BB&T

MUNICH, Germany — The noise and confusion from the bells and whistles being added to cardiology imaging are driving growth and greater revenues for manufacturers, but far more importantly, the steady stream of upgrades and new features is bringing breakthroughs in medical practice. Scientific sessions featuring abstracts and research papers using high-tech modalities for imaging the human heart have grown to more than 20% of the total 363 scientific sessions over the four days of the European Society of Cardiology's (ESC; Sophia Antipolis, France) annual congress here early last month.

It is a full-scale revolution in clinical practice, accelerating at a breakneck speed that is slowed only by the strict discipline of evidence-based practice. To put it another way, cardiologists simply have never seen such depth and detail on every component of the beating heart and pumping coronary arteries, simultaneously viewing anatomy, function and perfusion.

More startling, these vivid images are not abstract research but right-now 4-D pictures from inside the chest of the living and breathing and suffering patient lying on the examination table.

The profusion of panel discussions at the congress was a precursor to the necessary steps toward setting what will someday be guidelines for integrating imaging into clinical practice. Yet even as cardiologists struggle to focus on the known modalities and their applications, the horizon continues to expand further and further out.

To infinity and beyond!

At ESC, the cutting edge of integrating imaging and intervention technologies was presented in a session showing how magnetic navigation systems (MNS), already established in electrophysiology, are now being extended to other applications in cardiology, including percutaneous interventions and the delivery of stem cells.

In MNS, two large magnets positioned at either side of a patient create fields capable of generating sufficient force to steer magnetically tipped interventional devices through the vasculature while real-time fluoroscopy displays a road map on a display allowing the surgeon to guide the device from a remote room to controlled catheter ablation.

Professor Luc Jordaens from Rotterdam, the Netherlands, told cardiologists that MNS allows for extremely precise catheter movements, decreased procedure time and the opportunity to couple catheters with 3-D imaging. The approach also decreases the number of catheters needed, results in fewer complications at puncture sites, and reduces fluoroscopic exposure for both patients and physicians. Potential applications for the MNS platform beyond ablation include positioning pacing wires and replacing valves.

"One of the real advantages is that MNS catheters are like floppy spaghetti, so there's virtually no risk of perforation," Jordaens said.

Sabine Ernst of the Royal Brompton and Harefield Hospital (London) said, "Ultimately, the remoteness of the technique is likely to increase. If you can do the procedure from the next room, there's absolutely no reason why you couldn't perform it from another city, or even another planet."

Frank Rademakers, MD, of University Hospitals (Leuven, Belgium), in a session titled "Imaging: The Focus of Clinical Cardiology for Years to Come," told cardiologists: "It is time to start focusing again, not on what we can image, but on what we need to image to improve patient diagnosis and outcome." New techniques are welcome and dearly needed in many areas, he said, "but we have to create evidence showing an incremental value above existing techniques before including them in everyday practice."

Rademakers said cardiologists need to recognize a new subspecialty, the "cardiovascular imager," to integrate the waves of information coming from various techniques into a consistent answer to the clinicians. "This requires broad consensus-building among the different modalities and specialties and much more research into the area, but it is necessary to translate today's expanding imaging capabilities into a benefit for the cardiovascular patient," he said.

Meanwhile the drumbeat from industry continued during the ESC congress, with more announcements of even newer capabilities.

Full volume 'echo in a heartbeat' from Siemens

Another new product from Siemens (Erlangen, Germany) shown on the ESC exhibit floor was the Acuson SC2000, the world's first echocardiography system to acquire instantaneous, non-stitched full-volume images of the heart in a single heartbeat.

A significant achievement, a bold statement and a marketing claim with a short life expectancy.

Promoted as "Echo in a Heartbeat," the Acuson SC2000 is a full-volume imaging ultrasound system acquiring non-stitched, real-time, full-volume 3-D images. Siemens was clearly proud of getting to market first with this capability, comparing it to the landmark moment in 1953 when echocardiography pioneers Inge Edler and Hellmuth Hertz acquired the world's first cardiac ultrasound recording using Siemens technology.

Aquiring the heart in 90-degree pyramids in one second, every second dramatically reduces acquisition time, thereby improving workflow in the echocardiography suite. In other words, higher patient throughput, which translates into reduced waiting lists for patients and higher revenues for clinics.

