Transcatheter mitral valve repair

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1
De Backer O, et al. Open Heart 2021;8:e001564. doi:10.1136/openhrt-2020-001564
►
► Additional supplemental
material is published online only.
To view, please visit the journal
online (http://dx.doi.org/10.
1136/openhrt-2020-001564).
To cite: De Backer O, Wong I,
Taramasso M, et al.
Transcatheter mitral valve
repair: an overview of current
and future devices. Open Heart
2021;8:e001564. doi:10.1136/
openhrt-2020-001564
Received 31 December 2020
Revised 19 February 2021
Accepted 12 April 2021
1
Cardiology, Rigshospitalet,
Kobenhavn, Denmark
2
Department of Cardiothoracic
Surgery, University Hospital
Zurich, Zurich, Switzerland
3
Valve Center, Ospedale San
Raffaele, Milan, Italy
4
Hirslanden Klinik im Park,
Zurich, Switzerland
Correspondence to
Dr Ole De Backer;
ole.
debacker@gmail.com
Transcatheter mitral valve repair: an
overview of current and future devices
Ole De Backer ‍ ‍,1
Ivan Wong,1
Maurizio Taramasso,2
Francesco Maisano,3
Olaf Franzen,4
Lars Søndergaard1
Valvular heart disease
© Author(s) (or their
employer(s)) 2021. Re-
use
permitted under CC BY-
NC. No
commercial re-
use. See rights
and permissions. Published
by BMJ.
ABSTRACT
The field of transcatheter mitral valve repair (TMVr) for
mitral regurgitation (MR) is rapidly evolving. Besides the
well-
established transcatheter mitral edge-
to-
edge repair
approach, there is also growing evidence for therapeutic
strategies targeting the mitral annulus and mitral valve
chordae. A patient-
tailored approach, careful patient
selection and an experienced interventional team is crucial
in order to optimise procedural and clinical outcomes. With
further data from ongoing clinical trials to be expected,
consensus in the Heart Team is needed to address these
complexities and determine the most appropriate TMVr
therapy, either single or combined, for patients with severe
MR.
INTRODUCTION
Mitral regurgitation (MR) contributes to
significant morbidity and mortality. In degen-
erative MR, medical treatment may be insuf-
ficient and cardiac surgery has traditionally
been the only effective option. The manage-
ment of functional MR is more complex and
controversial. Functional MR is the result of
myocardial disease and treatment is directed
at the underlying cardiomyopathy. Guideline-
directed medical therapy (GDMT) and
cardiac resynchronisation therapy (CRT) are
the cornerstones of treatment, with a focus
on the reversal of adverse left ventricular
(LV) remodelling. Surgical intervention for
functional MR has yielded no difference in
clinical outcomes, with high rates of recur-
rent MR.
The advent of transcatheter mitral valve
repair (TMVr) therapies has provided feasible
and safe alternatives to medical and surgical
treatment—especially for those patients who
are not considered suitable candidates for
conventional mitral valve surgery. Transcath-
eter mitral edge-
to-
edge repair has been the
most successful and adopted TMVr therapy
to date; with some important new device iter-
ations and improvements in 2020. Besides
mitral edge-
to-
edge repair, there is also
growing evidence for therapeutic strategies
targeting the mitral annulus and mitral valve
chordae (box 1). This review article aims at
providing a comprehensive overview of all
TMVr devices in clinical use and preclinical
evaluation at the end of 2020.
Transcatheter mitral annuloplasty
The purpose of surgical and transcatheter
mitral annuloplasty is to reduce the annular
circumference and obtain better coaptation
of the mitral leaflets. Mitral annuloplasty
techniques using transcatheter approaches
can be classified as indirect or direct, based
on their relation to the mitral annulus.
