Transcatheter Tricuspid Valve Interventions: Landscape, Challenges, and Future Directions

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 71, NO.
25, 2018
ª 2018 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
THE PRESENT AND FUTURE
JACC STATE-OF-THE-ART REVIEW
Transcatheter Tricuspid
Valve Interventions
Landscape, Challenges, and Future Directions
Lluis Asmarats, MD,a Rishi Puri, MBBS, PHD,a,b Azeem Latib, MD,c José L. Navia, MD,d Josep Rodés-Cabau, MDa
ABSTRACT
Tricuspid regurgitation is a common finding in patients with left-sided valvular or myocardial disease, often being a
marker for late-stage chronic heart failure with a grim prognosis. However, isolated tricuspid valve surgery remains
infrequent and is associated with the highest mortality among all valve procedures. Hence, a largely unmet clinical need
exists for less invasive therapeutic options in these patients. In recent times, multiple percutaneous therapies have been
developed for treating severe tricuspid regurgitation, including tricuspid valve repair and, more recently replacement,
opening an entirely new venue for managing tricuspid regurgitation. The aim of this review is to provide an updated
overview and a clinical perspective on novel transcatheter tricuspid valve therapies, highlighting potential challenges and
future directions. (J Am Coll Cardiol 2018;71:2935–56) © 2018 by the American College of Cardiology Foundation.
T ricuspid regurgitation (TR) is estimated to

affect >1.5 million people in the United
States (1), with a yearly incidence of about
200,000 and >300,000 patients in the United States
stems from increased in-hospital mortality, particu-
larly following prior left-sided heart valve surgery
(6,7) or after initial tricuspid repair (8,9). Of note,
isolated TV surgery remains rare—only 5,005 isolated
and Europe, respectively. TR is most often functional, tricuspid procedures were performed in a large
primarily due to annular dilatation and leaflet teth- contemporary U.S. nationwide registry over a 10-
ering from right ventricular remodeling caused by year period—and continues to be associated with
left-sided heart disease, atrial fibrillation, or pulmo- the highest surgical risk among all valve procedures
nary hypertension (2). in contemporary practice, with operative mortality
The prognosis of untreated TR remains poor (3), rates of 8.8% to 9.7% (Figure 1) (10,11).
with most patients receiving lifetime medical ther- In recent years, a growing body of knowledge
apy until intractable right heart failure and along with multiple emerging transcatheter tricuspid
end-organ dysfunction appear. This is despite cur- technologies has spurred active investigation within
rent guidelines favoring early tricuspid valve (TV) the interventional and surgical communities alike,
repair in patients with tricuspid annular dilatation with ongoing rapid momentum. We provide an
undergoing left-sided cardiac surgery, even if TR is updated overview of the current landscape of
mild (4,5). Reluctance to perform tricuspid surgery transcatheter TV therapies, focusing on procedural
From the aQuebec Heart & Lung Institute, Laval University, Quebec City, Quebec, Canada; bDepartment of Cardiovascular Med-
Listen to this manuscript’s icine, Cleveland Clinic, Cleveland, Ohio; cInterventional Cardiology Unit, San Raffaele Hospital, Milan, Italy; and the dDepartment
audio summary by of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio. Dr. Asmarats was supported by a grant from Fundacion
JACC Editor-in-Chief Alfonso Martin Escudero. Dr. Rodés-Cabau holds the Canadian Research Chair “Fondation Famille Jacques Larivière” for the
Dr. Valentin Fuster. Development of Structural Heart Disease Interventions; and has received institutional research grant support from Edwards
Lifesciences. Dr. Latib has served as a consultant for Medtronic, Abbott Vascular, and Trialign. Dr. Navia is the inventor on patents
related to the Navigate device; and has served as a consultant and holds stock in NaviGate Cardiac Structures, Inc. All other
authors have reported that they have no relationships relevant to the contents of this paper to disclose. Deepak L. Bhatt, MD,
MPH, served as Guest Editor-in-Chief for this paper. Ankur Kalra, MD, served as Guest Editor for this paper.
Manuscript received February 3, 2018; revised manuscript received March 29, 2018, accepted April 15, 2018.
ISSN 0735-1097/$36.00 https://doi.org/10.1016/j.jacc.2018.04.031

2936 Asmarats et al. JACC VOL. 71, NO. 25, 2018
Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56
ABBREVIATIONS and midterm outcomes, remaining caveats, echocardiographic tricuspid annular threshold
AND ACRONYMS and future directions. of $40 mm (21 mm/m 2) for combined TV repair
(4,5,16), although a larger cutoff (70 mm) based on
CAVI = caval valve PRE-PROCEDURAL SCREENING AND
direct surgical measurements has also been proposed
implantation MULTIMODALITY IMAGING
(17). However, surgical measurements are often per-
CE = Conformité Européenne
formed under unloaded conditions and are highly
CT = computed tomographic TV ANATOMY. Accurate knowledge of the TV
dependent on the traction applied to the TA, and
IVC = inferior vena cava apparatus anatomy is key when planning
recent data cast doubt on their accuracy (18). Judging
NYHA = New York Heart transcatheter tricuspid interventions. The TV
the severity of TR by echocardiography remains
Association is a complex structure, with several anatomic
challenging and controversial. The American Society
QoL = quality of life peculiarities rendering it unique (Figure 2)
of Echocardiography and the European Association of
SVC = superior vena cava (12). Compared with the mitral valve, the
Cardiovascular Imaging currently consider 3 stages of
TA = tricuspid annulus tricuspid annulus (TA) is larger—the largest
functional TR: mild, moderate, and severe (Table 1)
TR = tricuspid regurgitation of all valves, with regurgitant orifice areas
(19,20). A comprehensive description of qualitative,
TTVR = transcatheter tricuspid
often twice those in the mitral position—and
semiquantitative, and quantitative echocardio-
valve replacement its leaflets are thinner and more fragile. The
graphic assessment of functional TR can be found
TTVr = transcatheter tricuspid TA is a saddle-shaped ellipsoid that becomes
elsewhere (21).
valve repair planar and circular as it dilates. Interest-
TV = tricuspid valve ingly, dilatation of the TA occurs primarily in
PATIENT SELECTION. The silent yet progressive
the anterolateral free wall in patients with left-sided
nature of functional TR consistently leads to delayed
heart disease with sinus rhythm, expanding mostly
referral of patients with end-stage heart failure with
along the posterior border with less prominent leaflet
extreme leaflet tethering and tricuspid annular
tethering in patients with functional TR secondary to
enlargement, carrying high perioperative mortality
chronic atrial fibrillation (Figure 3) (13). Because of
and adverse outcomes following correction (22). Ac-
preferential dilation of the anterior and posterior
curate patient screening by a multidisciplinary heart
leaflets, malcoaptation occurs primarily between the
team is paramount to optimize procedural results
anteroposterior and posteroseptal commissures
and effectiveness of transcatheter tricuspid thera-
rather than the anteroseptal commissure, with
pies. Invasive measurement of pulmonary artery
important mechanistic and therapeutic implications
pressures and resistances can be useful when clinical
for TV repair, especially for leaflet-based approaches
and noninvasive data are inconsistent, because
(14).
laminar TR and dynamic right atrial pressure in the
Four chief anatomic structures surround the TV
presence of a prominent V wave may preclude reli-
and are therefore at risk for impingement during
able noninvasive estimates (23). Clinical and echo-
transcatheter tricuspid interventions: the conduction
cardiographic predictors of TR recurrence (TV
system (atrioventricular node and right bundle of His)
tethering distance >0.76 cm or tethering area
coursing the membranous septum at 3 to 5 mm from
>1.63 cm2 [24], higher pre-operative regurgitation
the anteroseptal commissure, the right coronary ar-
grade, left and right ventricular dysfunction, per-
tery (encircling the right atrioventricular groove
manent pacemaker, suture annuloplasty [8],
w5.5 mm from the septal and posterior portions,
increasing pulmonary pressure [25]) or worse sur-
7 mm from the anterior portion), the noncoronary
vival (right ventricular end-systolic area $20 cm2 [6],
sinus of Valsalva, and the coronary sinus ostium be-
age, end-stage renal disease, and TV replacement
ing an important landmark of the posteroseptal
[10]) after TV surgery are important factors to
commissure. The TV apparatus poses additional
consider when assessing potential candidates for
challenging issues to overcome: lack of calcium,
transcatheter TV interventions. First and foremost,
angulation in relation to the superior vena cava (SVC)
efforts should focus on identifying those patients in
and inferior vena cava (IVC), a trabeculated and thin
whom transcatheter TV repair (TTVr) or trans-
right ventricle hindering a transapical approach, or
catheter TV replacement (TTVR) is likely to be futile,
the presence of pre-existing cardiac implantable
heeding the dictum of primum non nocere. At this
electronic devices (15).
early stage of the technology, TTVr and TTVR should
ECHOCARDIOGRAPHIC EVALUATION OF TR probably be reserved for patients with isolated TR
deemed at too high surgical risk because of prior
Echocardiography remains the cornerstone imaging open heart surgery or multiple comorbidities, in the
modality for initial assessment of the etiology and absence of severe right or left ventricular dysfunc-
severity of TR. Current guidelines establish an tion and severe pulmonary hypertension.
JACC VOL. 71, NO. 25, 2018 Asmarats et al. 2937
JUNE 26, 2018:2935–56 Transcatheter Tricuspid Valve Interventions
COMPUTED TOMOGRAPHIC
F I G U R E 1 Trends in U.S. In-Hospital Mortality After Isolated Tricuspid Valve Surgery,
PRE-PROCEDURAL DATA FOR 2003 to 2014
PERCUTANEOUS TV INTERVENTIONS
20
Computed tomographic (CT) imaging has become the
third-step imaging modality during pre-procedural 16
planning for transcatheter TV interventions after
transthoracic and transesophageal echocardiography
Mortality (%)
12
(26,27), because it provides valuable anatomic spatial
information of the TV apparatus sometimes
8
hampered by echocardiography because of its com-
plex geometry and anterior position in the chest. Of
4
note, individually tailored contrast media protocols
have been suggested to optimize CT TV imaging (28).
Several specifications should be considered during CT 0
2003-2006 2007-2010 2011-2014
TV assessment:
Year
1. Tricuspid apparatus morphology: Accurate mea- Isolated TVr p = 0.63 Isolated TVR p = 0.58 TVR and TVr
surement of the TA, including maximal ante-
roposterior and septolateral diameters, perimeter, Reprinted with permission from Alqahtani et al. (11). TVR ¼ tricuspid valve replacement;
area, and right ventricular geometry, is imperative TVr ¼ tricuspid valve repair.
when evaluating devices that directly interact with
the TV leaflets or during the screening process for
TTVR. In the former, maximal distance from the
TA to the right ventricular apex should also be planning heterotopic caval valve implantation
considered (Figure 4A) (29). (CAVI) procedures (Figure 4D) (32). Furthermore,
2. Landing zone geometry: CT imaging is essential to the height between the junction plane and the
identify the target anchoring site with some specific first hepatic/accessory vein is measured to ensure
devices. In patients undergoing TV repair with some for optimal valve positioning without hepatic
coaptation devices, the planned anchoring site is vein obstruction. Likewise, CT imaging is also
selected by drawing a perpendicular line linking the

