Background

It is now 10 years since the first human transcatheter aortic valve replacement (TAVR), a procedure performed in Rouen, France, in a patient with severe aortic stenosis (AS) . Currently, a decade after this historic event, most TAVR procedures performed and the majority of innovations in the field of transcatheter valve technologies occur outside the United States of America (USA). Nevertheless, the USA had a major role in the development and evaluation of this technology ( Fig. 1 ). It could be said that although TAVR was born in France, it matured in the USA. In the following review, we provide data on the development of TAVR in the USA, revealing the critical role the USA played in this extraordinary process.

Milestones in the development of transcatheter aortic valve devices in the USA and in Europe.

The early days

In early 2004, almost 2 years after the first human TAVR procedure, when only a total of 17 patients had been treated by this technology, TAVR entered into the ‘major league’ of the industry with the purchase of a small privately held medical technology company, Percutaneous Valve Technologies, Inc. (PVT, Caesarea, Israel), by the American-born Edwards Lifesciences Corporation (Irvine, CA, USA). This transaction allowed Edwards to accelerate the development of this breakthrough technology while providing the needed expertise and resources to ensure successful commercialization ( Fig. 2 ). Several months later, at the 2004 Transcatheter Cardiovascular Therapeutics (TCT) meeting held in Washington, DC, TAVR attracted major publicity as a widely discussed topic. One of the highlights was the live introduction of a patient 1-year post-TAVR.

Edwards SAPIEN device in preparation.

Feasibility evaluation of the Edwards SAPIEN device

The USA Food and Drug Administration (FDA) had a major influence on the evaluation of TAVR devices. The FDA, an agency within the United States Department of Health and Human Services, is responsible for protecting and promoting public health through the regulation and supervision of numerous materials, including medical devices. The Center for Devices and Radiological Health is the branch of the FDA responsible for the premarket approval of all medical devices in the USA, as well as overseeing the manufacturing, performance and safety of these devices. In January 2005, the FDA conditionally approved the first feasibility trial of the Cribier-Edwards percutaneous aortic heart valve. Six months later, Edwards Lifesciences announced a delay in enrolment in its percutaneous aortic heart valve clinical feasibility trials in the USA using the antegrade transseptal delivery, in order to incorporate the retrograde delivery system, which at that time had already been evaluated in several cases in Canada. The company took this action after some USA antegrade cases demonstrated a significant degree of clinical complexity and adverse outcomes. However, the ‘loss’ of the antegrade transseptal approach was rapidly replaced that year by the antegrade transapical approach, performed using the Ascendra system. Later that year, the FDA approved the re-enrolment of 20 patients in a non-randomized feasibility trial of its Cribier-Edwards percutaneous aortic heart valve using the retrograde transfemoral approach. This pioneering trial took place at three clinical sites in the USA (William Beaumont Hospital, Royal Oak, MI; New York-Presbyterian/Columbia University Medical Center, New York, NY; and The Cleveland Clinic Foundation, Cleveland, OH). From January to May 2006, the three centres completed 20 cases. The FDA then approved the enrolment of an additional 35 patients.

The PARTNER (Placement of AoRTic traNscathetER valves) trial

In March 2007, after submitting follow-up data from the original 55-patient feasibility study, Edwards Lifesciences received approval from the FDA to initiate a pivotal trial of its Edwards SAPIEN transcatheter aortic heart valve technology – the PARTNER trial (Placement of AoRTic traNscathetER valves). This trial was a randomized controlled multicentre study that assigned patients into one of two arms: a ‘non-surgical’ arm (Cohort B), in which the Edwards SAPIEN valve was compared with medical therapy and balloon valvuloplasty at the operator’s discretion; and a ‘surgical’ arm (Cohort A), in which the device was compared with traditional surgical aortic valve replacement (SAVR). The trial began enrolment initially at two study sites that were part of the earlier transfemoral feasibility study. This rapidly expanded to another 15 study sites in the USA. One year later, Edwards Lifesciences received FDA approval to add the Ascendra transapical delivery system to the PARTNER trial and also received approval to increase the trial sample size from 600 to 1040 patients. During that period, positive experiences by the operators led to rapid enrolment. By March 2009, enrolment of patients in the non-surgical study arm was completed and by August 2009 enrolment in the operable arm was completed as well. Subsequently, Edwards Lifesciences has received FDA approval for non-randomized continued access to the Edwards SAPIEN valve for actively enrolling PARTNER sites.

One of the points of strength in the PARTNER trial methodology was the use of web-based conference calls, conducted by the executive committee, to further review and approve the selection of each patient before randomization. Every case was reviewed by executive committee members, including relevant imaging studies. A total of 3105 symptomatic severe AS patients were screened at the investigator sites for enrolment eligibility and 1094 were presented at those conference calls. A total of 145 cases (13.2%) were rejected during these presentations and 21 cases changed their cohort or access designation after review (1.8%). Overall, 34% of the total number of initially screened patients were ultimately randomized in the PARTNER trial (22% to the cohort A and 12% to cohort B). These presentations have added power to the study by enrolling a homogenous population, and the discussion during these meetings helped to disseminate knowledge and catheterization techniques between sites. It is now obvious that appropriate patient selection is one of the most difficult tasks in a TAVR programme and the presentation methodology used in the PARTNER trial allowed support for inexperienced sites to avoid beginners’ mistakes.

In September 2010, the results of PARTNER Cohort B were published . This was a true milestone in the field of TAVR. For the first time, the cardiology community had solid scientific evidence based on a randomized trial showing the advantage of this technique in patients with severe AS who were not candidates for surgery. In 358 inoperable severe AS patients, TAVR, compared with standard therapy, significantly reduced the rates of death from any cause, the composite endpoint of death from any cause or repeat hospitalization, and cardiac symptoms, despite the higher incidence of major strokes and major vascular events. As a result, TAVR has become the new standard of care for patients with AS who are not suitable candidates for surgery.

Six months later, the results of PARTNER Cohort A were published . That trial compared outcomes after treatment with either the Edwards SAPIEN valve or traditional open-heart surgery in high-risk operable patients. The study was a ‘non-inferiority’ trial designed to evaluate whether patient outcomes after TAVR with the Edwards SAPIEN valve are similar to surgical outcomes. The study achieved its primary endpoint at 1 year, concluding that survival of patients treated with the Edwards SAPIEN transcatheter aortic valve was equivalent to survival of those treated with SAVR. In patients with AS at high-risk for surgery, TAVR was non-inferior to SAVR for all-cause mortality at 1 year. In addition, mortality at 30 days was lower than expected in both arms of the trial. Even with this early-generation device and limited operator experience, the TAVR mortality rate was the lowest reported in any multicentre series of clinical data for the Edwards SAPIEN valve.