Download Percutaneous Mitral Valve Interventions

CLINICAL REVIEW
Percutaneous Mitral Valve Interventions: Overview
of New Approaches
Mehmet Cilingiroglu, MD, FESC, FACC, FSCAI and Ted Feldman, MD, FESC, FACC, FSCAI
Abstract
Percutaneous therapy has emerged over the past few years as a rapidly progressing field of development for the treatment of mitral regurgitation. Most of the new percutaneous approaches are modifications
of previously-described surgical techniques that have been used for mitral valve repair for several decades. The main surgical approaches to
mitral valve repair are annuloplasty and leaflet repair. Catheter-based
devices mimic these surgical approaches with the aim of achieving outcomes similar to surgery, with less procedural morbidity and mortality
as a consequence of their much less invasive nature. Some of these concepts include mitral valve annulosplasty via either the coronary sinus
or directly from retrograde left ventricular access, and leaflet repair
using modifications of the surgical edge-to-edge technique. Many of
these percutaneous approaches have been accomplished with several
devices and have been used with enough acute success to demonstrate
proof of concept. Here, we will discuss these novel catheter-based therapies for the treatment of mitral regurgitation.
VASCULAR DISEASE MANAGEMENT 2010;7:E126–E134
Key words: mitral regurgitation, percutaneous valve repair,
surgical valve repair, mitral annuloplasty
Normal mitral valve closure, which prevents systolic backflow of blood into the left atrium during left ventricular systole,
depends on the complex interaction of each of the components
of the valve apparatus; the left atrial wall, annulus, mitral valve
leaflets, chordea tendineae, papillary muscles and the left ventricle (LV).1,2 Abnormalities in the anatomy and function of any
one of these components can lead to incompetence of the valve,
resulting in mitral regurgitation (MR). Normal mitral valve closure is thought to be a passive process mediated by flow deceleration though the valve with generation of vortices on the
ventricular side of the leaflets in conjunction with an adverse
From NorthShore University HealthSystem, Evanston, Illinois.
Disclosure: Dr. Feldman has received grant support from Abbott and
Edwards Lifesciences and has been a consultant to Abbott and Edwards
Lifesciences.
Address for correspondence: Ted Feldman, MD, FESC, FACC, FSCAI,
Evanston Hospital, Cardiology Division-Walgreen Building 3rd Floor, 2650
Ridge Avenue, Evanston, IL 60201. E-mail: [email protected]
E126
VASCULAR DISEASE MANAGEMENT
pressure gradient between the LV and left atrium.3–5 During systole, the mitral annulus moves toward the LV apex, whereas contraction of the LV myocardium underlying the posterior annulus
results in a decrease in annular area by approximately 25%.6
When MR is caused by pathology specific to the valve
leaflets such as myxomatous degeneration, it is referred to as
degenerative MR. On the other hand, mitral regurgitation that
is a consequence of ventricular or annular abnormalities including cardiomyopathy or left ventricular or papillary muscle dysfunction as a result of ischemia, is referred to as functional MR.
MR, a common finding, is clinically significant in part as a
result of its detrimental effect on LV function. Patients with
mild MR may remain asymptomatic for many years. However,
moderate-to-severe MR leads to either gradual or, at times,
acute ventricular dilation and contractile dysfunction with ultimate development of symptoms and left ventricular failure.7
In patients with symptomatic moderate-to-severe or severe
MR, surgical intervention is recommended. Surgery is also recommended for asymptomatic patients with severe MR who
have evidence of left ventricular dysfunction and/or new onset
atrial fibrillation or pulmonary hypertension.8
The preferred surgical therapy for MR is mitral valve repair.9,10 Patients undergoing mitral valve repair have demonstrated improved short- and long-term outcomes compared to
patients who receive valve replacement with mitral valve prosthesis in prior nonrandomized clinical experience.11 In spite of
these more favorable results with repair and the obvious limitations of prosthetic valve replacement, mitral valve repair is
still being performed in only about half of patients undergoing
mitral valve surgery.12 For functional MR, the most common
surgical intervention is annuloplasty.13 Annuloplasty for functional MR is usually performed in association with coronary
artery bypass surgery. Degenerative MR is typically treated
with leaflet repair, and has better long-term outcomes than isolated annuloplasty for functional MR.
These surgical procedures, though effective at reducing MR,
are associated with the expected mortality and morbidity of
open-heart surgery. Thus, the morbidity and mortality associated with open-heart surgery keeps many patients with clinically significant MR from receiving mitral valve surgery,
especially when they are older or at higher risk for surgery.
Thus, these basic surgical concepts of annuloplasty and leaflet
MAY 2010 I VOLUME 7, NUMBER 5
PERCUTANEOUS MITRAL VALVE INTERVENTIONS
Table 1. Percutaneous therapy of mitral regurgitation.
