Author + information
- aDepartment of Cardiac Surgery, Heart Hospital Baylor, Plano, Texas
- bDepartment of Cardiac Surgery, Baylor Scott and White Health, Dallas, Texas
- ↵∗Address for correspondence:
Dr. Michael Mack, Baylor Scott and White Health, 1100 Allied Drive, Plano, Texas 75075.
Transcatheter mitral valve (MV) repair and replacement (TMVR) are following rapidly on the heels of transcatheter aortic valve replacement (TAVR). However, there are some significant differences between the 2 treatments that serve to set different expectations. Whereas TAVR essentially treats 1 disease, calcific aortic stenosis, with 2 options, balloon-expandable or self-expanding valves, the causes of mitral regurgitation (MR) are multiple and the potential solutions consequentially are much more complex and diverse. There are at least 30 medical devices in various stages of development with the goal of either repairing or replacing the MV by a transcatheter approach.
MR can be divided generally into 2 categories, primary (degenerative) and secondary (functional). Primary MR is due to an abnormality of either or both mitral leaflets, usually either prolapse or flail cords, most commonly of the mid portion (P2) of the posterior leaflet. Optimal surgical treatment of primary MR is a repair involving either resection of the diseased segment with reconstruction or increasingly by replacement of the elongated or ruptured cords with artificial cords of expanded polytetrafluoroethylene (ePTFE). A partial or complete annuloplasty is also usually performed to correct the accompanying annular dilation.
Devices to correct primary MR by a transcatheter approach are also directed specifically at the leaflets. The first and only commercially approved device in the United States, the MitraClip device (Abbott Vascular, Santa Clara, California) replicates the surgical technique of Alfieri by using a metallic clip to perform an “edge to edge” approximation of the abnormal leaflet to its counterpart on the opposite leaflet. As of early 2017, >9,200 patients with primary MR had been treated with this approach in the United States (1). There are now 2 additional devices with clinical human experience in primary MR that attempt to replicate the surgical technique of MV reconstruction using ePTFE artificial cords. The first device in this class, Neochord (Neochord, Minneapolis, Minnesota) has a moderate clinical experience and is now conducting a randomized, pivotal trial in the United States, comparing TMVR with artificial cords with conventional MV repair (2,3). A report of the early experience with the second device, the Harpoon Mitral Valve Repair System (Harpoon Medical, Baltimore, Maryland) is contained in this issue of the Journal (4).
Gammie et al. (4) report the 6-month results of 30 patients treated in 6 centers in a regulatory approval trial in Europe. This follows a first-in-human experience in 11 patients treated with this device that was previously reported (5). The patients treated were low-risk surgical candidates whose mean age was 61 years, and 77% of them were male with a mean Society of Thoracic Surgery Predicted Risk of Mortality of 0.69% with normal left ventricular function. Of note is that 30% of patients were in atrial fibrillation pre-operatively. There was no mortality, stroke, nor need for permanent pacemaker, although 2 patients were converted to conventional MV surgery during the procedure.
There are some definite positive outcomes in this series of patients, but also some concerns and perhaps even some surprises. On the positive side, Gammie et al. (4) have demonstrated that it is feasible to routinely perform a MV repair on a beating heart under physiologic conditions without cardiopulmonary support or cardiac arrest. This allowed them to assess the adequacy of the repair in real time under normal loading conditions, which offers a distinct advantage compared with conventional surgery. Surgical MV repair uses pressurized saline testing at completion of the repair on an arrested, flaccid heart with echocardiographic assessment possible only after weaning from cardiopulmonary bypass. The investigators have also demonstrated that the procedure is quite safe with no mortality, stroke, or major complications. However, 3 patients (10%) were converted to surgery, 2 intraoperatively and 1 on day 27, and these were considered serious adverse events in the trial.
Some additional concerns have to be raised regarding the efficacy of the procedure. This was a low-risk patient population with isolated P2 prolapse that if treated surgically has a >95% successful repair rate in valve reference centers (6). In this series, by 6 months post-procedure, only 22 of 30 (73%) of patients had mild or lesser degree MR without conversion to surgery. This included the 3 patients converted to surgery. A fourth patient not included in the 6-month primary efficacy endpoint also required conversion to surgery at 8 months. At 6 months, 4 patients (13%) had an unacceptable repair result with severe (n = 2) or moderate (n = 2) residual MR. It should also be noted that the procedure is presently performed via a transapical approach through a left anterior thoracotomy and is heavily dependent on advanced transesophageal echocardiographic imaging with 2 patients having an inadequate result due to poor imaging quality. These patients were highly selected patients with only 1 of 3 screened patients enrolled in the trial.
