PARIS — Boasting a record participation of more than 30,000 cardiologists, the European Society of Cardiology (ESC; Sophie Antipolis, France) said this year's meeting is the largest cardiology meeting in the world, and Europe's largest medical meeting.
ESC 2011 is easily the most international of events with 144 countries represented, a tribute to the success of the society in gathering cardiologists from the four corners of the globe. The society today counts 53 national cardiac societies, five associations, and 35 affiliate national cardiac societies.
Being held outside Paris at the Parc des Expositions near the Charles de Gaulle airport, the 30-minute train ride from the central city is a cacophonous celebration of languages, even by the standards of this cosmopolitan city. Most participants say they are drawn by the strong educational program that features 521 scientific sessions and the presentation of 4,276 accepted abstracts.
Yet many admit the chance to take a long weekend in Paris at the end of the summer vacation season was equally attractive.
The new ESC President, Michel Komajda, MD, said this is “the year of registries“ at the congress with 15 presentations of data covering a broad range of treatments and conditions. He said the collection of registries is the fruit of ESC's drive to force greater study of safety and real world clinical practice.
The registry campaign is also a response to complaints by members of the heavy dependence on studies sponsored by industry that are narrowly focused, highly selective and centered on the performance of a specific device or drug.
Komajda highlighted the largest of the registries, Prospective Urban Rural Epidemiology (PURE), a large-scale study that recruited 150,000 individuals residing in 28 low-, middle-, and high-income countries around the world.
PURE is designed to examine the impact of urbanization on the development of primary risk factors for cardiovascular disease, such as obesity, hypertension, dysglycemia and dyslipidemia, and smoking.
Data collection includes medical history, lifestyle behaviors, dietary profiles, electrocardiogram, and anthropometric measures as well as blood collection and storage for biochemistry and future genetic analysis.
PURE and 14 other studies will be showcased in presentations at the ESC's trademark Hotline Sessions this week.
Drugs give ground to devices
Traditionally more pharma-oriented than the device-heavy congress of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) held in May, ESC has given ground to interventional cardiologists with five Hotline presentations devoted to drug-eluting-stent (DES) or PCI studies, and a further two presentations of results from implantable-cardioverter-defibrillator (ICD) studies.
The chair for the scientific program, Michael Böhm, MD, of Saarland University Hospital (Homburg, Germany) said highlights of the device studies will include a three-year study of new generation DES that shows reduced in-stent thrombosis, a registry comparing transfemoral versus transapical approaches for transcatheter aortic valve implantation (TAVI) and FRANCE II, the FRench Aortic National CoreValve and Edwards registry.
The Spotlight theme for ESC 2011 is “Controversial issues in Cardiology,“ and in the comments of both the new ESC President, Michel Komajda, MD, and Böhm, clearly place in this limelight the inroads made by interventional cardiology.
The recent scandals involving ICD implantations and the “runaway train“ of rapid adoption of TAVI procedures create a friction among cardiologists.
Valves are increasingly being implanted in younger patients and the jury is still out on the effectiveness of the $6 billion annual cost worldwide for stenting of arteries compared to optimal medical treatment, or drugs.
“It's a fact that we don't have a consensus in many areas of treatment and prevention,“ said Komajda who leads the Cardiovascular Medical and Surgical Departments at the Pitié Salpetrière Hospital in Paris.
“There are differing opinions on many topics, and these occur anywhere from basic science and research to the most complex interventional procedures,“ said Böhm.
“We want the ESC Congress to be the platform for a constructive debate on these issues based on evidence and experience,“ he said.
Expanded indication for Mitraclip
Even as cardiologists debate the merits of drugs versus devices for effective therapy, the innovation pipeline continues to produce new, alternative treatments.
Last year Abbott Laboratories (Abbott Park, Illinois) presented one year results from the Endovascular Valve Edge-to-Edge Repair Study (EVEREST) II study showing the percutaneous implantation of the MitraClip was noninferior against the conventional surgery for patients with significant mitral regurgitation.
At ESC 2011 Abbott expanded the potential indications for the device with the presentation of the investigator-led PERMIT-CARE study among 51 patients considered ineligible for mitral valve surgery.