Siemens' patented Coherent Volume Formation technology uses simultaneous, multiple beam acquisition on the Acuson SC2000 rather than the current standard for serial line-by-line acquisition.

This paradigm shift, coupled with the jacked-up Siemens 4Z1c transducer, which runs at over-the-limit power output thanks to a cooling technology that keeps it inside the regulatory limits, gives improved penetration, reduced noise and high-volume acquisition rates when compared to conventional 3-D transducers.

This muscular combination also can juggle volume imaging, 2-D, M-mode, color Doppler and spectral Doppler modalities. This new high-end system for cardiological examinations will "very likely" be available in Europe this fall, the company said.

Siemens also was showing a work-in-progress called IQ-SPECT with a SMARTzoom, a collimator engineered to magnify the heart while imaging the rest of the torso in the usual manner. With SPECT, the patient radiates the machine and not the other way around, as with computer tomography (CT).

Injected with a radioactive formulation, the function of the patient's organs become visible to the gamma detectors that render the radiation into a light image for humans to view. The resulting images, sliced in the same way as CT images, can shows a cardiologist where tissue is viable and where it is not, as in the case of muscles that are no longer working.

The high-resolution images of the IQ-Spect sharply indicate the vivid activity of active muscle tissue and the somber zones of dead tissue.

Indicating dead tissue can be extremely useful for a cardiologist, who may decide to forego the bypass of a vessel as there is no point pumping fresh blood to muscles that won't accept it.

Cardiac SPECT data is currently obtained with gantries positioning the detectors at 90 degrees to the body which then rotate centered mechanically on the middle of the table as the patient tries to lay perfectly still. With IQ-SPECT, Siemens re-engineered the mechanics of the Symbia S and T gantries allow an organ centric detector rotation where the detectors shift off the fixed centerline to focus on a specific organ. The heart, for example, is on the left side of the chest cavity and not in the center.

Putting the heart at the center of the oribtal axis of the gamma detectors focus makes the capture of radiation from the patient's heart more efficient, thereby "magnifying" it, while reducing truncations and artifacts. The efficiency of the IQ-SPECT also makes it faster. Engineers at the Siemens booth told BB&T the acquisition is almost four times quicker, reducing from 15 minutes to four minutes the time a patient needs to lie as perfectly still as possible.

Faster acquisition is good for everyone. Patients do not have to lie unnaturally rigid for a prolonged period and the radiology center is able to put through a greater number of patients.

Designed as an upgrade feature for the Siemens Symbia series, IQ-SPECT is field-upgradeable for the T-model that is a dual-modality unit with SPECT detectors and a CT, or the S-series that is a stand-alone SPECT unit. Siemens engineers said there are "several hundred Symbia systems installed around the world."

Handheld ultrasound replacing stethoscopes

Cardiologists are users and not direct customers for the big medical imaging companies who sell almost exclusively to radiology departments.

The large exhibitions set up at the 2008 ESC congress to demonstrate new diagnostic or guidance products are meant to influence opinions in the hope that once back at the hospital, the cardiologists will express a preference to radiology procurement and ultimately drive a big-ticket sale.

On the stand of one of the major vendors, a sales manager said he was forbidden by company policy to make a sale at the show.

Yet like other boundaries and traditions in cardiology, that wall is starting to crumble as the three major players in European imaging GE Healthcare (Waukesha, Wisconsin), Philips Healthcare (Andover, Massachusetts) and Siemens (Erlangen, Germany), in order of market share begin to target cardiologists' private practices, the offices of their referring physicians, and especially mobile cardiac response teams with light-weight and increasingly powerful ultrasound units.

Handheld echocardiography is becoming the stethoscope in doctors' everyday work, according to Professor Juhani Knuuti of the PET Centre in Turku, Finland, in comments during the ESC Congress session dedicated to "New Horizons in Imaging."

"We now see doctors in wards or during outpatient visits take out a pocket-sized echocardiography machine and check whether valves are OK or see if the patient's heart has sufficient pumping power," he said.

GE started the trend in 2005 with the introduction of the Vivid i, a laptop-sized cardiovascular ultrasound system aimed at urgent care, emergency room, critical care, and operating rooms.

Successfully tapping an unmet need in medical practice, sales of the Vivid i tore away market share from competitors, catapulting GE by 2006 to the lead position for ultrasound worldwide.

GE enjoyed the first-to-market advantages until 2007, when Siemens introduced the Acuson P-10, a pocket-sized model that pushed the portability challenge just as Blackberries took away many everyday tasks from the laptop computer.