annular plane with the right ventricular septal free
F I G U R E 2 Tricuspid Valve and Surrounding Structures
wall, on a sagittal reconstruction. CT imaging is also
used to identify a safe landing zone and confirm
adequate annular tissue and shelf for annuloplasty
devices (Figure 4B) (26,30).
3. Anatomic relationships and possible impediments:
CT imaging is of utmost importance when assess-
ing surrounding structures such as the right coro-
nary artery, especially for repair technologies
targeting the TA and for TTVR (Figure 4C) (12,31).
An unfavorable course of the right coronary artery
(#2 mm from the TA) has been reported in 40% of
patients with TR $3þ (12.5% and 27.5% at the level
of the anterior and posterior tricuspid leaflets,
respectively) (31). CT imaging is also an important
screening tool to assess anatomic structures (large
papillary muscles, trabeculations, or prominent
moderator band) that would preclude successful
device navigation.
Reprinted with permission from Taramasso et al. (12). Yellow dashed line ¼ triangle of
4. Vascular access assessment: Sizing of the IVC in Koch (formed by the septal leaflet, tendon of Todaro, and coronary sinus ostium);
the right atrium–IVC junction plane and at the star ¼ atrioventricular node. TV ¼ tricuspid valve.
level of the first hepatic vein is paramount when
F I G U R E 3 Pathoanatomy of Functional Tricuspid Regurgitation
Secondary tricuspid regurgitation results from preferential annular dilation along the anterolateral border in patients with left-sided heart
disease in sinus rhythm, expanding mostly along the posterior border in patients with chronic atrial fibrillation. Reprinted with permission
from Utsunomiya et al. (13). A ¼ anterior; AF-TR ¼ tricuspid regurgitation secondary to atrial fibrillation; AL ¼ anterolateral; Ao ¼ aorta;
IAS ¼ interatrial septum; LH-TR ¼ tricuspid regurgitation because of left-sided heart failure; MV ¼ mitral valve; P ¼ posterior;
PM ¼ posteromedial; TV ¼ tricuspid valve; VC ¼ vena contracta.
essential to assess the status (size and perme- Table 2 summarizes the most important device-
ability) of the venous access (jugular, subclavian, specific anatomic considerations during CT pre-
axillary veins). operative assessment.
5. Risk for right ventricular outflow tract obstruction:
In contrast to left-sided valves, the tricuspid and CARDIAC MAGNETIC RESONANCE FOR THE
pulmonary valves are open-angulated and widely ASSESSMENT OF TV DISEASE
separated by the crista supraventricularis, making
the risk for right ventricular outflow tract Given its excellent spatial resolution, cardiac magnetic
obstruction almost negligible (12). resonance imaging represents the gold standard for
6. Predicting the best fluoroscopic projection: Similar quantifying right ventricular volumes and
to transaortic and transmitral valve replacement, function using breath-held cine images or free-
CT imaging is helpful to provide coplanar fluoro- breathing, noncontrast, ECG-gated steady-state free
scopic projections yielding coaxial device deploy- precession sequences. Cardiac magnetic resonance
ment. Two essential fluoroscopic projections have might be also additive to 3-dimensional echocardiog-
been proposed: the right anterior oblique view raphy for anatomic and functional assessment of the
(obtaining a long-axis view to assess the device’s TV and TA. Quantifying TR severity by cardiac mag-
trajectory and coaxiality with the TA) and the left netic resonance might be performed using the indirect
anterior oblique caudal view (mimicking the sur- method by calculating TR volume (right ventricular
gical “en face” view seen from the right ventricular stroke volume forward pulmonic flow volume) or TR
side) (33). fraction ([TR volume/right ventricular stroke
volume] 100) or by direct measurement of the

T A B L E 1 Echocardiographic Grading of the Severity of Tricuspid Regurgitation
effective regurgitant orifice area, when possible (26).
Mild Moderate Severe
TRANSCATHETER TV REPAIR Structural
TV morphology Normal or mildly Moderately abnormal Severe valve
Multiple technologies for TTVr are currently under abnormal leaflets leaflets lesions
RV and RA size Usually normal Normal or mild dilatation Usually dilated*
preclinical or initial clinical evaluation (34). Accord-
IVC diameter Normal <2 cm Normal or mildly dilated Dilated >2.5 cm
ing to the anatomic therapeutic target, they can be 2.1–2.5 cm
grouped into coaptation or annuloplasty devices. Qualitative
Although most of these devices are still in their rela- Color flow jet area† Small, narrow, central Moderate central Large central jet or
eccentric wall-
tive infancy, early safety and feasibility trials con-
impinging jet
ducted to date have shown promising results. Flow convergence Not visible, transient Intermediate Large throughout
zone or small systole
COAPTATION DEVICES. F o r m a . The Forma Repair
CWD jet Faint/partial/parabolic Dense, parabolic or Dense, often
System (Edwards Lifesciences, Irvine, California) is a triangular triangular
transcatheter option designed to increase the native Semiquantitative
leaflet coaptation surface by occupying the regur- Color flow jet Not defined Not defined >10
area (cm2)†
gitant orifice area. The device, a passively expand-
VCW (cm)† <0.30 0.30–0.69 $0.70
able, foam-filled balloon spacer, is advanced via the
PISA radius (cm)‡ #0.50 0.60–0.90 >0.90
left subclavian or axillary vein through a 20- to 24-F Hepatic vein flow§ Systolic dominance Systolic blunting Systolic flow
sheath introducer and placed within the TA over a reversal
rail that is anchored at the septal portion of the Tricuspid inflow§ A-wave dominant Variable E-wave >1.0 m/s
right ventricular apex. The device is currently Quantitative

EROA (mm2) <20 20–39k $40
available in 3 different sizes—12, 15, and 18 mm—and
RVol (2D PISA) (ml) <30 30–44k $45
is fully retrievable during all steps of the procedure
(Figure 5A). *RV and RA size can be within the normal range in patients with acute severe TR. †With Nyquist limit >50 to
70 cm/s. ‡With baseline Nyquist limit shift of 28 cm/s. §Signs are nonspecific and are influenced by many other
Since the initial human experience in 2015 (35), 18
factors (RV diastolic function, atrial fibrillation, RA pressure). kThere are few data to support further separation of
patients treated under a compassionate clinical use these values. Reproduced with permission from Zoghbi et al. (19).
CWD ¼ continuous-wave Doppler; EROA ¼ effective regurgitant orifice area; IVC ¼ inferior vena cava;
program have been reported, with 15 patients having
PISA ¼ proximal isovelocity surface area; RA ¼ right atrial; RV ¼ right ventricular; RVol ¼ regurgitant volume;
completed 1-year clinical follow-up (29). Successful TR ¼ tricuspid regurgitation; VCW ¼ vena contracta width.
device implantation was achieved in 16 patients