The study results showed functional mitral regurgitation reduction with MitraClip treatment, substantial improvement in New York Heart Association (NYHA) functional classification and reversed left ventricle remodeling in approximately 70 % of patients.
“This study suggests that MitraClip treatment could offer, for the first time, a solution for heart failure patients who have severe mitral regurgitation and are unresponsive to cardiac resynchronization therapt,“ said Angelo Auricchio, MD, the lead investigator with the Fondazione Cardiocentro Ticino (Lugano, Switzerland).
“Surgery is not a good option for these patients because of their advanced left ventricular dysfunction and low ejection fraction,“ he said, adding “We have shown that they were significantly improved following treatment with the MitraClip device.“
The device is introduced by a catherter through the femoral vein to the right atrium of the heart and then punched through the septum to be passed through the mitral valve into the left ventricle.
Once the device is deployed it clips the free edge of the anterior mitral-valve leaflet to the posterior leaflet.
Electronic 'nose' smells heart failure
“Sometimes it takes something crazy to shake up our ideas,“ said session chairman Frank Ruschitzka, MD, with the Zurich University Hospital by way of introducing the presentation of a new device that proposes sniffing out heart failure.
The very serious Vasileios Kechagias, PhD, from the University Hospital Jena seemed far from crazy in presenting his invention, yet session participants could not supress their smiles as they heard out his proposal to attach an electronic sensor to the skin to detect odors indicative of heart failure patients.
Emphasizing that the results are from a pilot study and that the device is far from finished, Kechagias said the study succeeded in demonstrating among 126 patients that those with decompensated heart failure could be divided from compensated heart failure patients with 89% sensitivity and 88% specificity.
The “electronic nose“ consists of an array of three thick-film metal oxide based gas sensors with heater elements.
Each of the sensors has a slightly different sensitivity to various odorant molecular types.
Interactions between molecules and the sensor are caused by reactions with oxygen on the heated sensor surface leading to a change of the free charge carrier concentrations and thus to a change in conductivity in the metal oxide layer.
The odor components are divided by a statistical analysis into two principal components.
Further work is needed he said, adding the goal is to create a minimally invasive technique to rapidly screen, diagnose, and monitor chronic heart failure.
Version one seems to be something out of a 19th century laboratory with a long road to reach the 21st century.
The device is a bulky cube strapped to the forearm, and the detection session takes 30 minutes.
It also needs to be connected to a high-end gasometer and molecular analysis system at the University for Applied Sciences in Jena.
Yet the potential is intriguing with the possibility of one day seeing a miniaturized version for a skin patch that remotely transmits the readings.
Roughly 2% of the general population suffers from heart failure and present a heavy cost burden for healthcare systems. Among people older than 65, the affected population jumps five-fold to 10%.
Philips, Toshiba advance 3-D strain echography
The world of stress echography just became more stressful for the makers of two-dimension speckle tracking systems.
Suddenly this widely used assessment of heart tissue viability is so 1990s.
Or as one sales executive put it at the ESC meeting, “2-D speckle technology is from the last century.“ Both Toshiba Medical Systems Europe (Zoetermeer, the Netherlands) and Philips Healthcare (Eindhoven, the Netherlands) pushed the envelope to break into the third dimension for assessing deformation of heart wall motion with new ultrasound systems and software.
“Last year when we introduced 3-D speckle tracking, the theory sounded too good to be true,“ said Willem Gorisen, cardiac ultrasound market manager for Toshiba.
“This year we are presenting data that shows it is true and with a novel parameter for measurement that demonstrates a superiority over other 3-D data sets and visualizations,“ he said.
Meanwhile, Philips is promoting the built-for-purpose X5-1 transducer to break the barrier to adoption by offering a toggle choice between 2-D and 3-D scanning.
For its 3-D speckle tracking and strain analysis software Philips has partnered with Tomtec (Unterschliessheim, Germany) offering that company's 4-D Left Ventricle Analysis as a plug-in on its Xcelera platform to reconstruct full volume renderings from data acquire in 2-D slices or planes.
Toshiba has moved faster and further into 3-D speckle tracking by building a proprietary software for the Artida platform that is distinctive for acquisition and analysis of a full volume data set, rather than slices.
