EVOQUE TTVR for Tricuspid Regurgitation: A First-in-Human Study

JACC: CARDIOVASCULAR INTERVENTIONS
VOL. 14, NO. 5, 2021
ª 2021 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
NEW RESEARCH PAPERS
STRUCTURAL
Transfemoral Transcatheter Tricuspid
Valve Replacement With the
EVOQUE System
A Multicenter, Observational, First-in-Human Experience
Neil P. Fam, MD, MSC,a,* Ralph Stephan von Bardeleben, MD,b,* Mark Hensey, MB BCH, BAO,c
Susheel K. Kodali, MD,d Robert L. Smith, MD,e Jörg Hausleiter, MD,f,g Geraldine Ong, MD,a Robert Boone, MD,c
Tobias Ruf, MD,b Isaac George, MD,d Molly Szerlip, MD,e Michael Näbauer, MD,f,g Faeez M. Ali, MD,a
Robert Moss, MD,c Vinayak Bapat, MD,d Katharina Schnitzler, MD,b Felix Kreidel, MD,b Jian Ye, MD,c
Djeven P. Deva, MD,a Michael J. Mack, MD,e Paul A. Grayburn, MD,e Mark D. Peterson, MD,a Martin B. Leon, MD,d
Rebecca T. Hahn, MD,d John G. Webb, MDc
ABSTRACT
OBJECTIVES The purpose of this observational first-in-human experience was to investigate the feasibility and safety
of the EVOQUE tricuspid valve replacement system and its impact on short-term clinical outcomes.
BACKGROUND Transcatheter tricuspid intervention is a promising option for selected patients with severe tricuspid
regurgitation (TR). Although transcatheter leaflet repair is an option for some, transcatheter tricuspid valve replacement
(TTVR) may be applicable to a broader population.
METHODS Twenty-five patients with severe TR underwent EVOQUE TTVR in a compassionate-use experience. The
primary outcome was technical success, with NYHA (NYHA) functional class, TR grade, and major adverse cardiac and
cerebrovascular events assessed at 30-day follow-up.
RESULTS All patients (mean age 76 3 years, 88% women) were at high surgical risk (mean Society of Thoracic
Surgeons risk score 9.1 2.3%), with 96% in NYHA functional class III or IV. TR etiology was predominantly functional,
with mean tricuspid annular diameter of 44.8 7.8 mm and mean tricuspid annular plane systolic excursion of 16 2 mm. Technical success was 92%, with no intraprocedural mortality or conversion to surgery. At 30-day follow-up,
mortality was 0%, 76% of patients were in NYHA functional class I or II, and TR grade was #2þ in 96%. Major bleeding
occurred in 3 patients (12%), 2 patients (8%) required pacemaker implantation, and 1 patient (4%) required dialysis.
CONCLUSIONS This first-in-human experience evaluating EVOQUE TTVR demonstrated high technical success,
acceptable safety, and significant clinical improvement. Larger prospective studies are needed to confirm durability and
safety and the impact on long-term clinical outcomes. (J Am Coll Cardiol Intv 2021;14:501–11) © 2021 by the American
College of Cardiology Foundation.
From aSt. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada; bZentrum für Kardiologie, Universitätsmedizin
Mainz, Johannes Gutenberg Universität, Mainz, Germany; cSt. Paul’s Hospital, Centre for Heart Valve Innovation, University of
British Columbia, Vancouver, British Columbia, Canada; dNewYork-Presbyterian Hospital, Columbia University Medical Center,
New York, New York, USA; eBaylor Scott & White Heart and Vascular Hospital, Dallas, Texas, USA; fMedizinische Klinik und
Poliklinik I, Klinikum der Universität München, Munich, Germany; and gDZHK (German Center for Cardiovascular Research),
Partner Site Munich Heart Alliance, Munich, Germany. *Drs. Fam and von Bardeleben are joint first authors and contributed
equally to this paper.
ISSN 1936-8798/$36.00
https://doi.org/10.1016/j.jcin.2020.11.045
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JACC: CARDIOVASCULAR INTERVENTIONS VOL. 14, NO. 5, 2021
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EVOQUE Transfemoral TTVR for Severe TR
S
ABBREVIATIONS
evere tricuspid regurgitation (TR) is a
observational, nonrandomized, single-arm study. All
common valvular disease with signifi-
patients had right-sided HF (New York Heart Associ-
cant morbidity and mortality (1–4).
ation [NYHA] functional class II to IV) despite medical
Most patients have functional TR, which is
therapy and were deemed at high surgical risk or
usually treated conservatively with diuretic
inoperable by the local heart team. Eligible patients
agents given the burden of comorbidities
provided
IVC = inferior vena cava
and high risk of surgery in this patient cohort
included after acceptance from the corresponding
NYHA = New York Heart
(5,6). Given this unmet clinical need, trans-
national regulatory board on the basis of individual
catheter tricuspid intervention has emerged
patient characteristics. The study was approved by
as a promising treatment option for patients
the St. Michael’s Hospital research ethics board.