(89%), with no in-hospital mortality. Among the 14
patients with successful device implantation and 1- observed at 30 days. The main clinical data from
year follow-up, improvement in New York Heart As- these initial experiences are summarized in Table 3.
sociation (NYHA) functional class was observed in The Forma device has been successfully used in
86% of patients, with significant increases in 6-min patients with pacemakers or cardiac implantable
walking distance and in quality of life (QoL). Device- electronic devices in situ (17% and 24% of patients
related thrombosis occurred in 1 patient with a sub- included in the compassionate use and U.S. feasibility
therapeutic international normalized ratio, and there studies, respectively). However, post-procedural im-
was 1 rehospitalization for heart failure. Reduction in aging assessment of TR severity, often complex
TR from severe in 94% to moderate to severe or less in because of the presence of multiple small noncir-
46% was observed by 1 year. cular jets in Forma recipients, is particularly chal-
The 30-day outcomes of the US Early Feasibility lenging in this population. To overcome some
Study (n ¼ 29) were recently reported (36). Right procedural issues, next-generation Forma devices
ventricular perforation occurred in 2 patients, and 9 are being developed to ensure predictable anchoring
patients (31%) presented at least 1 adverse 30-day while minimizing the risk for dislodgement or
event, which included death (n ¼ 2), vascular injury perforation. The ongoing European Union and
(n ¼ 1), major or life-threatening bleeding (n ¼ 6), Canadian SPACER (Repair of Tricuspid Valve
device-related surgery (n¼3: one conversion to open- Regurgitation Using the Edwards Tricuspid Trans-
heart surgery due to perforation; two additional catheter Repair System; NCT02787408) trial, plan-
surgeries within the first 30 days due to device ning to enroll 78 patients, with the primary outcome
migration and infection, respectively), and acute being 30-day cardiac mortality, will evaluate safety
kidney injury (n ¼ 3). As with the compassionate-use and efficacy of the Forma device and substantially
experience, significant improvements in NYHA func- extend our understanding of the Forma device
tional class, 6-min walking distance, and QoL were performance (Table 4).
F I G U R E 4 Computed Tomographic Pre-Procedural Workup for Transcatheter Tricuspid Valve Procedures
(A) Forma: anatomic structures of the right heart: right atrium (RA), right ventricle (RV), tricuspid annular plane (white arrows), and moderator band (star). Reprinted
with permission from Perlman et al. (29). (B) TriCinch: ideal target site (asterisk) between the anteroposterior commissure and midanterior on computed tomography
and fluoroscopy. Reprinted with permission from Latib et al. (30). (C) Distance between the right coronary artery and the tricuspid annulus. Reprinted with permission
from Taramasso et al. (12) and from van Rosendael et al. (31). (D) Caval valve implantation: sizing is performed in the right atrium–inferior vena cava plane and at the
level of the first hepatic vein. Reprinted with permission from O’Neill et al. (32). APC ¼ anteroposterior commissure; ASC ¼ anteroseptal commissure; AV ¼ aortic
valve; MV ¼ mitral valve; RA ¼ right atrium; RV ¼ right ventricle; TV ¼ tricuspid valve.
T r i C l i p . The off-label use of the MitraClip System its anterior location, making the use of intracardiac
(Abbott Vascular, Santa Clara, California) has become echocardiography an appealing alternative to ensure
the first-choice approach for high-risk patients with coaxial alignment (38). Second, steering of the
functional TR, likely because of wide availability and MitraClip system in the right atrium is often restricted
operator familiarity. More than 650 procedures have using standard techniques. The miskey technique, by
already been performed worldwide, and patients inserting the clip delivery system 90 counterclock-
receiving this therapy represent >50% of patients wise from its typical locking position, has been pro-
included in the first international registry assessing posed to accommodate the system to the TV with an
different available transcatheter TR devices (37). orthogonal orientation (39). Third, huge coaptation
However, the interventional edge-to-edge repair gaps are commonly found in patients with functional
technique faces several technical issues when applied TR, often requiring multiple grasping attempts and
to the tricuspid position. First, intraprocedural clips. Grasping of the septal and anterior leaflets
transesophageal echocardiography imaging of the TV yielded the most favorable post-procedural outcomes
might be highly challenging and somewhat limited by in an ex vivo model (40). Indeed, tricuspid
T A B L E 2 Key Anatomic Considerations During Computed Tomographic Pre-Procedural Assessment According to Anatomic Therapeutic Target
Device Anatomic Features Imaging Views
Coaptation devices Tricuspid annular dimensions (anteroposterior and septal-lateral Short axis of the TA
diameters, perimeter, area), midventricular diameter Long-axis 4-chamber
Distance from the TA to the right ventricular apex RV long-axis 2-chamber
Target anchoring site Coronal reconstruction
Left subclavian and axillary vein
Annuloplasty devices Course of the RCA relative to the TA Volume-rendered reconstruction, long-axis 2- and 4-chamber,
Distance from RCA to the anterior and posterior tricuspid leaflet short-axis
insertion Short-axis of the TA and long-axis 4-chamber
Optimal anchoring target Short-axis of the TA
Heterotopic CAVI IVC size at the cavoatrial junction and at the level of the first hepatic Double oblique transverse plane of the inferior cavoatrial junc-
vein tion and at the level of the first hepatic vein
Distance between the cavoatrial junction and the first hepatic vein Single oblique sagittal plane of the IVC
Orthotopic TTVR Tricuspid annular dimensions (anteroposterior and septal-lateral Short axis of the TA
diameters, perimeter, area) Double oblique transverse plane
Right internal jugular vein and SVC size Volume-rendered reconstruction, long-axis 2- and 4-chamber,
Course of the RCA relative to the TA short-axis
Distance from RCA to the anterior and posterior tricuspid leaflet Short-axis of the TA and long-axis 4-chamber
insertion Sagittal oblique reconstruction and short axis of the RVOT
Risk for RVOT obstruction
Adapted with permission from van Rosendael et al. (31).

CAVI ¼ caval valve implantation; RCA ¼ right coronary artery; RVOT ¼ right ventricular outflow tract; SVC ¼ superior vena cava; TA ¼ tricuspid annulus; TTVR ¼ transcatheter tricuspid valve replacement;
other abbreviations as in Table 1.
bicuspidization by using a modified “zipping tech- repair. Fourth, clipping of the TV might be chal-
nique” of the anteroseptal commissure might enable lenging in the presence of the pacemaker leads
treatment of patients with extreme right ventricular (Figure 5B) (41). These patients can be treated by us-
dilatation or very large coaptation defects (39). Upon ing the aforementioned bicuspidization technique or
approximation of the leaflets with a first clip in the preferably with a “triple-orifice technique,” by
anteroseptal commissure (where the gap is mini- placing the clips between the septal and anterior as
mum), subsequent clips are placed inward. The next- well as the septal and posterior leaflets, while
generation MitraClip XT system with longer grip arms avoiding grasping between the posterior and anterior
might further facilitate the tricuspid edge-to-edge leaflets (42). Last, given the reduced subvalvular
F I G U R E 5 Coaptation Devices
(A) Forma Repair System. Two-dimensional transthoracic echocardiography before and after device implantation, fluoroscopy, and 3-dimensional transthoracic
echocardiography. (B) Interventional edge-to-edge repair with the MitraClip system in a patient with a pacemaker lead. Intraprocedural 2-dimensional and
3-dimensional transesophageal echocardiographic and fluoroscopic views. Reprinted with permission from Fam et al. (41). (C) Pascal repair system. Fluoroscopy
showing the unfolded and folded Pascal device sequentially; 3-dimensional transesophageal echocardiography and illustration showing double-orifice valve after
deployment. Reprinted with permission from Praz et al. (45). Abbreviations as in Figure 4.
T A B L E 3 Transcatheter Tricuspid Therapies: Clinical, Procedural, and Follow-Up Features
Forma TriClip Trialign TriCinch Cardioband CAVI NaviGate
Perlman Kodali Nickenig Orban Yzeiraj Hahn Denti Nickenig Lauten