Novel volume acquisition yields new metric
Building on the new analytic approach of 3-D volume acquisitions on the Toshiba technology, Sebastiaan Kleijn, MD of the Free University (Amsterdam, the Netherlands) developed a novel parameter for measuring deformations in heart wall motion that he proposes can replace existing speckle tracking parameters to provide a rapid and robust evaluation for everyday clinical use.
Published in the March issue of the Journal of the American Society of Echocardiography, Kleijn et al. describes the Automated Area Tracking metric in “three-dimensional speckle tracking echocardiography for automatic assessment of global and regional left ventricular function based on area strain.“
In their conclusion, the authors propose that area strain represents a promising novel automatic index to identify regional wall motion abnormalities that may provide an accurate and reproducible alternative to current echocardiographic standards, which rely on visual assessment by experienced echocardiographers.
The key words, Kleijns told BB&T, are reproducible and accurate.
“The ability to reproduce the same results each time with automated area tracking becomes very important, not only for the specific exam but for a consistency between different exams at different moments in time of the same patient,“ he said.
“Follow up exams and evaluations of patients are critical to know if the patient is improving as a result of treatment or is doing less well,“ he said. “We need to work fast and get results quickly, and this software gives very rapid analysis that is reproducible and accurate.“
Toshiba's Gorisen said the Artida 4D Area Tracking provides an automated assessment without the need for high-level expertise.
“Current speckle tracking parameters require great insight into the ultrasound technology itself and are sensitive to small changes in settings or patients, either of which will affect the results of the exam,“ he said. “This is a robust method that makes it ideal for clinical use.“
Because area tracking is performed on a volume and not calculated from points on a plane the speckles targeted and tracked for analysis over time do not move out of scan range, which can frequently be the case with plane-acquisition data.
According to Kleijn, the newly proposed parameter “provides basic information clinicians need to know, an everyday evaluation we perform on almost any patient in our clinic for interventions, for drug management or any other protocol of treatment.“
“You can repeat the experience, and for physicians all over the world, this reproducibility will help them come to believe in this parameter,“ he said.
'It's all about the transducer'
Philips spent the first half of its presentation at ESC on 3-D speckle tracking analysis describing why the technique is not ready for routine clinical use.
According to Jan Balzer, MD from the Duseldorf University Hospital, there is a need for more testing, a standardization of measurements and a standardization among manufacturers.
Having made the case to go slow on adoption, the Philips symposium strangely turned to an all-out promotion for a 3-D transducer capable of feeding data into the TomTec 4D analytic software offered on the Xcelera platform.
In the following presentation titled “Is 3-D echo ready for routine use?“ Jose Luis “Pepe“ Zamorano Gomez, MD, the director of the Cardio Vascular Institute at the University Hospital San Carlos (Madrid), responded with an unqualified “yes.“
The past president of the European Association of Echocardiography (EAE), Zamorano focused on the role of the transducer in volumetric image acquisition all the while praising the virtues of the Philips X5-1.
The all-in-one X5-1 combines Philips' xMATRIX array with PureWave crystal technology and supports 3-D, 2-D, color flow, M-mode, pulse wave Doppler, tissue Doppler imaging, and contrast-enhanced exams.
The show-stopping features are the ability to tilt and rotate the transducer scan without moving the transducer.
The scan angle can be electronically rotated in five-degree increments clockwise a full 360 degrees, he said.
Because the TomTec approach tracks and calculates speckle movements on a plane, a higher performance trandsducer becomes essential for a high quality data set and to minimize the potential of losing a targeted speckle with an out-of-plane movement during the twisting movement of the heart muscle.
“It is all about the transducer, the acquisition quality and the spatial and temporal resolution,“ said Ludwig, ultrasound product manager for Philips in Germany.
“You can only diagnose based on what you can see and what the system can make visible,“ he said.
Both Isken from Philips and Gorisen from Toshiba said their respective companies are participating in a newly formed work group with the EAE that hopes to set standard metrics and an interoperability between manufacturers platforms for 3-D speckle tracking.
As a first step the task force plans to tackle the same objectives for 2-D speckle tracking.
