Journal of the American College of Cardiology Vol. 57, No.

5, 2011 © 2011 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00 Published
by Elsevier Inc. doi:10.1016/j.jacc.2010.10.012
STATE-OF-THE-ART PAPER

Percutaneous Leaflet Repair and Annuloplasty for Mitral

Regurgitation
Ted Feldman, MD, Mehmet Cilingiroglu, MD ​Evanston, Illinois
Percutaneous therapy for the treatment of mitral regurgitation has emerged rapidly over the past few years. Most of the percutaneous approaches
are modifications of existing surgical approaches to mitral annuloplasty or leaflet repair. Catheter-based devices mimic these surgical approaches
with less procedural morbidity and mor- tality as a consequence of their less invasive nature. Percutaneous annuloplasty can be achieved
indirectly via the coronary sinus or directly from retrograde left ventricular access. Catheter-based leaflet repair is accom- plished using an
implantable clip to mimic the surgical edge-to-edge technique. Several of these percutaneous approaches have been successfully used in patients
to demonstrate proof of concept, while others have already stopped further development. There is increasing experience in both trials and practice
to begin to define the clinical utility of percutanenous leaflet repair, and annuloplasty approaches are undergoing significant development. (J Am
Coll Cardiol 2011;57:529–37) © 2011 by the American College of Cardiology Foundation
Minimally invasive approaches have been developed in almost every field in surgery. Beating-heart surgery and port
surgery are 2 approaches that have been used for many years for valvular heart disease, including the development
of robotic operations to minimize invasiveness and diminish the recovery time and morbidity of traditional surgery.
Over the last several years, the potential to treat patients with valvular disease using entirely catheter-based,
percutaneous methods has undergone rapid development. The new con- cepts and improvements in technology
responsible for this development are remarkable, and illustrate a substantial effort by cardiovascular surgeons
working in concert with cardiologists, engineers, and clinicians (​ 1,2​
).
Percutaneous therapies for mitral regurgitation (MR) parallel surgical approaches that have been in use for many
years, and have been largely evolved from concepts devel- oped by surgeons. The predominant form of surgical
mitral repair is annuloplasty. The placement of a ring around the mitral annulus, fixed by sutures to diminish the
mitral orifice, is the most frequently used surgical therapy. Annu- loplasty brings the leaflet edges closer together by
dimin- ishing the circumference of the mitral orifice, and also decreases the distance between the septal and lateral
dimen- sions of the mitral orifice. The unique geometry of the mitral valve (MV) and apparatus creates some
challenges for annuloplasty, and has led to the development of a variety of
asymmetric annuloplasty ring shapes to accommodate the saddle shape of the MV, and the displacement of the
posterior leaflet in cases of ischemic MR. Annuloplasty is used as an adjunctive therapy in all forms of MR repair,
including functional ischemic and functional heart failure- related MR, and in conjunction with leaflet resection for
patients with degenerative MR from MV prolapse. The other form of repair that is commonly used in surgery is
leaflet repair. This is applied to patients with mitral prolapse or fibroelastic deficiency.
Annuloplasty Approaches
Annuloplasty is the mainstay of surgery in patients with functional MR. Annular dilation due to dilation of the left
ventricle and geometric distortion of the mitral apparatus is the mechanism of MR in this group of patients. Surgical
annuloplasty has been the predominant approach for func- tional MR. Importantly, it has been difficult to
demonstrate clinical benefit from surgical mitral repair in the heart failure population. Pivotal trials of percutaneous
annuloplasty de- vices may thus make comparisons of device therapy with medical therapy for heart failure rather
than being compared to surgical annuloplasty. The degree of efficacy necessary to effect clinical improvements from
any form of annuloplasty in the heart failure population has not been clearly estab- lished from prior surgical
experience, and the trial pathway for developing these devices will necessarily answer many of
From the NorthShore University HealthSystem, Evanston, Illinois. Dr. Feldman
these long-standing questions (​3,4​). ​receives research grants and is a consultant to Abbott and Edwards. Dr. Cilingiroglu has reported that he has no
relationships to disclose.
Manuscript received September 8, 2010; revised manuscript received October 20, 2010, accepted October 28, 2010.
