BB&T

PARIS – Clinical professionalism was mixed with a healthy share of Gaullic pride as the FRANCE registry came home for a presentation at the annual congress of the French Cardiology Society.

The French Aortic National CoreValve and Edwards Registry (FRANCE) is the world's first national registry providing a head-to-head comparison between the only two valves approved for transcatheter aortic valve implantation (TAVI) on a beating heart.

First presented in November 2009 at the meeting of the American Heart Association (AHA; Dallas) in Orlando, the registry provides 30-day results across 30 risk factors for a cohort of 244 patients who received aortic valve replacements at one of 16 certified centers in France between February and September 2009.

A sneak preview of six-month follow up results for half of the FRANCE patients was presented at the French cardiology congress, ahead of the formal report expected later this year.

The registry proved critical in convincing French health authorities to approve reimbursement on Dec. 31, for the valve replacement procedure, where the valve is introduced percutaneously into the heart, positioned to replace the patient's failing valve, and then fixed in place by balloon inflation, similar to stenting procedures used in coronary arteries.

FRANCE also provided a wealth of information for clinicians on real-world performance for the two valves approved for the procedure in Europe, according to surgeons at the AHA conference in Orlando.

A transfermoral access was the surgeon's preferred route to the heart, accounting for 166 of the FRANCE surgeries, or 68%.

Significantly, transfermoral access is where where the Sapien valve from Edwards Lifesciences (Irvine, California) and the Medtronic CoreValve Percutaneous System compete head-to-head.

French surgeons employed the Edwards valve in 57% of these cases. Medtronic (Minneapolis) bought CoreValve (also Irvine) last spring for an initial payment of $700 million plus additional payments contingent upon the achievement of certain milestones.

The Edwards valve was used in a further 29% of cases, or 66 procedures, where surgeons elected to use a transapical access, a more direct route between two ribs that is an alternative for patients with compromised peripheral arteries who cannot risk the transfermoral approach.

The CoreValve system is not yet approved for this approach, offering instead a more direct alternative access through the subclavian artery beneath the collarbone, which was employed in 5% of procedures, or 12 patients.

Two-thirds of the centers participating in the FRANCE registry are dedicated to a single manufacture's system, limiting surgeon choice for the procedures.

Only patients unable to withstand a traditional open surgery valve replacement are eligible for the percutaneous procedure, and 50% have a life expectancy of less than one year, making for an extremely high-risk population.

Surgeon Hélène Eltchaninoff, MD, from the Rouen University Hospital, who assisted TAVI pioneer Alain Cribier, MD, with the first-in-man procedure in 2002, reported the FRANCE registry shows a 97% success rate for implantation and a combined mortality rate of 12.7% at 30 days.

In the six-month follow up, mortality increased to 23% among the first half of the patient cohort, reported Eltchaninoff, reminding the audience of the severity of illness and adding that echocardiography showed the initial excellent hemodynamic results were maintained for the survivors.

Patients in the FRANCE registry will be followed for three years.

Mortality was slightly higher in the 30-day results for the CoreValve transfermoral approach at 15% compared to 8% for Edwards, while the Edwards transapical approach resulted in a 16% mortality rate.

The only significant difference in the performance of the devices was the requirement for the patient to have a pacemaker implanted, which occurred in 5% of cases where the Sapien valve was used but in 27% of cases for CoreValve patients.

Cribier suggested the explanation is in the design of the CoreValve device, which is significantly longer and its placement in the left ventricular outflow tract touches the membranous septum, affecting the conduction of electrical impulses, requiring resynchronization with a pacemaker.

With reimbursement for TAVI approved on New Year's Eve, Cribier said he expected that 2010 would see 1,500 procedures performed in France and that the potential volume for TAVI is between 3,000 and 5,000 cases annually.

Over 11,000 valve replacement surgeries are performed in France annually.

Eltchaninoff said between 1% and 4% of the population over 65 is affected by severe calcific aortic stenosis, making them candidates for a valve replacement, and that 30% of these patients are considered to be high-risk for traditional surgery.

Among the patients eligible for TAVI, she said 40% couldn't be considered for the transfemoral route.

Cribier said the low number of patients enrolled in the FRANCE registry is explained by the lack of reimbursement in 2009, adding that government funding for 250 procedures enabled 16 of France's 33 approved TAVI centers to participate.

“We have only to look to Germany, which approved reimbursement one year ago, to see the pattern we can expect in France following approval of reimbursement,“ Cribier said.

He reported 2,000 TAVI procedures were performed at German centers in 2009, the first year of reimbursement, and that 5,000 TAVI surgeries are anticipated in 2010, the second year with reimbursement.

Germany pays e33,000 ($47,500) per surgery, including e18,000 ($25,900) for the Sapien valve system, the surgery and hospitalization.

Surgeons were disappointed with the e24,000 ($34,500) awarded for the TAVI procedure by French authorities.

France pays e15,000 ($21,500) for a valve replacement in an open surgical procedure with a cost of e3,000 ($4,300) for an Edwards valve, leaving a greater margin for the hospital and surgeon.

