The global structural heart device segment has enjoyed great success in the last decade, and is set to continue its strong growth into the next decade – with analysts predicting 10% CAGR leading to a $19 billion market by 2026[i]. By “structural heart devices” we mean devices and systems which enable interventionists to address structural issues in the heart (such as valve stenosis or regurgitation) in a minimally invasive way via a catheter, rather than by open heart surgery.
TAVR[ii] or Transcatheter Aortic Valve Replacement represents a major part of this growth forecast, which sees it continuing to gain traction as a safe, effective and – in an increasing number of cases – preferable alternative to the more established SAVR (surgical aortic valve replacement).
The aortic valve is one of 4 valves in the heart, and it performs an essential function: opening to enable the contracting left ventricle to deliver blood to the whole body through the aorta, and then closing to prevent backflow while the ventricle relaxes and refills ready for the next pulse.
The two main aortic valve diseases are stenosis (narrowing) and regurgitation (leakage), either of which can be present at birth or can develop later in life. Aortic valve disease causes chest pain, shortness of breath and dizziness on exertion. Causes are senile aortic calcification (stenosis caused by gradual build-up of calcium deposits), bicuspid aortic valve, or one of a number of underlying conditions that can damage the valve. Left untreated, severe aortic valve disease leads to heart failure and death, and the only available treatment is valve replacement (TAVR or SAVR).
SAVR remains the gold standard but requires a taxing operation – open heart surgery, usually followed by 1-2 days in ICU, with discharge in 5-10 days and rehabilitation for up to 3 months. TAVR is transformative, with patients able to stand and walk the same or next day, and rehabilitation for up to a fortnight. Whilst mechanical valves for SAVR have more proven durability, their poorer haemodynamics compared with TAVR bioprostheses require patients to take anticoagulants and sometimes anaemia treatment for life.
So what do the next 10 years have in store for this revolutionary treatment? Ros Lancaster (Healthcare Innovation Researcher) and Matt Brady (Partner) share their predictions in this 2-part blog.
Outline of the development of TAVR
Clinical reports suggest patients frequently ask for TAVR, perhaps rightly seeing it as a miraculous intervention – replacing a malfunctioning part of their heart, bringing about a step change in their fitness and extending life whilst leaving only a small incision – in place of a major surgery and long recovery. Indeed TAVR is clever, employing a complex catheter-based delivery system to deliver and precisely position a pre-loaded, collapsible valve which is then expanded and fixed in place.
Perhaps it’s not surprising that the road to clinical and commercial success was long. Whilst TAVR’s inventor Henning Rud Anderson first had the idea in 1988 and gained his patent in 1995, the first successful human procedure didn’t take place until 2002. It wasn’t until 2007 that EU regulatory clearance was achieved by Edwards Lifesciences, by then the holder of the IP, with FDA approval following in 2011.
The technical heritage goes back even further: Anderson was inspired by the then-new coronary artery stent, asking why it could not be enlarged to contain a pericardial heart valve (a valve whose flaps, or leaflets, are made from animal pericardium) – a technique itself pioneered by British surgeon Marian Ionescu in Leeds General Infirmary from as early as 1971.
Initially only indicated for inoperable cases (those patients who were unlikely to survive SAVR), TAVR’s growth has been fuelled by clinical evidence supporting successive reductions in risk indication – first high-risk, then intermediate, and as of 2019, Edwards’ Sapien 3 and Medtronic’s CoreValve are both approved for use with low surgical risk patients in the US (with only Edwards’ Sapien 3 to date enjoying the same indication in the EU).
Whilst the TAVR trail has now been impressively blazed for patients with low surgical risk, much remains to be achieved in the coming years if the technology is to fulfil its promise to displace SAVR even for younger patients.
Prediction 1: Improved Durability for Ever-Younger Patients
One key reason SAVR is still exclusively used for younger patients is device life. Whilst mechanical valves for SAVR are expected to last 20-30 years, for TAVR this is given as 10-20 years. Compounding the issue for younger patients, is that their device life is expected to be at the lower end due to higher average activity levels.
We expect the major players to work to address this shortcoming in evidence for TAVR durability relative to SAVR. A key enabler for this development pathway will be adoption of standard definitions for prosthesis dysfunction to better enable comparison in durability studies[iii]. E.g. did the valve material fail and cause regurgitation, or did it become stenosed through calcification?