Transcatheter indirect mitral annuloplasty
methods are based on the parallel rela-
tionship of the coronary sinus (CS) to the
mitral annulus; the Carillon Mitral Contour
System (Cardiac Dimensions, Washington,
DC, USA) received CE mark approval and
the ARTO system (MVRx, California, USA)
was studied in the Mitral Valve Repair Clin-
ical (MAVERIC) CE Mark trial. Direct mitral
annuloplasty eliminates some of the limita-
tions of the CS approach but represents a
technically more challenging and complex
procedural approach. Two systems that come
the closest to a surgical mitral annuloplasty
are the Cardioband Mitral System (Edwards
Lifesciences, California, USA) and the Milli-
pede Mitral Annuloplasty System (Boston
Scientific, Massachusetts, USA). Both systems
use a transseptal approach with a steerable
guide catheter.
Despite the fact that some of these tran-
scatheter mitral annuloplasty technolo-
gies were already developed and received
approval several years ago, none of these
technologies have seen the same diffusion
or adoption in daily clinical practice as the
MitraClip system (Abbott, Illinois, USA).
Not only engineering and procedural chal-
lenges but also mixed study results have
complicated and impacted the adoption
of these technologies in current prac-
tice. Also considering the high recurrence
rates of functional MR after surgical mitral
annuloplasty, future studies will have to
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2 De Backer O, et al. Open Heart 2021;8:e001564. doi:10.1136/openhrt-2020-001564
investigate whether transcatheter mitral annuloplasty
will provide sustained echocardiographic and clinical
effects or whether these techniques lend themselves
more to combined procedures—for example, tran-
scatheter mitral annuloplasty plus edge-
to-
edge mitral
valve repair. To date, only limited data are available on
combined procedures; the high cost of such combined
procedures is an item which cannot be ignored.
Carillon Mitral Contour System
The Carillon Mitral Contour System obtained CE
approval in 2011 and is indicated for use in patients
with functional MR who are symptomatic despite treat-
ment with GDMT and who are presenting with annulus
dilatation as primary contributor to the significant MR.
The Carillon Mitral Contour System consists of three
components: the sizing catheter, the delivery system
and the Carillon implant. The sizing catheter is used
to estimate the dimensions of the CS and great cardiac
vein (GCV), so that an appropriately sized implant
can be selected. The delivery system facilitates percu-
taneous delivery of the implant, engagement of the
locking mechanism, and repositioning or recapture
of the implant, if necessary. The Carillon XE2 implant
is composed of a distal anchor (positioned in the
GCV), proximal anchor (positioned in the CS), ribbon
connector (joining the anchors), and proximal and
distal crimp tubes (figure 1). The implant is designed
to be deployed, tensioned and secured in the coronary
vein. The MR reduction is immediate and can be modu-
lated during the procedure in the cathlab. The proce-
dure is performed through the jugular venous access
and is usually carried out without general anaesthesia.
Limitations of the Carillon System are (1) the distance
between the CS and the mitral annulus, which may limit
the therapeutic effectiveness; (2) the risk of compres-
sion on the left circumflex coronary artery by the distal
anchor—although the device can be repositioned or
retrieved, if needed and (3) the Carillon System is not
recommended in patients with a CRT device or pacing
lead in the CS.
In the randomised sham-
controlled REDUCE FMR
trial enrolling 120 patients, treatment with the Carillon
device was shown to significantly reduce MR volumes
(−7.1
mL/beat vs +3.3
mL/beat in the sham-
control
group) and LV volumes in symptomatic patients with
functional MR receiving GDMT.1
Recently published
5-
year follow-
up data also indicate durable functional
improvement and favourable 5-
year survival rates
following treatment with the Carillon System.2
These
results supported the CARILLON randomised trial
(ClinTrials.Gov: NCT03142152), which is ongoing at
75 sites in Europe and the USA, and is comparing the
device to GDMT in 352 patients with functional MR.
ARTO system
The ARTO system is a transcatheter indirect mitral
annuloplasty device which aims to improve mitral leaflet
coaptation and decrease functional MR via a ‘bridge
suture’ that connects anchors placed in the GCV and
the atrial septum.
