Annuloplasty
Transcatheter ring implantation technologies can be divided into direct
and indirect annuloplasty, depending on the type of interaction with the
native annulus11Colli A,
Fiocco A, Nadali M, Besola L, Pradegan N, Folino G et al.
Transcatheter mitral valve therapies for degenerative and functional
mitral regurgitation. 2020. In Emerging Technologies for Heart
Diseases (pp. 417-461).. Academic Press.. Indirect annuloplasty
devices are typically implanted into the coronary sinus and potentially
are simpler for deployment, but can perform a lower grade of reduction
in terms of native annular dimensions, compared to direct annuloplasty.
Direct approaches can mimic a surgical annuloplasty in a more effective
fashion, thus allowing for better annular stabilization and leaflet
coaptation restoring.
Currently, clinical experience on transapical technologies is very
limited, being Valcare Amend the only successfully implanted device in
humans9.
Valcare Amend
The AMEND (Valcare Medical, Herzliya Pituach, Israel) is a
transcatheter-implanting solution for direct mitral annuloplasty (Figure
1). The device is intended to deliver a complete semirigid D-shaped ring
to the LA, to anchor it to the annulus and stabilize it, resulting in
reduced antero-posterior dimensions and improved leaflet coaptation.
Three ring sizes are available (34, 40 and 46 mm), allowing to treat a
wide range of patients, by fitting a diseased annulus ranging from 29 to
50 mm. Currently the Company developed both transapical and transseptal
delivery options, through a 24F and 28F catheter,
respectively.22Mangieri A,
Laricchia A, Giannini F, Gallo F, Kargoli F, Ladanyi A et al … &
Latib, A. Emerging Technologies for Percutaneous Mitral Valve Repair.
Frontiers in Cardiovascular Medicine. 2019; 6.
The first-in-human successful implantation was performed and described
in 2016 by our Group 33Gerosa
G, Besola L, Manzan E et al. First-in-Human of Catheter-Delivered
Annuloplasty Ring to Treat Functional Mitral Regurgitation. JACC
Cardiovasc Interv. 2016 Nov 14;9(21):e211-e213.. Transapical
implantation is performed in a hybrid operating room, under general
anesthesia, using a conventional left anterior mini-thoracotomy. The
entire procedure is guided by transesophageal echocardiography (2D and
3D TEE) and fluoroscopy. After introduction into the LV, the 28-F AMEND
system is navigated over a wire through the mitral valve into the LA.
Once unsheated, the ring adoptes its closed D shape and can be
appropriately oriented by the use of multiple adjustment tools of the
delivery system. Once the desired position is confirmed by fluoroscopic
guidance, a two-step anchoring procedure is performed. First, multiple
anchors are deployed on the posterior segment of the ring, allowing for
a secure fixation of the device to the posterior annulus. During the
second step, the sheath is steered anteriorly toward the aortomitral
continuity and once good contact is achieved, the anterior anchors are
deployed, resulting in both complete fixation and antero-posterior
diameter reduction. The device is finally released and the delivery
system is retracted from the heart.
Current clinical experience includes a total of 14 implanted
patients10. Eight of them were treated for FMR as a
single annuloplasty therapy, while 2 patients were implanted to treat
DMR as a single therapy. In 4 other patients, AMEND ring implantation
was performed in a combination procedure, with MitraClip (3 patients)
and NeoChord (1 patient), thus representing a solid foundation for
stand-alone or combined repair, to improve both leaflet and chordal
repair
procedures10,44Meerkin
D. The AMEND Mitral Repair System: Technology and Clinical Updates.
Presentation CRT 2019. Chicago, IL 2019.. Post-procedural MR was ≤ 2+
in all performed implantations. In treated patients (n=14), 20% mean
reduction of AP diameter was achieved, no residual pulmonary flow
reversal in all cases was reported, mean reduction of the jet area was
74%10,12.
The AMENDTM trial (NCT02602613, Annuloplasty Ring Applied in a
Transcatheter Method) is currently recruiting to evaluate the efficacy
and safety of the device, with a target sample size of 40
patients10.