Percutaneous annuloplasty approaches have been both direct and indirect. Indirect approaches use the coronary sinus
as a route to deliver a device that partially encircles the
 mitral annulus. The coronary si- nus parallels the posterior mitral leaflet, and since there is a long history of
implantation of devices in the coronary sinus, this ap- peared to be an attractive route. Access to the coronary sinus
through jugular puncture is well developed and simple. The coronary sinus encircles about two-thirds of the mitral
annulus, so a device can capture most of the annular circumference. Early animal work demonstrated that coro- nary
sinus devices could reduce the annular circumference significantly both in the normal MV and in models of MR
created using pacing-induced heart failure (​ 5​ Indirect annuloplasty approaches. ​Several approaches to the
). ​
coronary sinus annuloplasty have been developed (​ Fig. 1​
). Fundamentally, all of them place a device that creates
tension or a constricting force transmitted to the MV and the mitral annulus. The obvious appeal of the coronary
sinus approach is simplicity and ease of use. The Cardiac Dimensions Carillon system (Cardiac Dimensions,
Kirkland, Washington), the Edwards Monarc system (Edwards Lifesciences, Irvine, Cali- fornia), and the Viacor
PTMA system (Viacor, Wilmington, Massachusetts) represent the coronary sinus devices that have some human
implant experience.
530 Feldman and Cilingiroglu JACC Vol. 57, No. 5, 2011 Percutaneous Mitral Valve Therapy February 1, 2011:529–37
Figure 1 ​Coronary Sinus Annuloplasty: The Cardiac Dimensions Carillon Device
The guide catheter is introduced through jugular venous access. The device is delivered in the distal coronary sinus, and then the guide catheter is pulled back to release the device
in the coronary sinus ostium. The insets show the wireform, made of nitinol wire. Figure illustration by Craig Skaggs.
Abbreviations and Acronyms
LV ​left ventricular
MR ​mitral regurgitation
MV ​mitral valve
The Cardiac Dimensions Carillon device (​Fig. 1​ ) is a simple nitinol wire that has been engineered into a form that
includes distal and proximal anchors and a bridge element (​ 6​). After jugular puncture, a 9-F guide catheter is
delivered into the distal coronary sinus. The distal anchor of the device is released, and using the guide catheter to
pull from above and place tension on the coronary sinus, the mitral circumference is shortened; then, the proximal
an- chor is released. The first generation of the device was challenged by difficulty in anchoring. This problem was
rapidly corrected with improvements in engineering, and some first-in-human experience has been successfully
achieved. The major findings with this device include the ability to reduce MR by at least 1 grade in the majority of
patients, with improvements in left ventricular (LV) vol- umes and dimensions. As a clinical measure, 6-min walk
test results have been improved in this group as well, up to 6 months after treatment (​ 7​). Defining clinical success
has been a challenge in the field of MR therapy. The subjectivity of New York Heart Association functional class is
well appreciated. There has been no real study of the correlation between MR grade reduction and measures of
functional improvement. While 6-min walk tests also have important limitations, this measure is at least
quantitative, and is being
adopted with increasing frequency in trials evaluating per- time of implant, and even before complete release of the
cutaneous valve therapies. device. Thus, if the degree of reduction in MR is not sufficient,
The Edwards Monarc device is similarly implanted the device can be retrieved and the procedure abandoned.
in the coronary sinus after cannulation with a guide catheter However, once the Edwards Monarc device is placed and
(​8,9​). The device is composed of proximal and distal self- released, there is no indication regarding the ultimate efficacy
expanding conventional nitinol stents connected by a bridge outcome until the spring has shortened several weeks later.
element. The distal anchor is delivered into the anterior Thus, there is no method to predict the outcome of MR
interventricular vein, and the proximal anchor is placed near reduction until after the implant has been completed and some
the coronary sinus ostium. Thus, this device captures a greater time has passed. Early experience with the Edwards Monarc
part of the circumference of the mitral annulus than does the device has also dem- onstrated reductions in MR grade 1 or 2
Cardiac Dimensions device. The bridge is a spring that is held grades in the majority of patients. Further study of the Monarc
in its open position by the placement of absorbable suture device has been stopped by the sponsor due to slow enrollment
material in the interstices of the spring. That holds the spring in in the EVOLUTION II (Clinical Evaluation of the Edwards
an open position. The bioabsorb- able material dissolves after 1 Lifesciences Percutaneous Mitral Annuloplasty System for the
to 2 months, with slow and steady shortening of the device as Treatment of Mitral Regurgitation) trial.