RV = right ventricular
with TR and right-sided heart failure (HF).
Given that this was a compassionate-use experience,
TAPSE = tricuspid annular
The most commonly used technique is trans-
there was no study protocol, and thus no formal pre-
AND ACRONYMS
CT = computed tomographic
FAC = fractional area change
HF = heart failure
Association
RA = right atrial
plane systolic excursion
TR = tricuspid regurgitation
TTVr = transcatheter tricuspid
valve repair
TTVR = transcatheter tricuspid
valve replacement
written
informed
consent
and
were
catheter leaflet repair, which has demon-
specified inclusion or exclusion criteria were defined.
strated
reasonable
All patients underwent informal external review by
efficacy for TR reduction (7–9). However, a
the sites and the sponsor to determine acceptable
number of predictors of procedural failure
anatomy for the procedure. In general, patients were
for
identified,
considered if the heart team judged that trans-
including baseline massive or torrential TR,
catheter leaflet repair would not be feasible (i.e., large
excellent
leaflet
repair
safety
have
and
been
significant leaflet tethering, and coaptation gap
[>10-mm] coaptation gaps, severe leaflet tethering,
>7 mm, potentially limiting its broad application
and/or pacemaker-induced TR), with suitable anat-
(7,8,10). These predictors are similar to those for fail-
omy
ure of surgical tricuspid repair, and currently the ma-
considered anatomically suitable for EVOQUE TTVR if
jority of surgical candidates with advanced TR
they had adequate screening transesophageal echo-
undergo tricuspid valve replacement (5).
cardiographic imaging of the tricuspid valve leaflets
SEE PAGE 512
for
EVOQUE
implantation.
Patients
were
for procedural guidance and computed tomography–
derived tricuspid valve annular dimensions compat-
Recently, the feasibility of transcatheter tricuspid
ible with 44- or 48-mm valves. There were no specific
valve replacement (TTVR) via thoracotomy or a
anatomic exclusions. Patients with severe right ven-
transjugular approach was reported but was associ-
tricular (RV) dysfunction or significant pulmonary
ated with significant risk for complications using a
arterial hypertension (pulmonary artery systolic
first-generation device (11–13). The EVOQUE valve
pressure >60 mm Hg) were excluded.
replacement system (Edwards Lifesciences, Irvine,
The primary outcome was technical success,
California) was first described for percutaneous,
defined as absence of procedural mortality; success-
transfemoral transcatheter mitral valve replacement
ful access, delivery, and retrieval of the device de-
(14) and recently for successful transfemoral TTVR
livery system; successful deployment and correct
(15). Our aim was to summarize the early experience,
positioning of the first intended device; and freedom
including feasibility, safety, short-term durability,
from emergency surgery or reintervention related to
and clinical outcome of patients with severe TR
the device or access procedure. At 30-day follow-up,
treated with the EVOQUE system for transfemoral
NYHA functional class, and TR severity grade were
TTVR.
assessed as major outcome parameters along with
major adverse cardiac and cerebrovascular events.
METHODS
Clinical endpoints were defined according to the
Mitral Valve Academic Research Consortium criteria
Twenty-five consecutive patients were treated for
(16). Furthermore, echocardiographic parameters of
symptomatic severe TR using the EVOQUE valve
RV size and function were determined.
replacement system between May 2019 and February
STUDY
2020 at 6 centers as part of a compassionate-use,
Procedures were performed under general anesthesia
DEVICE
AND
PROCEDURAL
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’
institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,
visit the Author Center.
Manuscript received September 29, 2020; revised manuscript received November 20, 2020, accepted November 24, 2020.
TECHNIQUE.