Using fluoroscopy, delivery of the ARTO system
is accomplished by venous access to the right atrium
where two procedural steps are performed: (1) the CS
is cannulated from the right jugular vein and a T-
bar
implant is deployed in the lateral wall via the GCV and
(2) an atrial septal implant is deployed through a trans-
septal puncture. A ‘bridge suture’ between these two
anchors provides the means for inward displacement
and subsequent reduction of the mitral annular antero-
posterior diameter (figure 2). The bridge length is
adjusted to achieve optimal MR reduction. Feasibility
of MitraClip treatment after ARTO has been shown,
despite presence of the bridge.
Results of the prospective, non-randomised MAVERIC
CE Mark trial using the ARTO system in 45 patients with
functional MR showed the ARTO system to be safe and
effective in decreasing functional MR up to 1-
year post-
procedure. The primary safety composite endpoint
(death, stroke, myocardial infarction, device related
surgery, cardiac tamponade, renal failure) at 30 days
and 1 year was 4.4% and 17.8%, respectively. The mitral
annular antero-
posterior diameter decreased from
41.4 mm (baseline) to 36.0 and 35.3 mm at 30 days and
1 year, respectively. Paired results for 36 patients showed
that 67% of patients had MR grade 3+/4+ at baseline vs
only 14% and 8% of patients at 30 days and 1-
year post-
procedure. In accordance, 69% of patients had New
York Heart Association (NYHA) Class III–IV symptoms
at baseline, decreasing significantly to 25% and 22% of
patients at 30 days and 1-
year post-
procedure, respec-
tively.3–6
Larger randomised controlled trials (RCTs)
studying the safety and efficacy of the ARTO system are
needed.
Cardioband Mitral System
The Cardioband Mitral System is a transcatheter, trans-
septal adjustable direct mitral annuloplasty device which
aims to reduce the annular circumference and improve
Box 1 Transcatheter mitral valve repair techniques (2020)
I. Transcatheter mitral annuloplasty.
IA. Indirect mitral annuloplasty.
►
► Carillon Mitral Contour System.
►
► ARTO system.
IB. Direct mitral annuloplasty.
►
► Cardioband Mitral System.
►
► Millipede Transcatheter Mitral Annuloplasty System.
II. Transcatheter edge-
to-
edge mitral valve repair.
►
► MitraClip G4 system.
►
► PASCAL Transcatheter Valve Repair System.
III. Transcatheter mitral valve chordal repair.
►
► NeoChord.
►
► HARPOON Mitral Valve Repair System.
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mitral leaflet coaptation. The Cardioband implant
consists of a polyester sleeve with radiopaque markers at
every 8 mm; the sleeve covers the delivery system which
deploys the screw anchors. Correct positioning of the
first anchor is crucial and multiplanar transesophageal
echocardiography (TEE) and 3D-
TEE views are neces-
sary to verify correct placement (figure 3). The first
anchor is placed lateral and as anterior as possible in the
mitral annulus; coronary angiography is performed to
rule out damage to the left circumflex coronary artery.
The anchors are repeatedly placed along the posterior
side at the mitral annulus until the implant catheter
tip reaches the last anchoring site at the medial side. A
contraction wire following the same path as the sleeve
is connected to an adjusting spool. Activating the spool
cinches the Cardioband device, thereby reducing the
mitral annular diameter. Adequate reduction of MR
severity is assessed by TEE under beating heart condi-
tions. The implant is available in different sizes.
The Cardioband Mitral System gained CE mark for
the treatment of functional MR in 2016. In a single-
arm,
multicentre prospective study, results obtained in 60
consecutive patients with moderate or severe functional
MR treated with the Cardioband System were reported.