et al. (29) et al. (36) et al. (43) et al. (44) et al. (49) et al. (50,51) et al. (52) et al. (58) et al. (65)
(n ¼ 18) (n ¼ 29) (n ¼ 64) (n ¼ 50) (n ¼ 14) (n ¼ 15) (n ¼ 24) (n ¼ 30) (n ¼ 25) (n¼11)*
Baseline characteristics
Age, yrs 76 10 76 8 77 10 77 8 73 11 74 7 74 8 76 6 74 8 76 17
Female 13 (72) 19 (66) 35 (55) 20 (40) 8 (57) 13 (87) 20 (83) 22 (73) 13 (52) 5 (45)
EuroSCORE II 9.0 5.7 8.1 5.3 27.8 16.7† 8.8 6.6 16.7 13.7† NA 5.5 4.2 18.2 12.9 NA
NYHA functional class $III 17 (94) 25 (86) 60 (94) 50 (100) 14 (100) 10 (67) 14 (58) 26 (87) 25 (100) NA
Prior cardiac surgery 13 (72) NA 26 (40) NA NA NA 12 (50) 11 (36) 19 (76) 8 (72)
Pacemaker lead 3 (17) 7 (24) 19 (30) 14 (28) 0 0 NA 4 (13) 9 (36) 1 (9)
Procedural and 30-day data
Implantation success 16 (89) 27 (93) 62 (97) 46 (92) NA 15 (100)‡ 18 (81) 30 (100) 23 (92) 10 (91)
Device embolization 1 (6) 1 (3) 0 1 (2) NA 3 (20) 5 (23) NA 2 (8) 0
Device-related surgery 1 (6) 3 (10) 0 1 (2) NA 0 NA 0 2 (8) 1 (9)
TR severity $3 16/16 (100) NA 49 (77) 12/46 (26) NA NA 11 (45) NA 25 (100) 0
30-day mortality 0 2 (7) 3 (5) 2 (4) 0 0 0 2 (7) 3 (12) 2 (18)
Follow-up data
Follow-up time, mo 12 1 1 6 NA 12 6 1 10 3
TR severity $3 12/13 (92) NA 49 (77) 9/39 (23) NA NA (w75) NA (100) 0
NYHA functional classes I and II 11/14 (79) 18/25 (72) 24 (37) 25/39 (64) NA 9/10 (90) NA 23/28 (82) NA NA
D6MWT, m 84 39 16 84 NA 49 130 31 NA NA
Mortality 0 2 (7) 3 (5) 8 (16) NA 1 (7) 0 2 (7) 14/22 (63) 3 (27)
Values are mean SD or n/N (%). *Courtesy from Dr J.L. Navia (Cleveland Clinic, Cleveland, Ohio), unpublished data. †Logistic EuroSCORE (%). ‡1 patient requiring right coronary artery stenting.
6MWT ¼ 6-min walking test; EuroSCORE ¼ European System for Cardiac Operative Risk Evaluation; NA ¼ not available; NYHA ¼ New York Heart Association; other abbreviations as in Tables 1 and 2.
space in the right ventricle, slow movements of the The ongoing TRILUMINATE Conformité Europé-
clip delivery system are needed to avoid entangle- enne (CE) Mark Trial (Trial to Evaluate Treatment
ment with the TV leaflets and chords. With Abbott Transcatheter Clip Repair System in Pa-
In a multicenter European registry reported by tients with Moderate or Greater Tricuspid Regurgita-
Nickenig et al. (43), 64 high-risk patients with mod- tion; NCT03227757) will prospectively enroll 75
erate to severe TR (88% functional) underwent TV subjects in up to 25 European Union and U.S. sites
clipping (of these, 22 patients underwent concomitant with up to 3-year follow-up to further evaluate per-
mitral repair). Procedural success was 97% ($2 clips in formance of this approach (Table 4).
w50% of cases, w80% at the anteroseptal commis- P a s c a l . The Edwards Pascal transcatheter mitral
sure), with $1 TR grade reduction in 91% of patients. valve repair system (Edwards Lifesciences) in-
No serious intraprocedural complications occurred, tegrates technical aspects from the Forma and the
with 3 in-hospital deaths (5%). Most patients showed MitraClip devices by combining a 10-mm central
significant post-procedural improvements in TR spacer and 2 paddles (w25 mm width) and clasps
severity and NYHA functional class, as well as exercise (10 mm length) that attach the device to the
capacity enhancement at 30-day follow-up. Orban valve leaflets, thus overcoming possible limitations
et al. (44) recently reported the 6-month outcomes of of the former devices separately. The system is
50 patients treated with the transcatheter edge-to- composed of a 22-F steerable guide sheath, a
edge TV repair technique, 36 of whom underwent steerable catheter, and an implantation catheter.
concomitant mitral valve repair. Procedural success The device is repositionable and recapturable if
was achieved in 46 patients (92%), with a mean of 1.9 needed (Figure 5C). The first-in-human experience
clips per patient, 84% being positioned between the of the Edwards Pascal system in patients with
anterior and septal leaflets. At 6-month follow-up, severe mitral regurgitation showed the feasibility
improvement of $1 NYHA functional class and $1 TR and promising preliminary efficacy data (45). The
grade was observed in 79% and 90% of patients, first successful case of TTVr using the Pascal for
respectively, with TR grade #2þ in 77% of the patients treating severe TR was recently reported (46).
and a 16% mortality rate. The chief clinical and pro- This leaflet coaptation device provides a new
cedural features of patients treated with the MitraClip appealing option for TTVr to be evaluated in further
system are outlined in Table 3. studies.
T A B L E 4 Summary of Ongoing and Future Studies on Transcatheter Therapies for Tricuspid Regurgitation
Device Study Study Design Patients Primary Endpoints
Forma SPACER (NCT02787408) Prospective 78 Safety: cardiac mortality at 30 days, compared with a research-derived performance
registry goal based on high-risk surgical outcomes for tricuspid repair/replacement
Early Feasibility Study of the Edwards Prospective 30 Procedural success defined as device success and freedom from device- or
Forma Tricuspid Transcatheter Repair registry procedure-related SAEs at 30 days
System (NCT02471807)
MitraClip TRILUMINATE (NCT03227757) Prospective 75 Echocardiographic tricuspid regurgitation reduction at least 1 grade (30 days)
registry Composite of MAE (6 months)
MitraClip for Severe TR (NCT02863549) Prospective 100 Tricuspid regurgitation grade and incidence of major adverse cerebrovascular events
registry (1–12 months)
Trialign SCOUT II (NCT03225612) Prospective 60 All-cause mortality at 30 days
registry
Early feasibility of the Mitralign PTVAS, Prospective 30 Technical success at 30 days, defined as freedom from death with successful access,
also known as Trialign registry delivery and retrieval of the device delivery system, and deployment and correct
(NCT02574650) positioning of the intended device, and no need for additional unplanned or
emergency surgery or reintervention related to the device or access procedure
TriCinch PREVENT (NCT02098200) Prospective 24 Safety: participants with MAE* within 30 days of the procedure
registry Efficacy: reduction of tricuspid regurgitation by at least 1 degree immediately after
the procedure and at discharge
Clinical Trial Evaluation of the Prospective 90 All-cause mortality of the per protocol cohort at 30 days post-procedure
Percutaneous registry
4Tech TriCinch Coil Tricuspid Valve
Repair System (NCT03294200)
MIA STTAR (not registered) Prospective 40 Safety: rate of MAEs at 30-day follow-up
registry Performance: technical success rate of MIA implant and reduction in the valve area
Cardioband TRI-REPAIR (NCT02981953) Prospective 30 Overall rate of major SAEs and serious adverse device effects at 30 days
registry Intraprocedural successful access, deployment and positioning of the Cardioband
device and septolateral diameter reduction
Change in septolateral dimension at 30 days
Edwards Cardioband Tricuspid Valve Prospective 15 Freedom from device or procedure-related adverse events (30 days)
Reconstruction System Early Feasibility registry
Study (NCT03382457)
Heterotopic CAVI HOVER (NCT02339974) Prospective 15 Procedural success at 30 days, defined as device success and no SAE†
registry Individual success at 30 days, defined by device success and positive clinical
outcomes‡
TRICAVAL (NCT02387697) Randomized 40 Maximum relative VO2 at 3 mo (difference of means in maximum relative VO2 at
open-label 3 months compared with control group)
*Including death, Q-wave myocardial infarction, cardiac tamponade, cardiac surgery for failed TriCinch implantation, stroke, and septicemia. †Including all death, all stroke, myocardial infarction, acute kidney
injury grade 3, life-threatening bleeding, major vascular complications, pericardial effusion or tamponade requiring drainage, and vena cava syndrome. ‡Positive clinical outcomes defined as no readmissions
to hospital for right-sided heart failure or right-sided heart failure equivalents including drainage of ascites or pleural effusions, new listing for heart transplantation, VAD, or other mechanical support;
improvement in 1 of 3 variables: KCCQ improvement >15 versus baseline and 6MWT improvement >70 m versus baseline, or VO2 peak improvement >6% versus baseline.
HOVER ¼ Heterotopic Implantation of the Edwards-SAPIEN Transcatheter Aortic Valve in the Inferior Vena Cava for the Treatment of Severe Tricuspid Regurgitation; KCCQ ¼ Kansas City Cardiomyopathy
Questionnaire; MAE ¼ major adverse vent; MIA ¼ minimally invasive annuloplasty; PREVENT ¼ Percutaneous Treatment of Tricuspid Valve Regurgitation With the TriCinch System; PTVAS ¼ percutaneous
tricuspid valve annuloplasty system; SAE ¼ serious adverse event; SCOUT ¼ Safety and Performance of the Trialign Percutaneous Tricuspid Valve Annuloplasty System; SPACER ¼ Repair of Tricuspid Valve
Regurgitation Using the Edwards Tricuspid Transcatheter Repair System; STTAR ¼ Study of Transcatheter Tricuspid Annular Repair; TRICAVAL ¼ Treatment of Severe Secondary Tricuspid Regurgitation in
Patients With Advanced Heart Failure With Caval Vein Implantation of the Edwards SAPIEN XT Valve; TRILUMINATE ¼ Evaluation of Treatment With Abbott Transcatheter Clip Repair System in Patients With
Moderate or Greater Tricuspid Regurgitation; TRI-REPAIR ¼ Tricuspid Regurgitation Repair With Cardioband Transcatheter System; VAD ¼ ventricular assist device; VO2 ¼ oxygen consumption; other
abbreviations as in Tables 2 and 3.
ANNULOPLASTY DEVICES. Most percutaneous annu- transcatheter annuloplasty system that mimics the
loplasty devices reproduce well-established surgical modified Kay bicuspidization surgical procedure, thus
techniques addressing the chief pathophysiological obliterating the posterior tricuspid leaflet. A deflect-
mechanism of secondary TR. Transcatheter annular- able catheter is first introduced through a transjugular
based systems can be categorized as direct suture approach to advance an insulated radiofrequency wire
(Trialign, TriCinch, minimally invasive annuloplasty, across the TA. Two pledgets are sequentially fixed at
pledget-assisted suture tricuspid annuloplasty) or the posteroseptal and anteroposterior commissures
ring (direct: Cardioband, Millipede IRIS; indirect: and thereafter cinched together using a dedicated
transatrial intrapericardial tricuspid annuloplasty) plication lock device, thus resulting in posterior leaflet
annuloplasty devices (47). Whereas better long-term plication and TV bicuspidization. A second pair of
outcomes should theoretically be expected with the pledgets might be implanted to obtain a greater
latter, suture annuloplasty devices have gained a annular reduction (Figure 6A) (48).
wider clinical experience to date. The first multicenter experience, including 14 pa-
Suture annuloplasty systems. Trialign. The Trialign de- tients with moderate to severe TR (86% functional)
vice (Mitralign, Tewksbury, Massachusetts) is a treated with the Trialign device for compassionate
F I G U R E 6 Suture Annuloplasty Systems
(A) Trialign system. Illustration and 3-dimensional echocardiography during device deployment. Two suture pledgets are sequentially delivered at the anteroposterior
and septoposterior commissures and therefore plicated until maximal reduction in annular dimensions and regurgitant orifice is achieved. The blue asterisk indicates
the wire delivery catheter; the red asterisk shows the Trialign device after deployment. Reprinted with permission from Hahn et al. (50). (B) TriCinch. Transesophageal
echocardiographic and fluoroscopic visualization of the device (red arrow) in the right atrium; right coronary angiography. Significant reduction of septolateral annular
diameter (SLD) post-cinching. Transthoracic subcostal view showing stent implanted in the inferior vena cava (small red arrow) and corkscrew implant at tricuspid
annulus (asterisk). Reprinted with permission from Ancona et al. (27). (C) Picture of MIA (minimally invasive annuloplasty technology), reprinted with permission from
Micro Interventional Devices; investigational device only. (D) Pledget-assisted suture annuloplasty. Illustration and magnetic resonance images showing double-orifice
valve creation by pledgeted sutures between the posteroseptal and mid-anterior annulus. Reprinted with permission from Khan et al. (55).
use, showed marked post-procedural alleviation of Failure Questionnaire (intention-to-treat cohort:

TR (reductions of 42%, 51%, and 34% in vena con- 47.4 17.6 to 20.9 14.8, p < 0.001) (50). At 12-month
tracta, effective regurgitant orifice area, and annular follow-up, 1 patient died (not device related) and
area, respectively), with a single procedural compli- another required elective reintervention, with sus-
cation (arrhythmia) (49). The SCOUT I (Early Feasi- tained improvements in NYHA status (90% in class I
bility of the Mitralign Percutaneous Tricuspid Valve or II) and QoL (intention-to-treat: from 47.4 to 25.5,
Annuloplasty System for Symptomatic Chronic p ¼ 0.013; as-treated group: from 49.6 15.7 to 19.2
Functional Tricuspid Regurgitation) feasibility trial, 12.4, p ¼ 0.003) (51). Table 3 outlines the main fea-
enrolled 15 symptomatic patients with at least mod- tures of these studies.
erate functional TR undergoing tricuspid annulo- The ongoing SCOUT II CE mark study will include
plasty with the Trialign device in the United States. up to 60 patients from 15 U.S. and European sites,
Implantation success was achieved in all patients, with up to 5-year follow-up (Table 4).
with 93% procedural success (1 patient requiring right Tricinch. The TriCinch system (4Tech Cardio, Galway,
coronary artery stenting because of extrinsic Ireland) is a Kay-like annuloplasty system that reduces
compression) and 80% technical success at 30 days (3 the septolateral diameter of the TA by cinching at the
instances of single-pledget dehiscence without rein- anteroposterior commissure. An 18-F steerable
tervention). At 30-day follow-up, no major adverse delivery system is first advanced through a 24-F
events had occurred, with significant reduction in femoral vein introducer sheath into the right atrium.
tricuspid annular area and effective regurgitant A corkscrew anchor is then fixed near the
orifice area and significant improvements in func- anteroposterior commissure. After right coronary
tional class (intention-to-treat cohort: reduction of $1 angiography, a self-expanding stent, connected to
degree in NYHA functional class, p ¼ 0.001; 6-min the anchor through a Dacron band, is deployed in the
walking distance: 245.2 110.1 m to 298.0 107.6 subhepatic region of the IVC, ensuring maintenance
m, p ¼ 0.008) and Minnesota Living With Heart of the tension applied to the TV (Figure 6B).
Preliminary data from the first 24 patients treated The first human compassionate-use cases were
with the first-generation TriCinch Screw Tip device in recently reported (56).
the PREVENT (Percutaneous Treatment of Tricuspid Ring annuloplasty systems. Cardioband. The Cardioband
Valve Regurgitation With the TriCinch System) trial Tricuspid Repair System (Edwards Lifesciences) is a
were reported. The device was successfully implan- direct, sutureless, and adjustable surgical-like Dacron
ted in 18 patients (81%), with significant ($1 grade) band, based on the CE-approved device for mitral
acute TR reduction in 94% of cases. Hemopericar- regurgitation treatment. The device is inserted
dium occurred in 2 patients (8%), while 5 patients through a transfemoral 24-F access sheath, and up to 17
(23%) experienced late annular anchor detachment. anchors are deployed on the atrial side of the anterior
Preliminary data showed severe 4þ TR reduction and posterior TA to fix the device. A size adjustment
from w80% to w40%, with sustained improvement in tool enabling bidirectional reshaping of the TA is
functional class and QoL at 6-month follow-up advanced over a wire, and the band is then cinched,
(Table 3) (52). providing a controlled reduction of the anteroposterior
Because of stability concerns, the second- and septolateral TA diameters (Figure 7A) (57).
generation TriCinch Coil System using an alternative The 30-day outcomes of the first-in-human TRI-
coil anchoring system (replacing the previous cork- REPAIR (Tricuspid Regurgitation Repair with Cardio-
screw) has been developed. A hemispiral-shaped band Transcatheter System; NCT02981953) CE EU
anchor is delivered in the pericardial space, thus trial were recently reported (Table 3) (58). Among 30
providing increased surface area, tensioning, and patients with functional TR $2þ and annular
stability. Following successful preclinical testing diameter $40 mm, procedural success was achieved
in 65 acute and chronic animals, the first-in-human in all patients, with a 17% average reduction in sep-
case with the second-generation TriCinch device tolateral diameter. Periprocedural events included 2
has been performed with no procedural complica- deaths (right ventricular failure, life-threatening
tions and 30-day improvement in TR severity and bleeding unrelated to device), 1 stroke, and 3 major
QoL (53). bleedings. At 30 days, significant reductions in
Minimally invasive annuloplasty. Minimally invasive effective regurgitant orifice area (50%) and vena
annuloplasty technology (MIA, Micro Interventional contracta (31%) were observed, with improvements in
Devices, Newtown, Pennsylvania) is a sutureless stroke volume (7%) and functional status. Enrollment
transcatheter annuloplasty system composed of of a further 30 patients is ongoing.
a thermoplastic elastomer (MyoLast) and low- Millipede IRIS. The Millipede IRIS system (Boston
mass polymeric, compliant, self-tensioning anchors Scientific, Marlborough, Massachusetts) is a com-
(PolyCor), allowing TV annular reduction (Figure 6C). plete, adjustable, semirigid annuloplasty ring that
The device is surgically implanted through a 16-F mimics the surgical gold-standard complete
steerable delivery system that allows deployment of annuloplasty ring for treatment of both functional
the device in a 270 partial ring pattern. The STTAR mitral and TR. The device consists of a zigzag-frame
(Study of Transcatheter Tricuspid Annular Repair) collapsible nitinol ring, with individual collars at
trial will enroll 40 patients to assess the safety and each zigzag’s peak and corkscrew-shaped anchors
efficacy of the minimally invasive annuloplasty attaching the ring to the fibrous annulus. The device
device (Table 4). To date, 5 patients have been is fully repositionable and retrievable. The anchor
included in the surgical arm of the study, 2 of them near the atrioventricular node is removed to
using a bicuspidization approach. All patients were minimize the risk for conduction disturbances.
successfully treated, with no procedural adverse The IRIS ring has been surgically implanted in the
events and significant reduction of TV area. Early TV in 2 patients undergoing concomitant mitral valve
launching of the percutaneous arm of the STTAR repair, showing a sustained TA diameter reduction of
study is expected (54). about 40%, with no TR after 12 months (Figure 7B,
Pledget-assisted suture tricuspid annuloplasty. Table 3) (59). A dedicated transcatheter delivery sys-
Transcatheter pledget-assisted suture tricuspid annu- tem for the TV IRIS ring is currently being developed.
loplasty is a transannular “double-bite” pledgeted The device requires no anticoagulation and preserves
suture technique that reproduces the Hetzer double- the native anatomy, enabling other concomitant or
orifice suture technique. Using marketed devices, future percutaneous options as well as serving as a
2 sutures and 1 pledget are sequentially placed at dock for implantation of a transcatheter heart valve.
the midanterior and the posteroseptal TA. Each Transatrial intrapericardial tricuspid annuloplasty.
suture is tightened using a Cor-Knot device (31 cm, Transatrial intrapericardial tricuspid annuloplasty
LSI Solutions, New York, New York) (Figure 6D) (55). is an indirect, fully retrievable, transpericardial
F I G U R E 7 Ring Annuloplasty Systems
(A) Cardioband system. Transesophageal echocardiographic and fluoroscopic images before and after cinching of the Cardioband. #Cardioband cinching catheter.
*Coronary wire in the right coronary artery. Reprinted with permission from Schueler et al. (57). (B) Millipede. Fluoroscopic and computed tomographic imaging of a
double implant of the Millipede device in the tricuspid and mitral position. Courtesy of Dr. Jason Rogers, University of California, Davis, Medical Center (Sacramento,
California). (C) The transatrial intrapericardial tricuspid annuloplasty system. Illustration and fluoroscopy showing the device implanted in the atrioventricular groove,
final right atrial appendage closure with a nitinol closure device (arrow). Reprinted with permission from Rogers et al. (60).
annuloplasty system under preclinical evaluation. A prevent caval backflow of TR and mitigate systemic
memory-shaped delivery system is advanced through venous congestion. Hemodynamic proof of pulsatile
the femoral vein into the pericardium through a blood flow and caval backflow is required prior
right atrial appendage puncture. An adjustable to heterotopic implantation. CAVI can be single
circumferential implant is then placed along (IVC only) or bicaval, depending on anatomic suit-
the atrioventricular groove, exerting external ability. To date, 2 different devices have been used
compression over the TA from the pericardial space. for CAVI: nondedicated balloon-expandable devices
The right atrial appendage puncture is finally sealed commonly used for transcatheter aortic valve
using a nitinol occluder (Figure 7C). The device was replacement and dedicated self-expandable CAVI
successfully implanted in preclinical experience in 16 devices (TricValve, P&F Products Features Vertriebs,
swine with functional TR, leading to significant TV Vienna, Austria).
geometry changes (reductions in annular area and Feasibility of heterotopic off-label use of the 29-
perimeter, increase in coaptation length) (60). A mm balloon-expandable SAPIEN valve (Edwards
newer version of the device—including a balloon Lifesciences) was first reported by Laule et al. (62).
anchor pericardial sheath, the annuloplasty system, Because the IVC and SVC might dilate up to 35 and
and a bioresorbable closure device—for human use is 40 mm, respectively, landing zone preparation and
currently being developed by the National Institutes downsizing with caval pre-stenting or surgical band-
of Health and Cook Medical (Bloomington, Indiana). ing are required. Because of the deploying mecha-
An early feasibility study is planned for 2018 (61). nism and limited sizes of currently available valves
(#29 mm), balloon-expandable CAVI should prefer-
HETEROTOPIC CAVI ably be restricted to IVC only (for IVC
diameters #30 mm). Furthermore, considering the
The objective of heterotopic CAVI, which does not low-pressure system, lifelong anticoagulation is often
specifically address the severity of TR per se, is to required.
F I G U R E 8 Heterotopic Caval Valve Implantation
The self-expandable TricValve and the Edwards SAPIEN balloon-expandable valve. Computed tomographic angiography, 3-dimensional
reconstruction, echocardiographic short- and long-axis views after device implantation. Reprinted with permission from Lauten et al. (63).
IVC ¼ inferior vena cava; LA ¼ left atrium; PA ¼ pulmonary artery; RA ¼ right atrium; RV ¼ right ventricle.
The TricValve is a dedicated self-expandable peri- pressure in the IVC and right atrium) were observed,
cardial valve mounted on a nitinol belly-shaped stent with no detrimental impact on cardiac index. Thirty-
with little radial force, not requiring pre-stenting of day mortality was 12% (3 of 25), with high 1-year
the landing zone, specially designed for low-pressure mortality (14 of 22 [63%]) due mainly to high comor-
circulation (Figure 8) (63,64). Implantation of the bid burden.
TricValve can be safely performed using a single- or Despite being the first transcatheter TV therapy
dual-valve approach, with landing zone used in humans (63), hemodynamic concerns
diameters #35 mm. The maximum available sizes are following CAVI including the long-term impact of
38 and 43 mm for the SVC and IVC, respectively. right atrial ventricularization, persistent right atrial
A multicenter registry including 25 patients treated volume overload, and increases in right ventricular
by compassionate use with either the SAPIEN valve or afterload on right chamber function (although not
the TricValve between 2010 and 2017 was recently confirmed in the latest experiences [65,66]) have
reported (Table 3) (65). Single IVC valve implantation perhaps prevented the broader use of CAVI for
was performed in 19 patients (76%). Balloon- treating TR. Two ongoing trials are currently evalu-
expandable valves were mostly used in single valve ating the feasibility of CAVI with the balloon-
procedures (16 of 19 [84%]), while self-expandable expandable SAPIEN valve for treating TR (Table 4).
valves were most commonly used in double-valve
procedures (5 of 6 [83%]). Procedural success was TTVR
achieved in 92% of cases. In-hospital complications
included 2 device embolizations requiring surgical Since the first preclinical experience with a dedicated
removal. Significant improvements in NYHA class and self-expandable bioprosthetic TV in 8 ewes reported
in hemodynamic backflow (reduction of mean in 2005 by Boudjemline et al. (67), preclinical models
F I G U R E 9 Orthotopic Transcatheter Tricuspid Valve Replacement
(A to C) The NaviGate valve. (A) Inflow and lateral views. (B) Fluoroscopy: transatrial tricuspid valved stent. (C) Three-dimensional and 2-dimensional echocardiog-
raphy. (D) The LUX-Valve, Courtesy of Dr. Fang-Lin Lu, Changhai Hospital (Shanghai, China).
with fully percutaneous TTVR platforms have been of the current delivery system, sufficient space
scarce (68). (w75 mm) is required to coaxially align and accom-
The first case of TTVR in a human native TV modate the capsule and the bar distal to the steering
was reported in 2014 by Kefer et al. (69) using TA segment of the delivery catheter, from the SVC to the
pre-stenting with 2 covered stents followed by TA. The catheter shaft is 24-F and allows a 70 artic-
nondedicated balloon-expandable SAPIEN valve im- ulation to enable controlled valve release and secure
plantation. However, the specific anatomic features valve engagement. Combination of aspirin and
of the TV have precluded expansion of the off-label warfarin is the recommended antithrombotic regimen
use of these devices in the native TV. following valve implantation.
NAVIGATE BIOPROSTHESIS. The NaviGate bio- The NaviGate valved stent was first evaluated in
prosthesis (NaviGate Cardiac Structures, Lake Forest, a swine model (70). In this first preclinical experi-
California) is currently the only available dedicated ence, 12 healthy swine underwent NaviGate TTVR
device allowing fully orthotopic TTVR in humans. It through both transjugular (n ¼ 6) and transatrial
consists of an atrioventricular valved stent and a de- (n ¼ 6) approaches. All valves were successfully
livery system. The Gate self-expanding tricuspid implanted, with 100% procedural success. All ani-
atrioventricular valved stent is a cone-shaped nitinol mals but 1 (which developed acute severe TR due to
tapered stent with 3 xenogeneic pericardial leaflets, annulus-prosthesis mismatch with subsequent
with a low (21-mm) height profile and annular wing- prosthesis migration into the right ventricle and
lets for secure anchoring of the TA and TV leaflets death) survived the intervention. There was no
(Figures 9A to 9C). It is currently available in 5 obstruction of the right ventricular outflow tract,
different sizes: 36, 40, 44, 48, and 52 mm. Slight coronary arteries, or subvalvular apparatus. During
oversizing of the device < 10% to the TA is generally follow-up (range: 30 to 210 days), no significant
recommended. The Gate system’s delivery catheter is residual TR or increased transvalvular gradients
introduced through a 42-F introducer sheath via the were observed.
transjugular vein (when venous access is $15 mm) or The first-in-human successful implantations of the
via the transatrial approach (right anterolateral mini- NaviGate bioprosthesis were performed by Navia
thoracotomy). Because of the long angulatory aspect et al. (71) in November 2016 and April 2017, in a
whereas the other 8 patients were alive at 3 weeks

