Author + information
- Josep Rodés-Cabau, MD∗ ()
- ↵∗Address for correspondence:
Dr. Josep Rodés-Cabau, Quebec Heart and Lung Institute, Laval University, 2725 chemin Ste-Foy, G1V 4G5, Quebec City, Quebec, Canada.
Several transcatheter mitral valve repair technologies have emerged over the last decade as an alternative to surgery for the treatment of mitral regurgitation (MR) in patients at high or prohibitive surgical risk (1). The MitraClip device (Abbott Vascular, Santa Clara, California), which consists of an edge-to-edge leaflet repair, is the most common transcatheter mitral valve repair technology used worldwide and the only one approved by the U.S. Food and Drug Administration to date. The use of the MitraClip device has been associated with high rates of significant reductions in MR, with a low incidence of safety issues (1,2). However, not all cases of MR are addressable by this therapy, and the rates of at least moderate residual MR are >10% (1,2). More recently, transcatheter mitral valve replacement (TMVR) has appeared as another less invasive alternative to surgery for treating MR (3). Up to 9 TMVR devices have already been used in humans, and at least 5 are in preclinical development (3). The Intrepid TMVR system (Medtronic plc, Dublin, Ireland) consists of a tri-leaflet bovine pericardial valve contained in a self-expanding nitinol frame with 3 leaflets of bovine pericardium that are inserted through the transapical approach by using a 35-F access sheath. The valve has an outer fixation frame (43, 46, or 50 mm) and an inner stent frame (27 mm), and valve anchoring is achieved by oversizing/radial force along with specific design features of the stent frame to fix the valve in the subannular space.
In this issue of the Journal, Bapat et al. (4) have reported the results of the initial experience with the Intrepid TMVR system. Of 166 patients screened, a total of 50 patients were finally included, with a mean age of 73 ± 9 years; 58% were men, and patients had a mean Society of Thoracic Surgery Predicted Risk of Mortality score of 6.4 ± 5.5%. Patients were considered at high or extreme surgical risk by the local heart team; the predominant mechanism of MR was secondary in most patients (>80%); and the mean left ventricular ejection fraction (LVEF) was 43 ± 12%. Forty-eight patients (96%) underwent successful valve implantation; bleeding issues during apical access (n = 1) and valve undersizing leading to malpositioning (n = 1) were the reasons for unsuccessful valve implantation. Although there were no acute conversions to open heart surgery, 8 patients (16%) required hemodynamic support with an intra-aortic balloon pump or extracorporeal membrane oxygenation. Valve function was appropriate in all patients, with no cases of moderate to severe residual MR (none/trace and mild in 76% and 24% of patients, respectively), a mean transvalvular gradient of 4 ± 1 mm Hg, and no left ventricular outflow tract (LVOT) obstruction. The 30-day mortality and stroke rates were 14% and 4%. The 7 cases of early mortality were related to apical bleeding issues (n = 3), device malpositioning (n = 1), or post-operative heart failure (n = 3). At a mean follow-up of approximately 6 months, 4 more patients died (sudden death in 3 patients, and intracranial hemorrhage in 1 patient), leading to a total mortality rate of 22%. There were no cases of valve malfunction, thrombosis, or embolization, and most patients had improved their functional class at follow-up.
These results support the feasibility of TMVR with the Intrepid valve. However, they should be put into perspective from patient selection to procedural results, valve performance, and early to midterm outcomes.
1. Patient selection. The clinical characteristics of the patients included in this study are similar to those in other previous TMVR studies (3), with most patients exhibiting a low left ventricular ejection fraction (LVEF) and MR of secondary origin. Whereas treating secondary MR in patients with heart failure has been associated with improvements in functional status and quality of life in observational studies/registries, no randomized studies to date have shown the benefit of mitral valve repair/replacement in such patients (1). Up to 3 randomized trials comparing optimal medical treatment versus repair with the MitraClip device are ongoing and will shed some light on the treatment of secondary MR in the coming years. Also, the fact that approximately two-thirds of the patients screened were excluded, mainly for anatomical reasons, highlights some of the limitations of current TMVR platforms as well as the need for a greater variety of valve sizes.
2. Procedural and 30-day outcomes. The very high rate of successful valve implantation, with no cases of valve embolization, reflects both the good anchoring properties of the valve system and the accuracy of the patient selection process. Pre-procedural computed tomography imaging allows a precise 3-dimensional evaluation of the mitral valve apparatus and its spatial relationship to surrounding structures (e.g., LVOT) and would seem to be mandatory in the proper anatomical evaluation of TMVR candidates (3). This requirement has probably contributed to the lack of cases of LVOT obstruction in this series (a significant number of patients were excluded due to a higher risk of LVOT obstruction), along with the characteristics of the valve (low profile, with a device length <20 mm). LVOT obstruction is one of the most important potential complications of TMVR procedures, and future studies need to better define the cutoff values (LVOT diameter/area, angle) determining a higher risk.