With a flip-up monitor and thumb controls, the P10 brought basic ultrasound further out of the hospital and successfully created a personal data assistant feel for cardiologists, as well as ob/gyns.

Philips was the laggard in this fast-developing market, but finally arrived here at ESC 2008 with its CompactXtreme technology and the CX50.

Joris van den Huck, vice president for cardiology programs at Philips, told BB&T, "Yes, the CX-50 answers the P-10 from Siemens last year, but we have gone further."

CompactXtreme is promoted as a tool for "timely triage," to enable the early recognition of heart disease and to reduce door-to-balloon time in an urgent-care setting.

"There is also a lot that can be done in transit," he said, "specifically [in] transmitting to the hospital echo readings of a patient en route so that the care pathway is established before he even arrives."

van den Huck said, "Triage is not something you only do for urgent care," adding that Philips interprets the early detection of heart disease as a kind of triage of patients.

"You want to do this as close as possible to the patient in the primary care settings, such as GP offices," he said. "This requires giving the GP the means to visualize heart disease, to measure it, and then to determine the significance of these readings."

"It is a huge market," van den Huck said, adding that while he can not give a dollar figure, there are 1,000 hospitals in the U.S. out of a possible 1,800 which have agreed to clinical guidelines for managing patients with heart disease and that there are 5 million chest pain cases annually in the U.S. alone.

"In Europe, where there is a different measure called acute coronary syndrome, there are 1 million prospective patients each year for this modality," he told BB&T.

The CX50 offers enhanced clarity and edge definition, thanks to Philips' PureWave piezoelectric transducer and XRES adaptive image processing for reduced speckle and haze.

With wireless transmission of DICOM-compatible data and a laptop-like look and feel, the CX50 is nonetheless the bulkiest unit in the portable ultrasound market, weighing in at 13 pounds.

As these competitors bring new offerings to the market that move further out from the hospital, GE meanwhile is taking the Vivid i deeper into cardiology with a new offering for interventionalists.

At ESC 2008, GE extended the applications of Vivid i with a bolt-on capability for intra-cardiac echocardiography (ICE) that provides ultrasound images from inside the heart to assist in percutaneous valve replacement or guiding trans-septal punctures.

"We are making a new entry into interventional echo with ICE imaging," said Omar Ishrak, CEO of clinical systems for GE, adding that the ICE catheter is also compatible with the new Vivid q model showcased at ESC.

GE built the adapter and interface for the existing ICE catheter and probe from Biosense Webster (Waterloo, Belgium) that combines with the Vivid i portability, enabling it to join the growing suite of imaging modalities in the cath lab or the new Hybrid ORs that combine a cath lab with a traditional surgical arena.

Another trend driving growth in the ultrasound market for cardiology is the 3-D imaging capability.

Adding the dimension of depth and space renders the often strange views of 2-D ultrasound into a very intuitive display of a patient's anatomy familiar not only to physicians but any caregiver with any kind of diploma in medical studies.

With real-time processing capabilities, these 3-D machines are actually four-dimensional, showing a beating heart and acquiring fresh views of blood flow, valve performance and ejection fractions with every new heartbeat.

4-D is the new buzz on the exhibition floor, with vendors boasting full-volume, single-image acquisition against stitched image processing from scattershot acquisition and real-time "in a heartbeat" acquisition of images against delayed processed images.

Heinrick Beckermann, cardiology marketing manager for Philips, told BB&T, "The 3-D market is growing and is important for cardiology development because people can now see the images they understand right away, identify what is happening and can take a decision."

He said that growth in cardiology ultrasound is twice the global rate of growth for all ultrasound, which he put at "inflation plus a point," and that 3-D sales are running far ahead of any other application in cardiology.

Beckermann estimated the worldwide market for ultrasound transducers, including every application from veterinarians to hospitals, at $3 billion.

Philips may have been slow getting to market with the CX50, but it is years ahead of competitors with a unique offering for trans-esophageal echocardiography (TEE), according to van den Huck, who added that "TEE is selling like hotcakes."

Beckermann said because the TEE is unique to Philips, once a customer sees the images of the beating heart and wants that, "we win the deal every time. In this first year we have had 800 installations, counting both new units and installations within existing customers systems."