T A B L E 5 Initial Global Clinical Experience With Transcatheter
Tricuspid Therapies (n ¼ 282)
(n ¼ 4), 3 months (n ¼ 2), 6 months (n ¼ 1), and
9 months (n ¼ 1). Overall, this preliminary experi-
Patient characteristics
Age, yrs 76 9
ence showed feasibility and safety of the NaviGate
Female, % 60 (40–87) tricuspid valved stent, with 91% successful device
EuroSCORE II 8.8 7.5 implantation and good hemodynamic performance,
Functional TR, % 96 (86–100) with good prosthesis anchoring and sealing and
NYHA functional class $III, % 90 (58–100) low device-related complications. Modifications in a
Prior cardiac surgery, % 51 (36–76)
shortened distal angulation part of the delivery
Pacemaker lead, % 22 (0–36)
system are under current development in order
Atrial fibrillation, % 85 (67–93)
to improve coaxiality with the TA and device
Devices
MitraClip 114 (40) sealing.
Forma 47 (17) UPCOMING DEVICES FOR ORTHOTOPIC TTVR. The
Cardioband 30 (11)
LUX-Valve (Jenscare Biotechnology, Ningbo, China) is
Trialign 29 (10)
a self-expanding bovine pericardial tissue valve
CAVI 25 (9)
mounted on a nitinol stent frame and inserted
TriCinch 24 (9)
NaviGate 11 (4)
transatrially through a minimally invasive thoracot-
Millipede 2 (1) omy. The device has a self-adaptive skirt to minimize
Procedural data paravalvular leak and a special anchoring mechanism
Successful implantation, % 93 (81–100) for secure anchoring within the right ventricle. Initial
Device embolization, % 6 (0–23) experimental data in a chronic goat model were
Conversion to open heart surgery, % 2 (0–9)
recently reported, with promising results at 6 months
30-day outcomes
(Figure 9D) (73). Further studies assessing the safety
TR severity $3, % 60 (0–100)
and long-term efficacy of this and other emerging
NYHA functional class I and II, % 62 (37–90)
D6MWT, m 47 (16–130) orthotopic TTVR devices (TRiCares, Aschheim, Ger-
Mortality, % 5 (0–18) many) are warranted.
Values are weighted mean SD, weighted mean (range), or n (%), derived from CLINICAL PERSPECTIVES ON
previously presented data in Table 3 (29,36,43,44,49,50,52,58,59,65,72).
Abbreviations as in Tables 1 to 3.
TRANSCATHETER TRICUSPID THERAPY
Most patients enrolled in the early clinical experi-