the spring spaces approx- imate. The effect of the Cardiac The Viacor PTMA device has a somewhat different
Dimensions Carillon device can be assessed immediately at the mechanism (​10–12​
). Subclavian puncture is used to deliver a
trilumen plastic cannula into the coronary sinus. Stiff nitinol
rods are passed through the lumens of the catheter to apply
pressure to the central part of the posterior mitral leaflet and
compress the septolateral dimension, rather than to encircle and
constrict or cinch the mitral annulus. Rods of varying stiffness
may be used. During the implant process, a sequence of rods
may be placed through the lumens to determine the optimal
amount of compression of the posterior annulus to result in a
reduction in MR. Another attractive feature of this device is
that the subclavian access may be re-accessed at a later date to
remove rods if there is some problem with the device; or if
efficacy for reduction of MR is diminished, stiffer rods may be
used to replace those that were chosen during the initial
implant process. The first several patients treated with this
system have shown con- tinued compression of the mitral
orifice for as long as 1 year after initial implantation. The
company has subsequently stopped further development of the
device.
There are several limitations common to all of the
coronary sinus devices. Long-standing prior experience with
coronary sinus pacemaker lead implantation suggested that
the integrity of the devices would not be a significant problem,
but all 3 of these devices have experienced metal fatigue, with
device fracture in several cases. Apparently, the mechanical
stresses of the coronary sinus are greater than had been
anticipated, and the complex geometric motion patterns of the
coronary sinus create greater torsional forces on these devices
than had been initially modeled using finite element analysis.
Re-engineering of all 3 of these devices has led to better
outcomes, with improvements in the frequency device fracture.
Long-term study will be necessary to determine whether this
remains a persistent late problem. Importantly, device fracture
has not resulted in coronary sinus perforation or other
important adverse events. Inter- estingly, device fracture in
patients treated with the carillon device has not been associated
with loss of efficacy in MR reduction.
A second important limitation common to this class
of devices is the potential for compression of the circumflex
531 JACC Vol. 57, No. 5, 2011 Feldman and Cilingiroglu February 1, 2011:529–37 Percutaneous Mitral Valve Therapy
coronary artery. The coronary sinus crosses over the circum-
flex coronary artery or 1 of its obtuse marginal branches in
between two-thirds and three-quarters of patients (​ 13–15​ ).
With the Cardiac Dimensions Carillon device, this com-
pression can be appreciated at the time of implant. The position
of the implant can be adjusted to diminish com- pression, or if
needed, the device can be removed and the procedure
abandoned. With the Edwards Monarc device, the potential for
compression cannot be completely assessed until after
shortening of the bridge element occurs several weeks later.
Computed tomography scans to evaluate the relationship of the
coronary sinus and the coronary arteries before device
implantation are therefore particularly impor- tant with these
devices. While the Viacor PTMA device does not encircle as
much of the circumference of the mitral annulus, compression
of the circumflex may still occur with this device as well (​
16​).
Thus, evaluation of the coronary circulation both before the
procedure using computed to- mography scanning and during
the implant procedure using concurrent coronary arteriography
is important as part of the implant procedure. In early human
experience, this group of devices was successfully implanted in
about two- thirds of patients. In the remaining one-third, the
procedure was not successful because of either unfavorable
coronary sinus geometry, difficult coronary sinus access by the
guiding system, or coronary artery compression.
Despite the indirect nature of the coronary sinus ap-
proach and the challenges that have been encountered with
these devices, the coronary sinus route remains highly
attractive because of the simplicity of the approach. The
potential for transvenous implantation makes the procedure
accessible to a large population of patients and a wide range of
physician operators. ​Direct annuloplasty approaches. ​Direct
implantation of a device into the mitral annulus would
overcome some of the limitations of the indirect, coronary
sinus approach (​17​). Direct annuloplasty might more closely
mimic surgical annuloplasty ring implantation. Reaching the
mitral annu-
 Direct annuloplasty has the advantage of obviating
cor- onary compression. Arterial access as the delivery route
adds some complexity and morbidity to this procedure in com-
parison with a transvenous coronary sinus approach. The
potential for greater efficacy in reduction of MR through the
direct approach is highly attractive. The direct annuloplasty
technologies are in early development, and more human
experience is anticipated.