He said Philips "can be very happy with its position in ultrasound. GE is still the leader in Europe, but we used to be No. 3 and last year we moved up to second position."

He added that Siemens is still quite close to Philips, but expressed the opinion that Philips "is in trouble in imaging. They did not do some things right."

GE enjoys a better position, he said, "but they really need to replace products that are getting old."

Growth of minimally invasive and so-called "keyhole" surgeries is going to continue driving growth in ultrasound, Beckermann said. "When you open a patient up with a knife, you see what is happening, but when it is minimally invasive, then you must have image guidance for that surgery, and a portable ultrasound unit is the only way to see it quickly and precisely."

Philips, GE get in the swing

As part of the imaging revolution on display in the exhibit hall at the ESC congress, Philips was showing the result of a Franco-America collaboration to update and enhance old-fashioned angiography.

ESC 2008 was the first showing for the XperSwing, featuring a dual-axis C-arm that operates on two axes simultaneously, creating a 3-D arc around the patient, or "swinging," as the marketing engineers prefer. This flexibility in movement enables coronary image acquisition in fewer runs in contrast to the non-swingers that move either from side-to-side or up-and-down but not in both directions simultaneously.

Non-swingers are a bit stiff, as well. The C-arms on conventional angiography units need to be positioned before each image, not unlike framing a photograph before snapping the shutter, such that obtaining the required images take a higher number of static snapshots. The Philips XperSwing is fully automated

The benefit to patients of this enhanced technology is reduced exposure to X-rays and reduced contrast medium dosages, according to an initial study evaluating26 patients randomized to either XperSwing or conventional non-rotational angiography.

XperSwing patients required 18% less contrast agent dosage and were exposed to half the radiation dose, though for all the automation and swinging there was no significant difference in procedure time between the two approaches.

A broader clinical evaluation of XperSwing is underway at four medical centers in Europe.

Philips developed XperSwing in collaboration with John Carroll, MD, head of cardiology at the University of Colorado, Denver, and Philippe Guyon, MD, an interventional cardiologist at the Centre Cardiologique du Nord in France.

XperSwing is scheduled for commercial release in spring 2009 and Philips said it plans to incorporate its XperSwing functionality future releases of its FD systems.

GE Healthcare demonstrated the Vivid e9 ultrasound system that it said is the first system designed by GE from the ground up specifically for 4-D imaging that acquires a full view of the heart, literally in a heartbeat. Using what it terms "accelerated volume architecture" (AVA) that falls shy of full-volume acquisition, GE says the image processing is ungated and unspliced. The re-engineered matrix array transducer combined with a single crystal design also produces greatly enhanced 2-D echography images.

Omar Ishrak, CEO of clinical systems, said, "We expect the e9 to revolutionize the field of echo by making 4-D imaging easy, providing not only 4-D images of the heart but also providing new user tools like Easy 4D and Scanassist one-touch controls to assist the user by streamlining the 4-D exam."

Simon Robson, a UK product manager, said that "Moore's law has indeed arrived" at GE with the introduction of the Vivid e9. He said image processing speeds are four times greater than speeds found on the existing Vivid e7. "This is the equivalent of what we have all seen with laptop computers where the new generation of ultralights is faster, better and more portable with less weight and a smaller size."

GE also is "raising the bar for compact ultrasound" in introducing the Vivid q, according to Ishrak. The M4S matrix probe technology of the Vivid 7 unit with electronic beam focusing in three dimensions was migrated to this newer lightweight model.

The automated function imaging feature of the Vivid 7 also was moved to the Vivid q to enhance decision support giving a high level of processing of acquired image data to boost diagnostic decision-making.

'Damage control' for supporters of DES

It was supposed to be a stunning victory for drug-eluting stents (DES). Instead, the release of the SYNTAX study during the ESC congress left some 24,000 participating cardiologists scratching their heads over the conclusions and sent the supporters of DES scrambling for damage control.

In the wake of the devastating reports in 2006 that DES was not superior to surgery, and perhaps even dangerous, interventionalists said they would meet criticisms head-on with SYNTAX, which stands for Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery.

Taxus is a global leader among drug-eluting stents and the manufacturer, Boston Scientific (Natick, Massachusetts) sponsored the SYNTAX trial.

Unfortunately for Boston Sci, SYNTAX concludes that the primary end-point of DES being non-inferior to coronary artery bypass graft (CABG) was not met.