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EVOQUE Transfemoral TTVR for Severe TR
F I G U R E 1 EVOQUE Transcatheter Tricuspid Valve Replacement System
(A) EVOQUE transcatheter heart valve: self-expanding Nitinol frame with bovine pericardial leaflets, intra-annular sealing skirt, and ventricular anchors. (B) The 28-F EVOQUE tricuspid delivery system.
with transesophageal echocardiographic and fluoro-
are positioned beneath the leaflet segments as well as
scopic guidance. After percutaneous right femoral
final depth and trajectory adjustment, the atrial
venous access, a 12-F deflectable sheath (Oscor, Palm
inflow portion of the valve with its sealing skirt is
Harbor, Florida) is placed in the right atrium, and
subsequently expanded at the annular level, followed
subsequently a Safari Extra Small guidewire (Boston
by release of the valve. The delivery system is then
Scientific, Marlborough, Massachusetts) is advanced
removed and the femoral puncture site is closed with
through the tricuspid valve into the RV apex. To
previously placed percutaneous or subcutaneous su-
confirm that the wire path is free of the subvalvular
ture. Patients were treated with intravenous heparin
apparatus, a balloon is passed across the tricuspid
during the procedure, targeting an activated clotting
valve to the RV apex (Reliant, Medtronic, Minneap-
time of >300 s. After the procedure, all patients
olis, Minnesota). Alternatively, free wire motion is
received oral anticoagulation with or without aspirin
confirmed in multiple echocardiographic views. The
for a minimum of 6 months.
28-F EVOQUE valve replacement system for TR
(Figure 1), which is identical to the system for mitral
regurgitation (14), is then introduced over the wire
and advanced to the tricuspid valve. The available
EVOQUE valve sizes were 44 and 48 mm, and the
device consists of a self-expanding Nitinol frame,
ECHOCARDIOGRAPHY. The
severity
of
TR
was
graded using transthoracic echocardiography according to current guidelines at baseline, before
discharge, and at 30-day follow-up. We reported the
grade of TR using a 5-grade scheme (17).
bovine pericardial leaflets, and a fabric skirt to mini-
STATISTICAL ANALYSIS. Continuous variables are
mize paravalvular leak. The valve has a unique
presented as mean SD. We used the Fisher exact
anchoring mechanism that uses the annulus, leaflets,
test to compare categorical variables and the Wil-
and chords for stable implantation. The EVOQUE de-
coxon signed rank test for the comparison of contin-
livery system allows 3 planes of motion: primary
uous variables. A 2-tailed p value <0.05 was
flexion is first used to move perpendicular to the
considered to indicate statistical significance. All
tricuspid annulus, and secondary flexion is then used
patients
to ensure coaxial alignment within the tricuspid
treat analysis.
were
included
using
an
intention-to-
valve. Depth of implantation is adjusted with a depth
knob while maintaining coaxial alignment. The sys-
RESULTS
tem is secured in a stabilizer to allow ease of use
BASELINE CHARACTERISTICS. Baseline patient charac-
during the procedure.
Once the system has been advanced across the
teristics are summarized in Table 1. A total of 25
tricuspid valve annulus to an appropriate depth with
consecutive patients (88% women) with a mean age
confirmation of device position and trajectory, the
of 76 3 years were at high surgical risk as expressed
ventricular anchors are exposed by slowly with-
by an Society of Thoracic Surgeons risk score of 9.1 drawing the outer restraining capsule (Figure 2).
2.3% and a European System for Cardiac Operative
Further expansion results in positioning of the U-
Risk Evaluation II score of 7.7 3.8%. All patients had
shaped anchors on the ventricular side of the
right-sided HF due to severe TR (TR $3þ), 96% were
tricuspid
in NYHA functional class III or IV, 84% were in atrial
leaflets,
dimensional
and
which
is
confirmed
3-dimensional
by
2-
transesophageal
echocardiography. After confirming that all 9 anchors
fibrillation or flutter, 44% had previous left-sided
valve
intervention,
and
36%
had
permanent
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F I G U R E 2 Case Example of EVOQUE Tricuspid Replacement
Continued on the next page
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EVOQUE Transfemoral TTVR for Severe TR
pacemaker leads. The majority of patients (71%) had
T A B L E 1 Baseline Characteristics (n ¼ 25)
chronic kidney disease, 28% had coronary artery
Age (yrs)
76 3
disease, with elevated N-terminal brain natriuretic
Female
22 (88)
peptide (mean 3,106 2,028 pg/ml). Baseline medical
EuroSCORE II (%)
7.7 2.2
therapy included loop diuretic agents in 100%, aldo-
STS score (%)
9.1 2.3
sterone antagonists in 68%, and anticoagulant agents
NYHA functional class
II
III
IV
3 (12)
19 (76)
3 (12)
Coronary artery disease
7 (28)
The etiology of TR was functional in 19 patients
1 (4)
(76%), degenerative in 1 patient (4%) (carcinoid), and
5 (20)
mixed in 5 patients (20%) (annular dilatation with
2 (8)
tricuspid valve prolapse in 3 patients, annular dila-
Previous valve intervention
AVR (5.6 3.9 yrs)
MVR (13.1 3.4 yrs)
TV DeVega annuloplasty (11 yrs)
11 (44)
7 (28)
6 (24)
1 (4)
tation with rheumatic disease in 2 patients). TR was
Transtricuspid PM/ICD lead
9 (36)
Renal impairment
15 (60)
Previous myocardial infarction
Previous CABG
Previous PCI
COPD
3 (12)
Atrial fibrillation
21 (84)
Previous TIA/stroke
6 (24)
Hypertension
17 (68)
Diabetes
8 (32)
Peripheral edema
18 (72)
Ascites
14 (56)
in 92% of patients.