Approach
Device
Feature
Manufacturer
Status
Leaflet repair
MitraClip
Edge-to-edge clip
Evalve (Abbott Labs., Abbott Park, Ill.)
Trial complete
Coronary sinus
annuloplasty,
indirect
Monarc
Mitral annulus
remodeling
Mitral annulus
remodeling
Mitral annulus
remodeling
Edwards Lifesciences (Irvine, Calif.)
Phase 1
Viacor (Wilmington, Mass.)
First-in-man
Cardiac Dimensions (Kirkland, Wash.)
Phase 1
Transaortic LV
approach
Mitralign (Tewksbury, Mass.)
First-in-man
Transaortic LV
approach
Guided Delivery Systems
(Santa Clara, Calif.)
First-in-man
PTMA
Carillon
Direct annuloplasty
Mitralign
Guided
Delivery
Chamber
remodeling
QuantumCor Direct radiofrequency QuantumCor (Lake Forest, Calif.)
to the annulus
Preclinical
Coapsys
Surgical trial
complete
First-in-man
PS3
LV chamber
remodeling
Transatrial cord
Myocor (Minneapolis, Minn.)
Ample Medical (Foster City, Calif.)
LV = left ventricular; PS3 = percutaneous septal sinus shortening system; PTMA = percutaneous transvenous mitral
annuloplasty.
repair have been adapted for the development of novel
catheter-based percutaneous approaches with the goal of expanding the pool of patients who might benefit from a less invasive approach to a reduction in MR. Advances in both
technique and development of novel devices have led to a variety
of methods to treat MR using a percutaneous route (Table 1).
Percutaneous approaches for mitral valve repair have been recently implemented in clinical trials for treatment of MR.
Leaflet Repair with the Evalve MitraClip™
Among all of the percutaneous approaches for MR, the
greatest amount of experience has been developed with the
Evalve MitraClip™ (Abbott Laboratories, Abbott Park, Illinois)
(Figure 1). Initially described by the Italian surgeon Ottavio Alfieri for surgical repair of anterior leaflet prolapse in 1991, the
edge-to-edge technique involves apposing the middle scallops
of the anterior and posterior leaflets with a stitch creating a
so-called “dual” or “double-orifice” mitral valve.14 The apposition of the leaflets leads to effective reduction of MR. The
tissue bridge that is created when the sutured segment heals
may also prevent further annular dilatation (Figure 2). In addition, the anchorage of the leaflets together through the
chordae tendinea may exert a supporting or tethering effect
on the LV, and help to counteract the progression of ventricular remodeling and recurrence of MR. This approach has
been successfully used to treat MR resulting from prolapse of
either one or both leaflets involving the mid-segment of the
MAY 2010 I VOLUME 7, NUMBER 5
valve, as well as for selected patients with functional regurgitation secondary to ischemia or cardiomyopathy.15,16
In a recent report from Alfieri’s group, central double-orifice
repair was performed in 260 patients followed for up to 7
years,17 survival was 94% and freedom from reoperation was
90%. The clinical success and simplicity of this technique has
thus prompted interest in the development of a catheter-based
technology that would enable the interventional cardiologist
to perform a percutaneous endovascular repair in the cardiac
catheterization laboratory.
A percutaneous method to accomplish the double-orifice
repair was subsequently developed (Figure 3). A technique that
facilitates valve repair without adjunctive annuloplasty potentially allows for more physiologic ventricular contraction, as
annular motion contributes significantly to ventricular dynamics. By fastening the leaflets together, edge-to-edge repair ensures a fixed area of effective coaptation. With this technique,
the remainder of the coaptation line closes physiologically
without disturbing subvalvular or annular architecture and
function. This might significantly impact LV hemodynamics
and avoid the compromise in cardiac output frequently seen
in patients after mitral valve replacement.
The system consists of a 24 Fr steerable guide catheter with
a 22 Fr distal end, a separately steerable clip delivery system
and an implantable clip. Mounted on the distal end of the delivery system, the MitraClip, is a two-armed, soft tissue-grasping and approximating device that, when closed, has an outside
VASCULAR DISEASE MANAGEMENT E127
Cilingiroglu and Feldman
diameter of 15 Fr, and in its grasping position, it spans 20 mm.
It is designed to vertically hold up to 8 mm of leaflet height
and 4 mm of width to recapitulate the Alfieri’s surgical approach in length and width of tissue apposition. It is constructed of implant-grade cobalt-chromium alloy and the clip
is covered with polyester. On the atrial side of the clip are
“grippers”, which are small, flexible, multipronged friction elements that appose and stabilize tissue against the clip arms.
After tissue is captured between the arm and the gripping components, the clip is closed and deployed in a locked position.
The clip is designed to promote leaflet-to-leaflet healing around
and into the device in order to allow the development of a tissue-supported permanent leaflet approximation. The clip can
be opened, the leaflets released, and the clip can then be repositioned using real-time echocardiographic assessment to attain
the best possible result before final deployment.