In fairness, the study designers set the bar very high for DES, intending to deliver overwhelming evidence in favor of DES. The medical community agreed the final measure would be the rate of major adverse cardiac events (MACE) caused by percutaneous intervention (PCI) using DES during the 12 months following the procedure.

To meet the endpoint, PCI MACE needed to be not more than 5.5 percentage points greater than the rate of these adverse events experienced by CABG patients. DES missed the mark by a mile against surgery (see related story).

Lead investigator Patrick Serruys, MD, of Erasmus University Medical Center (Rotterdam, the Netherlands), said he was "totally surprised" by the quality of surgeries, a comment echoed in a press conference by fellow DES supporters who said surgical techniques, such as off-pump procedures and perioperative care, had improved in recent years.

In clinical trials, MACE includes the number of patients who die and the number who experience a cerebrovascular accident (CVA) or a myocardial infarction (MI).

To close the door on criticisms of DES, the investigators in the SYNTAX study included in the MACE measure the number of times a patient had to return to the cardiologist for a repeat procedure called revascularization because the first intervention did not relieve the conditions.

This turned out to be the undoing of the DES supporters who had hoped SYNTAX would end the debate over the viability of DES procedures and create the opportunity to tell cardiologists that PCI is as good as surgery for their patients. It was a tough break for DES defenders, as all other results except revascularization in the trial were quite good against CABG.

This means that DES is not dangerous for patients and, in fact, that it is indeed a viable alternative for cardiologists to recommend to their patients compared to CABG, which one cardiologist described as "a voluntary submission to willful bodily harm."

Not unexpectedly, Boston Scientific put a positive spin on the study findings. "For PCI patients to do so well with such complex anatomy and advanced disease is extraordinary," said Keith Dawkins, MD, associate chief medical officer of Boston Scientific, said in a company statement. "These patients, the majority of whom are normally treated with surgery, are the most challenging group ever studied in a DES clinical trial." He also cited the SYNTAX trial's findings demonstrating a significant decrease in the rate of stroke for patients treated with PCI as compared to CABG.

"The significant difference in the stroke rate between the PCI and the CABG groups is an important finding," said Dawkins. "Physicians and their patients will now have the necessary information to weigh the risk of stroke associated with CABG versus the known higher rate of revascularization with PCI. We were also surprised to find that the rate of symptomatic graft occlusion in the CABG group was equivalent to the rate of stent thrombosis in the PCI group."

With more than 3,000 participants at the ESC Congress watching in the lecture hall and overflowing to the theater outside, where the presentation was broadcast, Christian Hamm from the Kerchhoff Heart Center (Bad Nauheim, Germany) took the stage to deliver the "Cardiologists' Perspective" of the findings. "The conclusions of the study are difficult to understand, but the bottom line is that PCI failed to be shown as non-inferior," he said. "CABG is shown to be better and the hard end-point of reintervention is the issue."

Noting that cardiologists serve as the gatekeepers for patients entering the surgical arena, he shared suggestions for the take-home messages for fellow physicians so that they could describe these two options to patients. The positive points for PCI are less chance of stroke, a shorter hospitalization and good-to-excellent repair of the damaged vessels.

For surgery there is less chance of returning for a second procedure and a more complete revascularization. Hamm noted that the results showed the incidence of thrombosis in stent patients, one of the sharp criticisms of DES in 2006 that shocked regulatory agencies are identical to the incidence of symptomatic graft occlusion occurring in CABG.

In the real world of discussing options with patients, however, he said the less-invasive nature of PCI is very attractive, with patients typically preferring to opt for the stent and risk the possibility of revascularization. "None of our patients is going to say that if PCI is an option they want to do surgery first and then try the stent if that does not work," he said.

The SYNTAX study clearly shows that revascularization is the single issue limiting DES, he said. "Tell patients about their choices and say that if they want to see you again, choose PCI," Hamm said.

The impact of the criticisms of DES starting at the EuroPCR congress for interventionalists in Barcelona in 2006, and the subsequent release of the Swedish SCAAR study, was a sudden drop in DES usage.

European usage dipped slightly, staying between 40% to 50% of PCI procedures, but sales of DES in the U.S. plummeted from over 90% usage in early 2006 to around 55% before the end of that year, where it has plateaued today, according to figures presented in a separate session here at the congress titled "Two Years After Barcelona."

Clinical trials come and go in prominence, but the results of the SYNTAX study are here to stay, likely with a significant lasting effect.

