Percutaneous
Mitral Valve
Repair Techniques
Abstract
This chapter describes established and emerging
percutaneous mitral valve repair techniques. The goal of any percutaneous
procedure is to achieve a durable correction of mitral disease with clinical
efficacy similar to that of well-established open surgical interventions.
Knowing which patients will benefit most from percutaneous approach and which
approach to apply is exceedingly challenging given the complex and varied
pathophysiology and anatomy of mitral valve disease. Surgical risk is often
prohibitive given that mitral valve disease is both caused by and develops in
parallel to many comorbidities that increase surgical risk. By applying
concepts that have made surgical repair successful to the engineering of
percutaneous technologies, restoring proper mitral valve function with catheter
based techniques can be performed without many of the risks inherent to
surgery. Percutaneous therapies therefore represent an expanding toolbox for
the modern valvular heart disease center that strives to repair mitral valve
disease in patients at all levels of surgical risk. Although catheter based
repairs for MR are only approved in patients at prohibitive surgical risk, as
more data is collected, percutaneous repair may one day be used as a viable option to surgical candidates who wish to avoid surgery.
Keywords :
percutaneous mitral valve repair, mitral stenosis, degenerative
mitral regurgitation, functional
mitral regurgitation, balloon mitral
valvuloplasty, MitraClip, EVEREST trials, COAPT trial, Carillon Mitral Contour System, AMADEUS trials, TITAN trials, AccuCinch
Ventriculoplasty System, Cardioband
System, IRIS complete annuloplasty ring
· Percutaneous therapies have changed how the modern cardiothoracic
surgeon approaches the treatment of valvular heart disease. Although much of
this evolution has come with the advent of transcatheter aortic valve
replacement, considerable obstacles inherent to mitral valve disease have been
overcome to develop multiple percutaneous technologies.
· Surgery is often difficult because mitral valve disease is both caused
by and develops in parallel to many comorbidities that increase surgical risk.
This has been demonstrated by reports that as many as 50% of patients with
severe mitral regurgitation (MR) are not candidates for surgery.
· The challenge of developing effective percutaneous mitral valve repair
technology stems from the complexity and variation of both the pathophysiology
of mitral valve disease and the anatomy of the mitral valve apparatus.
· Degenerative MR (DMR; Video 22.1) develops when disease of the valve
itself prevents sufficient mitral leaflet coaptation via leaflet or chordal
elongation, chordal rupture, or annular deformation, whereas functional MR
(FMR) develops when left ventricular dysfunction and deformation prevent
sufficient coaptation of anatomically normal leaflets via annular dilation or
leaflet tethering.
· Patients with central, discrete regurgitant jets with relatively narrow
bases and single-leaflet prolapse or flail may benefit from percutaneous
edge-to-edge repair.
· Patients with enlarged hearts, annular dilation, minimal tenting, and
central jets may benefit from percutaneous annuloplasty.
· Successful coronary sinus based annuloplasty is more easily achieved in
patients with a large coronary sinus and a large great cardiac vein, with
minimal tortuosity. Moreover, effective reduction of the septolateral diameter
can only be achieved if the coronary sinus and great cardiac vein lie in the
same plane as the mitral annulus (Fig. 22.1).
· The goal of any percutaneous procedure is to achieve a durable
correction of mitral disease with clinical efficacy similar to that of
well-established open surgical interventions. Most approaches to percutaneous
mitral valve repair are modeled after established surgical techniques.
· By applying concepts that have made surgical repair successful to the
engineering of percutaneous technologies, restoring proper mitral valve
function can be performed without the risks inherent to surgery.
1. Percutaneous Treatment of Mitral Stenosis
· Worldwide, mitral stenosis (MS) most commonly results from rheumatic
valvular disease, typically with fusion of the leaflets at the commissures.
· Balloon mitral valvuloplasty (BMV) splits the fused commissures,
allowing the mitral valve to open more fully, and is the most well-established
catheter-based repair of mitral disease since the 1990s.
· The applicability and efficacy of BMV are limited, with optimal outcomes
in patients with a mitral valve that is relatively thin and free of
calcification, resulting in greater leaflet mobility when the fused commissures
are divided and minimizing the risk of embolic complications.
· BMV lacks utility when concomitant left atrial clot or more than mild to
moderate MR is present. Once either of these is present, mitral valve surgery
is preferred unless the patient is at prohibitive surgical risk.