Chordal Repair
Transcatheter chordal repair technologies are primarily intended to
treat DMR. Although the disease can involve multiple components of the
MV apparatus, rupture of native chordae represents one of the leading
mechanisms.
In the past decades, surgical practice introduced chordal replacement by
polytetrafluorethylene (PTFE) sutures implantation55Zussa C,
Frater RW, Polesel E, et al. Artificial mitral valve chordae:
experimental and clinical experience. Ann Thorac Surg 1990;50:367-73.,
alone or together with the positioning of a ring, demonstrating
excellent results in terms of long-term clinical outcomes. Further
validation of the chordal therapy was later achieved, after the
introduction of the “respect rather than resect” principle66Carpentier
A. Cardiac valve surgery–the ”French correction”. J Thorac
Cardiovasc Surg. 1983 Sep;86(3):323-37.,77Frater
RW1, Vetter HO, Zussa C, Dahm M. Chordal replacement in mitral valve
repair. Circulation. 1990 Nov;82(5 Suppl):IV125-30.,88Adams
DH1, Rosenhek R, Falk V. Degenerative mitral valve regurgitation: best
practice revolution.Eur
Heart J. 2010 Aug;31(16):1958-66., becoming a mainstay in open
heart MVRe techniques.
Several years later, the expanding field of Transcatheter Mitral Valve
Repair (TMVRe) technologies has embraced the chordal repair philosophy.
Mostly by beating-heart transapical approach99Noack T, Borger
MA. Chordal replacement: future surgical gold standard or first-line
option as bridge to definitive therapy in primary mitral
regurgitation? Ann Cardiothorac Surg 2020. doi:
10.21037/acs-2020-mv-22, this technique stresses the concept of
micro-invasiveness and is currently the only one in clinical practice to
allow a real-time heart-beating assessment of residual MR during the
chordal tensioning phase, with a filled left ventricle through live
three-dimensional intraoperative trasesophageal echocardiography . It
has become a feasible, safe and reproducible option in selected patients
with non-complex primary MR and can be potentially adopted in combined
procedure, together with other-targeting transcatheter technologies,
covering in that way the wide spectrum of MV lesions. In the scenario of
transapical chordal repair systems, we focus on currently available
devices in clinical practice: Neochord DS 1000 and Harpoon Mitral Valve
Repair System (MVRS).
Neochord DS 1000:
The Neochord DS 1000 device (Neochord Inc, St. Louis Park, MN) is a
transapical off-pump MVRe system based on expanded
polytetrafluorethylene (ePTFE) chordal implantation. Currently more than
1,200 patients have been already treated with Neochord in the
world1010Fiocco A, Nadali M, Speziali G, Colli A. Transcatheter
mitral valve chordal repair: current indications and future
perspectives. Front Cardiovasc Med. 2019;6:128.
https://doi.org/10.3389/fcvm.2019.00128..
In December 2012, the results reported by the TACT Trial (Transapical
Artificial Chordae Tendinae - NCT01777815) allowed this technology to
gain CE mark approval1111Seeburger, J., Rinaldi, M., Nielsen, S.
L., Salizzoni, S., Lange, R., Schoenburg, M., … & Aidietis, A.
(2014). Off-pump transapical implantation of artificial neo-chordae to
correct mitral regurgitation: the TACT Trial (Transapical Artificial
Chordae Tendinae) proof of concept. Journal of the American College of
Cardiology, 63(9), 914-919. 1212https://www.clinicaltrials.gov/ct2/show/NCT01777815,
being the first transcatheter chordal repair device available on the
market. In the US it received the investigational device exemption (IDE)
approval from the United States Food and Drug Administration (FDA), and
early clinical experience has been recently reported in Asian countries,
mainly represented by China.1313Wang, L. H., Pu, Z. X., Kong, M.
J., Jiang, J. B., Ren, K. D., Gao, F., … & Liu, X. B. (2019). The
first four cases of successful NeoChord procedure in mainland
China. World journal of emergency medicine, 10(3), 133. Preoperative
anatomic and echocardiographic selection criteria as well as progressive
technique refinement, contributed to create a solid procedural
framework, thus the procedure evolved into a reproducible and safe
technique, with good results in selected patients.