Percutaneous edge-to-edge repair with the MitraClip in humans is performed in the catheterization laboratory with a
combination of echocardiographic and fluoroscopic guidance
under general anesthesia. Access to the left atrium is obtained
via the femoral vein and a 24 Fr guide catheter is placed across
the interatrial septum using the transseptal approach. A multidirectional steerable system is introduced through the guide
and using a series of iterative steps, positioned above the mitral
leaflets at the location of the regurgitant jet. The two arms of
the clip are opened in the left atrium once the clip is aligned
with the long axis of the heart near the origin of the MR jet.
Under echocardiographic guidance, the arms are rotated until
they are perpendicular to the line of leaflet coaptation. The
open, aligned clip is advanced across the mitral orifice and then
retracted to grasp the leaflets during systole. The atrial grippers
Figure 1. The MitraClip™ device (Abbott Laboratories,
Abbott Park, Illinois). The MitraClip™ device is covered
with polyester and attached to the clip delivery system.
with frictional elements are lowered onto the atrial side of
leaflets, approximating (capturing) and stabilizing leaflet tissue
against the arms on the ventricular side of the leaflet. When a
double orifice and reduction in MR jet are demonstrated by
echocardiography, the clip arms are closed in a locked position.
The acute result is then evaluated with two-dimensional colorflow and pulsed Doppler imaging. If inadequate reduction in
MR is the case, the leaflets can be released and the clip repositioned. In some cases, a single clip is not sufficient to adequately decrease the magnitude of MR. In that situation a
second clip can be placed adjacent to the first clip on the side
Figure 2. Edge-to-edge repair with suture apposing anterior and posterior leaflets. Mitral valve is viewed from the
left atrial side. The middle scallops of the anterior and posterior leaflets have been approximated with the MitrClip™,
which creates a double orifice, edge-to-edge or bow-tie repair.
E128
VASCULAR DISEASE MANAGEMENT
MAY 2010 I VOLUME 7, NUMBER 5
PERCUTANEOUS MITRAL VALVE INTERVENTIONS
Figure 3. (a) MitraClip™ advanced out of the guide catheter into the left atrium. (b) Open clip is advanced into the
left ventricle. (c) Clip is pulled back to grasp the leaflets. (d) Clip is closed on the leaflets. (e) Clip is detached. (f)
Left ventricular angiogram showing absence of residual mitral regurgitation.
of the residual MR jet. Repeat hemodynamic and echocardiographic assessments are then made to verify final results, at
which point the delivery system is removed.
Chronic animal studies in a porcine model showed that at 4
weeks, the entire clip was encapsulated in a layer of tissue. There
was evidence of tissue deposition and leaflet-to-leaflet healing. At
12 weeks, tissue encapsulation was further developed with leafletto-leaflet bridging between the arms of the clip. At 24 weeks, development of a mature tissue bridge was present (Figure 2).18
The procedure requires a dedicated team of physicians. In
addition to an interventional physician, a skilled echocardiographer and an anesthesiologist all work together during the
procedure. Clear communication between the interventionalist
and the echocardiographer providing the transesophageal
echocardiographic guidance is critical to achieve an optimal result.19 While evaluating hemodynamics, changes in blood pressure, afterload and vascular tone need to be kept in mind in
the anesthetized patient.
The Mitraclip system has been successfully evaluated in a
U.S. phase I clinical trial (Endovascular Valve Edge-to-edge Repair Study; EVEREST I).20,21 The study population consisted of
surgical candidates with moderate-to-severe or severe MR and
clinical symptoms. Asymptomatic patients were eligible if
echocardiographic evidence of LV dysfunction was present.
MAY 2010 I VOLUME 7, NUMBER 5
American College of Cardiology/American Heart Association
(ACC/AHA) guidelines criteria for surgical intervention were
followed and patients were closely screened using American
Society of Echocardiography quantitative methods for assessment of MR severity.22,23 All of the echocardiographic exams
were reviewed in a core laboratory. Echocardiographic
anatomic inclusion criteria included specific leaflet morphologic findings to determine if adequate tissue was available and
the location of the MR jet origin (from the central two-thirds
of the line of coaptation) (Figure 4).