Not only did the cardiology community set the bar high with the MACE endpoint, they also agreed the study results would create a SYNTAX Score for the stratification of patients facing a revascularization. In other words, once a patient returns to a cardiologist after a procedure complaining of recurring symptoms, or is hospitalized, the options for the subsequent surgery will be guided by the SYNTAX scoring.

The study team concluded that CABG remains the only treatment option for one-third of these patients.

Demand for better data, tighter standards

The controversy over the use of drug-eluting stents for treating coronary disease could be heard throughout the sessions, seminars, press conferences and even hallway discussions at the congress. Without clear practice guidelines, cardiologists are left to choose among competing views and conflicting study results to find guidance for patients choosing how to have blocked arteries reopened.

Adding to the confusion were further clinical trials and sessions that aimed to address the issues head on but just as often left participants as uncertain coming out as they were going into the debate.

In a session dubbed "Safety of drug-eluting stents two years after Barcelona," Carlo DiMario, MD, from the Royal Brompton Hospital (London), said the positive side of the debate over DES since their usage was challenged at the ESC meeting in 2006 is that existing randomized trials and registries have been intensely scrutinized and plans have been made for more adequately powered trials with results applicable to the majority of patients treated for coronary artery disease and not just the high-risk, off-label uses that set off the concerns.

Another benefit has been the sharp fall in DES prices, which has forced a reappraisal of cost-effectiveness analyses such as was recently seen in England with new guidelines from the influential National Institute for Health and Clinical Excellence.

But like all presenters, DiMario was forced to inconclusively wrap up, saying that "more data is needed from dedicated trials addressing the long-term safety and efficacy of DES in high-risk subgroups like diabetics, and patients with stent thrombosis (ST) and non-ST segment elevation, myocardial infarctions or complex lesions."

The demand for solid data, and not more randomized trials, was emphatically put to journalists during a press conference on "Coronary stents: Safety and Long-term Results," by Jean Marco, director of the annual Paris Course on Revascularization (EuroPCR) meeting and founder of the interventional cardiology unit at the Clinique Pasteur (Toulouse, France). "We need 30,000 patients measured for not less than 12 parameters before we will have the evidence we need for practice guidelines," he said.

William Wijns, MD, president of the European Association for Percutaneous Cardiovascular Interventions (EAPCI), the sponsor of EuroPCR, said, "The question is when will we be ready such a trial. It will be years before we will have such results, many years." Wijns took up one side of a debate at the ESC congress titled "Drug-eluting Stents and Diabetes: Pros and Cons," arguing what he called an extreme position that DES should not be used at all for diabetic patients.

Both he and his opponent in the debate, Sigmund Silber, MD, of Mueller Hospital (Munich), started out agreeing, again, that there was insufficient data to even be debating the issue of DES for diabetics.

Wijns added, "It is naive, and even arrogant, to think that with a piece of metal, coated with a drug or not, that we are going to change this complex coronary condition. By the time a diabetic patient hits the cath lab, he already has a 20-year history with this condition."

A special ESC forum on DES, held at the organization's European Heart House in Sophia Antipolis in late-September 2007, reviewed data on long-term efficacy and safety with the goal of identifying specific indications, to specify guidelines for current and possible future trial design, and significantly, to review the DES registration process in Europe.

The conclusions of the forum are to be published in an upcoming edition of the European Heart Journal, although Wijn, who is the lead author, declined to specify when the text would finally be approved for the meeting held almost one year ago.

In his comments, DiMario hinted at some of the findings of the task force set up during the ESC forum. He said ESC will ask for randomized controlled trials that have fewer inclusion and eclusion criteria, the so-called "all-comers" trials similar to the just-released SYNTAX trial.

DiMario said cardiologists will ask that these studies provide data on hard end-points, such as death, cerebrovascular accident and myocardial infarction (MI), between three and five years, and also similar to SYNTAX, and that randomized trials be followed by large-scale all-comers registries.

He also reported that ESC will promote unified criteria for assessment of DES to be defined by European Commission for the Competent Authorities of the Member States and the Notified Bodies who issue the CE mark allowing products to be sold and distributed in Europe.

DiMario said future initial market approvals of DES in Europe might be based on assessment of restenosis from angiography or intraveneous ultrasound, or neointimal formation and stent coverage using optical coherence tomography or endothelial function studies.

