JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 69, NO.

17, 2017

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN 0735-1097/$36.00

PUBLISHED BY ELSEVIER http://dx.doi.org/10.1016/j.jacc.2017.02.045

THE PRESENT AND FUTURE

STATE-OF-THE-ART REVIEW

Transcatheter Mitral Valve Replacement

Insights From Early Clinical Experience and Future Challenges

Ander Regueiro, MD,a Juan F. Granada, MD,b François Dagenais, MD,a Josep Rodés-Cabau, MDa

ABSTRACT

Transcatheter mitral valve repair, particularly edge-to-edge leaflet repair, is a well-established alternative for patients
with severe primary mitral regurgitation (MR) considered at high or prohibitive surgical risk. More recently, transcatheter
mitral valve replacement (TMVR) has emerged as a potential therapeutic option for the treatment of severe MR. TMVR
may offer some advantages over transcatheter repair by providing a more complete and reproducible MR reduction.
Several devices are under preclinical and clinical evaluation, and the early experience with more than 100 patients has
demonstrated the feasibility of TMVR. In this review, we describe the TMVR systems currently in development and
the results obtained from early clinical experiences. We also discuss the main challenges in and future perspectives on
this emerging field. Future studies with a much larger number of patients are needed to provide consistent safety
and efficacy data on each of the TMVR systems. (J Am Coll Cardiol 2017;69:2175–92) © 2017 by the American College of
Cardiology Foundation.

M itral regurgitation (MR) is the most preva-

lent form of valve disease in developed
countries, affecting w10% of people older
than 75 years of age (1,2). MR management is depen-
dent on the cause, pathophysiology, natural history,
and expected treatment efficacy. Mitral valve repair
or replacement is the gold standard treatment for
MR, but some studies have shown that up to one-
half of the patients with severe symptomatic MR are
not referred for surgery (3,4). The mortality rate in
such patients reaches 50% at 5 years of follow-up,
and up to 90% of surviving patients had at least 1 hos-
pitalization for heart failure within the 5 years after
the diagnosis of severe MR (3,4). Lack of surgical
referral is related, in part, to the perceived risk of
the procedure, and an alternative, less invasive
approach in vulnerable patients would be desirable.
It should be noted, however, that a significant pro-
portion of patients with severe MR suffer from
secondary MR, and no strong evidence exists yet for
the efficacy of any valve intervention in terms of sur-
vival or improvement in quality of life in such
patients (5).
Over the last decade, several transcatheter mitral
valve repair technologies adapted from different
surgical techniques have emerged for treating MR in
patients at high or prohibitive surgical risk. The
transcatheter mitral valve repair “tool box” is rapidly
expanding, with up to 5 devices already approved in
Europe, including the MitraClip (Abbott Vascular,
Inc., Santa Clara, California), the DS1000 device
(NeoChord, Inc., St. Luis Park, Minnesota), the
Carillon (Cardiac Dimensions, Inc., Kirkland, Wash-
ington), the CardioBand (Valtech Cardio, Or Yehuda,
Israel), and the Mitralign device (Mitralign, Inc.,
Tewksbury, Massachusetts). In current practice,
transcatheter mitral valve repair is mainly limited to
the MitraClip device, which mimics the edge-to-edge

Listen to this manuscript’s

audio summary by
JACC Editor-in-Chief
Dr. Valentin Fuster.
From the aQuebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada; and the bCardiovascular Research
Foundation, Skirball Center for Innovation, Orangeburg, New York. Drs. Rodés-Cabau and Dagenais have received research grants
from Edwards Lifesciences. The CRF Skirball Center for Innovation has received research support from Edwards Lifesciences,
Neovasc, Abbott Vascular, Sinomed, and Cephea. Dr. Granada is a cofounder of Cephea. Dr. Regueiro was supported by a grant
from the Fundacion Alfonso Martin Escudero (Madrid, Spain). Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this
paper. Patrick O’Gara, MD, served as Guest Editor for this paper.