A Phase I trial has been completed in a cohort of 55 patients. Registry data from a nonrandomized group of 107 patients,21 as well as outcomes in a high-risk cohort of 78 patients,
have been reported. The primary endpoint of the EVEREST I
trial was safety at 30 days. Safety was defined as freedom from
death, myocardial infarction, cardiac tamponade and cardiac
surgery for failed clip or device, clip detachment, permanent
stroke or septicemia. A clip was placed successfully in about
90% of cases. Of those who achieve acute procedural success,
defined as adequate reduction in MR without a procedural
complication, two-thirds were alive and had no need for repeat
procedures after 2-year follow-up. In a high-risk group of 78
patients, in addition to improvement in New York Heart Association functional class, favorable ventricular remodeling
VASCULAR DISEASE MANAGEMENT E129
Cilingiroglu and Feldman
Figure 4. Specific morphologic features of the mitral valve are required for the Evalve MitraClip™ to have a good
probability of success. There must be enough coaptation length for the clip to be grasped. A flail gap larger than 10
mm makes success of adequate reduction in MR unlikely, as does a flail width of more than 15 mm. The need for
some coaptation length effectively excludes patients with an extremely dilated mitral annulus. In these cases, left
ventricular failure with chamber dilatation and annular dilatation causes the leaflet edges to be pulled apart. Annuloplasty is more likely necessary in this anatomic setting.
with a decrease in LV systolic and diastolic dimensions and reduction in the need for hospitalizations among high-risk patients have been demonstrated. Compared to match-controls
who were also considered high risk for surgery, there was improved 1-year survival.
A phase II randomized trial (EVEREST II) comparing the
clip with surgical therapy in 279 patients has been completed. In this study, eligible patients were prospectively randomized to percutaneous repair versus surgery using 2:1
allocation and are undergoing clinical and echocardiographic
follow-up. The trial is prospective, core lab-evaluated and
event-monitored. None of the past surgical trials of mitral
repair therapy have been prospective, with intention-to-treat
methods or core labs. Thus, in most surgical reports, the proportion of patients for whom repair is intended but in whom
replacement is ultimately performed is not clearly defined.
The MR reduction results of surgical mitral repair have not
been assessed using objective criteria through an echocardiography core lab with quantitative MR grading. Thus, EVEREST phase II trial is groundbreaking not only in the
development of the percutaneous therapy, but also in defining the results of the mitral valve surgery in a multicenter
trial. At the end of 2009, patient enrollment was completed
and the 1-year follow-up time point had been reached for the
entire group. The results of the trial have not been reported
at the time of this writing.
The MitraClip has been approved in Europe, and early use
shows a pattern weighted towards high-risk patients with
about two-thirds with functional and one-third with degenerative MR. Patients treated in the initial European experience
have usually been referred by surgeons.
E130
VASCULAR DISEASE MANAGEMENT
Potential limitations of this technique include large device
size (a 24 Fr guide catheter), technically demanding procedures
and uncertainty about the long-term-durability of the results
since results beyond 3 years have yet to be reported. Surgical
leaflet repair is almost always done in conjunction with an annuloplasty, and the surgical community sees the lack of annuloplasty as an important limitation of this approach. In
addition, the feasibility and efficacy of this technique is limited
to specifically suitable anatomy and is not applicable in subsets
of patients with extreme pathology of leaflets including rheumatic disease or ruptured papillary muscle. The MitraClip™
appears to serve a clear unmet need in patients who are high
risk for surgery. The role of this therapy for surgical candidates
will be defined by the randomized EVEREST II trial.
Percutaneous Mitral Annuloplasty
Annuloplasty techniques using percutaneous approaches are
either indirect or direct. Indirect methods are based on the relationship of the coronary sinus to the mitral annulus. The
Coronary sinus parallels the posterior mitral annulus, and thus
provides a route for annuloplasty device delivery.
Coronary Sinus Annuloplasty
Functional MR is primarily the result of incomplete coaptation of normal leaflets as a result of progressive mitral annular
dilation, alteration in LV geometry and/or papillary muscle dysfunction.24,25 This secondary MR frequently accompanies ischemic
or chronic heart failure and triggers a vicious cycle of continuing
volume overload, ventricular dilation, progression of annular dilation and increased LV wall tension, and thus further worsening
of MR and heart failure.26,27 In addition, this functional disorder
MAY 2010 I VOLUME 7, NUMBER 5
PERCUTANEOUS MITRAL VALVE INTERVENTIONS
of 3–6 weeks with dissolution of the absorbable suture. In an animal model, the
average reduction in anterior-posterior
distance of the mitral annulus was 24%
at 9 weeks, resulting in significantly improved MR. Among the first 5 reported
patients, the bridge fractured in 3, without any clinical complications, but with
loss of efficacy. This has led to redesign of
the device, and the trial has been resumed
with implants in an additional 80 patients. In this second group, reductions of
1 to 2 grades of MR were seen in 60% of
patients. Coronary compression that was
clinically evident occurred in 3 with an
Figure 5. Monarc™ device (Edwards Lifesciences, Irvine, Calif.). Two selfacute MR resulting in death in 1 patient,
expandable nitinol stent anchors connected by a spring bridge element.
and device fractures were noted in a few.