There were two in-
hospital deaths (none device-
related), one stroke, two coronary artery complications
Figure 1 Carillon Mitral Contour System. (A) Components of the Carillon implanted device—the distal and proximal anchor
are implanted in the great cardiac vein (GCV) and coronary sinus (CS), respectively. (B) Components of the Carillon Handle
Assembly. (C and D) The implant is designed to be deployed, tensioned and secured in the coronary vein; the reduction of the
mitral regurgitation is immediate and can be modulated during the procedure. Images courtesy of and provided by Cardiac
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and one tamponade. Anchor disengagement, observed
in 10 patients, resulted in device inefficacy in 5 patients
and led to device modification half way through the
study to mitigate this issue. Technical, device and proce-
dural successes were 97%, 72% and 68%, respectively.
At 1-
year, overall survival, survival free of readmission
for heart failure and survival free of reintervention
(performed in seven patients) were 87%, 66% and
78%, respectively. MR grade at 12
months was ≤grade
2+ in 61% of the overall population and in 95% of the
39 patients who underwent a transthoracic echocardi-
ography at 1 year; but worsened by at least one grade in
11 patients (22%). The latter suggests some recurrence
of functional MR in this population. Functional status
(79% vs 14% in NYHA Class I/II), quality of life and
exercise capacity (+58
m by 6MWT) improved signifi-
cantly.7
In summary, the Cardioband Mitral System
demonstrated reasonable performance and safety;
however, a larger RCT is absolutely needed. In the
ACTIVE trial, patients will be randomised 2:1 to receive
either TMVr with the Cardioband Mitral System plus
GDMT versus GDMT alone.
Millipede Transcatheter Mitral Annuloplasty System
The Millipede System is a transcatheter, transseptal
direct mitral annuloplasty device currently under
development and investigation. The technology has
demonstrated proof-
of-
concept in more than 20 human
Figure 2 ARTO system. (A) Insertion of a guide wire in the great cardiac vein (GCV) via the right jugular vein and transseptal
insertion of a guide wire and 12 Fr sheath into the left atrium (LA). (B) Insertion of GCV and LA magnetic catheters, which
should connect at the side of the posterior mitral leaflet. (C) Insertion of the crossing wire from GCV to LA side through the
magnetic catheters. (D) Following removal of the magnetic catheters and exchanging the crossing wire with the bridge-
extension wire, implantation of the T-
bar device in the lateral wall via the GCV. (E) Next, implantation of the septal device. (F)
Tensioning of the ‘bridge wire’ between the T-
bar in the GCV and septal anchor, resulting in shortening of the mitral annulus
anterior–posterior diameter and mitral regurgitation reduction. Images courtesy of and provided by MVRx.
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clinical procedures8–10
and is currently enrolling in a
global feasibility study.
The Millipede device has a complete semi-
rigid ring
design that conceptually follows the full-
ring surgical
predicates most commonly used as a stand-
alone mitral
valve repair for patients with functional MR. It has a
nitinol zig-
zag stent frame that is circumferentially
fixed to the annulus by eight helical anchors. The top
of the frame has eight slider components that can be
individually cinched to achieve tailored downsizing of
the mitral annulus (figure 4). The delivery catheter is
designed for the transvenous transseptal delivery route
and has a 27 Fr profile.
A unique feature of the Millipede technology is the
possibility of using an integrated intracardiac echocar-
diography catheter through the central lumen of the
delivery catheter, providing unobstructed near-
field
imaging of the mitral annulus. This imaging modality is
primarily used for control of device anchoring.
Transcatheter edge-to-edge mitral valve repair
Alfieri and colleagues first described the surgical repair
of prolapse of the anterior mitral valve leaflet using an
edge-
to-
edge technique by opposing the middle scal-
lops of the anterior and posterior leaflets with a stitch,
creating a so-
called ‘double-
orifice’ mitral valve.11
Since
the Alfieri repair is acting at the leaflet level, it can be
applied independently of the underlying mechanism of
MR. It is the only therapy which can be effective both to
degenerative and functional MR.
During the past decade, the MitraClip system (Abbott)
has been increasingly adopted as a method of creating
Figure 3 Cardioband Mitral System. (A) The Cardioband delivery system. (B) Correct positioning of the first anchor at the
anterior and lateral side of the mitral annulus. (C) The anchors are repeatedly placed at the mitral annulus—covered by the
polyester sleeve—until the implant catheter tip reaches the last anchoring site at the medial side. (D and E) Cinching of the
Cardioband device, resulting in a reduction of the mitral annular diameter and mitral regurgitation severity. Images courtesy of
and provided by Edwards Lifesciences.