Manuscript received November 15, 2016; revised manuscript received February 12, 2017, accepted February 12, 2017.
2176 Regueiro et al.
Transcatheter Mitral Valve Replacement
ABBREVIATIONS leaflet repair described by Alfieri et al. (6).
AND ACRONYMS Since the introduction of MitraClip in 2003,
more than 35,000 patients have been treated
CT = computed tomography
(7) with high success and safety rates, trans-
LVEF = left ventricular ejection
lating into some degree of functional
fraction
improvement in most patients (8–11).
LVOT = left ventricular outflow
tract Transcatheter mitral valve replacement
MR = mitral regurgitation
(TMVR) may offer several theoretical advan-
tages over transcatheter repair. Considering
TAVR = transcatheter aortic
valve replacement the complexity and heterogeneity of mitral
TMVR = transcatheter mitral valve disease, the development of a trans-
valve replacement catheter mitral valve repair device to
target all anatomic variations and patient risk profiles
will be difficult and presents several challenges.
TMVR could offer a more universal concept for
treating mitral valve disease, with a more predictable
decrease in MR severity, in a procedure that could
potentially be less invasive compared with current
surgical techniques (12). Additionally, the utility of
TMVR will need to be further assessed due to the
fact that surgical mitral valve repair has excellent
results in patients with severe primary MR (5), and
it is unknown whether intervention will result in
any changes in outcome in patients with severe
secondary MR.
The objectives of this review were to provide an
overview of the main technical characteristics of
different TMVR devices under preclinical and clinical
evaluation and to analyze the main clinical results
and challenges experienced in the initial phases of
clinical validation. TMVR using transcatheter aortic
valve systems in patients with severely calcified
mitral annuli (13) and valve-in-valve procedures for
the treatment of mitral surgical bioprosthetic
dysfunction (14) are beyond the focus of this review.
CHALLENGES FOR TMVR DEVELOPMENT
TARGET VALVE AND/OR DISEASE. One of the main
challenges presented by TMVR relates to the position
and complex anatomy of the mitral valve. Transseptal
access and a delivery catheter with high-flexure ca-
pabilities are needed in order to reach the native
mitral valve with a fully percutaneous approach.
Also, several aspects of the valve anatomy may in-
crease the difficulty of TMVR: asymmetrical annulus
and irregular geometry of valve leaflets; large di-
mensions; no calcified structure in most cases; and a
complex subvalvular anatomy (which should be
preserved).
MR is a very heterogeneous disease resulting from
the dysfunction of any of the components of the
mitral valve apparatus or surrounding structures. MR
has multiple causes with different stages of severity.
JACC VOL. 69, NO. 17, 2017
MAY 2, 2017:2175–92
As MR evolves, there are changes to the ventricle
associated with geometrical distortion, which have a
wide range of variations as the disease progresses
over time. Due to this extensive variability, it is
challenging to develop a “universal device concept”
tailored to target all potential anatomic variations
seen in all MR types and patient risk profiles.
DEVICE DELIVERY. Similar to the transcatheter aortic
valve replacement (TAVR) experience, a fully percu-
taneous transfemoral (venous) procedure would be
the less invasive and preferred approach for TMVR.
However, that approach faces the challenges of a
high-profile delivery system (to accommodate a large
valve prosthesis) that has to negotiate an extreme
angle within a relatively small space (through the
transseptal approach) to reach the mitral valve. This
is partially the reason why most TMVR systems to
date have been developed to deliver the valve pros-
thesis transapically, following a puncture of the
ventricular apex. The transapical approach has been a
common alternative in TAVR for patients without
iliofemoral access and has the advantage of a very
short distance between the access and the target
valve, also allowing good alignment of the valve
prosthesis with small movements of the delivery
system. However, many studies have reported
poorer outcomes associated with transapical TAVR
(compared with transfemoral access), likely related to
a higher degree of myocardial injury, along with the
negative effects of a thoracotomy in a high-risk and
frail population (15–17). The transition from trans-
apical to transseptal delivery of clinically available
TMVR devices will require important engineering
modifications in size and possible valve designs and
anchoring mechanisms.
VALVE PROSTHESIS ANCHORING AND SEALING. The
pathophysiology and anatomic substrate of MR is
complex and heterogeneous. One of the main chal-
lenges in the development of TMVR is trying to obtain
prosthesis stability similar to that of surgical mitral
valve replacement. In contrast to TAVR, where the
landing zone for the prosthesis is a tubular calcified
structure, the valve prostheses used to treat MR in
native valves need to be anchored into a dynamic,
D-shaped noncalcified structure. To tackle this issue,
several mechanisms have been proposed (18,19),
including: 1) application of counteracting axial forces,
tensioning the device between a proximal and a distal
constraint (apical tether; Tendyne valve; Abbott
Vascular, Abbott Park, Illinois); 2) ventricular anchors
to grasp the free margins of the native leaflets (native
leaflet engagement; Tiara valve; Neovasc, Richmond,
British Columbia, Canada); 3) atrial and ventricular
JACC VOL. 69, NO. 17, 2017
MAY 2, 2017:2175–92
flanges that engage the mitral annulus and mitral
leaflets/chordae (mitral annulus clamping; CardiAQ-
Edwards; Edwards Lifesciences, Irvine, California);
4) a series of anchors around the edge of the valve
that either pierce the mitral valve tissue or provides
friction with radial interference (annular winglets;
NaviGate valves; NaviGate Cardiac Structures, Lake
Forest, California); 5) a “champagne cork-like” effect
produced by a radial force along the valve stent
(radial force; Intrepid valve; Medtronic, Minneapolis,
Minnesota); and 6) simultaneous creation of a landing
zone by implanting a ring or a docking system
(external anchor; Caisson [anchor is fixed by mitral
annulus clamping]; Maple Grove, Minnesota), MValve
(subannular mitral ring; Herzliya, Tel Aviv, Israel),
and HighLife valves (dock is anchored by mitral
annulus clamping; HighLife Medical, Irvine, Califor-
nia) (Central Illustration).
Valve sealing is also a major challenge in TMVR.
The complex 3-dimensional (3D) anatomy with a dy-
namic morphology of the mitral annulus, along with
the high-pressure gradient generated by the ventricle
during systole, may contribute to the occurrence of
significant paravalvular leakage following valve
implantation.
LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION.
Left ventricular outflow tract (LVOT) area is
decreased following mitral surgery with annuloplasty
rings and prostheses (20), and LVOT obstruction after
surgical mitral valve procedures has also been
described (21). This phenomenon has not been limited
to the use of surgical prostheses, and it has also been
described following transcatheter mitral procedures
with nondedicated devices. The reported rate of
acute LVOT obstruction with transcatheter mitral
valve-in-ring procedures is 8.2% (14), and it increases
up to 9.3% following TMVR in the presence of severe
mitral annular calcification (13). Multiple factors
should be evaluated when determining the risk of
LVOT obstruction after TMVR (22,23): the aortomitral-
annular angle, which is the angle between the
annular planes of these 2 valves (if the angle is
obtuse, there may be a higher risk of obstruction, as
the struts of the prosthesis will encroach on the
LVOT); degree of septal hypertrophy; left ventricle
size; and device protrusion and flaring into the LVOT.
PRE-PROCEDURAL PLANNING AND MULTIMODALITY
IMAGING. Pre-procedural multimodality imaging is
essential for TMVR planning. Pre-procedural imaging
is used to define the presence, type, and severity of
MR; to confirm patient eligibility according to the
anatomic characteristics and the prosthetic valve
designs; to identify patients at risk for possible
Regueiro et al. 2177
Transcatheter Mitral Valve Replacement
specific TMVR complications (e.g., LVOT obstruc-
tion); and to determine pre-operative prediction of
fluoroscopic angulation and access location.
Echocardiography remains the gold standard for
diagnosing MR (5). A comprehensive echocardio-
graphic examination helps to establish the cause,
mechanism, and severity of MR and the impact of MR
on myocardial function. Additionally, echocardiog-
raphy with 3D segmentation of the mitral annulus can
be used as the initial screening imaging modality for
TMVR in patients with impaired renal function who
are at risk for acute kidney injury with contrast
computed tomography (CT).
Although echocardiography is the primary imaging
modality for the diagnosis and quantification of MR,
CT is the preferred imaging modality for pre-
procedural TMVR evaluation. However, with
improving 3D technology, transesophageal echocar-
diography could assume a more important role over
time. Electrocardiogram (ECG)-gated cardiac CT of-
fers 3D volumetric data sets with submillimeter
spatial resolution, enabling a comprehensive assess-
ment by providing an exact characterization of the
anatomy of the subvalvular apparatus and the ge-
ometry of the mitral valve (24). This process has also
been shown to be highly reproducible (25,26). In
addition to ECG-gated cardiac CT, non–ECG-gated CT
data acquisition of the thorax may be performed to
evaluate thoracic wall anatomy for device deploy-
ment in transapical approaches and of the pelvis to
evaluate the iliofemoral venous diameter in patients
undergoing transfemoral TMVR. Three-dimensional
CT reconstruction data are used during the
screening process to assess mitral valve anatomy and
determine the appropriateness of different devices
for each individual patient. Although it is currently
the preferred modality for pre-procedural TMVR
evaluation, there is still uncertainty about the most
important variables, as many of the measurements
are empirical, requiring validation (Figure 1). It is
anticipated that the ideal means of measuring mitral
valve anatomy to guide device and patient selection
will be refined with increasing clinical experience.
The most important information that should be
included in a pre-procedural TMVR comprehensive
systematic CT analysis is described in Table 1. The
definitions and methodology for each measurement
are beyond the scope of this paper. More information
can be found elsewhere (18,25–31).
PROSTHETIC VALVE STRUCTURAL DEGENERATION.
Although no long-term durability data exist for
TMVR, there are some factors that should be consid-
ered regarding the possibility of bioprosthesis
2178 Regueiro et al. JACC VOL. 69, NO. 17, 2017

Transcatheter Mitral Valve Replacement MAY 2, 2017:2175–92

C E N T R A L IL LU ST R A T I O N Transcatheter Mitral Valve Replacement for Native Mitral Regurgitation

Regueiro, A. et al. J Am Coll Cardiol. 2017;69(17):2175–92.