The 30-day mortality rate was high (14%) and exceeded the risk estimated according to the Society of Thoracic Surgery Predicted Risk of Mortality score (approximately 6%) (4). Although this outcome may be partially related to the learning curve process, the causes of early mortality merit some consideration. Importantly, only 1 death seemed to be directly related to the device (malpositioning). Up to 3 deaths (6%) were secondary to apical hemostasis issues. This finding reflects the known limitations of this approach, especially with the use of large bore catheters (35-F), and highlights the importance of both reducing the sheath size and developing TMVR systems that can be implanted through the transfemoral venous approach. This has been a challenge considering the need for a high-profile delivery system that needs to negotiate an extreme angle within a relatively small space to reach the mitral valve. This is likely the reason why most TMVR systems developed to date are implanted by using a transapical approach, which is a much more direct method for the mitral valve (3). Currently, only 2 TMVR systems have been implanted transfemorally (CardiAQ, Edwards Lifesciences, Irvine, California; Caisson, LivaNova, London, United Kingdom), and future engineering efforts are necessary to increase and simplify transfemoral TMVR procedures.
Three additional patients (6%) died within the 3 weeks after TMVR due to heart failure decompensation (4). It has been shown that a higher degree of myocardial injury is associated with transapical procedures (5), which may be particularly deleterious in patients with low LVEF. In addition, the acute reduction of the volume overload in patients with significant MR and reduced LVEF may be associated with a temporary reduction in LVEF, and this finding may have contributed to heart failure decompensation post-operatively (6). Careful patient selection, probably avoiding those patients with very low (<30%) LVEF (particularly in the presence of limited coronary reserve), might play a major role in improving results in the future. This may also contribute to better procedural hemodynamic tolerance, with lower requirements for mechanical hemodynamic support.
3. Valve performance. The absence of moderate-to-severe residual mitral regurgitation or significant transvalvular gradient in all cases reflects a high degree of optimal valve performance. This outcome is consistent with the results obtained by other TMVR systems and seems to be close to the results obtained after standard surgical mitral valve repair/replacement and superior to those obtained by transcatheter mitral valve repair systems (including MitraClip) (1–3). Future studies will need to evaluate whether these improved results regarding valve performance compensate for the higher rate of early safety issues associated with TMVR compared with repair.
4. Midterm outcomes. The absence of valve dysfunction or thrombosis after a mean follow-up of 6 months is reassuring. Valve thrombosis has been an issue after TMVR, and strict anticoagulation therapy (in addition to antiplatelet therapy) seems to play an important preventive role in such cases. In addition, valve durability remains an important unresolved aspect of TMVR. TMVR is a young technology, and few data exist on the long-term hemodynamic performance of these valve systems. Recently, Regueiro et al. (7) reported the absence of valve degeneration at 2-year follow-up after TMVR with the Fortis valve (Edwards Lifesciences, Irvine, California) in a small series of patients. We will need a close follow-up of these patients to obtain longer term valve hemodynamic data in a larger population.
TMVR has emerged as an alternative treatment for MR in patients at high or extreme surgical risk. The results of this initial experience (4) with the Intrepid valve reflect the main potential advantages and limitations of TMVR technology, with a high rate of successful valve implantation and optimal valve performance, and relatively high periprocedural mortality and complication rates. These findings may be partially related to the approach (transapical), learning curve, and patient selection process (co-morbidities + secondary MR with low LVEF). Also, the technology seems to be currently limited to a small proportion of patients with MR, mainly due to anatomical issues and valve size availability. TMVR technology will undoubtedly evolve, and peri-procedural complications will be reduced with increasing experience and improved device and delivery system iterations. The ongoing prospective randomized APOLLO trial (NCT03242642) compares standard mitral valve replacement versus TMVR with the Intrepid valve, with the primary endpoint of all-cause mortality, disabling stroke, reoperation (or reintervention) and cardiovascular hospitalization at 1-year follow-up. This trial will determine the role of TMVR as an alternative to standard valve replacement in patients with severe MR. Conversely, transcatheter mitral valve repair has been associated with higher rates of residual MR but a much better safety profile, which may be very important in the high-risk group of patients selected for transcatheter procedures to date. Also, improvements in transcatheter mitral valve repair technology and the possible combination of multiple techniques (annuloplasty + edge-to-edge repair) may be associated with improved results in the near future.
As has occurred in the surgical field, selecting transcatheter mitral repair or replacement will soon be a choice for the treatment of patients at high surgical risk. The 2 options will likely be complementary, considering the complexity and variability of mitral valve disease, and some patients will probably be better suited to TMVR (e.g., those with more advanced disease, greater leaflet tethering and annular dilation, with suboptimal anatomy for repair) and others to mitral repair. However, we may expect that moving toward the transcatheter treatment of low risk populations will take a longer time compared with the aortic valve field.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Rodés-Cabau has received institutional research grants from Edwards Lifesciences and Medtronic; and holds the Canadian Research Chair “Fondation Famille Jacques Lariviére” for the Development of Structural Heart Disease Interventions. Ted Feldman, MD, served as Guest Editor for this paper.
- 2018 American College of Cardiology Foundation
- Chiarito M.,
- Pagnesi M.,
- Martino E.A.,
- et al.
- Regueiro A.,
- Granada J.F.,
- Dagenais F.,
- Rodés-Cabau J.
- Bapat V.,
- Rajagopal V.,
- Meduri C.,
- et al.
- Ribeiro H.B.,
- Nombela-Franco L.,
- Munoz-Garcia A.J.,
- et al.
- Gaassch W.H.,
- Meyer T.E.
- Regueiro A.,
- Ye J.,
- Fam N.,
- et al.