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an edge-to-edge mitral valve repair using a percutaneous
transseptal approach. The MitraClip system received
CE mark approval in 2008 and has since then known a
steady growth in its use12–15
; it also received Food and
Drug Administration (FDA) approval for degenerative
and functional MR in 2013 and 2019, respectively. It has
been implanted in more than 100 000 patients in over
50 countries and is the only TMVr therapy to complete
prospective trials comparing the device to conventional
mitral valve surgery16 17
and GDMT.18–21
The PASCAL Transcatheter Valve Repair System
(Edwards Lifesciences) received CE mark approval for
the treatment of MR and was introduced in 2019 after
showing acceptable outcomes in the CLASP study in
a patient population of functional, degenerative and
mixed aetiology.22
MitraClip system
The MitraClip system is a therapeutic option for patients
with moderate-
to-
severe and severe degenerative, func-
tional or mixed MR who are not considered suitable
candidates for conventional mitral valve surgery. Some
valve morphologies are more suitable for MitraClip
therapy than others (see online supplemental file 1).
TheMitraClipsystemconsistsofasteerableguidecatheter
and a clip delivery system (CDS), which includes the detach-
able clip. The steerable guide and CDS allow manoeuvring
the clip in all different planes (figure 5A). MitraClip G4 is
the 4th-
generation device which comes with four enhance-
ments. A Controlled Gripper Actuation feature allows for
simultaneous or independent leaflet grasping to optimise
leaflet grasping and insertion (figure 5B). MitraClip G4
also comes with the choice between four clip sizes (NT,
XT, NTW, XTW) offering more options for patient-
tailored
TMVr (figure 5C). Integrated left atrial pressure moni-
toring enables real-
time MR assessment. Finally, a simpli-
fied system preparation and deployment should further
streamline the procedure.
The MitraClip procedure is performed under general
anaesthesia using fluoroscopy and TEE guidance. The
clip consists of two arms that are opened and closed by
control mechanisms on the CDS and two ‘grippers’ that
match up to each arm and help stabilising the leaflets as
they are captured during closure of the clip arms. Leaflet
Figure 4 Millipede Transcatheter Mitral Annuloplasty System. (A and B) The Millipede device has a complete semi-
rigid ring
design and consists of a nitinol zig-
zag stent frame that is circumferentially fixed to the annulus by eight helical anchors. (C and
D) The top of the frame has eight sliders that can be individually cinched to achieve patient-
tailored downsizing of the mitral
annulus. Images courtesy of and provided by Boston Scientific.
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tissue is secured between the arms and each side of the
gripper, and the clip is then closed and locked to maintain
leaflet coaptation. Prior to clip deployment, a leaflet inser-
tion and haemodynamic assessment should be performed
(figure 5D–F). Pressure gradients are assessed to ensure
there is no clip-
induced mitral stenosis. If needed, the
physician may also place a second or third clip to optimise
MR reduction.
Figure 5 MitraClip G4 System. (A) All components of the new-
generation MitraClip G4 System. (B) Two independent gripper
levers allow for independent grasping of the mitral leaflets. (C) The MitraClip G4 includes four clip sizes (NT, XT, NTW and XTW)
offering more options for patient-
tailored mitral valve repair. (D) After steering the clip above the mitral valve and opening the
clip arms, the clip is passed across the mitral leaflets into the left ventricle, the clip is gently pulled back and the leaflets are
grasped by the grippers. (E) Next, the clip is closed and a double orifice mitral valve opening can be seen by 3D-
TEE surgeon’s
view. (F) Final result after MitraClip implantation with approximation of the anterior and posterior mitral leaflets and reduction of
the mitral regurgitation. Images courtesy of and provided by Abbott.