Doctors, not industry, drive clinical case for stents
The clinical case for revascularization using drug-eluting stents advanced modestly at this year's meeting.
The third-generation of drug-eluting stents (DES) won a green light for effectiveness, and a national strategy for rushing acute cases directly to the cath lab for immediate revascularization was shown to result in lower mortality.
Yet another study showed that for complex cases where patients have triple vessel disease, percutaneous coronary intervention (PCI) was associated with a significantly higher risk for serious adverse events.
What was especially significant is that not one of these studies was sponsored by industry, and all had large-scale patient populations reflecting real-world practice, precisely the long-awaited evidence ESC has called for.
The absence of industry's heavy footprint in stents was remarkable at ESC 2011, a stunning silence after the blaring grandstanding for DES at past congresses.
With the exception of the French manufacturer Hexacath (Rueil-Malmaison) that set up a counter and modest backdrop, there was no promotion of stents on the exhibition floor, nor in the distributed publications and literature.
This retreat from the floor is all the more surprising considering the worldwide market for stents is estimated to be well north of $4 billion.
Despite the overwhelming commercial success that stents have brought to medical device companies and the rapid clinical adoption, the evidence that the metal sleeves are better than optimal medical therapy or traditional bypass surgery has remained dubious.
Findings about DES were criticized as coming from underpowered studies with selective data or masked p-values, which show the significance of results.
In May, the European Association of Percutaneous Cardiovascular Interventions (EAPCI; Sophia Antipolis, France) went so far as to ask manufacturers to retrospectively report their data by recasting the results using criteria for patient-oriented outcomes rather than device-oriented outcomes.
New generation DES win SCAAR approval
Five years ago stent utilization was soaring and sales were cresting $5 billion.
Then came the firestorm in Barcelona when the efficacy of DES was criticized during a packed plenary session at the ESC congress.
If this was the spark, it was the report at that same congress from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) that threw gasoline on the fire by questioning the long term safety of DES due to blood clotting.
European usage of DES dipped slightly after the ESC meeting, but sales in the U.S. crashed from over 90% usage in PCI procedures in early 2006 to around 55% before the end of that year.
At ESC 2011, SCAAR was back, this time to report that third generation DES are associated with a 38% lower risk of clinically meaningful restenosis and a 50% lower risk of stent thrombosis compared to old generation DES.
The study included 94,384 stent implantations in Sweden from November 2006 to October 2010 using a national registry where all consecutive patients undergoing coronary angiography or PCI are included.
The performance up to two years of 10,551 different types of DES considered “new“ was evaluated in an un-selected large real-world population – including patients with myocardial infarction, three-vessel and/or left main disease, bifurcation lesions, graft disease, restenotic lesions and chronic total occlusions.
The new stents needed to be represented by more than 500 cases to be include, according to Giovanna Sarno, MD, with the Department of Cardiology at Uppsala University (Sweden).
Sarno told BB&T the three dominant stents in the new generation analysis of the SCAAR registry were Xience V and Xience Prime from Abbott, PROMUS Element from Boston Scientific and Endeavor Resolute from Medtronic (Minneapolis).
Also included were 64,631 bare metal stents, as well as 19,202 DES considered to be “old,“ and including the Taxus line from Boston Scientific (Natick, Massachusetts), Cypher from the Cordis division of Johnson & Johnson (New Brunswick, New Jersey) and Endeavor from Medtronic.
Sarno attributed the improved performance for the new generation to stent designs with thinner struts, and especially greater biocompatibility of polymers that bind the therapeutic to the strut, which “may have an important impact on drug elution profiles, endothelial coverage, and functional recovery.“
She concluded that patients treated with PCI with “new generation“ DES have a considerably lower risk of restenosis and stent thrombosis at two years compared to older generation DES in a large real world population.
The most remarkable finding in the SCAAR study was the lack of any cardiac events after 15 months for patients receiving the new DES, where such adverse events continued, and even increased beyond that point for patients with older generation stents and even more so with bare metal stents.
The risk of mortality was reduced 23% with the newer stents compared to other versions.
A 'protective effect' of by-pass surgery
The SYNTAX study will not go away.
