Abstract
Alain Cribier was a unique individual, combining brilliant creativity with a deeply human personality, who was admired and loved by his collaborators and friends.
Photo of Alain Cribier.
Already as a medical student, he had a passion for cardiology and cardiac surgical interventions, taking on calls to work at night in the operating room at Broussais Hospital in Paris, a department led by Charles Dubost at the time.
Alain often said that his fellowship at Cedars-Sinai in Los Angeles working with Jeremy Swan and William Ganz, was pivotal in his career; it marked the birth of his innovative spirit.
Upon returning from the U.S. to Rouen University Hospital in France, he joined the Cardiology Department led by Brice Letac. Very early in his career, he insisted on the importance of prioritizing both innovative research and patient care; and his vision and leadership has inspired and led us, the younger generation.
I first heard about Alain Cribier in 1985 when I had to choose a location for my residency (Figure 1). One of the senior cardiologists, Serban Mihaileanu, advised me to go to Rouen, where a young and audacious cardiologist had performed the first balloon aortic valvuloplasty (BAV) for calcified aortic stenosis—an absolutely unthinkable procedure at the time. 1 That was enough to convince me.
For several years, fellow residents and I were fascinated by the number of physicians coming from all over the world to train for BAV procedure, participate in seminars, and by the patients coming from many countries to undergo the procedure in Rouen. Alain Cribier was already a star.
When the issue of restenosis occurring early after BAV came out, I vividly remember him telling me during cardiology rounds in 1988, ‘No problem, we will place a valve through the groin to keep the aortic valve open’. I could not even imagine that this would be feasible. Nowadays, younger cardiologists cannot fathom how impossible the idea seemed since the innovation has quickly become routine practice. Back then, this concept was utterly unrealistic.
It became clear that my career would be in Rouen, working alongside Alain Cribier and the team on his audacious project. Thus began the challenging years when Alain had to transform the idea into a reality and create a prototype.
In the early 90 s, together with Alain Cribier and René Koning, we conducted a crucial study on cadavers from patients who had died from aortic stenosis, validating the concept of a stented valve and demonstrating the advantages of a short balloon-expandable metallic frame. Alain Cribier filed a patent. Finding a company to develop the concept became an obsession, highlighting a key aspect of Alain Cribier's personality: perseverance and determination. He never gave up despite the cycles of optimism, doubt, and failure. Every company he contacted declined the project, deeming it impossible, too dangerous, or worse.
While waiting for responses from companies (all negative), Alain Cribier developed other research projects and innovations including a coronary stent we experimented in dogs in the late 80 s, the evaluation of the impact of prolonged inflations on myocardial ischemia, and above all, the development of a metallic mitral commissurotome. 2 This was driven by the observation that hundreds of patients, mainly young women, suffered from mitral stenosis in India and could not afford the Inoue balloon, leaving them untreated. Once again, the foundation for his research was based on unmet clinical needs.
We travelled a lot, in particular in India, Pakistan, Bangladesh, and Russia to teach the technique, which was very effective and appealing due to its reusability—sometimes up to one hundred times. This advantage for the patient eventually became a disadvantage commercially and led the company to abandon the development of the device.
The light at the end of the tunnel came in 1997 when Alain Cribier met two engineers from Johnson & Johnson, Stan Rabinovitch and Stan Rowe. They were the first to believe in the project and, together with Martin Leon, created a startup company named Percutaneous Valve Technologies (PVT). This venture enabled them to collaborate with a company in Israel (Aran) and, most importantly, a remarkable engineer, Assaf Bash, who developed the first prototypes. Assaf Bash transformed Alain Cribier's dream into reality, producing a “piece of jewellery,” as Alain was used to say. This prototype, a 23-mm stented valve, allowed us to conduct a series of trials in sheep (around one hundred). The first experiment in a sheep was a success and was presented at TCT meeting in Washington in 2000. The following cases were much more challenging, as the animals did not have aortic stenosis, leading to issues like valve embolization.
Undeterred, Alain, again, found a solution by implanting the valve in the descending aorta after creating massive aortic regurgitation by using a biotome to rip off one or two leaflets of the native valve. This kept the sheep alive for chronic evaluation, a mandatory step for regulatory authorities. At the same time, with over a hundred BAV cases a year, he had the brilliant idea of rapid pacing to stabilize the balloon and later the transcatheter valve.
