catheter to perform a balloon valvuloplasty of the pulmonic valve. 6
The development of balloon angioplasty of coronary arteries helped
to drive interest and technological advancements in dedicated
balloon catheters for valvular heart disease. Dr. Jean Kan at Johns
Hopkins University further refined the technique and equipment,
first using an animal model and then in humans starting in 1982. 7
The success of pulmonary valvuloplasty lead to interest in treating
mitral and aortic stenosis.
Expanding catheter-based therapies to other valves proved more
challenging as there was not a direct antegrade route to the valve, as
there is with the pulmonary valve. For this reason, the first balloon
valvuloplasty performed by Kanji Inoue were done via an open surgical
approach in 1984. Given the success of the procedure to address
rheumatic mitral stenosis, James Lock adapted the procedure and
accessed the left atrium and mitral valve via a transeptal puncture,
to perform the first percutaneous mitral valve commissurotomy
that same year. 8 This approach is now considered the preferred
initial approach to address rheumatic mitral stenosis by delaying
the need for valve replacement in younger individuals in the hope
to avoid multiple surgeries.
Use of valvuloplasty balloons in the aortic position to treat
aortic stenosis came soon after. Alain Cribier at Charles Nicole
University in France performed the first balloon aortic valvuloplasty
in 1985. 9 Although there was initial improvement in patients after
valvuloplasty, the durability of the results was only temporary.
This approach did not provide a long-term treatment option for
patients who were not surgical candidates. The procedure did help
provide a bridge to surgery for patients who may at first not be good
surgical candidates due to acute decompensated heart failure or
other confounding issues. As a result, balloon aortic valvuloplasty
is still in use today for this purpose. Given the early re-stenosis that
occurred with balloon aortic valvuloplasty, the search for a more
durable therapy continued.
The first transcatheter valve was developed by Dr. Andersen
and consisted of an intact porcine valve which was sutured to a
wire frame that could be crimped onto a balloon. Although using a
similar design to current transcatheter valves, this first-generation
valve was very large at approximately 41 F in diameter and required
the use of a midline laparotomy to access the abdominal aorta to
insert the valve. Early studies in a pig model demonstrated success in
treating the stenosis. However, due to the valve’s large size, coronary
artery obstruction was also frequent, so this was never expanded to
humans. 10 Fortunately, Cribier continued his research into a catheter-based
valve. His group was able to refine the idea of a “stented
valve” by implanting Palmaz stents into the aortic valve of human
cadavers. He was able to demonstrate that the stent strut effectively
opened the valve in a circular manner allowing for valve leaflets to
function inside similar to bioprosthetic surgical valves. These studies
also helped determine appropriate sizing of the valve to prevent
coronary obstruction. 11 Initial attempts to get industry to help with
developing the technology were unsuccessful, with no company
showing any interest due to concerns about potential complications
from a non-surgical valve. After being told by one executive that
his valve concept was “the most stupid” idea, this finally prompted
Cribier and other leaders in interventional cardiology to form their
own company Percutaneous Valve Technologies (PVT) to engineer
and design the first models of Cribier valves. These have served
as the foundation for the current balloon expandable valves used
today. Based on the successful implantation of his valve in sheep, 12
the valve was approved for compassionate use in humans with the
first TAVR implanted in a human on April 16, 2002. 13
Based on the success of the early “feasibility” of human trials,
PVT was bought by Edwards Lifesciences in 2004, which allowed for
more rapid development of valve design and delivery system. This
same year, Medtronic also began developing its own valve platform
that consisted of a self-expanding valve which could also address
aortic stenosis. With the industry now interested in catheter-based
valves, enrollment in the PARTNER trial began in 2007. This trial
randomized inoperable patients to TAVR versus medical therapy
and high-risk surgical patient to TAVR versus SAVR. The results
demonstrated clear benefit in the inoperable group receiving TAVR
and noninferiority of TAVR compared to SAVR, prompting FDA
approval in 2012. 14 Further comparison trials in intermediate-risk
patients 15,16 were able to demonstrate similar noninferiority of TAVR
to SAVR, which led to commercial approval for TAVR in intermediate-risk
patients in 2016. Commercial approval for TAVR in lowrisk
patients occurred in 2019 based on the PARTNER III Trial. 17
After just 18 years of use of transcatheter valves in humans, the
future of TAVR in some ways is already in practice. What started
out as a treatment option for inoperable or high-risk patients has
now expanded to a treatment option that is comparable to surgery.
Now as the multi-disciplinary heart team meets to discuss treatment
options for patients, both TAVR and SAVR are considered,
allowing more patients to be appropriately treated as well as receive
the best-tailored treatment option. Just like techniques and
technology for valvuloplasty were expanded from the pulmonic
to mitral to aortic, balloon expandable TAVR valve are now being
used to replace pulmonary 18 and mitral valves. 19 The history of this
rapidly developing technology has demonstrated that we are likely
only at the early stages of the transcatheter valve innovation. More
is yet to come.
References:
GETTING TO THE HEART OF MEDICINE
1
Osnabrugge RL, et al. Aortic stenosis in the elderly: disease prevalence and
number of candidates for transcatheter aortic valve replacement: a meta-analysis
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