Baseline echocardiographic and computed tomographic (CT) parameters are summarized in Table 2.
graded as torrential in 56%, massive in 28%, and severe in 16% of patients. The mean left ventricular
ejection fraction was 58.3 8.6%, mean RV basal
diameter was 50.8 7.2 mm, and mean RV/right atrial
(RA) gradient was 35 4 mm Hg. Overall, RV function
was mildly to moderately reduced, with mean
tricuspid annular plane systolic excursion (TAPSE) of
16 2 mm (64% with TAPSE <17 mm), RV fractional
area change (FAC) of 37 11% (36% with FAC <35%),
and RV dP/dt of 423 240 ms. CT analysis demonstrated mean tricuspid annular diameter of 45.2 2.7 mm, inferior vena cava (IVC)–tricuspid annulus
Loop diuretic agent
25 (100)
Aldosterone antagonist agent
19 (68)
Anticoagulant
Warfarin (AVR or MVR)
DOAC (AF)
23 (92)
11 (44)
12 (48)
diastole was 3.0 4.1%. Figure 3 shows CT analysis of
GFR (ml/min/1.73 m2)
52 8
jectory of the delivery system in a patient with
NT-BNP (pg/ml)
3,106 2,028
AST (U/l)
30 4
ALT (U/l)
25 10
GGT (U/l)
137 7
Bilirubin (mg/dl)
1.9 1.7
distance of 5.8 1.8 mm, and IVC–tricuspid annulus
angle of 83 13 . The degree of valve oversizing in
tricuspid annular dimensions, device sizing, and trapacemaker leads.
PROCEDURAL OUTCOMES. Sixteen patients (64%)
received 48-mm valves and 8 (32%) received 44-mm
valves (Table 3). Technical success was achieved in
23 of 25 patients (92%). One patient had an unsuc-
Values are mean SD or n (%).
cessful procedure with no valve implanted because of
AF ¼ atrial fibrillation; ALT ¼ alanine aminotransferase; AST ¼ aspartate
aminotransferase; AVR ¼ aortic valve replacement; CABG ¼ coronary artery bypass
graft; COPD ¼ chronic obstructive pulmonary disease; DOAC ¼ direct oral anticoagulant agent; EuroSCORE ¼ European System for Cardiac Operative Risk
Evaluation; GFR ¼ glomerular filtration rate; GGT ¼ gamma-glutamyl transferase;
ICD ¼ implantable cardioverter-defibrillator; MVR ¼ mitral valve replacement; NTBNP ¼ N-terminal B type natriuretic peptide; NYHA ¼ New York Heart Association;
PCI ¼ percutaneous coronary intervention; PM ¼ pacemaker; STS ¼ Society of
Thoracic Surgeons; TIA ¼ transient ischemic attack; TV ¼ tricuspid valve.
a noncoaxial approach, and the delivery system was
removed without complications. One patient had a
low implantation (too ventricular) with severe residual central TR secondary to native leaflet interference,
successfully
SAPIEN
3
treated
(Edwards
acutely
Lifesciences)
with
29-mm
valve-in-valve
F I G U R E 2 Continued
(A) Baseline echocardiogram demonstrating lead adherent to posterior tricuspid leaflet. (B) Baseline echocardiogram with color Doppler
showing massive tricuspid regurgitation (TR). (C) Fluoroscopy of initial position of EVOQUE delivery system across the tricuspid annulus. (D)
Corresponding 3-dimensional (3D) transesophageal echocardiographic (TEE) imaging of delivery system position and trajectory. (E) Fluoroscopy showing ventricular anchors deployed. (F) Corresponding 3D TEE imaging of tricuspid leaflet capture. (G) Fluoroscopy after atrial
expansion and valve release. (H) Transthoracic echocardiography at follow-up showing trace TR. (I) Three-dimensional TEE imaging
showing pacemaker lead in posteroseptal commissure.
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EVOQUE Transfemoral TTVR for Severe TR
pacemaker implantation through the EVOQUE valve.