severely dilated native TA and in a failed tricuspid ences with transcatheter tricuspid therapies were at
annuloplasty ring, under transatrial and transjugular high or prohibitive surgical risk, treated under
access, respectively. Initial data were first presented compassionate or feasibility clinical programs. The
at 2017 Transcatheter Cardiovascular Therapeutics overall main patient characteristics and procedural
meeting (72). Since then, 11 compassionate-use cases and 30-day outcomes reported with currently avail-
have been performed worldwide, with a high proce- able transcatheter TV therapies to date are summa-
dural success rate and a low rate of significant pro- rized in Table 5. Most patients undergoing TTVr or
cedure-related complications (Table 3). All patients TTVR were high-risk patients (mean European
underwent fluoroscopy and transesophageal or System for Cardiac Operative Risk Evaluation II
intracardiac echocardiographic guidance. Marked score 9), predominantly women (60%), past the
improvements in TR severity were documented in seventh decade of life. As anticipated, the chief
all patients (prior 4þ TR in all patients, no post- mechanism of TR was functional in 96% of these
operative paravalvular leak in 6 patients, trivial TR patients, due mostly to right ventricular dysfunction,
in 3 patients and mild TR in 2 patients). Significant tricuspid annular dilatation, and impaired leaflet
reduction in central venous pressure was also coaptation, probably exacerbated by a high preva-
observed (mean pre-operative and post-operative lence (85%) of atrial fibrillation. One-half of patients
central venous pressures of 26.9 and 10.7 mm Hg, had undergone a prior open-heart surgery, and one-
respectively). No patient developed tricuspid stenosis quarter of patients (up to one-third among MitraClip
after the procedure (mean transtricuspid gradient and CAVI recipients) had prior permanent trans-
2.7 mm Hg). One patient required a permanent tricuspid leads, which did not preclude procedural
pacemaker implantation. Three patients died during success among those devices specifically targeting
follow-up (two after 1 week, one 6 months after), leaflet coaptation (29,39,43). Interestingly, recent
experiences have shown the feasibility of TTVr in reverse right ventricular remodeling, and increased
patients with pacemaker leads using annuloplasty TV coverage) (75). Considering that a more aggressive
systems, such as the Cardioband and Trialign approach for TR treatment is increasingly promoted,
devices (58,74). a shift toward a less symptomatic target population
Transcatheter treatment of TR was associated with with moderate to severe TR with tricuspid annular
high procedural success rates (>90%) and relatively dilatation ought to be expected in coming years.
low procedure-related complications (2% conversion Determining the subset of patients who may benefit
to open heart surgery, 6% device dislodgement). from earlier intervention, as well as the potential role
This is particularly reassuring if we consider that for dynamic training of the right ventricle linked to
most of these first-generation devices are still in their progressive TR reduction with emerging trans-
relative infancy, and many of them were (initially) catheter therapies, will require further evaluation.
transcatheter mitral devices that were used in DEVICE SELECTION. Accurate diagnosis of the un-
the tricuspid space. To date, the average 30-day derlying anatomy and pathophysiology is essential
mortality rate following transcatheter tricuspid ther- when assessing different available transcatheter
apies has been 5.1%. These outcomes compare tricuspid therapies. To date, coaptation devices have
favorably with the recently reported 8.8% and 9.7% been the most commonly used technologies (>50%),
in-hospital mortality rates in 2 contemporary series particularly interventional edge-to-edge repair in up
evaluating outcomes of isolated TV surgery from to 40% of cases, followed by annuloplasty systems
2003 to 2014 among 5,005 and 1,364 patients, (30%). Specific anatomic features from the TV complex
respectively (10,11). might vary according to the causing mechanism (pri-
A common finding among most early studies con- mary vs. secondary) and throughout the progressive
ducted to date with transcatheter therapies address- stages of ventricular remodeling in patients with
ing functional TR correction in severely enlarged functional TR. Thus, individual patient-specific device
native TVs has been the presence of marked im- selection is paramount to be ultimately successful.
provements in functional status (w60% of patients in Primary TR accounts for w10% of cases of TR and
NYHA functional class I or II, average increase of can be due to congenital (Ebstein’s anomaly, pro-
w50 m in 6-min walking distance) and QoL, despite lapse) or acquired diseases (rheumatic, endocarditis,
modest reductions in TR (at least moderate residual carcinoid, endomyocardial fibrosis, intracardiac
TR in 60% of patients). In contrast to transcatheter leads, or bioptome-related iatrogenic trauma).
aortic valve replacement, residual mild to moderate Although the inclusion of patients with primary TR
regurgitation may be judged acceptable for compas- has been anecdotal in the early clinical experience
sionate patients with advanced heart failure status with transcatheter TV technologies, some selected
often presenting with long-standing torrential TR, patients deemed at too high risk for standard TV
with scant therapeutic options. However, the results surgery could still benefit from lesser invasive alter-
regarding residual TR are still clearly inferior to those natives. The use of MitraClip might be suitable for
obtained with surgery, and this may translate into cases of leaflet prolapse. In patients with lead-
negative hemodynamic and clinical effects at mid- to induced TR, coaptation devices may be prioritized,
long-term follow-up. Future studies are needed to whereas TTVR could be considered for patients with
determine the minimal degree of TR improvement intracardiac leads and extreme tricuspid annular
associated with improved symptoms and clinical dilation, as well as for rheumatic TR.
outcomes. Secondary TR has been divided into 3 stages for
Thus far, on the basis of data from the very early therapeutic purposes (76). In the early stage, initial
experiences reported to date (Table 5) and in agree- dilation of the right ventricle leads to tricuspid
ment with those reported by Taramasso et al. (37) in annular dilation without significant leaflet teth-
the international TriValve Registry, transcatheter TV ering. Annular-based systems should easily repair
therapies should be reserved for high-risk patients, TR in these first stages. In the absence of long-term
with symptomatic functional TR, before extreme durability data for transcatheter TV therapy and on
dilatation of the right ventricle and leaflet tethering the basis of a surgical predicate, ring may be
occur. Of keen interest, remarkable plasticity of the preferred over suture annuloplasty when possible in
right ventricle and TA has been shown in response to order to reduce TR recurrence (77,78). In the second
TR regression, leading to important geometric stage, progressive right ventricular and tricuspid
changes (reduction in TA diameter and TV tenting, annular dilation develop, impairing leaflet
F I G U R E 1 0 Proposed Algorithm for Transcatheter Tricuspid Valve Device Selection Based on Mechanism and Pathoanatomy of Tricuspid Regurgitation
Severe TR at high surgical risk
Primary Secondary
Prolapse Rheumatic Lead-induced Phase I Phase II Phase III

Mild TA dilation Moderate TA Severe TA
dilation / tethering dilation / tethering
MitraClip TTVR Annuloplasty