TAVI procedure gains acceptance

Advances in transcatheter aortic valve implantation (TAVI) over the past year marks a turning point for this novel surgery, according to Alain Cribier, MD, who pioneered the technique with the first-in-man procedure in 2002.

“We passed 10,000 patients in 2009, which is much more than a psychological milestone,“ he said.

“I am delighted, of course,“ he told colleagues at the annual meeting of the French Society of Cardiology.

“We have opened the door to a new treatment for high-risk patients, people who are condemned to a short life expectancy,“ he said.

“There has been a sharp increase of interest judging by the sudden increase in published papers and presentations made at professional society congresses,“ he continued.

The European arm of Edwards Lifesciences' (Irvine, California) Placement of AoRTic TraNscathetER Valve (PARTNER) trial reported first year results, he said, while in the U.S. enrollment was completed for the PARTNER trial, a 1,040-patient randomized controlled Investigational Device Exemption (IDE) study.

Closer to home, he said the publishing of the FRANCE registry and the approval of reimbursement for the procedure will encourage greater acceptance and further clinical assessment of the procedure.

The number of TAVI procedures reported in Europe increased a staggering five-fold in 2009, jumping from 923 procedures in 2008 to more than 5,000 procedures.

In Europe, where 95% of all TAVI is performed, the number of cardiac centers completing training for this multi-disciplinary surgery with either Edwards or CoreValve, jumped from 89 in April, 2008 to 276 reported in April, 2009.

The past year also saw two significant commercial developments in TAVI as Medtronic (Minneapolis) entered this market segment with the acquisition of CoreValve (Irvine, California) for $700 million, and Edwards earned a CE mark for the slimmer delivery system, designed specifically for transfermoral procedures.

Valve replacement and repair using minimally invasive percutaneous cardiac intervention (PCI) techniques is proving disruptive for traditional open cardiac surgery, which has already seen interventional cardiologists capture a growing significant share of coronary by-pass procedures with stenting.

For the moment, TAVI is restricted to patients with Euroscores higher than 20 who are unable to withstand an open heart procedure, who are typically over 75 years old, and who present with co-morbidities such as pulmonary and renal dysfunctions and arterial complications.

The less invasive TAVI technique has given new hope to this class of patients, as well as a justification for interventionalists of responding to an unmet medical need.

Yet as techniques and patient outcomes improve, it is clear that TAVI could become an alternative for younger and less severely ill patients who today are accepted for traditional aortic valve replacement.

There is already a trend, if not a pressure, to move to patients with lower scores, noted Patrick Serruys, MD, from Erasmus Medical Center (Rotterdam, the Netherlands), who is also the Editor-in-Chief of the EuroIntervention Journal.

Martyn Thomas, MD, from Kings College Hospital (London) at EuroPCR 2009 in Barcelona acknowledged “there are procedures being done in Europe with Euroscore less than 20 in significant numbers.“

In sharp contrast with the competition between surgeons and interventionalists in stenting, many cardiac surgeons have been among the early adopters of TAVI, and these surgeons already replace valves in traditional open surgeries for patients as young as 70 years and with a Euroscore below 20.

Serruys has repeatedly called for a combined large-scale trial and registry, saying, “If TAVI is not evidence-based medicine and does not take into account the health economic factors, it will not be considered legitimate or justified in the eyes of the health authorities and therefore not reimbursed.“

“In exclusively treating end-of-life patients,“ he said, “there is for the moment an open question regarding TAVI as to whether it is cost-effective and justifiable for the healthcare systems of European countries to offer an expensive surgery that extends the quality of life for a patient population with a limited life expectancy.“

Marking a “first“ in cardiology with the FRANCE registry of transcatheter aortic valves implants (TAVI), the French Cardiology Society seized the opportunity to remind colleagues at the annual congress of other “firsts“ for France reinforcing its reputation as a pioneer in cardiac surgery, including:

• The first-in-man implantation of a valvular bioprosthesis in 1968 by Alain Carpentier in Paris. The patient survived for 18 years with the home-made device.

• First-in-man implantation of a coronary stent in 1986 by Jacques Puel in Toulouse.

MRI-compatibility in pacemakers

Ahead of the commercial release in Europe of its MRI-compatible pacemaker, Medtronic (Minneapolis) launched a scientific campaign here last week aimed at convincing cardiologists to consider the case for the novel devices.

The Advisa MRI and Ensura SureScan pacemakers will be available for implantation in France by June, according to Christèle Pelade, Manager for Implanted Diagnostic & Monitoring Devices with the Medtronic subsidiary Vitatron (Issy-les-Moulineaux, France).

Approximately 62,000 pacemakers are implanted in France annually.

Pelade said these second-generation models replace the first generation EnRhythm that was implanted in 211 patients for the EnRhythm MRI SureScan System Clinical Trial.

Ensura is a standard model pacemaker, she explained, while Advisa offers higher end features for monitoring impedance for prevention and treatment of atrial fibrillation.