Leaflet Repair

Surgical leaflet repair has mainly utilized annuloplasty in

lus directly is more challenging than using the coronary sinus
approach. A guide catheter must be passed retrograde
transarterially across the aortic valve and maneuvered into a
position within the left ventricle under the posterior mitral
leaflet, adjacent to the mitral annulus. Two companies, Mitralign
and Guided Delivery Systems, have utilized a direct access
approach. Retrograde access to the left ventri- cle and posterior
mitral annulus is shared by both of these devices, but each device
is unique.
The Mitralign system (Mitralign, Tewksbury,
Massachu- setts) involves placement of the guide catheter under
the middle scallop of the posterior mitral leaflet. Radiofre-
quency wires are used to penetrate the mitral annulus and gain
access to the left atrial side of the annulus. Pledgets are passed
over the wires and connected with a drawstring. Plication of the
string results in drawing of the pledgets closer together. The
current system employs 2 pairs of pledgets, and this results in
shortening of the mitral circum- ference by 1 to 3 cm. The
system has been employed in pre-clinical and first-in-human
experiences. Clinical out- come data will require additional
experience.
The second direct annuloplasty approach is the Guided
Delivery Systems device (Guided Delivery Systems, Santa Clara,
California) (​Fig. 2​). After access to the annulus, a series of as
many as 12 nitinol anchors are placed in the mitral annulus.
These are connected with a tether or cord that is tensioned to
draw the anchors together. This device has been implanted
surgically, and first-in-human experi- ence has demonstrated the
technical feasibility of percuta- neous use.
532 Feldman and Cilingiroglu JACC Vol. 57, No. 5, 2011 Percutaneous Mitral Valve Therapy February 1, 2011:529–37
conjunction with the techniques of leaflet resection and sliding
annuloplasty. Surgical leaflet approaches are used for MV
prolapse to remove some of the redundant leaflet tissue, and help
to restore leaflet coaptation. No percu- taneous version of leaflet
resection is currently available and has yet to be developed. A
less commonly utilized surgical leaflet repair approach is the
edge-to-edge, or double-orifice repair (​ 18,19​). The repair is
accomplished by suturing the free edges of the mitral leaflets
together to form a double orifice. This surgical procedure was
pio- neered by Alfieri et al. (​ 18​
) in the early 1990s. In most
cases, annuloplasty is performed in conjunction with leaflet
surgical repair. Isolated use of the edge-to-edge repair has been
controversial, because most surgical experience has utilized the
combination of annuloplasty and the leaflet repair. Follow-up for
as long as 12 years in a small group of patients who have
undergone isolated surgical edge-to-edge repair without
annuloplasty has demonstrated durable clinical outcome, and
thus proof of principle, with this surgical technique (​ 19​
).
Additional study will be needed to show how well the principle
translates into clinical outcome in various populations of
Evalve MitraClip. ​A percutaneous approach has been
patients. ​
developed that uses a clip to create the double-orifice repair
(​
20,21​). The MitraClip system uses a guide catheter, a clip
delivery catheter, and an implantable clip (​ Fig. 3​
). The guide is
placed using transseptal puncture. It is 24-F proximally and
tapers to 22-F at the level of the atrial septum, and is delivered
over a dilator. A knob on the end of the guide is used for
deflection of the tip. The delivery catheter passes coaxially
through the guide, and has the MitraClip attached to its distal
end. This delivery system uses 2 knobs that control mediolateral
and anteroposterior steering. The MitraClip device is a
4-mm-wide cobalt- chromium implant with 2 arms. The clip
arms are opened
 Figure 2 ​Direct Annuloplasty

The Guided Delivery Systems Accucinch device is delivered through retrograde catheterization of the left ventricle. (Left) Anchors are placed in the posterior mitral
annulus and (right) connected with a “drawstring” to cinch the annular circumference. Figure illustration by Craig Skaggs.
clip has a locking mechanism to maintain closure. On the
inner portion of the clip are small barbs or “grippers” to
secure the leaflets when the clip arms are closed. The clip is
covered with polyester fabric.
The procedure is performed with general
anesthesia, using fluoroscopy and transesophageal
echocardiography guidance (​ 22​
). Most of the maneuvering of
the system is done using echocardiography (​ Fig. 4​ ).
Transseptal access is used to place a guide catheter into the
left atrium.