In the short term, one way of addressing the durability challenge is to simply insert a new valve when the original implant fails. Valve-in-valve TAVR is now considered a sufficiently mainstream option that the UK’s National Institute for Health and Care Excellence released draft recommendations in February 2019. Valve-in-valve is an option which mechanical SAVR devices don’t realistically share, and adding this to developments enhancing the life of the TAVR devices themselves, may prove to be a powerful strategy to extend TAVR’s effective durability well beyond that of SAVR.
Depending on the outcomes of ongoing durability trials, we expect to see a focus on developing improved leaflet materials and assembly methods which prevent or reduce calcification of the prosthetic valve leaflets – whether by improved preparation of the animal pericardial material, or by exploration of exotic polymers.
The natural conclusion to materials improvement would be delivery of tissue engineered heart valves (TEHV). The TAVR technology promises to be the perfect platform for delivery of autologous grafts or even tissue engineered valves – with the patient’s own cells growing on flexible scaffold which slowly dissolves away over time, leaving only fresh new valve tissue. Research is underway to develop TEHV using scaffolds which may be biological or fabricated. Perhaps the metallic stent or frame would remain present in the aortic wall, albeit quickly covered over by epithelium. Or perhaps TAVR could once again borrow from the coronary artery field and find a new application for bioresorbable stent technology.
Prediction 2 : Stroke Risk Reduction
As anyone attending conferences like PCR London Valve or TCT in the US can tell you, risks specific to TAVR remain. Despite TAVR’s obvious perioperative benefits, only recently have studies been able to claim superiority over SAVR for 1-year outcomes[iv].
The risks which garner most attention are paravalvular leakage, endocarditis, heart rhythm disruption and stroke risk. One key cause of the first three is believed to be valve frame insertion too far into the heart – driven partly by valve length and partly by the need to avoid covering the coronary artery opening. These risks are reducing through shorter valve frames and improved training targeting more precise placement.
Mitigating the fourth risk – stroke – may prove more complex. We were fascinated by a panel discussion on TAVR’s neurological risk at PCR London Valves in late 2019. Panellists addressed the apparent disconnect between reported rates of perioperative stroke (up to 5%), and the rate at which particulates are known to be released into the carotid arteries from the implantation site – with some studies observing captured particles larger than 1mm in >50% of cases. Particles can be biologic (e.g. calcium deposits) or of device origin. To bridge this gap, researchers have sought to improve stroke reporting by evaluation of possible “silent” (asymptomatic) stroke via perioperative neurological evaluation or MRI imaging.
In the context of “silent stroke,” questions persist around impact on outcomes, especially where imaged brain lesions appear to have healed on later follow-up. One panellist pointed out that as lower-risk (often younger) patients are increasingly indicated for TAVR, such “self-healing” lesions may become increasingly important to prevent as they may yet have significant downstream impacts – see recent advances regarding long-term outcomes of sports-related concussions. His memorable summary: “You can debate the risks back and forth, but honestly if it’s my brain, I’d like the filter please.” We doubted that many in that room would disagree!
Boston Scientific, emerging from a difficult few years with its LOTUS Edge TAVR line-up, appears to hold a trump card in its Sentinel Cerebral Protection System – acquired in 2018 – which deploys a pair of filter elements to arteries feeding the brain, to capture and remove procedure debris before it can cause damage.
Whilst we will undoubtedly see continued discussion of how best to prioritise use of these filter devices, we expect them to continue to gain traction – and with this in mind, new market entrants seem likely. Indeed recent months have seen Keystone Heart receive a CE Mark for their TriGuard 3, and we’re aware of others in development which deploy a single large filter in the aortic arch itself. We look forward to seeing how a TAVR device is navigated through the aorta with such a filter in place!
Look out for our next TAVR blog for more predictions!
Panel discussion: the future of aortic valve replacement
Rosalind Lancaster and Matt Brady will be joined by Professor Geoff Moggridge and Lin Bowker-Lonnecker to share further insights on what the future holds for TAVR (Transcatheter Aortic Valve Replacement).
23rd September 2020, 2pm BST
[i] Databridge Market Research
[ii] Also known as TAVI, Transcatheter Aortic Valve Implantation
[iv] See, for example, PARTNER 3 clinical trial
Healthcare Innovation Researcher
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Partner & Head of Medical Therapy
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