T A B L E 2 Baseline Echocardiographic Parameters
There were 3 patients (12%) with major bleeding
TR etiology
Functional
Degenerative
Mixed
19 (76)
1 (4)
5 (20)
TR severity
Grade 5þ
Grade 4þ
Grade 3þ
14 (56)
7 (28)
4 (16)
complications: 1 gastrointestinal bleed, 1 spontaneous
thigh intramuscular hematoma, and 1 retroperitoneal
bleed from the nonaccess site, all in the context of
combination
LVEF (%)
58.3 3.6
RV diameter base (mm)
50.7 3.1
RV diameter mid (mm)
40.1 3.2
Tricuspid annular S-L (mm)
44.7 7.1
RVEF (%)
49.2 3.4
TAPSE (mm)
15.6 2.5
423.5 109.2
RV dP/dt (mm Hg/s)
15.4 4.2
RV free wall strain
37.6 5.1
RV FAC (%)
12.2 2.1
TR vena contracta (mm)
85.7 20.7
2
TR EROA (mm )
TR regurgitant volume (ml)
60.2 8
TV mean gradient (mm Hg)
1.5 0.4
RVSP (mm Hg)
34.6 4.3
IVC (mm)
28.4 2.1
therapy
with
anticoagulation
and
aspirin. Two patients (8%) with baseline moderate to
severe RV dysfunction developed afterload mismatch
with worsening RV function and required short-term
inotropic support. One patient (4%) developed
asymptomatic leaflet thickening with increased valve
gradient in the context of subtherapeutic anticoagulation, which completely resolved once therapeutic anticoagulation was achieved. No other major
adverse cardiac and cerebrovascular events were
observed. There was a significant improvement in
NYHA functional class in 76% of patients (19 of 25)
(Central Illustration). In addition, the incidence of
patients in NYHA functional class $III was reduced
from 96% (24 of 25 patients) at baseline to 24% (6 of
25 patients) at 30-day follow-up (p < 0.001) (Central
Illustration). Moreover, clinical signs of right-sided
HF including peripheral edema (72% vs. 24%;
p < 0.001) and ascites (56% vs. 8%; p < 0.001)
Values are n (%) or mean SD.
significantly improved, and diuretic agent doses
dP/dt ¼ change in pressure/change in time; EROA ¼ effective regurgitant orifice
area; FAC ¼ fractional area change; IVC ¼ inferior vena cava; LVEF ¼ left ventricular ejection fraction; RV ¼ right ventricular; RVEF ¼ right ventricular ejection
fraction; RVSP ¼ right ventricular systolic pressure; S-L ¼ septal-lateral;
TAPSE ¼ tricuspid annular plane systolic excursion; TR ¼ tricuspid regurgitation;
TV ¼ tricuspid valve.
could be reduced in 28% of patients at follow-up.
There was no significant change in renal function
from baseline to follow-up (glomerular filtration rate
52 8 ml/min vs. 58 9 ml/min; p ¼ 0.14), but
biochemical
measures
of
hepatic
congestion
improved, including bilirubin (1.9 1.7 mg/dl vs. 0.9
0.2 mg/dl; p ¼ 0.01) and gamma-glutamyl transimplantation. No patient experienced peri-procedural
ferase (137 77 U/l vs. 99 58 U/l; p ¼ 0.08). All
myocardial infarction, stroke, or device embolization.
patients were anticoagulated with either warfarin
After valve implantation, TR was reduced to #1þ in 23
(80%) or direct oral anticoagulant agents (20%)
of 25 patients (92%), with a mean tricuspid valve
indefinitely; 68% of patients also received aspirin.
gradient of 2.1 1.1 mm Hg (Central Illustration). In
patients with residual mild TR, the location was paravalvular in 44% and intravalvular in 56%. One
patient had moderate paravalvular TR due to device
canting within the annulus, with stable position.
Mean RA pressure was reduced from 15.0 3.3 to 12.8
5.1 mm Hg (p ¼ 0.03) and mean RA V-wave pressure
from 24.6 9.0 to 15.4 6.9 mm Hg (p ¼ 0.005). Total
procedure time was 140 79 min, device time was 68
47 min, and contrast volume was 25 36 ml.
