Author + information
- Published online December 17, 2018.
- Philippe Pibarot, DVM, PhD∗ ()
- Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart & Lung Institute, Department of Medicine, Laval University, Québec, Canada
- ↵∗Address for correspondence:
Dr. Philippe Pibarot, Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Sainte-Foy, Québec G1V-4G5, Canada.
The objective of aortic valve replacement (AVR) is to replace a native aortic valve with severe dysfunction with a prosthetic valve that ideally has no residual stenosis or regurgitation. However, a substantial proportion of patients undergoing AVR have high residual transprosthetic pressure gradients due to prosthesis–patient mismatch (PPM), and a large proportion of those undergoing transcatheter AVR (TAVR) have some degree of paravalvular aortic regurgitation (PVR). The indication of TAVR is expanding to lower-risk patients, and in such a population, the optimization of valve hemodynamic performance and durability is essential. In this issue of JACC: Cardiovascular Interventions, Abdelghani et al. (1) compared the valve hemodynamic performance of the second versus the third generations of self-expanding (SE) and balloon-expandable (BE) transcatheter heart valves (THVs) according to the size of the aortic annulus (small vs. large) in the cohorts of patients included in the randomized CHOICE (A Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis) trial (N = 241) and nonrandomized CHOICE-Extend registry (N = 434) (Figure 1). The rate of PPM and ensuing residual transvalvular gradient were lower in SE than in BE valves, regardless of the generation or the annulus size. The second-generation BE THV (SAPIEN XT) was associated with a lower rate of PVR compared with SE THV (CoreValve, Medtronic, Minneapolis, Minnesota) in the patients with a large aortic valve annulus, but not in those with a small annulus. With the use of the third generation, the rate of PVR decreased markedly in both SE (Evolut R, Medtronic) and BE (SAPIEN 3, Edwards Lifesciences, Irvine, California) THVs, particularly in the patients with a large annulus (Figure 1).
Valve Hemodynamic Performance of TAVR vs. SAVR
In a pioneer study published in 2009, Clavel et al. (2) reported that TAVR with the first generation of BE SAPIEN THV was associated with a lower rate of severe PPM and lower residual gradients but higher rate of PVR compared with surgical AVR (SAVR) with a stented or stentless bioprosthesis. Several randomized trials then subsequently confirmed that TAVR is associated with more PVR but larger effective orifice areas (EOAs), lower gradients, and less PPM compared with SAVR, and these differences (both for PVR and PPM) appeared to be more pronounced with SE than with BE TAVR (3,4). However, in a post hoc analysis of the PARTNER 1A (Placement of AoRTic TraNscathetER Valve) trial conducted by Rodés-Cabau et al. (5), the difference in the rate of PVR between TAVR versus SAVR was small and not statistically significant in the patients with a small aortic annulus, whereas the rate of severe PPM was much lower with TAVR versus SAVR in this subset. On the other hand, the rate of PVR was much higher and the difference in PPM smaller with TAVR versus SAVR in the subset of patients with a large aortic annulus. There was also a trend for better survival with TAVR versus SAVR in patients with a small aortic annulus and vice versa in those with a large annulus. The third generation of BE (SAPIEN 3) and SE (Evolut R) THVs harbors new features aiming at improving the sealing between the stent and aortic annulus. This modification in the valve design, along with optimization of valve sizing and positioning, contributed to a marked reduction in the incidence of PVR compared to the previous generation of THVs (Figure 1). In the SAPIEN valves family, the rate of moderate/severe PVR was reduced by ∼4-fold (from 12% to 13%, to 3% to 4%) with the SAPIEN 3 (third generation) versus the SAPIEN (first generation) (6–8). However, on the other hand, the SAPIEN 3 exhibited somewhat smaller EOAs, higher gradients, and slightly more PPM compared with the previous generation (1,6,7). This may be attributable to the addition of a subannular cuff that reduces the risk of PVR in the SAPIEN 3 but may, on the other hand, somewhat decrease the EOA.
Valve Hemodynamic Performance of BE Versus SE THVs
In cohorts of patients with first-generation THVs matched for aortic annulus size, Nombela-Franco et al. (9) found that the CoreValve was associated with more PVR but, in contrast, less PPM and residual gradients compared with the SAPIEN THV. The CHOICE trial then subsequently confirmed and expanded these findings in a randomized comparison of CoreValve versus SAPIEN XT using both Doppler echocardiography and magnetic resonance imaging to assess PVR and PPM (10). In the elegant study by Abdelghani et al. (1) they provide an important additional piece of information on the CHOICE trial. They indeed report that the SAPIEN XT is associated with less PVR than the CoreValve in patients with a large annulus, but not in those with a small annulus (Figure 1) (1). Furthermore, in the CHOICE-Extend registry that assessed the hemodynamic performance of the third generation of THVs, the rate of PVR was markedly reduced compared with the second generation and did not significantly differ between SAPIEN 3 versus Evolut R, regardless of the annulus size (Figure 1). On the other hand, the rates of PPM appeared to be higher in the third versus second generations of THVs, especially in BE valves. The rate of PPM was indeed ∼2-fold higher in the SAPIEN 3 versus the Evolut R in both small and large annulus categories (Figure 1). These findings suggest that the type and generation of THV as well as the size of the patient’s aortic annulus are the main factors determining the incidence of PVR and PPM following TAVR. However, other factors such as the aortic valve calcium burden may also have an impact on the hemodynamic outcomes of TAVR.
