide database on the Internet that will enable clinicians and other interested parties to track where minimally-invasive coronary artery bypass is being performed and the results surgeons are getting.

And MIS needs a broad experience base before it can be widely adopted. “We were groomed in an academic environment to do things in a logical progression, starting in the laboratory, experimenting with what works and what doesn’t, before taking it to the next clinically applicable stage,” says Thomas Burdon. Such an approach, he says, necessarily implies a learning curve where surgeons report every case to the scientific community; if a clinician isn’t doing that, what he’s doing is wrong and potentially unsafe to patients. “I’m not saying that the first cases we do aren’t with additional risk,” he says. “But we’ve done 10 cases so far; when we’ve done 100, I’ll be able to stand up and say either, ‘This is the way it will work,’ or ‘We should rethink this.’”

A Cautious Note

Finally, increased cost scrutiny is the flip side of the consumer/payer enthusiasm that so many MIS advocates think will do much to promote minimally-invasive cardiovascular surgery, and that, too, could limit the opportunity for product suppliers. Payers and providers, particularly those working in capitated or global payment environments, will see this new procedure as a way of eliminating costs such as longer inpatient stays, ICU days, and cardiopulmonary equipment. But they’ll resist widespread adoption if those cost advantages are lost in higher technology costs.

Despite concerns that the early hype will lead to potential backlash, clinicians like Mack and Fonger aren’t pessimistic about MIS. Indeed, they see tremendous opportunity, both for surgeons and for product companies. Tea Acuff argues that cardiovascular MIS is in an intermediary stage right now, and that the full flowering will come as the procedure addresses more complex procedures used to treat multi-vessel disease. Such procedures, he says, will only come with new technology, such as new support systems that will replace cardiopulmonary bypass—focusing perhaps on a fibrillating heart rather than an arrested or beating heart—as well as new devices that can stabilize the heart wall itself.

Acuff and Mack are even looking at new ways of doing surgery; the team has begun a project with a robotics motion laboratory which will attempt to pace robotic instruments to the heartbeat so that you can actually sew on a beating heart. Under such a system, a computer model would project an image of still instruments working on a still heart, while inside the chest, the robotics would track the instrumentation to the beating heart. “If this works, it could revolutionize surgery,” says Mack.

But they argue, such advanced procedures increase the complexity of the operation and the technical skill required of surgeons. More to the point, says Acuff, surgeons used to open procedures may be frustrated by MIS, which entails “taking something simple and making it very difficult. And the benefits aren’t going to be that obvious to begin with.” The analogy with MIS in the early days of laparoscopic cholecystectomy may be apt. Following the rapid penetration of laparoscopic cholecystectomy, the next generation of procedures proved elusive—they were harder to do, surgeon resistance intensified, and the benefits, particularly to providers, were less clear. Indeed, in retrospect, cholecystectomy proved not the beginning of a broader trend, but almost uniquely appropriate for the new minimally-invasive techniques.

For product suppliers, the disappointment translated into a market almost harshly unforgiving. Dozens of small companies, and even large ones, scrambled to offer what they believed were innovative products only to find customer appetite for innovation sated and the distribution channels locked up by larger players.

Clearly CTS and HeartPort believe their technology will allow them to succeed where the dozens of small companies marketing a new line of trocars failed. Still, there’s the risk that the opportunities in cardiovascular MIS may prove disappointing to product suppliers unless surgeons are willing to embrace, and payers to pay for, new technology that differs from the MIS technology developed for laparoscopic cholecystectomy.

Perhaps the best analogy with the first generation of MIS isn’t with cholecystectomy, but with a procedure like nissen fundoplications—where the availability of new technology did make a difference, but the complexity of the procedure and the learning curve necessary created a smaller market in the near term. Says Leon Hirsch, “I think the potential is real, but not certain. We’ll only be successful in this if we’re able to develop the instrumentation that surgeons really need to do this. This will not be a huge market with the current instruments.”

And that means, in turn, that product companies will have to deliver on the promises they’re making about their technology. Says Leon Hirsch, “The opportunity here is totally dependent on our ability to give surgeons what they really need” to do the more advanced procedures. Says one industry observer, “If you listen to what [the HeartPort executives] are telling investors and what their doctors are telling medical meetings, they’re miles apart in what they can actually deliver.”

Expecting Too Much

For now and the foreseeable future at least, it is hard to tell which product companies, if any, are benefitting from an adoption curve for minimally-invasive coronary artery bypass that is growing more rapid with each passing month.

Will cardiovascular’s minimally-invasive revolution be doubly qualified for product suppliers, opening new markets, but with limited opportunities for precisely the kind of technological innovation that has historically come from small companies? Cautioning against the kind of hype that took over the first wave of MIS, Baltimore’s James Fonger notes, “We’re doing this surgery on a daily basis with no additional hardware. I think the excitement about the procedure is real, but currently it’s about the procedure, not about the devices. The procedure without the devices works very well. Will the devices be able to make it faster or simpler for less technically-oriented surgeons? That remains to be seen. But I can tell you that the surgery is being safely and effectively done without any additional devices at this point in time.”