Results in a cohort of 70 patients have
can eventually lead to loss of systolic sphinteric contraction of
been presented.35 These initial data confirm feasibility, but also
the mitral annulus and retraction of the chordea tendinea with
the challenges of percutaneous coronary sinus-based annular
fibrosis. Functional MR secondary to LV dysfunction is a signifremodeling in humans, and demonstrate a potential beneficial
icant clinical problem, representing an independent and strong
effect on functional MR in selected groups of patients.
predictor of mortality in patients with both ischemic and nonisThe Carillon™ device (Cardiac Dimensions, Kirkland,
28
Washington) is constructed of a nitinol wire with distal and
chemic heart failure. Although medical therapies play a role in
alleviating symptoms, they do not arrest or slow the deterioraproximal figures of eight anchors connected by an intervening
tion of LV function caused by chronic MR. In the absence of
wire, also placed via jugular venous access (Figure 6). The disstructural mitral valve abnormalities, the dimension of the mitral
tal anchor is released from the 9 Fr guide catheter and placed
valve annulus is the most significant determinant of mitral leaflet
in the great cardiac vein and the guide catheter is mechanically
coaptation, regurgitant orifice area and subsequent MR. Hence,
pulled upward, resulting in tension on the coronary sinus with
the dominant modality of the current surgical approach is inserresultant shortening of the circumference of the coronary sinus.
tion of a mitral annuloplasty ring that reduces annular circumIn animal models of heart failure, after device insertion, the miference and pushes the posterior leaflet forward for better
tral annular septal-lateral dimension was reduced by 25%,
coaptation, thereby decreasing MR.24,29
with substantial improvement in heart failure-induced MR and
However, relatively high mortality and morbidity rates may
significant improvement in pulmonary capillary wedge presrender surgical treatment prohibitive in the majority of heart failsure.34,36 Initial experience involving 50 patients clearly demonure patients.29 Furthermore, clear survival benefits from surgical
strates the ability to reduce MR by 1 or 2 grades. The reduction
annuloplasty for functional MR have yet to be demonstrated.30,31
in MR is immediate and can be modulated during the proceThus, several less invasive percutaneous annuloplasty modalities
dure in the catheterization laboratory. If the distal anchor
crosses over the circumflex artery or an obtuse marginal
via the coronary sinus have become the target of clinical rebranch, it can be pulled back to relieve coronary compression.
search. The anatomic proximity of the coronary sinus to the posOf course, if the device is pulled back, there is less efficacy for
terior mitral annulus, coupled with ease of percutaneous access
MR reduction. Although investigation continues in Europe, the
to this large vein, offers a basis for the development of less invadevice has not yet had a trial in the United States.
sive catheter-based mitral annuloplasty.32,33
Another coronary sinus device, the Viacor™ (Viacor, Inc.,
Some of the initial permanent human implants of a coroWilmington, Massachusetts) uses a 7 Fr triple-lumen delivery
nary sinus annuloplasty device were reported using the Edcatheter from a subclavian venous access into the coronary
wards Monarc™ device34 (Edwards Lifesciences, Irvine,
sinus and tracked into the great cardiac vein. The implant conCalifornia). The prototype device consisted of three elements:
sists
of a composite nitinol and stainless-steel construct coated
two anchor self-expanding stents, one to be deployed distally
with medical-grade Teflon and polyethylene plastic. Nitinol
in the great cardiac vein and the second, larger anchor is derods of varying stiffness are placed into the three lumens
ployed in the coronary sinus ostium proximally, and a spring
within the delivery catheter so that pressure is placed in the
connector bridge (Figure 5). The bridge element is held in the
mid-coronary sinus compressing the septal-lateral dimension.
open position by absorbable suture material. The mitral annuRod stiffness can be changed until some diminution in MR is
lar circumference decreases as the bridge shortens over a period
MAY 2010 I VOLUME 7, NUMBER 5
VASCULAR DISEASE MANAGEMENT E131
Cilingiroglu and Feldman
Figure 6. Coronary sinus annuloplasty (Carillon™, Cardiac Dimensions, Inc., Kirkland, Washington). Proximal and
distal anchors and the nitinol wire bridge. Once delivered, the device is pulled to cinch the coronary sinus.
achieved. The rod can be swapped out at a future time if additional stiffness is needed. Preliminary human experience with this
device also shows its ability to reduce MR.37,38 While the major
tension is placed in the center of the posterior leaflet, it is still
possible for circumflex coronary artery compression to occur
with this device. Further studies will define its ultimate utility.
A heat energy approach could be a unique alternative to the
implantable coronary sinus annuloplasty devices (QuantumCor™, Lake Forest, California). The principle mechanism is to
reduce the circumference of the mitral annulus by shrinkage of
collagen via application of the noncoagulating heat generated
with a coronary sinus radiofrequency probe, thus improving
mitral competence without implanted materials. The effects of
the collagen shrinkage are immediate and the shrinkage does
not regress over time because the collagen, heated to a selected
level, retains its intrinsic strength. Additionally, the fibrotic healing response to the annular heating can add strength and possibly further enhance the initial shrinkage of the annulus. The
prototype catheter has eight electrodes and the tip of the probe
is malleable to conform to the annulus shape. Delivery of radiofrequency energy to the electrodes is computer-controlled by
maximum temperatures sensed by adjacent thermocouples. In a
preliminary sheep study, variable degrees of acute annular contraction was achieved; the reduction in A-P distance of the mitral
annulus was to 26%.39 At necropsy, there was no evidence of
thrombosis or damage to the coronary arteries or cardiac vein.