There are also some intriguing outcomes in this series that need further study and confirmation. A standard surgical operation in these patients would have included an annuloplasty in all patients with either a partial band or complete ring to correct the accompanying annular dilation and a Maze procedure in the 9 patients who were in pre-operative atrial fibrillation (AF). Despite no annuloplasty being performed in these patients, there was a significant decrease in the mean anterior posterior mitral annular diameter and mean mitral annular area. It is important to know whether patients with concomitant annular dilation were excluded from the trial before any conclusions can be drawn about this. Further information as to whether annular remodeling occurred in all patients by individual patient reporting especially those with most annular dilation is also important to know. It is also noteworthy that there was very little post-operative AF (10%), and all 9 patients who were in pre-operative AF were in sinus rhythm at 30 days without an ablative procedure. However, we do not have enough information regarding the AF (paroxysmal vs. persistent, duration, atrial size, etc.) nor the method of follow-up (single electrocardiogram or event monitoring) to judge the meaning of this outcome. These results do raise questions of whether an annuloplasty and AF ablation, current standards in surgical mitral valve repair, will be routinely necessary.
There are a number of further interesting questions and concerns to be addressed about this therapy:
1. The investigators stated that 2 failures were due to poor imaging quality (4). Clearly, excellence in imaging including 3-dimensional and X-plane echocardiography with experienced imaging specialists is necessary for any catheter-based MV procedure. One wonders why this was not identified before the procedure and should serve as a cautionary note going forward.
2. Is the repair durable long term especially with no annular support?
3. What are the endpoints of a pivotal trial of this technique, presuming that standard surgery is the comparator in a low-risk population or perhaps MitraClip in a higher risk study cohort? Clearly the study arm of a pivotal trial will need to have better results if they are to be compared with those of low-risk surgical patients.
4. Can this procedure be converted to a totally percutaneous approach either transapically as is done with paravalvular leak closure in some centers or optimally by a transvenous, transseptal approach? We must be circumspect about trading a small right thoracotomy, albeit with cardiopulmonary bypass, for surgical MV repair that restores normal life expectancy to patients for a left thoracotomy with unknown durability especially in low surgical risk patients.
5. Can this technique be combined with other transcatheter techniques such as transcatheter annuloplasty to completely replicate standard surgical techniques?
6. The other interesting question raised by this study is the patient population chosen to study a first-in-man/early feasibility use of a new device. Most new devices are introduced into clinical patients in compassionate-use cases or high-risk patients in which there are not great treatment options. The choice of a study population here in which patients reliably do well with standard surgical therapy must be questioned. The goals of this therapy, which are to produce a less invasive, more reproducible treatment of MR, are laudable. However, does the end justify the means? One wonders whether the more appropriate study population be those high surgical risk patients currently being treated with MitraClip. Although the safety of MitraClip is unquestioned, the efficacy of MR correction can be improved. This therapy may prove to be more efficacious and consideration should be given to a comparison trial with MitraClip, the current treatment standard in the prohibitive surgical risk patient population.
In summary, TMVR is not TAVR redux. The problem is more complicated to address and the solutions are more diverse and complex. The challenges will be greater and the road steeper. Is transcatheter placement of artificial cords another step forward along that road? Only time and more experience will tell.
↵∗ 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. Mack is a coprincipal investigator for research trials for Edwards Lifesciences, Medtronic, and Abbott Vascular. Dr. Smith is a coprincipal investigator for research trials for Edwards Lifesciences; and is a consultant to Edwards Lifesciences and Abbott Vascular.
- 2018 American College of Cardiology Foundation
- Sorajja P.,
- Vemulapalli S.,
- Feldman T.,
- et al.
- Seeburger J.,
- Rinaldi M.,
- Nielsen S.L.,
- et al.
- Gammie J.S.,
- Bartus K.,
- Gackowski A.,
- et al.
- Gammie J.S.,
- Wilson P.,
- Bartus K.,
- et al.
- Bonow R.,
- Adams D.