Download Percutaneous Mitral Valve Repair

JACC: CARDIOVASCULAR INTERVENTIONS
VOL. 4, NO. 7, 2011
© 2011 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-8798/$36.00
PUBLISHED BY ELSEVIER INC.
DOI: 10.1016/j.jcin.2011.05.010
ACC INTERVENTIONAL SCIENTIFIC COUNCIL: NEWS AND VIEWS
Percutaneous Mitral Valve Repair
Lessons From the EVEREST II (Endovascular Valve Edge-to-Edge REpair Study)
and Beyond
Jon C. George, MD,* Vincent Varghese, DO,* George Dangas, MD, PHD,†
Ted E. Feldman, MD‡
Browns Mills, New Jersey; New York, New York; and Evanston, Illinois
The 24-month results of the EVEREST II (Endovascular Valve Edge-to-Edge REpair Study),
presented at the American College of Cardiology
2011 Scientific Sessions/i2 Summit and recently
published (1), investigating the safety and efficacy
of the MitraClip (Abbott Vascular, Santa Clara,
California) device, validated the interest in percutaneous approaches to the treatment of mitral
regurgitation (MR) compared with the current
gold standard, which is surgical mitral valve repair
or replacement (2). The MitraClip is a percutaneously inserted device that mimics the surgical
edge-to-edge repair developed by Dr. Ottavio
Alfieri in 1991, by attaching to the tips of the
anterior and posterior mitral leaflets, securing them
together to form a double-orifice mitral inlet, and
thereby reducing the amount of regurgitation (3).
Trial Results and Implications
The EVEREST II randomized 279 patients with
severe (3 to 4⫹) MR to percutaneous mitral valve
clip or open surgical valve repair or replacement.
Patients were followed for 30 days and 1 year with
primary endpoints of major adverse events and
clinical success rate, respectively. Clinical success
was defined as freedom from death, open mitral
valve repair or replacement, and improvement of at
least 2 grades of MR. At 30 days, there was a
significant reduction in the composite endpoint of
major adverse events (including death, myocardial
infarction, stroke, reoperation, blood transfusion, and
From the *Division of Interventional Cardiology and Endovascular
Medicine, Deborah Heart and Lung Center, Browns Mills, New Jersey;
†Division of Interventional Cardiology, Mount Sinai Medical Center,
New York, New York; and the ‡Cardiology Division, Evanston Hospital, Evanston, Illinois. Dr. George is a consultant for Boston Scientific
and ev3 Endovascular. Dr. Feldman received research grants from and is a
consultant for Abbott, Boston Scientific, and Edwards Lifesciences. All
other authors have reported that they have no relationships to disclose.
renal failure) at 9.6% in the percutaneous mitral clip
group compared with 57% in the surgical group. At 1
year, clinical success was higher in the surgically
treated group compared with the mitral clip arm. At
2 years, intention-to-treat analysis revealed that the
primary composite endpoints were still significantly
better in the surgery group compared with the mitral
clip group.
The conclusion of the EVEREST II is that
percutaneous mitral valve repair, although less
effective at reducing MR, is not inferior to surgical
repair or replacement, with a significantly reduced
adverse event rate; however, several questions remain. First, an edge-to-edge repair would only be
suitable for a select group of patients with central
MR or flail leaflet and would not address the other
leaflet morphologies of MR. Almost one-third of
patients in the MitraClip group had functional
MR with reportedly no difference in outcome
(reduced left ventricular volume/dimension and
improved symptoms) compared with the degenerative MR patients; however, the durability of this
result beyond 2 years remains to be seen. Second,
the improvement in symptoms and left ventricular
size, although similar in both groups, may begin to
diverge as patients are followed because a 3-fold
greater percentage of device-treated patients had
2⫹ or greater MR severity compared with surgically treated patients. In addition, although most
patients remain candidates for surgical repair after
MitraClip therapy, there have also been reports of
mitral clip patients with persistent severe MR who,
due to significant mitral leaflet scarring, are unable
to have surgical mitral valve repair and must
undergo valve implantation. More than 15% of
patients in the device arm subsequently underwent
mitral valve surgery due to persistent severe MR.