Similar to the guidelines for clinical trials, ESC would recommend to the regulatory authorities that these assessments of products for initial market approvals include one-year clinical follow up and that data should be followed by the assessment of death, MI and stent thrombosis over longer follow-up periods, extending out to five years.

Diabetes remains a divisive DES issue

If a diabetic patient does not mind the high likelihood of going back on the table for a repeat percutaneous intervention (PCI), then a drug-eluting stent (DES) is, "if not a good alternative, then at least OK."

This conclusion to a debate focused on PCI for diabetic patients, delivered by Marko Noc, MD, an interventional cardiologist at the University Medical Center Ljubljana in Slovenia, was half-hearted and inconclusive, but typical of all discussion centered on DES during the ESC congress.

It also is the state-of-the-art guidance for cardiologists treating diabetics, despite industry promotions to the contrary, and it will be many years before there is sufficient data to say otherwise, according to speakers taking positions on both sides of the highly controversial use of DES to treat coronary complications for diabetics. Diabetes in Europe, as elsewhere in the world, is approaching epidemic proportions, with an estimated 4% of the European population affected, or roughly 10 million diabetics.

That represents, potentially, a lot of stents to be sold as 100% of Europe's diabetic population is destined to sooner or later undergo some form of cardiovascular intervention. During the debate, independent of industry sponsorship, the consensus was that it is impossible to form a consensus.

Both William Wijns, MD, president of the European Association for Percutaneous Cardiovascular Interventions (EAPCI), who took up the position against DES, and Sigmund Silber, MD, from Mueller Hospital (Munich), who in his effort to defend DES found himself constrained to a "balanced viewpoint," ended up agreeing that there is no study and no evidence with a clear endpoint that allows for any evidence-based practice guideline.

Yet there seemed to be no end of clinical trials testing DES with diabetics.

At its booth on the exhibit floor, Boston Scientific promoted a special logo claiming CE-mark approval for diabetes for the Taxus Liberté stent. The CE mark is strictly an approval of safety for an implantable medical device, and unlike FDA approval in the United States, there is not a requirement to demonstrate efficacy. While strictly correct, according to a European expert on regulatory affairs, the promotion by Boston Scientific is an aggressive extrapolation of CE-mark approval for a suggested use included in the product design documentation that was submitted by the company.

"No, it is not mandatory," explained a Boston Scientific spokesman at the booth, "it is an update to the instructions for use, which is normal. What Dr. Wijns is saying is right, and we do not disagree" he said. "We do not have a diabetic study that is dedicated and sufficiently powered with a clinical endpoint comparing the technologies. But what we are saying is that there are multiple trials in which the diabetic cohort is sufficient and as such gives what we believe is sufficient clinical proof for recommending use of DES in diabetic patients."

He said that Boston Sci believes the drug paclitaxel, which is coating the Taxus stent, makes the difference compared to the sirolimus-eluting Cypher stent from Cordis (Warren, New Jersey), "and we are happy to show here on the stand our evidence that there is a big difference in results for Taxus compared to Cypher."

Back in the scientific sessions, the CARDia clinical trial (Coronary Artery Revascularization in Diabetes Trial) was presented, with one-year results for PCI among diabetic patients with multi-vessel coronary disease compared to coronary artery bypass graph (CABG) procedures.

With 510 patients randomized between the two procedures, CARDia is the largest trial to date specifically comparing the technologies. Among the 256 patients undergoing PCI, a subgroup of 179 PCI patients received Cypher stents rather than bare-metal stents.

Presenting the results, Akhil Kapur from the London Chest Hospital, said the non-inferiority parameters were not met in the study due to the trial being insufficiently powered and that recruitment was only 85% of the design requirements. This study confirmed that except for equal rates of death and a slightly higher incidence of non-fatal myocardial infarction (MI), drug-eluting stents came out favorable for a lower number of strokes experienced within the first year but the number was dramatically higher for repeat revascularization at 9.9% compared to 2% for CABG.

Kapur's conclusion was consistent, nonetheless, with other industry-sponsored clinical studies, saying "PCI may now be considered a reasonable strategy in diabetic patients." In other words, details aside, DES is viable.

Not so, argued Wijns in a presentation that bordered on passionate within the context of a cardiology conference. "DES should be avoided in diabetics," he said.