The system has been used in a preclinical model, and significant
development is necessary for a percutaneous system.
Coronary sinus-based mitral valve repair is still in its early
development. Enough preliminary work has been done to provide proof of principle. Several limitations remain. The relative
position of coronary sinus is about 1 cm away from the true
mitral annulus, which may detract from the effectiveness of
this technique. Preliminary work in autopsy specimens and
early implants have shown that the postulated position of the
E132
VASCULAR DISEASE MANAGEMENT
coronary sinus in the left posterior coronary sulcus was found
in only 12% of the cases. The branches of the left circumflex
coronary artery frequently cross under the coronary sinus, and
have been compressed with resultant myocardial infarction in
early human trials. Thus, compression of a coronary artery by
the device may limit the degree to which the coronary sinus
may be encircled.
Direct Annuloplasty
Direct annulopasty eliminates some of the limitations of the
coronary sinus approach, but it requires access to the LV. Two
devices that can be implanted directly into the mitral annulus
are in the early phases of development.
The Mitralign™ percutaneous annuloplasty system (Mitralign, Inc., Tewksbury, Massachusetts) uses a transaortic approach for direct cannulation of the LV to deliver a guide
catheter into the space just beneath the posterior mitral leaflet
on the LV side. Four wires are driven through the mitral annulus
and anchored to the annulus using pledgets. The anchors are
connected by a drawstring, which can be used to apply tension
to the mitral annulus and shorten its circumference by 20%. The
current version of the device uses two pairs of anchors to plicate
the mitral annulus. The technique has been used in only a few
patients, and phase I clinical trials have yet to be undertaken.
The Guided Delivery System™ (Guided Delivery System, Santa
Clara, California) follows a similar approach, placing up to 12
nitinol anchors in the mitral annulus with a tether. This device has
been implanted during conventional cardiac surgery, with some
patients having results at least beyond 1 year. The percutaneous
method is in the early phases of development, and favorable acute
results from first-in-man procedures have been presented.
Chamber and Annular Remodeling
A novel approach to treating functional MR by remodeling
the LV chamber has been evaluated surgically using the Coapsys™
MAY 2010 I VOLUME 7, NUMBER 5
PERCUTANEOUS MITRAL VALVE INTERVENTIONS
device (Myocor, Inc., Minneapolis, Minnesota). It is composed
of a pair of epicardial pads that are anchored on the LV surface with a tensioning cable passed through the LV cavity to
pull the pads together, thereby reducing the septal-to-lateral
dimension of the mitral annulus and diminishing the LV chamber diameter.40,41 Experience with the surgical device has shown
sustained reductions in MR and LV chamber dimensions for
more than 1 year. The iCoapsys™ device is a percutaneous
transpericardial version of the surgical system.42,43 Successful
percutaneous placement has been completed in 2 patients. Another chamber remodeling approach uses a cord passed through
the left atrial cavity with anchors in the coronary sinus and fossa
ovalis. The PS3™ percutaneous septal sinus shortening system
(Ample Medical, Foster City, California) has been shown to
acutely and chronically reduce functional MR in an ovine model
tachycardia model, and has been applied in temporary human
implants before planned conventional mitral valve surgery.44
The companies that were developing both of these devices are
no longer in operation, and it remains to been seen if other devices or systems for chamber remodeling will emerge.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Conclusion
18.
With the advent of novel catheter-based techniques, an exciting new era for percutaneous management of patients with
MR is evolving. The evaluation of these new devices for MR
therapy poses new challenges. Comparisons with surgical results are inevitable. Annuloplasty devices may develop as heart
failure therapies, with trial comparisons to medical therapy.
On the other hand, there are almost no prospective data on the
results of mitral repair surgery. Intention-to-treat analyses of
mitral repair surgery have not been performed in the past. Multicenter trials, core echocardiographic laboratories and events
committees have not been utilized for surgical trials. Thus,
comparisons with surgery will require randomized trials such
as EVEREST II.
The obvious lesser invasiveness of these devices, by avoidance of an open chest incision, cardiac arrest and cardiopulmonary bypass, makes the treatment of MR in higher-risk
patients attractive, and at the other end of the spectrum offers
the chance to evaluate MR reduction earlier in the course of
heart failure. None of these devices are likely to result in a treatment for all patients with MR, and also it is likely that not all
will be ultimately successful.45 Continued development will require strong collaboration between surgeons and interventional
cardiologists.46–48 Ongoing trials will ultimately define how
these devices will be used clinically, alone or in combination.
