Recent low-risk trials for TAVI look set to expand its indications for use. Amar Krishnaswamy and Samir Kapadia assess the impact of the findings on everyday practice, and look at areas where uncertainties remain.
Transcatheter aortic valve implantation (TAVI) is a mature procedure for the treatment of patients with severe and symptomatic aortic valve stenosis (AS). From the time of its inception in 2002 until it received FDA approval—initially for inoperable patients in 2012, then for high surgical-risk patients in 2013, followed by medium-risk patients in 2016—TAVI has ushered in a revolution in the treatment of AS.
Importantly, this shift in care has been the result of consistent improvements in TAVI device technology and operator experience, with robust and randomised clinical trial data demonstrating either non-inferiority or superiority to surgical aortic valve replacement (SAVR). Given the favorable results from the recently published low surgical-risk trials, TAVI is set to again change the paradigm of AS treatment.1,2
Recent low surgical risk trials
Among 1,000 low surgical risk patients who were randomised to the balloon-expandable Sapien 3 valve (Edwards Lifesciences) or to SAVR in the PARTNER 3 trial, those undergoing TAVI demonstrated superiority at two years with respect to stroke rates at 30 days (0.6% vs. 2.4%, p=0.02) and mortality at one year (1% vs. 2.5%, p=0.001), with a similar permanent pacemaker implantation (PPI) rate and lower hospital length-of-stay (three vs. seven days) for both procedures.1 The CoreValve low surgical risk trial randomizsed 1,468 patients to receive either the Medtronic Evolut-R/Evolut-Pro self-expanding TAVI platform or routine surgery. Similar outcomes were noted to those found in the Partner 3 trial, including for stroke (0.5% vs. 1.7%) and mortality (4.5% vs. 4.5%). However, there was a higher rate of PPI among the TAVR group (17.4% vs. 6.1%), consistent with previous trials of the self-expanding valve platform. Given these robust data, patients and physicians eagerly anticipate FDA approval of TAVI for this low-risk group of patients. But some issues are still to be cleared up.
Stroke risk in TAVI vs. SAVR
Unfortunately, all patients undergoing cardiac procedures have an inherent risk of embolic stroke. Though initial trials of TAVI compared to SAVR questioned whether there was a higher risk of stroke with TAVI among high surgical-risk patients, longer-term follow-up proved that this was not the case; the more recent trials among medium and low surgical risk patients have shown that stroke risk is in fact lower with TAVI. Nevertheless—and despite improvements in devices and operator experience, and a changing patient risk profile—stroke rates have not really declined for TAVI or SAVR and therefore remain clinically relevant.
In SAVR, the stroke risk is directly related to cross-clamping the aorta, and therefore it cannot be further reduced beyond that brought about through careful aorta manipulation and haemodynamic management; in TAVR, it can be mitigated by the use of cerebral embolic protection (CEP) filters. Though many CEPs are currently under clinical trial, the Sentinel device (Boston Scientific) is the only one that is approved by the FDA for use during TAVI. Various clinical trials, single-centre experiences, and meta-analyses have demonstrated a consistent 60–80% relative risk reduction in stroke when using this device, in comparison to “unprotected” TAVI.3 Meta-analyses have also shown a reduction in magnetic resonance imaging (MRI) detected brain lesions without clinically apparent stroke; whether this may exert a long-term influence on “silent-infarct” related cognitive decline has yet to be determined.
Valve durability and leaflet thrombus
Though recent reports of valve leaflet thrombus of TAVI prosthetics have appropriately raised concerns, it is important to realise that the clinical ramifications of this are, as yet, unclear.4 In fact, these papers have led to an increased recognition of leaflet thrombus among surgical valves, further complicating our understanding. Although available data suggest that leaflet thrombosis is may be higher with TAVR valves than with surgical valves, well-conducted head-to-head comparisons are not available.
What is known is that among randomised trials of TAVR vs SAVR there is no clinical signal of early valve degeneration of TAVI prosthetics, (CITE PARTNER DATA) and in fact some reports have even suggested an earlier deterioration of SAVR valves.5,6 The computed tomography (CT) substudies of the low surgical risk trials will provide important data about the true incidence of leaflet thrombus in transcatheter and surgical valves, as well as the clinical consequences. Long-term follow-up is also needed for thorough risk–benefit assessment of TAVR versus SAVR.
It is important to understand that the excellent results achieved for TAVI in the low surgical risk trials have been achieved at centres that have high TAVI volume and experienced operators, and they were obtained following a thorough evaluation of patients’ anatomic and clinical suitability. If patients are to receive the ideal treatment all of these factors must remain consistent.
Patients with other cardiovascular pathologies, such as mitral regurgitation, severe coronary artery disease, and aortic aneurysm, should be considered for complete surgical correction. Simply offering TAVI at every opportunity will not provide optimal results.7 Furthermore, a detailed imaging analysis (preferably by the operators and performing sites) to understand anatomic feasibility, valve choice, and facility with techniquespotential needs for “bailout” when necessary (that is, in the case of threatened coronary compromise, vascular complication, or annular trauma) is imperative if these exemplary results are to be maintained. This is important not only in the performance of TAVI, but also to identify those patients—low-risk or otherwise—who would be better suited to traditional SAVR.
1. Mack MJ, et al. Transcatheter aortic valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med 2019; 380(18): 1695–1705.
2. Popma JJ, et al. Transcatheter aortic valve replacement with a self-expanding valve in low risk patients. N Engl J Med 2019; 380(18): 1706–15.
3. Seeger J, et al. Rate of peri-procedural stroke observed with cerebral embolic protection during transcatheter aortic valve replacement: a patient-level propensity-matched analysis. Eur Heart J 2019; 40(17): 1334–40.
4. Makkar RR, et al. Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N Engl J Med 2015; 373(21): 2015–24.
5. Daubert MA, et al. Long-term valve performance of TAVR and SAVR: a report from the PARTNER I trial. JACC: Cardiovasc Imaging 2016.
6. Sondergaard L, et al. Durability of transcatheter and surgical bioprosthetic aortic valves in patients at lower surgical risk. J Am Coll Cardiol 2019; 73(5): 546–53.
7. Vemulapalli S, et al. Procedural volume and outcomes for transcatheter aortic valve replacement. N Engl J Med 2019.
Amar Krishnaswamy and low-risk are at the Cleveland Clinic, Ohio, USA.