“The launch of Advisa and Ensura marks the first milestone toward a truly MRI-safe device,“ she said.

Medtronic, the pacemaker pioneer, holds a considerable lead over competitors in addressing the difficult technical challenges of MRI-compatibility, a first-to-market advantage that may last for years.

Yet, executives from St. Jude's French operations said the company would be introducing an MRI-compatible product before the end of 2Q10.

The Medtronic MRI-compatible pacemakers minimize ferrous components to minimize the level of energy transmitted through the lead to the device connection point, a potential source for over-heating under magnetic forces.

The device and leads also contain radiopaque marks, viewable via X-ray, to indicate that the system is MRI-compatible.

The proprietary feature for Medtronic's novel pacemakers is the SureScan programming that can be enabled during the scan to eliminate the impact of MRI-generated electrical noise, such as disruptions to the pacing therapy, or can cause the device to oversense and deliver unnecessary pacing therapy.

The SureScan feature temporarily suspends data collection and monitoring functions while allowing the device to continue providing asynchronous pacing if needed.

Medtronic offered a box lunch and a panel of leading French cardiologists during the society's annual congress for a déjeuner-débat that left little time for the promised debate and raised few questions from the audience.

One reason is that there is no argument that magnetic resonance imaging (MRI) scans are dangerous for patients with an implanted pacemaker, and there is complete agreement that someone needs to do something about this.

Jean-Nicolas Dacher, MD, from the celebrated cardiac center at the Centre Hopitalière Universitaire (CHU) in Rouen established the medical need.

Seventeen percent of pacemaker patients in France will have a need for an MRI scan for some disease condition within the first year of receiving the implant, while fully half to three-quarters of all pacemaker patients will require a scan during their life after receiving the device.

The MRI scan is “unmatched, irreplaceable and the indispensable reference for the diagnosis of cancers, neurological disorders, and increasingly, cardiac conditions“ he said, noting that though pacemaker patients can easily undergo computed tomography scans or ultrasound, “there is not a suitable alternative to MRI for many conditions.“

Pierre Bordachar, MD, with the Hôpital Haut-Lévêque at the CHU-Bordeaux responded to the question of just how dangerous an MRI may be for a patient with a pacemaker.

“There are few reasons for excluding a patient from an MRI, and nearly all of them are having a pacemaker,“ he said, adding that 200,000 patients with pacemakers are denied scans each year in the United States.

A pacemaker or an implantable cardioverter-defibrillator (ICD) is an “absolute“ contra-indication for an MRI according to international guidelines, he said, unless there are extenuating circumstances, specifically of life-or-death.

Bordachar cited the only study of deaths from MRI by Werner Irnich, MD, with the University Hospital Giessen (Giessen, Germany), who compiled reports from 30 German medical centers and found that from 1992 through 2001 six deaths resulted when pacemaker patients underwent an MRI scan.

Despite the strong discouragement in practice guidelines, MRI scans are conducted on patients with pacemakers under careful protocols, he said, admitting that as many as 12 such patients per year undergo the exams at CHU-Bordeaux each year.

The luncheon debate moderator Salem Kacet, MD, the head of cardiology at CHU-Lille, acknowledged there is “a great pressure by neurologists for MRI scans, and we have used MRI on defibrillator patients, but not on pacemakers.“

Officially, David Steinhaus, MD, medical director of the cardiac rhythm business unit at Medtronic acknowledges that despite well-documented risks and warnings, “pacemaker patients do receive MRI scans off label.“

Bordachar said in these cases, even after following careful and time-consuming protocols, “there are always going to be unpredictable complications.“

These protocols include reprogramming the MRI scanner, careful patient monitoring by a cardiologist during the scan and a thorough follow-up over several months.

An MRI has three magnetic fields, he explained to colleagues, and can provoke diverse effects including arrhythmia, device damage, interference with the pacing function and provoking electronic reset.

“At 1.5 Tesla there are negligible effects, yet there will always be a patient with problems,“ he said, adding that “at 3 Tesla, problems only become greater.“

In addition to the concern for immediate super heating of lead wires on the device, the follow up is required because force and torque exerted by the whipsaw effects of magnetic cross currents can shake or dislodge an implanted device.

Frédéric Anselme, MD, from CHU-Rouen presented the findings from the Medtronic-sponsored EnRhythm MRI SureScan clinical trial, that are preliminary as cardiologists await the completion of the follow up with patients for final results.

A randomized study enrolling 445 patients from 41 centers, including 21 in Europe and 13 in the U.S., the endpoints were to assess safety and effectiveness of the new pacing system in 445 patients.

Only 211 patients with the new pacemaker underwent head and lumbar scans with 1.5 Tesla scanner while the remaining patients served as a control group.

“The big news is that patients have been 100% complication-free,“ reported Anselme saying there were incidents of ventricular arrhythmias or asystole, no differences in pacing and sensing, nor evidence of either clinical or device complications.“