30-DAY ECHOCARDIOGRAPHIC RESULTS. Echocardio-
graphy demonstrated sustained TR reduction, with
TR grade #2þ in 96% and #1þ in 88% at 30-day
follow-up (Central Illustration). Overall, the mean TR
grade was reduced from 4.4 0.3 to 0.8 0.5
(p < 0.001). The mean tricuspid valve gradient was 3.2
0.6 mm Hg. We observed a slight worsening of RV
function (TAPSE 16 2 mm vs. 14 3 mm [p ¼ 0.11]
and FAC 37 11% vs. 30 8% [p ¼ 0.01]), as expected
given significant reduction of TR. IVC diameter
30-DAY CLINICAL OUTCOMES. At follow-up, mor-
decreased from 28 2 mm to 20 3 mm (p < 0.001),
tality was 0%. There was no myocardial infarction,
while RV systolic pressure remained similar (34.6 stroke, valve reintervention, or HF hospitalization
4.3 mm Hg vs. 42 5.5 mm Hg; p ¼ 0.21). Further-
(Table 4). One patient (4%) with baseline stage IV
more, there was evidence of favorable RV remodel-
renal impairment developed progressive renal failure
ing: RV basal diastolic diameter decreased from 50.8
requiring dialysis. Two patients (8%) developed
7.2 mm at baseline to 46.4 6.3 mm at 30-day
conduction
follow-up
disturbances
requiring
permanent
(p
¼
0.009).
Selected
patients
also
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F I G U R E 3 Computed Tomography for Procedural Planning
(A) Cross-sectional dimensions of the tricuspid annulus in systole. (B) Cross-sectional dimensions of the tricuspid annulus in diastole. (C) Valve
sizing and spatial relationship to pacemaker leads. (D) Projected trajectory of delivery system.
underwent follow-up CT assessment, which demon-
(7–9). However, in the recently reported prospective
strated reductions in RV volume with RV reverse
TRILUMINATE study of the TriClip system, TR
remodeling and no instances of hypoattenuating
grade #2þ was achieved in only 57% of patients by
leaflet thickening (Figure 4).
echocardiography core laboratory assessment at 30day
DISCUSSION
follow-up
(21).
The
presence
of
baseline
massive or torrential TR, significant leaflet tethering,
and large coaptation gaps are predictors of proce-
Here, we demonstrate for the first time in a
dural failure with transcatheter leaflet repair, which
compassionate-use cohort the feasibility and safety of
percutaneous, transfemoral TTVR with the EVOQUE
system in patients with severe TR. In this early
experience, we observed a high rate of technical
success of valve implantation (92%), with no mortality, myocardial infarction, stroke, or HF hospitalization. Furthermore, the results seem to be durable and
associated with significant improvement in functional status at short-term follow-up.
Given the high risk of tricuspid surgery (5,6,18)
and
poor
(19,20),
outcomes
transcatheter
with
conservative
tricuspid
therapy
intervention
has
recently emerged as a viable alternative. Transcatheter leaflet repair is the most common strategy,
with excellent safety and site-reported procedural
success (TR grade #2þ) ranging from 72% to 86%
T A B L E 3 Procedural Outcomes (n ¼ 25)
Technical success
Mortality
23 (92)
0 (0)
Myocardial infarction
0 (0)
Stroke
0 (0)
Device embolization
0 (0)
Major bleeding
0 (0)
Conversion to surgery
0 (0)
Reintervention
Tricuspid regurgitation #1þ
Procedure time (min)
Values are n (%) or mean SD.
1 (4)
23 (92)
140 79
507
508
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C E N T R A L IL L U ST R A T I O N Outcomes After EVOQUE Transfemoral Transcatheter Tricuspid Valve
Replacement for Severe Tricuspid Regurgitation
EVOQUE Transfemoral TTVR Impact on Clinical Outcomes
N = 25
A
NYHA Functional Class
100%
90%
NYHA IV
NYHA IV
NYHA III
80%
B
Tricuspid Regurgitation
100%
70%
60%
60%
NYHA III
40%
20%
20%
0%
Baseline
TR 1+
TR 1+
TR 4+
TR 0+
TR 0+
Procedural
1 Month
40%
30%
NYHA II
TR 5+
50%
NYHA II
30%
10%
TR 5+
TR 2+
80%
70%
50%
TR 5+
TR 2+
90%
NYHA I
1 Month
10%
0%
TR 3+
Baseline
Fam, N.P. et al. J Am Coll Cardiol Intv. 2021;14(5):501–11.
(A) New York Heart Association (NYHA) functional class at baseline and 1-month follow-up showing significant improvement (p < 0.001). (B)
Tricuspid regurgitation (TR) grade at baseline, post-procedure, and 1-month follow-up demonstrated significant TR reduction (p < 0.001).
is associated with increased risk for mortality and
patients with severe RV dysfunction and/or pulmo-
HF hospitalization at follow-up (7,8). In the present
nary hypertension. All patients underwent compre-
study of EVOQUE transfemoral TTVR, TR grade #2þ
hensive assessment prior to intervention with both
was achieved in 96% and #1þ in 88% of patients at
right and left heart catheterization in addition to
30-day follow-up, even though massive or torrential
echocardiography, which may underestimate pulmo-
TR was present in 84% of patients at baseline.
nary artery pressure in the setting of severe TR (22).
