This year marks 2 decades since the first transcatheter aortic valve replacement procedure was performed on an inoperable patient with severe symptomatic aortic stenosis — a historic moment that would change interventional cardiology.
In the years since, TAVR, also referred to as transcatheter aortic valve implantation, or TAVI, has moved from a curiosity that drew excited crowds to become the standard of care for patients with symptomatic heart disease due to severe native calcific aortic stenosis. Procedural expertise and equipment have markedly improved; subsequent clinical trials have validated the clinical use of TAVR in a variety of patient settings.
Today, TAVR is becoming the procedure of choice over surgical AVR for patients and many clinicians. Demand has continued to rise as more trial data affirm its safety and efficacy in new patient groups. Globally, TAVR procedures are expected to exceed 300,000 per year by 2025.
“In the beginning, TAVR was more like a surgical case with an anesthesiologist,” Cardiology Today Editorial Board Member Dipti Itchhaporia, MD, FACC, FESC, immediate past president of the American College of Cardiology; the Eric & Sheila Samson Endowed Chair in Cardiovascular Health and director of disease management for Jeffrey M. Carlton Heart and Vascular Institute at Hoag Memorial Hospital, Newport Beach, California; and assistant clinical professor of medicine at University of California, Irvine, said in an interview. “Now, we have improved to the point where there is conscious sedation, no monitoring lines, 23-hour stays and same-day discharge. The prevalence of permanent pacemaker implantation has fallen from 15% down to 5% to 7% or even lower. Stroke risk is reduced due to more flexible, lower-profile devices. We have worked at better case selection. Now, the technique is being applied to all comers, including patients with bicuspid valves.”
The rapid evolution of TAVR was driven in no small part by key collaborations from stakeholders that included industry and FDA, setting a precedent for data collection and allowing for expanded indications based in part on registry data, according to Cardiology Today Editorial Board Member David R. Holmes Jr., MD, professor of medicine at the Mayo Clinic College of Medicine and a consultant in the division of cardiovascular diseases and the department of internal medicine at Mayo Clinic in Rochester, Minnesota. At the same time, technology enhancements allowed for simplification of the procedure and a striking reduction in complications, he said.
“We have taken TAVR from something people were always concerned about and always drew a crowd to a procedure that is performed at many centers in the U.S., with many patients sent home same day,” Holmes told Cardiology Today. “It has been a huge initiative, brought together and based upon the heart team, collaboration between the [Society of Thoracic Surgeons] and ACC, cardiac surgery and interventional cardiology. This was the result of everyone working together, bringing in other stakeholders to make this difference that has truly transformed medical care.”
The ‘beginning’ of the story
For decades, surgical AVR was the standard of care for patients with severe symptomatic aortic stenosis. Often, the prognosis was poor.
“Patients who were high risk for surgery often underwent operation with significant morbidity and mortality,” Howard C. Herrmann, MD, FACC, MSCAI, the John W. Bryfogle Professor of Cardiovascular Diseases in the Perelman School of Medicine at the University of Pennsylvania and health system director for interventional cardiology, told Cardiology Today. “Those patients who were considered inoperable or had prohibitive risk could be treated with balloon aortic valvuloplasty, with some short-term improvement in symptoms, but no improvement in survival. It was a palliative option.”
In April 2002, G. Alain Cribier, MD, FACC, FESC, performed the first-in-human TAVR on a man, aged 57 years, with severe aortic stenosis who presented in cardiogenic shock. The patient had major left ventricular dysfunction, an ejection fraction of just 12% and multiple comorbidities contraindicating surgery. After a failed balloon aortic valvuloplasty, TAVR was the patient’s only option. Additionally, severe contralateral atherosclerosis prevented the use of the planned transfemoral retrograde access.
In an interview, Cribier recalled a sleepless night before performing that first procedure.
“When I started the case, I was extremely worried,” Cribier told Cardiology Today. “I thought it was a mistake to put this patient on the table as the first study case, because he was doing so poorly. He had all of the contraindications for TAVI. I had to announce to my partners that we had this very bad case and I was proposing to do the TAVI on him because he would die. When I saw him on the day, I was very pessimistic. I said, ‘He’ll never be able to make it.’”
The procedure was successfully performed using a challenging approach: the antegrade transseptal approach via the femoral vein. The transcatheter heart valve was accurately deployed in the middle of the valvular calcification.
“After the case, we watched the clock,” Cribier said. “We decided if the patient survived for 30 minutes, we would say the procedure was a success. In 30 minutes, the patient was smiling, moving his hands, thanking everyone for what we did. Five hours later, we drank champagne in his room. It was the beginning of the story.”