· BMV has limited efficacy in those with senile calcific MS because it is
caused not by commissural fusion but by calcification that extends into the
leaflets from their origination in the annulus.
2. Percutaneous Treatment of Mitral Regurgitation
Percutaneous Edge-to-Edge Repair
· Although uncommonly used in conventional surgical repair of MR, the
edge-to-edge repair, first described by Alfieri in 1991, has been shown to be
effective at decreasing MR without significant risk of MS in selected patients.
The MitraClip procedure (Abbott Laboratories, Abbott Park, IL) is a
percutaneously delivered device that mimics the sutures placed in an Alfieri
repair. Whereas the original Alfieri technique (Fig. 22.2) combined an
edge-to-edge suture with annuloplasty, the MitraClip procedure is currently
performed in isolation without annuloplasty. Although debated, isolated
reports have documented adequate outcomes with surgical edge-to-edge repair
without annuloplasty, providing the basis for the use of the MitraClip procedure as a sole therapy.
· Degenerative and functional MR often necessitate very different
treatment approaches but, as an intervention that was hoped to offer benefit to
patients with either cause, the MitraClip procedure was initially studied in a
heterogeneous population. Surgical mitral repair has provided excellent
outcomes for patients with DMR, but the benefit to patients with FMR is
controversial. Although there exists a gold standard for treating FMR in
nonsurgical patients, no such standard exists for treating DMR. Given the
inferior efficacy when compared to surgical repair and the lack of a gold
standard for nonsurgical patients with degenerative pathology, the US Food and
Drug Administration (FDA) approved the MitraClip procedure in 2013 as an
alternative treatment option for symptomatic patients with severe (≥ 3+) DMR at
prohibitive surgical risk.
· Currently, a functional cause of MR is not an approved indication for
the MitraClip procedure. Severe FMR certainly worsens heart failure physiology
and symptoms by contributing to volume overload and progressive dilation, but
it is yet unclear whether correcting the MR actually improves survival. The
EVEREST II (Endovascular Valve Edge to Edge Repair Study) trial has shown that
FMR is a significant predictor of mortality on multivariable analysis (hazards
ratio [HR], 2.7; confidence interval [CI], 1.4–5; p = 0.003),15 so
although the repair of MR may improve symptoms, it may not address the causal
pathophysiology or affect the clinical trajectory likely determined by the
underlying left heart dysfunction. FMR is primarily treated via goal-directed
medical therapy aimed at improving underlying left ventricular dysfunction with
beta blockade, diuretic use, angiotensin-converting enzyme inhibitors and, if
indications are found, cardiac resynchronization. It is therefore recommended
to ensure that patients receive maximal medical therapy prior to considering
mitral intervention.
· Patients with DMR must meet many anatomic criteria to have the MitraClip
device placed. Although reported to have caused only one case of MS after 5
years of follow-up in the clinical trial, there have been other reports of MS
following MitraClip placement. As such, a resting effective orifice area over 4
cm2 is required to minimize
this long-term risk of MS.19
· Considering that the Alfieri technique can only address poor coaptation
at one place along the valve orifice, multiple foci of MR preclude the use of
the MitraClip. Ideally it should be used when a single primary regurgitant jet
is present.
· Although initial studies excluded patients with excessively calcified
leaflet edges out of concern for capture failure, this has often been overcome
in subsequent clinical experience with multiple clip placement, with reports of
as many as 40% of patients receiving a second clip and some even receiving a
third.
Percutaneous Annuloplasty
· Surgical repair of MR is often accomplished by reducing the septolateral
diameter of the mitral annulus, thereby increasing coaptation with the
placement of a rigid, undersized annuloplasty ring. Several technologies have
been developed to accomplish annuloplasty percutaneously and, because it can
halt the progressive dilation of the mitral annulus often responsible for FMR,
it may be of greater benefit than MitraClip placement for those with functional
pathology. These therapies have been developed either to anchor a device to the
annulus directly or indirectly reduce septolateral diameter with a device in
close proximity to the annulus.
· As the only available technology that indirectly reduces mitral annular
diameter, the Carillon Mitral Contour System (Cardiac Dimensions, Kirkland, WA)
takes advantage of the proximity of the coronary sinus to the mitral annulus.