(Top) Main challenges for transcatheter mitral valve replacement for treating native mitral regurgitation. (Bottom) Anchoring mechanisms of
transcatheter mitral valve prostheses. Ao ¼ aorta; LA ¼ left atrium; LV ¼ left ventricle; LVOT ¼ left ventricular outflow track.
JACC VOL. 69, NO. 17, 2017 Regueiro et al. 2179
MAY 2, 2017:2175–92 Transcatheter Mitral Valve Replacement

F I G U R E 1 CT Pre-Procedural Data for TMVR

CT pre-procedural data showing several different measurements used to screen patients for TMVR on the basis of anatomic criteria. (A) Mitral
annulus measurements showing septal-to-lateral distance (dotted line) and intercommisural distance (solid line). (B) Distance between
papillary muscles heads. (C) Projected distance from papillary muscle head to the mitral annulus plane (solid line), projected distance between
papillary muscle head and the center of the mitral annulus (dashed line), and distance between papillary muscle head and ventricular wall
(dotted line). (D) Posterior leaflet length at the P2 level. (E) Aortomitral angulation. (F) Left atrium height (solid line) and short-axis
diameter (dotted line). CT ¼ multislice computed tomography; TMVR ¼ transcatheter mitral valve replacement.

degeneration. First, surgical mitral bioprosthetic
valves are more likely to suffer from early structural
degeneration than surgical aortic bioprostheses. Also,
surgical bioprostheses tend to degenerate more
rapidly in younger patients (32). Although this may be
of lesser concern in patients with a relatively short
life expectancy, young patients with MR may have a
longer life expectancy, which raises concerns about
long-term durability. A systematic clinical and echo-
cardiographic follow-up of patients
TMVR will be critical to provide consistent data for
valve durability and structural valve failure in the
coming years.
TMVR DEVICES UNDER
CLINICAL EVALUATION
CardiAQ-EDWARDS TRANSCATHETER MITRAL VALVE. The
CardiAQ-Edwards transcatheter mitral valve is a
self-expanding trileaflet valve composed of bovine
undergoing pericardial tissue (Table 2, Figure 2). The nitinol frame
is composed of 2 sets of circumference-oriented,
2180 Regueiro et al. JACC VOL. 69, NO. 17, 2017

Transcatheter Mitral Valve Replacement MAY 2, 2017:2175–92

system (above the papillary muscles); 3) the left

T A B L E 1 CT Pre-Procedural Assessment for TMVR
ventricular anchors are released by turning the
Exam Anatomical structure Measurement retraction wheel to initiate leaflet capture; 4) the
Cardiac CT scan Mitral annulus Intercommisural distance valve is expanded to finalize leaflet capture; and
(ECG-gated) Septal-to-lateral distance
5) after a correct position is confirmed, the valve is
Trigone-to-trigone distance
released (33).
3D perimeter
Projected area
The first-in-human implantation of the first-
Projected perimeter generation CardiAQ was done in 2012 (34). Since
Mitral annular trajectory then, 13 cases have been reported, including 1
Mitral annular calcification additional patient treated through a transfemoral
En face view fluoroscopic angulation approach with the second-generation valve (35,36).
Compromise-view angulation
The main clinical results of this initial clinical expe-
Mitral leaflets Mitral leaflet length
rience are summarized in Table 3. An early feasibility
Mitral leaflet calcification
study, which plans to enroll 28 patients, using the
Papillary muscles Distance between heads
Projected distance to the mitral
transfemoral and transapical delivery systems is
annulus plane currently enrolling patients, and a larger prospective
Distance to the ventricular wall registry including 200 patients started in 2016
Left atrium Long-axis diameter
(Table 4).
Short-axis diameter
Left atrium height NEOVASC TIARA MITRAL TRANSCATHETER HEART
LAA ostium to mitral annulus distance
VALVE. The Tiara valve is a self-expanding trileaflet
Left ventricle Long-axis diameter
valve made of bovine pericardium and a nitinol
Width in long-axis view
Interventricular septum thickness
frame (Table 2, Figure 3). The valve is designed to
LVOT Aorto-mitral angle fit the D-shaped mitral annulus. The atrial portion
Neo-LVOT cross-sectional area helps to seat the prosthesis into the atrial portion
Thorax CT scan Left ventricle apex Ideal intercostal space for of the mitral annulus and has a full atrial skirt.
transapical approach
The ventricular anchors (2 anterior and 1 posterior)
(Non-ECG-gated) Distance from sternal midline
fix the valve onto the fibrous trigon and the posterior
Angulation for coaxial deployment
Abdominopelvic Iliofemoral vein Iliofemoral venous diameter for
part of the annulus. There are 2 valve dimensions:
CT scan transfemoral approach the 35-mm valve has internal dimensions of 30 mm
and 35 mm (area ranges: 6.3 cm2 to 9.0 cm 2), and
3D ¼ 3-dimensional; CT ¼ multislice computed tomography; ECG ¼ electrocardiogram; LAA ¼ left-
atrial appendage; LVOT ¼ left ventricular outflow tract ejection fraction; TMVR ¼ transcatheter the 40-mm valve has internal dimensions of 34.2 mm
mitral valve replacement. and 40 mm (area ranges: 9.0 cm 2 to 12.0 cm 2) (37).
The valve is implanted using the transapical
approach (38).
The procedure can be summarized in 4 steps: 1) the
opposing anchors which secure the device to the left ventricular apex is exposed through a left mini-
mitral annulus. The ventricular anchors rest behind thoracotomy, a needle puncture is performed, and
the mitral leaflets and subvalvular apparatus, pre- a J-tip wire is introduced across the mitral valve;
serving the chords and using native leaflets as sup- 2) the Tiara delivery system is introduced directly
port. The symmetrical design requires no rotational and across the mitral valve, and the atrial portion of
alignment. The frame is covered by a polyester fabric the prosthesis is unsheathed, oriented, and aligned
skirt designed to reduce the risk of paraprosthetic with the D-shaped mitral annulus to allow proper fit;
leakage. The valve has a supra-annular position 3) the delivery system is then pulled back to seat
intended to minimize the ventricular profile and, the atrial part of the valve; and 4) the ventricular
therefore, the risk of LVOT obstruction. The valve can anchors are released to secure and release the
be implanted using a transapical or transfemoral prosthetic valve (39).
approach. The first cases using the Tiara mitral valve system
The procedure can be summarized in 5 steps: 1) the implants were performed in January 2014 in Vancouver
delivery system is advanced across the interatrial (38). Since then, 19 cases have been reported, 5 patients
septum in the transseptal approach or using the apex in the TIARA-1 early feasibility study and 14 patients
in the transapical access approach; 2) after crossing under a special access program (Table 3) (40). An early
the mitral valve, a ventriculogram is obtained to feasibility trial is currently enrolling patients and plans
reassess the mitral plane and correct the height of the to include a total of 30 patients (Table 4).
JACC VOL. 69, NO. 17, 2017 Regueiro et al. 2181
MAY 2, 2017:2175–92 Transcatheter Mitral Valve Replacement