The inclusion of requiring blood transfusions, instead of the incidence of major bleeding, as an
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George et al.
Percutaneous Mitral Valve Repair
adverse event in the study has drawn criticism; however, it
should be noted that adverse events continue to favor
device-treated patients even if major bleeding is taken into
account and that transfusion after cardiac surgery is associated
with increased acute and long-term mortality (4 – 8).
Summary and Future Direction
The EVEREST II was a novel evaluation that compared
percutaneous mitral valve repair with surgical repair or
replacement. Although the study demonstrated the feasibility of a percutaneous treatment option for select patients
with severe functional MR, it is currently not yet approved
by the U.S. Food and Drug Administration (FDA) to supplant surgical mitral valve repair or replacement. Although
the EVEREST II has completed enrollment, further study
and long-term follow-up are ongoing with the REALISM
(Real World Expanded Multicenter Study of the MitraClip
System), a continued access registry. The MitraClip device
has received CE Mark approval in Europe and is currently
under review for FDA approval in the United States.
Meanwhile several other technologies are being developed as
alternative strategies for the management of MR (9). The
AMADEUS (cArillon Mitral Annuloplasty Device European
Union Study) (10) evaluated the use of the Carillon device
(Cardiac Dimensions, Kirkland, Washington), which consists
of an arched nitinol wire with looped anchors at each end that
is delivered percutaneously via the coronary sinus and anchored
in the great cardiac vein, restoring the natural shape of the
mitral annulus by modifying the tension of the device. At 6
months, MR reduction and improvement in 6-min walk
distance and quality of life were achieved with permanent
implantation in 30 of 48 patients enrolled (11).
Two indirect annuloplasty devices are no longer being studied,
but some clinical results are reported. The EVOLUTION phase
I study (Clinical Evaluation of the Edwards Lifesciences
Percutaneous Mitral Annuloplasty System for the Treatment of Mitral Regurgitation) (12) used the MONARC
coronary sinus device (Edwards Lifesciences, Irvine, California), which consists of 2 stent anchors with a connecting
spring bridge and a biodegradable element within the
bridge. At 12 months, MR reduction more than 1 grade was
observed in 50% of implanted patients and in 85.7% of
patients with baseline MR more than 3 grades (12). The
EVOLUTION phase II study of a second-generation
coronary sinus ring for patients with at least 3⫹ MR has
been concluded, but results have not yet been made available. The Percutaneous Mitral Annuloplasty (PTMA) device (Viacor Inc., Wilmington, Massachusetts) is a trilumen
plastic cannula that is used to deliver nitinol rods into the
coronary sinus to compress the septolateral dimension and
allow improved leaflet coaptation. MR reduction was observed in 13 of 19 patients who received a diagnostic PTMA
device (13).
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JULY 2011:825–7
Two direct mitral annuloplasty approaches including the
Mitralign system (Mitralign, Tewksbury, Massachusetts)
and the Guided Delivery Systems device (Guided Delivery
Systems, Santa Clara, California) have undergone first-inhuman feasibility studies, but larger clinical outcome trials
are pending.
The MitraClip is the first step in catheter-based strategy
for percutaneous treatment of MR. The initial study describing the surgical Alfieri technique for treatment of MR
(14) demonstrated 22% greater freedom from reoperation
when double-orifice repair was combined with an annuloplasty procedure. The effectiveness of percutaneous mitral
valve repair may be improved when performed in conjunction with the use of other catheter-based annuloplasty
devices that are currently in development. At this point, it is
clear that the MitraClip procedure is safe, with clinical
benefits in selected patients who are stable at least for 2
years. The regulatory steps involved in evaluation for FDA
approval and the subsequent rate of incorporation into
clinical practice will determine future developments of the
MitraClip and other mitral valve devices.
Reprint requests and correspondence: Dr. Jon C. George, Division
of Interventional Cardiology and Endovascular Medicine, Deborah
Heart and Lung Center, 200 Trenton Road, Browns Mills, New
Jersey 08015. E-mail: [email protected].
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10. Siminiak T, Hoppe UC, Schofer J, et al. Effectiveness and safety of
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