and closed by a knob on the delivery catheter handle. The

533 JACC Vol. 57, No. 5, 2011 Feldman and Cilingiroglu February 1, 2011:529–37 Percutaneous Mitral Valve Therapy
Figure 3 ​The Evalve MitraClip

(A) The Evalve MitraClip. The clip arms are open (left) when the device is passed across the mitral leaflets from the left atrium into the left ventricle. The gripper is the barbed piece seen in the upper
left panel, parallel to the shaft of the delivery system. When the leaflets are grasped, the gripper helps to fix the leaflets within the clip arms (middle). The clip is covered with polyester fabric (right).
(B) The steering knobs are shown on the right-hand side of the device for maneuvering the clip within the left atrial cavity. At the far left of the picture is the knob that is used to open and close the
clip, and the release mechanism.
 Figure 4 ​Basic Steps of the Evalve MitraClip Clip Procedure
(Top) The left panel shows the clip being steered through the left atrium toward the center of the mitral orifice. The middle panel illustrates the device across the mitral valve (MV) with the clip arms
open, before the clip has been pulled back to grasp the mitral leaflets. The right panel shows, in the cartoon, the clip has been released. (Bottom) In the fluoroscopic figure, the leaflets have been
grasped and clipped closed partially, before full closure and release of the clip.
Through the guide catheter, the clip delivery system is
maneuvered to center the clip over the mitral orifice. The clip
is partially opened and passed across the leaflets, through the
chordae tendineae, and into the left ventri- cle. The open clip
is pulled back to grasp the mitral leaflets. When the leaflets
have fallen into the clip arms, the grippers are lowered, and
the clip is closed. A key step at that point is evaluation of the
insertion of leaflet tissue into the clip. If the leaflets have
been adequately grasped, a determination of the degree of
reduction in MR can be made. If needed, a second clip can be
placed. The clip may be opened and closed to grasp the mitral
leaflets several times. If the leaflet insertion is not adequate,
or if reduction of the MR is insufficient, the clip is opened,
withdrawn into the left atrium, and repositioned before
crossing the leaflets and attempting another grasp. If after
several attempts it appears that the degree of MR cannot be
effectively reduced, the clip can be completely re- moved.
Thus, the ability to assess the results of the procedure in real
time is an important asset of this therapy.
Patients have been referred for surgical mitral
repair after unsuccessful clip procedures, both with and
without a clip in place. Successful surgical repair has been
accomplished in this setting (​ 23​
). The appearance of the
leaflets in the operating room after unsuccessful clip
procedures without placement of a clip has demonstrated
some reddening of the leaflets, but actual tissue damage or
damage to the chordae has been rare. Successful surgical
repair has also been accomplished after placement of a clip.
In most of these instances, MR was either not adequately
controlled or it recurred after placement of a clip. The clips
can be removed and surgical repair can be accomplished in
the majority of patients without needing valve replacement.
Patients who have required valve replacement after failed clip
therapy usually have predictors for replacement such as
advanced age, annular calcification, or leaflet calcification.
Thus, the potential for utilization of the clip without
substantial penalties regarding future surgical repair is
possible.
Patients treated in the Evalve EVEREST
(Endovascular Valve Edge-to-Edge Repair Study) have been
selected using the American Heart Association/American
College of Car- diology guideline recommendations for
surgical MV repair. Patients with moderate to severe or
severe MR (3 to 4 ), judged by quantitative assessment of the
degree of regurgi- tation using the American Society for
Echocardiography quantitative scoring system have been
included. All of the echocardiograms have been evaluated in
a core laboratory. Use of the American Society for
Echocardiography quanti- tative scoring system is important
because, in usual practice, although noninvasive approaches
have been widely accepted to assess severity of MR, there
remain significant limita- tions. There is overlap in
measurements for effective regur- gitant orifice area,
regurgitant volume, and regurgitant fraction between mild (1
) and severe (4 ) angiographic MR. In practice, patients with
qualitative “severe” MR by
echocardiography are frequently found to have no or mild (1 )
MR on angiography. In the EVEREST and EVEREST II
trials, it was our experience that about one-quarter of patients
referred with a clinical assessment of 3 or 4 MR had only 2
MR in the core echocardiography laboratory. Patients were
symptomatic, or if asymptomatic, had evi- dence of LV
dysfunction for inclusion for treatment with the MitraClip.
