Part 2. Professor Alain Cribier and the TAVI odyssey

Take-home message:

Transfemoral transcatheter aortic valve implantation has emerged as the gold standard therapy in Europe for patients over 75 years old suffering from severe symptomatic aortic stenosis.

Keywords:

Alain Cribier, TAVI, aortic stenosis

The TAVI odyssey

Alain Cribier passed away on 16 February 2024. His name is eternally linked to aortic stenosis and his groundbreaking innovations, from balloon aortic valvuloplasty (BAV) to transcatheter aortic valve implantation (TAVI).

After medical school in Paris, he joined the Cardiology Department in Rouen, led by Professor Brice Letac. His fellowship at Cedars-Sinai in Los Angeles, working with Dr. Jeremy Swan and Dr. William Ganz, the inventors of the Swan-Ganz catheter, was pivotal in his career and sparked his innovative spirit, as he used to say.

Alain Cribier made his first major impact in 1985 when, at the age of only 40, he performed the first balloon aortic valvuloplasty for acquired calcified aortic stenosis on a 72-year-old woman suffering from heart failure and recurrent syncope [1]. His invention generated immense enthusiasm within the cardiology community as it offered, for the first time, a solution for thousands of patients with severe symptomatic aortic stenosis who were rejected for surgery, often because of their age.

For several years, cardiologists came from all over the world to train in BAV and participate in seminars, and accordingly, hundreds of patients were sent to our department to undergo the BAV procedure. Simultaneously, scores of trials and publications emerged worldwide during this period, leading to the U.S. Food and Drug Administration’s approval of the procedure and its inclusion in the guidelines as an alternative to surgery for selected patients.

Despite the initial "fairytale", it became clear by the late 1980s that restenosis after BAV was a limitation to the expansion of the technique and BAV could not serve as an alternative to surgical aortic valve replacement. It is a true reflection of Alain Cribier’s character that he did not abandon ship when faced with this challenge; instead, he transformed this negative finding into a search for a solution. He had an audacious new concept: implanting a “stented-valve”, a new aortic valve sutured within a stent using catheter-based techniques, with the native diseased aortic valve serving as the anchor for the stent.

In the early 1990s, in collaboration with Alain Cribier and René Koning, we conducted a critical study on hearts from patients who had died from aortic stenosis. This study validated the concept of a stented valve and demonstrated the advantages of a short balloon-expandable metallic frame. Indeed, a short-frame stent had the great advantage of respecting the anatomical native structures, such as the coronary arteries, septum, and mitral valve. Alain Cribier filed a patent for this innovation.

Finding a company to develop the concept and a prototype became an obsession. Every company he contacted declined the project. It was deemed impossible, dangerous, even foolish. During this difficult period, Alain Cribier, ever the true innovator and driven again by a clinical need, developed another approach: the metallic mitral commissurotome [2]. While travelling in India for coronary interventions, he observed that many patients with severe mitral stenosis could not afford mitral balloon commissurotomy, leaving them with no treatment options. Alain Cribier’s idea was to create a reusable (up to 100 times) metallic device resembling Dubost’s surgical commissurotome.

Nearly 10 years later, in 1997, Alain Cribier met two engineers from Johnson & Johnson, Stan Rabinovitch and Stan Rowe. They were the first to believe in the stented valve project and they joined forces with Martin Leon and Alain Cribier to create a start-up named Percutaneous Valve Technologies (PVT). They collaborated with a company, Aran, in Israel, where Assaf Bash, an impressive engineer, developed the first prototypes. The first prototype was a 23mm stented bioprosthetic valve. This major step allowed us to conduct a series of implantations in ~100 sheep. The first successful results obtained in sheep were presented at the TCT meeting in Washington in 2000.

The first-in-human (FIH) procedure took place on Tuesday, 16 April 2002, on a 57-year-old patient from northern France who had been denied surgery and admitted for emergency BAV, which unfortunately did not lead to sufficient clinical improvement. After extensive discussions with Martin Leon, they decided that this particular patient would be the first human case [3].

In the cath lab with Alain Cribier, each of us had a role for this groundbreaking procedure. The implantation had to be performed through transseptal catheterisation because the femoral arteries were inaccessible, a technique we had mastered over the years with BAV. The valve had to pass the septum, follow the wire externalised via the contralateral femoral artery, and reach the aortic valve. Positioning the valve correctly was very challenging in a very unstable patient. The valve was implanted, aortic pressure recovered immediately, and the patient showed impressive haemodynamic improvement. Within minutes, we realised that the concept had become a reality. This first case confirmed that non-surgical implantation of a prosthetic heart valve could be successfully and safely achieved. Tuesday, 16 April 2002 was an unforgettable day for us.

The FIH procedure was followed by a challenging period due to regulatory issues, with authorisation granted only for compassionate cases and the exclusive use of the transseptal approach. At the same time, while still performing over a hundred BAV cases a year, Alain Cribier had another brilliant idea: using rapid pacing to stabilise the balloon during the implantation of the transcatheter valve.

In 2004, we performed the first planned retrograde arterial implantation, the approach initially imagined and developed by Alain Cribier for TAVI. Despite treating only compassionate patients, the clinical results were remarkable, leading to significant recoveries and impressing those who had been sceptical [4,5].

In subsequent years, several randomised trials (PARTNER 1-3; COREVALVE/EVOLUT) and international registries, including the FRANCE and FRANCE 2 registries [6,7] have been conducted and led to the recognition of TAVI as the gold standard therapy in the vast majority of patients in the European and US Guidelines [8,9]. In parallel in the mid 2010’s, our team expanded its research programme to explore the disease itself. We have been investigating the mechanisms and progression of aortic stenosis, evaluating durability, and exploring new therapeutic options like non-invasive lithotripsy while raising awareness about cardiac valve disease. Alain Cribier was part of the Advisory Board, involved in our research consortium RHU-STOP AS, which includes clinicians, researchers, academics, and industrial partners.

The number of patients who have benefited from TAVI is now approaching 4 million in over 80 countries. Since 2019, the number of TAVI procedures has exceeded the number of surgical valve replacements in many countries. The continuous expansion of TAVI can be predicted in the future for many reasons, including an ageing population, an increased number of qualified centres, advanced technologies, new indications, and a desirable reduction in the cost of TAVI.

Looking back over the last 20 years, we are amazed by the impact this procedure has had. TAVI has been seminal for the transcatheter treatment of other valve diseases, such as mitral and tricuspid insufficiency. TAVI also played a crucial role in bringing together specialists in the Heart Team concept, influencing medical culture as a whole. This is where we are 22 years after the first case, with this disruptive technology that has become, against all odds, the predominant therapy for treating patients with severe aortic stenosis.

Alain Cribier is THE individual who was both the source and motor of this extraordinary odyssey in patient care, and it is through his hard work, his commitment and talent, that the field of Structural Heart Disease exists today.