The procedure is performed, under general anesthesia, selective lung
intubation and real-time 2D/3D TEE guidance. Through an antero-lateral
left mini-thoracotomy in the fifth-intercostal space, the pericardium is
opened and suspended, and the left lung is selectively excluded,
exposing the left ventricle (LV) apex. The ideal entry side is
identified about 2 cm–4 cm postero-lateral from the real apex
1414Colli, A., Bizzotto, E., Manzan, E., Besola, L., Pradegan, N.,
Bellu, R., … & Gerosa, G. (2017). Patient-specific ventricular
access site selection for the NeoChord mitral valve repair
procedure. The Annals of Thoracic Surgery, 104(2), e199-e202.and
confirmed with a gentle digital palpation under 2D-TEE imaging. Two
pledgeted round purse-string are sutured around the identified
entry-site which is then scalpeled with an 11 inch blade, performing a
trans-wall ventriculotomy. The device is first gently introduced inside
the LV and then carefully navigated trough the LV avoiding papillary
muscles damage and interference with subvalvular apparatus of anterior
mitral leaflet (AML). Ventricular navigation is real-time guided through
TEE X-plane view. Once the valve is crossed, a 3D imaging assessment
allows for a precise positioning of the tip on the targeted scallop
which is grasped by closing the jaws of the device. A fiberoptic display
gives a feedback on the secured leaflet capture, before grasping. The
grasped leaflet is then pierced at its edge, allowing for the deployment
of a single pair of chords (Figure 2). The device is subsequently opened
and gently retrieved from the ventricle, leading outside the chordal
loop. The two ends of the suture are then passed in the loop, forming a
girth hitch knot that is advanced till the free edge of the scallop. The
procedure is repeated for each pair of chords deployed. Finally under 2D
and 3D TEE control, the chords are tensioned, until adequate leaflet
coaptation is achieved and all the chordal free ends are then secured to
the LV wall 1515Colli, A., Adams, D., Fiocco, A., Pradegan, N.,
Longinotti, L., Nadali, M., … & Gerosa, G. (2018). Transapical
NeoChord mitral valve repair. Annals of cardiothoracic surgery, 7(6),
812. on a Teflon felt.
The learning curve needed to perform optimally NC procedure, combining
procedure standardization, technical refinements and adequate
patient-selection, has been analyzed in a single center study.1616Colli
A, Bagozzi L, Banchelli F, Besola L, Bizzotto E, Pradegan N, et al.
Learning curve analysis of transapical NeoChord mitral valve
repair. Eur J Cardiothorac Surg. (2018) 54:273–80. doi:
10.1093/ejcts/ezy046 In the CUSUM analysis performed by Colli et.al,
the procedure demonstrates to be safe and effective. Threshold, beyond
which the number of deaths or ineffective procedures would be
unacceptable, was never reached, showing a good surgical performance
even at the beginning of the experience. The study estimates a need for
50 cases per surgeon to standardize the technique and reach the “good
performance period”. The Authors underline that most of the early
failures were linked to technical errors during MV crossing phase, which
were subsequently avoided with the improvement of the intraventricular
navigation technique and adoption of different imaging views to cross
the MV. To reduce the learning curve effect, acting on the technical
refinement and procedure standardization, a dedicated preclinical
training program was introduced, by the use of proctored highly
realistic simulation on ex-vivo pulsatile models.1717Leopaldi AM,
Wrobel K, Speziali G, van Tuijl S, Drasutiene A, Chitwood WR Jr. The
dynamic cardiac biosimulator: a method for training physicians in
beating-heart mitral valve repair procedures. J Thorac Cardiovasc
Surg. (2018) 155:147–55. doi: 10.1016/j.jtcvs.2017.09.011
Concerning echocardiographic selection criteria, both the extension of
prolapsing segments and the annular dimension demonstrated to have an
impact in term of outcomes on Neochord repair procedure. The
prolapse/flail anatomical aspects were classified based on growing
complexity as “Type A” isolated central posterior leaflet
prolapse/flail, “Type B” posterior multi-segment prolapse/flail,
