Author + information
- Saibal Kar, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Saibal Kar, Heart Institute, Cedars-Sinai Medical Center, 8631 West 3rd Street, Suite 415E, Los Angeles, California 90048.
Significant mitral regurgitation (MR) is one of the most common heart valve disorders in the United States (1). If left untreated it leads to progressive left ventricular dysfunction, heart failure, and death. The two most common causes of MR are due to degenerative or functional etiologies. Degenerative MR occurs as a result of prolapse or flail of one or more segments of the mitral leaflets due to a primary degenerative process, whereas functional MR results from malcoaptation of leaflets caused by localized or generalized dysfunction/scarring of the left ventricle. Although surgical repair or replacement is the established treatment for degenerative MR, this does not hold true for functional MR. Additionally, there are patients in whom the associated comorbidities or left ventricular dysfunction put them at very high surgical risk. Therefore a need exists for less invasive, safer options for selected patients with significant MR.
The MitraClip device (Abbott Vascular, Santa Clara, California) is one such novel transcatheter treatment option (Fig. 1). This technology is adapted from a surgical repair pioneered by Alfieri et al. (2). The procedure involves a transvenous transseptal deployment of one or more clips at the site of maximal malcoaptation of leaflets, converting an incompetent single-orifice valve into a competent double-orifice valve. The procedure is an echo-guided transvenous procedure performed in a beating heart, and the clip itself is retrievable and repositionable. These features contribute to the safety of the device and procedure. Moreover, the lack of need for large bore arterial sheaths and contrast media minimize vascular or renal complications. While several critics have questioned the durability of the MitraClip procedure in the absence of the use of an annuloplasty ring, the preservation of the contractile function of the annulus may have a benefit, which is yet to be proven. The device was systematically evaluated in a series of prospective studies in the United States (3,4), before being made commercially available in Europe in 2008. The device is commercially available in 40 countries; it is still investigational in the United States. More than 10,000 patients have been treated throughout the world, with 1,200 patients having participated in clinical trials in the United States. The predominant usage in a commercial setting is high-surgical-risk patients with functional MR.
In this issue of the Journal, Maisano et al. (5) report the early and 1-year results of the MitraClip therapy (ACCESS-EU, prospective, multicenter, nonrandomized post-market approval study) in Europe. The ACCESS-EU study is unique in that it is the largest reported cohort of the use of the MitraClip device in a real-world setting. As expected most of the patients treated in this cohort were high-surgical-risk MR patients, primarily due to functional etiology.
This study reconfirms the relative safety of this complex procedure in a high-risk population in a commercial setting with experienced operators. The site reported 30-day mortality rate of 3.4% and stroke rate of 0.7%, with no cases of intra-procedural deaths or clip embolization—definitely superior to that observed in other contemporary transcatheter valve therapy studies (6–9) (Table 1). Single leaflet detachment incidence of 4.8% is still an issue, although reduced in time with experience and better case selection. In the absence of a control population the investigators demonstrated the efficacy of the procedure by comparing the clinical outcomes before and after the procedure. At 1-year the majority of patients demonstrated an improvement of functional class, 6-min walk test, and sustained reduction of MR. Mortality benefit could not be ascertained in the absence of a prospective well-matched control group. While mortality is an important endpoint, one can argue that in high-risk patient populations with multiple comorbidities, enhancement of a quality of life is a valid and important objective of therapy (10). The ACCESS-EU study demonstrated this point.
The patient population studied in the cohort is similar to the EVEREST II (Endovascular Valve Edge-to-edge REpair STudy II) Integrated high-surgical-risk cohort that was recently presented at the U.S. Food and Drug Administration (FDA) panel and the American College of Cardiology conference (9). All data for this study was adjudicated, and the echocardiographic parameters were analyzed by an independent core laboratory. The low peri-procedural complication rate and significant improvement of functional class and MR at 1 year in EVEREST II Integrated High surgical Cohort are very similar to that reported by Maisano et al. (5).
While providing meaningful data in support of the MitraClip therapy, the ACCESS-EU data has important limitations. The data lacks the vigor of a well-conducted controlled trial where blinded and independent reviewers conduct all clinical adjudication and imaging data is analyzed by an unaffiliated core laboratory. Echocardiographic data presented in this article are consistent with the real-world as reported in most surgical series. Finally, although the data suggest that there was an improvement of symptoms, in the absence of a control group, it is impossible to ascertain whether there was mortality benefit from this procedure. Reduction of mortality, though of course highly desirable ought not to be the sole metric upon, which such procedures are evaluated. Durable functional improvement is sufficient to justify intervention in carefully selected high-risk patients deemed poor candidates for surgery.
The MitraClip device is the only percutaneous approach that is applicable for selected patients with both degenerative and functional MR. Although surgery is helpful in some cases, most cases of functional MR are treated with medications. The COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Patients) and RESHAPE (Randomized Study of the MitraClip Device in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation) trials have been designed to evaluate the MitraClip therapy in functional MR, where surgery is not indicated. At the same time, for patients with degenerative MR, where surgery is the gold standard, it would be unethical and unrealistic to conduct a randomized study comparing MitraClip with medical treatment in patients too high risk for surgery. Randomized studies comparing surgery with MitraClip for moderate surgical risk degenerative MR patients similar to the ongoing PARTNER (Placement of AoRTic TraNscathetER Valves) IIA and SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trials in aortic stenosis are warranted in the future.
Ten years have elapsed since the first clip was successfully placed in a human; we still await approval in the United States. The members of the recently conducted FDA advisory panel unanimously agreed on the safety and voted 5 - 3 in favor of the device, saying that the benefits outweighed the risks for use of the MitraClip in symptomatic significant MR in patients who have been determined by a cardiac surgeon to be too high risk for open mitral valve surgery and in whom existing comorbidities would not preclude the expected benefit from correction of the MR. One can only hope that the data from the ACCESS-EU study will lend further credence to FDA approval of this life enhancing if not yet proven life extending technology.
The MitraClip procedure is a technological tour-de-force and it has an impeccable safety record when performed by competent operators. It improves valvular regurgitation and patient well-being. To be sure, patients with primary and functional MR must be carefully selected before their candidacy is established. The data set available to us is far from complete and we shall continue to learn as more data from controlled clinical trials becomes available. Like all devices, the MitraClip is undergoing both physician and community learning curves. Nonetheless, the body of data and experience would seem to mandate that the United States join several other nations around the world and permit the use of this important tool in those patients who are too high risk for surgery and have exhausted all other medical options. For this subset of patients the MitraClip has added life to years in most and even years to their lives to some.
↵∗ 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. Kar has served as consultant to and is a recipient of research grants from Abbott Vascular and Boston Scientific; and has received research grants from St. Jude Medical.
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