BARCELONA, Spain — On the heels of clinical studies confirming the safety and efficacy of transcatheter implanted heart valves, the number of implants reported at centers across Europe practicing this less-invasive alternative to open heart surgery increased a staggering five-fold in a single year.

Where 923 implants were reported for 12 months ending April, 2008, more than 5,000 procedures were performed over the next 12 months, 95% of them in Europe where the device is approved for use.

Adoption of this novel approach by medical centers jumped from 89 cardiac cath labs in April, 2008 to more than 276 reported in April of this year. (See charts, below).

"This is the dawn of a new era as we are moving beyond the early adopters to the early majority," Patrick Verguet, vice president for Europe at Edwards Lifesciences (Saint-Prex, Switzerland), told Medical Device Daily, adding that both the procedure and devices are now developing rapidly.

EuroPCR 2009 marked a milestone for transcatheter aortic valve implantation (TAVI) with the first full year of clinical evaluation of the Edwards Sapien valve presented in the PARTNER EU trial and the compelling SOURCE Registry that gathered no-holds-barred data on every case from 32 European centers for review and adjudication and covers outcomes for more than 1,000 patients.

Carlos Ruiz, MD, of Lenox Hill Heart and Vascular Institute (New York), reported that 6,500 valves have been implanted since the first-in-human procedure in 2002 and then added that another 3,500 would be implanted this year alone.

Clinicians study early results for TAVI

"We have come to a moment of change," intoned Peter de Jaegere, MD, who chaired the Forum on TAVI that preceeded the presentation of TAVI clinical studies at EuroPCR here last week.

When de Jaegere called for a show of hands by physicians in the audience who had already placed a valve using the transapical procedure, necessarily performed by a cardiac surgeon or in partnership with one, more than 100 participants raised their arms.

"It is clearly happening now," he said, "and the infomation that is now coming back becomes very relevant at this point, the first trials and the first registry."

Three measures of performance for the aortic valves that were routinely called "headline results" by presenting physicians and discussed during the sessions were mortality, stroke and a phenomenon called simply, the "learning curve."

The critical measure of mortality, charmingly called "freedom from death at 30 days," improved among Sapien patients from 87% in the early REVIVE trial to 92.7% in the later REVIVAL trial.

The SOURCE registry of Sapien implants showed a 93.7% survival rate for patients receiving a valve via the transfemoral route and 89.7% survival for those receiving a valve in a transapical procedure, a result that is "hypothesis generating," according to the presenter, Martyn Thomas, MD, of Kings College Hospital (London), who suggested transapical patients tend to present greater complications.

In the CoreValve trials, patient survival at one month was 88.6% in a trial reaching back to procedures in 2007 and 90.4% in a later study with an expanded registry of CoreValve results recording 89.6% overall survival.

A comparison with traditional valve surgery, which remains the gold standard, is problematic as patients for TAVI procedures by definition were too risky for the operating table.

The only presentation to show comparative mortality for surgical valve replacement, made by Patrick Serruys, MD, of Erasmus Medical Center in the Netherlands, showed the survival rate today is 97.4%, improving from 96.6 10 years earlier in a registry of 108,687 patients.

Serruys, who also is editor-in-chief of the EuroIntervention Journal, proposed colleagues join him in organizing a larger scale clinical trial for TAVI that would put the novel procedure head-to-head with surgical aortic valve replacement (SAVR) in a study similar to the recent SYNTAX trial.

That trial design, which compared drug-eluting stents (DES) to coronary bypass surgery (CABG), included both a randomized trial and a registry and, significantly, was an all-comers trials removing exclusion criteria typical of industry-sponsored trials that narrow patient selection to a subset favorable for the tested device rather than reflecting the true population seen by cardiologists.

Without such a study, Serruys said, "the medical community will say this off-label practice is not legitimate, not responsible and not evidence-based."

After mortality and parsing the actual causes of death among patients who suffer multiple medical complications, stroke was the key indicator for practicing interventionalists who debated the merits of routine use of a screen mesh to prevent contaminating blood flow.

Thomas showed that results for freedom from stroke was similar for patients undergoing either transfemoral or transapical procedures and said he hoped improved skill and experience of interventionalists coming off the learning curve will help "bring down this dreaded complication."

The rapid adoption of TAVI for high-risk patients over the past year by medical centers places a majority of practitioners on the learning curve and tends to skew results in the current registries, several presenters noted.

Edwards, for example, reported the number of medical centers in Europe practicing TAVI jumped from 70 to 100 between 3Q08 and 4Q08 and that it then introduced another 25 new centers before the close of 1Q09.

And because Edwards has a longer history of clinical trials, the learning curve was most apparent in the company's side-by-side presentation of results that effectively traced an improving mortality rate among patients as the intervention team became more experienced with the procedure.

Asked if there was a magic number of procedures required before a physician acquires the experience necessary to assure improved outcomes, the dean of proctors for Edwards, John Webb, MD, of St. Paul's Hospital of the University of British Columbia (Vancouver), said that after 10 cases an interventionalist begins to plateau on the learning curve, "and after 50 cases you think you know more than everyone else."

Caution and prudence urged

This annual congress for cardiac interventionalists in Europe has traditionally been focused on angioplasty and stenting of coronary arteries, an emphasis reflected in the original name of the event, the Paris Course on Revascularization (PCR).

The acceptance and adoption of percutaneous cardiac intervention (PCI) has seen not only rapid growth but an expanded application, for example to peripheral arteries in the leg, which is another emerging area of practice now covered at EuroPCR. (See MDD, May 26, 2009).

The move to valve replacement and repair using PCI techniques holds the potential to be just as disruptive for cardiac surgery, which has already seen interventional cardiologists claim with stenting a significant share of procedures that previously would have been treated with by-pass surgery.

For the moment, TAVI is restricted to patients who are denied open heart surgery and the procedure has given new hope to this class of patients and a justification of responding to an unmet medical need for interventionalists.

In other words, TAVI is beginning with the sickest of patients who are typically over 75 years old and have co-morbidities such as pulmonary and renal dysfunctions and arterial complications.

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

Where TAVI today is restricted to patients with Euroscores higher than 20, there is a trend, if not a pressure, to move to patients with lower scores, acknowledged Serruys.

In his presentation of the SOURCE registry, Thomas commented that "there are procedures being done in Europe with Euroscore less than 20 in significant numbers."

In sharp contracts 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 for patients as young as 70 years and with a Euroscore below 20.

In his presentation on the "Future Evolution of TAVI in Europe," Serruys returned to his call for a large-scale study, 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, 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.