“Type C” anterior or bi-leaflet prolapse/flail, “Type D”
para-commissural prolapse/flail or presence of significant
leaflet/annular calcifications. Several studies underlined differences
between these groups, reporting better results in terms of outcomes when
posterior leaflet disease (A and B type) was treated, compared to more
complex leaflet lesions (Type C-D). 1818Colli, A., Manzan, E.,
Rucinskas, K., Janusauskas, V., Zucchetta, F., Zakarkaitė, D., … &
Gerosa, G. (2015). Acute safety and efficacy of the NeoChord
procedure. Interactive cardiovascular and thoracic surgery, 20(5),
575-581 1919 Colli A,
Manzan E, Besola L, et al. One-Year Outcomes After Transapical
Echocardiography-Guided Mitral Valve
Repair. Circulation 2018;138:843-5. 10.1161/CIRCULATIONAHA.118.033509
The leaflet-to-annulus index (LAI) was further introduced to improve the
patient-selection process. LAI was calculated by the ratio between the
sum of anterior and posterior leaflet length and the antero-posterior
diameter. It represents the amount of overriding tissue that is
potentially responsible of coaptation, considering annular dilatation in
relation to the extension of the leaflets and not as an absolute
concept. An excess of leaflet tissue of at least 20% (corresponding to
LAI >1.2) has shown to be a positive predictor of MR ≤ mild
at 1 year follow-up2020Colli A, Besola L, Montagner M, Azzolina D,
Soriani N, Manzan E, et al. Prognostic impact of leaflet-to-annulus
index in patients treated with transapical off-pump echo-guided mitral
valve repair with NeoChord implantation. Int J Cardiol
2018;257:235–7.. Thus, LAI can be used to identify patients without
leaflet-to-annulus mismatch, who could benefit from a ringless repair
procedure such as Neochord.
Since its first in human application in 20102121Seeburger, J.,
Borger, M. A., Tschernich, H., Leontjev, S., Holzhey, D., Noack, T.,
… & Mohr, F. W. (2010). Transapical beating heart mitral valve
repair. Circulation: Cardiovascular Interventions, 3(6), 611-612.,
the device demonstrated good outcomes in reducing mitral regurgitation
along with safety feasibility in patients with DMR2222Rucinskas K,
Janusauskas V, Zakarkaite D, et al. Off-pump transapical implantation
of artificial chordae to correct mitral regurgitation: early results
of a single-center experience. J Thorac Cardiovasc Surg 2014;147:95-9.
10.1016/j.jtcvs.2013.08.012. The TACT trial (Transapical Chordae
Tendinae, NCT01777815) was the first prospective, multicenter, single
arm study designed to evaluate the safety profile and efficacy of
NeoChord DS 10002323Seeburger,
J., Rinaldi, M., Nielsen, S. L., Salizzoni, S., Lange, R., Schoenburg,
M., … & Aidietis, A. (2014). Off-pump transapical implantation of
artificial neo-chordae to correct mitral regurgitation: the TACT Trial
(Transapical Artificial Chordae Tendinae) proof of concept. Journal of
the American College of Cardiology, 63(9), 914-919.. Thirty patients
with severe MR due to isolated posterior prolapse scheduled for off-pump
transapical implantation of neo-chordae were included between 2009 and
2014. Acute procedural success, defined as the placement of at least 1
neochord and reduction of MR from 3+ or 4+ to at least 2 grades was
achieved in 86.7% of patients (26). The trial highlighted the link
between improvement of results and increased experience, since durable
reduction in MR to ≤2+ at 30 days was achieved in 5 of the first 15
patients and 12 of the last 14 patients. The procedure was technically
safe and feasible and yields further potential for improvement of
efficacy and durability31,2424https://www.clinicaltrials.gov/ct2/show/NCT01777815. Of 6 patients initially enrolled in the early experience of the TACT
trial at Leipzig-Heart Center, 3 of them reach a 5 year follow up
showing up to mild-to moderate MR and good clinical condition. In these
patients a trend toward reverse remodeling of the left ventricle and no
increase in mitral annular dilatation was observed2525Kiefer, P.,
Meier, S., Noack, T., Borger, M. A., Ender, J., Hoyer, A., … &
Seeburger, J. (2018). Good 5-year durability of transapical beating
heart off-pump mitral valve repair with neochordae. The Annals of
thoracic surgery, 106(2), 440-445..