· Although the Carillion System obtained CE Mark approval in 2011 for
commercial use in the European Union, it continues to be investigational in the
United States with the first randomized controlled trial anticipated to begin
enrollment in 2017. It is yet to be seen whether this technology will be able
to overcome the challenges encountered in initial efficacy studies. Sufficient
reduction in MR could not be achieved in many patients because anatomic
variability led to device placement in a coronary sinus too far removed from
the annulus or above the annular plane in the wall of the left atrium.
· Furthermore, because as many as 80% of patients have been reported to
have a coronary artery course between the coronary sinus and mitral annulus,
the device had to be withdrawn in 16% of patients due to impingement of the
left circumflex artery or its major branches.
· Several technologies have emerged to anchor either an annuloplasty ring
or plication sutures directly to the mitral annulus via transvenous,
transseptal, or retrograde transaortic valve delivery systems.
· Although the company that developed the only technology available for
percutaneous placement of individual suture plication stitches has shifted
focus to its application to tricuspid disease, the various technologies that
accomplish more complete annuloplasty are in the early stages of development,
and the patient populations that will most likely benefit from each have yet to
be identified.
Step 3. Operative Steps
1. Percutaneous Treatment of Mitral Stenosis
· BMV is performed by introducing a long, specially curved, retractable needle
in a sheath through the femoral vein into the right atrium and puncturing the
atrial septum at the fossa ovalis to gain access to the left atrium (Fig.
22.3A). One or two large, high-pressure balloon catheters are then positioned
across the stenotic mitral orifice (see Fig. 22.3B) and inflated until the
orifice is stretched or adhesions between leaflets are torn, thus increasing
the valve area and decreasing the transvalvular
pressure gradient (see Fig. 22.3C).
2. Percutaneous Treatment of Mitral Regurgitation
Percutaneous Edge-to-Edge Repair
· The MitraClip system (Fig. 22.4) is composed of a steerable guide
catheter through which the MitraClip device is delivered and then positioned by
a highly maneuverable clip delivery system (CDS).
· The 24 F guide catheter is advanced into the left atrium over a
guidewire that is placed via the right femoral vein across the fossa ovalis
under fluoroscopic and echocardiographic guidance. The septum is ideally
perforated posteriorly, away from the aortic valve, and at a height of 3.5 to 4
cm (Fig. 22.5; Video 22.2). The height depends on the plane of leaflet
coaptation with DMR often necessitating higher placement due to coaptation
closer to the annular plane and FMR often necessitating lower placement due to
coaptation below the annular placement.
· Once appropriate positioning has been confirmed, the guidewire is
exchanged for a 0.035-inch Amplatz Super Stiff guidewire (Boston Scientific,
Marlborough, MA) with a 7-cm floppy tip; systemic heparin is administered for
an activated clotting time (ACT) goal of more than 250 seconds before the 24 F
guide catheter is advanced into the left atrium.
· The MitraClip at the tip of the CDS is advanced through the guide
catheter into the left atrium, where it is opened to 180 degrees (Fig. 22.6A)
to allow for easier orientation perpendicular to the mitral leaflets under
three-dimensional echocardiographic guidance (see Fig.
22.6B). The device is then advanced across the mitral valve and closed to 120
degrees to allow for mitral leaflet insertion as the device is slowly withdrawn
(Fig. 22.7).
· The leaflets are captured between cobalt chromium outer grasper and
inner gripper arms (see Fig. 22.4B; Video 22.3). Once adequate leaflet
insertion has been ensured on multiple two- dimensional transesophageal
echocardiography (TEE) views, the previously partially closed arms are fully
closed, and the MR reduction is assessed (Fig. 22.8; Video 22.4). If MR
reduction is inadequate, the graspers can be released and the device
repositioned, or additional devices can be placed.
· Once MR reduction is satisfactory, the device is deployed, the CDS and
guidance catheter are withdrawn, protamine is given until the ACT normalizes,
and the femoral sheath is removed.
Percutaneous Annuloplasty
· The Carillon Mitral Contour System (Cardiac Dimensions, Kirkland, WA) is
delivered via a 9 F catheter placed through the right internal jugular vein and
anchored in the coronary sinus near the ostium and anterior commissure.
· Annular circumference is reduced as the nitinol ribbon connecting the
distal and proximal anchors is shortened, allowing for improved leaflet
coaptation (Fig. 22.9)
· Two technologies exist for both retrograde-transaortic valve and
transvenous-transseptal device delivery.