Commissioned by ESC after the Barcelona disaster, and funded by Boston Scientific, the Synergy between PCI with Taxus and cardiac surgery was a head-to-head comparison between clinical outcomes for bypass surgery and DES.
But instead of closing the door on criticisms of DES, it turned out PCI is not always as good as surgery for patients, and that among patients with severe coronary artery disease (CAD), CABG was found to have a benefit).
The legacy of SYNTAX is an objective scoring system for assessing the complexity of a patient's CAD.
Now the trial has inspired a Japanese study to retrospectively assess a 26-center registry enrolling consecutive patients having a first coronary revascularization between January 2005 and December 2007.
CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) PCI/CABG registry cohort-2 is a physician-initiated non-company sponsored study that looked at 2,981 patients with triple vessel disease where 1,825 patients underwent PCI and 1, 156 patients had coronary bypass surgery.
The primary endpoint of the study was a composite of all-cause death, myocardial infarction (MI) and stroke.
Presenting the findings, investigator Hiroki Shiomi, MD, from Kyoto University Hospital (Japan), reported PCI was associated with significantly higher risk for serious adverse events in these patients.
PCI as compared with CABG was associated with a higher 3-year risk for this primary endpoint, though the risk for cardiac death was not found to be significantly different.
Yet the risk for all-cause death was found to be significantly higher after PCI.
“Especially remarkable was a protective effect of CABG for myocardial infarction,“ according to Shiomi.
Frans Van de Werf, MD, with the University Hospitals (Leuven, Belgium) was the discussant for the presentation of the CREDO-Kyoto during a ESC signature Hotline plenary session.
“This study confirms the overall findings of the SYNTAX trial in a large, real-world population,“ he said, adding it also confirms the usefulness of the SYNTAX score in clinical practice.
“A big surprise was to see there is a benefit with CABG, even among patients with a low syntax score,“ he said.
'Get thee to a cath lab'
Forget the door-to-balloon time, the critical measure for success in revascularization is call-to-balloon time.
“Americans are obsessed with reducing the time from door-to-balloon,“ said Christian Juhl Terkelsen, MD, with the University Hospital of Aarhus (Denmark).
“Yet when they do not see improved outcomes they wonder what they are doing wrong,“ he said.
Door-to-balloon time improvements have failed to produce changes to survival and long-term risk of subsequent cardiac events for patients who do survive, he said.
The answer turns out to be what he called the system delay, of the call-to-balloon time.
By reducing the critical moments between the onset of symptoms and the inflation of the angioplasty balloon to reopen the culprit artery, the informed patient and a well-trained emergency medical technician with the ambulance.
If you are having a cardiac crisis, he said, do not take a taxi.
“It's unbelievable, but that is how some of our patients arrive,“ he said.
Results of a registry analysis for 9,514 patients treated by a regional cath lab from 1999 to 2009 included 1,656 of the self-presenters, 4,805 patients transferred from a hospital and 3,053 who were delivered direct to the center after calling the emergency hotline.
These patients did the best, leading Terkelsen to suggest that in the event of a heart attack, patients should not go to the nearest hospital.
“Field triage by the EMT cuts out an hour of hospital processing,“ he said.
The exception is where the hospital is also a qualified cath lab, which Terkelsen defines as one performing PCI 24/7.
More than 50% of PCI patients in the region are today brought direct to the cath lab and the program's goal is 85%, he said.
In 2003 the western Denmark region decided on a strategy for reperfusion by PCI rather than with medical treatment.
The healthcare system covering 3 million people was realigned to assure fast response among three regional centers in coordination with EMT services. Public education was also a critical factor for success, Kristensen said.
Steen Dalby Kristensen, MD, with the Skejby Hospital (Aarhus, Denmark) today leads a Europe-wide program called Stent for Life that is backed by ESC and the European Association for PCI.
The goal is to expand the Denmark experience to participating countries.
Home monitoring of ICDs fails to lower mortality
Implantable cardiac defibrillators (ICDs) are routinely implanted in patients at risk of sudden cardiac death as a result of rhythm disturbances.
So much so that cardiologists' offices are overwhelmed by the required follow-up visits scheduled every 3 months.