T A B L E 2 TMVR Technologies Under Clinical Evaluation

CardiAQ-Edwards Neovasc Tiara Tendyne Intrepid TMVR

Valve shape Circular D-shaped D-shaped (outer stent) Circular

Circular (inner frame)
Frame Nitinol, self-expandable Nitinol, self-expandable Nitinol, double frame; Nitinol, double stent;
Self-expandable Self-expandable
Anchoring mechanism Mitral annulus capture with native Fibrous trigone capture with Apical tether Radial force and subannular
leaflet engagement native leaflet engagement cleats
Leaflets Trileaflet Trileaflet Trileaflet Trileaflet
Bovine pericardium Bovine pericardium Porcine pericardium Bovine pericardium
Valve position Supra-annular Intra-annular Intra-annular Intra-annular
Access Transapical Transapical Transapical Transapical
Transseptal
Delivery system size 33-F 32-F 36-F 35-F
Recapture No No Fully recapturable system after No
complete deployment
Valve size(s) 30 mm 35 mm and 40 mm Outer frame ranges from 30–43 mm 27 mm with 3 outer stent sizes
in the SL dimension and (43, 46, and 50 mm)
34–50 mm in the IC dimension
Additional features Supra-annular position 2 anterior and 1 posterior Single inner valve size; Multiple Dual stent design; Outer frame
Intra-annular sealing skirt anchoring structures outer frame sizes provides fixation and isolates
Tapered outflow the inner stent

T A B L E 2 Continued

Caisson HighLife TMVR MValve system NCSI NaviGate Mitral

Valve shape D-shape Circular – Circular

Frame 2 components (anchor and valve); 2 components (ring and valve); Dock system to be used with Nitinol, self-expandable;
Nitinol, self-expandable. Nitinol, self-expandable commercially available valves Xenogeneic pericardium
Anchoring mechanism External anchor; Mitral annulus External anchor; Valve in External anchor; Mitral annulus Annular winglets
capture with engagement at subannular mitral ring capture
subannular fibrous groove
Leaflets Trileaflet Trileaflet – Trileaflet
Porcine pericardium Bovine pericardium
Valve position Supra-annular –
Access Transseptal Transapical (Transfemoral artery Transapical Transapical, transatrial or
for loop placement) transfemoral
Delivery system size 31-F NA 32-F 30-F
Recapture Fully recapturable and retrievable No Fully retrievable NA
Valve size(s) 35–40 mm 31 mm NA Inflow/outflow: 30 mm/36 mm;
30 mm/40 mm; 33 mm/44 mm
Additional features SAM Management feature NA Universal dock system NA
1 delivery catheter for each system
(anchor and valve)

IC ¼ intercommissural; NA ¼ not available; SAM ¼ systolic anterior motion of the mitral valve; SL ¼ septal-lateral; TMVR ¼ transcatheter mitral valve replacement.

TENDYNE BIOPROSTHETIC MITRAL VALVE SYSTEM. The
Tendyne mitral valve system is composed of a trileaflet
porcine pericardial valve on a self-expanding nitinol
double-frame stent, an adjustable tether, and an apical
fixation/sealing pad (Table 2, Figure 4). The valve is
designed to fit the mitral annulus and can accommo-
date a wide range of sizes. The inner stent is one size
and circular to maintain an effective orifice area of
>3.2 cm 2. There is an atrial cuff designed to provide
sealing (prevention of diastolic paravalvular leak) and
anchoring (preventing valve from pulling into the
ventricle when force is applied to the tether). A left
ventricular apical tethering system with an apical pad
anchors the device and assists with apical closure. The
device is implanted using a transapical approach and
can be fully retrieved or repositioned even after full
deployment (41).
The procedure can be summarized in 4 steps: 1)
Standard transapical approach through a left mini-
thoracotomy and left ventricle access. 2) A balloon-
tipped catheter is advanced into the left atrium to
deliver a standard 0.035-inch guidewire. The 36-F
delivery system is advanced over the guidewire. The
valve is brought into the left atrium and positioned
above the mitral annulus and allowed to partially
expand. 3) The valve’s rotational orientation is veri-
fied and corrected if necessary to assure the D-shaped
outer stent is oriented so that the straight side is
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Transcatheter Mitral Valve Replacement MAY 2, 2017:2175–92

F I G U R E 2 CardiAQ-Edwards Valve

(A) Valve prosthesis (provided by Edwards Lifesciences). (B) Fluoroscopy. (C) Three-dimensional transesophageal echocardiography from the
surgeon’s point of view.

aligned with the anterior aspect of the mitral orifice. tension tool is used to adjust the tether length from
The valve is deployed into the mitral orifice. 4) The the valve to the ventricular apex to provide valve
apical pad is threaded over the tether and positioned stability. The apical pad is secured and assists with
on the epicardium at the left ventricular access; a closure of the apex (42).

T A B L E 3 TMVR System Preliminary Clinical, Procedural, and Follow-Up Features

CardiAQ-Edwards Intrepid TMVR Fortis* Neovasc Tiara Tendyne† Caisson HighLife

(N ¼ 13) (N ¼ 27) (N ¼ 13) (N ¼ 19) (N ¼ 30) (N ¼ 5) (N ¼ 6)