Similar to surgical tricuspid valve replacement,
Further studies are needed to define optimal thresh-
TTVR potentially allows treatment of a broader
olds of RV function and pulmonary vascular resis-
TR patient population, particularly those with pre-
tance in patients being considered for TTVR.
dictors of tricuspid repair failure and advanced
tricuspid disease.
In this early experience with EVOQUE transfemoral
T A B L E 4 Clinical Outcomes at 30-Day Follow-Up (n ¼ 25)
TTVR, we observed significant improvements in
Mortality
NYHA functional class, signs of right-sided HF, and
Myocardial infarction
0 (0)
biochemical indexes of hepatic congestion, with a
Stroke
0 (0)
subset of patients requiring fewer diuretic agents at
Conversion to surgery
0 (0)
30-day follow-up. As expected, RV function was
Reintervention
0 (0)
slightly reduced at follow-up, but this was offset by
Heart failure hospitalization
0 (0)
significant reductions in pre-load and RV volumes
Major bleeding
3 (12)
with evidence of reverse remodeling by echocardio-
Conduction abnormality requiring pacemaker
2 (8)
graphic and CT assessment. Importantly, clinically
Dialysis
1 (4)
significant afterload mismatch was uncommon in this
patient cohort, likely because of avoidance of TTVR in
Values are n (%).
0 (0)
Fam et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 14, NO. 5, 2021
MARCH 8, 2021:501–11
EVOQUE Transfemoral TTVR for Severe TR
F I G U R E 4 CT Analysis of RV Volumes
(A) Baseline computed tomographic (CT) volumetric analysis indicating right ventricular (RV) diastolic volume of 228 cm3. (B) Follow-up CT imaging at 3 months
indicating reduction in RV diastolic volume to 168 cm3.
Our results are notable for an absence of mortality
and other major adverse outcomes acutely and at 30-
timing of valve intervention, and the relative roles of
TTVr and TTVR.
day follow-up, particularly given the compassionate-
The main complications of EVOQUE transfemoral
use cohort treated. In comparison, the TriValve
TTVR in the present series were valve reintervention
registry reported 30-day mortality of 3.6% in patients
in 4%, new conduction abnormalities requiring per-
predominantly treated with transcatheter tricuspid
manent pacemaker implantation in 8%, and major
valve repair (TTVr) devices, with 2.8% mortality in
bleeding in 12%. The patient who required acute SA-
those treated with tricuspid leaflet repair (7,8). The
PIEN 3 valve-in-valve reintervention had a low valve
early compassionate-use experience with TTVR using
implantation in the setting of a small right ventricle
the Navigate device with access mainly by mini-
and entrapment of the EVOQUE anchors in the ven-
thoracotomy reported in-hospital mortality of 10%
tricular trabeculations and chordal arcades near the
(13), similar to that reported in recent studies of sur-
tips of the papillary muscles. The atrioventricular
gical tricuspid valve replacement (5,6). We used a
node is in close proximity to the anteroseptal
percutaneous, transfemoral approach, which likely
commissure of the tricuspid valve, and it is likely that
contributed to the safety of the procedure compared
the observed conduction abnormalities resulted from
with other vascular or surgical access routes, as has
either direct compression by the valve frame or ven-
been
transfemoral
tricular anchors. Of note, 1 patient had right bundle
transcatheter aortic valve replacement (23). Only a
branch block at baseline, while the other had normal
small fraction (<5%) of patients with TR are offered
conduction. Future iterations in device design along
surgery, and they represent a highly selected popu-
with improved CT valve-sizing algorithms may
lation (18). Compared with patients undergoing
reduce the risk for atrioventricular block and subse-
tricuspid surgery, patients considered for trans-
quent pacemaker implantation. The observed major
catheter tricuspid intervention are older, with a
bleeding events all occurred in the setting of thera-
greater burden of comorbidities and advanced HF
peutic anticoagulation with warfarin in combination
(7,8). Furthermore, such patients are often not can-
with aspirin. Notably, 20% of patients instead
didates for TTVr, because of advanced tricuspid dis-
received direct oral anticoagulant agents (the major-
ease, making TTVR potentially generalizable to a
ity of these patients received apixaban) and had
larger subset of patients. Analogous to surgical ap-
normal valve function and stable gradients at short-
proaches to TR, TTVr is likely preferred in earlier
term follow-up. Avoidance of combination therapy
stages of the disease, before large coaptation gaps
and/or use of direct oral anticoagulant agents may
and/or severe tethering develop, with TTVR reserved
reduce bleeding risk in this comorbid cohort, but the
for more advanced disease (5–7,24). Further studies
optimal antithrombotic regimen has yet to be
are needed to refine patient and device selection,
established.