30.
References
31.
2.
32.
1.
3.
4.
Perloff JK, Roberts WC. The mitral apparatus: Functional anatomy of mitral regurgitation. Circulation 1972;46:227.
Roberts WC. Morphologic features of the normal and abnormal mitral valve. Am J
Cardiol 1983;51:1005–1028.
Lee CS, Talbot TL. A fluid-mechanical study of the closure of heart valves. J Fluid
Mechanics 1979;91:41–63.
Bellhouse BJ, Bellhouse FH. Fluid mechanics of the mitral valve. Nature
MAY 2010 I VOLUME 7, NUMBER 5
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
33.
1969;224:615.
Bellhouse BJ. Fluid mechanics of a model mitral valve and left ventricle. Cardiovasc
Res 1972;6:199.
Ormiston JA, Shah PM, Tei C, et al. Size and motion of the mitral valve annulus in
man. I. A two-dimensional echocardiographic method and findings in normal subjects. Circulation 1981;64:113–120.
Enriquez-Sarano M, Nkomo V, Mohty D, et al. Mitral regurgitation: Predictors of
outcome and natural history. Ad Cardiol 2002;39:133–143.
Bonow RO, Carabello B, de Leon AC Jr, et al. Guidelines for management of patients
with valvular heart disease: Executive summary. Circulation 1998;98:1949–1984.
Miller DC. Ischemic mitral regurgitation redux-to repair or replace? J Thoracic Cardiovasc Surg 2001;122:1059–1062.
Lawrie GM. Mitral valve repair vs replacement: Current recommendations and longterm results. Cardiol Clin 1998;16:437–448.
Enriquez-Sarano M, Schaff HV, Orszulak TA. Valve repair improves the outcome of
surgery for mitral valve regurgitation: A multivariate analysis. Circulation
1995;91:1022–1028.
STS U.S. Cardiac Surgery Database. Mitral valve repair and replacement patients:
incidence of complications summary. www.sts.org (accessed 2002).
Calafiore AM, Gallina S, Di Mauro M, et al. Mitral valve procedure in dilated cardiomyopathy: Repair or replacement? Ann Thorac Surg 2001;71:1146–1152.
Alfieri O, Maisano F, De Bonis M, et al. The double-orifice technique in mitral valve
repair: A simple solution for complex problems. J Thoracic Cardiovasc Surg
2001;122:674–681.
Umana JP, Salehizadeh B, DeRose JJ, et al. “Bow-tie” mitral valve repair: An adjuvant
technique for ischemic mitral regurgitation. Ann Thorac Surg 1998;66:1640–1646.
Maisano F, Schreuder JJ, Oppizzi M, et al. The double orifice technique as a standardized approach to treat mitral regurgitation due to severe myxomatous disease:
Surgical technique. Eur J Cardiothorac Surg 2000;17:201–215.
Maisano F, Caldarola A, Blasio A, et al. Midterm results of edge-to-edge mitral valve
repair without annuloplasty. J Thoracic Cardiovasc Surg 2003;126:1987–1997.
Fann JI, St Goar FG, Komtebedde J, et al. Beating heart catheter-based-edge-to-edge
mitral valve procedure in a porcine model; efficacy and healing response. Circulation
2004;110:988–993.
Silvestry FE, Rodriguez Ll, Herrmann HC, et al. Echocardiographic guidance and
assessment of percutaneous repair for MR with the Evalve MitraClip: Lessons learned
from EVEREST I. J Am Soc Echocardiogr 2007;20:1131–1140.
Feldman T, Wasserman HS, Herrmann HC, et al. Percutaneous mitral valve repair
using the edge-to-edge technique: Six-month results of the EVEREST Phase I Clinical Trial. J Am Coll Cardiol 2005;46:2134–2134.
Feldman T, Kar S, Rinaldi M, et al. Percutaneous mitral repair with the MitraClip
system: Safety and midterm durability in the initial EVEREST cohort. J Am Coll
Cardiol 2009;18;54:686–694.
Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for the evaluation
of the severity of native valvular regurgitation with two-dimensional and Doppler
echocardiography. J Am Soc Echocardiogr 2003;16:777–802.
Bonow RO, Carabello BA, Chaterjee K, et al. ACC/AHA guidelines for the management of patients with valvular heart disease: A report of the American College of
Cardiology/American Heart Association Task Force on practice guidelines. Circulation 2006;114:450–457.
Miller DC. Ischemic mitral regurgitation redux-to repair or to replace? J Thorac Cardiovasc Surg 2001;122:1059–1062.
Gillinov AM, Wierup PN, Blackstone EH, et al. Is repair preferable to replacement
for ischemic mitral regurgitation? J Thorac Cardiovasc Surg 2001;122:1125–1141.
Lamas GA, Mitchell GF, Flaker GC, et al. Clinical significance of mitral regurgitation
after acute myocardial infarction. Survival and ventricular enlargement investigators.