A single-center experience (144 patients) reports early procedural
success of 98.6% (142), early mortality of 1.4% (2) and patient
success (endpoint composite by MR ≤ 2 and freedom from reoperation) of
89% at 1 year27. A multicenter European study
published in 2018 enrolling 213 patients reported an excellent
procedural success rate. Procedural success was achieved in 206 (96.7%)
patients, at 1-year follow-up, overall survival was 98 ± 1% and
composite end point was achieved in 84 ± 2.5% for the overall
population.2626Colli, A., Manzan, E., Aidietis, A., Rucinskas, K.,
Bizzotto, E., Besola, L., … & Drasutiene, A. (2018). An early
European experience with transapical off-pump mitral valve repair with
NeoChord implantation. European Journal of Cardio-Thoracic
Surgery, 54(3), 460-466.
As above mentioned, in the United States the NeoChord technology has
received investigational device exemption (IDE) approval from FDA.
Patients are being enrolled in a prospective, multicenter, randomized
controlled clinical trial (ReChord trial NCT02803957) comparing
traditional surgical repair with NeoChord repair with a 1:1
randomization2727https://clinicaltrials.gov/ct2/show/NCT02803957.
Neochord technology was already employed in combined transcatheter MVRe
procedures with a simultaneous two-step annuloplasty and chordal repair
session2828Colli, A., Raanani, E., Cobiella, J., Wrobel, K.,
Nombela, L., Maroto, L., … & Meerkin, D. (2020). Transapical and
transfemoral combined mitral valve repair with annular and leaflet
therapies. The Annals of Thoracic Surgery. 2929Von Bardeleben,
R. S., Colli, A., Schulz, E., Ruf, T., Wrobel, K., Vahl, C. F., … &
Beiras-Fernandez, A. (2018). First in human transcatheter COMBO mitral
valve repair with direct ring annuloplasty and neochord leaflet
implantation to treat degenerative mitral regurgitation: feasibility
of the simultaneous toolbox concept guided by 3D echo and computed
tomography fusion imaging. European heart journal, 39(15), 1314-1315..
During the first step AMEND ring was implanted, obtaining annular
stabilization, A-P dimension reduction and thus increasing the
overriding of the flailing leaflets. In a second phase, deployment of
artificial chords with Neochord procedure allowed for flail treatment
and restored leaflet coaptation.
Anecdotal cases of non-conventional use of Neochord device have been
recently reported.
In 2018 the first in human edge-to-edge MVRe with neochord technology
was applied on a high-risk surgical patient rejected for MitraClip due
to unfavorable anatomy3030Colli, A., Besola, L., Bizzotto, E.,
Peruzzo, P., Pittarello, D., & Gerosa, G. (2018). Edge-to-edge mitral
valve repair with transapical neochord implantation.. Furthermore, a
transcatheter mitral valve replacement (MVR) case, combined with
neochord implantation was reported. In the presence of a long AML, the
risk of neo left ventricular outflow tract obstruction was reduced by
previous neochord deployment on the AML and subsequent artificial
tethering of the leaflet3131Beiras-Fernandez A, Ruf, T. F, Obadia
J. F. I., Münzel T, Kreidel F, & von Bardeleben R. S. Neochord
anterior leaflet treatment to facilitate transcatheter mitral valve
replacement with 3D real-time echocardiography. European Heart
Journal. 2020.
An interesting case of MVRe through neochord implantation in a patient
affected by dextrocardia and situs-inversus, reporting no significant
issues during the procedure was also described 3232Bhatia, I.,
Chan, D. T. L., Lam, S. C. C., & Au, T. W. K. (2020). Feasibility of
novel transapical off pump beating heart mitral valve repair in a
patient with dextrocardia and situs inversus. European Journal of
Cardio-Thoracic Surgery..