Indeed, despite the sense among both surgeons and suppliers that the hype surrounding cardiovascular MIS may actually be justified, even the most committed advocates of MIS’ potential in this area argue for a cautious approach by product companies—at least in the short term. “Right now, there isn’t a whole lot of surgical instrumentation needed to do the procedures we’re doing,” says Dallas’ Michael Mack. “You can take the same needle holders and forceps that we use in the open situation and make them longer and put different angles on them, but that’s going to be the limit of it right now. I don’t think there’s a lot of other things you can do. I can’t see building a $500 million company around this opportunity.”

For small companies and large as well, perhaps the caution is against expecting too much. Adds Stanford’s Thomas Burdon, “If companies are smart, they’ll sit back and watch what happens in assessing where the product [opportunities] are. I’m no businessman, but if I were sitting in a product company, my approach would be to let clinicians do another 100 cases, report on them and see what happens. I know that’s not the way the world works. No one wants to be left behind, so there’s tremendous pressure to get on the bandwagon. But I’d approach this in a conservative fashion.”

Angioplasty and the MIS Threat

Even in its early stages of adoption, it’s clear that MIS will change the way traditional cardiovascular surgery is done. What is less clear is the degree to which it will change coronary artery treatment more broadly by cannibalizing other, catheter-based procedures that address the problem of occluded arteries, especially angioplasty and to a lesser degree, stents.

Those who see MIS reducing the number of angioplasties argue that both angioplasty and minimally-invasive bypass target the same patient population—those with relatively simple, single vessel disease. Traditional open bypass surgery is actually indicated for cases that most surgeons would today deem inappropriate for a minimally-invasive approach.

Moreover, both minimally-invasive bypass and angioplasty rest on the same appeal to patients and payers: their non-invasive nature. Says one industry executive, “The angioplasty companies have the most to lose if MIS takes off. Today, if you want a less invasive approach, angioplasty is your first choice. But if minimally-invasive bypasses allows you to do the procedure less invasively and guarantees far better results in terms of patency, without restenosis rates of 30%, a fair number of people will choose not to do angioplasties.”

Talk of MIS replacing angioplasty bothers some surgeons, in part because they think it diverts attention from the real clinical goal. Says Baltimore’s James Fonger, “I don’t think we [i.e., the early adopters] want to send a message that one is going to replace the other. We’re trying to develop a safe procedure that makes a contribution toward treating coronary artery disease with the focus on demonstrating that the quality of the results we achieve is equal to conventional coronary surgery.” And many observers think MIS will be used as a secondary therapy for single vessel disease—i.e., for patients for whom angioplasty has been tried and not worked—rather than routinely as a primary therapy.

Still, the advent of MIS resurrects the historic rivalry between interventional cardiology and cardiac surgeons. For product companies, the battle lines are drawn not just between two different technologies and two different customers, but also between two different attitudes about technology. Many industry executives note that interventional cardiologists have been much more receptive to technological innovation than surgeons.

Perhaps that’s why the market for interventional cardiology products has historically been hotter than that for cardiac surgical instruments. But because of the competition between surgeons and interventional cardiologists, some industry executives believe the advent of MIS will spur cardiac surgeons to redress the balance as they look to take back patients lost to angioplasty.

For now, some product company executives are hoping that the turf battles can be resolved through a more rational approach to care. Says St. Jude’s Terry Shepherd, “In the future, I think we’ll see people coming to the table and rather than fighting about whose patient it is, will begin to acknowledge that there are some patients best treated by angioplasty and some by surgery.” Officials at CTS, who stand to benefit if MIS takes off, actually agree. “We don’t see this as a turf issue,” says Kate Marshall, who started her career at angioplasty leader ACS. “What’s driving health care today is finding the optimal care for the least amount of cost. A patient with LAD disease may be better off having his procedure done minimally-invasively but that’s not to say all patients would be.”

As CTS sees it, MIDCABs represent another option in the armamentarium of surgeons and interventional cardiologists, not a necessary replacement for either traditional open bypasses or angioplasty. Gone will be the days when ICs and CV surgeons “argue over patients,” says Marshall. “Both interventionists and surgeons are being forced to look at how they can deliver quality care at the lowest cost,” particularly if they’re under some kind of capitated program, she goes on. “Successful hospitals aren’t going to be arguing over small patient bases. We know that turf battle happens now, but it’s an expensive battle.”

Still, particularly in the short term, such turf battles may be unavoidable and the implications for product companies could be great. Says one advocate of minimally-invasive bypasses, “All I know is if I were the president of a stent company, I’d be looking at alternative ways my company should be going down the road because this technology [i.e., minimally-invasive bypass] is extremely exciting.”