Circulation 1997;96:827–833.
Trichon BH, O’Connor CM. Secondary mitral and tricuspid regurgitation accompanying left ventricular systolic dysfunction: Is it important, and how is it treated?
Am Heart J 2002;144:373–376.
Blondheim DS, Jacobs LE, Kotler MN, et al. Dilated cardiomyopathy with mitral
regurgitation: Decreased survival despite a low frequency of left ventricular thrombus.
Am Heart J 1991;122:1468–1475.
Harris KM, Sundt TM 3rd, Aeppli D, et al. Can late survival of patients with moderate ischemic mitral regurgitation be impacted by intervention on the valve? Ann
Thorac Surg 2002;74:1468–1475.
Wu AH, Aaronson KD, Bolling SF, et al. Impact of mitral valve annuloplasty on
mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction. J Am Coll Cardiol 2005;45:381–387.
Mihaljevic T, Lam BK, Rajeswaran J, et al. Impact of mitral valve annuloplasty combined with revascularization in patients with functional ischemic mitral regurgitation.
J Am Coll Cardiol 2007;49:2191–2201.
Liddicoat JR, Mac Neill BD, Gillinov AM, et al. Percutaneous mitral valve repair: A
feasibility study in an ovine model of acute ischemic mitral regurgitation. Catheter
Cardiovasc Interv 2003;60:410–416.
Kaye DM, Byrne M, Alferness C, Power J. Feasibility and short-term efficacy of percutaneous mitral annular reduction for the therapy of heart failure-induced mitral
VASCULAR DISEASE MANAGEMENT E133
Cilingiroglu and Feldman
regurgitation. Circulation 2003;108:1795–1797.
34. Webb JG, Harnek J, Munt BI, et al. Percutaneous transvenous mitral annuloplasty:
Initial human experience with device implantation in the coronary sinus. Circulation
2006;113:851–855.
35. Schofer J. Presentation, American College of Cardiology, 2008, Chicago, March.
36. Byrne MJ, Kaye DM, Mathis M, et al. Percutaneous mitral annular reduction provides continued benefit in an ovine model of dilated cardiomyopathy. Circulation
2004;110:3088–3092.
37. Dubreuil O, Basmadjian A, Ducharme A, et al. Percutaneous mitral valve annuloplasty for ischemic mitral regurgitation: First in man experience with a temporary
implant. Cathet Cardiovasc Diagn 2007;69:1053–1061.
38. Feldman T. Percutaneous mitral annuloplasty: Not always a cinch. Catheter Cardiovasc Interv 2007;69:1062–1063.
39. Heuser RR, Witzel T, Dickens D, et al. Percutaneous treatment of mitral regurgitation: The QuantumCor system. J Interv Cardiol 2008;21:178–182.
40. Grossi EA, Goldberg JD, LaPietra A, et al. Ischemic mitral valve reconstruction and
replacement: Comparison of long-term survival and complications. J Thorac Cardiovasc Surg 2001;122:1107–1124.
41. Grossi EA, Saunders PC, Woo YJ, et al. Intraoperative effects of the coapsys annuloplasty system in a randomized evaluation (RESTOR-MV) of functional ischemic mitral regurgitation. Ann Thorac Surg 2005;80:1706–1711.
E134
VASCULAR DISEASE MANAGEMENT
42. Pedersen WR, Block PC, Feldman TE. The iCoapsys repair system for the percutaneous treatment of functional mitral insuffiency. Eurointervention 2006;1(Suppl
A):A44–A48.
43. Pederson WR, Block P, Leon M, et al. iCoapsys mitral valve repair system: Percutaneous implantation in animal model. Catheter Cardiovasc Interv 2008;72:125–131.
44. Rogers JH, Macoviak JA, David A, et al. Percutaneous septal sinus shortening: A
novel procedure for the treatment of functional mitral regurgitation. Circulation
2006;113:2329–2334.
45. Feldman T. Percutaneous valve repair and replacement: Challenges encountered, challenges met, challenges ahead. Circulation 2006;113:771–773.
46. Vassiliades TA, Block PC, Cohn LH, et al. Society of Thoracic Surgeons: American
Association of Thoracic Surgery; Society of Cardiovascular Angiography and Intervention. The clinical development of percutaneous heart valve technology: A position
statement of the Society of Thoracic Surgeons (STS), the American Association for
Thoracic Surgery (AATS), and the Society of Cardiovascular Angiography and Intervention (SCAI). Catheter Cardiovasc Interv 2005;65:73–79.
47. Rosengart TK, Feldman T, Borger MA, et al. American Heart Association statement
on percutaneous and minimally invasive valve procedures. Circulation
2008;117:1750–1767.
48. Feldman T, Leon MB. Prospects for percutaneous valve therapies. Circulation
2007;11:2866–2877.
MAY 2010 I VOLUME 7, NUMBER 5