· The Mitralign device (Mitralign, Tewksbury, MA) reduces annular
dimensions via direct suture plication. Two wires are delivered retrograde up
the aorta and across the aortic valve and penetrate the mitral annulus at adjacent
points. Under TEE and fluoroscopic guidance, the wires are used to place
pledgets on both atrial and ventricular sides of the annulus, and a suture is
placed through both pledgeted points and then tightened until the desired
plication is achieved before being held in place by a steel lock (Fig. 22.10).
· The AccuCinch Ventriculoplasty System (Ancora Heart, Santa Clara, CA)
provides a near- circumferential plication system delivered retrograde through
the aortic valve and anchored to the ventricular side of the annulus. The
AccuCinch delivers a series of anchors into the basal ventricle directly
beneath the annulus that are connected via a nitinol wire, which is tightened,
thereby reducing mitral annular and left ventricular basilar circumference
(Fig. 22.11). The developers thought that this system would have a greater
impact on ventricular geometry than with other approaches to annuloplasty.
· The Cardioband System (Edwards Lifesciences, Irvine, CA) is a tubular
Dacron band that is anchored every 8 mm as it is extruded from a 24 F sheath
around the posterior circumference of the mitral annulus from the posterior to
anterior commissure. The internal tension cable connecting each anchor is
tightened and adjusted until the desired reduction in mitral dimen- sions has
been achieved (Fig. 22.12).
· The IRIS complete annuloplasty ring (Millipede, Santa Rosa, CA) is also
placed above the mitral annulus and delivered transvenously through the atrial
septum. Instead of a system that transmits tension between anchors connected by
cable, IRIS is a collapsible nitinol ring whose interlaced double-zigzag frame
is anchored at every intersection. The distance between each anchor can be
adjusted individually via a screw at the apex of each zigzag, allowing for the
device to decrease annular dimensions while maintaining the saddle-shaped
geometry of the valve.
Step 4. Postoperative Care
1. Percutaneous Treatment of Mitral Stenosis
· Patients are monitored
for the return of MS with serial transesophageal echocardiograms, as well as
for symptoms of pulmonary edema and low cardiac output.
2. Percutaneous Treatment of Mitral Regurgitation
Percutaneous Edge-to-Edge Repair
· Aspirin is started postprocedurally, and patients are observed for 1 to
2 days before discharge.
· In addition to routine cardiac medical optimization, serial
echocardiograms are obtained to evaluate the degree and durability of the
reduction of MR.
· Although there are legitimate concerns that the presence of MitraClip
devices impairs the ability to perform subsequent surgical repair, surgical MV
reconstruction can be performed in select cases as late as 5 years after the
implantation. Unfortunately, the feasibility of surgical repair cannot be
predicted at the time of MitraClip insertion should severe MR recur.
Percutaneous Annuloplasty
◆ Both the feasibility
study AMADEUS and the initial safety and efficacy trial TITAN have demonstrated
that the Carillon system improves MR and functional status as well as provides
favorable LV remodeling up to 2 years after device placement.
◆ In addition to routine
cardiac medical optimization, similar to percutaneous edge-to-edge repair,
serial echocardiograms are obtained to evaluate the degree and durability of
the reduction of MR.
1. Percutaneous Treatment of Mitral Stenosis
· Although the increase in valve area provided by BMV is occasionally
short-lived and usually inferior to the increase provided by surgical repair or
replacement, BMV can be repeated multiple times, often allowing surgery to be
delayed for decades or avoided altogether.
· Careful patient selection is necessary because performing BMV on some
valves will result in the development of problematic MR or systemic emboli.
2. Percutaneous Treatment of Mitral Regurgitation
Percutaneous Edge-to-Edge Repair
· After the safety and feasibility of MitraClip was established with the
EVEREST I clinical trial, EVEREST II evaluated the safety and efficacy of
MitraClip when compared to conventional surgical mitral repair.
· Although EVEREST II demonstrated the superior safety of MitraClip, with
significantly fewer major adverse events at 30 days (15% vs. 48% with surgery; p
< 0.001), there was no difference when the main driver, bleeding
requiring transfusion (13% vs. 42% with surgery; p < 0.001), was
excluded (5% vs. 10% with surgery; p = 0.23).
· In terms of efficacy, EVEREST II has demonstrated that surgical repair
performs better than percutaneous repair with greater combined freedom from
death, surgery for mitral valve dysfunction, and the recurrence of 3+ or
greater MR both at 12 months (73% vs. 55% with MitraClip; p = 0.007) and
5 years (64% vs. 44% with MitraClip; p = 0.007).