Importantly, patients with severely reduced LV dysfunction
with LV ejection fraction of 25% were excluded.
On an intent-to-treat basis, 96 (90%) of the 107 EVEREST
trial registry patients achieved a reduction in MR from either
the clip or subsequent MV surgery after attempted clip. Of
the patients with acute procedure success, 64% were
discharged with mild MR (1 ), and 13% had MR graded as
mild to moderate (1 to 2 ). Thus, 77% had 2 MR. About 40%
of patients were treated with 2 clips. The composite primary
efficacy end point (freedom from MR 2 , cardiac surgery for
valve dysfunction) and from death for the per-protocol
population at 1 year was 66%, not including crossover to
surgery. Three-year freedom from reoperation was just under
80%. Results have been similar in both degenerative and
functional MR.
534 Feldman and Cilingiroglu JACC Vol. 57, No. 5, 2011 Percutaneous Mitral Valve Therapy February 1, 2011:529–37
In-hospital and 30-day complications in the EVEREST trial
registry included major adverse events in 9% of 107 patients.
There was no procedural mortality. Bleeding requiring
transfusion was the most common event, compris- ing almost
one-half of the adverse events. There was 1 peri- procedural
stroke and 1 post-procedure death. One patient underwent
reoperation for failed surgical MV repair 19 days after valve
repair after an unsuccessful MitraClip procedure, and 1
patient required ventilation for 20 days. No clip embolization
has occurred at any time point. Partial clip detachment is the
most important mechanical problem with the procedure. That
occurred in 9% of the initial cohort, and was most often
detected at the protocol-mandated 30-day echocardiography
examination. These partial detachments were generally not
associated with symptoms. Most were treated with mitral
surgery, but more recently in the registry and in European
experience, an additional clip has been placed. With better
methods for assessment of leaflet insertion into the clip at the
time of the procedure, the incidence of partial clip
detachment has declined to 3%. Careful evaluation of the
echocardiographic morphology of the mitral leaflets is critical
for good patient selection (​Fig. 5​ ). Patients with either
degenerative or functional MR have been successfully
treated. A coaptation length of at least 2 mm is needed. Thus,
some tissue from both leaflets should be in contact, so there is
some tissue to grasp with the clip. With a flail mitral leaflet, a
flail gap 10 mm or a flail width on short-axis estimation 15
mm are also important anatomic features. The MR jet must
arise from the central two-thirds of the line of coaptation as
seen on short-axis color Doppler examination. It is common
for most clinical transthoracic echocardiographic
examinations to either omit or have very little short-axis color
Doppler

interrogation of the MV. Adequate evaluation for this therapy
requires careful scanning of the mitral funnel in the short-axis view
to ensure that the jet origin is central, and ideally, relatively discrete.
The baseline MV area should be 4 cm​2​, because placement of the
clip significantly dimin- ishes the MV area, and this attentiontes
baseline mitral area is necessary to avoid the creation of mitral
stenosis. Clini- cally important mitral stenosis has not been created
535 JACC Vol. 57, No. 5, 2011 Feldman and Cilingiroglu February 1, 2011:529–37 Percutaneous Mitral Valve Therapy
our experience to date because of careful attention to the baseline
V area during the patient screening and selection process.
A randomized phase II clinical trial comparing the
traClip with either surgical valve repair or replacement has been
mpleted. In all, 279 patients have been random- ized using a
o-1 scheme, and 12-month follow-up has been completed. The
ults of the trial were presented at the American College of
rdiology annual scientific ses- sions in 2010. Safety end points
re reached in about 50% of surgery patients and 15% of
traClip patients, showing superiority of safety for the
rcutaneous approach by intention to treat. A large component of
safety end point is blood transfusion, which is much more
quent with valve surgery than with the MitraClip procedure.
tients
ho receive transfusions after cardiac surgery have a higher
ortality rate extending beyond 5 years post-operatively compared
ith that of patients who do not receive transfu- sions,
emonstrating the importance of transfusion as a safety end point
4​ ). The 1-year efficacy end point of the combined incidence of
eath, MV surgery, or reoperation for MV dysfunction was reached
about three-quarters of surgery patients and in two-thirds of
itraClip patients, meeting the noninferiority hypothesis for
ficacy. A larger proportion of surgery patients had 0 to 1 MR.
eductions in LV volumes and dimensions were achieved in both
oups after 1 year, as were improvements in New York Heart
ssociation functional class.