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MitraClip is supported by the largest body of evidence of
all TMVr therapies. More than 30
000 patients have been
treated in MitraClip clinical trials representing 16 years of
clinical research published in more than 2050 scientific
papers. An overview of key MitraClip studies can be found
in online supplemental file 2.
Results of two RCTs comparing MitraClip with
GDMT—MITRA-FR18
and COAPT20
—in patients with
functional MR became available in 2018, with 2-
year and
3-
year follow-
up data released in 2019 and 2020, respec-
tively.19 21
The RCT findings were conflicting, with the
MITRA-
FR study showing no benefit on the primary
endpoint at 1
year (composite of death or rehospitalisa-
tion for heart failure), while the COAPT study showed
positive results on the primary endpoint at 2 years
(cumulative rate of rehospitalisation for heart failure) as
well as on all-
cause mortality. These different outcomes
observed in both RCTs may be explained by the following
aspects: (1) COAPT enrolled a subset of patients who
had more severe MR and less LV dilation compared with
MITRA-
FR patients; (2) the GDMT used in the two trials
differed—the rates of drug use and medication titration
throughout the MITRA-
FR trial course were not tracked,
and although guideline-
directed, they may not have been
guideline optimised; (3) technical success was different
between the two trials—residual MR class ≥3+ was higher
post-
MitraClip in the MITRA-
FR as compared with the
COAPT trial, both acutely (9% vs 5%) and at 12 months
(17% vs 5%). Taken together, it may be concluded
that MitraClip therapy seems to give the best result for
patients with severe MR and less advanced LV dilatation
and when MR reduction can be obtained. Under these
conditions, the MitraClip system is the only TMVr device
to show improved survival in heart failure patients with
functional MR.18–21 23–25
PASCAL Transcatheter Valve Repair System
The PASCAL Transcatheter Valve Repair System consists
of a guide sheath, steerable sheath and implant catheter
which includes the PASCAL or PASCAL Ace implant.
The ability to independently move these catheters allows
manoeuvring in three different planes; intending to assist
the operator in the treatment of challenging anatomies.
The PASCAL (10
mm width) and PASCAL Ace (6
mm
width) implants consist of two paddles, two clasps and
a central spacer: (1) the two paddles promote leaflet
approximation; (2) the two clasps allow for independent
leaflet capture and adjustment of leaflet insertion—a
clasp only has 1 row of grippers versus 4–6 rows in grip-
pers in the MitraClip system and (3) the central spacer
should reduce the tension on the leaflets and fill the
regurgitant orifice area to minimise MR. A feature of the
PASCAL implant is its ability to elongate, which promotes
safe retraction from the subvalvular apparatus, thereby
reducing the risk of damaging the chords (figure 6). The
procedure is performed under general anaesthesia using
fluoroscopy and TEE guidance and follows the same
procedural steps as a MitraClip procedure.
The PASCAL System received CE mark approval for
the treatment of MR after showing acceptable safety and
feasibility in the CLASP study in a patient population of
functional, degenerative and mixed aetiology. The proce-
dural and clinical success rate was 92% and 87%, respec-
tively. There was reduction of MR grade 3/4+ at baseline
to MR grade ≤2 in 98% of patients and to MR grade ≤1 in
86% of patients at 30 days.22 26
One-
year outcomes of the
CLASP study demonstrated a high survival rate of 92%
for the overall population and 89% and 96% for the func-
tional and degenerative MR populations, respectively.
There was evidence of sustained MR reduction with 82%
of patients having MR grade ≤1%
and 100% having MR
grade ≤2. Improvement in exercise capacity and quality
of life were also significant at 1 year.27
The PASCAL Transcatheter Valve Repair System
and MitraClip System are being compared in patients
with both degenerative and functional MR within the
CLASPIID/IIF Pivotal Clinical Trial (ClinTrials.Gov:
NCT03706833).