· The decreased efficacy of MitraClip was driven by the increased rate of
recurrence of 3+ or greater MR (12.3% vs. 1.8% with surgery; p = 0.02)
and the need for surgery or reoperation for mitral valve dysfunction (27.9% vs.
8.9% with surgery; p = 0.003) with no significant difference in
mortality at 5 years of follow-up (21% vs. 27% with surgery; p = 0.4)
and treatment strategy not being associated with survival on multivariable
analysis (HR, 0.94; 95% CI, 0.51–1.7; p = 0.85).
· However, investigators identified an early hazard of surgery for mitral
valve dysfunction in the percutaneous group, with 78% of surgeries being
performed before 6 months, beyond which there was no difference (78% with
MitraClip vs. 76% with surgery; p = 0.77). Furthermore, combined efficacy
was no different at 5 years in the patient population that was event-free at 1
year, suggesting that the lower efficacy of percutaneous therapy may be
minimized as more is learned about optimal patient selection and device
placement.
· Despite there being more residual or recurrent severe MR after the
MitraClip procedure, percutaneous repair succeeds in providing a durable
improvement in left ventricular dimensions, New York Heart Association
functional classification, and quality of life measures. These are findings
that have been confirmed in multiple studies other than those performed by the
EVEREST group.
· EVEREST II was not able to provide a rationale for approval in patients
with FMR because 73% of the study population had degenerative pathology. The
EVEREST II high-risk follow-up study has helped address the question of whether
the MitraClip procedure can provide clinical benefit to patients with FMR,
demonstrating a trend toward increased survival with MitraClip when compared to
medical management only (76% vs. 55%; p = 0.05) and a 46% reduction in
readmission rate for congestive heart failure exacerbations.
· In combination with the results of many nonrandomized European studies
and registries, evidence has mounted to support the claim
that the risk of recurrent MR with the MitraClip procedure may outweigh the
risks of mitral valve surgery in high-risk patients. In all of these studies,
investigators found that despite percutaneous repair being associated with a
higher rate of recurrent MR, percutaneous repair provides a substantial
proportion of patients with a reduction in MR, as well as lasting symptomatic
relief and positive left ventricular remodeling.
· To determine whether the MitraClip procedure provides benefit beyond
that seen with optimal medical therapy more definitively, the Cardiovascular
Outcomes Assessment of the MitraClip Percutaneous Therapy (COAPT) for Heart
Failure Patients with FMR trial has been enrolling patients (NCT #01626079).
This study, which compares groups randomized to standard medical therapy or
MitraClip placement in addition to standard medical therapy, should clarify the
appropriate role of the MitraClip procedure in patients with FMR at a high or
prohibitive surgical risk.
Percutaneous Annuloplasty
Indirect: Annuloplasty via Device Placement Inside the
Coronary Sinus
· Although deemed safe, early generations of the Carillon System were
found to have asymptomatic fractures on follow-up imaging; thus, TITAN II was
performed to confirm the safety of an updated iteration. The results of TITAN
II were consistent with the findings of previous studies, except that only one
fracture occurred. The updated Carillon device will soon be evaluated in a
randomized, blinded clinical trial (NCT #02325830) in the United States.
Direct: Annuloplasty via Device Attachment to the
Mitral Annulus
· Similar to the limited efficacy of annular plication sutures in open
repair, Mitralign has shown modest improvements in MR grade and symptomatic
relief at 6 months. The company has therefore abandoned efforts to obtain FDA
approval for the use of their technology for mitral annular plication and has
instead focused their efforts on applying the Mitralign technology on tricuspid
annuloplasty, with the first safety and efficacy study evaluating the newly
termed TriAlign technology due to finalize enrollment in 2018.
· The first study evaluating the safety and efficacy of the AccuCinch
system has been actively recruiting participants at multiple centers in Austria
and Germany (NCT #00800046), with plans to begin enrollment soon in the United
States.
· Cardioband obtained CE Mark approval in 2015 and has since been shown to
be safe and to have provided significant improvement in MR and heart failure
symptoms at 6 months.41 A trial in the United States will soon begin, with the
goal of obtaining FDA approval.
· The IRIS complete annuloplasty ring has been placed in multiple
patients, with the first study to evaluate the safety and efficacy of the
device expected to complete enrollment in 2018 (NCT #02607527).
