The clinical consensus remains unshaken. Data across diverse patient registries presented at Europe's largest congress for interventional cardiologists consistently shows that TAVI is an effective alternative for patients suffering degenerative aortic stenosis who are considered a high risk for conventional open surgery for valve replacement.
A deeper dive into the data opened debate and discussion touching concerns for lowering the incidence of stroke among TAVI patients, defining better criteria for patient selection and developing new devices to fix shortcomings in the first-generation of valves.
‘We know the procedure is feasible, predictable and quite safe,’ said Jean Fajadet MD, from the Clinique Pasteur, Toulouse, France, who is the newly elected president of the European Association for Percutaneous Intervention that organises EuroPCR. ‘Where there are problems is when the patient selection is wrong and the issue is screening,’ he said during a plenary session. ‘Do we need to perform TAVI on patients with a high rate of comorbidity when we know that the survival will be low?’
Behind the clinical code words the message is one that was repeated throughout EuroPCR, which is a need to expand TAVI beyond its original indication as a last hope for frail and inoperable patients.
As TAVI enters a new stage in its development the commercial pressure for moving to a larger population of patients and the demand by the patients themselves, who want to avoid the risks of open surgery, are compelling.
Until now, TAVI has been uniquely European. The technique was invented here, the technology perfected at European centres, and the procedure won the first regulatory approvals and reimbursement in Europe.
Since TAVI was approved for European use at the end of 2007, over 40,000 valves have been implanted using this minimally invasive technique, the majority of those cases in France, Germany and Italy. More than half of those procedures were performed in the past 18 months, a rapid uptake that may be running faster than clinical evidence can be collected to support the widening use of what remains a controversial intervention.
Attention is shifting this year to the USA, where the manufacturers of the two systems approved for use in Europe, Edwards LifeSciences and CoreValve/Medtronic, are seeking Food & Drug Administration (FDA) approval.
This new level of regulatory scrutiny combined with the growing experience at European heart centres is ratcheting up the pressure for manufacturers to produce more compelling and conclusive clinical evidence.
At EuroPCR 2011, the data presented by both companies covered results for 4,456 patients with most of the procedures dating back before 2009, before utilisation doubled.
Medtronic consolidated data previously presented from seven European registries in order to create a single meta-analysis of 2,156 patients.
The patient selection criteria across the different studies are highly variable with self-reported clinical outcomes, a lack of standardised definitions and under-reported events. ‘The data cannot give a clear answer to the scope of the issues raised, but this meta analysis is absolutely fundamental for furthering the science and is important for planning future studies,’ declared Carlos Ruiz MD, from Lenox Hill Hospital, New York, who presented the results at EuroPCR 2011. ‘I would not make any black-and-white conclusions from this data, but it is very informative and in a way it is beautiful for showing what is really going on,’ he said, adding: ‘This is absolutely fundamental for furthering the science,’ he added.
One-month survival rates were consistent across five CoreValve registries at 93.8%, while all-cause mortality at one year using the transfemoral route was 17.1%. The average age of patients was 81.6 years.
This finding is consistent with the data from the monitored results of the Edwards SOURCE registry that also covers European centres and was updated at EuroPCR 2011 with an additional 1,269 patients bringing the total registry enrolment to 2,300.
Survival for Edward's Sapien valve patients who underwent a transfemoral procedure was 93.7%, while all-cause mortality at one year was 19.9%, reported Olaf Wendler MD, from King's College Hospital (London). The average age of Sapien valve patients was 81 years.
One result of the wide variation in the reporting from the European TAVI experience is a consensus document from the Valve Academic Research Consortium (VARC) that sets terminology for adverse events and recommendations for clinical endpoints for future studies.
Medtronic is conducting two large-scale studies using the VARC standards, one that is aimed at winning FDA approval, and the second, called SURTAVI, that aims to directly challenge the sick-and-frail threshold for patients by comparing results for moderate risk patients.
Meanwhile as the FDA considers approval of first-generation devices, European cardiologists are pressing forward with a next-generation of valves and delivery systems to refine the procedure further.
In his presentation, Dr Fajadet described the key elements for future devices, saying they will be better adapted to the anatomy of the aorta to reduce problems with leakage (European Hospital, 04/19/2011), they will have a lower profile for less intrusive delivery and ‘certainly the next generation valve will be based on the principle of being repositionable and retrievable, which is not the case today’.
At EuroPCR 2011, Joerg Kempfert MD, of the University of Leipzig Heart Centre, reported six-month results for the first 40 patients to receive the Symetis Acurate transapical aortic valve. Enrolment for Symetis CE mark trial is now completed, he said.
In June, sector analyst Wells Fargo Securities reported St Jude Medical implanted for the first time a retrievable and repositionable TAVI device in Canada. The company expects to launch its transcatheter valve in Europe by 2013.
JenaValve (Munich) is now completing a CE-mark pivotal study for a new transapical valve and said it expects to enter the European market in 2011. JenaValve’s second-generation TAVI systems are designed to enable re-positioning and retrievability.
The most critical quality of these valves – their long-term durability -- will remain unknown for quite some time. Providing an extra eight years of life for a patient that is 81 years old is unquestionably a tremendous benefit. Yet, as cardiologists push to perform TAVI on younger patients, the unknown durability of the devices becomes a more critical factor in a patient decision.