Baseline characteristics
Age, yrs NA 74 (58–90) 71  8 73 (39–89) 75.9 (55–91) 77.4 (70–91) 69 (57–79)
Female 2/13 (15.4) 9/27 (33.3) 3/13 (23.1) 6/19 (31.6) 5/30 (16.7) 3/5 (60.0) 2/6 (33.3)
STS PROM score NA 6.2 (1.0–23.3) 7.2  3.6 10.7 (2.09–47.7) 7.3 (2.0–16.0) 8.8 (5–10) 3.3 (2.5–4.9)
NYHA functional class $III NA 23/27 (85.3) 13/13 (100) 19/19 (100) 16/30 (53) 5/5 (100) 6/6 (100)
LVEF, % 40 (20–72) NA 34 34 (15–65) 47.1  9.2 42.6 (28–58) 33.7 (20–50)
<30% NA 5/27 (18.5) NA 5/19 (26) 3/29 (10.3) 1/5 (20.0) 1/6 (16.7)
30%–49% NA 14/27 (51.8) NA 13/19 (68) 14/29 (48.3) 2/5 (40.0) 4/6 (66.7)
$50% NA 8/27 (29.6) NA 1/19 (5) 12/29 (41.4) 2/5 (40.0) 1/6 (16.7)
Ischemic/functional MR 9/13 (69.2) 21/27 (77.8) 12/13 (92.3) 12/19 (63.2) 23/30 (76.7) 3/5 (60.0) 3/6 (50.0)
Procedural and 30-day data
Technical success 12/13 (92.3) 24/26 (92.3)‡ 10/13 (76.9) 16/19 (84.2) 28/30 (93.3) 4/5 (80.0) 5/6 (83.3)
Valve dislocation/embolization NA NA 2/15 (15.4) 3/19 (15.8) 0/30 (0.0) 0/5 (0.0) 0/5 (0.0)
Conversion to open-heart surgery NA NA 2/15 (15.4) 3/19 (15.8) 0/30 (0.0) 0/5 (0.0) 1/6 (16.7)
Post-procedural $ moderate MR NA 0/26 (0.0) 0/9 (0.0) NA 1/30 (3.3) 0/4 (0.0) 0/6 (0.0)
LVOT obstruction NA 0/26 (0.0) 0/9 (0.0) 0/19 (0.0) 1/30 (3.3) 0/4 (0.0) 0/6 (0.0)
Procedural mortality 2/13 (15.4) 4/27 (14.8) 4/13 (30.8)§ 0/19 (0.0) 0/30 (0.0) 0/5 (0.0) 1/6 (16.7)
30-day moderate or severe MR NA NA NA NA 0/26 (0.0)k 0/3 (0.0) 0/4 (0.0)
All-cause 30-day mortality 7/13 (53.8) 6/25 (24.0) 5/13 (38.5) 3/19 (15.8) 1/30 (3.3) 1/4 (25.0) 2/6 (33.3)
Follow-up
Follow-up, months NA 8.1 (0–20.7) 6 (1–15) NA NA¶ 3.4 (3–4) 4.1 (3–6)
MR $ moderate NA 0/24 (0.0) 0/8 (0.0) 0/14 (0.0) 0/5 (0.0) 0/4 (0.0) 0/4 (0.0)
NYHA functional class $III NA 2/18 (11.1) 2/8 (25.0) NA NA 0/3 (0.0) 0/4 (0.0)
Mortality 7/13 (53.8) 7/27 (25.9) 6/13 (46.2) 3/19 (15.8) 0/5 (0.0) 1/4 (25.0) 2/6 (33.3)

Values are mean (range), mean  SD, or n/N (%). *In late 2015, Edwards Lifesciences stopped the FORTIS program. The valve is not currently available. †>50 implants up to June 2016; 32 early feasibility
study implants, 5 compassionate use implants. Results of the first 30 early feasibility study cases are available (43). ‡In 1 patient, deployment was not attempted. §In-hospital mortality. kRepeated
echocardiography was performed in 26 of the 27 patients with a prosthesis in situ. ¶Follow-up data for longer than 30 days from 5 patients, 2 patients with follow-up for up to 6 months, and 3 patients with
follow-up for up to 18 months.
LVEF ¼ left ventricular ejection fraction; MR ¼ mitral regurgitation; NYHA ¼ New York Heart Association; STS PROM ¼ Society of Thoracic Surgeons’ perioperative mortality risk; other abbreviations as in
Tables 1 and 2.
JACC VOL. 69, NO. 17, 2017 Regueiro et al. 2183
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T A B L E 4 Ongoing and Future Studies on TMVR Therapies for Treating MR

Estimated
Device Manufacturer Study Study Design Enrollment Primary Outcome Measures

CardiAQ-Edwards Early feasibility study Prospective registry 28 patients Safety assessed by freedom from device or procedure-related
(NCT02718001) adverse events at 30 days
CardiAQ-Edwards RELIEF trial (NCT02722551) Prospective registry 200 patients Freedom from major adverse cardiac and cerebrovascular
events at 30 days per MVARC definition.
Freedom from individual adverse events at 30 days
Neovasc Tiara TIARA-I (NCT02276547) Prospective registry 30 patients Freedom from all-cause mortality and major adverse events,
EFS trial defined as disabling stroke, myocardial infarction, renal
failure requiring dialysis, life-threatening bleeding, and
cardiac surgical or transcatheter reintervention at 30 days
Tendyne Early feasibility study of the Prospective registry 110 patients Safety assessed by freedom from device or procedure related
Tendyne Mitral valve system EFS trial adverse events at 30 days
(NCT02321514) Performance assessed by freedom from device malfunction at
30 days
Intrepid Twelve Transcatheter Mitral Valve Prospective registry 10 patients Adverse events associated with the delivery and/or
Replacement Pilot Study* EFS trial implantation of the device at 30 days
(NCT02428010)
Caisson PRELUDE (NCT02768402) Prospective registry 20 patients Freedom from major adverse events including death, stroke,
EFS trial myocardial infarction, and surgical reintervention through
30 days
MValve DOCK 1 (NCT02719912) Prospective registry 30 patients Composite serious adverse cardiac events and stroke at
EFS trial 30 days

*Information submitted to ClinicalTrials.gov in April 23, 2015, before Medtronic acquisition of Twelve, Inc.
DOCK I ¼ Mitral Valve Replacement With MValve Dock and Lotus; EFS ¼ early feasibility study; Mfr ¼ manufacturer; MVARC ¼ Mitral Valve Academic Research Consortium; PRELUDE ¼ Caisson
Transcatheter Mitral Valve Replacement (TMVR) System Early Feasibility Study; RELIEF ¼ CardiAQ-Edwards Transcatheter Mitral Valve Replacement (TMVR) Study; TIARA ¼ Early Feasibility Study of the
Neovasc Tiara Mitral Valve System; other abbreviations as in Tables 1 and 3.

The first-in-human implantation of the Tendyne
valve was performed in October 2014 (41). The results
of the first 30 patients treated with this valve have
been reported and are summarized in Table 3 (43). An
early feasibility study of the Tendyne mitral valve
system is currently recruiting patients (Table 4).
MEDTRONIC INTREPID TMVR. The Intrepid TMVR is
a tri-leaflet bovine pericardial valve contained in a
self-expanding nitinol frame, which has dual structure
design consisting of a circular inner stent to house the
valve and a conformable outer fixation ring to engage
the mitral anatomy. The outer fixation ring is designed
to accommodate the variability of the native mitral
annulus while isolating the inner valve assembly
throughout the cardiac cycle. A flexible brim is
attached to the atrial end of the fixation ring, which
facilitates imaging during the procedure (44). The

F I G U R E 3 Tiara Valve

(A) Valve prosthesis. (B) Fluoroscopy. (C) Three-dimensional transesophageal echocardiography from the surgeon’s point of view. Reprinted with permission from
Cheung et al. (38).
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Transcatheter Mitral Valve Replacement MAY 2, 2017:2175–92

F I G U R E 4 Tendyne Valve

(A) Valve prosthesis. (B) Fluoroscopy. (C) Three-dimensional transesophageal echocardiography from the surgeon’s point of view. Reprinted
with permission from Muller et al. (43).