Remote monitoring features have since proven to help reduce this burden and throughout the developed western countries, ICDs and the new monitoring technology have seen a rapid adoption.
Except in France.
Where the implantation rate is 140 ICDs per one million population in western countries, penetration in France hovers at 88 ICDs per million.
At the meting, two studies designed to yield cost-benefit and resource utilization data for remote monitoring of ICD patients in France were presented, offering new insights into the effectiveness of home monitoring.
Sponsored ICD studies consistently show that remote monitoring is safe, and that they are effective in reducing unnecessary office visits.
But the EVATEL study (EVAluation of TELe follow-up) is the first controlled trial aiming to assess the impact of remote follow up on mortality.
“An important achievement of this study is that it was investigator initiated, included multiple vendors and featured a large patient population,“ said Angelo Auricchio, MD, from Rondazione Cardiocentro Ticino (Lugano, Switzerland) who critiqued the study as a discussant during the ESC Hotline session.
Unfortunately much-anticipated financial data was withheld pending further review by the French government that commissioned the study.
The study was also limited by the caveat that it was technically underpowered, enrolling 1,501 patients rather than the required 1,600.
According to Luc Cheminot, who leads French operations for Biotronik (Berlin), the government funding of the study also came with a strict timeframe forcing the investigators to go forward without waiting for the last 99 patients.
The study also suffered from poor telecommunications with more than 50 patients from the remote-monitoring group converting to the control group due to an inability to transmit data remotely.
There was yet another disappointment for EVATEL investigators in missing the primary endpoint.
EVATEL hypothesized that remote monitoring would affect the rate of major cardiovascular events, defined as all cause death, hospitalization for a cardiovascular event, unsuccessful ICD therapies, and inappropriate ICD therapies.
It did not. There was no difference in survival at one year between the monitored group and the control group.
There were also no statistically significant differences between the two groups for a secondary outcome measures of the time to onset of the first major cardiovascular event and the one-year survival rate.
EVATEL did demonstrate that demonstrate across multiple vendor platforms the safety and efficacy benefits from the remote follow-up of ICD patients.
The one good piece of news was a significant reduction in inappropriate therapy in the remote monitoring group.
Thirty French centers participated in the study and the remote reporting ICDs came from Biotronik, Medtronic, St. Jude Medical (St. Paul, Minnesota) and Boston Scientific.
“The remote follow-up of patients implanted with an ICD seems to be a safe alternative to conventional in-office follow-up,“ said principal investigator Dr Philippe Mabo from the University Hospital of Rennes (France).
“However, for the widespread uptake of this new strategy — at least in France — reimbursement from the healthcare system will be needed,“ he said.
Biotronik's Cheminot said that France currently pays a supplement of €1,000 for an ICD that is capable of home monitoring, requiring in exchange a validation report that the device was actually used and not merely switched on.
Fewer shocks, longer battery life
The ECOST trial (Effectiveness and Cost of ICD Follow-Up Schedule with Telecardiology) sponsored from Biotronik investigated the safety, effectiveness, and costs of long-term follow-up over 27 months with Home Monitoring.
Once again, the cost figures have been withheld for review by the French Ministry of Health, apparently still on vacation at the end of August.
Cheminot told BB&T that the forthcoming results of the cost study will be worth the wait, adding that Biotronik has a unique agreement with the government that will allow the company access to the entire healthcare cost of ICDs per patient, including paramedic interventions, pharmaceutical impacts and monitoring.
A total of 433 patients were followed for 27 months in 43 centers for ECOST with all patients seen in the clinic within the first three months after implantation.
Patients were then randomized to a remote monitoring group or an in-clinic follow-up control group with the remote patients seen in the ambulatory department only once a year unless an anomalous ICD function or an event of clinical concern was reported by remote monitoring.
In the control group, the patients were followed in the ambulatory department at 6-month intervals.
ECOST principal investigator Professor Salem Kacet with the Lille University Hospital Center (Lille, France) reported a clear benefit for home monitoring with a 52% reduction of the number of patients with inappropriate shocks and a 72% reduction in the risk of hospitalizations related to inappropriate shocks compared to the control group.
ECOST also demonstrated a 76% reduction in the number of charged shocks with a significant impact on ICD battery longevity.