previously
demonstrated
for
509
510
Fam et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 14, NO. 5, 2021
MARCH 8, 2021:501–11
EVOQUE Transfemoral TTVR for Severe TR
Pacemaker lead–induced TR has an estimated
speaker honoraria from Abbott Vascular and Edwards Lifesciences.
prevalence of 10% to 25% (25) and is associated with
Dr. Ye is a consultant to Edwards Lifesciences, JC Medical, and Cry-
the onset of right-sided HF and adverse prognosis
oLife. Dr. Moss is a consultant to Edwards Lifesciences. Dr. Hausleiter
has received speaker honoraria and research support from Abbott
(26,27). In the present study, 36% of patients had
Vascular and Edwards Lifesciences; and is a consultant to Abbott
pacemaker leads, and all had successful TTVR with
Vascular and Edwards Lifesciences. Dr. George is consultant to
either no or mild paravalvular TR at the site of the
VDyne, CardioMech, Atricure, MitreMedical, Neptune Medical, and
lead,
with
no
change
in
pacemaker
function,
W.L. Gore. Dr. Nabauer has received speaker honoraria from Abbott
Vascular. Dr. Mack is co–principal investigator of the PARTNER
including patients who were pacemaker dependent at
(Placement of Aortic Transcatheter Valves) 3 trial for Edwards Life-
baseline.
sciences; is co–principal investigator of the COAPT (Cardiovascular
Patients
with
lead-induced
TR
are
frequently encountered in clinical practice and
represent a therapeutic challenge, given the potential
risks
of
lead
extraction
or
tricuspid
Outcomes Assessment of the MitraClip Percutaneous Therapy for
Heart Failure Patients With Functional Mitral Regurgitation) trial for
Abbott; and is study chair of the APOLLO (Transcatheter Mitral Valve
surgery.
Replacement With the Medtronic Intrepid TMVR System in Patients
Furthermore, these patients are usually not candi-
With Severe Symptomatic Mitral Regurgitation) trial for Medtronic
dates for transcatheter leaflet repair or annuloplasty.
(all uncompensated). Dr. Hahn has received speaker fees from
Edwards Lifesciences; is a consultant for Abbott Vascular, Boston
Thus, TTVR may represent an ideal solution for many
Scientific, Gore & Associates, and Medtronic; holds equity with
such patients, who often have no other therapeutic
Navigate; and is the chief scientific officer for the Echocardiography
options.
Core Laboratory at the Cardiovascular Research Foundation for
STUDY LIMITATIONS. The major limitations of our
industry compensation. Dr. Webb is a consultant to and has received
multiple industry-sponsored trials, for which she receives no direct
report include small sample size, observational
design, and a lack of standardized protocols for patient management. In addition, clinical and echocar-
research funding from Edwards Lifesciences, Abbott Vascular, Boston
Scientific, Becton Dickinson, and ViVitro Medical. All other authors
have reported that they have no relationships relevant to the contents of this paper to disclose.
diographic results were site reported, without core
laboratory adjudication. Furthermore, these out-
ADDRESS FOR CORRESPONDENCE: Dr. Neil P. Fam,
comes are from expert, high-volume centers familiar
Division of Cardiology, St. Michael’s Hospital, 30
with transcatheter tricuspid intervention and thus
Bond Street, Toronto, Ontario M5B 1W8, Canada.
may not be generalizable to less experienced centers.
E-mail: [email protected].
CONCLUSIONS
PERSPECTIVES
This first-in-human experience evaluating percutaneous, transfemoral TTVR with the EVOQUE system
demonstrated
high
technical
success,
excellent
WHAT IS KNOWN? TR is associated with significant
morbidity and mortality, and many patients are not
candidates for surgery or TTVr.
safety, and significant clinical improvement in patients with severe TR and HF. Larger studies with
WHAT IS NEW? In this compassionate-use experi-
long-term follow-up are needed to confirm these
ence, EVOQUE transcatheter tricuspid replacement
initial promising results and further define patient
demonstrated high technical success, acceptable
selection criteria, timing of intervention, and the
safety, and significant clinical improvement.
impact of EVOQUE tricuspid valve replacement on
WHAT IS NEXT? Large prospective studies are
clinical outcomes.
needed to determine the impact of EVOQUE trans-
FUNDING SUPPORT AND AUTHOR DISCLOSURES
catheter tricuspid replacement on long-term clinical
outcomes.
Dr. Fam has received speaker honoraria from Abbott Vascular; and is a
consultant to Edwards Lifesciences. Dr. von Bardeleben received
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KEY WORDS EVOQUE, transcatheter
tricuspid valve replacement, tricuspid
regurgitation
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