Despite rapid improvement after TAVR, the patient died 4 months later due to non-procedure-related complications; however, Cribier had confirmed the feasibility of TAVR via a transseptal approach.
“It was a retrograde case, very difficult but incredibly successful,” Roxana Mehran, MD, FACC, FACP, FCCP, FESC, FAHA, FSCAI,professor of medicine and director of interventional cardiovascular research and clinical trials at the Zena and Michael A. Weiner Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai, told Cardiology Today. “It opened doors very early on for the sickest patients who were not surgical candidates.”
‘This was a slightly crazy idea’
Before the first-in-human TAVR procedure, Cribier and fellow investigators said they believed that a valvular structure could be inserted with a balloon-expandable stent to mimic native valve structure and function. After failed attempts to develop a commercial interest, a startup company, Percutaneous Valve Technologies (PVT), was formed in 1999; founding members included Cribier and Martin B. Leon, MD, FACC. PVT was acquired by Edwards Lifesciences in 2004.
“I was thinking this was a slightly crazy idea, but crazy ideas sometimes can work,” Leon, professor of medicine at Columbia University Irving Medical Center, director of Columbia Interventional Cardiovascular Care and director of the Cardiac Catheterization Laboratories, recalled during a panel discussion on the history of TAVR at the American College of Cardiology Scientific Session in April. “I was frustrated with the state of technology for aortic stenosis. I had wonderful experiences trying to follow [Cribier’s] path and had the opportunity to work with some very creative engineers to form a startup that had an ambitious role in trying to come up with a technology that might be a solution in the sickest patients. We gave it about a 1 in 20 chance that it could work, even for a small patient subset.”
The first TAVR procedure was performed in the U.S. in 2004 and followed in 2007 by two investigational device exemption randomized trials — the PARTNER trials of the balloon-expandable Sapien valve (Edwards Lifesciences) and the CoreValve/Evolut trials of a self-expanding valve (CoreValve/Evolut family of products, Medtronic). The trials, which enrolled more than 9,600 inoperable patients and showed clear superiority of TAVR to medical therapy, led to FDA approval for use in this patient group, in 2011 for the balloon-expandable valve and in 2014 for the self-expanding valve.
“I began to embrace it when we did our first extreme-risk cases,” Michael J. Reardon, MD, FACC, co-investigator for the Evolut Low Risk Trial, the Allison Family Distinguished Chair of Cardiovascular Research and professor of cardiovascular surgery at Houston Methodist Hospital, recalled during the panel discussion. “They were all intubated, they all went to an ICU. I have learned that if you want to find out how a surgeon’s case is going, you do not ask the surgeon. You go to the ICU and you ask the nurses. After the third case, I found out the nurses were begging to have the TAVR patients placed in their beds. Not because it was an exciting new technology, but because they did so well that they required no care. The nurses were the ones that convinced me these patients are doing great, and if it works in these people, the sickest patients, it is going to work in other people.”
The randomized trials — both the balloon-expandable and self-expanding platforms — became the largest evidence base for treatment of valvular heart disease ever conducted, Herrmann said.
“It started a collaboration between interventional cardiologists and cardiac surgeons — the heart team approach — which resulted in cooperative and better care for patients,” Herrmann said.
TAVR volume rising
After unveiling of the PARTNER 3 and Evolut Low Risk Trial data, presented at the ACC Scientific Session in 2019, the expansion of TAVR to patients with severe symptomatic aortic stenosis and low surgical risk became inevitable. At the time, long-term data comparing outcomes of TAVR with surgical AVR were lacking, but 2-year results from PARTNER 3 provided a glimpse into how the two procedures compare.
In PARTNER 3, TAVR with a third-generation balloon-expandable valve (Sapien 3, Edwards Lifesciences) was superior to surgery for the primary composite endpoint of death, stroke or rehospitalization at 1 year in patients with severe aortic stenosis at low surgical risk. Likewise, in Evolut Low Risk, which had a similar patient population, TAVR with a self-expanding supra-annular bioprosthesis (CoreValve Evolut R or Evolut Pro, Medtronic) was noninferior to surgery, with the estimated incidence of the primary endpoint of death or disabling stroke lower with TAVR at 2 years.
The 2020 ACC/American Heart Association Guideline for the Management of Patients with Valvular Heart Disease reflected the new data, embracing less-invasive interventions and shared decision-making between patients and clinicians.