Extreme TA
(ring or suture) Coaptation
dilation Preserved -
Combined End-stage
mild/moderate
approach CHF
RV function
(Annuloplasty +
coaptation)
No Yes
TTVR
TTVR
Coaptation TTVR Medical
treatment
TTVR /
CAVI
(compassionate)
CAVI ¼ caval valve implantation; CHF ¼ chronic heart failure; RV ¼ right ventricle; TA ¼ tricuspid annulus; TR ¼ tricuspid regurgitation; TTVR ¼ transcatheter tricuspid
valve replacement.
coaptation. The likelihood for successful TTVr using contemplating the possibility of compassionate
annuloplasty alone is less suitable in cases with TTVR or CAVI for carefully selected patients. A
progressive tethering and tricuspid annular dilation. potential strategy to choose transcatheter TV treat-
In such cases, coaptation devices or combination of ment on the basis of mechanisms and patient-
different approaches (e.g., combined edge-to-edge specific anatomy is proposed (Figure 10).
repair and annuloplasty, or Trialign with Cardio- DRAWBACKS AND FUTURE DIRECTIONS. Standardized
band) may lead to more pronounced TR reduction imaging for transcatheter tricuspid interventions. Because
(79,80). Interestingly, the use of the NaviGate bio- of the heterogeneity and complex nature of the TV
prosthesis in these intermediate stages could result disease, comprehensive imaging assessment of the
in complete TR elimination, preventing further right ventricle and TV is essential to achieve optimal
disease progression, which may exert a positive and lasting procedural results. Limitations and lack of
impact on functional status and on survival over consistency among current echocardiographic pa-
time. Finally, as the right ventricle continues to rameters along with notable discrepancies between
remodel, further leaflet tethering worsens, resulting marked clinical improvements in symptoms and QoL
in a lack of coaptation and massive or torrential TR. and modest reductions in TR severity in most TTVr
When severe tethering occurs, any repair attempt and TTVR studies conducted to date, underscore a
could be considered futile, and TTVR should be compelling need for novel quantification methods for
preferred over TTVr (81). Orthotopic TTVR should assessing TR severity in this unusual population.
be first considered for patients with preserved or Extending the grading scheme beyond severe TR,
mild to moderate right ventricular dysfunction. In including massive and torrential TR (82), or consid-
more advanced stages of chronic heart failure, ering a threshold percentage reduction of quantifi-
comprehensive estimation of clinical benefit is cation parameters above severe (e.g., 25% reduction
paramount to prevent potential TTVR-related futil- in vena contracta or effective regurgitant orifice area)
ity, and medical treatment should be considered, may help better identify those patients with
significant clinical benefit after TV interventions. into a more refined and tailored risk stratification and
Besides, given the complex anatomy of both the TA improved patient selection.
and right ventricle, an increasing role of alternative D u r a b i l i t y a n d l o n g - t e r m o u t c o m e s . Durability
imaging techniques such as cardiac magnetic reso- remains the Achilles heel of most surgical in-
nance, CT imaging, and intracardiac echocardiogra- terventions addressing the TV. Many factors, such
phy ought to be expected in the coming years. as right ventricular remodeling and dysfunction,
Further studies are needed to determine the exact tricuspid annular size progression, and pulmonary
role of these novel imaging technologies in this field. hypertension, may contribute to the high rates of
Standardized definitions and endpoints in TR recurrence observed following surgical TR
f o r t h c o m i n g s t u d i e s . The lack of consistency in correction. Surgical experience has shown more
definitions, efficacy, and safety endpoints used sustained durability of ring annuloplasty compared
in studies assessing transcatheter TR therapies with suture annuloplasty (78), as well as for TV
precludes an accurate comparison between different replacement over repair (88). However, concerns
available devices and approaches. Of note, the about increased perioperative mortality for TV
implementation of traditional endpoints used in replacement compared with repair in contemporary
previous trials on aortic or mitral valvular disease series—somewhat linked to selection bias of patients
may not be appropriate in this unique and with larger tricuspid annular dilation and more se-
extremely sick target population. Future trial de- vere right ventricular dysfunction—have led to a
signs evaluating transcatheter therapies in this trend over time toward TV repair rather than
advanced heart failure population should probably replacement (10). To date, no long-term durability
focus on reduction in TR grade, diuretic down- data exist for transcatheter TV interventions. How-
titration, improvements in specific QoL measure- ever, it is anticipated that TTVr and TTVR will need
ments, and enhanced functional capacity as an to overcome the same barriers as their surgical
endpoint, in addition to harder endpoints such as counterparts, because most of these percutaneous
death or heart failure hospitalization. Also, it is devices replicate open surgical techniques. Because
imperative to standardize definitions and specific of the very early experience of transcatheter
outcomes in this patient population, highlighting tricuspid technologies, long-term clinical and echo-
the need for a specific tricuspid academic research cardiographic data for TTVr and TTVR are currently
consortium that would enable accurate and uniform lacking and therefore will need to be carefully
interpretation and comparison between clinical evaluated in coming trials.
studies, as have been adopted for transcatheter A n t i t h r o m b o t i c t h e r a p y . Optimal antithrombotic
aortic and mitral valve interventions (83,84). therapy following transcatheter TV interventions
T r i c u s p i d - s p e c i fi c r i s k s c o r e s . Determining pa- remains a controversial issue. Notably, nearly 90% of
tient eligibility for transcatheter TV procedures is one patients treated with percutaneous TV devices to date
of the major decision issues to be faced. Several risk presented with pre-existing atrial fibrillation, thus
scores have been validated to determine short-term necessitating underlying systemic anticoagulation.
morbidity and mortality after cardiac surgery. The However, in the absence of atrial fibrillation, the best
European System for Cardiac Operative Risk Evalua- post-procedural antithrombotic therapy remains un-
tion II score and the Society of Thoracic Surgeons clear. Current guidelines recommend 3 months of oral
score are the most widely used scores in contempo- anticoagulation after surgical TV repair or replace-
rary practice (85,86). Although initially designed and ment (5). Despite the very low rate of device throm-
validated to predict mortality in cardiac surgical co- bosis following transcatheter TV procedures (a single
horts, their use has been accepted for transcatheter Forma device thrombosis in the setting of subthera-
aortic and mitral valve interventions. Likewise, most peutic anticoagulation), anticoagulation therapy for
initial studies assessing transcatheter devices for the initial months following TTVr or TTVR is advis-
treating TR have used the same risk scoring systems. able, considering that the implantation of these de-
Nonetheless, adoption of the Society of Thoracic vices occurs in right-sided low-pressure circulation
Surgeons score in the tricuspid space might be regions of the heart more prone to thrombosis.
improper, as it has not been previously validated for Larger studies with longer-term follow-up are
TV surgery. Recently, novel specific scores for iso- warranted to determine the real incidence of device-
lated TV surgery have been proposed, although not related thrombosis, as well as to elucidate the
validated yet (87). Identification and validation of optimal post-procedural antithrombotic therapy in
novel dedicated risk scoring systems should translate this population.
C ENTR AL I LL UST RA TI O N Transcatheter Tricuspid Landscape
Asmarats, L. et al. J Am Coll Cardiol. 2018;71(25):2935–56.
Coaptation devices (Forma, MitraClip, Pascal), suture annuloplasty (Trialign, TriCinch, minimally invasive annuloplasty technology, pledget-assisted suture annulo-
plasty), ring annuloplasty (Cardioband, Millipede, transatrial intrapericardial tricuspid annuloplasty), heterotopic caval valve implantation (SAPIEN, TricValve), and
transcatheter tricuspid valve replacement (NaviGate).
CONCLUSIONS minimal residual TR in most cases, represent a

landmark step forward in the transcatheter treat-
Despite the increase in the number of TV proced- ment of TR. Steady device innovation and iteration
ures observed in the past decade, isolated TV sur- together with increased experience are anticipated
gery remains infrequent and continues to be to improve procedural and clinical outcomes in the
associated with one of the highest risks among all coming years. Nevertheless, selection of optimal
cardiac valve procedures in contemporary practice. intervention timing, standardized TR grading
This has resulted in a large number of untreated TR schemes and definitions, and long-term clinical
patients. In response to this unmet clinical need, outcomes and device performance durability remain
several less invasive transcatheter-based therapies important caveats that need to be addressed in
addressing different anatomic therapeutic targets future trials.
have emerged as an alternative to surgery in high-
risk patients with functional TR (Central ACKNOWLEDGMENT The authors thank Dr. Sergio
Illustration). Although the field is still in its in- Pasian of the Quebec Heart and Lung Institute for
fancy, multiple studies have already shown the assistance in generating Table 2.
feasibility and safety of different transcatheter TV
therapies. Preliminary efficacy data has also shown
significant improvements in functional status and ADDRESS FOR CORRESPONDENCE: Dr. Josep Rodés-
QoL, despite modest reductions in TR according to Cabau, Quebec Heart & Lung Institute, Laval Univer-
conventional definitions following TTVr. The recent sity, 2725 Chemin Ste-Foy, Quebec City, Quebec G1V
first-in-human cases of orthotopic TTVR, with no or 4G5, Canada. E-mail: [email protected].
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Transcatheter Tricuspid Valve Interventions: Landscape, Challenges, and Future Directions

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Transcatheter Tricuspid Valve Interventions: Landscape, Challenges, and Future Directions

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 71, NO.

ª 2018 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

THE PRESENT AND FUTURE

JACC STATE-OF-THE-ART REVIEW

T ricuspid regurgitation (TR) is estimated to

ISSN 0735-1097/$36.00 https://doi.org/10.1016/j.jacc.2018.04.031

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

selected by drawing a perpendicular line linking the

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

F I G U R E 3 Pathoanatomy of Functional Tricuspid Regurgitation

volume] 100) or by direct measurement of the

right ventricular apex. The device is currently Quantitative

device implantation was achieved in 16 patients

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

F I G U R E 4 Computed Tomographic Pre-Procedural Workup for Transcatheter Tricuspid Valve Procedures

Device Anatomic Features Imaging Views

Adapted with permission from van Rosendael et al. (31).

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

T A B L E 3 Transcatheter Tricuspid Therapies: Clinical, Procedural, and Follow-Up Features

Forma TriClip Trialign TriCinch Cardioband CAVI NaviGate

Perlman Kodali Nickenig Orban Yzeiraj Hahn Denti Nickenig Lauten

Device Study Study Design Patients Primary Endpoints

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

F I G U R E 6 Suture Annuloplasty Systems

use, showed marked post-procedural alleviation of Failure Questionnaire (intention-to-treat cohort:

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

F I G U R E 7 Ring Annuloplasty Systems

F I G U R E 8 Heterotopic Caval Valve Implantation

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

F I G U R E 9 Orthotopic Transcatheter Tricuspid Valve Replacement

whereas the other 8 patients were alive at 3 weeks

Most patients enrolled in the early clinical experi-

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

Severe TR at high surgical risk

Prolapse Rheumatic Lead-induced Phase I Phase II Phase III

MitraClip TTVR Annuloplasty

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

C ENTR AL I LL UST RA TI O N Transcatheter Tricuspid Landscape

Asmarats, L. et al. J Am Coll Cardiol. 2018;71(25):2935–56.

CONCLUSIONS minimal residual TR in most cases, represent a

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

Transcatheter Tricuspid Valve Interventions JUNE 26, 2018:2935–56

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