Definition, Predictors, and Impact on Outcomes of PVR and PPM
One of the mechanisms proposed to explain the higher rate of PVR observed in the SE versus BE THVs is that the stent of the SE valves has lower radial force and may thus have greater propensity for underexpansion and noncircular/irregular deployment (11). Furthermore, several patient-related factors may increase the risk of PVR, regardless of the type of TVH, including: 1) large aortic annulus size because there is a longer annulus circumference that needs to be covered and sealed by the THV stent; and 2) the burden and distribution of aortic valve/annulus calcification because this can cause deformation and lack of sealing at the stent-annulus interface. These 2 factors appear to have a more pronounced impact on the shape of the THV stent and thus on the occurrence of PVR in SE versus BE valves (11). With the introduction of new-generation THVs harboring features that improve the stent–annulus sealing, the difference in the rate of PVR between SE and BE THVs has shrunk even in the subset of patients with unfavorable aortic annulus size and morphology (Figure 1).
PPM is usually defined on the basis of the prosthetic valve EOA measured by Doppler echocardiography (continuity equation method) and indexed to the patient’s body surface area. PPM is considered absent or not clinically significant when the indexed EOA is >0.85 cm2/m2, moderate when it is between 0.66 and 0.85 cm2/m2, and severe when ≤0.65 cm2/m2 (12); and this is the definition that has been used in the CHOICE trial (1). However, given that the indexed EOA may lead to an overestimation of PPM in obese patients, recent recommendations suggest using lower cutoff values of indexed EOA when a patient’s body mass index is ≥30 kg/m2 (0.70 to 0.56 cm2/m2 for moderate PPM, and ≤0.55 cm2/m2 for severe PPM) (12). The definition of PPM used in the present paper on the CHOICE trial (1) did not account for obesity, which may have resulted in an overestimation of the true rate of PPM, particularly in the BE registry group, which appeared to have a somewhat larger body mass index compared with the SE registry group. The main factor responsible for the lower rate of PPM and high residual gradients in the SE versus BE THVs is believed to be the supra-annular position of the neonative valve leaflets within the stent of the CoreValve or Evolut R. In the BE valves, the stent is short and cylindrical, and the leaflets are positioned at the annular level. In SE valves, the stent has an hourglass shape, and the internal stent orifice area and valve EOA are therefore larger at the supra-annular level than at the annular level. With the third-generation THVs, the addition of a sealing cuff outside of the stent has resulted in a slight decrease in EOA compared with the previous-generation THVs (Figure 1) (1). Although this small deterioration in forward valve hemodynamics occurred in both SE and BE THVs of the third generation, it appeared to be somewhat more pronounced in BE versus SE valves.
The study of Abdelghani et al. (1) has significant limitations, one the most important being that the CHOICE-Extend registry, which compared the hemodynamic performance of third-generation SE versus. BE THVs, was not randomized. As a matter of fact, patients who received the SAPIEN 3 in this registry had on average a smaller indexed aortic annulus and larger aortic valve calcification burden compared with those receiving an Evolut R. These differences in the patients’ baseline characteristics may have biased the comparison of BE versus SE with regard to the rates of PVR and PPM. Furthermore, in the CHOICE trial and Extend registry, the echocardiographic and cardiac magnetic resonance imaging data were site-reported, and there were no centralized analyses in core laboratories.
Besides the incidence of PVR and PPM, it is also important to consider the impact of these complications on clinical outcomes. According to meta-analyses, the presence of at least moderate PVR after TAVR is associated with a 2- to 2.5-fold increase in mortality, whereas moderate PPM and severe PPM are associated with a 1.2- and 1.8-fold increase in the risk in mortality, respectively, following SAVR or TAVR (3,8,13). Hence, for a given degree of severity, PVR appears to have a greater impact than PPM on clinical outcomes. This may be explained by the fact that patients undergoing TAVR generally have severe aortic stenosis and their left ventricle is thus adapted to pressure overload, but not to volume overload. Hence, the acute onset of an aortic regurgitation may have more detrimental impact on LV function, pulmonary circulation and outcomes than a high residual gradient related to PPM. In the selection of a type of THV for TAVR, it thus appears logical to prioritize the prevention of moderate/severe PVR before that of PPM, especially in patients being at risk for PVR following TAVR (e.g., patients with a large, noncircular, and/or heavily calcified aortic annulus).
Conclusions and Clinical Perspectives
Rather than attempting to generalize a given type (SE or BE) of THV to all patients undergoing TAVR, it might be preferable to balance the pros and cons of each type of THV and to individualize the valve selection process according to the morphology and size of the patient’s aortic annulus. In patients with a small aortic annulus, as well as in those with small, degenerated surgical bioprostheses, a SE THV of third generation should probably be preferred for TAVR or a valve-in-valve procedure. On the other hand, in patients with a larger annulus and/or large/bulky/asymmetric aortic annulus/valve calcification, a BE of third generation should be considered.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Pibarot is the Canada Research Chair in Valvular Heart Disease; his research program is funded by the Canadian Institutes of Health Research (grant FDN-143225), Ottawa, Ontario, Canada. Dr. Pibarot has received research grants from Edwards Lifesciences and Medtronic for echocardiography core laboratory analyses in transcatheter heart valves.
- 2018 American College of Cardiology Foundation
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