With 30 randomized trials being circulated, Wijns said there is still no reliable data with the majority of studies, including only subgroups of patients with diabetes and not dedicated to patients with diabetes in particular. He declined to comment on the CARDia trial, as it was to be presented after the "DES in diabetics" debate. "CABG has been associated with mortality benefit for patients with multi-vessel disease, while no such effect was observed with bare-metal stenting, nor is to be expected from stenting using DES," he said.

The key is recognizing diabetes as an equivalent to cardiovascular disease, said Wijns. "The very presence of diabetes should give pause and given the complexity it needs to be recognized that it is going to take more than a 16mm stent to improve the dismal outcomes for these patients," he said.

Defending DES, Silber said, "It will be years until we get results, and yet we need to make decisions today. My conclusion is DES should be used with the major factor being whether the patient can tolerate the risk of a repeat revascularization and where the expected compliance with platelet drug therapy is expected to be high.

New bioabsorbable DES holds up in trial

A new-generation drug-eluting stent, the BioMatrix III from Biosensors Europe (Morges Switzerland) using a bioabsorbable polymer compares well at nine months to a first generation equivalent, but longer terms results are needed before the safety and efficacy of the new product will be known.

Results of the LEADERS study (Limus Eluted from a Durable versus Erodable Stent Coating) presented at the congress showed that BioMatrix III met the study's primary endpoint to prove it is not inferior to the venerable Cypher stent from Cordis (Warren, New Jersey), which has a durable polymer coating carrying the anti-restenosis therapeutic sirolimus.

The endpoint was the rate of major adverse cardiac events defined as cardiac death, myocardial infarction and justified targeted valve revascularization at nine months.

Coated with a a sirolimus equivalent called biolimus, the BioMatrix stent platform is covered with a polylactic acid polymer that dissolves into carbon dioxide and water during a period of 6-9 months.

Laura Mauri from the Harvard Clinical Research Institute (Cambridge, Massachusetts) was invited to comment on the report at the ESC congress and offered a guarded endorsement of the trial.

While congratulating LEADERS as one of the first industry sponsored all-comers trials, and saying the consistency of results across patient subgroups was reassuring, Mauri noted, "There is not sufficient power to determine the safety or efficacy in each of these subgroups."

While a fully biodegradable polymer might have a unique advantage over a durable polymer the durability of the clinical results is unknown for a polymer that dissolves at nine months and therefore "the hypothesis that the new biolimus-eluting stent has improved late safety and preserved efficacy compared to sirolimus-eluting stent remains to be proven in further follow-up."

One-year data from the LEADERS trial, sponsored by BioSensors, will be presented at the October Transcatheter Cardiovascular Therapeutics conference in Washington.

Monitoring alerts reduce hospitalizations

Data presented by Italian researchers show that Medtronic (Minneapolis) cardiac devices equipped with OptiVol Fluid Status Monitoring Alerts may give physicians advance warning of their heart failure patients' worsening condition, thus reducing the rate of heart failure hospitalizations and clinically relevant events.

Two-year follow-up data, presented by Maurizio Landolina, MD, shows this may be as much as a 50% reduction.

"Heart failure is a progressive condition, frequently marked by worsening symptoms such as fluid build-up in the chest cavity, which often must be addressed in hospital," said Landolina, of Fondazione Policlinico S. Matteo IRCCS (Pavia, Italy). "Our research team concluded that devices with OptiVol may detect this decompensation in a broad population of heart failure patients. By allowing the chance for timely discovery and prompt intervention, the alerts could lead to a reduced number of events such as heart failure hospitalizations."

Involving 532 patients at 34 Italian centers, the purpose of the study was to describe the use of intrathoracic impedance monitoring in clinical practice, and evaluate the clinical usefulness of the associated alert in reducing clinically relevant events and heart failure hospitalizations.

OptiVol Fluid Status Monitoring is found only on Medtronic cardiac resynchronisation therapy-defibrillators (CRT-Ds) and implantable cardioverter-defibrillators (ICDs). It uses low electrical pulses that travel across the thoracic cavity (the chest area encompassing the lungs and heart) to measure the level of resistance, indicating fluid in the chest a common symptom of heart failure. Since normal fluid levels vary from patient to patient, and fluid accumulation can be either slow or rapid, OptiVol's ability to measure fluid status trends over time can provide important insights that are used in conjunction with ongoing monitoring of other patient symptoms.

OptiVol Alerts are for investigational use only in the U.S.