outer stent is being investigated in 3 sizes of 43, 46,
and 50 mm. The circular inner stent houses a 27-mm
valve across the 3 outer stent sizes (Table 2, Figure 5).
There is no need for rotational alignment or to search
for leaflets. Fixation and sealing are achieved through
a combination of design features: 1) the outer fixation
ring is larger in circumference than the native mitral
valve annulus with varying degrees of radial stiffness
along its axial length; 2) the flexible atrial portion de-
flects inward while the stiff ventricular mid-section
resists compression and maintains its shape, produc-
ing a final ‘champagne cork-like’ conformation (nar-
row neck and wider body) to resist migration under
systolic pressures and; 3) 3 circumferential rings of
frictional elements on the outer stent further help
fixation. The prosthesis is designed to preserve the
native leaflets and chordae and leverage them to seal
around the device (44).
The Intrepid TMVR delivery system is currently
designed for transapical access only and consists of
an apical introducer sheath (with dilator) and a hy-
draulically actuated delivery catheter. The procedure
can be summarized in 5 steps: 1) after standard
transapical access, the system is advanced across the
mitral valve; 2) the valve is expanded until the brim is
completely deployed; 3) the system is retracted into
the desired position on the annulus; 4) the fixation
ring is expanded; and 5) the valve is released, the

F I G U R E 5 Intrepid TMVR

(A) Valve prosthesis. (B) Fluoroscopy. (C) Three-dimensional transesophageal echocardiography from the surgeon’s point of view.
TMVR ¼ transcatheter mitral valve replacement. A was reprinted from Meredith et al. (44), printed with permission from Europa Digital &
Publishing. B and C are courtesy of Dr. Vinayak Bapat, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom.
JACC VOL. 69, NO. 17, 2017 Regueiro et al. 2185
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F I G U R E 6 Caisson Valve

(A) Valve prosthesis. (B) Fluoroscopy. (C) Two-dimensional transesophageal echocardiography. A was provided by Caisson Interventional.
B and C are courtesy of Dr. Mathew Williams, NYU Langone Medical Center, New York, New York.

sheath is removed, and the incision is closed. Steps 3
through 5 are performed under rapid ventricular
pacing. Duration of rapid pacing has averaged at 30 s
during deployment (45).
The first case to use an Intrepid TMVR in a human
was performed in September 2014. Since then, 27
patients have been treated, and the main clinical re-
sults are summarized in Table 3 (44,46,47). A pro-
spective registry is ongoing (Table 4).
CAISSON TMVR SYSTEM. The Caisson TMVR system
consists of 2 main components, an anchor and a
valve (Table 2, Figure 6). The anchor is a D-shaped,
self-expanding nitinol structure. It serves as a foun-
dation that grips the native valve annulus. The
anchor is implanted onto the mitral valve such that
the tips of the ventricular feet engage under the
mitral valve annulus, and the atrial holding features
engage with the atrial surface of the mitral valve
annulus. The valve is composed of a self-expanding
nitinol frame with a trileaflet porcine pericardial
valve and is designed to nest in the anchor. Both the
valve and the anchoring system are retrievable (48).
The valve is delivered completely percutaneously,
using the transfemoral approach with a 31-F delivery
system (49).
Five patients were treated through October 2016,
4 in a U.S. early feasibility study and 1 patient under
the Canadian special access program (49). The main

F I G U R E 7 HighLife Valve

(A) Valve prosthesis. (B) Fluoroscopy. (C) Transesophageal echocardiography from the surgeon’s point of view. Courtesy of Dr. Rüdiger Lange,
German Heart Center Munich, Munich, Germany.
2186 Regueiro et al.
Transcatheter Mitral Valve Replacement
F I G U R E 8 MValve
(A) Valve prosthesis. (B) Fluoroscopy. (C) Transesophageal echocardiography from the surgeon’s point of view. Courtesy of Dr. Maurice
Buchbinder, Stanford University/VA Palo Alto Healthcare System, Palo Alto, California.
clinical results of this initial experience are summa-
rized in Table 3. The first-in-human early feasibility
study is ongoing and plans to include 20 patients in
5 centers (Table 4).
HighLife TMVR DEVICE. The HighLife device is
composed of 2 components: a ring that is placed
around the native leaflets (subannular implant) and a
prosthetic valve that is placed inside the ring (Table 2,
Figure 7). The valve prosthesis is composed of a
31-mm nitinol frame and a trileaflet bovine pericardial
valve that has a pre-formed groove in the annular
region. The subannular implant consists of a polymer
tube with nitinol hooks for ring closure that is placed
around the prosthesis to avoid displacement of the
valve into the left ventricle. In its final position, the
native leaflets are trapped between the subannular
implant and the prosthetic valve (50).
The procedure can be summarized in 3 steps: 1) a
guidewire is introduced through the femoral artery
and is looped around the native mitral valve leaflets;
2) the subannular implant ring is placed over the
guidewire loop; and 3) the prosthetic valve is
implanted through a transapical approach similar to a
valve-in-ring implant. A single-center early feasibility
and safety study is ongoing. Results from the first
6 patients treated with this device have been reported
and are summarized in Table 3 (51).
MValve SYSTEM. The MValve system is not a valve
but a docking device designed to fit other trans-
catheter prostheses that are anchored within the
docking system (Table 2, Figure 8). The MValve sys-
tem can be implanted using a transapical approach
and is designed to be compatible with a variety of
JACC VOL. 69, NO. 17, 2017
MAY 2, 2017:2175–92
commercially available transcatheter valves. The
anchoring of the docking system is designed to allow
preservation of the native leaflet function, offering a
true chord-sparing approach. The MValve system
enables positioning due to its fluoroscopic visibility,
atrioventricular positioning, and a sealing element
that is intended to minimize the risk of paravalvular
leak. The docking system can be recaptured and
retrieved after full deployment (52).
The first-in-human implantation was performed in
September 2015. There were no major periprocedural
complications, and immediate post-operative echo-
cardiography revealed no residual MR and good valve
position. The patient died 20 days after the procedure
due to pneumonia. The early feasibility and safety
study of the MValve in conjunction with the Lotus
transcatheter heart valve (Boston Scientific, Marl-
borough, Massachusetts) is planned to start by the
second quarter of 2017 (Table 4). The company is
currently also working on the design of the next-
generation MValve device. The goal for this new-
generation device is implantation in a single-step
procedure, and it will have a proprietary valve built
and secured within the MValve dock. It will be
adaptable for transseptal implantation with a profile
of 24-F (53).
NCSI NaviGate MITRAL VALVE. The NaviGate valve
is a self-expandable TMVR system composed of a
nitinol stent-frame with a truncated cone 21 mm in
height (Table 2, Figure 9). Several annular winglets
anchor the valve within the mitral annulus. The valve
can be delivered using transatrial, transapical, or
transseptal access. The delivery system has a
JACC VOL. 69, NO. 17, 2017 Regueiro et al. 2187
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F I G U R E 9 NaviGate Valve

(A) Valve prosthesis. (B) Valve prosthesis after explantation in an animal model. (C) The 2-dimensional transesophageal echocardiography
short-axis view during preclinical evaluation. Images provided by NaviGate Cardiac Structures.