“[Those studies] caused a total flip in thinking, from a mentality of who is a TAVR candidate to who is not a TAVR candidate,” Michael J. Mack, MD, FACC, medical director of cardiothoracic surgery at Baylor Scott & White Health, told Cardiology Today. “The consequence of that is you determine local factors that make a patient high-risk for TAVR. Age is probably the biggest deciding criteria, because you have to shift your thinking to the lifelong management of valvular heart disease.”
In a state-of-the-art review published in the Journal of the American College of Cardiology in November 2020, researchers reported TAVR volumes have increased every year, exceeding surgical AVR in 2019 (72,991 vs. 57,626). Since 2011, the 30-day mortality rate has decreased (7.2% to 2.5%) and stroke has started to decrease (2.75% to 2.3%), though pacemaker need has remained unchanged (10.9% to 10.8%). Alive with acceptable patient-reported outcomes was achieved in eight of 10 patients at 1 year, according to the analysis of registry data.
The volume of TAVR procedures performed in the U.S. will continue to rise, Itchhaporia said.
“The number of low-risk surgical AVR has dropped by 50%,” Itchhaporia said.
‘Put the patient in the center’
The average age of participants in PARTNER 3 was 74 years; however, a less-invasive procedure is equally appealing to younger patients. With the removal of surgical risk from the equation, clinicians rely on age and life expectancy as the two of the biggest determinants of who is best suited for TAVR vs. surgical AVR, Itchhaporia said.
“If you are in your 80s, you are only going to need one procedure,” Mack said. “If you are in your late 60s or early 70s, you are probably going to need two procedures. Younger than that, you are going to need three procedures, and one of them is going to have to be surgery. You need to think about where surgery falls. That is the decision-making process now.”
The ACC/AHA guideline states that the choice of type of intervention for a patient with severe aortic stenosis should be a shared decision-making process that considers the lifetime risks and benefits associated with the type of valve (mechanical vs. bioprosthetic) and type of approach (transcatheter vs. surgical).
“I do not think one size fits all,” Mehran said. “It is so important that, first, we put the patient in the center. To be frank, it all depends on operator expertise, center expertise, the patient’s age and comorbidities. If you have a young patient, with all things being equal, the patient can also help make the decision with you, if you give them all the information.”
Looking to the future
The TAVR story is far from over, according to Cribier.
“The next step is to continue with increasing indications,” Cribier said. “Now, TAVI is applied for people with severe aortic stenosis. The next step would be moving to patients who are asymptomatic.”
More procedural advances will follow soon, Holmes said.
“We will learn how to minimize our longevity issues, so we will have prostheses that last for the rest of a person’s life,” Holmes said. “We will minimize the need for anticoagulants, both for surgery and TAVR. And we will then use the technology in patients who have not been treated in the past, because we did not realize their need for it.”
Ongoing studies will focus on long-term outcomes data related to durability and valve deterioration in the younger, low-risk patient population. Trialists are also assessing TAVR intervention in asymptomatic patients; results from the EARLY TAVR trial are expected in early 2024.
“It is important that we not stand still,” said Leon, who also is the founder of the Cardiovascular Research Foundation. “We are still treating the minority of symptomatic severe aortic stenosis patients, and it is based upon a trigger point and guidelines that say we treat patients only at a certain point in the life spectrum of their disease. We need to break those barriers and talk about different ways of approaching patients.”
Those approaches include increasing access to care for underserved patients, as well as “preemptive TAVR” as a treatment in patients who are less symptomatic or asymptomatic if they have at-risk features, Leon said.
“When you have a technology that is less invasive and very low risk, you can begin to explore those kinds of studies,” Leon said. “I would also say that pharmacologic treatment of calcific aortic valve disease has been neglected. There are new pharmacologic approaches that could delay the progression of aortic stenosis.”
Honoring a milestone
At this year’s ACC Scientific Session, Cribier received the presidential citation in recognition of the 20th anniversary of the first clinical TAVR procedure.
It was a full-circle moment for many cardiologists, who still recall the excitement surrounding the first TAVR procedure, Itchhaporia said.
“There are many things to celebrate,” Itchhaporia said. “First, we want to honor Dr. Cribier who performed the first TAVR, a disruptive technology that has transformed the lives of so many patients. We are also celebrating the concept of team-based care, which has clearly been very successful. In honoring Dr. Cribier, we are celebrating the global collaboration involved. COVID-19 drove home the importance of global collaboration. We are a global cardiovascular community. It is only by working together do we produce outstanding solutions that will transform care. It is an important moment in history. So many people took part in this journey. It is innovation at its best when you think about it. This is how it is supposed to be.”