Transcatheter mitral valve chordal repair
Transcatheter mitral valve chordal repair systems have
been developed to treat severe degenerative MR due
to a prolapse or flail posterior, anterior or both mitral
valve leaflets. The two systems that are currently under
investigation in an FDA Pivotal and CE Mark trial are
the NeoChord Artificial Chordae Delivery System
(NeoChord, Minnesota, USA) and HARPOON Mitral
Valve Repair System (MVRS; Edwards Lifesciences),
respectively. Both systems are designed for transapical,
beating heart, off-
pump mitral valve repair and require a
left lateral thoracotomy incision.
NeoChord
NeoChord implantation is currently indicated for severe
degenerative MR due to a prolapse or flail posterior,
anterior or both mitral valve leaflets. Patients with a
central posterior leaflet (P2) prolapse or frail are the
best candidates for NeoChord treatment; it should also
be performed at an early stage of mitral valve pathology,
before annular dilatation occurs.28 29
The procedure is performed under general anaesthesia
with intraprocedural TEE guidance. Following a standard
left lateral mini thoracotomy, the apical access site should
be confirmed by real-
time 2D-
TEE imaging using gentle
‘finger poking’ approximately 2–3
cm lateral from the
true LV apex (figure 7A,B). Correct localisation of the
ideal entry site allows the operator to navigate the device
towards the mitral valve while maintaining a correct
alignment and without interfering with the subvalvular
apparatus . When an appropriate position of the device
is reached, the jaws of the device are opened (figure 7C),
and the leaflet edge is grasped by withdrawing the device
from the left atrium. A loop of the suture and a girth
hitch knot can then be formed through the mitral leaflet
(figure 7D,E). The device can be reloaded with a new
suture and the procedure can be repeated until enough
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neo-
chordae have been implanted; usually 3–4 neo-
chordae are implanted. The length of each neo-
chordae
can be adjusted to achieve maximal MR reduction under
normal LV filling conditions (figure 7F,G). Each of the
neo-
chordae can then be tied to the LV epicardial pledget
(figure 7H).
The Trans-
Apical Chordae Tendineae trial showed
satisfying immediate safety and efficacy of the NeoChord
system, leading to CE approval.30
The ongoing AcChord
Registry will provide more long-
term outcome data in
a post-
market setting. The RECHORD trial (
Clinical-
Trials.
gov: NCT02803957) is an ongoing prospective,
multicentre, randomised FDA pivotal trial intended to
establish the safety and effectiveness of the device as an
alternative to standard surgical mitral valve repair. The
company is currently working on a fully percutaneous
transseptal system, which is at the moment under pre-
clinical evaluation.
HARPOON MVRS
The HARPOON Beating Heart MVRS is intended to
reduce the degree of MR in patients with severe degen-
erative MR caused by posterior mitral leaflet prolapse
by delivering and anchoring e-
polytetrafluoroethylene
Figure 6 PASCAL Transcatheter Valve Repair System. (A) The three components of the PASCAL delivery system. (B) The
PASCAL implant consists of two paddles, two clasps and a central spacer. (C) Independent leaflet capture should enable
operators to adjust leaflet insertion and capture leaflets in difficult pathologies. (D) The newest generation PASCAL Ace implant
has 6 mm wide paddles and a smaller spacer that fills the regurgitant orifice and reduces the leaflet approximation distance.
(E) Elongation of the PASCAL device facilitates retraction of the device from the left ventricle, if needed, with a reduced risk of
getting entangled in the chords. Images courtesy of and provided by Edwards Lifesciences.
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(ePTFE) chords to the prolapsed mitral valve leaflet in a
beating heart.
The procedure is performed under general anaesthesia
using a left lateral thoracotomy incision (figure 8A). As
soon as TEE confirms that the delivery system does not
move and that the end effector stays in contact with the
targeted site on the mitral leaflet, the plunger is released
to deploy a double-
helical knot through the free-
edge
of the leaflet (figure 8B–D). These steps are repeated
until the desired number of ePTFE chords have been
implanted starting from a lateral to medial target loca-
tion. Next, all ePTFE chords are passed through a stiff
Teflon pledget and simultaneously tensioned. While
observing the cardiac cycles in X-
plane 3D-
TEE, the
sutures are adjusted one at a time to obtain the desired
leaflet coaptation (figure 8E).