diameter of 30-F at the distal part and 18-F at the
level of the catheter shaft (54). The first-in-human
implantation of the NaviGate valve was performed
in October 2015. According to the manufacturer’s in-
formation, the early feasibility and safety study with
a transatrial approach is planned to start during 2017
and will include 30 patients in 2 centers (55). Further
information regarding this trial has is not yet
available.
TECHNOLOGIES UNDER
PRECLINICAL EVALUATION
AccuFit TMVR SYSTEM. The AccuFit TMVR system
(Sino Medical Science Technology, Inc., Tianjin,
China) is composed of a circular, self-expanding, self-
centering frame device that has an atrial flange, a
ventricular flange, and an annulus
(Figure 10). It has a supra-annular design and is self-
centering. The valve is made of 3 bovine pericardial
leaflets. The valve is anchored mainly through sand-
wiching the annulus and native valve leaflets be-
tween the atrial and ventricular flanges.
prosthetic valve is implanted using a transapical
approach with a 38-F caliber system (56). The first-in-
human study will be initiated in the first quarter of
2017 (57).
CARDIOVALVE TMVR SYSTEM. The Cardiovalve
TMVR is a self-expandable trileafleat
(Figure 10). The system is advanced using the trans-
femoral approach with a 28-F introducer. The height
of the crimped valve is 32 mm. Once the valve is
deployed, the protrusion into the left ventricle is
approximately 12 mm. The valve is anchored into the
mitral annulus over 24 focal “sandwiching” points,
with a symmetrical design that does not require
rotational positioning. There are 3 differently sized
valves with diameters that range from 40 to 50 mm.
The system is under preclinical evaluation, and
the first-in-human implantations are planned for
2017 (58).
CEPHEA TMVR SYSTEM. The Cephea TMVR system
(Cephea Valve Technologies, San Jose, California)
consists of a self-expanding double-disk structure
and a bovine trileaflet valve (Figure 10). The pros-
thesis has a multilevel conformability design, making
the valve capable of adapting to various anatomies.
The atrial disc rests on the floor of the left atrium, the
center column provides a stable platform for leaflet
support, and the ventricular disc anchors to the sub-
support annular region. This modular architecture isolates the
prosthesis from external annular and myocardial
deformation. The prosthesis can be deployed using an
antegrade approach (transatrial or transseptal) and
can be fully recaptured. There is a 2-step deployment
The that uses multiple redundant mechanism to anchor
the valve. During the first step, the frame aligns and
self-orients to the subannular plane, and anchors
using the native annulus as a support, and during the
second step, the frame self-centers and seals by
supra-annular fixation (59,60). The first-in-human
valve implantations are planned for 2017.
SATURN TMVR TECHNOLOGY. The Saturn technol-
ogy (InnovHeart Srl, Milan, Italy) is composed of an
annular structure that encircles the mitral valve and
provides support for the valve prosthesis (Figure 10).
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F I G U R E 1 0 TMVR Technologies Under Preclinical Evaluation

(A) AccuFit TMVR. (B) Cardiovalve. (C) Cephea. (D) Saturn TMVR. (E) Abbott TMVR. TMVR ¼ transcatheter mitral valve replacement. A was reprinted from Abdelaghani
et al. (56), with permission from Europa Digital & Publishing. B is reprinted with permission from De Backer et al. (69). D was provided by InnovHeart. E was provided
by Abbott Vascular.

Both parts are designed to be connected by means of procedure is done using the transapical approach
guidewires. The transapical procedure has already (62). A transfemoral delivery system is in
been preclinically validated. The procedure using a development.
transseptal approach is under development. The first There are several other devices under preclinical
part of the procedure consists of positioning a pair of evaluation. However, design features of and preclin-
guidewires to embrace the mitral leaflets at a level ical results using these devices are very limited at the
immediately below the mitral annulus. The annular present time.
structure is then introduced over-the-wire in the left
ventricle. The second part consists of introducing INSIGHTS FROM TMVR EARLY
onto the left ventricle the collapsed central stent CLINICAL EXPERIENCE
engaged over the connecting guidewires to reconnect
the component to the annular structure, followed PATIENT CLINICAL CHARACTERISTICS AND SELECTION.
by the final positioning and release of the central According to early observations reported with
stent (61). various systems, patients currently selected for
ABBOTT TMVR. The Abbott TMVR system (Abbott TMVR are those considered at high or prohibitive
Vascular, Abbott Park, Illinois) is a self-expanding surgical risk, as determined by surgical risk scores
bovine trileaflet valve with 2 components: a nitinol and evaluation by the heart team. To date, most
annular portion and a braided nitinol atrial section patients have been treated on the basis of compas-
(Figure 10). The atrial section is intended to avoid sionate clinical use programs. There are, however,
paravalvular leakage. Fixation of the valve is accom- scarce data for the reasons for selecting TMVR
plished by leaflet capture and atrial sealing. The over other approved transcatheter therapies, such as
JACC VOL. 69, NO. 17, 2017 Regueiro et al. 2189
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procedure for the different transcatheter valve plat-