The First-in-Man transcatheter aortic valve implantation (TAVI) procedure took place on Tuesday, April 16, 2002: a 57-year-old patient from northern France, denied surgery and admitted for emergency BAV, but had limited efficacy and failed to improve the patient's status. After extensive discussions with Martin Leon, it was decided that this particular patient would be the first human case. In the cath lab with Alain Cribier and Christophe Tron, each of us had a very specific and important role. We had to go transeptal due to inaccessible arteries, a technique mastered over years with BAV. The catheter passed the septum with difficulty, standing on it before following the extra-stiff wire externalized via the contralateral femoral artery. Positioning the valve correctly was challenging; it was jumping either into the aorta or the left ventricle. Finally, the valve was implanted, aortic pressure recovered, as well as the patient and we were all watching the screen fascinated by the sustainable hemodynamic measurements. We understood within minutes, even seconds that the concept had become a reality. This first case confirmed that, in opposition to the unanimous opposition of experts, non-surgical implantation of a prosthetic heart valve could be successfully and safely achieved. 3
The first-in-man procedure was followed by administrative challenges, limiting us to treating only compassionate cases using the transeptal approach for the next series of patients. However, in 2004, we successfully performed the first ever planned TAVI in a patient with concomitant mitral stenosis using the retrograde arterial approach, which had been foreseen since the beginning by Alain Cribier. The most compelling demonstration of this disruptive procedure was when the cardiology community saw on stage an 83-year-old patient, who had traveled from France to TCT in Washington with her family, celebrating the one-year anniversary of her valve implantation. This had a profound impact on those who had been skeptical.
While randomized trials and registries on TAVI were ongoing, our team expanded the research program to explore the disease itself—searching for mechanisms and progression of aortic stenosis, evaluating durability and new therapeutic options like noninvasive lithotripsy (Cardiawave), and raising awareness about heart valve disease. Alain Cribier was an integral part of this effort, serving also on the Advisory Board, always supporting with great interest, insights, and enthusiasm, our French consortium RHU-STOP AS (Search Treatment and improve Outcome of patients with Aortic Stenosis), which included clinicians, researchers, academic, and industrial partners) with great interest, insights, and enthusiasm.
Alain Cribier passed away suddenly on February 16th, 2024, but for us, he will remain immortal. He dedicated his life to patients, finding innovative solutions to offer them and their families a better life, enabling them to return to their activities. He was beloved by his patients, always making time for everyone, explaining with simple words, answering their questions with kindness and his incredible smile.
Alain was a true leader for us in Rouen, inspiring the entire team with his passionate nature and vision. Despite his numerous trips around the world, he was tireless; preparing conferences over weekends and at night, returning from meetings, and jumping straight into the cath lab to perform the most complex procedures. His enthusiasm was legendary, as was his smile. After each TAVI case, he would say, “C’est magnifique,” and kiss each of us. He was ambitious for us, proud of our successes, and pushed us to advance despite difficulties, never giving credit to obstacles.
Alain was an excellent interventional cardiologist, training the team and interventional cardiologists worldwide, particularly in India, for coronary interventions and mitral metallic commissurotomy. India was his “second country,” where he was considered a god in this country.
His innovations were applied to many of us, and he rapidly left Christophe Tron and myself as the first operators, even in the early transeptal era, thereby demonstrating the importance of proctoring. Hundreds of fellows and physicians (cardiologists, cardiac surgeons) came to Rouen for days or years for training or they were trained in their own cath labs. He, along with the past Director of our Hospital, Bernard Daumur, created and coordinated the Medical Training Center, organizing TAVI workshops leaving each time the participants forever marked by the teaching delivered by Alain Cribier.
Despite his busy schedule, he has always enjoyed taking time with us, to have fun, to laugh and converse. I was impressed by his curiosity and his culture. He was always reading while traveling, attending concerts with his family, and above all, playing the piano as much as he could, having hesitated between pursuing piano or medicine when he was a student.
Alain Cribier is the Father of Transcatheter Intervention in Structural Heart Disease. He received numerous prestigious awards and recognitions over the years for his innovations, always aiming to find solutions for patients without therapeutic options, addressing the “unmet clinical need"—the unique goal of medical research. He was nominated Doctor Honoris Causa by the Académie de Médecine in 2023, one of only seven physicians in 200 years in France to receive this honor, four of whom were Nobel Prize laureates. We nominated him for the Nobel Prize in 2022, 2023, and lastly in January 2024.
Alain Cribier deserved the Nobel Prize for his major innovations, driven by an exemplary clinical approach and a remarkable person full of humanity.