Background

If the development of transcatheter aortic valve implantation (TAVI) by our group in France can be considered a “success story” today, it is nothing short of a miracle, as the project appeared particularly challenging — not to say totally unrealistic — at its origin in the early 1990s. It is quite thrilling, therefore, to observe the current acceptance and expansion of this technology worldwide, 10 years after the “heroic” first-in-man TAVI procedure performed in Rouen on April 16th, 2002.

We report here the main phases of this 20-year odyssey and briefly consider future prospects, as TAVI remains in a process of continuous development.

Birth of a concept

The starting point of this adventure took place at the end of the 1980s, with the evidence of the limitations of balloon aortic valvuloplasty (BAV), a technique that we had pioneered since 1985 for the treatment of non-operable calcific aortic stenosis (AS). The goal of BAV was to provide a therapeutic option for patients considered at that time to be inoperable, often because age more than 75 years per se was a customary contraindication to aortic valve replacement (AVR) in the 1980s. BAV was associated with midterm improvement in quality of life , explaining its rapid adoption and explosive growth worldwide. However, the lack of survival benefit and a recurrence rate of 80% at 1 year led to a dramatic decline in its use.

For us, addressing the issue of post-BAV valvular restenosis soon became an obsession. The idea of placing within the diseased valve a large-size stent containing a mounted prosthesis (stented valve) was rapidly considered an optimal potential option.

Actually, the concept of transcatheter heart valve implantation was not new. In the 1970s, several projects aimed at treating aortic regurgitation remained experimental. In 1989, Henning-Rud Andersen first implanted an original model of a balloon-expandable catheter-mounted stented valve within the aorta of pigs, using a handmade mesh containing a porcine valve. The results, published in 1992 , were not followed by human application. Other experimental concepts emerged thereafter . In 2000, Philip Bonhoeffer developed a stented valve made of a bovine jugular vein conduit inserted in a platinum-iridium stent, which was implanted in the pulmonary artery of lambs . Bonhoeffer performed the first human implantation of this device in a right ventricle to pulmonary artery conduit in 2000 , followed by intense development of the technology in this indication. Simultaneously, we specifically addressed degenerative AS, a highly challenging indication, regarding the specificity of the calcific aortic valve and surrounding structures.

First observations, enthusiasm and frustration

In 1993 to 1994, we demonstrated in 12 fresh specimens of calcific AS that a Palmaz stent, 23 mm in diameter, could circularly open each native valve, regardless of the amount of calcification. The ideal height of the stent appeared to be 14 to 16 mm to avoid impinging on the coronary ostia, the intraventricular septum or the anterior mitral valve leaflet, thus duplicating the subcoronary position of any surgical bioprosthesis. The stents were well anchored within the aortic annulus, requiring a high traction force to be dislodged, thus limiting the risk of embolization. This study, which validated the concept of aortic valvular stenting in a model of human calcific AS, was a fundamental milestone. However, at that time, the type of valve prosthesis and its physical properties were still at the drawing stage.

Over a 4-year period, the search for a biomedical company that was interested in the project failed completely. A long list of engineering issues and potential complications was consistently pointed out, including coronary obstruction, aortic and mitral valve complication, early dislodgement of the device, stroke, mechanical complications, etc. The project was even considered “the most stupid ever heard”!

Percutaneous valve technologies: the end of the tunnel

To accomplish this venture, a start-up company, “Percutaneous Valve Technologies” (PVT, NJ, USA) was finally formed in 1999. Engineers from Israel were able to design the first models of balloon-expandable transcatheter heart valve (THV), which consisted of a stainless steel stent integrating a tri-leaflet polyurethane valve. Considerable laboratory work was done before obtaining the first frozen THV model.

Animal trials: first promising results

With the help of my collaborator Helene Eltchaninoff, animal experiments on the sheep model started in September 2000 at the Centre d’experimentation et de recherche appliquée (CERA; Institute Montsouris, Paris). Through the brachiocephalic trunk, the first successful implantation of a THV within the native aortic valve was achieved, with excellent results and no complications. After this case, we had the inkling that it was the start of an important story. The presentation of this case at various meetings aroused memorable and encouraging enthusiasm from the medical community! More than 100 implantations at different cardiac sites were subsequently performed by us. Soon, with experience, we switched to bovine pericardium for the valve prosthesis. We learned a lot from this experiment, with case after case contributing to substantial improvements in the THV and in the delivery systems and implantation techniques. We also conceived an original model for the chronic evaluation of the THV in the systemic circulation , which demonstrated the persistence of excellent valve function and the integrity of the THV on pathological examination at 5 months.

First-in-human implantation

April 16th, 2002 — the date of the first-in-human implantation — will remain a memorable day. A 57-year-old patient with severe AS presented in cardiogenic shock with major left ventricular dysfunction (the ejection fraction was 12%!) and multiple comorbidities contraindicating AVR. After failed emergent BAV, TAVI appeared to be the last-resort option for this young patient. The indication was particularly challenging in this critically ill patient who also had subacute leg ischaemia related to an aortofemoral bypass occlusion and severe contralateral atherosclerosis preventing the use of the transfemoral retrograde access. All information concerning this never-used therapeutic option was given to the patient’s relatives and the patient himself, all of whom gave their consent with no hesitation. The procedure was performed the following day with my collaborators Helene Eltchaninoff and Christophe Tron, using the antegrade transseptal approach. This unplanned approach added stress to the procedure, although we had experience of using it in a few BAV cases with no arterial access. Actually, each step of the procedure was amazingly straightforward. Stabilizing the THV across the native valve was quite challenging, but after some time, we succeeded and rapidly deployed it. Haemodynamic and echocardiographic results were incredibly improved, with no transvalvular gradient and a return of blood pressure to normal, allowing discontinuation of vasopressors. There was no impairment of the coronary ostia or the mitral valve, no atrioventricular block and only mild paravalvular aortic regurgitation. On transoesophageal echocardiography, valve function was excellent. No words can express the emotion felt by the whole team. We were witnessing a true resurrection. Despite an episode of pulmonary embolism, the patient continued his clinical recovery. Unfortunately, the perfusion of his leg continued to worsen and after an above-knee amputation that never healed properly, the patient passed away 4 months after TAVI.

This first case confirmed the feasibility of implanting a THV in a human on the beating heart using transcatheter techniques, with perfect subcoronary position and no interference with the surrounding structures, thus translating our postmortem observation of 1993.

The international reaction to this spectacular case defied imagination. The deafening silence during the video presentation of this case in meetings was testament to the degree of emotion and stupefaction of the medical community. Clearly, this first-in-man case can be considered a breakthrough in the history of interventional cardiology.