The Early Feasibility Study and CE Mark TRACER trial
investigated the early feasibility and safety of treatment
with the HARPOON system in 13 and 52 patients, respec-
tively.31–33
Of 65 patients enrolled in the two studies, 62
(95%) achieved technical success, 2 patients required
conversion to open surgery and one procedure was
terminated. The primary endpoint was met in 91% of
patients.32
At 1 year of follow-
up, 98% of patients were in
NYHA Class ≤II; MR was ≤mild in 75% and ≤moderate in
98% of patients.33
In Europe, Post-
Market Clinical Follow-
Up trials are
currently underway and will collect additional safety and
device performance data on the HARPOON MVRS in
patients with severe degenerative MR. The RESTORE
IDE pivotal trial (ClinTrials.Gov: NCT04375332) is being
initiated in North-
America to evaluate the safety and
effectiveness of the HARPOON MVRS in patients with
severe degenerative MR presenting with mid-
segment
posterior mitral leaflet prolapse.
CONCLUSION
TMVr represents a wide spectrum of percutaneous treat-
ment modalities targeting different parts of the mitral
apparatus (mitral annulus, mitral valve leaflets and mitral
valve chordae). These modalities should be regarded
Figure 7 NeoChord Transcatheter Mitral Valve Repair. (A) Components of the NeoChord system. (B) NeoChord is a
transapical, beating heart, off-
pump mitral valve repair system. (C) The jaws of the device are opened and the leaflet edge is
grasped by withdrawing the device from the left atrium. (D and E) A loop of the suture and a girth hitch knot can be formed
through the mitral leaflet. (F and G) The length of each neo-
chordae can be adjusted to achieve maximal mitral regurgitation
reduction under normal left ventricular (LV) filling conditions as assessed by transesophageal echocardiography. (H) Each of the
neo-
chordae is tied to the LV epicardial pledget. Images courtesy of and provided by NeoChord.
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11
as complementary rather than competing in their goal
to reduce MR, which itself not rarely has complex and
multiple aetiologies. With further data from ongoing
clinical studies to be expected, consensus in the Heart
Team approach is needed to address these complexities
and to determine the most appropriate TMVr therapy,
either isolated or combined, for patients with severe
symptomatic MR.
Twitter Ivan Wong @ivanwongm12
Contributors ODB and IW collected all data and information and wrote the first
draft. All other coauthors critically reviewed the manuscript.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-
for-
profit sectors.
Competing interests ODB received institutional research grants and consulting
fees from Abbott and Boston Scientific. MT is a consultant for Abbott Vascular,
Boston Scientific and 4tech; received personal fees from Edwards Lifesciences,
Mitraltech, CoreMedic and Swissvortex; and is a shareholder of 4Tech. FM obtained
grant and/or research institutional support from Abbott, Medtronic, Edwards
Lifesciences, Biotronik, Boston Scientific Corporation, NVT, Terumo, Consulting fees,
Honoraria personal and institutional from Abbott, Medtronic, Edwards Lifesciences,
Xeltis, Cardiovalve, Occlufit, Simulands, Occlufit; has Royalty Income/IP Rights
Edwards Lifesciences; and is shareholder (including share options) of Cardiogard,
Magenta, SwissVortex, Transseptal solutions, Occlufit, 4Tech, Perifect. LS received
institutional research grants and consulting fees from Abbott, Boston Scientific,
Medtronic and Edwards Lifesciences. All other coauthors have no conflict of
interest to disclose concerning this manuscript.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement No data are available.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-
NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-
commercially,
and license their derivative works on different terms, provided the original work is
properly cited, appropriate credit is given, any changes made indicated, and the use
is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
ORCID iD
Ole De Backer http://orcid.org/0000-0002-9674-0278
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