The device has received continuing education approval and
undergoing increasingly wide use in Europe. The experience in
inical practice has shown several trends. Current use in Europe
cludes a high proportion of patients at high risk for surgery. A
ajority of the patients in the EVEREST registry had degenerative
R, but about three-quarters of those being treated in European
actice have functional MR. The learning curve for new clinical
to has benefitted from the aggregate experience with this novel
ocedure. New sites are having high implant success
 Figure 5 ​Echocardiographic Evaluation of Morphology of Mitral Leaflets Is Critical for Good Patient Selection

(Top) A coaptation length of at least 2 mm is needed. Thus, some tissue from both leaflets should be in contact, so there is some tissue to grasp with the clip. (Bottom) With a flail mitral leaflet, a flail
gap 10 mm and a flail width on short-axis estimation 15 mm are also important anatomic features. The mitral regurgitation jet must arise from the central two-thirds of the line of coaptation, as seen
on short-axis color Doppler examination. Figure illustration by Craig Skaggs. Modified, with permission, from Feldman et al. (20).
rates and good clinical outcomes, with average procedure possible comparator, especially in high-risk surgery patients.
device times (guide catheter insertion to guide catheter Measurement of differences in outcome in com- parisons of
removal) under 2 h, and for cases with 1 clip implanted, medical therapy with devices may be difficult if patients with 2
frequently under 1 h. This reflects continued improvements in MR are studied, whereas patients with 3 to 4 functional MR are
procedure technique, and the ability to teach new operators less common. In addition to assessing decreases in MR grade
proper patient selection, the technique, and the use of and LV dimensions, functional results such as 6-min walk
intraprocedure echocardiographic guidance. tests, and quality of life measures such as the Short Form-36
and the Kansas City Cardiomyopathy questionnaires, are
Future Developments important to de- termine the utility of MR therapy devices.
Several novel concepts are in the earliest stages of
The best methods for study of these new MV therapeutic develop- ment. Beating-heart transapical chordal replacement
approaches are difficult to establish. Percutaneous annulo- is 1 of these concepts. Another is catheter-based, percutaneous
plasty approaches have been directed primarily at functional MV replacement. Percutaneous MV replacement is in
MR. Surgical annuloplasty has been most commonly per- pre-clinical evaluation. Challenges include the asymmetric
formed in conjunction with coronary bypass or other valve shape of the mitral orifice, and finding an adequate anchoring
operations. Thus, isolated percutaneous annuloplasty is not mechanism for a percutaneous prosthesis. Radiofrequency
easily compared with surgical annuloplasty. The EVEREST II energy has been used as an annuloplasty approach to shrink the
trial was unique in being able to compare percutaneous leaflet mitral annulus (​
25​
).
therapy directly with surgery. Medical therapy is the other
 A fundamental problem with annuloplasty for
treatment of functional MR is that MV dysfunction is caused
by LV geometric distortion and LV chamber dysfunction.
While annuloplasty treats MR, it has no impact on the
underlying LV dysfunction. A novel therapy that effected
chamber remodeling has been developed and tested in a
significant human experience (​26–30​). Unfortunately, lack of
funding during the recent financial crisis led to the demise of
this effort. The Coapsys system (Myocor, Maple Grove, Min-
nesota) used a tether placed through the LV cavity, either
during beating-heart surgery or through transpericardial
percutaneous access. The ventricle is compressed between 2
external pads placed on the epicardial surface of the anterior
and posterior walls and connected by the transventricular
tether. This device both remodels the LV chamber and
compresses the mitral annular septolateral dimension. A
randomized trial comparing Coapsys surgical therapy with
mitral annuloplasty for ischemic MR without ventricular
remodeling has been completed, and demonstrates both
sustained reductions in MR and improved survival (​ 31​
). It is
hoped this technology will come back into development and
further testing.
Reprint requests and correspondence: ​Dr. Ted Feldman, Evan- ston
Hospital, Cardiology Division, Walgreen Building, 3rd Floor, 2650
Ridge Avenue, Evanston, Illinois 60201. E-mail:
tfeldman@northshore.org​.
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Key Words: ​mitral regurgitation y mitral valve y percutaneous valve
therapy.