T A B L E 5 Early Clinical Experience With TMVR in Native
Severe MR (N ¼ 115)*
forms, the screening failure rate at this stage seems to
be high. It will be very important to collect this in-
Patient characteristics
Age, yrs 73.8 (39–91)
formation in future studies in order to better deter-
Female 30/115 (26.1) mine the subset of patients who may potentially
STS score 7.5 (1.0–47.7) benefit from this technology.
NYHA functional class $III 83/101 (82.2)
PROCEDURAL ASPECTS. A total of 115 cases with
Ischemic/functional MR 85/114 (74.6)
9 different dedicated transcatheter mitral valve
LVEF <50% 65/86 (75.6)
Valve type and approach
prosthetic devices have been reported to date. The
Devices majority of procedures (94%) were performed using a
Tendyne 30/115 (26.1) transapical approach under general anesthesia and
Intrepid 27/115 (23.5) fluoroscopic and transesophageal echocardiographic
Neovasc Tiara 19/115 (16.2) guidance. One device in particular was used exclu-
CardiAQ-Edwards 13/115 (11.3)
sively in the transfemoral approach (Caisson pros-
FORTIS† 13/115 (11.3)
thesis), whereas another could be implanted using
HighLife 6/115 (5.2)
transapical or transfemoral approach (CardiAQ
Caisson 5/115 (4.3)
MValve 1/115 (1.0)
device).
NCS NaviGate 1/115 (1.0) Although these were the very early and/or first-in-
Transfemoral approach 7/115 (6.1) human phase experiences with different TMVR
Procedural and 30-day outcomes devices, the average technical success (valve suc-
Technical success 100/113 (88.4) cessfully implanted with a normally functioning
Procedural mortality 10/114 (8.8)
valve post-procedure) was high (88%; ranging from
LVOT obstruction 1/96 (1.0)
75% to 100%). The main technical issues were related
Post-procedural $ moderate MR 1/77 (1.3)
to: 1) transcatheter valve instability or inappropriate
30-day mortality 26/112 (23.2)
valve fixation due to incomplete capture of the pos-
Values are weighted mean (range) or n/N (%). *Patient baseline and procedural terior mitral leaflet; 2) issues with the subvalvular
characteristics are derived from previously presented data. Patients who were
treated but not reported are not included in the analysis. †In late 2015, Edwards mitral apparatus; 3) problems with the hemostasis of
Lifesciences stopped the FORTIS program because of valve thrombosis. The valve the transapical access (usually due to myocardial
is not currently available.
Abbreviations as in Tables 1 and 3. tears); 4) leaflet malfunction following valve im-
plantation; and 5) interaction with a previously
implanted aortic valve. Of note, the fact that most
current TMVR systems are not fully retrievable led to
conversion to open heart surgery and valve explan-
the MitraClip device. In fact, no data exist as to tation in most patients experiencing technical issues
whether or not the patients selected for TMVR were during the TMVR procedure.
considered suboptimal candidates for MitraClip
L V O T o b s t r u c t i o n . This life-threatening complica-
therapy.
tion occurred in a single case (<1%) in these initial
The main clinical characteristics of the patients
series of TMVR. This probably reflects appropriate
undergoing TMVR are summarized in Table 5. Pa-
patient selection criteria using 3D CT, excluding those
tients who have undergone TVMR were in their mid-
patients with very small LVOTs that would predict
70s, and most of them (74%) were male. Most pa-
excessive risk. Also, the fact that several TMVR plat-
tients (76%) had low left ventricular ejection frac-
forms involve capturing the anterior leaflet among
tions (LVEF), and MR was of ischemic origin in the
the mechanisms for valve anchoring might have
majority. Comorbidities such as chronic kidney dis-
decreased the risk of this complication.
ease and chronic pulmonary obstructive disease
were among the most frequently reported. Of note, Valve performance: hemodynamic results.
secondary MR was diagnosed in most patients who Results of valve performance associated with the
underwent TMVR, despite the lack of definite evi- different transcatheter valve platforms have been
dence supporting a clinical benefit with this clinical very good, with mean transvalvular gradients
approach. of #3 mm Hg in all cases and a very low rate (<2%) of
Unfortunately, scarce data exist for patient inclu- significant paravalvular leakage. These results
sion and/or exclusion criteria and patient screening. compare favorably with those obtained with trans-
Although there are no definite data on the number of catheter mitral valve repair systems and are close to
patients screened versus those finally undergoing the those reported following surgical mitral valve repair
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Transcatheter Mitral Valve Replacement MAY 2, 2017:2175–92

and/or replacement. However, the presence of mitral scarce information about the risk of valve throm-
annular calcification has been an exclusion criterion bosis after TMVR. The TMVR program with the
for all TMVR systems, and there are no data on how Fortis valve was temporarily halted due to issues of
these devices would perform in the setting of severe valve thrombosis (66). No details about this
annular calcification, where paravalvular leakage and complication were provided, but 1 of the patients in
anchoring could be issues. the current series had a clinically relevant episode
of valve thrombosis a few weeks after TMVR with
3 0 - d a y m o r t a l i t y . To date, the average 30-day
the Fortis valve. One episode of valve thrombosis
mortality rate following TMVR has been 23%,
was reported following implantation of the Ten-
ranging from 0% to 53%. Approximately one-half of
dyne valve. The patient, whose anticoagulation
the deaths occurred periprocedurally and were
therapy was subtherapeutic (INR ¼ 1.5), had an
mainly related to unsuccessful TMVR, frequently
increased mitral gradient at the 30-day follow-up
leading to conversion to open-heart surgery. Also,
and evidence of leaflet thrombosis on CT imaging.
access site management issues were responsible for
Complete resolution of the thrombus with normal-
some episodes of death in this initial experience,
ization of the prosthetic valve function was docu-
mainly secondary to myocardial tears. The other half
mented by echography and CT following
of in-hospital and/or 30-day deaths occurred later on,
intensification of oral anticoagulation therapy (43).
following the initial periprocedural period. In these
Anticoagulation is recommended for at least the
cases, multiorgan failure was the most commonly
first 3 months after surgical mitral valve replace-
reported cause of death. Although procedural com-
ment (67,68). While waiting for more data on
plications and failure to achieve technical success
antithrombotic therapy post-TMVR, anticoagulation
contributed to these deaths in many cases, other pa-
therapy for the first months following the proced-
tients died within the weeks following a successful,
ure should probably be used. Future studies should
uncomplicated TMVR procedure. In these cases,
also determine the risk and efficacy of adding an-
the reasons explaining post-TMVR mortality are
tiplatelet therapy in addition to anticoagulation in
probably multifactorial. First, patients’ comorbid-
such patients.
ities, including noncardiac diseases and frailty issues,
might have played a role. Second, the transapical
CONCLUSIONS
approach has been associated with a higher rate of
periprocedural complications (particularly major
TMVR is evolving to become a potentially new
and/or life-threatening bleeding) and mortality in the
alternative for treating patients with severe MR who
TAVR field (63). In addition to the negative effects of
are at very high or prohibitive surgical risk. The
thoracotomy in an elderly and frail population, the
complexity of the mitral valve apparatus and the
higher degree of myocardial injury associated with
heterogeneity of the disease have limited the
the transapical approach may be particularly delete-
implementation of this therapy to date. Several de-
rious in patients with reduced LVEF pre-procedurally,
vices are under clinical evaluation, and the early
such as those harboring severe functional MR.
experience with more than 100 patients has
Finally, acute abolishment of the volume overload
demonstrated the feasibility of TMVR. Presently,
associated with severe MR in patients with severely
multiple TMVR systems are being evaluated in
depressed (<30%) LVEF may have temporary nega-
several centers in an overall small number of highly
tive effects, including a further reduction in LVEF
selected patients. Future studies with a much larger
that may complicate the post-operative period. This is
number of patients are needed to provide consistent
well known in the surgical field (64) and should be
safety and efficacy data for each of the TMVR sys-
considered when evaluating these patients for TMVR.
tems. This will determine whether or not TMVR
LATE OUTCOMES. Intermediate term data for out- could become a real alternative for the increasing
comes after TMVR are limited to only 2 platforms number of patients with severe MR for whom more
(Intrepid and Fortis [Edward Lifescience). There have aggressive approaches are not suitable.
been no reports of structural valve degeneration,
valve dislocation requiring reintervention, or new or ADDRESS FOR CORRESPONDENCE: Dr. Josep
worsening paravalvular leakage over 6 to 12 months Rodés-Cabau, Quebec Heart and Lung Institute, Laval
of follow-up. University, 2725 Chemin Ste-Foy, G1V 4GS Quebec
Concerns have arisen regarding the risk of valve City, Quebec, Canada. E-mail: josep.rodes@criucpq.
thrombosis after TAVR (65). There is, however, ulaval.ca.
JACC VOL. 69, NO. 17, 2017
MAY 2, 2017:2175–92
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KEY WORDS mitral regurgitation, mitral
valve surgery, transcatheter cardiac
therapeutics